Alnylam Pharmaceuticals Inc. - 500 Beiträge pro Seite

[Zadek]

Alnylam Pharmaceuticals gelingt Durchbruch auf dem Gebiet der RNAi-Forschung
Erstmalig Beweis für den erfolgreichen Einsatz der RNA-Interferenz mittels systemischer Verabreichung erbracht

11.11.2004 - Alnylam Pharmaceuticals hat den in vivo-Funktionsnachweis der RNAi-induzierten Inaktivierung einzelner Gene (Gene Silencing) in Säugern erfolgreich durchgeführt und veröffentlicht. Das Unternehmen nimmt damit eine Vorreiterposition auf diesem Gebiet ein. Dabei wurde eine Methode eingesetzt, die potenziell für systemische RNAi-Therapeutika bei Humanerkrankungen anwendbar sind.

Die jetzt in Nature veröffentlichten Forschungsergebnisse stellen einen bedeutenden Fortschritt bei der Entwicklung systemischer RNAi-Therapeutika dar. Die Verabreichung über die Blutbahn ermöglicht RNAi-Therapeutika im Prinzip jedes für den Ausbruch einer Krankheit verantwortliche Gen abzuschalten. Damit eröffnen sich völlig neue Perspektiven für eine breite Anwendung von RNAi-Therapeutika zur Behandlung einer Vielzahl von Krankheiten.

In der Veröffentlichung der Forschungsergebnisse beschreiben die Alnylam-Wissenschaftler die erfolgreiche in vivo-Inaktivierung des Gens für das Apolipoprotein B (apoB), einem Schlüsselprotein des Cholesterin-Stoffwechsels, sowie die damit einhergehende Senkung des Cholesterinspiegels im Blut. Dies wurde mit Hilfe der intravenösen Gabe speziell konstruierter, kurzer doppelsträngiger Ribonukleinsäuren (auch siRNAs genannt) erzielt. Die siRNA-Moleküle lösen in den Zellen RNA-Interferenz aus. Die synthetischen siRNA-Moleküle wurden mit patentierten chemischen Methoden so modifiziert, dass sie auch gezielt die entsprechenden Zellen erreichen und in sie eindringen konnten. Die intravenöse Injektion dieser modifizierten siRNA-Moleküle in Mäuse reduzierte die apoB-Messenger-RNA (mRNA) in der Leber und im Darm, was eine deutlichen Senkung des apoB-Protein- und Gesamtcholesterinspiegels im Blut zur Folge hatte.

Parallel dazu konnten die Wissenschaftler in einem transgenen Mausmodell die Inaktivierung des menschlichen apoB-Gens durch siRNA-Moleküle nachweisen. Das apoB-Gen ist ein klinisch höchst relevantes Zielgen, da es bis heute mit traditionellen Methoden, das heisst mit niedermolekularen Wirkstoffen, Proteinen oder Antikörpern, keine wirksame Therapie gibt, die direkt in diesen Stoffwechselweg eingreift.

"Mit dem ersten Nachweis einer RNAi-induzierten Inaktivierung eines Gens durch systemische Verabreichung von siRNAs konnten wir den Wissensstand auf dem Gebiet der RNAi-Forschung bedeutend erweitern. Wir haben damit den ersten konkreten Beweis für die vielfältigen potenziellen Anwendungsmöglichkeiten von RNAi-Therapeutika geliefert", sagte Dr. Hans-Peter Vornlocher, Forschungsleiter von Alnylam Europe AG. "Die jüngste Veröffentlichung unserer Forschungsergebnisse im renommierten Fachmagazin Nature betrachten wir als grosse Auszeichnung. Sie ist gleichzeitig auch ein Ansporn für Alnylams fortlaufende Forschungsarbeiten an vorderster Front der Therapeutika-Forschung, die Anwendungen der RNAi als völlig neue Wirkstoffklasse ermöglicht."

Alnylams Wissenschaftler lieferten erstmals den eindeutigen Beweis, dass siRNAs im lebenden Organismus für den RNAi-induzierten Abbau einer Ziel-mRNA verantwortlich sind. Mit Hilfe hochempfindlicher Analysemethoden konnte die Spaltung der apoB-mRNA an der vorausgesagten Stelle nachgewiesen werden. Die Bestätigung des spezifischen Wirkmechanismus von siRNAs verdeutlicht das therapeutische Potenzial bei der Anwendung des natürlich auftretenden Phänomens der RNA-Interferenz für die Behandlung von Krankheiten.

"Diese wichtigen Ergebnisse sind ein entscheidender Fortschritt für unsere Forschungsarbeiten an systemischen RNAi-Therapeutika und bei der breiten Anwendung der RNAi bei häufigen Erkrankungen wie Herz-Kreislauf-Beschwerden, Diabetes, Fettleibigkeit, Hepatitis und Krebs sowie vielen Infektionskrankheiten", erklärt Dr. John Maraganore, Chief Executive Officer von Alnylam Pharmaceuticals. "Alnylam wird auch weiterhin seine gesamte wissenschaftliche Expertise und seine patentierten Verfahren für die Weiterentwicklung sowohl direkter als auch systemischer RNAi-Anwendungen einsetzen. Dies schliesst natürlich die weitere Verbesserung der systemischen RNAi-Technologie zur Anwendung für Humantherapeutika ein."


Die Marktkapitalisierung beträgt nur rd. 125 Mio-$.
Ein Unternehmen mit der man sich befassen sollte.

Zadek

[Zadek]

Wieder auf dem Weg zu den Höchstkursen nach der Emission?
Die Umsätze ziehen bei steigenden Kursen an.

[Zadek]

Über RNAi

RNA-Interferenz, oder RNAi, ist ein natürlicher, in den Zellen
ablaufender Mechanismus zur selektiven Inhibierung und Regulation der
Expression spezifischer Gene und könnte die Grundlage für eine völlig
neuartige Klasse von Wirkstoffen sein. Da viele Krankheiten ihre
Ursache in einer fehlerhaften Aktivität bestimmter Gene haben, könnte
die selektive Inaktivierung und Regulation dieser Gene mit Hilfe der
RNAi neue Möglichkeiten bieten, eine Vielzahl bislang nicht heilbarer
Krankheiten zu behandeln. Die Entdeckung der RNAi wird von vielen als
wesentlicher wissenschaftlicher Durchbruch angesehen. So benannte das
Fachmagazin Science die RNAi als wichtigsten wissenschaftlichen
Durchbruch des Jahres 2002, und als einen der Top-10
wissenschaftlichen Fortschritte des Jahres 2003.

[Zadek]

Der US-Pharmariese Merck hat seine Kooperation mit Alnylam Pharmaceuticals ausgeweitet. In einem langfristigen Abkommen betreibe man fortan gemeinsam die Entwicklung neuartiger Therapien gegen Augenkrankheiten im Alter, die durch Abnutzung, außergewöhnliche Linsen-Größe oder beschädigte Blutgefäße zustande kommen würden. Dabei würden Alnylams bestehende Therapien eingebunden. Der kleinere Partner erhalte eine einmalige Vergütung und weitere Erfolgsprämien sowie Anteile an den Umsätzen in den USA.

Zadek

[Zadek]

zu Alnylam:

Alnylam ist ein biopharmazeutisches Unternehmen, dessen Vision es ist, neuartige Therapeutika auf Basis der RNA-Interferenz (RNAi) zu entwickeln und zu vermarkten.

Ausgehend von seiner Gründung als weltweit erstes Unternehmen, das sich auf die Entwicklung RNAi-basierter Therapeutika spezialisiert hat, baut das Unternehmen heute auf seine hervorragenden Gründer und Berater sowie auf die Stärke der für eine erfolgreiche Kommerzialisierung von RNAi-basierten Therapeutika notwendigen grundlegenden Patente, Herstellungsverfahren und Know-how auf.

Mit Hilfe der Direct RNAi(TM)-Technologie entwickelt das Unternehmen Produkte zur Behandlung von Augen-, ZNS- und Atemwegserkrankungen sowie mit Hilfe der Systemic RNAi(TM )-Technologie Produkte zur Behandlung einer Vielzahl von Erkrankungen aus den Bereichen Krebs, Stoffwechsel- und Autoimmunerkrankungen. Das Unternehmen hat seinen Hauptsitz in Cambridge, Massachusetts. Weitere Informationen erhalten Sie unter
http://www.alnylam.com .

Die Aktien der Gesellschaft werden auch in Berlin gehandelt.

Zadek

[traumstrand]

Ja, Zadek, Alnylam ist interessant - ein wahrer Technologieträger. Zum Glück haben Dransfeld/Glasauer in dieser Firma quasi nix mehr zu melden, Anteil irgendwo bei 1%.

Das macht ein Investment bedenkenswert. Habe grad vor einigen Tagen mit einem Pharmakologie-(oder Pharmazie-?)-Prof. gesprochen, der sagte, die SiRNA sind die nächste Revolution nach Biotech für die Medikamentenentwicklung...

Einziger Nachteil: ich würde lieber etwas mehr Liquidität in Deutschland (Börse Berlin) haben...

[Zadek]

Zur Ergänzung:
Alnylam hat Mitte 2003 den deutschen RNAi Pionier Ribopharma AG übernommen.

Die Pressemeldung hierzu:

RNAi-Merger: Ribopharma und Alnylam fusionieren
Mit dem Ziel, das weltweit führende Unternehmen bei der Entwicklung von Therapeutika auf Basis der RNA-Interferenz zu bilden, haben die deutsche Ribopharma AG, Kulmbach, und die US-amerikanische Alnylam Pharmaceuticals Inc. Mitte Juli ihre Fusion beschlossen. Das neue Unternehmen mit dem Namen Alnylam Holding Co. wird zwei Standorte unterhalten – den Hauptsitz in Cambridge, Massachusetts, und einen in Kulmbach.

Die Fusionsvereinbarung sieht einen Aktientausch vor, so daß die bisherigen Eigentümer von Alnylam und Ribopharma anteilig Aktien der neuen Firma erhalten werden. Zeitgleich mit dem Zusammenschluß sicherte sich das entstehende Unternehmen eine Finanzierung in Höhe von 21,5 Mio. Euro. Damit ist es laut Ribopharma eines der bestfinanzierten Unternehmen auf dem Gebiet der RNAi- Therapeutika. An der Finanzierung sind die Polaris Venture Partners, Abingworth Management, Cardinal Partners, Atlas Venture sowie ARCH Venture Partners beteiligt. Das neue Unternehmen plant, die Finanzmittel zur Intensivierung der Forschungsaktivitäten und Kommerzialisierung der RNAi-Therapeutika einzusetzen. Zu diesem Zweck sollen die Abteilungen Vertrieb und Forschung deutlich vergrößert werden.

Dr. John Maraganore, bisheriger Vorstandsvorsitzender von Alnylam Pharmaceuticals, übernimmt diesen Posten auch im neuen Unternehmen. Ihm zur Seite stehen unter anderem Dr. Roland Kreutzer, Gründer und bislang Vorstandsvorsitzender von Ribopharma, der in Zukunft als COO den Ribopharma-Geschäftsbereich führen wird, sowie Dr. Stefan Limmer, Gründer und zuvor Vorstand für Forschung und Entwicklung bei Ribopharma, der als Leiter Technologie in den Vorstand des Gesamtunternehmens berufen wurde.

Zadek

[puhvogel]

Sehr schön, Zadek, du ersparst mir einiges an Researcharbeit. Die dahinterstehende Technologie ist wirklich schon sehr spannend.
http://science.orf.at/science/news/86066

Wenn ich das richtig sehe, haben die aber keine eigene Pipeline sondern wollen als Pharmazulieferer/-zuarbeiter wirken?!?

[BrauchGeld]

Hi

Alfacell (ACEL) ist auch in dem bereich tätig ,ist meiner meinung auch besser aufgestellt und haben auch produkt in phase 3.

Gruss
B.M.

[Zadek]

@BG

ALFACELL...muß ich mich erst mit beschäftigen.

Bei ALNYLAM sieht es heute jedenfalls gut aus:

Nasdaq ALNY USD 6,91 7,40 + 0,490 + 7,09 % 113.630 72.484 24. Nov 18:21
Berlin DUL EUR 5,11 5,60 + 0,490 + 9,59 % 6.680 1.201 24. Nov 15:42

Zadek

[Zadek]

Ribopharma AG sichert sich wichtiges Patent zur Medikamentenentwicklung
Neue Wirkstoffe im Kampf gegen Krebs und Viruserkrankungen
Eine neuartige Klasse von Wirkstoffen, die die Entwicklung neuer Medikamente beispielweise gegen Krebs und Viruserkrankungen entscheidend voranbringen kann, hat das Biotech-Unternehmen Ribopharma AG beim Europäischen Patentamt in München angemeldet - jetzt wurde das erste europaweite Patent erteilt.

Die in Kulmbach ansässige Firma stellt mit Hilfe der nun geschützten Verfahrensanwendung naturidentische Substanzen her, die bereits in niedriger Konzentration und mit geringen Nebenwirkungen bestimmte krankheitsverursachende Vorgänge in Zellen hemmen.

Die international tätige Ribopharma AG entwickelt diese als SIRPLEX-Moleküle (Small Interfering RNA Duplex) bezeichneten Substanzen für verschiedene Indikationen. Mit ihnen soll die Bildung von tumor- oder virusspezifischen Genprodukten beziehungsweise solchen, die für das Wachstum oder die Vermehrung eines Virus verantwortlich sind, gezielt verhindert werden. Erste Therapeutika sollen bereits im kommenden Jahr in die klinische Prüfung gehen.

"Mit der Erteilung des Patents ist ein wesentlicher Meilenstein unseres Businessplans erreicht, der es uns erlauben wird, frühzeitig starke Kooperationen aufzustellen", freut sich Dr. Roland Kreutzer, Gründer und Geschäftsführer von Ribopharma. Das wirtschaftliche Potential lasse sich anhand abgeschlossener Entwicklungskooperationen im mittleren dreistelligen US-$-Bereich bereits erahnen. "Das Interesse an unserer Technologie war schon seit seit der Firmengründung unvergleichbar groß. Nach der Erteilung des Patents bin ich sicher, daß wir sc hon in Kürze den Abschluß erster signifikanter Lizenz- und Partnering-Deals vermelden können", ergänzte Dr. Ulrich Bodner, Vice President Business Development. Potenzielle Anwender der SIRPLEX-Moleküle sind alle Biotechnologie- und Pharma-Unternehmen, die auf der Suche nach neuen Angriffsorten für Wirkstoffe (Targetvalidierung) sind beziehungsweise bereits über validierte Zielmoleküle (drugable Targets) verfügen, deren Blockade einen heilenden Effekt hat.

Zur Technologie:
Bei den von Ribopharma eingesetzten Molekülen handelt es sich um kurze Genabschnitte (doppelsträngige RNA-Moleküle), die komplementär zu einer zuvor definierten Stelle der Erbsubstanz (ein Gen) in einer Zelle sind und die Umsetzung der Information, die im Gen enthalten ist, verhindern. So können beispielsweise Tumor-Wachstumsgene ausgeschaltet oder die Mechanismen, mit denen Viren sich in tierischen Zellen vermehren, blockiert werden. Die Entdeckung des als RNA-Interferenz oder kurz als RNAi bezeichneten Effekts und die Entwicklung der RNAi-induzierenden Moleküle, der sogenannten siRNAs (small interference RNAs), eröffnet daher vielversprechende Möglichkeiten für neue effektivere Therapeutika im Kampf gegen Krebs, Virusinfektionen oder andere lebensbedrohende Erkrankungen, die mit der Expression spezifischer Gene einhergehen.

Das nun erteilte Basis-Patent "Verfahren und Medikament zur Hemmung eines vorgegebenen Gens" (Nr. 00 910 510.7-2107) zur gesamten RNAi/siRNA-Technologie schützt sowohl das Verfahren als auch die Entwicklung und herstellung von Medikamenten zur Hemmung der Genexpression mit Hilfe kurzer doppelsträngiger RNA-Moleküle bis zu einer Länge von 25 Basenpaaren (die sogenannten SIRPLEX-Moleküle), die eine zum Zielgen identische Sequenz aufweisen. Bereits im April dieses Jahr hatte das deutsche Patent- und Markenamt der Ribopharma AG das weltweit erste Patent zur gewerblichen Nutzung der RNA-Interferenz-Technologie erteilt. vorgeschlagen.


Ribopharma AG fusionierte inzwischen erfolgreich mit der amerikanischen Alnylam Pharmaceuticals .

Zadek

[traumstrand]

Hat jemand versucht, in Deutschland Stücke zu erwerben? Organisiert einem die Börse Berlin welche "übern großen Teich"? Heute waren ja auch nur 1200 Stück Umsatz, aber sonst ist die Liquidität noch viel mieser.

Oder muß ich in den sauren Apfel beissen und die höhere Auslandsbörsengebühr blechen?

[Zadek]

Intraday fast exakt am ATH gescheitert...aber das war nicht der letzte Versuch. Bald ist der Weg nach oben frei.



Zadek

[Zadek]

Schlusskurs gestern:

Nasdaq ALNY USD 7,86 + 0,950 + 13,75 % 1,31 Mio. Umsatz

Zadek

[Zadek]

ATH kommt näher; bei hohen Umsätzen.
(Intraday bereits bei 8,50 gewesen.)

Nasdaq ALNY 8,10 + 3,05 % 1,01 Mio. 26. Nov 19:01

In Berlin für weniger als 6 € zu haben

Zadek

[Zadek]

Verschnaufpause.

Nasdaq ALNY USD 8,25 + 1,85 % 876.689 29. Nov 22:01

Zadek

[Fruehrentner]

CAMBRIDGE, Mass., Jan. 25 /PRNewswire-FirstCall/ -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading therapeutic RNA interference (RNAi) company, today announced that it is initiating a program to develop RNAi therapeutics for spinal cord injury as part of its previously announced strategic collaboration with Merck & Co., Inc. to develop RNAi therapeutics and technology. The new program will focus on a specific drug target proposed by Merck, and Alnylam will proceed with preclinical development of an RNAi therapeutic for this target. The drug target is in the Nogo pathway, which plays a key role in preventing regeneration of nerves after injury, such as spinal cord injuries. An RNAi therapeutic that inhibits this pathway could potentially reduce or prevent paralysis caused by such injuries.

"The initiation of this program is another important step in our development of a robust pipeline of RNAi therapeutics for major unmet medical needs," commented John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "We are hopeful that the breakthrough therapeutic potential of RNAi can provide relief to the thousands of patients whose lives are dramatically impacted by spinal cord injuries."

Alnylam and Merck have entered into two separate, but complementary, strategic collaborations. The program to develop an RNAi therapeutic for spinal cord injury falls within the first of these collaborations, initiated in September 2003. The goals of this collaboration are to advance RNAi technology and to apply this technology to develop RNAi therapeutics that selectively target human diseases. For therapeutics development, Merck proposes potential targets to Alnylam, and if Alnylam develops a candidate RNAi therapeutic against a "Merck target" to a defined point in preclinical development, Merck may then opt to co-develop and co-promote this RNAi therapeutic with Alnylam. If Merck exercises this option it will pay Alnylam an option fee, reimburse Alnylam for fifty percent of its expenses previously incurred on the candidate RNAi therapeutic, and co-fund development from that point.

The second collaboration between Alnylam and Merck, initiated in June 2004, is focused on age-related macular degeneration (AMD) and other ocular diseases caused by abnormal growth or leakage of small blood vessels in the eye. This collaboration includes Alnylam`s most advanced program, to develop a Direct RNAi(TM) Therapeutic targeting vascular endothelial growth factor (VEGF) for the treatment of the "wet" form of AMD.

About RNAi

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes that is potentially the basis for a new class of therapeutic products. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence and regulate such genes selectively through RNAi could provide a means to treat a wide range of human diseases. The discovery of RNAi has been heralded by many as a major breakthrough, and the journal Science named RNAi the top scientific achievement of 2002, as well as one of the top 10 scientific advances of 2003.

About Alnylam

Alnylam is a biopharmaceutical company seeking to develop and commercialize novel therapeutics based on RNA interference, or RNAi. Growing from its foundation as the world`s first company focused on RNAi therapeutics, the company`s leadership in the field of RNAi is supported by its preeminent founders and advisors and its strengths in fundamental patents, technology, and know-how that underlie the commercialization of RNAi therapeutics. Alnylam is developing a pipeline of RNAi products using Direct RNAi(TM) to treat ocular, central nervous system, and respiratory diseases and Systemic RNAi(TM) to treat a broad range of diseases, including oncologic, metabolic, and autoimmune diseases. The company`s global headquarters are in Cambridge, Massachusetts. For additional information, please visit http://www.alnylam.com

[Zadek]

Alnylam Phama erhält Zahlung von Merck


Das Biotechnologieunternehmen Alnylam Pharmaceuticals (Nachrichten) hat von Merck & Co. eine Meilensteinzahlung von $7 Mio erhalten. Wie Alnylam am Montag weiter mitteilte, resultiert die Zahlung aus einer strategischen Allianz zur Entwicklung der RNAi-Gen-Technologie und des Einsatzes von Therapien. Die Zahlung beinhalte $2 Mio in bar und $5 Mio an Kapitalinvestitionen zum Preis von $7 je Aktie.

Zadek

[Zadek]

Sorry, vorheriges Posting ohne Datum. Meldung ist schon etwas älter, vom 3-01-05. Aber die erste Reaktion ist da:

NEW YORK, February 2 (newratings.com) – Analysts at Banc of America Securities upgrade Alnylam Pharma (ALNY.NAS) from "neutral" to "buy." The target price has been raised from $6.50 to $9.50.

In a research note published this morning, the analysts mention that Alnylam Pharma is likely to benefit from its leading position in the fast-growing RNAi-based therapies market going forward. Banc of America Securities anticipates significant positive newsflow for the company this year, including the announcement of several new programmes and the accomplishment of various business development targets

Zadek

[traumstrand]

@ Zadek

Die Umsätze in ALNY in Deutschland sind ja marginal. Wo handelst Du? Wer ist ein günstiger und komfortabler Anbieter für Trades an der NASDAQ? Danke für den Tip.

[Zadek]

@traumstrand

Für meine Zwecke ist CORTAL CONSORS ausreichend.

Zadek

[Zadek]

Nasdaq ALNY USD 7,61 8,11 + 0,500 + 6,57 %

Zadek

[Fruehrentner]

ALNYLAM heute +4,25 % an der NASDAQ



RNA-Interferenz eröffnet neue Therapie-Chancen
In Berlin startet ein Europäisches Forschungskonsortium zur RNA-Interferenz, das von der EU mit 11 Millionen Euro gefördert wird
28.01.2005 - Ein europäisches Forschungsprojekt zur Weiterentwicklung der viel versprechenden RNA-Interferenz-Technologie für die Therapie schwerer Erkrankungen beim Menschen, wie Krebs, degenerative Erkrankungen und Infektionskrankheiten, nimmt am 27. Januar 2005 seine Tätigkeit auf. Das RIGHT-Konsortium (RNA Interference Technology as Human Therapeutic Tool) wird vom Max-Planck-Institut für Infektionsbiologie koordiniert und vereinigt führende Forschungsgruppen von 24 Forschungseinrichtungen und Unternehmen aus ganz Europa. In den kommenden vier Jahren wird das Projekt durch die Europäische Union mit 11 Millionen Euro gefördert. Das Projekt startet mit einem Treffen der beteiligten Wissenschaftler aus Belgien, Dänemark, Deutschland, Finnland, Frankreich, Griechenland, Großbritannien, Italien, Polen und Schweden sowie mit einer Pressekonferenz in Berlin.

Die RNA(Ribonukleinsäure)-Interferenz-Technologie basiert auf einem natürlichen Mechanismus, bei dem kurze RNA-Moleküle spezifisch die Bildung bestimmter Genprodukte hemmen. Diese Technik hat in den vergangenen Jahren die biologische Grundlagenforschung revolutioniert, weil sie eine vergleichsweise einfache Möglichkeit bietet, die Funktion von Genen zu untersuchen. Sie ermöglicht dadurch den wichtigen Schritt von der bloßen Kenntnis der Gensequenz zum Verständnis ihres Wirkens sowie der anschließenden Nutzung dieses Wissens für neuartige Therapieansätze.

Bei vielen schwerwiegenden Krankheiten wie Krebs, degenerativen Erkrankungen oder Infektionskrankheiten ist die Regulation bestimmter Gene gestört. Gerade hier setzt die RNA-Interferenz-Technologie an, indem sie die Bildung ganz spezifischer Genprodukte hemmt. Doch eine therapeutische Anwendung stellt hohe Anforderungen sowohl an die eingesetzten Reagenzien selbst als auch an die Strategien für ihren Einsatz im menschlichen Organismus: So müssen die Substanzen im Körper äußerst spezifisch wirken, ausreichend lang stabil bleiben und effektiv aufgenommen werden.

Im Rahmen des RIGHT-Konsortiums haben es sich nun Experten aus den Fachrichtungen Chemie, Molekularbiologie, Zellbiologie und Medizin zur Aufgabe gemacht, genau bei diesen Problemen anzusetzen. Ihre Ziele sind, das Verständnis der molekularen Basis von RNA-Interferenz und micro-RNA zu verbessern, - verbesserte Inhibitoren mit höheren Sensitivität, Spezifität und Kosten-Effektivität zu entwickeln, - potentielle virale und nicht-virale Vektoren zu erzeugen und zu testen, - synthetische und genetische RNAi-Reagenzien mit pharmakokinetischen Methoden in Tiermodellen zu testen, - an ausgewählten Krankheitsmodellen die Einsatzmöglichkeiten von RNAi als therapeutisches Instrument zu zeigen.

"Wir sind überzeugt, dass die RNA-Interferenz-Technologie ein unvergleichliches Potential für die Behandlung schwerer Krankheiten in sich birgt", sagt Professor Thomas F. Meyer, Direktor am Max-Planck-Institut für Infektionsbiologie in Berlin und Koordinator des RIGHT-Projekts.

http://www.bionity.com/news/d/40776/?sort=3

[Zadek]

02-09-05 10:43 AM EST
MINNEAPOLIS (Dow Jones)--Medtronic Inc. (MDT) and Alnylam Pharmaceuticals Inc. (ALNY) will together pursue potential therapies designed to treat neurodegenerative disorders such as Huntington`s, Alzheimer`s and Parkinson`s disease.

In a news release, the companies said the collaboration will focus on developing novel drug-device combinations incorporating RNAi therapeutics. RNAi, or RNA interference, refers to a technique for silencing targeted genes in a cell, inhibiting their ability to produce particular proteins involved in specific diseases, the companies noted.

Initially, development will focus on delivering RNAi therapeutics to specific areas of the brain using novel infusion systems.

The companies said that, under their agreement, after successful completion of an initial joint technology development program and a joint decision to initiate product development, Alnylam would be responsible for the discovery and early development of candidate RNAi therapeutics, and Medtronic would be responsible for late-stage development and commercialization of any drug-device products that result. Medtronic also would adapt or develop medical devices to deliver the candidate RNAi therapeutics to targeted locations in the nervous system.

After the completion of the initial joint technology development program and a joint decision to start product development, Medtronic would make an equity investment in Alnylam and could make additional investments upon successful completion of certain pre-defined milestones, they said. They didn`t provide specifics.

Alnylam would be eligible to receive additional cash milestone payments for each product developed, and royalties on sales of any RNAi therapeutic component of novel drug-device combinations that result from the collaboration.

Medtronic, Minneapolis, is a medical technology company.

Alnylam, Cambridge, Mass., is a biopharmaceutical company seeking to develop and commercialize novel therapeutics based on RNAi.

Company Web Sites: http://www.medtronic.com and http://www.alnylam.com

-Carolyn King, Dow Jones Newswires; 416-306-2100

Zadek

[Zadek]

Alnylam Pharmaceuticals and the LudwigMaximilian University Munich Publish Data on Short Interfering RNAsand Immune Stimulation Mechanisms

CAMBRIDGE, Mass. Feb. 22, 2005


Scientific Insights Published in Nature Medicine Advance the Development of RNAi Therapeutics

Alnylam Pharmaceuticals, Inc., a leading RNAitherapeutics company, and its collaborators at the Ludwig MaximilianUniversity Munich announced today the online publication of an articlein Nature Medicine identifying specific immunostimulatory motifs ofshort interfering RNAs (siRNAs), the molecules that induce RNAinterference. The identification of these motifs enables the design ofsiRNAs that avoid interferon induction, an important goal forachieving safe RNAi therapeutics. These data have applications fordeciphering the biological mechanisms of gene silencing andunderstanding how to design and optimize siRNA sequences that are bothsafe and efficacious as therapeutics.
In the paper, immune stimulation, as measured by interferoninduction, was found to occur in association with some siRNA sequencesbut not others. These findings were observed in vivo in associationwith the use of liposomal delivery of the siRNAs. In connection withthe Nature Medicine publication, Alnylam has licensed certainintellectual property relating to Dr. Gunther Hartmann´s work from theLudwig Maximilian University Munich.
"Understanding the sequence-specific regulation of the immuneresponse toward short interfering RNA is a tremendous advancement inRNAi biology and the development of therapeutics based on RNAi," saidDr. Hartmann, M.D., Division of Clinical Pharmacology, LudwigMaximilian University Munich Hospital, Germany.
"Alnylam is committed to developing safe and efficacious RNAitherapeutics," said John Maraganore, Ph.D., President and ChiefExecutive Officer of Alnylam Pharmaceuticals. "Elucidating themechanism of action responsible for siRNA immunostimulation will allowfor efficient selection of appropriate siRNA molecules."

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanismwithin cells for selectively silencing and regulating specific genes.Since many diseases are caused by the inappropriate activity ofspecific genes, the ability to silence and regulate such genesselectively through RNAi could provide a means to treat a wide rangeof human diseases. The discovery of RNAi has been heralded by many asa major breakthrough, and the journal Science named RNAi the topscientific achievement of 2002, as well as one of the top 10scientific advances of 2003.

About Alnylam

Alnylam is a biopharmaceutical company seeking to develop andcommercialize novel therapeutics based on RNA interference, or RNAi.Growing from its foundation as the world´s first company focused onRNAi therapeutics, the company´s leadership in the field of RNAi issupported by its preeminent founders and advisors and its strengths infundamental patents, technology, and know-how that underlie thecommercialization of RNAi therapeutics. Alnylam is developing apipeline of RNAi products using Direct RNAi(TM) to treat ocular,central nervous system, and respiratory diseases and Systemic RNAi(TM)to treat a broad range of diseases, including oncology, metabolic, andautoimmune diseases. The company´s global headquarters are inCambridge, Massachusetts. For additional information, please visitwww.alnylam.com.

Alnylam Forward Looking Statement

Various statements in this release concerning our futureexpectations, plans, prospects and future operating results constituteforward-looking statements for the purposes of the safe harborprovisions under The Private Securities Litigation Reform Act of 1995.Actual results may differ materially from those indicated by theseforward-looking statements as a result of various important factors,including risks related to: our approach to discover and develop noveldrugs, which is unproven and may never lead to marketable products;our ability to obtain additional funding to support our businessactivities; our dependence on third parties for development,manufacture, marketing, sales and distribution of our products; thesuccessful development of products, all of which are in early stagesof development; obtaining regulatory approval for products;competition from others using technology similar to ours and othersdeveloping products for similar uses; obtaining, maintaining andprotecting intellectual property utilized by our products; and ourshort operating history; as well as those risks more fully discussedin the "Certain Factors That May Affect Future Results" section of ourmost recent Form 10-Q filed with the Securities and ExchangeCommission. In addition, any forward-looking statements represent ourviews only as of today and should not be relied upon as representingour views as of any subsequent date. We do not assume any obligationto update any forward-looking statements.

Autor: © Business Wire , 14:05 22.02.05

Zadek

[traumstrand]

Hallo, Zadek!

Bist Du weiter in ALNYLAM investiert? Wie beurteilst Du die Aussichten der Aktie in den kommenden 6-12 Monaten?

Die News der letzten Zeit waren aus meiner Sicht durchaus vielversprechend. Allerdings ist die Bewertung der Firma auch nicht so ganz ohne, und das ohne marktfähiges Produkt in absehbarer Zeit von 2-3 Jahren. Die Kursausschläge sind relativ groß, die Umsätze an den deutschen Börsen hingegen dürftig. (Und an die US-Börsen habe ich mich, obwohl bei der Comdirect ohne große Probleme möglich, wegen der relativ hohen Gebühren bislang nicht gewagt.)

Gruß, ts.

[traumstrand]

Kann mir jemand hier z.B. mit Charttechnik weiterhelfen???

[chancenmaster]

Bin zwar selbst nicht investiert. Ich habe aber einen Artikel dazu in der "Bild der Wissenschaft",Ausgabe 5/2005, Seite 36 und 37 dazu gefunden. Ich habe leider keine Möglichkeit diesen hier reinzustellen.
Anscheinend sind mehrere Biotechfirmen hier schon tätig. Namentlich genannt sind Acuity Pharmaceuticals (Begann bereits im Oktober 2004 eine klinische Studie) aus Philadelphia, Sirna Therapeutics (Studie ab November 2004) aus Boulder, Colorado und Alnylam (will in 2005 mit Freiwilligen Tests beginnen).

Gruß chancenmaster

[cyberhai]

Hallo !

Ist von Euch noch jemand bei Alnylam investiert?

Gruß Cyberhai

[cyberhai]

Alnylam legt heute wieder im 2-stelligen Prozentbereich zu



Gruß Cyberhai

[parakeet_luck]

ist auf jeden fall auch ein kandidat - siehe SIRNA

[traumstrand]

Ich denke, daß die Technologie von Alnylam sehr vieelversprechend ist, aber die Firma ist doch bereits extrem teuer bewertet, oder?

[cyberhai]

Die sind aktuell mit 208.64 Mio. Dollar bewertet, sollte die Technologie erfolgreich sein, kann sich der Wert einiges mehr als verzehnfachen...

Gruß Cyberhai

[cyberhai]

Hier die Meldung für das heutige Plus von mehr als 40 %:

Novartis kooperiert mit Alnylam und beteiligt sich mit 20 Prozent

Die schweizerische Novartis AG (ISIN CH0012005267/ WKN 904278), der viertgrößte Pharmakonzern in Europa, meldete am Mittwoch, dass sie mit der amerikanischen Alnylam Pharmaceuticals Inc. (ISIN US02043Q1076/ WKN A0CBCK) eine mehrjährige Kooperation geschlossen hat.

Bei der Zusammenarbeit im Bereich der Gentherapie RNAi (RNA interference) wird Novartis zunächst 56,8 Mio. Dollar an Alnylam zahlen und sich zudem mit 19,9 Prozent an dem US-Unternehmen beteiligen. Man wird demnach 4,2 Millionen Alnylam-Aktien zu je 11,11 Dollar erwerben. Ohne Lizenzgebühren beläuft sich das Gesamtvolumen der Zahlungen an Alnylam - im Rahmen der auf zunächst drei Jahre angelegten Kooperation - auf voraussichtlich über 700 Mio. Dollar.

Die Aktie von Novartis notiert an der virt-x aktuell bei 61,00 Schweizer Franken (+0,08 Prozent), die von Alnylam Pharmaceuticals schloss gestern an der NASDAQ bei 9,56 Dollar.

Gruß Cyberhai

[traumstrand]

@ Zadek

Gibt es einen Grund für den Rückgang des Kurses in den letzten Wochen? Oder nur News-Flaute?

[cyberhai]

Alnylam Added to NASDAQ Biotechnology Index
Monday November 14, 8:00 am ET

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 14, 2005--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that it will be added to the NASDAQ Biotechnology Index (Nasdaq: NBI - News), effective with the U.S. market open on Monday, November 14, 2005.

ADVERTISEMENT
"We are proud to be selected to join the NASDAQ Biotechnology Index," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "We believe our inclusion in this index reflects the increased awareness in the investment community of the potential of RNAi for therapeutic applications, and the importance of translating this breakthrough in biology into innovative medicines."

The NASDAQ Biotechnology Index was launched in 1993 and includes biotechnology and pharmaceutical companies listed on the NASDAQ National Market that meet minimum requirements for market value, average daily share volume and seasoning as a public company. The NASDAQ Biotechnology Index is ranked on a semi-annual basis in May and November and serves as the basis for the iShares NASDAQ Biotechnology Index Fund(SM) (AMEX:IBB - News). For more information about the NASDAQ Biotechnology Index, including eligibility criteria, visit www.nasdaq.com.

[Zadek]

[posting]18.333.361 von traumstrand am 18.10.05 19:16:09[/posting]Sieht doch wieder gut aus, auch ohne news:



Zadek

[traumstrand]

[posting]19.261.777 von Zadek am 12.12.05 18:22:04[/posting]Hättest Du mir ja auch im Oktober sagen können, daß man hier wieder 40% machen kann...

[cyberhai]

Alnylam Announces Pandemic Flu as Next Development Program
Wednesday December 14, 6:00 am ET
Obtains Initial Federal Funding to Develop RNAi Therapeutics for Pandemic Influenza and Identifies Dowpharma(SM) as Potential Source for Domestic Manufacturing

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 14, 2005--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today its decision to advance its pandemic flu project as a development program, adding to the company`s growing pipeline of RNAi therapeutics. Alnylam also announced that it has received initial government funding for the program from the Department of Defense`s `Defense Advanced Research Projects Agency` (DARPA). Alnylam expects to submit an investigational new drug (IND) application for an RNAi therapeutic for pandemic flu as early as the end of 2006.

In addition, Alnylam also announced today that Dowpharma(SM) contract manufacturing services, a business unit of The Dow Chemical Company (Midland, Michigan), has signed a letter of support indicating its desire and intent to cooperate with Alnylam relating to the manufacture of an RNAi therapeutic for pandemic flu, creating the opportunity for domestic production.

Alnylam will continue its ongoing research collaborations relating to influenza with the University of Georgia and researchers at St. Jude Children`s Research Hospital.

"We believe that RNAi therapeutics can play an important role in effective preparedness for a global influenza pandemic, providing a new option for the treatment and prevention of highly virulent strains of flu," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "Our recent success in initiating clinical studies for ALN-RSV01, an RNAi therapeutic for respiratory syncytial virus infection, lays the groundwork for rapidly developing a therapeutic for flu. Moreover, with initial federal funding, the support of Dowpharma, and our relationships with world-leading academic centers, we are building a strong collaborative network in both the private and public sectors to address a potentially major global health issue."

The Alnylam pandemic flu program is focused on the development of an RNAi therapeutic targeting sequences that are highly conserved across all flu genomes, including those of avian origin such as the H5N1 strain. This RNAi therapeutic would be expected to have anti-viral activity against any newly emerging strain of influenza that could cause human disease. The company believes that such an RNAi therapeutic could be stockpiled in advance of a flu pandemic as a complement to vaccines and other anti-virals.

Alnylam will be presenting updates on its research and development programs, including its pandemic flu program, at its R&D Day to be held this morning at 9:00 a.m. ET at Le Parker Meridien in New York City. The event will be webcast live on the "Investors" section of the company`s website at www.alnylam.com. A replay of the presentation will be posted on the Alnylam website approximately three hours after the event, and will be archived for 30 days.


Gruß Cyberhai

[Zadek]

Die Analysten von Banc of America Sec. bewerten in ihrer Analyse vom Freitag, 16. Dezember 2005 die Aktie von Alnylam Pharmaceuticals Inc. neu mit dem Rating "Buy". Das Kursziel für die Aktie liegt momentan bei 18 $.

Zadek

[cyberhai]

Press Release Source: Alnylam Pharmaceuticals, Inc.

Alnylam Initiates Second Phase I Clinical Study of ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection
Monday December 19, 8:00 am ET
Both U.S. and European Trials Now Underway

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 19, 2005--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that it has initiated a Phase I study in the U.S. to evaluate the human safety and pharmacology of ALN-RSV01, an RNAi therapeutic, in healthy volunteers. Earlier this month, Alnylam initiated its first Phase I study in Europe and reported the clearance of its investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA).

"RSV infection is a cause of serious disease and hospitalization in infants, the elderly, and others with compromised immune systems," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "ALN-RSV01 has the potential to be a novel approach for the treatment of RSV, an area where an effective anti-viral is clearly needed. We look forward to continuing to advance this important program through the clinic. We expect that combined results from our two Phase I studies will provide us with safety data from over 90 volunteers, representing one of the most extensive human clinical experiences with an RNAi therapeutic."

Trial Details

Alnylam is currently conducting two Phase I trials with ALN-RSV01. The trial underway in the U.S. is expected to enroll 35 healthy adult male volunteers. According to the protocol, drug or placebo will be administered intranasally in single ascending doses across five cohorts. The second trial, underway in Europe, was designed to enroll 57 healthy adult male volunteers. The protocol states that drug or placebo will be administered intranasally in both single ascending doses across three cohorts and in multiple ascending doses daily for five consecutive days across three cohorts. In both studies, ALN-RSV01 will be evaluated for safety, tolerability, and pharmacokinetics. Alnylam expects to have preliminary data available from these trials in the first half of 2006.

Pre-clinical Data

ALN-RSV01 is a small interfering RNA (siRNA) that is designed to selectively and potently silence the RSV nucleocapsid `N` gene. This gene is among the most highly conserved genes in the virus and is essential for RSV replication. Data presented to date show both in vitro and in vivo efficacy of ALN-RSV01 in pre-clinical studies. Intranasally delivered ALN-RSV01 specifically inhibits RSV replication in animals and is active in the prevention and treatment of RSV infection. Additionally, Alnylam scientists have reported completion of GLP toxicology studies for ALN-RSV01 without any significant toxicities being observed.

About Respiratory Syncytial Virus (RSV)

RSV is a highly contagious virus that causes infections in both the upper and lower respiratory tract. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems, and others. RSV infection typically results in cold-like symptoms but can lead to more serious respiratory illness such as croup, pneumonia, bronchiolitis, and in extreme cases, death. RSV infection in the pediatric population accounts for more than 100,000 hospitalizations per year in the U.S. The development of childhood asthma is also known to occur after childhood RSV infection. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. These synthetic siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

[Zadek]

Alnylam Shares Jump on 2006 Outlook
Monday January 9, 3:36 pm ET
Alnylam Shares Rise As Company Projects Strong Funding in 2006


CAMBRIDGE, Mass. (AP) -- Alnylam Pharmaceuticals Inc. shares jumped Monday after the drug developer forecast strong funding in 2006 and an analyst said the company`s technology appeared to be developing more quickly than expected.
The company`s stock rose $1.04, or 8 percent, to $14.06 in afternoon trading on the Nasdaq.

Alnylam said that it expects $15 million in alliance-based funding in 2006, including performance-based payments from Merck, Medtronic and Novartis.

Rodman & Renshaw`s Michael G. King said this figure is larger than he had expected, suggesting a quickened pace for the company`s technology development.

The company also said it plans to submit an application to regulators for a treatment for pandemic flu as soon as the end of 2006.

King kept his price target at $16 for Alnylam and said he expects the stock to outperform its sector.

Zadek

[cyberhai]

Neue Patentsache:

http://biz.yahoo.com/bw/060124/20060124005595.html?.v=1

[Aberhallox]

Hallo zusammen,

interessanter Thread, interessantes Unternehmen - und es gibt News in Form von Insiderkäufen. Ein gewisser Paul Schimmel (Director) hat 100.000 Stück für 13 Dollar gekauft (Ende Januar). Ein Zeichen für weiter steigende Kurse?

Gruß
Aberhallox

[cyberhai]

Hallo Aberhallox,

dieser Insiderkauf ist glaube ich im Rahmen der Kapitalerhöhung erfolgt. Bei Yahoo steht: * Indicates that some (or all) shares are held indirectly (e.g. in a trust, by a spouse, etc.). Hier der Link: http://biz.yahoo.com/t/96/1041.html. Der Director hält jetzt mehr als 500 k Aktien, was mich sehr positiv stimmt.

Jedenfalls könnte die Technik von Alnylam und Sirna im Biotechsektor eine Revolution auslösen. Das haben die Big Player erkannt und sind eingestiegen.

Gruß Cyberhai

[cyberhai]

Hier mal ein Überblick der Pipeline:



Gruß Cyberhai

[cyberhai]

Alnylam Receives Biotechnology Industry`s Most Prestigious Award For Corporate Excellence
Tuesday February 14, 4:18 pm ET
Awarded the James D. Watson Helix Award at BIO CEO & Investor Conference

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 14, 2006--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced that it has been awarded the James D. Watson Helix award for corporate excellence in the `emerging/mid-cap` category. The award was announced today at the 8th Annual BIO CEO & Investor Conference in New York. The Helix award, the biotechnology industry`s sole award for outstanding corporate achievement, honors biotechnology companies that display leadership in three distinct areas: product development, economic growth, and corporate citizenship.

"We are deeply honored to be chosen as a recipient of the Helix award," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "We have made great progress at Alnylam over the last year in our effort to advance the field of RNAi for the development of innovative medicines to make a significant difference in patients` lives. In 2005, we transitioned to a clinical-stage company and signed a major collaboration with Novartis to discover and develop RNAi therapeutics. We are sincerely grateful to our industry peers for their recognition of our progress and accomplishments."

"When we founded Alnylam in 2002, we recognized the potential of harnessing the impact and discovery of RNAi to create a whole new class of human therapeutics," said Phillip A. Sharp, Ph.D., Institute Professor of MIT, Nobel Laureate, and co-founder of Alnylam and Biogen Idec. "It is truly gratifying to see Alnylam`s efforts recognized by the biotechnology industry, as we aim to create a leading biopharmaceutical company such as those that emerged from other important biological discoveries like recombinant DNA and monoclonal antibody technologies."

As this year`s recipient, Alnylam becomes the fifth `emerging/mid-cap` biotechnology company to receive the Helix award. Alnylam joins Genentech and Novo Nordisk who are this year`s large cap and international Helix award recipients, respectively.

[cyberhai]

Falls es jemand interessiert, die Quartalszahlen sind da:

http://biz.yahoo.com/bw/060215/20060215006088.html?.v=1

Gruß Cyberhai

[cyberhai]

Novartis and Alnylam Announce New Collaboration to Develop RNAi Therapeutics for Pandemic Flu
Tuesday February 21, 7:00 am ET

CAMBRIDGE, Mass. & BASEL, Switzerland--(BUSINESS WIRE)--Feb. 21, 2006--Novartis (NYSE: NVS - News) and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that they have formed a new collaboration to develop RNAi therapeutics for pandemic flu. This collaboration is in addition to the collaboration formed by the two companies in September 2005, and significantly reinforces the development program for pandemic flu announced by Alnylam in December 2005. In the newly formed collaboration, Alnylam and Novartis will advance RNAi therapeutics for pandemic flu to initial clinical testing and, if successful, regulatory approval. This new alliance leverages Alnylam`s expertise in RNAi and Novartis` capabilities and experience in bringing innovative therapeutics to patients. Financial terms were not disclosed.

"We are delighted to work with our colleagues at Alnylam to devise new therapies for influenza. The influenza virus, through rapid mutation and potential inter-species transfer, represents an epidemic threat to the citizens of all countries. Multiple therapies are likely to be required both to prevent and to treat influenza," said Mark Fishman, M.D., President of the Novartis Institutes for BioMedical Research. "An RNAi therapeutic could be an innovative modality, crippling the virus through incapacitating several genes. In addition, such drugs might be adapted to new strains as they emerge. Of course, the technology is young and is just now being tested in early clinical trials, but our hope is that it will open new therapeutic frontiers."

In December 2005 Alnylam announced that it had selected its pandemic flu program as a development program. The company also announced that it had received initial government funding for the program from the Department of Defense`s `Defense Advanced Research Projects Agency` (DARPA). The focus of the program is the development of an RNAi therapeutic targeting sequences both specific for particular strains and conserved across all flu strains, including those of avian origin. This RNAi therapeutic would be expected to have anti-viral activity against any newly emerging strain of influenza capable of causing human disease and leading to a pandemic, including any variant of the H5N1 strain.

"Having experienced the benefits of collaborating with Novartis over the last several months, we are delighted to partner with them in tackling what may be the biggest public health threat facing the world today," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "Working together with Novartis and government agencies, we are confident in our ability to harness the power of RNAi to help prepare for the possibility of a global influenza pandemic. This new collaboration significantly enhances the efforts we announced in December 2005 to advance our RNAi therapeutic program in pandemic flu toward the clinic."

Quelle: http://biz.yahoo.com/bw/060221/20060221005432.html?.v=1

[cyberhai]

Alnylam hat heute auf 52-Wochen-Hoch geschlossen:

ALNYLAM PHARMACEUT (RT-ECN)
Symbol: ALNY
Last Trade: 15.43 3:59PM ET
After Hours Change: N/A
Today`s Change: Up 1.39 (9.90%)
Bid: 15.37
Ask: 15.50

52wk Range: 6.80 - 15.43

Gruß Cyberhai

[Zadek]

ATH Intraday heute über 17 Dollar

Zadek

[cyberhai]

Habe heute nochmals nachgekauft.

Gruß Cyberhai

[cyberhai]

Alnylam ist auch im avian flu index:

http://yahoo.smartmoney.com/aheadofthecurve/index.cfm?story=…

Gruß Cyberhai

[traumstrand]

Kann mich nachwievor nicht entscheiden, ALNY zu kaufen, da für meine Größenordnung (comdirect) die Orderkosten in USA zu hoch sind und in Dutschland kein sinnvoller Handel stattfindet.


@ Zadek:

Schaust Du noch hin und wieder zu November AG (NBX) ??? - Die sind eigentlich auch beim Thema Vorgelgrippe gut mit dabei und vielleicht mit mehreren Ihrer Produkte rasch am Start zu Diagnostik und Impfstrategien... Dort scheint sich die Aktionärskommunikation verbessert zu haben, größere positive News könnten bevorstehen... Wäre nett, mal wieder Deine Meinung dort im Thread zu vernehmen!

[cyberhai]

Ich habe meinen größten Posten auch in Deutschland gekauft, in Frankfurt wir immer ein Kurs gestellt, nur der Spread ist natürlich etwas höher als in den USA...

Gruß Cyberhai

[cyberhai]

Gen-Probe Licenses HPA Technology to Alnylam to Measure Interfering RNAs in Drug Development
Thursday March 9, 4:05 pm ET

SAN DIEGO, March 9 /PRNewswire-FirstCall/ -- Gen-Probe Incorporated (Nasdaq: GPRO - News) announced today that it has licensed to Alnylam Pharmaceuticals, Inc.,(Nasdaq: ALNY - News), a leading RNAi therapeutics company, non-exclusive rights to use Gen-Probe`s hybridization protection assay (HPA) technology in the development of therapeutic RNA interfering (RNAi) molecules. Financial terms were not disclosed.

"This agreement enables us to generate economic value from our proprietary technologies in an exciting, growing area that is outside our molecular diagnostic focus," said Martin Edelshain, Gen-Probe`s vice president of corporate development.

Alnylam is a leader in developing therapeutics based on RNAi, which is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human disease.

In developing RNAi therapeutics, researchers must be able to monitor the biodistribution of the drugs throughout the body. Gen-Probe`s HPA technology detects these circulating RNAi molecules. With this technology, a specific DNA probe is labeled with an acridinium ester detector molecule that emits light when the probe hybridizes (binds) with its specified target. A luminometer detects and measures the light emitted from the reaction, if any. If no light is generated, the target RNAi molecule is not present in the sample. Based on the high sensitivity of HPA, researchers can use it to detect target molecules without employing cumbersome and time-consuming amplification steps.

[cyberhai]

First Demonstration of Therapeutic Gene Silencing in Primates with Systemic RNAi Published in Nature by Alnylam Scientists
Sunday March 26, 12:00 pm ET
Systemic RNAi Shown to have Durable Effect and Feasible Dosage for Future Human Clinical Studies
Company Holding Conference Call at 8:30 a.m. Monday, March 27, 2006 to Discuss Results

CAMBRIDGE, Mass.--(BUSINESS WIRE)--March 26, 2006--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today the first published demonstration in primates that a systemically delivered RNAi therapeutic can potently silence an endogenous disease-causing gene in a clinically relevant manner. Alnylam and its collaborators at Protiva Biotherapeutics, Inc., demonstrated silencing in primates of the gene for apolipoprotein B (apoB), a protein involved in cholesterol metabolism, with clinically significant efficacy as demonstrated by reductions in levels of cholesterol and low-density lipoproteins (LDL). This peer-reviewed research, published in the world-leading scientific journal Nature, represents a major advance because it suggests that an RNAi therapeutic can be effective when delivered systemically using a dosage appropriate for application in future human clinical studies.

In the published research, Alnylam scientists and collaborators demonstrated potent silencing in primates of the gene for apoB, a disease-causing protein which to date has not been amenable to targeting with traditional small molecule, protein, or antibody therapies. The achievement of this result by systemic administration through the bloodstream demonstrates the broad potential of RNAi therapeutics to target disease-causing genes, and significantly expands the previously demonstrated opportunity for RNAi therapeutics to treat human disease by direct administration to sites of disease, such as with respiratory or ocular delivery.

"We believe that these findings both advance the field of RNAi and expand the opportunity for RNAi therapeutics, as they represent a launching pad to extend beyond our current clinical efforts with direct RNAi therapeutics and address the broader potential of this promising technology with systemic RNAi. These data give us confidence that with further optimization of our systemic RNAi platform we can move a systemic RNAi therapeutic candidate into human clinical trials as early as the next 18-24 months," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "Publication of these robust and well-controlled results in a prestigious journal such as Nature is also further demonstration of Alnylam's leadership position in the field of RNAi, our commitment to scientific excellence and to applying this expertise for development of innovative medicines."

In the study published in Nature, Alnylam scientists and collaborators showed that systemic delivery in non-human primates of a chemically optimized small interfering RNA, or siRNA, can result in silencing of the apoB messenger RNA (mRNA), leading to significant reductions in blood levels of the apoB protein. These effects were proven to occur through an RNAi-mediated mechanism, and resulted in immediate, potent, and durable therapeutic efficacy. The siRNAs were formulated with liposomes that enable delivery to liver cells. The observed therapeutic effects included significant reductions in serum levels of cholesterol and LDL, which together represent the so-called "bad cholesterol" associated with development of atherosclerosis and coronary artery disease. Following administration of a single intravenous bolus dose at low dosages from 1.0-2.5 mg/kg, these reductions were observed as early as 24 hours after treatment and lasted for at least 11 days. A single siRNA injection resulted in dose-dependent silencing of apoB mRNA expression, with maximal silencing of over 90%. The silencing of apoB was proven to occur through an RNAi-mediated mechanism of action. In addition, plasma apoB levels were reduced by more than 75%, cholesterol levels by more than 60%, and LDL levels by more than 80%. In the study of 18 animals, the treatment was well tolerated with only transient liver enzyme elevation observed at the highest dose. We believe the rapid and durable silencing of apoB with RNAi is of clinical relevance, as it may represent a novel strategy for reducing LDL-cholesterol in several clinical settings.

[Zadek]

Alnylam schließt Lizenzabkommen mit Inex und MIT


Die amerikanische Alnylam Pharmaceuticals Inc. (ISIN US02043Q1076/ WKN A0CBCK), an der die schweizerische Novartis AG (ISIN CH0012005267/ WKN 904278) mit fast 20 Prozent beteiligt ist, meldete am Montag, dass sie zwei Lizenzabkommen geschlossen hat.
Demnach wurden Lizenzabkommen unterzeichnet, die dem US-Konzern Zugang zu Schlüsseltechnologien für die systematische Lieferung von RNAi-Therapeutika verschaffen. Die erste Vereinbarung wurde mit der kanadischen Inex Pharmaceuticals Corp. (ISIN CA4499221030/ WKN 899964) geschlossen, die zweite mit dem Massachusetts Institute of Technology (MIT). Finanzielle Einzelheiten wurden dabei nicht genannt.

Die Aktie von Alnylam Pharmaceuticals schloss am Freitag an der NASDAQ bei 17,05 Dollar, die von Inex Pharmaceuticals in Toronto bei 0,50 Kanadischen Dollar.

[Buddah]

Bird Flu is Back!
zudem gefällt der Chart.Alnylam könnte an der 200Tage Linie wieder nach oben drehen.


Gruss B.

P.S. andere Vogelgrippe Aktien sind bereits angesprugen!

[[KERN]Codex]

Antwort auf Beitrag Nr.: 21.776.461 von Buddah am 24.05.06 12:30:44

[Fruehrentner]

News vom Wettbewerb:


First proof of concept
for a siRNA therapy

Acuity Pharmaceuticals has shown the first clinical proof of
concept for a siRNA-based therapy, with positive Phase II
results for its wet age-related macular degeneration treatment,
bevasiranib sodium. Phase III trials are planned for next year.
The Phase II study, which began last October (Scrip No 3101,
p 31), tested the first-in-class siRNA (short interfering RNA) in
129 patients with wet AMD and showed a dose-related
treatment effect across endpoints that included near vision,
lesion size and time to rescue.

Top-line results, which were presented at the American
Society of Gene Therapy meeting recently in Baltimore, US,
also showed bevasiranib was safe and well tolerated. Full
results will be presented at the American Society of Retinal
Specialists in September.

Commenting on the initial findings, the study’s lead
investigator Dr Lawrence Singerman from Case University
said: “Bevasiranib and its unique mechanism has the strong
potential to be useful as a maintenance therapy, first using a
VEGF antagonist to ‘mop-up’ existing VEGF and then using
bevasiranib to stop further production in the eye, and it may
also be an effective new therapy for wet AMD on its own.”
Bevasiranib (formerly Cand5) uses RNA interference to
silence the VEGF genes that promote the retinal
neovascularisation that leads to vision loss in wet AMD.
Other therapies for wet AMD, including Pfizer/Eyetech
Pharmaceuticals’ approved Macugen (pegaptanib sodium),
also target VEGF but inhibit it after it has been produced in
the eye. Acuity’s president and CEO Dr Dale Pfost says that
because bevasiranib stops VEGF production at the source it
should have efficacy advantages over other therapies.

...new siRNA formulations

Meanwhile, SR Pharma has made a technical discovery that
allows its lyophilised, liposomally formulated siRNA
(AtuRNAi) drugs to be stored at room temperature and
reconstituted simply by being mixed with water.
Reconstitution was previously a complicated multi-step
process, so the new formulation will make the AtuRNAi
drugs easier to use when they enter the clinic.
SR Pharma, which acquired the RNAi company Atugen last
June, is concentrating its pipeline on the systemic treatment
of solid tumours and metastases in prostate, lung and
pancreatic cancers and hepatocellular carcinoma. It also has
agreements with Sanofi-Aventis, testing siRNAs in a number
of proof-of-concept animal studies, and Quark Biotech,
covering AMD and other indications.

[Fruehrentner]

Meldung von gestern:


06.07.2006 14:00:00

Alnylam Announces Amendment to Merck Collaboration to Increase Focus on Development of RNAi Therapeutics; Milestone Payments to Alnylam Could Exceed $120 Million


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has amended its two existing RNAi collaboration agreements with Merck and consolidated the efforts into a single ongoing collaboration. The revised terms provide Merck with a more active role in the development of RNAi therapeutic products, and Alnylam with an opportunity to receive accelerated research and development (R&D) funding at an earlier stage and the potential for significant milestones in addition to royalty payments or profit-sharing on any commercialized products resulting from the collaboration.

The collaboration has been amended to focus on the nine new therapeutic targets that remain to be nominated by Merck. Under the revised terms, Merck may participate at an earlier stage in the research and development of these nine targets whereas under the previous agreement, Merck had the right to nominate these new targets for initial development by Alnylam. These new programs are in addition to the existing program directed to the NOGO pathway on which Alnylam and Merck are already collaborating. Also under the revised terms, Alnylam may select three of the nine new programs as joint development programs, which Merck will co-fund and participate in from the outset, thereby providing Alnylam with accelerated R&D funding for its efforts. Previously, the agreement was structured so that co-funding by Merck would not begin until after the completion of defined pre-clinical work. In the U.S., Alnylam will have the right to co-promote RNAi therapeutic products developed in these three programs. Merck will assume primary responsibility for the remaining six programs and Alnylam is eligible to receive milestone payments and royalties on RNAi therapeutic products developed and commercialized by Merck in these programs. Specifically, under the revised terms the successful development and approval of three RNAi therapeutic products developed solely by Merck on a worldwide basis would result in milestone payments to Alnylam of over $120 million.

"We look forward to continuing our productive collaboration with Alnylam," said Stephen Friend, M.D., Ph.D., Executive Vice President, Merck Research Laboratories. "We have seen significant progress in the RNAi field over the past three years and are truly excited by the opportunity to play a continued role in the development of this new class of drugs."

"We are delighted by Merck's continued and increasing enthusiasm for RNAi therapeutics, and their commitment to play an expanded role in our collaboration. We deeply value the commitment from Merck to advance RNAi therapeutic products as a new approach for the discovery of innovative medicines," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "The amended agreement represents a new and stronger phase of our relationship, and significantly increases the ability of both companies to realize value from our collaboration. Indeed, the accelerated funding will bolster our efforts as we aim to bring RNAi therapeutics to patients."

As part of the amended terms, Alnylam will continue its ongoing efforts with Merck to develop an RNAi therapeutic product directed to the NOGO pathway for the treatment of spinal cord injury. However, in light of advances in the treatment of age-related macular degeneration (AMD) and the newly modified agreement, Alnylam and Merck will not jointly advance their July 2004 Ocular Disease alliance and all rights to ALN-VEG01 will be retained by Alnylam. Alnylam is evaluating partnership opportunities for this program, which has shown encouraging pre-clinical efficacy data and has successfully completed investigational new drug (IND) enabling toxicology studies.

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase 1 human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, and Novartis. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans, and prospects, including with respect to the development of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including without limitation risks related to: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; our ability to collaborate successfully with Merck and our other collaborators; obtaining, maintaining, and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties, including without limitation Merck, for development, manufacture, marketing, sales, and distribution of products; the successful development of our product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on Merck and our other collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We do not assume any obligation to update any forward-looking statements.


Quelle:BUSINESS WIRE

[Fruehrentner]

Alnylam and Inex accelerate RNAi collaboration
17th July 2006

By Tom Neilson

Alnylam and Inex Pharmaceuticals are to accelerate their collaboration focused on the systemic delivery of RNAi therapeutics, after the companies made good early progress in the alliance.
Alnylam and Inex formed the collaboration in March 2006. The results to date encourage both parties to believe that Alnylam's RNAi therapeutics can be efficiently encapsulated in Inex's liposomes and effectively delivered to disease sites in animal models to carry out the desired effect of silencing the gene target.

Advertisement"We are enthusiastic to be working with Alnylam on solutions for the systemic delivery of RNAi therapeutics," said Timothy Ruane, president and CEO of Inex. "It is very gratifying to see such promising results after only a few months of working with Alnylam and we are pleased to enter the next phase of our collaboration ahead of schedule."

As part of the collaboration, Alnylam has the option to take worldwide exclusive licenses to use Inex's technology for RNAi therapeutics directed to specific gene targets.

In conjunction with the decision to accelerate the collaboration, Alnylam will make certain payments to Inex totaling approximately $1.9 million, $1 million of which relates to an option to take a broad exclusive license to Inex's technology.


http://www.pharmaceutical-business-review.com/article_news.a…

[Fruehrentner]

Alnylam and University of Texas form cholesterol alliance

17th July 2006
By Tom Neilson

Alnylam Pharmaceuticals has entered into a collaboration with University of Texas to evaluate new approaches for reducing LDL-cholesterol levels using RNAi therapeutics.
In the collaboration, researchers from the company and the University's Southwestern Medical Center will evaluate the use of RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9.

PCSK9 is an important gene involved in the metabolism of LDL-cholesterol, or so-called bad cholesterol. The normal role of the PCSK9 protein is to break down the LDL receptor (LDL-R); when there is less PCSK9 protein, there is more LDL-R on the cell surface.

Research at UT Southwestern Medical Center has shown that reductions in the levels of PCSK9 protein can lead to significant reductions of LDL in the blood, and in fact mice lacking PCSK9 have significantly decreased cholesterol with no other adverse phenotype.

"Although PCSK9 is validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. Therefore, we believe it is an ideal target for a systemic RNAi approach in light of our recent progress with systemic delivery of RNAi therapeutics," Dr Victor Kotelianski, vice president of research for Alnylam Pharmaceuticals.


http://www.pharmaceutical-business-review.com/article_news.a…

[david1]

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Dieser Beitrag wurde vom System automatisch gesperrt. Bei Fragen wenden Sie sich bitte an [e-mail]

[Fruehrentner]

18.07.2006 13:07:00

Alnylam erhält neu erteiltes US-Patent, das 'small interfering RNAs' breit abdeckt, und stärkt damit seine führende Rolle bei Patenten zu RNAi-Therapeutika


Neues Tuschl-II-'196-Patent umfasst Methoden für die Herstellung von 'small interfering RNAs' mit und ohne chemische Modifikationen

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), ein auf dem Gebiet der RNAi-Therapeutika führendes Unternehmen, gab heute bekannt, dass das US-Patent- und Markenamt (USPTO) ein grundlegendes Schlüsselpatent der von Alnylam exklusiv lizensierten "Tuschl-II"-Patentfamilie erteilt hat. Das neu erteilte US-Patent (Nr. 7,078,196 oder "'196-Patent") erfasst breit Methoden für die Herstellung von 'small interfering RNAs' (siRNAs), den Molekülen, die RNAi vermitteln. Es beinhaltet u.a. 79 Ansprüche gerichtet auf chemische RNA-Modifikationen, die zum Einführen von medikamentenartigen Eigenschaften in RNAi-Therapeutika benötigt werden. Alnylam besitzt für das erteilte Patent aufgrund eines Abkommens mit der Garching Innovation GmbH, der Lizenzstelle der Max-Planck-Gesellschaft, die weltweite, exklusive Lizenz für RNAi-Therapeutika. Das '196-Patent stärkt Alnylams Führungsrolle auf dem Gebiet der RNAi-Patente weiter. Zu dieser trägt auch ein weiteres Tuschl-II-Patent (US-Patent Nr. 7,056,704 oder "'704-Patent") bei, das Methoden zur Herstellung von siRNAs zur Adressierung einer beliebigen mRNA in einer Säugerzelle einschließt, sowie auch der jüngste erfolgreiche Ausgang des Europäischen Einspruchsverfahrens gegen das Kreutzer-Limmer-I-Patent (EP 1144623 oder "'623-Patent"). Hierbei wurden überarbeitete Patentansprüche aufrechterhalten, die siRNAs mit u.a. 15-21 Basenpaaren abdecken.

"Wir sind dankbar, dass das USPTO die Schlüsselerfindungen von Professor Thomas Tuschl anerkannt hat, die er am Max-Planck-Institut in Göttingen gemacht hat," sagte Professor Peter Gruss, Präsident der Max-Planck-Gesellschaft. "Dieses entscheidende Patent für RNAi-Therapeutika gehört der Max-Planck-Gesellschaft und wurde exklusiv an Alnylam zur Kommerzialisierung auslizenziert. Wir sind beeindruckt vom Fortschritt Alnylams bei seinen Bemühungen, unter Verwendung einer der bedeutendsten wissenschaftlichen Entdeckungen unseres Instituts innovative Medikamente zu entwickeln."

Das neue '196-Patent ist Teil der im Jahr 2001 von Prof. Dr. Thomas Tuschl, einem Mitgründer von Alnylam, in der Zeitschrift Nature publizierten, wegweisenden Forschungsergebnisse. In dieser bahnbrechenden Arbeit, die ausschließlich am Max-Planck-Institut durchgeführt wurde, haben Prof. Tuschl und seine Max-Planck-Kollegen den ersten, von unabhängigen Experten begutachteten, publizierten Hinweis darauf geliefert, dass RNAi von kurzen doppelsträngigen RNAs mit definierten strukturellen Eigenschaften vermittelt wird, und dass synthetische siRNAs, mit oder ohne chemischen Modifikationen, dazu verwendet werden können, RNAi in Säugerzellen auszulösen. "Dieses neue Patent erweitert unser, wie wir glauben, unvergleichbares und dominantes Patentportfolio für RNAi-Therapeutika, das über 150 Patente in den weltgrößten pharmazeutischen Märkten umfasst", sagte Dr. John Maraganore, Präsident und Vorstandschef der Alnylam Pharmaceuticals, Inc.. "Das '196-Patent stärkt, zusammen mit den anderen Patenten von Alnylam, unsere anhaltenden Bemühungen, Wert durch Partnerschaften und Lizenzabkommen mit größeren pharmazeutischen Unternehmen, Biotechnologiefirmen und Vertreibern von Forschungsprodukten zu schöpfen. Die unerreichte Stärke unseres Patentportfolios ist in der Tat ein weiterer Beleg für die Erfolgsgeschichte des Unternehmens mit derzeit über 20 Partnern und Lizenznehmern, die uns bisher Mittel von über $ 100 Mio. eingebracht haben und auch in Zukunft eine nachhaltige Quelle weiterer zugesagter Mittel darstellen. Strategisch betrachtet unterstützt diese für Alnylam wichtige Geldquelle unsere Bemühungen, RNAi-Therapeutika in effizienter Weise auf den Markt zu bringen."

Die 79 Ansprüche des '196-Patents umfassen die Herstellung von doppelsträngiger RNA mit bestimmten strukturellen Elementen, die für die therapeutische Aktivität von siRNAs als wesentlich erachtet werden, wie

-- einer doppelsträngigen Region aus zwei RNA-Strängen mit einer Länge von 19-25 Nukleotiden und

-- einem oder mehreren 3'-Überhängen an den Enden des doppelsträngigen Moleküls.

Die Ansprüche erfassen siRNAs mit oder ohne chemische Modifikationen, die zum Einführen von medikamentenartigen Eigenschaften in siRNAs, wie Stabilität und Delivery", verwendet werden. Diese chemischen Modifikationen sind dabei breit formuliert, unter anderem die 2'-Hydroxy-Position des Ribose-Rückgrats betreffend, deren Verwendung auch zu sogenannten "no-ribose" oder "siNA" -Formen von RNAi-Therapeutika führt. Insbesondere sind auch die Verwendung von Thiophosphat-Rückgratverknüpfungen, 2'-O-Methyl-, und/oder 2'-Fluoro-Verbindungen beschrieben, und zwar unabhängig vom Prozentsatz der modifizierten Nukleotide und dem Ausmaß solcher Modifikationen.

Die neu erteilten Ansprüche des US-Patents Nr. 7,078,196 werden auf Alnylams Internetseite unter folgendem Link zugänglich gemacht werden: www.alnylam.com/patent-estate.

"Mit der zunehmenden Erteilung von Patenten auf diesem Gebiet sollte es immer klarer werden, dass Alnylam der alleinige Eigentümer von entscheidenden Patenten ist, die für die Entwicklung von RNAi-Therapeutika benötigt werden, oder zu solchen Zugang hat," sagte Robert Millman, Chief Intellectual Property Counsel von Alnylam Pharmaceuticals. "Wegen der Ausführbarkeit und dem frühen Prioritätsdatum des '196-Patents wird es von Patentämtern weltweit häufig als neuheitsschädlich gegenüber später angemeldeten Patentanmeldungen zitiert, die chemisch modifizierte siRNAs beanspruchen."

Über das neu erteilte Tuschl-II-Patent (US-Patent Nr. 7,078,196) hinaus umfasst Alnylams Patentportfolio noch weitere erteilte grundlegende Patente auf den weltgrößten pharmazeutischen Märkten, die breite strukturelle und funktionelle Eigenschaften von synthetischen RNAi-Produkten beanspruchen. Dies betrifft in den USA und Europa allein

-- das Tuschl-II-'704-Patent (US-Patent Nr. 7,056,704), erteilt im Juni 2006, das Methoden zur Herstellung von siRNAs zum Stummschalten jedes beliebigen Krankheitszielgens breit abdeckt,

-- das Kreutzer-Limmer-I-'623-Patent (EP 1144623), erteilt im August 2002 und aufrechterhalten im Juni 2006, das Methoden, Medikamente und die Verwendung von siRNAs mit einer Länge von 15-21 Basenpaaren, neben anderen Merkmalen, abdeckt,

-- das Kreutzer-Limmer-I-'945-Patent (EP 1214945), erteilt im Juni 2005, das die Zusammensetzung, Methoden und die Verwendung von siRNAs mit einer Länge von 15-49 Nukleotiden abdeckt,

-- das Kreutzer-Limmer-II-'061-Patent (EP 1352061), erteilt im Mai 2006, das die Zusammensetzung, Methoden und die Verwendung von bestimmten siRNAs und Derivaten abdeckt, die gegen mehr als 125 Krankheitszielgene gerichtet sind,

-- weitere grundlegende Patente und Patentanmeldungen, die Alnylam exklusiv oder nicht exklusiv lizenziert hat, wie die von Crooke (US-Patent Nr. 5,898,031 und 6,107,094), Fire und Mello (US-Patent Nr. 6,506,559) und Glover et al. (EP 1230375), sowie

-- einige anhängige Teilanmeldungen der vorgenannten erteilten Patente und weitere anhängige Patentanmeldungen, einschließlich Tuschl-I".

Darüber hinaus hat Alnylam die weltweite Lizenz für RNAi-Therapeutika von Isis Pharmaceuticals, Inc. für mehr als 150 erteilte Patente, die bestimmte chemische Modifikationen von Oligonukleotiden zur Einführung von medikamentenartigen Eigenschaften in siRNAs betreffen, insbesondere

-- Thiophosphat- und 2'-O-Methyl-Modifikationen (Buhr, US-Patent Nr. 6,473,205) und

-- 2'-Fluoro-Modifikationen (Cook, US-Patent Nr. 5,670,633; 6,005,087 und 6,531,584).

Alnylam ermöglicht interessierten Lizenznehmern, zusätzlich zu den im '196-Patent erteilten Ansprüchen, die Einsicht in erteilte Ansprüche von Alnylams Schlüsselpatenten unter www.alnylam.com/patent-estate.

Über RNA-Interferenz (RNAi)

Die RNA-Interferenz (RNAi) ist ein natürlicher, in den Zellen ablaufender Mechanismus zur selektiven Inhibierung und Regulation spezifischer Gene. Da viele Krankheiten ihre Ursache in einer fehlerhaften Aktivität bestimmter Gene haben, könnte das selektive Stummschalten dieser Gene mit Hilfe der RNAi neue Möglichkeiten bieten, eine Vielzahl von Krankheiten beim Menschen zu behandeln. Die RNAi wird von kurzen doppelsträngigen RNA-Molekülen vermittelt. Eine Methode zum Auslösen der RNAi stellt die Verwendung von chemisch synthetisierten 'small interfering RNAs' oder siRNAs dar. Dies sind kurze doppelsträngige RNAs, die gegen ein bestimmtes krankheitsassoziiertes Gen gerichtet sind. Diese siRNA-Moleküle werden von der natürlichen RNAi-Maschinerie der Zellen für ein hoch spezifisches Stummschalten von Genen verwendet.

Über Alnylam

Alnylam ist ein biopharmazeutisches Unternehmen, das neuartige Therapeutika auf Basis der RNA-Interferenz (RNAi) entwickelt. Das Unternehmen setzt seine Expertise im Bereich der therapeutischen RNAi ein, um Krankheiten anzugehen, bei denen der medizinische Bedarf groß ist und die mit kleinen Molekülen oder Antikörpern als den beiden größten derzeit gängigen Medikamentengruppen nicht behandelt werden können. Alnylam arbeitet an einer Reihe von RNAi-Therapeutika, wobei sich das am weitesten fortgeschrittene Projekt in der Phase I der klinischen Prüfung zur Behandlung einer Infektion mit dem Respiratory Syncytial Virus (RSV) befindet, die der Hauptgrund für Krankenhauseinlieferungen von Kindern in den USA ist. Die Führungsposition des Unternehmens bei grundlegenden Patenten, der Technologie und dem Know-How zur RNAi hat bedeutende Allianzen mit führenden Firmen möglich gemacht, darunter die mit Merck, Medtronic und Novartis. Das Unternehmen, das 2002 gegründet wurde, hat seinen Hauptsitz in Cambridge, Massachusetts, USA, und eine weitere operative Einheit in Kulmbach, Deutschland. Alnylam fühlt sich geehrt, 2006 bei den "aufstrebenden/mittelständischen" Unternehmen Preisträger des James D. Watson Helix Award zu sein, dem Preis der Biotechnologie für hervorragende Leistungen. Weitere Informationen erhalten Sie unter http://www.alnylam.com.

Über die Max-Planck-Gesellschaft / Garching Innovation

Die 1948 als Nachfolgeorganisation der Kaiser-Wilhelm-Gesellschaft gegründete Max-Planck-Gesellschaft zur Förderung der Wissenschaften (MPG) ist eine unabhängige, gemeinnützige wissenschaftliche Forschungsorganisation. Die MPG unterhält ungefähr 80 Forschungsinstitute vorwiegend in Deutschland. Die Forschungsinstitute widmen sich den Natur- und Lebenswissenschaften, den Sozialwissenschaften und den Geisteswissenschaften. Die MPG ist besonders im Bereich von neuen und innovativen Forschungsgebieten aktiv, die nicht im Fokus deutscher Universitäten liegen. Seit ihrer Gründung hat die MPG 16 Nobelpreisträger hervorgebracht. Die Garching Innovation GmbH, eine von der MPG gehaltene Tochtergesellschaft, fungiert als Technologietransferstelle. Garching Innovation ist für die Vermarktung von geistigem Eigentum zuständig, das in den Forschungsinstituten der MPG entsteht, indem es der Industrie Lizenzen gewährt und die Ausgründung von Unternehmen aus der MPG unterstützt. Bitte besuchen Sie http://www.mpg.de/ und http://www.garching-innovation.de, um weitere Informationen zu erhalten.

Alnylams Aussagen über zukünftige Ereignisse - 'Forward-Looking Statements'

Verschiedene Stellungnahmen in dieser Pressemeldung enthalten gemäß den 'Safe-Harbor'-Vorgaben des US 'Private Securities Litigation Reform Act' von 1995 definierte zukünftige Erwartungen, Pläne, sowie unsere Sichtweise zum Zeitablauf und der zukünftigen Erteilung von Patenten, der Bedeutung und dem Geltungsbereich unserer Schutzrechte und der Entwicklung von RNAi-Therapeutika, so genannte 'Forward-looking Statements'. Tatsächliche Resultate können aufgrund von Risiken und Unwägbarkeiten in beträchtlichem Umfang von den Aussagen über zukünftige Ereignisse abweichen. Solche betreffen insbesondere unseren Ansatz zur Erforschung und Entwicklung neuartiger Medikamente, der bislang noch nicht vollständig belegt ist und möglicherweise nicht zu vermarktbaren Produkten führt, die Erteilung, Pflege und den Schutz von Patentrechten am geistigen Eigentum, das von unseren Produkten angewendet wird, die Fähigkeit, unsere Patente gegen Verletzer durchzusetzen und unser Patentportfolio gegen Anfechtungen Dritter zu verteidigen, unsere Fähigkeit zusätzliches Kapital zur Finanzierung unserer Geschäftstätigkeit einzuwerben, unsere Abhängigkeit von Dritten bei der Entwicklung, Herstellung, Vermarktung, dem Vertrieb und Verkauf unserer Produkte, die erfolgreichen Entwicklung unserer Produkte, von denen sich alle in frühen Entwicklungsphasen befinden, die Erteilung von Zulassungen für Produkte, unsere Wettbewerber, die mit ähnlichen Technologien ähnliche Produkte für ähnliche Anwendungen entwickeln, unsere Abhängigkeit von Kooperationspartnern, die kurze Unternehmensgeschichte, sowie Risiken, die im Abschnitt 'Risk Factors' unseres jüngsten Quartalsberichts im US 10-Q-Dokument (Form 10-Q) diskutiert werden, das wir bei der amerikanischen Securities and Exchange Commission eingereicht haben. Darüber hinaus repräsentieren alle Aussagen über zukünftige Ereignisse unsere heutige Sicht der zukünftigen Entwicklung und dürfen nicht als vorausschauende Aussagen gültig ab einem zukünftigen Zeitpunkt gewertet werden. Einer Verpflichtung zur Aktualisierung von vorausschauenden Aussagen wird hiermit ausdrücklich widersprochen.

Sollte eine Interpretation des oben stehenden deutschen Texts im Widerspruch zu den Aussagen des englischen Originals dieser Pressemitteilung stehen, so gilt das englische Original; das englische Original kann eingesehen werden unter:

http://www.alnylam.com/news


Quelle:BUSINESS WIRE

[Fruehrentner]

es gibt News:


21.08.06 15:45


NEW YORK (AFX) - Drug maker Alnylam Pharmaceuticals Inc. said Monday it has granted Arrowhead Research Corp.'s unit Calando Pharmaceuticals a license to develop a new drug.

The license allows Calando to discover, develop and commercialize an RNAi therapeutic using a synthetic siRNA, together with Calando's proprietary technology, that is directed toward a cancer target. RNAi, or RNA interference, is a naturally occurring mechanism in cells for selectively silencing and regulating specific genes.

Financial terms of the agreement were not disclosed, but include upfront, annual, and milestone payments, and royalties on sales of products covered by the license. Under the agreement, Calando also has an option to acquire a license for a second target gene.


Copyright 2006 Associated Press. All rights reserved. This material may not be
published, broadcast, rewritten, or redistributed.

[Fruehrentner]

Alnylam and Calando sign cancer licensing agreement

22nd August 2006

By Helen Marshall
Alnylam Pharmaceuticals has granted Calando Pharmaceuticals, a majority-owned subsidiary of Arrowhead Research Corporation, a license to discover, develop, and commercialize an RNA interference therapeutic directed towards a cancer target.
RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases.

Detailed financial terms of the deal were not disclosed, but include upfront, annual, and milestone payments, and royalties on sales of any products covered by the licensing agreement.

As part of the agreement, Calando also has an option to acquire an InterfeRx license for a second target gene.

Alnylam created the InterfeRx licensing program to grant licenses under this intellectual property to biotech and pharmaceutical companies wishing to pursue RNAi therapeutics against specific targets outside Alnylam's core strategic interests. In addition to Calando, Alnylam's InterfeRx licensees include Nastech Pharmaceutical, GeneCare Research Institute, and, under an option agreement, Benitec.


http://www.pharmaceutical-business-review.com/article_news.a…

[Fruehrentner]

Meldung vom 06. September:

06.09.2006 14:00:00

Alnylam Awarded Federal Grant to Develop RNAi Therapeutics for Pandemic Flu


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), has awarded the company a Small Business Innovation Research (SBIR) grant to advance the development of RNAi therapeutics for pandemic influenza. The SBIR grant will provide Alnylam with approximately $590,000 in funding over a one-year period to support the company's research efforts on small interfering RNAs (siRNAs), the molecules that mediate RNAi, as anti-viral drugs with broad spectrum activity toward multiple influenza strains including the H5N1 virus.

"This grant recognizes the potential of RNAi therapeutics as a new class of anti-viral drugs for the treatment and prevention of highly virulent strains of flu and the promising pre-clinical data emerging from our flu program," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "This grant also represents a continuation of our ongoing public sector-private sector partnership to advance RNAi therapeutics for pandemic flu. In addition to this grant from the NIAID, we have submitted a response to the Request for Proposal from the Department of Health and Human Services for advanced development of new anti-viral agents for influenza."

Alnylam's flu program, partnered with Novartis, is focused on the development of RNAi therapeutics targeting sequences that are common to all flu genomes, including those of avian origin such as the H5N1 strain. Earlier this year, Alnylam scientists and academic collaborators demonstrated in vitro anti-viral activity toward a human clinical isolate of the H5N1 virus. These potent effects toward H5N1 were achieved with multiple siRNAs that also showed anti-viral activity toward other flu strains. The alliance's lead RNAi therapeutic candidate, ALN-FLU01, is comprised of two siRNAs that target distinct, highly conserved gene sequences of the flu genome. Studies for the flu program are currently being conducted under ongoing research collaborations with the University of Georgia and St. Jude Children's Research Hospital. The company has received initial government funding for its pandemic flu program from the Department of Defense's "Defense Advanced Research Projects Agency" (DARPA). In addition, Alnylam has the support of Dowpharma(SM) contract manufacturing services, a business unit of The Dow Chemical Company, relating to the manufacture of an RNAi therapeutic for pandemic flu, creating the opportunity for domestic production.


About Pandemic Influenza

An influenza pandemic is a global outbreak of disease that occurs when a new flu virus appears in the human population, causes serious illness, and spreads easily from person to person. Experts believe that current vaccines and existing anti-viral agents may not be sufficient to protect against newly emerging strains of influenza virus. Over the last several years, a highly virulent new strain of avian flu (H5N1) has become endemic in the poultry population in Southeast Asia, has spread to parts of Europe and Africa, and has caused significant mortality in humans that have been infected. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) have expressed major concern about the potential for this virus to mutate into a form that could cause a global pandemic of human disease.


About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, and Novartis. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans, and prospects, including our plans with respect to the discovery and development of an RNAi therapeutic for pandemic influenza, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of our product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Quelle:BUSINESS WIRE

[Zadek]

CAMBRIDGE, Mass (AFX) - Drug developer Biogen Idec Inc. (Nachrichten/Aktienkurs) and Alnylam Pharmaceuticals Inc. (Nachrichten) said Wednesday they are collaborating to develop a treatment for a deadly neurological disorder.
The companies will research RNAi technology to develop a treatment for progressive multifocal leukoencephalopathy, caused by a virus infection of the central nervous system. The condition occurs in immune-suppresed patients and affects the brain, often causing death or disability.
RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules.
Cambridge, Mass.-based Biogen will fund all research and development activities and pay a $5 million upfront fee to Alnylam, which is also based in Cambridge. Alnylam could receive up to $51 million in milestone payments and royalties if a successful product is developed from the technology.

[BrokerPK]

wie ist die aktuelle Meinung zur Aktie Alnylam und im Vergleich zur Aktie Sirna von euch??

Sind ja beide im aussichtsreichen RANi-Bereich aufgestellt...!!

[Zadek]

NEW YORK (AFX) - Alnylam Pharmaceuticals Inc. (Nachrichten) said Tuesday it licensed two genes to Quark Biotech Inc., which turned around and licensed one to drugmaker Pfizer Inc. to develop a treatment for wet age-related macular degeneration.

Alnylam licensed the genes p53 and RTP801 to Quark for an undisclosed amount. The agreement includes upfront, annual, and milestone payments, along with royalties on any product that makes it to market. The licenses cover RNAi, or RNA interference therapeutics, or drugs that use a naturally occurring mechanism in cells for selectively silencing and regulating specific genes.

Quark said it granted an exclusive worldwide license to Pfizer to develop the RTP-801 gene as a treatment for wet age-related macular degeneration. Financial details were not disclosed.

Wet AMD is a condition where abnormal blood vessels grow over the retina and leak, causing scar tissue and destroying a person's central field of vision. The Federal Trade Commission still needs to approve the deal.

Pfizer already has a partnership with OSI Pharmaceuticals Inc. for the FDA-approved wet AMD treatment Macugen. Pfizer spokesman Paul Fitzhenry said that the RTP801 gene is still in very early preclinical development and that the company could not comment on what a resulting drug's possible profile might be.

A competing drug to Macugen, Genentech Inc.'s Lucentis, received FDA-approval in June.

The p53 gene is likely to be developed for the treatment of kidney disease.

Alnylam shares added 45 cents, or 3.3 percent, to $14.09, while OSI shares rose 9 cents to $37.21 in morning trading on the Nasdaq. Shares of Pfizer were down 1 cent to $28.34 on the New York Stock Exchange.


Copyright 2006 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

[Fruehrentner]

Der Nobelpreis 2006 für die Entdeckung der RNA-Interferenz beflügelt offenbar derzeit Alnylam!

[Fruehrentner]

04.10.2006 14:00:00

Alnylam Notified of Defense Appropriation Funding for Ongoing Development of RNAi Therapeutics


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the Department of Defense Appropriations Act of 2007, passed by Congress last week, includes $1.1 million of funding dedicated to Alnylam's ongoing development of RNAi therapeutics. Congressional support for this effort builds upon existing public sector-private sector partnerships that the company has formed to develop RNAi therapeutics for public health. This appropriation, combined with earlier funding from the government, supports the goal of Alnylam Biodefense to build a robust platform for developing RNAi therapeutics to combat natural or man-made biological threats that pose a potential risk to public health and national security.

"We are pleased to receive this support from the U.S. Congress to develop a broad-spectrum RNAi therapeutics platform," said Barry Greene, Chief Operating Officer of Alnylam. "We believe this additional funding recognizes the potential of RNAi therapeutics as a broad platform technology that could enable the rapid and reproducible generation of pharmacological countermeasures against bioterrorism threats. With this funding and additional funding from the National Institutes of Health for the development of an RNAi therapeutic targeting the Ebola virus, we are advancing our Alnylam Biodefense efforts to meet bio-preparedness needs for U.S. military personnel and the nation. In addition, we intend to use this appropriation funding to strengthen our overall platform capabilities and its applications for discovery of RNAi therapeutics for traditional clinical indications."

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, and Biogen Idec. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans, and prospects, including our plans with respect to building a platform to discover and develop RNAi therapeutics to combat biological threats, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of our product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Quelle:BUSINESS WIRE

[Fruehrentner]

Alnylam initiates early stage trial of respiratory treatment

12th October 2006
By Staff Writer

RNAi therapeutics company Alnylam has initiated a phase I trial of an inhaled form of ALN-RSV01 for the treatment of respiratory infection.

The trial has been launched in the US to determine the safety, tolerability, and pharmacokinetics of the drug in healthy adult volunteers.

The inhaled formulation of ALN-RSV01 used in this phase I study is a nebulized formulation, and advances previous clinical work for ALN-RSV01 administered as an intranasal spray. ALN-RSV01 is an RNAi therapeutic in clinical development for the treatment of respiratory syncytial virus (RSV) infection.

This newly initiated phase I trial with inhaled ALN-RSV01 uses a formulation that is designed to deliver the RNAi therapeutic to the lungs, and is the expected formulation for the treatment of RSV in naturally infected patients. Models of this aerosolized formulation of ALN-RSV01 predict that it can be delivered to the alveoli and the small airways of the infant and adult human lung.

Alnylam previously completed two phase I human clinical trials of ALN-RSV01 using an intranasal formulation. The previous studies demonstrated that ALN-RSV01 was safe and well tolerated when administered intranasally in relevant doses to human volunteers and had a profile comparable to placebo.

Later this year, the company expects to initiate an experimental infection, or "viral challenge," study with the intranasal formulation of ALN-RSV01 in healthy adult volunteers.


http://www.pharmaceutical-business-review.com/article_news.a…

[Fruehrentner]

16.10.2006 15:00:00

Alnylam Announces Progress in Pre-clinical Programs at the 36th Annual Society for Neuroscience Meeting


Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it presented pre-clinical data at the 36th Annual Society for Neuroscience Meeting being held in Atlanta, Georgia from October 14-18, 2006. Alnylam, in an alliance with Medtronic, Inc., and with its academic collaborators, presented pre-clinical data from four ongoing neurology programs including Huntington's disease, neuropathic pain, Parkinson's disease, and dystonia. Accumulating data show that small interfering RNAs (siRNAs), the molecules that mediate RNAi, can be administered in vitro and in vivo in animal models of neurological diseases to achieve therapeutic silencing of disease-causing genes.

"Data presented at the Society for Neuroscience meeting demonstrate in pre-clinical studies that RNAi provided a highly selective and effective inhibition of disease targets involved in pathologies of the nervous system," said Dinah Sah, Ph.D., Senior Director of Research at Alnylam. "We believe these results support our strategy of advancing RNAi therapeutics to treat serious neurological diseases and reflect the progress that Alnylam and our partners and collaborators are making in developing this promising therapeutic modality for significant unmet medical needs."

Huntington's Disease

In a poster titled "Widespread distribution of siRNAs targeting Huntingtin in the CNS after chronic intrastriatal infusion," Alnylam and Medtronic presented pre-clinical data demonstrating that siRNAs specific for the huntingtin gene, which is mutated in Huntington's disease, were administered in vivo to achieve silencing of the disease-causing gene. In addition, the majority of the siRNAs tested were effective at reducing levels of Huntingtin protein, and in reducing messenger RNA (mRNA) levels by at least 70 percent in cultured cells. Selected siRNAs were also found to be stable in rat cerebrospinal fluid. Additional pre-clinical studies by Alnylam and Medtronic showed that siRNAs administered into the brain were taken up by neurons in the brain region that is most affected in the early stages of Huntington's disease and that the huntingtin gene was silenced significantly in vivo in a relevant brain region after administration of siRNAs designed to target the huntingtin gene. Alnylam believes these findings support further studies of RNAi therapeutics for the treatment of Huntington's disease.

Neuropathic Pain

Alnylam collaborators Dr. Frank Porreca and Dr. Josephine Lai from the University of Arizona presented a poster titled "Small interfering RNA targeting NaV1.8 alleviates experimentally induced chronic pain." Results showed that intrathecal injection of an siRNA targeting NaV1.8, a disease target associated with neuropathic pain, provided more than 75 percent pain relief in a model of chronic inflammatory pain. The silencing of NaV1.8 mRNA was found to be dose-dependent and the siRNAs were found to be stable in cerebrospinal fluid. These in vivo results suggest that siRNAs can be used to silence NaV1.8 and provide pain relief.

Parkinson's Disease

Alnylam has designed and synthesized siRNAs that are specific to the alpha-synuclein gene, a gene associated with Parkinson's disease. In a poster titled "An inducible mouse model of synucleinopathy," collaborators Dr. Matthew Farrer and Dr. Jada Lewis at Mayo Clinic presented in vivo data demonstrating that siRNAs administered into the brain were effective in reducing alpha-synuclein levels. Two complementary methods showed significant lowering of alpha-synuclein mRNA levels in vivo, suggesting the applicability of RNAi therapeutics as a possible disease-modifying therapy for Parkinson's disease.

Dystonia

Alnylam has designed and synthesized siRNAs that are specific to the normal dystonia gene, torsinA, or the mutant form of this gene, which causes a debilitating movement disorder known as dystonia. In a poster titled "Knockdown of torsinA by RNAi decreases secretion of humanized Gaussia luciferase from control fibroblasts," Alnylam collaborator Dr. Xandra Breakefield and colleagues from Massachusetts General Hospital presented in vitro data demonstrating that siRNAs targeting the normal gene were highly effective in cultured cells, lowering torsinA mRNA as well as protein levels. Studies are ongoing to evaluate siRNAs specific for the mutant form of the torsinA gene in culture.

[Fruehrentner]

23.10.2006 14:00:00

Alnylam Announces Progress in Pre-Clinical Hypercholesterolemia RNAi Therapeutic and microRNA Programs

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it presented pre-clinical data at the 2nd Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held October 19-21, 2006 in New York City. Alnylam scientists presented pre-clinical in vivo efficacy data from its hypercholesterolemia program evaluating new approaches for reducing LDL-cholesterol levels using RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9. Alnylam is conducting this program in collaboration with researchers at University of Texas Southwestern Medical Center at Dallas with a focus on developing RNAi therapeutics for PCSK9, a key gene involved in the regulation of LDL cholesterol. An update on Alnylam's microRNA (miRNA) effort was also presented at the meeting.

Data presented at the OTS meeting showed for the first time that small interfering RNAs (siRNAs), the molecules that mediate RNAi, can silence the PCSK9 gene in mice as measured by reductions in messenger RNA (mRNA) levels. Further, gene silencing of the PCSK9 mRNA resulted in meaningful reductions in cholesterol levels, yielding the first in vivo evidence that pharmacologic targeting of PCSK9 can result in potential therapeutic benefit. The in vivo efficacy data for PCSK9 was obtained using systemic RNAi delivery technologies such as those described by Alnylam earlier this year in primate studies (Nature 441: 111-114, 2006) where systemic RNAi targeting apolipoprotein B (apoB), another protein involved in cholesterol metabolism, resulted in reduced levels of apoB mRNA and protein, and significant lowering of LDL cholesterol.

"We are very encouraged that within months of the initiation of our program, we have obtained data demonstrating that systemic RNAi targeting PCSK9 showed in vivo efficacy in animal models," said Victor Kotelianski, M.D., Ph.D., Vice President, Research at Alnylam. "PCSK9 is a compelling target for the novel treatment of hypercholesterolemia where there is substantial clinical validation from human genetics, and where a systemically delivered RNAi therapeutic represents an exciting approach for disease intervention."

In addition, Dr. Markus Stoffel, Professor at The Rockefeller University and Alnylam collaborator and Scientific Advisory Board member, presented an update on antagomirs, an RNAi therapeutic strategy to silence microRNAs (miRNAs.) miRNAs are a recently discovered category of genes that encode small RNAs that in turn regulate a larger number of genes in the human genome through the RNAi pathway. Abnormal expression or mutation of miRNAs has been implicated in disease processes including cancer, viral infection, and metabolic disease. Antagomirs are a potential new class of chemically modified RNA-based drugs that specifically silence miRNAs following therapeutically relevant administration in animals, and their discovery was first reported by scientists at Alnylam and The Rockefeller University in the journal Nature (Nature 438: 685-689, 2005). The company believes that this research creates the opportunity to design antagomirs that target miRNAs in the context of human diseases.

The data presented from the miRNA program builds on previous studies showing that intravenous administration of antagomirs resulted in profound reduction of corresponding miRNA expression in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries, and adrenals. New findings demonstrated that direct administration of antagomirs to the central nervous system resulted in silencing of miRNAs expressed in the brain. In addition, the key structural features of antagomirs and their mechanism of action was further explored, showing that antagomirs as short as 19 nucleotides in length maintain a high degree of selectivity, and that antagomirs can mediate enzymatic degradation of the targeted miRNA.

"Antagomirs have the potential to be a new RNAi therapeutic approach to regulate miRNAs in vivo, possibly representing a novel strategy for silencing miRNAs involved in the cause or pathway of human disease," said Muthiah Manoharan, Ph.D., Vice President, Drug Discovery at Alnylam. "We continue to make important advances with our antagomir platform, which we view as an important component of our leading capabilities for discovery and development of innovative medicines that harness the RNAi pathway."

Alnylam and The Rockefeller University have a collaboration agreement for research in the field of RNAi. Alnylam has taken an exclusive license to all of The Rockefeller University's interest in antagomir technology.

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About microRNA (miRNA)

RNAi can also be induced by microRNAs, or miRNAs, that occur naturally within all mammalian cells. The miRNA molecules are encoded by the cell's own genes, giving rise to small RNA molecules that are similar in structure to siRNAs. There are believed to be over 250 confirmed miRNA genes in the human genome and there are many other predicted miRNAs. miRNAs are thought to work through RNAi to regulate the activity of an estimated one-third of genes in the genome. The inappropriate absence or presence of specific miRNA molecules in various cells has been shown to be associated with specific human diseases, including cancer and viral infections. Alnylam scientists and collaborators have discovered antagomirs, a class of chemically modified RNA-based drugs that are designed to specifically silence miRNAs in human disease.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, and Biogen Idec. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans, and prospects, including with respect to the potential for RNAi therapeutics, the development of RNAi therapeutics targeting PCSK9, and the development of antagomirs for the treatment of disease, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; our ability to fund and the results of further pre-clinical and clinical trials; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of our product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Quelle:BUSINESS WIRE

[Fruehrentner]

Merck kauft SIRNA, daher die heutige Kursbewegung um satte 20 % nach oben aktuell!

[cyberhai]

Merck kauft Sirna für 1,1 Milliarden Dollar. Die aktuelle MK von Alnylam ist 587 Mio Dollar. Könnte gut sein, dass Novartis gleichfalls eine Übernahme anstrebt, haben immerhin bereits ca. 16 % der Aktien. Die Patente und die Pipeline dürften mindestens gleichwertig sein.

[cyberhai]

Sector Wrap: RNAi Drug Developers
Friday November 3, 3:36 pm ET
By Damian J. Troise, AP Business Writer
Merck's Buyout of Sirna Highlights Developers of Drugs Based on Promising RNAi Technology

NEW YORK (AP) -- As if drawing a Nobel Prize wasn't enough, fledgling RNA interference technology was again validated this week when Merck & Co. agreed to buy Sirna Therapeutics Inc. for $1.1 billion.

Sirna is developing treatments for diseases ranging from macular degeneration to hepatitis and asthma using RNA interference, or RNAi. The process works by "silencing" the specific genes at the root of a condition or disease.

How promising is RNAi? Last month, American scientists Andrew Z. Fire and Craig C. Mello were awarded the Nobel Prize for Physiology or Medicine for discovering it in 1998.

Merck's planned purchase of Sirna was seen by many observers as a validation of RNAi and the smaller companies developing a new class of drugs based on it, among them Alynlam Pharmaceuticals Inc. and CytRx Corp., whose shares spiked along with Sirna's after Merck's announcement.

"We believe the (Sirna) acquisition demonstrates the tremendous interest in RNAi therapeutics among major pharmaceutical companies," said Bear Stearns analyst Avanish Vellanki, in a note to Alnylam investors.

Alnylam's lead product candidate, currently in Phase I clinical trials, is aimed at treating a viral lung infection common in children, and in adults whose immune systems are compromised. The company has a long list of collaborators, including Novartis AG, Biogen Idec and Merck.

Alnylam also received a $23 million contract from the federal government to use RNAi to develop a treatment for Ebola. The company also is developing RNAi-based drugs to fight almost any form of influenza, including the H5N1 strain, or "bird flu."

Alynlam Pharmaceuticals President and Chief Executive John Maraganore said the first RNAi-based drugs are at least three to five years away from hitting the market. "But the progress in the field has been remarkably fast," he said.

Analysts expect Alynlam to become the dominant independent developer of RNAi-based drugs, now that its larger competitor Sirna is being acquired by Merck.

Nobel laureate Mello currently sits on the scientific advisory board of CytRx, which plans to spin off its RNAi division as a direct competitor to Alnylam.

Ongoing programs at CytRx show the diversity of possible RNAi-based treatments, according to company President and Chief Executive Steven A. Kriegsman. The company is developing a treatment for Lou Gehrig's disease, and another treatment for obesity.

Kriegsman said the treatment for Lou Gehrig's disease could be expedited to the market, because it would likely be given orphan drug status -- the fast-track status given to treatments of rare diseases.

Kriegsman said the burgeoning interest in RNAi is "exciting from our perspective. We are definitely looking at other opportunities."

[aktianer]

Company Expects to File IND for PCSK9 Program in 2007

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 5, 2006--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it will advance a systemically delivered RNAi therapeutic for the treatment of hypercholesterolemia as its next clinical development program. This program, in collaboration with University of Texas (UT) Southwestern Medical Center at Dallas, is focused on evaluating new approaches for reducing LDL cholesterol levels using RNAi therapeutics directed to the disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9. Alnylam expects to submit an investigational new drug (IND) application for this program in 2007.

PCSK9 is an important gene involved in the metabolism of LDL cholesterol, or so-called "bad cholesterol." The normal role of the PCSK9 protein is to break down the cell surface receptor for LDL; when there is less PCSK9 protein, there is more receptor on the cell surface to remove LDL from the bloodstream. In human studies, researchers at UT Southwestern Medical Center have discovered that mutant forms of PCSK9 that have increased activity are linked with a familial form of hypercholesterolemia. Conversely, recent research published in the New England Journal of Medicine (N. Engl. J. Med. 354, 1264-1272, 2006) has demonstrated that other mutations in humans, those that lower PCSK9 function, are associated with decreased cholesterol levels and an 88 percent risk reduction in cardiovascular disease.

"PCSK9 is a compelling target for a potential breakthrough treatment of hypercholesterolemia and complications of acute coronary syndromes," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "Although PCSK9 is well validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. As a result we believe it is an ideal target for a systemic RNAi approach, particularly in light of our recent progress with systemic delivery of RNAi therapeutics."

"There is a clear unmet medical need for novel agents that can lower LDL cholesterol and PCSK9 appears to be an excellent target for disease intervention in hypercholesterolemia," said Jay Horton, M.D., Associate Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. "Based on its novel mechanism of action and pre-clinical data to date, we believe an RNAi therapeutic targeting PCSK9 has the potential to lower LDL cholesterol, while functioning synergistically with statins in the treatment of hypercholesterolemia."

Data recently presented by Alnylam scientists at the Oligonucleotide Therapeutics Society meeting have shown that small interfering RNAs (siRNAs), the molecules that mediate RNAi, can silence the PCSK9 gene in mice as measured by reductions in messenger RNA (mRNA) levels. Further, gene silencing of PCSK9 mRNA resulted in meaningful reductions in cholesterol levels, yielding in vivo evidence that pharmacologic targeting of PCSK9 may result in potential therapeutic benefit. The in vivo efficacy data for PCSK9 were obtained using systemic RNAi delivery technologies such as those described by Alnylam earlier this year in primate studies (Nature 441: 111-114, 2006) where systemic RNAi targeting apolipoprotein B (apoB), another protein involved in cholesterol metabolism, resulted in reduced levels of apoB mRNA and protein, and significant lowering of LDL cholesterol.

Alnylam will be presenting updates on its research and development programs, including its hypercholesterolemia program, at its R&D Day to be held this morning beginning at 8:30 a.m. ET at the Sofitel New York in New York City. A replay of the presentation will be posted on the Alnylam website approximately three hours after the event, and will be archived for 30 days.

[aktianer]

Heutiger Kursrücksetzer dürfte auf die u.a. Kapitalerhöhung zurückzuführen sein:

Alnylam to offer and sell about 4.7 mln shares + 0,7 Mio.Stück zusätzlich
Mon Dec 11, 2006-- 4:42pm ET147

Dec 11 (Reuters) - Alnylam Pharmaceuticals Inc. (ALNY.O: Quote, Profile , Research) said it will offer and sell about 4.7 million common shares in a public offering.

The biopharmaceutical company said it intends to grant the underwriter a thirty-day option to purchase up to about 705,000 additional shares. (Reporting by Neetha Mahadevan in Bangalore)

© Reuters 2006. All Rights Reserved.

[aktianer]

Antwort auf Beitrag Nr.: 26.129.033 von aktianer am 12.12.06 16:59:40

13-Dec-2006
Other Events
Item 8.01. Other Events.
On December 12, 2006, Alnylam Pharmaceuticals, Inc. ("Alnylam") entered into an underwriting agreement (the "Underwriting Agreement") with Banc of America Securities LLC (the "Underwriter") relating to the issuance and sale of 4,700,000 shares (the "Shares") of the common stock, $.01 par value per share ("Common Stock"), of Alnylam. Pursuant to the Underwriting Agreement, the Underwriter has agreed to purchase the Shares from Alnylam at a price of
$ 21.57 per share
and has advised Alnylam that the price at which the Shares will be sold to the public is initially
$ 22.00 per share.

[aktianer]

Alnylam geht optimistisch ins Jahr 2007; nachfolgend die Meldung mit den Zielen für 2007:

Alnylam Announces Key Product and Business Goals for 2007
Monday January 8, 2007, 8:01 am ET
Company Expects to Advance Proprietary and Partnered Pipeline of RNAi Therapeutics Toward Human Proof-of-Concept and to Form Significant New Alliances

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today its key product and business goals for 2007, including financial guidance.

"The year 2006 was transformational for Alnylam, and for the field of RNAi. We intend to build significantly on this progress in 2007 with important advances in our pipeline of proprietary and partnered RNAi therapeutics, including human proof-of-concept data within the next 12 to 18 months," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "Further, with the heightened level of interest in RNAi therapeutics as a source of innovative medicines, combined with Alnylam's unparalleled intellectual property estate, we plan to form at least one significant new alliance in 2007. Finally, we aim to execute on our product and business goals while maintaining a solid financial position with over $180 million in cash at year-end."

Product Goals

* Demonstrate Human Proof-of-Concept Data. Alnylam expects to publish or present human proof-of-concept data demonstrating the effectiveness of an RNAi therapeutic to target a specific disease in human subjects within the next 12 to 18 months.
* Advance ALN-RSV01 for the Treatment of Respiratory Syncytial Virus (RSV) Infection. Alnylam plans to present data from its ongoing Phase I inhalation trial in adult volunteers in the first half of 2007. The company is also conducting an experimental infection study in adult volunteers and expects to begin the treatment protocol for this study in the first half of 2007 and present data in the second half of 2007. In addition, the company intends to initiate a Phase II trial in naturally infected patients in the second half of 2007.
 Expand Clinical Development Pipeline. Alnylam expects to file investigational new drug applications (INDs) for two programs in 2007; candidates include ALN-FLU01 for the treatment of pandemic influenza and ALN-PCS01 for the treatment of hypercholesterolemia. In addition, the company expects to announce two new development candidates as it continues to expand its pipeline of RNAi therapeutics.

* Maintain Leadership Position with Systemic Delivery and microRNAs. The company expects to continue its efforts to optimize systemic delivery for RNAi therapeutics and plans to present or publish new non-human primate data in the first half of 2007. Also this year, Alnylam plans to publish two or more major papers related to in vivo efficacy for RNAi therapeutics delivered systemically and two or more papers from its research progress on microRNAs and "antagomirs," chemically synthesized molecules that can work to silence disease-causing microRNAs.

Business Goals

* Form Major New Alliance(s). Alnylam intends to form one or more new alliance(s) with leading companies to continue to develop and fund its growing pipeline of RNAi therapeutics.
* Expand Intellectual Property (IP) Position. The company expects to further augment its fundamental IP position by obtaining multiple patent issuances and grants in the U.S. and Europe over the course of the year.
* Monetize IP Position. The company plans to realize additional near-term value from its IP estate by granting more than five new InterfeRx(TM) or research product licenses.
* Leverage Alliances. Alnylam expects to receive more than $25 million in alliance-based funding in 2007, which includes expected R&D funding and achievement of additional objectives under its alliances with collaborators including Merck, Medtronic, Novartis, and Biogen Idec.
* Maintain Solid Financial Performance. Alnylam is on track to meet its revised guidance of finishing 2006 with more than $215 million in cash. In 2007, Alnylam aims to maintain a solid financial position while executing on its product and business goals, and expects to end the year with greater than $180 million in cash.

[Fruehrentner]

Alnylam and Inex Form Strategic Technology Alliance to Discover and Develop RNAi Therapeutics with Lipid-Based Delivery Formulations

09 Jan 2007

Announced today that Alnylam has taken a worldwide exclusive license to Inex's liposomal delivery formulation technology for the discovery, development, and commercialization of RNAi therapeutics, and that the companies have expanded their technology research and manufacturing alliance on lipid-based delivery technology.

CAMBRIDGE, MA, USA and VANCOUVER, Canada | Jan 09, 2007 | Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, and Inex Pharmaceuticals Corporation (TSX:IEX) announced today that Alnylam has taken a worldwide exclusive license to Inex's liposomal delivery formulation technology for the discovery, development, and commercialization of RNAi therapeutics, and that the companies have expanded their technology research and manufacturing alliance on lipid-based delivery technology. In addition, Inex will receive three InterfeRx(TM) license options, subject to Alnylam review and third-party obligations, to develop its own RNAi therapeutic products. Inex will also receive exclusive access to Alnylam's intellectual property to develop oligonucleotide drugs that act through an immune stimulation mechanism, outside the RNAi pathway.

"This new, exclusive license further enhances Alnylam's delivery capabilities and intellectual property estate, and continues to strengthen our leadership position in RNAi therapeutics," said Barry Greene, Chief Operating Officer of Alnylam. "We view Inex as having important intellectual property and capabilities in the area of lipid-based drug delivery systems, and believe that access to this technology is important as we advance systemic RNAi therapeutics and continue to build a leading biopharmaceutical company."

"We are pleased to be expanding and strengthening our overall relationship with Alnylam, which provides Inex the opportunity to develop RNAi therapeutics through our InterfeRx licenses," said Timothy M. Ruane, President and Chief Executive Officer of Inex. "We view Alnylam as the leading company in the development of RNAi therapeutics, and by working with Alnylam, Inex and its stakeholders will be best positioned to realize the value of lipid-based delivery technologies in the RNAi field."

Under the terms of the agreement, Inex will receive an upfront payment of $8.0 million in newly issued shares of Alnylam common stock and/or cash, at Alnylam's option. In addition, Inex will receive $4.0 million in R&D funding over the next two years to continue to identify and develop lipid-based delivery systems for Alnylam. Inex will provide contract manufacturing services on an exclusive basis for Alnylam proprietary products in the collaboration and Alnylam will make available a $5.0 million loan for capital equipment expenditures related to manufacturing capabilities. Inex is also eligible to receive $13.0 million in potential milestone payments for each product utilizing Inex technology, of which $9.5 million are due upon regulatory approval and successful commercialization with over $500 million in cumulative product sales, plus royalties on product sales. All figures quoted are in U.S. dollars.

As part of the collaboration, Alnylam has also granted Inex an option for three InterfeRx RNAi therapeutic target licenses, subject to Alnylam review and Alnylam third-party obligations. Finally, Alnylam has granted Inex an exclusive license to Alnylam technology and intellectual property for discovery, development, and commercialization of immune stimulatory oligonucleotides that do not function through an RNAi mechanism.

Liposomal and/or lipid nanoparticle formulations are important technologies for systemic delivery of RNAi therapeutics. Inex's intellectual property estate is comprised of certain key, issued patents, such as those derived from the Wheeler and Semple patent series (U.S. Patent Nos. 5,976,567, 6,815,432, and 6,858,225), that are considered important for the development and commercialization of liposomal and/or lipid nanoparticle formulations of oligonucleotide therapeutics, including small interfering RNAs (siRNAs), the molecules that mediate RNAi. Alnylam published groundbreaking results in March 2006 demonstrating, for the first time, therapeutic gene silencing in primates with systemically delivered RNAi therapeutics; these results were obtained using liposomal formulations. Alnylam intends to advance its RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia to an investigational new drug (IND) application in 2007. The systemically administered RNAi therapeutic is expected to employ a lipid nanoparticle formulation.

"The licensing of Inex's delivery technology is another example of Alnylam's strategy of consolidating intellectual property critical for the development and commercialization of RNAi therapeutics," said Robert Millman, Chief Intellectual Property Counsel of Alnylam. "Exclusive access to such intellectual property relating to delivery formulations complements our leading position in fundamental intellectual property related to RNAi."

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. The discovery of RNAi has been widely acknowledged as a major breakthrough in biology, and the technology was recognized for its potential broad impact in medicine with the award of the 2006 Nobel Prize for Physiology or Medicine. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause targeted gene silencing.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, and Biogen Idec. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. For more information, visit www.alnylam.com.

About INEX

INEX is a Canadian biopharmaceutical company developing and commercializing proprietary drugs and drug delivery systems to improve the treatment of cancer. Further information about Inex and this news release can be found at www.inexpharm.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans, and prospects, including with respect to the development and systemic delivery of RNAi therapeutics, the importance of liposomal and/or lipid nanoparticle formulations for systemic delivery and the timing for filing and IND for, and the development of, an RNAi therapeutic targeting PCKS9 for the treatment of hypercholesterolemia, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; Alnylam's ability to fund and the results of further pre-clinical and clinical trials; obtaining, maintaining and protecting intellectual property utilized by Alnylam's products; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of Alnylam's product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and its short operating history; as well as those risks more fully discussed in the "Risk Factors" section of Alnylam's most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

INEX Forward-Looking Statements

There are forward-looking statements by INEX contained herein that are not based on historical fact, including without limitation statements containing the words "believes," "may," "plans," "will," "estimate," "continue," "anticipates," "intends," "expects," and similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from any future results, events or developments expressed or implied by such forward-looking statements. Such factors include, among others, INEX's stage of development, lack of product revenues, additional capital requirements, risks associated with the completion of clinical trials and obtaining regulatory approval to market INEX's products, the ability to protect its intellectual property and dependence on collaborative partners. These factors should be considered carefully and readers are cautioned not to place undue reliance on such forward-looking statements. INEX disclaims any obligation to update any such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments.

CONTACT: Alnylam Pharmaceuticals
Cynthia Clayton (Investors)
617-551-8207
or
KMorrisPR
Kathryn Morris (Media)
845-635-9828
or
Inex Pharmaceuticals Corporation
Ian Mortimer (Investors)
604-419-3200
or
James Hoggan and Associates
Karen Cook Boas (Media)
604-739-7500

SOURCE: Alnylam Pharmaceuticals, Inc.

[aktianer]

Alnylam mit positiven vorklinischen Daten:

Alnylam Presents Pre-clinical Results from Hypercholesterolemia, Huntington's Disease and Neuropathic Pain Programs at Keystone Symposium on RNAi
Thursday February 1, 8:00 am ET
- New Results Expand In Vivo Efficacy Data for Direct and Systemic RNAi Therapeutic Applications -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that it presented new pre-clinical data at the "RNAi for Target Validation and as a Therapeutic" Keystone Symposium held January 28 - February 2, 2007 in Keystone, Colorado. The new results were presented from Alnylam's RNAi therapeutics program targeting PCSK9 for the treatment of hypercholesterolemia and from Alnylam collaborations in Huntington's disease and neuropathic pain. The data demonstrate that small interfering RNAs (siRNAs), the molecules that mediate RNAi, can be administered in animal models to achieve therapeutic silencing of disease-causing genes, and that effective and clinically relevant delivery can be achieved with both direct and systemic RNAi applications.

ADVERTISEMENT
"Alnylam scientists and our collaborators continue to make significant progress in achieving delivery for RNAi therapeutics and in demonstrating in vivo efficacy in animal models of human disease. Indeed, the new data presented this week further extend Alnylam's scientific leadership in advancing RNAi therapeutics as a new class of innovative medicines," said Victor Kotelianski, M.D., Ph.D., Vice President, Research at Alnylam. "We are especially encouraged by the new findings in our PCSK9 program for hypercholesterolemia that show considerable potency and durability in a mouse model after a single dose of our RNAi therapeutic. These new data support ongoing efforts to advance our PCSK9 program toward a planned IND filing in 2007."

Hypercholesterolemia

Alnylam is developing a systemically delivered RNAi therapeutic for the treatment of hypercholesterolemia targeting PCSK9, a key gene involved in the metabolism of LDL cholesterol. In a talk titled "Achieving Therapeutic Gene Silencing in vivo with RNAi," results were presented on ALN-PCS01, Alnylam's RNAi therapeutic targeting PCSK9 which comprises an optimized siRNA formulated in a liposomal nanoparticle.

Data presented include the following.

* In vivo systemic administration of ALN-PCS01 in mice was associated with dose-dependent and rapid silencing of the PCSK9 messenger RNA to more than 70 percent of control levels, with peak silencing effects observed as soon as 48 hours after dosing.
* After a single intravenous injection, the RNAi therapeutic showed a durable biological effect with more than 50 percent silencing of PCSK9 maintained through two weeks, and full recovery of PCSK9 to normal levels at 23 days after dosing.
* Therapeutic efficacy for ALN-PCS01 was demonstrated with up to 30 percent reduction in total cholesterol levels at doses that were well tolerated.

Alnylam intends to file an investigational new drug (IND) application for ALN-PCS01 in 2007.

Huntington's Disease

In a talk titled "Advances in the use of Synthetic siRNAs in the Treatment of Huntington's Disease Models," Alnylam collaborator Dr. Neil Aronin, Professor of Medicine and Cell Biology and Director of Endocrinology and Metabolism at the University of Massachusetts Medical School presented in vivo data demonstrating that an siRNA targeting the huntingtin gene inhibited the progression of Huntington's disease in a mouse model. These results showed both a reduction of neuronal pathology and an improvement in abnormal behavior in the disease model with administration of a cholesterol-conjugated siRNA. Pathological protein aggregates in the neuropil were decreased by about 70 percent. Two types of abnormal behavior - clasping and footslips - were ameliorated by approximately 50 percent and 70 percent, respectively. In addition, levels of the huntingtin messenger RNA, which encodes the protein that mediates Huntington's disease, were reduced by about 70 percent. Alnylam believes these findings support further studies of RNAi therapeutics for the treatment of Huntington's disease.

Neuropathic Pain

In a poster titled "RNAi of Neuropeptide Y for Neuropathic Pain," Alnylam collaborator Dr. Josephine Lai, Professor of Pharmacology at the University of Arizona, presented results showing that intrathecal injection of an siRNA targeting neuropeptide Y (NPY) prevented the development of neuropathic pain in a rat model. A more effective siRNA, designed by Alnylam, has been identified from in vitro studies and will be tested in vivo for enhanced activity. Further, in a talk titled "Treating Neuropathic Pain with RNA Interference," Dr. Lai presented results demonstrating that a single intraparenchymal injection of a very small dose of siRNA targeting the receptor of NPY in a lipid formulation was efficacious against neuropathic pain in a rat model. Alnylam believes these findings further support the use of RNAi as a highly potent therapeutic approach for the treatment of disorders of the nervous system.

[cyberhai]

RNA-Interferenz

Heilsames Schweigen der Gene

Von Christina Hohmann

Die Entdeckung der RNA-Interferenz, mit der sich einzelne Gene stummschalten lassen, hat bei der Pharmaindustrie hohe Erwartungen geweckt. Prinzipiell ließen sich mit der Methode viele Krankheiten therapieren: von Virusinfektionen über Krebs bis Chorea Huntington. Erste RNAi-Wirkstoffe befinden sich bereits in klinischer Erprobung.

Selten hat eine wissenschaftliche Entdeckung so schnell zu einem Nobelpreis geführt wie die Erstbeschreibung der RNA-Interferenz (RNAi). Im Dezember 2006 erhielten die Biologen Andrew Fire und Craig Mello, neun Jahre nach ihrer »Nature«-Publikation, diese Auszeichnung. Die Methode zum Stummschalten von Genen ist seitdem zu einem der wichtigsten Werkzeuge von Molekularbiologen geworden, um die Funktion von Genen zu untersuchen. Was die Methode, die das Fachmagazin »Science« 2002 zum »Durchbruch des Jahres« kürte, so besonders macht, ist ihre potenzielle therapeutische Bandbreite. Da sich durch die RNAi die Produktion jedes beliebigen Proteins ausschalten lässt, könnte sie bei einer Vielzahl von Krankheiten eingesetzt werden: So kann das Ausschalten von Onkogenen bei der Therapie von Krebserkrankungen helfen, und das Stilllegen von viralen Genen hemmt die Replikation von Viren wie HIV, RSV oder das Hepatitis-C-Virus.

Die RNA-Interferenz stellt vermutlich einen natürlichen Abwehrmechanismus gegen Viren dar. Wenn doppelsträngige Ribonukleinsäure (dsRNA), die dem Genom von Viren ähnelt, in die Zelle gelangt, springt das Programm an. Die Endonuklease Dicer bindet an die dsRNA und zerschneidet sie in etwa 21 Nukleotide lange Stücke, die sogenannten siRNA (small interfering RNA). Diese immer noch doppelsträngigen Fragmente lagern sich mit mehreren Enzymen zum sogenannten »RNA induced silencing complex« (RISC) zusammen. Zu diesem gehört auch die Endonuklease Argonaut, die einen Strang der siRNA zerschneidet. Dieser wird entfernt, und der andere Strang im Komplex dient als Vorlage, um komplementäre RNA-Stücke zu finden und zu zerstören. Wenn der Komplex auf eine komplementäre Boten-RNA (mRNA) trifft, wird diese zerschnitten und kann somit nicht mehr als Anleitung zum Bau eines Proteins verwendet werden. Wenn die dsRNA, die in die Zelle kam, von Viren stammt, wird auf diese Weise die Produktion viraler Proteine und die Replikation der Pathogene verhindert.

Nun versuchen Forscher, diesen Mechanismus zu nutzen, um an Krankheiten beteiligte Gene auszuschalten. Sofern sie die Sequenz des Zielgens kennen, können sie siRNA künstlich herstellen und in die Zellen einbringen, wo sie dann den Mechanismus in Gang setzen, der mit der Zerstörung der entsprechenden mRNA endet. Das gewünschte Gen ist stummgeschaltet.

Steiniger Weg bis zum Patienten

In Zellkulturversuchen hat sich die RNAi in Hunderten von Experimenten als erfolgreich erwiesen. Doch auf dem Weg von der Petrischale zum Patienten bestehen noch einige Hürden. Ein Problem ist die Stabilität: Nackte siRNA überlebt im Körper nicht lange, da sie von Endo- und Exonukleasen angegriffen wird. Außerdem können unerwünschte Nebenwirkungen auftreten. Diese »Off-target-Effekte« können entweder darauf beruhen, dass die siRNA das Immunsystem unspezifisch aktiviert. Oder sie kommen dadurch zustande, dass wichtige Gene aus Versehen mitausgeschaltet werden, weil sie eine ähnliche Sequenz besitzen.

Das wohl größte Problem ist allerdings das gezielte Einbringen der siRNA in die gewünschten Organe und schließlich ins Zellinnere. In Venen injizierte siRNA wird schnell mit dem Blutstrom in die Leber transportiert und dort entsorgt. Eine systemische RNAi-Therapie gestaltet sich daher bislang schwierig. Deutlich einfacher sind dagegen isolierte Zielorgane zu erreichen wie etwa das Auge. Auch die Atemwege beziehungsweise die Lunge sind für die siRNA durch Inhalation oder nasale Applikation gut zu erreichen.

Im Organ selbst stellt aber die Zellmembran noch eine Barriere für den Wirkstoff dar. Ein ganzes Bataillon verschiedener Methoden wird derzeit entwickelt, um diese zu überwinden. Zum einen können Zellen des Patienten isoliert, in Zellkultur mit der siRNA bestückt werden und dann dem Patienten wieder injiziert werden. Zum anderen können Viren als Genfähren benutzt werden, wie es bereits bei der Gentherapie versucht wurde. Diese Methode birgt aber auch Gefahren, da die Vektoren eine starke Immunreaktion oder Krebs auslösen können.

An einer ganz innovativen Methode arbeitet derzeit Judy Liebermann von der Harvard Medical School. Sie kombinierte monoklonale Antikörper mit dem Enzym Protamin, das Erbgut verpacken kann. Dieses Protein bindet die therapeutische siRNA, die somit huckepack ins Zellinnere gelangt. Wie die siRNA aufgenommen wird, ist nicht vollständig verstanden, doch in ersten Versuchen funktionierte die Methode gut. In HIV-infizierten Zellen konnte Liebermann die Virusreplikation mithilfe der an Antikörper gekoppelten siRNA unterdrücken (»Nature Biotechnology«, Band 23, Seite 709). Auch chemische Modifikationen der siRNA können hilfreich sein. Sie erhöhen nicht nur die Stabilität des Wirkstoffs im Körper, sondern verbessern auch die Aufnahme in bestimmte Organe. So konjugierten Forscher der Pharmafirma Alynlam eine lipophile Cholesterol-Gruppe an ihre gegen Apolipoprotein B gerichtete siRNA. Injizierten sie Mäusen das Molekül, sank sowohl die Produktionsrate von ApoB, das an der Synthese von Cholesterol beteiligt ist, in Leber und Dünndarm, als auch der Cholesterol-Spiegel der Tiere.

Erfolgreich in Phase I und II

Der erste erfolgreiche Einsatz der RNAi im Tierversuch gelang bereits im Jahr 2002: Anton McCaffrey und Mark Kay von der Stanford University konnten bei Mäusen die Reproduktion des Hepatitis-C-Virus unterdrücken. Viren sind ohnehin ein geeignetes Ziel für die neue Technik, da es sich bei der RNA-Interferenz um einen natürlichen Viren-Abwehrmechanismus handelt. Außerdem beeinflusst das Stilllegen von viralen Genen ausschließlich das Virus, kann also keine Off-target-Effekte hervorrufen. Gegen die meisten Viren gibt es bislang keine geeignete kausale Therapie. Das soll sich mit der RNAi ändern. Eine Gruppe um Ian MacLachlan von der Firma Protiva testet derzeit eine siRNA gegen das Ebola-Virus bei Meerschweinchen. Auch gegen das HI-Virus verfolgen Forschergruppen weltweit verschiedene Ansätze.

Am weitesten fortgeschritten ist ein siRNA-Wirkstoff namens ALN-RSV01 der Firma Alynlam, der sich gegen das Respiratorische Syncytialvirus (RSV) richtet. Der Wirkstoff wurde bereits in zwei doppelblinden Phase-I-Studien an 101 gesunden Freiwilligen getestet. Der nasal verabreichte Wirkstoff wurde nach Herstellerangaben gut vertragen und hat sich als sicher erwiesen. In Kürze sollen weitere Studien mit ALN-RSV01 folgen.

Bereits in Phase II der klinischen Entwicklung befindet sich ein RNAi-Therapeutikum, das sich gegen altersbedingte Makuladegeneration (AMD) richtet. Diese Erkrankung eignet sich für eine RNAi-Therapie besonders, da der Wirkstoff direkt ins Auge gespritzt werden kann. Durch diese direkte Applikation kann die siRNA unverpackt und ungeschützt verabreicht werden, da sie nicht im Blut zu ihrem Zielorgan gelangen muss. Außerdem ist die Ursache der Erkrankung bekannt: Der Vascular endothelial growth factor (VEGF) lässt Blutgefäße in den Bereich der Netzhaut einwandern, der für das scharfe Sehen verantwortlich ist, die Makula. Dadurch geht das Sehvermögen verloren.

In einer Phase-I-Studie hat die Firma Sirna ihren Wirkstoff Sirna-027 an 26 AMD-Patienten getestet. Bei rund 23 Prozent der Patienten verbesserte sich die Sehschärfe acht Wochen nach der Injektion. Bei den restlichen Patienten trat zumindest keine Verschlechterung des Sehvermögens ein, meldet der Hersteller. Auch eine Phase-II-Studie mit Patienten, die unter schwerer, fortschreitender AMD litten, brachte positive Resultate. Ein siRNA-Wirkstoff gegen Makuladegeneration könnte vielleicht schon 2009 auf den Markt kommen. Andere RNAi-Therapeutika, vor allem systemisch zu applizierende, werden noch deutlich länger auf sich warten lassen.

Quelle: http://www.pharmazeutische-zeitung.de/

Gruß Cyberhai

[Fruehrentner]

hier ein Artikel aus der FTD über Phil Sharp, dem Mitbegründer von BIOGEN und ALNYLAM:

Phil Sharp: Forscher Unternehmer

von Sascha Karberg (Boston)

Er ist Wissenschaftler aus Überzeugung - und mehrfacher Millionär. Nobelpreisträger und Biogen-Gründer Phil Sharp beweist, dass exzellente Forschung und geschicktes Management kein Widerspruch sein müssen.

[...]

http://www.ftd.de/karriere_management/koepfe/160063.html

[cyberhai]

Hier nochmals zur Übersicht die Pipeline:



Eine evtl. Übernahme dürfte wesentlich teurer werden als bei Sirna...

Gruß Cyberhai

[Aliberto]

aktueller Anteil von Novartis an Alynlam 14%

[Fruehrentner]

Noch einer da?

Kurs scheint sich wieder zu erhohlen.

[cyberhai]

Antwort auf Beitrag Nr.: 28.793.208 von Fruehrentner am 13.04.07 13:14:24

Bin noch da

Entscheidend für den kurzfristigen Kursverlauf ist zunächst die Phase I bezügich der RSV-Infektion...

Ansonsten bin ich vom Alnylam nach wie vor sehr überzeugt bzw. denke, dass das Unternehmen ein langfristiger Outperformer im Biotechsektor sein wird.

Die neuesten Meldungen sind jeweils hier abrufbar:

http://finance.yahoo.com/q?s=ALNY

Gruß Cyberhai

[aktianer]

Antwort auf Beitrag Nr.: 28.803.813 von cyberhai am 13.04.07 21:47:18

bin auch noch investiert - bleibe auch, wenn nichts grundlegend Negatives passiert, langfristig dabei.

Gruß

[Aliberto]

Antwort auf Beitrag Nr.: 28.803.813 von cyberhai am 13.04.07 21:47:18

Warum läßt Du Dich nicht einfach auf der Homepage registrieren und Dir jeweils die aktuellsten Meldungen zumailen?

Bin noch nicht investiert, aber die Story und vor allen Dingen die Aussichten erscheinen mir ebenfalls sehr attraktiv. Werde noch etwas an der Seitenlinie bleiben und bei einer stärkeren allgemeinen Marktkorrektur einsteigen (bis die ersten Studien bzw. die ersten Phase III-Tests erfolgreich abgeschlossen sind, dürfte es ja noch einige Zeit dauern). Langfristig kann man bei Anylam wahrscheinlich nicht viel falsch machen (ausser die ständige Verwässerung durch Mitarbeiter/Führungskräfte-Optionen).

[cyberhai]

Antwort auf Beitrag Nr.: 28.833.597 von Aliberto am 16.04.07 11:06:13

Ich habe mit Registrierungen schlechte Erfahrungen gemacht (Junk-Mails nehmen dadurch zu), daher hatte ich bisher auf die Registrierung verzichtet. Trotzdem danke für den Tipp. Bin ansonsten fast jeden Tag bei Yahoo-Finance online und sehe dann die Nachrichten. Könnte da jedoch im entscheidenden Moment evtl. zu spät sein...

[Aliberto]

Habe mich vor ca. 3 Monaten auf der Homepage registrieren lassen und bisher wirklich nur sehr gute Erfahrungen gemacht.
Habe mir auch den sehr interessanten und informativen "Conference Call" Anfang Februar angehört; von der PR bzw. Investor-Relation-Arbeit kann sich jedes Unternehmen eine Schnitte abschneiden.

[Fruehrentner]

bevor der thread hier historisch wird.

[aktianer]

Antwort auf Beitrag Nr.: 30.345.840 von Fruehrentner am 27.06.07 12:18:43

News von Alnylam:

Alnylam Announces Achievement of Key Milestone in Collaboration Agreement
Wednesday June 27, 8:00 am ET
- Alnylam Advances RNAi Therapeutic Program into IND-Enabling Studies using Isis Intellectual Property -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News) announced today the achievement of an important milestone in its strategic alliance with Isis Pharmaceuticals, Inc. (Nasdaq: ISIS - News). Alnylam has initiated IND-enabling studies with an RNAi therapeutic clinical candidate that utilizes technology and intellectual property licensed exclusively from Isis. Under the 2004 strategic alliance agreement, Alnylam obtained an exclusive license to Isis intellectual property for double-stranded oligonucleotide therapeutics that mediate RNAi, such as small interfering RNAs (siRNAs), in return for upfront cash payments, milestone payments, and royalties. The achievement of the development milestone demonstrates the importance of Isis technology for the advancement of RNAi therapeutics.

ADVERTISEMENT
"The advancement of RNAi therapeutics into development stages has occurred at a rapid pace, in part due to the pioneering work of Isis across virtually all categories of oligonucleotide therapeutics," said Barry Greene, Chief Operating Officer of Alnylam. "Isis technology and intellectual property have proven to be critical components in developing siRNAs with needed 'drug-like' properties."

"Our exclusive strategic alliance with Alnylam highlights the significance of the Isis intellectual property estate and technology for the development and commercialization of oligonucleotide therapeutics, including those that function through an RNAi mechanism," said Lynne Parshall, Executive Vice President and Chief Financial Officer of Isis. "We view Alnylam as the leader in RNAi, and our agreement provides a unique opportunity for Isis to benefit in the continued progress in the entire field of RNAi therapeutic products as we focus our primary efforts on single-stranded antisense oligonucleotides."

http://biz.yahoo.com/bw/070627/20070627005317.html?.v=1

[Aliberto]

09.07.2007 11:06:00
Roche und Alnylam schließen Allianz für RNAi-Therapeutika
(aktiencheck.de AG) - Der schweizerische Pharmakonzern Roche Holding AG (ISIN CH0012032113/ WKN 851311) meldete Montag, dass er mit der amerikanischen Alnylam Pharmaceuticals Inc. (ISIN US02043Q1076/ WKN A0CBCK) eine bedeutende Allianz geschlossen hat, in deren Rahmen Roche eine nicht-exklusive Lizenz für Alnylams Technologieplattform zur Entwicklung von RNAi-(RNA-Interferenz)-Therapeutika erhält.

Unternehmensangaben zufolge wird die Allianz zunächst die vier Therapiegebiete Onkologie, Atemwegserkrankungen, Stoffwechselerkrankungen und bestimmte Lebererkrankungen umfassen. Alnylam und Roche werden auch bei der Erforschung von RNAi-Therapeutika für krankheitsspezifische Ansätze auf diesen Gebieten zusammenarbeiten. Zudem übernimmt Roche nach Zustimmung der Behörden die europäische Forschungsniederlassung von Alnylam in Kulmbach, Deutschland (Bayern). Diese Niederlassung wird zum Center of Excellence von Roche für die Erforschung von RNAi-Therapeutika.

RNAi ist eine potenzielle Basis für eine komplett neue Klasse von Humanarzneimitteln. RNAi ist ein natürlicher Mechanismus, mit dessen Hilfe der Körper die Expression bestimmter Gene hemmt. Die Nutzbarmachung der RNAi-Aktivität ermöglicht so, spezifische und hochwirksame Medikamente gegen schwer behandelbare Krankheiten zu entwickeln.

Alnylam hat Roche eine nicht-exklusive Lizenz erteilt, die Roche Zugang zum breiten geistigen Eigentum und Know-How von Alnylam gewährt, darunter zu Eigentumsrechten in Grundlagenwissenschaften, Chemie und pharmazeutischen Trägersystemen. Als Anwendungsgebiete sind zunächst Onkologie, Atemwegserkrankungen, Stoffwechselerkrankungen und bestimmte Lebererkrankungen vorgesehen. Alnylam behält das Recht, nicht-exklusive Lizenzen auch an weitere Partner zu vergeben. Zudem werden Alnylam und Roche bei bestimmten noch zu definierenden krankheitsspezifischen Ansätzen gegen Zahlungen für erreichte Ziele sowie Lizenzgebühren zusammenarbeiten.

Die Transaktion beinhaltet überdies die Übernahme der europäischen Forschungsniederlassung von Alnylam in Kulmbach (Deutschland) mit etwa 40 Mitarbeitenden durch Roche. Das Team in Kulmbach wird als neues Center of Excellence für RNAi-Therapeutika innerhalb der globalen Forschungsorganisation von Roche weiter auf diesem Gebiet forschen.

Der Wert der Zusammenarbeit könnte sich aufgrund der Vorauszahlungen, der potenziellen Zahlungen nach Erreichen bestimmter Etappenziele für mehrere Produkte sowie von Zahlungen bei Ausweitung der therapeutischen Anwendungsgebiete auf über 1 Mrd. Dollar belaufen. Dabei sind potenzielle Lizenzgebühren auf künftige Umsätze kommerzieller Produkte nicht mit eingerechnet. Im Rahmen der Vereinbarung wird Roche Alnylam 331 Mio. Dollar als Bar-Vorauszahlungen sowie Kapitalinvestitionen leisten. Dazu gehören 1,975 Alnylam-Aktien, die zum Preis von je 21,50 Dollar durch den Roche Venture Fund erworben werden. Das sind etwas weniger als 5 Prozent der ausstehenden Alnylam-Aktien. Roche wird Alnylam auch beim Erreichen bestimmter Etappenziele in der Entwicklung und Kommerzialisierung von Produkten Zahlungen leisten sowie Lizenzgebühren auf künftige Umsätze kommerzieller Produkte zahlen. Des Weiteren kann Roche dem US-Unternehmen Zahlungen für die Ausweitung der Anwendungsgebiete leisten, um deren Anzahl zu erhöhen.

Die Aktie von Roche Holding notiert in Zürich aktuell bei 245,70 Schweizer Franken (+0,24 Prozent), die von Alnylam Pharmaceuticals schloss am Freitag an der NASDAQ bei 15,20 Dollar. (09.07.2007/ac/n/a)

[aktianer]

Antwort auf Beitrag Nr.: 30.588.826 von Aliberto am 09.07.07 11:14:43

ein schöner Tag heute für alle Alnylam-Aktionäre;
akt.Kurs 17,40 Euro +58%.

[Fruehrentner]

Antwort auf Beitrag Nr.: 30.591.197 von aktianer am 09.07.07 13:31:30

Was ist denn da los??!!

[Fruehrentner]

Antwort auf Beitrag Nr.: 30.588.826 von Aliberto am 09.07.07 11:14:43

aah ok, Roche-Deal

[Fruehrentner]

Breaking News on Drug Discovery

AstraZeneca and Roche jump on siRNA bandwagon

By Mike Nagle

09/07/2007- AstraZeneca (AZ) and Roche have became the latest big pharma firms to invest in RNA interference (RNAi), having penned separate licensing deals with two of the industry's leading specialists in the field.

Roche has today announced it has committed "over a billion dollars" to a deal with Alnylam Pharma. This includes $331m (€243m) to license Alnylam's RNAi technology and also buy its research site in Germany, which will become Roche's 'Center of Excellence' for RNAi.

Meanwhile, AZ has agreed to pay Silence Therapeutics up to £200m (€295m) to develop RNAi drugs based on small interfering RNA (siRNA) technology for up to five disease targets nominated by AZ. The two companies stated that although these are "primarily" respiratory diseases, the deal could be extended to cover other therapeutic areas.

The two firms are just the latest in a string of pharma heavyweights that have invested heavily in RNAi technology for drug design - as opposed to its other main uses, such as gene screening and target identification and validation. Of those investors, only Merck & Co. has bought a whole company, rather than doing licensing deals. It bought Sirna Therapeutics for $1.1bn (€850m), and one company insider told DrugResearcher.com, the move has "re-invigorated" the company.

In addition to the upfront payment, Roche has also set aside over $700m - the exact amount is undisclosed - for a joint research programme with Alnylam against one or more disease targets in oncology, respiratory diseases, metabolic diseases and certain liver diseases.

Roche's head of global pharma research, Lee Babiss, said the deal provides it "with new capabilities to target complex diseases within our focus areas."

Similarly, AZ entered its collaboration with Silence to build on investments in biopharma and vaccines. Jan Lundberg, head of discovery research at AZ, explained that it will enable the company to "target disease mechanisms intractable to small molecules and other approaches."

Silence Therapeutics, which changed its name from SR Pharma in April, will receive a much smaller initial fee of £7.5m and the rest of the £200m will be in the form of undisclosed milestone payments. Should the three-year collaboration bear fruit, it will also receive royalties on product sales.

"This transaction provides further validation of the potential application of Silence Therapeutics' proprietary AtuRNAi molecules and our leading position in the fast developing field of RNAi therapeutics," said Iain Ross, chairman of Silence Therapeutics.

That technology comes from Silence's acquisition of Atugen back in 2005. Ross explained that its technology may prove to be superior to other siRNAs for several reasons. It is chemically modified to be blunt-ended and stabilised against nuclease degradation. This could lead to a longer half-life, lower doses and less frequent administration. Also, AtuRNAi molecules are based only on naturally occurring RNA and so there are no toxic metabolites.

Should this latest deal between AZ and Silence Therapeutics be extended beyond respiratory diseases, it may be worth noting that Silence Therapeutics is a self-confessed cancer specialist and, of all of the drugs in the smaller company's pipeline, only its anticancer programmes remain unlicensed.

That is because this is actually the second time Silence has benefited from big pharma interest in its research. Another of its drugs was licensed - from Atugen - to Quark Biotech, which subsequently licensed it to Pfizer.

RTP-801i, which blocks the REDD-1 gene, is in development for three separate indications. The only programme to have reached the clinic so far is for wet Age-related Macular Degeneration (AMD) where aberrant blood vessels beneath the retina leak blood and fluid into the eye, causing vision loss. The other two indications that Pfizer and Quark are pursuing are diabetic retinopathy and chronic obstructive pulmonary disease.

It is also the second time Alnylam has attracted big pharma attention: Novartis has a stake in the company that was founded by the leading scientists who pioneered the discovery of RNAi. Alnylam currently has one product in clinical development - ALN-RSV01 - in Phase I trials for Respiratory Syncytial Virus.

It is unusual, but becoming less so, for big pharma to throw large sums of money at such early stage technology: there are currently only five siRNA drugs in clinical trials. Until more clinical data is released, the companies involved will be holding their collective breath to see how worthwhile their investment has been.

"If RNAi can be shown to be delivered systemically, we will see a new drug class," concluded Ross.

http://www.drugresearcher.com/news/ng.asp?n=78021-astrazenec…

[aktianer]

Antwort auf Beitrag Nr.: 30.611.261 von Fruehrentner am 10.07.07 12:03:07

Kurs zieht heute schon kräftig an (im Moment 26,5 U$) - wäre schön, wenn die morgen kommenden Quartalszahlen und vor allem die News dies auch bestätigen würden:

Alnylam Pharmaceuticals Earnings Call scheduled for Thu, Aug 9
live tomorrow at 4:30 pm ET

[Fruehrentner]

Antwort auf Beitrag Nr.: 31.082.102 von aktianer am 08.08.07 16:49:37

oha!! Tatsächlich satter Aufschlag heut!

Ich hatte diese Perle schon in 2005 ausgegraben, da wusste noch keiner, was mRNAI bedeuet - nur dummerweise hab ich nicht investiert

[aktianer]

Antwort auf Beitrag Nr.: 31.083.948 von Fruehrentner am 08.08.07 18:22:09

Aufschlag ist gestern leider im späteren Handel zu einem kleinen Abschlag geworden; vor Publizierung der Zahlen biet Alny aber noch ein kleines Schmankerl:

Alnylam Awarded $38.6 Million U.S. Government Contract to Develop RNAi Therapeutics for Biological Threats
Thursday August 9, 8:00 am ET
- Funding to Support Alnylam Biodefense(TM) and RNAi Technology Development Efforts -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that it has been awarded a $38.6 million contract over 33 months from the United States Defense Threat Reduction Agency (DTRA) to develop a broad spectrum RNAi anti-viral therapeutic for the treatment of viral hemorrhagic fever. Viral hemorrhagic fevers are considered by federal agencies to be high priority agents that pose a risk to national security because they can be easily disseminated from person to person, result in high mortality rates, and require special action for public health preparedness.

ADVERTISEMENT
The Alnylam Biodefense initiative has the potential to create near-term value from the company's RNAi therapeutic platform, such as obtaining FDA approval for products in an accelerated timeframe and revenues from government stockpiling. In addition, funding from this initiative allows Alnylam to further extend its capabilities in a manner that can be leveraged across its entire proprietary and partnered pipeline.

"This funding represents continued federal government support of RNAi as a potential therapeutic platform for biodefense and biopreparedness, while allowing us to continue to develop our technology as we advance our pipeline programs," said Barry Greene, Chief Operating Officer of Alnylam. "Combined with our Ebola contract from the National Institutes of Health for $23 million awarded in September 2006 and other sources of federal funding, we have now been granted more than $63 million in federal contracts for Alnylam Biodefense."

The goal of this research program is to develop an RNAi therapeutic for the treatment of hemorrhagic fever virus infection. Alnylam's program will investigate the silencing of endogenous host targets believed to be involved in viral pathogenesis and disease progression. This new contract fully supports all activities from program initiation through Phase I trials. With this program, as with its Ebola program, Alnylam is working with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), an organization uniquely experienced in the handling, safety, and security requirements of specialized biological agents. Alnylam will be producing drug candidates which will be sent to USAMRIID for in vitro and in vivo testing against viral hemorrhagic fevers.

This new federal contract (No. HDTRA1-07-C-0082) is with the DTRA 2007 Medical Science and Technology Chemical and Biological Defense Transformational Medical Technologies Initiative (TMTI), whose mission is to protect the warfighter from conventional or genetically engineered biological threats, known or emergent, by accelerating the seamless discovery and development of broad spectrum medical countermeasures through the use of novel technology platforms and innovative management approaches.

[aktianer]

Zahlen 2.Quartal 2006:

Alnylam Posts Wider Loss

By Elizabeth Trotta
Staff Reporter
8/9/2007 7:15 PM EDT

RNAi therapeutics company Alnylam Pharmaceuticals (ALNY - Cramer's Take - Stockpickr - Rating) reported a widened second-quarter loss late Thursday but upped year-end cash estimates.

Alnylam recorded a net loss of $12.7 million, or 34 cents a share, compared with $9.9 million, or 31 cents a share, in the year-prior period. That's including a 5-cent-per-share stock-based compensation expense in both quarters.

Analysts surveyed by Thomson Financial had expected a loss of 24 cents a share on revenue of $7.1 million.

Alnylam reported revenue of $9.1 million, compared with $6 million during the year-ago quarter. This year's revenue included $4.4 million related to Alnylam's collaborations with Novartis (NVS - Cramer's Take - Stockpickr - Rating), $2.8 million from the National Institutes of Health for Ebola, and $1.9 million of expense reimbursement and amortization revenues from
Biogen Idec (BIIB - Cramer's Take - Stockpickr - Rating), Merck (MRK - Cramer's Take - Stockpickr - Rating), research reagent and services licensees, and other sources.

The company increased its year-end 2007 cash guidance to greater than $435 million from greater than $180 million to reflect its alliance with Roche. Alnylam also announced that it has completed the previously announced deal with the Swiss drugmaker.

The company's shares closed up 2.1% at $25.98 and rose another 0.9% to $26.20 in postmarket trading.


http://www.thestreet.com/_yahoo/newsanalysis/biotech/1037349…

[aktianer]

Alnylam Closes Roche Deal
Thursday August 9, 4:58 pm ET
Alnylam Pharmaceuticals Closes on Strategic Alliance With Roche

CAMBRIDGE, Mass. (AP) -- Alnylam Pharmaceuticals Inc. said Thursday it is closed on its previously announced alliance with Roche.

In July, the company said Switzerland-based Roche licensed rights to Alnylam's gene-silencing technology. Roche is required to make aggregate payments to Alnylam of about $331 million including an upfront cash payment within 10 days of the closing. The Roche Venture Fund also bought about $42.5 million in Alnylam common stock.

Roche also completed the buyout of Alnylam's European research site in Kulmbach, Germany.

Gene-silencing technology works by silencing the gene at the root of a condition or disease.

Shares of Alnylam rose 53 cents, or 2.1 percent, to close at $25.98.

http://biz.yahoo.com/ap/070809/alnylam_pharmaceuticals_contr…

[aktianer]

Alnylam, Isis form venture to target microRNA drugs
Fri Sep 7, 2007 12:33AM EDT

NEW YORK, Sept 7 (Reuters) - Alnylam Pharmaceuticals Inc (ALNY.O: Quote, Profile, Research) and Isis Pharmaceuticals Inc (ISIS.O: Quote, Profile, Research) said on Friday they had formed a joint venture focusing on development of microRNA drugs, which regulate networks of genes that can be involved in disease processes.

The venture, Regulus Therapeutics LLC, will be operated as an independent company with an independent board of directors and management team, the companies said.

Alnylam will initially invest $10 million, and after that the companies will share funding of Regulus. They will grant exclusive licenses to Regulus to their intellectual property for therapeutic applications, as well as to certain early fundamental patents in the field.

Alnylam and Isis will retain rights to develop and commercialize on pre-negotiated terms products that Regulus decides not to develop either itself or with a partner, the companies said.

MicroRNAs are a recently discovered class believed to regulate the expression of a large number of human genes, the companies said.

"The opportunity to antagonize microRNAs could create a new frontier for pharmaceutical research where an entire disease pathway is targeted for intervention, not just a single disease target," Alnylam CEO John Maraganore said in a statement.

(Reporting by Lewis Krauskopf)

http://www.reuters.com/article/marketsNews/idUKN074083982007…

[aktianer]

Alnylam Shares Rise on Cantor Upgrade
Tuesday September 11, 10:05 am ET
Alnylam Pharmaceuticals Shares Rise on Cantor Fitgerald's MicroRNA Technology Outlook

NEW YORK (AP) -- Shares of Alnylam Pharmaceuticals Inc. rose Tuesday after Cantor Fitgerald upgraded the stock, citing the company's deal with Isis Pharmaceuticals Inc. and a positive outlook for microRNA technology.

ADVERTISEMENT
On Friday, Alnylam and Isis Pharmaceuticals Inc. launched a joint venture called Regulus Therapeutics LLC, to develop microRNA-based therapies. The independent company's board is being chaired by Nobel Laureate David Baltimore, who won the Nobel Prize for physiology and medicine in 1975.

Cantor Fitgerald analyst Pamela Bassett upgraded Alnylam to "Buy" and raised her price target to $32 from $20. Shares of Alnylam rose $1.34, or 5.1 percent, to $27.58 in morning trading. The stock reached a 52-week high of $27.60 early in the session.

MicroRNA technology controls protein production within cells and could be used to turn off certain genes, in effect treating a condition at the genetic level.

"We think assembling microRNA assets into Regulus strengthens Alnylam's position to further leverage its RNAi licensing success into a next generation RNA technology platform and consolidates Alnylam's leadership position," she wrote in a note to clients.

Bassett has a positive outlook on the technology, also reaffirming a "Buy" rating for biotechnology Rosetta Genomics Ltd. Rosetta, which had its IPO March 6, focuses on developing therapies and diagnostics based on microRNA.

"We consider microRNA a rapidly emerging technolgy that will enable the development of therapeutics operating at the master-swittch level of genetic control," Bassett wrote.

Rosetta is also collaborating with Isis and could start preclinical testing on several compounds aimed at decreasing liver cancer by the end of the year. In addition, Rosetta controls the vast majority of all validated human therapeutic targets, giving it a strong patent position in the emerging technology.

"We expect microRNA technology to drive breakthroughs in diagnostics, biotherapeutics and small molecule drug discovery, condense development timelines and provide a vast store of new therapeutics targets and biomarkers," Bassett said.

Shares of Rosetta were unchanged at $5.30 in morning trading.

http://biz.yahoo.com/ap/070911/alnylam_pharmaceuticals_mover…

[aktianer]

Zusammenarbeit mit Merck wird beendet - trotzdem: vorbörslicher Kurs bewegt sich deutlich nach oben und liegt zwischen 32 und 33U$:

19-Sep-2007
Termination of a Material Definitive Agreement
Item 1.02. Termination of a Material Definitive Agreement.
On September 18, 2007, Alnylam Pharmaceuticals, Inc. ("Alnylam") and Merck & Co., Inc. ("Merck") agreed to terminate their Amended and Restated Collaboration and License Agreement, effective as of July 3, 2006 (the "Collaboration Agreement"), pursuant to which Alnylam and Merck collaborated in the research, development and commercialization of RNAi products directed to certain targets (as defined in the Collaboration Agreement).
Pursuant to the Termination Agreement between Alnylam and Merck, all license grants of intellectual property to develop, manufacture and/or commercialize RNAi therapeutic products under the Collaboration Agreement cease as of the date of the Termination Agreement, subject to certain specified exceptions. The Termination Agreement further provides that, subject to certain conditions, Alnylam and Merck will each retain sole ownership and rights in their own intellectual property.

[aktianer]

Hintergrund zum Abbruch der Zusammenarbeit mit Merck & Co.:

Alnylam ends agreement with Merck amid tensions
Wed Sep 19, 2007 9:44am EDT

BOSTON, Sept 19 (Reuters) - Alnylam Pharmaceuticals Inc. (ALNY.O: Quote, Profile, Research), which is developing a promising drug discovery technology known as RNAi, said on Wednesday it has broken a partnership with Merck & Co. (MRK.N: Quote, Profile, Research) amid tensions following Merck's acquisition of a rival company.

Barry Greene, Alnylam's chief operating officer, said Alnylam initiated the termination of the agreement and rescinded access to its intellectual property.

Ian McConnell, a spokesman for Merck, said the big drugmaker wanted more freedom than it had under its agreement with Alnylam.

Alnylam has formed dozens of partnerships with big pharmaceutical companies, and said ending the one with Merck will have no bearing on its finances. It maintained guidance that it will have $435 million in cash by the end of the year.

Alnylam's shares rose 2.3 percent to $31.80 in early trading on Nasdaq.

In October 2006, Merck agreed to pay $1.1 billion for Sirna Therapeutics Inc., a rival developer of RNAi technology. (Additional reporting by Martinne Geller)

[aktianer]

26.09.2007 - 1:49PM - Alnylam Pharmaceuticals and collaborators note new research shows that RNAI efficacy can be achieved without disruption of the Endogenous microRNA pathway (ALNY) 34.04 +0.82 :

ALNY announces the publication of a key study in the journal Nature by Alnylam and scientists at Roche Kulmbach, together with collaborators from the Swiss Federal Institute of Technology, UT Southwestern Medical Center at Dallas, and the Massachusetts Institute of Technology. In the study, acute and repeated dosing of small interfering RNAs (siRNAs), the molecules that mediate RNAi, was found to achieve specific and robust silencing of target genes in vivo without any disruption of the endogenous microRNA pathway.

http://finance.yahoo.com/marketupdate/inplay#alny

[Fruehrentner]

Alnylam Presents First Ever Non-Human Primate Data with an RNAi Therapeutic Targeting PCSK9 Showing Significant and Durable Reductions in LDL Cholesterol Levels

08 Oct 2007

New Findings for RNAi Therapeutic Targeting PCSK9 Presented at the XVI International Symposium on Drugs Affecting Lipid Metabolism

CAMBRIDGE, MA, USA | October 8, 2007 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it presented new pre-clinical data from its hypercholesterolemia program at the XVI International Symposium on Drugs Affecting Lipid Metabolism held in New York City, October 4 - 7, 2007. This program is in collaboration with UT Southwestern Medical Center at Dallas and is focused on evaluating new approaches for reducing LDL cholesterol levels using RNAi therapeutics directed to the disease target proprotein convertase subtilisn/kexin type 9, or PCSK9, a target believed to be undruggable with conventional therapeutic strategies.

Alnylam scientists and collaborators presented new non-human primate data demonstrating PCSK9 antagonism with an RNAi therapeutic. Data presented at the meeting include the following:

-- in vivo systemic administration of an RNAi therapeutic in non-human primates resulted in efficient silencing of the PCSK9 gene as measured by circulating PCSK9 plasma levels which were reduced by up to 70 percent of pre-dose levels;

-- RNAi-mediated gene silencing was associated with rapid reductions in LDL cholesterol ("bad cholesterol") levels by 40 to 60 percent of pre-dose levels;

-- reduction in circulating apolipoprotein B (apoB) levels - a constituent of the LDL particle - by 30 to 40 percent of pre-dose levels were also demonstrated;

-- after a single intravenous injection, which was well tolerated in these studies, the RNAi therapeutic showed a durable biological effect with levels of LDL cholesterol decreased for up to three weeks; and

-- therapeutic efficacy was observed with an overall decreased ratio of total cholesterol to HDL cholesterol ("good cholesterol") - a result which has been shown in humans to correlate with clinical benefit.

"We are very excited about the significance of these findings, which show for the first time a strong effect for acutely and durably improving cholesterol levels by antagonizing PCSK9 with an RNAi therapeutic in non-human primates," said Victor Kotelianski, M.D., Ph.D., Vice President for Research at Alnylam. "Although PCSK9 is well validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. It is gratifying to have obtained non-human primate efficacy data within one year of initiating our PCSK9 program, a clear positive for drug discovery efforts on RNAi therapeutics."

PCSK9 is an important gene involved in the metabolism of LDL cholesterol. The normal role of the PCSK9 protein is to break down the cell surface receptor for LDL; when there is less PCSK9 protein, there is more receptor on the cell surface to remove LDL from the bloodstream. In human studies, researchers at UT Southwestern Medical Center at Dallas have discovered that mutant forms of PCSK9 that have increased activity are linked with a familial form of hypercholesterolemia. Conversely, recent research published in the New England Journal of Medicine (N. Engl. J. Med. 354, 1264-1272, 2006) has demonstrated that other mutations in humans, including those that lower PCSK9 function, are associated with decreased cholesterol levels and an 88 percent risk reduction in cardiovascular disease.

"There is a clear unmet medical need for novel agents that can lower LDL cholesterol, and PCSK9 appears to be an excellent target for disease intervention in hypercholesterolemia," said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center at Dallas. "Based on its novel mechanism of action and pre-clinical data to date, an RNAi therapeutic targeting PCSK9 has the potential to lower LDL cholesterol, while possibly functioning synergistically with statins in the treatment of hypercholesterolemia."

Alnylam is developing ALN-PCS01, an RNAi therapeutic targeting PCSK9, for the treatment of hypercholesterolemia; ALN-PCS01 is a systemically delivered RNAi therapeutic comprised of an optimized small interfering RNA (siRNA) encapsulated in a cationic liposomal nanoparticle formulation. Alnylam expects to file one investigational new drug (IND) application this year from its portfolio of systemically delivered RNAi therapeutic programs, which include ALN-PCS01 and ALN-VSP01, an RNAi therapeutic for the treatment of liver cancers and potentially other solid tumors. As these are Alnylam's first systemic delivery programs, the timing of this IND will depend on many development efforts, including the results of GLP toxicology studies, which are currently ongoing.

In addition, at the International Symposium Third Annual Meeting of the Oligonucleotide Therapeutics Society held October 4-6, 2007 in Berlin, Alnylam scientists presented an overview of the company's development programs, including its lead program, ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection. ALN-RSV01 is in a Phase II trial to evaluate its safety and anti-viral efficacy in an experimental infection model. This blinded, placebo-controlled trial is currently enrolling subjects on schedule and the company goal is to announce top-line results by the end of this year, with complete data from this trial to be presented at a scientific meeting in early 2008.

About RNA Interference (RNAi)
RNAi is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today, and was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of influenza, hypercholesterolemia, and liver cancers, among other diseases. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. The company, founded in 2002, maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including the timing for the filing of an investigational new drug application for, and statements regarding the development of, ALN-PCS01 and ALN-VSP01, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; our ability to attract and retain highly qualified employees; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales and distribution of products; the successful development of Alnylam's product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We do not assume any obligation to update any forward-looking statements.

SOURCE: Alnylam Pharmaceuticals, Inc.

http://www.pipelinereview.com/joomla/content/view/15076/114/


Ärgere mich immer noch, dass ich vor 2,5 J. nicht eingestiegen bin (Kurs damals: um 5 EUR).

[Fruehrentner]

Weiss jemand, wie hoch aktuell die Marktkapitalisierung von Alnylam ist?

[aktianer]

Antwort auf Beitrag Nr.: 31.909.904 von Fruehrentner am 09.10.07 13:58:38

beim aktuellen kurs von 32,87 U$ beträgt die Marktkap 1.24 Mrd.U$.
Vielleicht kommt nochmals eine Einstiegschance - im Moment scheinen doch einige Anleger ihre Gewinne zu realisieren.

[Fruehrentner]

Alnylam granted German patent for RNAi therapeutics

27th November 2007
By Staff Writer

The German Patent Office has granted Alnylam Pharmaceuticals a patent that includes 52 claims broadly covering medicaments comprising of small interfering RNAs.


The covered small interfering RNAs (siRNAs) are 15 to 49 nucleotide pairs in length. Alnylam said that the new Kreutzer-Limmer patent extends the worldwide scope for issued claims covering siRNA technology to Germany, the largest national pharmaceutical market of the European Union.

The patent series has been licensed to Alnylam's four pharmaceutical collaboration partners, seven biotechnology companies in Alnylam's InterfeRx program and 15 companies in the research reagent and services market. The patent is enforceable in Germany against potential infringers using the patented technology without an Alnylam license.

John Maraganore, president and CEO of Alnylam, said: "Our intellectual property estate for RNAi therapeutics remains unparalleled in the industry, and represents an important component of our efforts to bring our innovative medicines to patients.

"Importantly, the newly granted DE 10080167 patent covers a broad scope of medicaments containing siRNA structures having a length of 15 to 49 nucleotides which includes the so-called 'blunt end' or 'dicer substrate' design with or without chemical modifications, as well as other possible features."

[Fruehrentner]

Alnylam Reports Continued Progress in Clinical Development of ALN-RSV01 for the Treatment of Respiratory Syncytial Virus (RSV) Infection

13 Dec 2007

Company Reports Phase I Clinical Safety Results with Inhalation Dosing of ALN-RSV01 and New Pre-clinical Multi-Dose Data


CAMBRIDGE, MA, USA | December 13, 2007 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the presentation of results from its Phase I trial with ALN-RSV01 delivered via inhalation at the 18th Annual Drug Delivery to the Lungs meeting being held in Edinburgh, U.K. These data represent an important milestone in the company's efforts to advance ALN-RSV01 as an anti-viral drug for the treatment of RSV infection in patients. The Phase I study represents the first-ever clinical study of an RNAi therapeutic administered via inhalation.

This Phase I study was a randomized, double-blind, placebo-controlled trial in healthy adult volunteers to assess the safety, tolerability, and pharmacokinetics of inhaled ALN-RSV01 administered via nebulizer. All major objectives of the trial were met, including definition of a safe and well-tolerated dose and regimen for advancement of ALN-RSV01 into further Phase II development.

"These results put us firmly into Phase II development with the ongoing experimental infection study, and now with a planned multi-dose inhalational Phase II strategy in naturally infected adults," said Akshay Vaishnaw, M.D., Ph.D., Vice President, Clinical Research of Alnylam. "With these data in hand, and the upcoming Phase II data expected in the first quarter of 2008, we are excited about the continued development of this novel RNAi therapeutic."

In total, 109 subjects were enrolled in the Phase I trial; 71 were exposed to drug and 38 to placebo. Both single and multiple doses were evaluated, ranging from the equivalent of 0.1 mg/kg to 3 mg/kg in the single dose arm, and 0.01 mg/kg to 0.6 mg/kg, administered once daily for 3 days in the multi-dose arm. Data showed that the efficiency of delivery of ALN-RSV01 delivered via inhalation, as measured by plasma levels, was significantly greater in humans than observed pre-clinically. Adverse events reported for both drug and placebo were predominantly mild; there were no severe or serious adverse events. In the single dose arm, a mild to moderate flu-like adverse event was observed at the higher doses. This was found to be transient and was potentially linked to the enhanced efficiency of delivery. In the multi-dose arm, daily doses up to 0.6 mg/kg for 3 days were found to be safe and well tolerated, pointing to a dose and regimen of ALN-RSV01 for further Phase II evaluation.

Other updates from the presentation in Edinburgh today included the following.

-- New Pharmacology Data. Previous pre-clinical data had shown the ability of a single dose of ALN-RSV01 to potently reduce virus load in a mouse RSV model. Additional pre-clinical data
reported today now significantly extend these observations.
Comparison of multi-dose and single dose ALN-RSV01 treatment paradigms demonstrated that a multi-dose regimen (once daily for 3 days) is significantly more efficacious than a single dose, for the same total amount of drug.

-- Ongoing Phase II Experimental Infection Study with ALN-RSV01. The company announced today that the Phase II study in experimentally infected adult volunteers is now fully enrolled with 88 subjects and top-line data are expected early in the first quarter 2008.

"In addition to our Phase I inhalational data, we are particularly encouraged by the new complementary pre-clinical data demonstrating enhanced anti-viral activity for ALN-RSV01 administered in multiple doses," said Sara Nochur, Ph.D., Vice President, Regulatory Affairs of Alnylam and RSV Program Leader. "Indeed, our current Phase II study of ALN-RSV01 in experimentally infected subjects, that has now completed enrollment and remains blinded, has incorporated the use of a multi-dose treatment both prior to and after viral inoculation."

"I am excited by the rapid progress that has been made with ALN-RSV01, as there is significant need for a novel therapy to treat RSV, a serious viral infection that hospitalizes over 320,000 pediatric and adult patients in the U.S. annually," said John P. DeVincenzo, M.D., Associate Professor of Pediatrics and Infectious Diseases at the University of Tennessee Health Science Center. "These new inhalational tolerability data greatly extend our understanding of ALN-RSV01 and add to the existing encouraging safety profile via the intranasal route. In aggregate, the significant safety database supports continued Phase II development of ALN-RSV01 in RSV-infected children and adults."

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of influenza, hypercholesterolemia, and liver cancers, among other diseases. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. The company, founded in 2002, maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation statements concerning the commencement of clinical trials and studies, the availability of results of clinical trials and studies, the need for novel RSV therapeutics, the expected formulation for an RSV therapeutic, and our views with respect to the potential for RNAi therapeutics, including ALN-RSV01, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and Alnylam's short operating history; as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

SOURCE: Alnylam Pharmaceuticals, Inc.

[aktianer]

kleinerer Zahlungseingang:

Alnylam and Collaborators Receive LEAPS Award from Michael J. Fox Foundation for Parkinson's Research; Enter into Research Collaboration
Friday January 4, 1:29 pm ET
- New Grant Totaling $3.8 Million Awarded for Development of RNAi Therapeutics for the Treatment of Parkinson's Disease -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, today announced that it was part of a research team awarded a new $3.8 million grant from The Michael J. Fox Foundation (MJFF) to further develop an RNAi therapeutic for the treatment of Parkinson’s disease. The four-year grant, which is part of the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson’s Institute and Clinical Center of Sunnyvale, California. MJFF fosters collaboration between industry and academia through its LEAPS program as one strategy to accelerate progress toward the development of new and improved interventions for Parkinson’s disease.

“We are excited to be continuing our work with Mayo Clinic and the Parkinson’s Institute that builds upon a MJFF Target Validation award granted to Alnylam in 2005. We look forward and remain committed to advancing this therapeutic strategy to patients,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “We believe that RNAi therapeutics, due to their novel mechanism of action, may have a significant impact in the treatment of Parkinson’s disease and address this neurodegenerative disorder in a fundamentally new way.”

“Available Parkinson’s treatments mask symptoms but do nothing to halt or slow underlying disease progression,” said Katie Hood, chief executive officer of MJFF. “More and more scientific evidence supports the hypothesis that lowering alpha-synuclein levels in the brain could achieve the so-called ‘Holy Grail’ of PD research, a neuroprotective therapy. But no drugs have been identified to date that are capable of reducing alpha-synuclein expression; new approaches are needed. This LEAPS grant is characteristic of how The Michael J. Fox Foundation goes about its work – making big bets on fresh ideas with great potential to impact patients’ quality of life.”

The LEAPS award will fund research focused on the further development of an RNAi therapeutic targeting alpha-synuclein. Alpha-synuclein may play a role in the development of Parkinson’s disease. Continued research will look at whether reducing levels of alpha-synuclein in the brain can slow or halt disease progression. Alnylam and collaborators have designed and synthesized small interfering RNAs (siRNAs), the molecules that mediate RNAi, that are specific to the alpha-synuclein gene. Previously reported in vivo data show that siRNAs administered into the brain were effective in reducing alpha-synuclein levels. To date, no drugs have been identified that are capable of lowering alpha-synuclein levels in the brain. These data suggest the applicability of RNAi therapeutics as a possible disease-modifying therapy for Parkinson’s disease.

“With this generous and important grant we share an exciting optimism regarding RNAi therapeutics. This completely novel approach may well be the next big step toward releasing people with Parkinson’s from the disabilities they endure every day,” said J. William Langston, M.D., Scientific Director and Chief Executive Officer, Parkinson’s Institute and Clinical Center. “We are proud to join in taking this major scientific leap forward.”


http://biz.yahoo.com/bw/080104/20080104005494.html?.v=1

[aktianer]

Antwort auf Beitrag Nr.: 32.968.669 von aktianer am 07.01.08 16:38:08

Alnylam eyes four or more new deals; shares rise
Mon Jan 7, 2008 11:07am EST

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(Adds planned deals, trials; changes dateline, previously Chicago)

NEW YORK, Jan 7 (Reuters) - Alnylam Pharmaceuticals Inc (ALNY.O: Quote, Profile, Research), developer of a promising drug technology known as RNA interference, on Monday said it expects at least four major new collaborations by late 2010, including two or more this year with leading companies.

Alnylam, whose shares rose 3.5 percent, provided its outlook ahead of a planned appearance later Monday at the annual JP Morgan Healthcare Conference in San Francisco.

The tiny biotechnology company, whose technology is designed to shut down the body's production of harmful proteins by interfering with specific genes, in July signed a drug-development deal with Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) potentially worth up to $1 billion, and has a major partnership with Swiss drugmaker Novartis AG (NOVN.VX: Quote, Profile, Research).

Alnylam said the four or more major new business deals it expects to complete by late 2010 include alliances "similar to the company's July 2007 partnership with Roche."

The company said it aims this year to ask regulators for permission to conduct human testing of another drug, possibly one to treat high cholesterol or liver cancer.

Alnylam said it now expects to have closed 2007 with cash holdings of more than $450 million, up from an earlier forecast of more than $435 million.

The Cambridge, Massachusetts-based company also said it expects to finish 2008 with more than $390 million in cash as it aims to form new delivery technology partnerships.

Alnylam shares were up $1.01 at $30.01 in morning trading on the Nasdaq. (Reporting by Ransdell Pierson with additional reporting by Susan Kelly in Chicago; editing by Maureen Bavdek)

http://www.reuters.com/article/marketsNews/idUKN073986452008…

[Fruehrentner]

07.01.2008 14:01:00

Alnylam Launches its RNAi 2010 Outlook for Key Scientific, Clinical, and Business Initiatives; Announces Goals and Guidance for 2008

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today announced that it has launched its “RNAi 2010” outlook for key scientific, clinical, and business initiatives as the company maintains its commitment to translating the science of RNAi into innovative medicines and building a leading biopharmaceutical company. The company also announced its product and business goals for 2008, the initiation of a development program, and updated its 2007 year-end cash position.

“We are more confident than ever regarding the significance of the RNAi opportunity and Alnylam’s leadership in realizing its fullest potential. Accordingly, we have launched our ‘RNAi 2010’ plan as a new initiative focused on achieving major scientific, clinical, and business milestones by the end of 2010,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Execution on this ‘RNAi 2010’ plan will continue to advance RNAi therapeutics as a transformative approach for new medicines and our mission of building a leading biopharmaceutical company founded on RNAi.”

RNAi 2010 Plan

Scientific Leadership. By the end of 2010, Alnylam expects to broaden its leadership and significantly expand the scope of delivery solutions for RNAi therapeutics. This will be achieved by the continued scientific leadership of Alnylam scientists and current academic and industry collaborators, but also a significant external effort to form new delivery technology partnerships. Further, this effort will include the significant expansion of the range of tissues and cell types where the company aims to achieve efficient delivery of RNAi therapeutics with both direct and systemic delivery approaches.
Clinical Pipeline. By the end of 2010, Alnylam expects to have four or more RNAi therapeutic programs in clinical development. These include direct and systemic RNAi programs, Alnylam proprietary and 50/50 partnership programs, and siRNA (short interfering RNA) and miRNA (microRNA) therapeutics.
New Business Collaborations. Based on its scientific, clinical, and intellectual property leadership, the company also expects to form four or more new major business collaborations by the end of 2010. These are expected to include the completion of additional broad platform alliances similar to the company’s July 2007 partnership with Roche. Completion of these business collaborations is expected to provide the company significant resources and funding to advance Alnylam’s proprietary and 50/50 partnership pipeline programs.
2008 Goals and Guidance

Opportunity to Demonstrate Human Proof-of-Concept with RNAi Therapeutic. Alnylam’s lead program, ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, is currently in a Phase II experimental infection study in adult volunteers. Enrollment for this study was completed in December and the study remains blinded. Top-line results from this study are expected early in the first quarter of 2008 and offer the industry’s first opportunity to demonstrate human proof-of-concept with an RNAi therapeutic.
Advance Clinical Pipeline. Assuming a positive outcome for its current Phase II experimental infection study, Alnylam intends to initiate an additional Phase II study with ALN-RSV01 for the treatment of RSV in an adult patient population in the first half of 2008. The company also expects to file a new investigational new drug (IND) application from its development pipeline in 2008, with candidates including ALN-PCS for the treatment of hypercholesterolemia and ALN-VSP for the treatment of liver cancer. Finally, the company expects that several clinical stage compounds under development by third party Alnylam licensees will continue to advance the expanding field of RNAi therapeutics.
Publish 10 or More Key Scientific Papers. Alnylam expects to continue its leading scientific efforts with the publication of key data related to in vivo efficacy and systemic delivery of RNAi therapeutics, as well as advancements with miRNA therapeutics.
Form Two or More Major New Alliances. In 2008, Alnylam intends to form two or more new alliances with leading companies to continue to develop and fund its growing pipeline of RNAi therapeutics. This includes potential platform license agreements such as the company’s July 2007 collaboration with Roche.

Continue Significant Intellectual Property (IP) Leadership. In 2008, Alnylam expects to receive many additional patent issuances or grants from patent offices around the world for fundamental, chemistry, delivery, target, and miRNA therapeutic IP elements.
Maintain Solid Financial Performance. Alnylam announced today that it now expects to achieve a 2007 year-end cash position of greater than $450 million, as compared with its previous 2007 cash guidance of greater than $435 million. In 2008, the company aims to maintain a solid financial position while executing on its product and business goals, and expects to end the year with greater than $390 million in cash.

“Overall, 2007 was a very successful year in our efforts to deliver on the promise of RNAi therapeutics. In 2008, consistent with our ‘RNAi 2010’ plan, we intend to build on this substantial progress across the four key dimensions of our business: scientific leadership, products, intellectual property, and business execution,” said Barry Greene, President and Chief Operating Officer of Alnylam. “Importantly, we believe that advancement of our science and product pipeline will continue to demonstrate the importance of RNAi therapeutics as an innovative new class of drugs, and that these achievements together with our intellectual property estate will continue to support our ability to execute on major business opportunities.”

Huntington’s Disease Program

Alnylam also announced today that it has advanced an RNAi therapeutic development program targeting the huntingtin gene for the treatment of Huntington’s disease. Huntington’s disease is an autosomal dominant neurodegenerative genetic disease that afflicts approximately 30,000 patients in the U.S., with an estimated 150,000 additional patients having a 50 percent risk of developing the disease. The disease is caused by mutations in the huntingtin gene leading to expression of a toxic mutated protein. This program, designated ALN-HTT, is in partnership with Medtronic, Inc., which is structured as a 50/50 co-development/profit share relationship in the U.S. market. In Europe, Medtronic is solely responsible for development and commercialization. Alnylam scientists and collaborators have published and presented in vivo data demonstrating efficacy for an siRNA targeting the huntingtin gene in a mouse model of Huntington’s disease (DiFiglia et al., PNAS, 104, 17204 - 17209 (2007)).

“The scientific teams at Alnylam and Medtronic have made excellent progress in our joint Huntington’s program and we’re excited to advance ALN-HTT as a development program, extending our pipeline of RNAi therapeutics,” said Akshay Vaishnaw, M.D., Ph.D., Vice President, Clinical Research of Alnylam. “Pre-clinical data from our Huntington’s disease program provide a strong rationale to advance an RNAi therapeutic program for this important disease where there are simply no effective therapies for patients today.”


About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including without limitation, the need for novel RNAi therapeutics, Alnylam’s views with respect to the potential for RNAi therapeutics, including ALN-RSV01, and its expectations with respect to the timing and success of its clinical and pre-clinical trials, the timing of regulatory filings, its expectations regarding the development of efficient delivery of RNAi therapeutics, the formation of new alliances, and its cash position at the end of 2007 and 2008, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Media
Yates Public Relations
Kathryn Morris, 845-635-9828

Quelle:BUSINESS WIRE

[Fruehrentner]

03.01.2008 14:00:00

Alnylam Announces Continued Progress on Development of its Intellectual Property Estate Covering RNAi Therapeutics

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that the European Patent Office has granted the previously allowed Tuschl II patent. The European patent (EP 1407044 or “ ’044 Patent”) broadly covers compositions, methods, and uses of small interfering RNAs (siRNAs), the molecules that mediate RNAi. In addition, the company announced today that the German Patent Office has granted a new patent (DE 10066235 or “ ’235 patent”) in the Kreutzer-Limmer I patent series broadly covering methods, uses, and medicaments for siRNAs with a length of 15 to 49 nucleotide pairs expressed via vectors.

“The scope of our intellectual property estate, which we believe is required for the development and commercialization of RNAi therapeutics, will only continue to expand as key Alnylam patents advance through the examination stages in patent offices around the world,” said Barry Greene, President and Chief Operating Officer of Alnylam. “Importantly, access to our patent estate is enabling the creation of an entire new class of innovative medicines for patients, both through our own proprietary pipeline efforts as well as the efforts of our growing number of pharmaceutical partners and licensees.”

“We’re particularly pleased with our continued progress in the worldwide examination of the Tuschl II patent series, which includes issued or granted patents in several countries to date including the U.S. and European Union,” commented Donna Ward, Ph.D., Vice President of Intellectual Property of Alnylam. “The Tuschl II patent series stems from work performed by Dr. Tuschl and colleagues while at the Max Planck Society and is exclusively licensed to Alnylam for all therapeutic uses worldwide. This scientific work led to the first peer-reviewed publication on siRNAs and their ability to mediate RNAi in mammalian cells. Further, Dr. Tuschl’s work demonstrated the ability to use siRNAs with a broad range of lengths, chemical modifications and various design motifs, including so-called ‘blunt ends’.”

The claims for the newly granted Tuschl II ’044 patent cover compositions, methods, and uses of double-stranded RNAs having key structural elements that are widely recognized as important for the therapeutic activity of siRNAs, including, in general terms:

a double-stranded region formed from two RNA strands with a length of 19-23 nucleotides;
one or more 3'-overhangs at the ends of the double-stranded molecule;
compositions with chemical modifications on the 3'-end of the siRNA to protect against degradation and/or the use of one or more nucleotide modification, such as 2'-O-Me or 2'-F, without any limitation to the number of such modifications; and,
the use and pharmaceutical compositions of such an siRNA molecule to modulate the function of mammalian or pathogen-derived genes both in vitro and in vivo.
The claims for the newly granted Kreutzer-Limmer ’235 patent cover methods, uses, and medicaments of double-stranded RNAs, including, in general terms:

a double-stranded RNA with a length of 15 to 49 base pairs expressed in a mammalian cell through a vector; and,
methods, uses, or medicaments of such siRNAs to inhibit the expression of mammalian target genes, where such genes are oncogenes, cytokine genes, developmental genes, or infectious disease genes.
The claims of the Tuschl II ’044 and Kreutzer-Limmer ’235 patents are provided on the company’s website, together with claims from other Alnylam owned or licensed patents.

About Alnylam Intellectual Property (IP)

Alnylam’s IP estate includes issued, allowed, or granted fundamental patents in many of the world’s major pharmaceutical markets that claim the broad structural and functional properties of RNAi therapeutic products. As it applies to the U.S. and EU, these include:

the Crooke Patents (U.S. Patent Nos. 5,898,031 and 6,107,094) issued in over 12 countries and licensed exclusively from Isis Pharmaceuticals, Inc. to Alnylam for RNAi therapeutics, which cover compositions, methods, and uses of modified oligonucleotides to inactivate a target mRNA mediated by a double-stranded RNase, such as “RISC”, which is the cellular enzyme complex that mediates RNAi;
the Tuschl II ’704 patent (U.S. Patent No. 7,056,704) issued in June 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs to silence any and all disease targets;
the Tuschl II ’196 patent (U.S. Patent No. 7,078,196) issued in July 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs with or without chemical modifications;
the Tuschl II ’044 patent (EP 1407044), whose grant is announced today and is exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, and uses of siRNAs;
the Kreutzer-Limmer I ’623 patent (EP 1144623) granted in August 2002, maintained in amended form in June 2006 and owned by Alnylam, which covers methods, medicaments, and uses of siRNAs having, among other structural features, a length of 15 to 21 base pairs;
the Kreutzer-Limmer I ’945 patent (EP 1214945) granted in June 2005 and owned by Alnylam, which covers compositions, methods, and uses of siRNAs with a length between 15 and 49 nucleotides;
the Kreutzer-Limmer I ’167 patent (DE 10080167) granted in October 2007 and owned by Alnylam, which covers pharmaceutical compositions and uses of siRNAs with a length between 15 and 49 nucleotides that target certain broad categories of mammalian genes;
the Kreutzer-Limmer I ’235 patent (DE 10066235), whose grant is announced today and owned by Alnylam, which covers methods, uses, and medicaments of siRNAs, with a length between 15-49 nucleotides, expressed through a vector;
additional fundamental patents and patent applications licensed to Alnylam on an exclusive or non-exclusive basis, including those of Fire and Mello (U.S. Patent No. 6,506,559) and Glover (EP 1230375); and,
many divisional patent applications pending of the aforementioned issued or granted patents and additional patent applications pending, including patents and patent applications covering inventions by Tuschl, Hannon, and Kay.
In addition to fundamental patents, Alnylam is the exclusive licensee in the field of RNAi therapeutics for more than 150 issued chemistry patents owned or controlled by Isis Pharmaceuticals, Inc. broadly covering chemical modifications, including motifs and patterns of modifications of oligonucleotides, including RNAi therapeutics. These patents include:

phosphorothioate and 2’-O-methyl modifications of oligonucleotides (Buhr, U.S. Patent No. 6,476,205);
2’-Ribose modifications of oligonucleotides (Cook, U.S. Patent Nos. 5,670,633; 6,005,087; 6,531,584; and 7,138,517); and,
chemical conjugates of oligonucleotides (Manoharan, U.S. Patent No. 6,153,737).
In addition to fundamental and chemistry patents, Alnylam is also the exclusive licensee in the field of RNAi therapeutics for certain delivery patents, including those owned and controlled by Tekmira Pharmaceuticals, Inc. covering delivery of oligonucleotides, including RNAi therapeutics, with liposomal formulations. These patents include:

formulations of oligonucleotides, including siRNAs, in cationic liposomes (Wheeler, U.S. Patent Nos. 5,976,567 and 6,815,432; and Semple, U.S. Patent No. 6,858,225).
About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

[Fruehrentner]

23.01.2008 13:45:00

Alnylam Reports Positive Phase II Data for ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today reported positive data for the ALN-RSV01 Phase II experimental infection study, now called “GEMINI.” The GEMINI study was designed to evaluate the safety and anti-viral activity of ALN-RSV01, an RNAi therapeutic for the treatment of RSV infection. Top-line results show that ALN-RSV01 was safe and well tolerated and demonstrated statistically significant anti-viral activity. The complete results of the study will be presented at the International Symposium on Respiratory Viral Infections meeting, to be held February 28 – March 2, 2008 in Singapore.

“We are very pleased with the results of GEMINI and look forward to advancing this program to its next stage of development, a Phase II study in naturally infected adult patients which we expect to initiate in the first half of this year,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “These new data, to be presented at an upcoming scientific meeting, represent important progress for our RSV program and more generally for RNAi therapeutics, perhaps the biopharmaceutical industry’s most promising new approach for innovative medicines.”

The GEMINI study was a double-blind, placebo-controlled, randomized study of ALN-RSV01 or placebo in 88 adult subjects experimentally infected with a wild type clinical strain of RSV. The study was designed to measure the safety and anti-viral activity of ALN-RSV01, with efficacy measures including the incidence of viral infection and the effects of treatment on the degree of viral infection and resulting clinical symptoms. The study was performed using ALN-RSV01 or placebo administered intranasally for five consecutive days -- two days prior and three days after viral inoculation.

“ALN-RSV01 offers a potential new therapeutic approach for the treatment of RSV infection, a serious respiratory viral disease that leads to hospitalization in nearly 300,000 pediatric and adult patients annually in the U.S. alone,” said John P. DeVincenzo, M.D., Associate Professor of Pediatrics and Infectious Diseases at the University of Tennessee Health Science Center and Principal Investigator for the GEMINI study. “I am very encouraged by these promising new human data which demonstrate anti-viral activity for an RNAi therapeutic in a major respiratory infectious disease, and support continued development of ALN-RSV01 for the treatment of RSV infection.”



About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.


About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.


Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Media
Yates Public Relations
Kathryn Morris, 845-635-9828

Quelle:BUSINESS WIRE



Alnylam hält sich wacker in der derzeitigen, dramatischen Marktlage

[Fruehrentner]

Alnylam Patent in England erteilt!


28.01.2008 14:00:00

Alnylam Announces Grant of New Patent Covering RNAi Therapeutics in the United Kingdom

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that the United Kingdom Patent Office has granted a patent (UK 2417727 or “’727 patent”) for the Woppman et al. patent series, entitled “Double-stranded ribonucleic acid with increased effectiveness in an organism.” The newly granted patent includes 32 claims broadly covering compositions and methods, including pharmaceutical compositions, for small interfering RNAs (siRNAs), the molecules that mediate RNAi. The claims cover siRNA molecules of any length that contain “overhang” and “blunt end” design features, including siRNAs containing chemical modifications and certain novel motifs.

“Our intellectual property estate for RNAi therapeutics continues to grow substantially as evidenced by this new patent grant, the first in a distinct patent series that describes important design features for RNAi therapeutics. With this progress, we are extending the scope of our comprehensive ‘first-mover’ consolidation of early filed RNAi fundamental patents and patent applications,” said Barry Greene, President and Chief Operating Officer of Alnylam. “We expect that many additional patents owned or licensed exclusively to Alnylam will be awarded this year and in the years to come, broadening the sphere of our patent portfolio for siRNAs in markets across the world.”

“This first grant of the Woppman et al. patent covers a broad range of design features, including ‘overhangs,’ ‘blunt ends,’ and certain nucleotide motifs, that may be important for optimizing siRNAs for pharmaceutical uses,” commented Donna Ward, Ph.D., Vice President of Intellectual Property of Alnylam. “We look forward to the continued examination of this patent in other territories.”

The claims for the ’727 patent cover compositions and methods for siRNAs, including, in general terms:

a double-stranded RNA of any length having effectiveness in inhibiting a target gene by RNAi;
with “overhang” and “blunt-end” design features and certain nucleotide pair motifs;
with or without chemical modifications, with no limitations as to the number of such modifications;
including pharmaceutical compositions of the claimed siRNAs for inhibiting the expression of a target gene by means of RNAi; and/or,
methods for the selection of such an siRNA molecule or methods for inhibiting the expression of a target gene in a cell.
The claims of the Woppman et al. ’727 patent are provided on the company’s website, together with claims from other Alnylam owned or licensed patents.

About Alnylam Intellectual Property (IP)

Alnylam’s IP estate includes issued, allowed, or granted fundamental patents in many of the world’s major pharmaceutical markets that claim the broad structural and functional properties of RNAi therapeutic products. As it applies to the U.S. and EU, these include:

the Crooke Patents (U.S. Patent Nos. 5,898,031 and 6,107,094) issued in over 12 countries and licensed exclusively from Isis Pharmaceuticals, Inc. to Alnylam for RNAi therapeutics, which cover compositions, methods, and uses of modified oligonucleotides to inactivate a target mRNA mediated by a double-stranded RNase, such as “RISC,” which is the cellular enzyme complex that mediates RNAi;
the Tuschl II ’704 patent (U.S. Patent No. 7,056,704) issued in June 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs to silence any and all disease targets;
the Tuschl II ’196 patent (U.S. Patent No. 7,078,196) issued in July 2006 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers methods of making siRNAs with or without chemical modifications;
the Tuschl II ’044 patent (EP 1407044), granted in January 2008 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, and uses of siRNAs;
the Kreutzer-Limmer I ’623 patent (EP 1144623) granted in August 2002, maintained in amended form in June 2006 and owned by Alnylam, which covers methods, medicaments, and uses of siRNAs having, among other structural features, a length of 15 to 21 base pairs;
the Kreutzer-Limmer I ’945 patent (EP 1214945) granted in June 2005 and owned by Alnylam, which covers compositions, methods, and uses of siRNAs with a length between 15 and 49 nucleotides;
the Kreutzer-Limmer I ’167 patent (DE 10080167) granted in October 2007 and owned by Alnylam, which covers pharmaceutical compositions and uses of siRNAs with a length between 15 and 49 nucleotides that target certain broad categories of mammalian genes;
the Kreutzer-Limmer I ’235 patent (DE 10066235), granted in January 2008 and owned by Alnylam, which covers methods, uses, and medicaments of siRNAs, with a length between 15 and 49 nucleotides, expressed through a vector;
the Kreutzer-Limmer II ’061 patent (EP Patent No. 1352061), granted in May 2006 and owned by Alnylam, which covers therapeutic compositions, methods, and uses of siRNA and derivatives directed toward over 125 disease targets;
additional fundamental patents and patent applications licensed to Alnylam on an exclusive or non-exclusive basis, including those of Fire and Mello (U.S. Patent No. 6,506,559) and Glover (EP 1230375); and,
many divisional patent applications pending of the aforementioned issued or granted patents and additional patent applications pending, including patents and patent applications covering inventions by Tuschl, Hannon, and Kay.
In addition to fundamental patents, Alnylam is the exclusive licensee in the field of RNAi therapeutics for more than 150 issued chemistry patents owned or controlled by Isis Pharmaceuticals, Inc. broadly covering chemical modifications, including motifs and patterns of modifications of oligonucleotides, including RNAi therapeutics. These patents include:

phosphorothioate and 2’-O-methyl modifications of oligonucleotides (Buhr, U.S. Patent No. 6,476,205);
2’-Ribose modifications of oligonucleotides (Cook, U.S. Patent Nos. 5,670,633; 6,005,087; 6,531,584; and 7,138,517);
chemical conjugates of oligonucleotides (Manoharan, U.S. Patent No. 6,153,737); and,
“overhang,” blunt-end,” and nucleotide pairing design motifs (Woppman et al., UK 2417727).
In addition to fundamental and chemistry patents, Alnylam is also the exclusive licensee in the field of RNAi therapeutics for certain delivery patents, including those owned and controlled by Tekmira Pharmaceuticals, Inc. covering delivery of oligonucleotides, including RNAi therapeutics, with liposomal formulations. These patents include:

formulations of oligonucleotides, including siRNAs, in cationic liposomes (Wheeler, U.S. Patent Nos. 5,976,567 and 6,815,432; and Semple, U.S. Patent No. 6,858,225).
About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including its views with respect to the timing and the future issuance of patents and the expected importance and scope of its intellectual property rights, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Media
Yates Public Relations
Kathryn Morris, 845-635-9828


Quelle: BUSINESS WIRE

[Fruehrentner]

Alnylam präsentiert sich auf der

BIO CEO & Investor Conference im Februar

http://ceo.bio.org/opencms/ceo/2007/program/presenters.jsp

[Fruehrentner]

Antwort auf Beitrag Nr.: 33.282.879 von Fruehrentner am 06.02.08 13:18:22

04.02.2008 22:00:00

Alnylam to Webcast Presentation at the 10th Annual BIO CEO & Investor Conference

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today announced that management will present a company overview at the 10th Annual BIO CEO & Investor Conference on Monday, February 11, 2008, at 1:15 p.m. ET at the Waldorf-Astoria in New York City.

A live audio webcast of the presentation will be available on the “Investors” section of the company’s website, www.alnylam.com. A replay of the presentation will be available on the Alnylam website within 48 hours after the event and will be archived for 14 days.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.


Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Media
Yates Public Relations
Kathryn Morris, 845-635-9828

[Fruehrentner]

07.02.2008 22:00:00

Alnylam Pharmaceuticals Reports Fourth Quarter and 2007 Financial Results

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today reported its consolidated financial results for the fourth quarter and year ended December 31, 2007 and company highlights.

“Overall, 2007 was a game changing year for Alnylam -- one in which we achieved major scientific, pipeline, and business milestones which together advance our mission of building a leading biopharmaceutical company founded on RNAi,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Based on these accomplishments, we are more confident than ever in the broad potential of the RNAi opportunity and in our leadership in realizing the technology’s promise. To set the stage for the future, we have recently launched our ‘RNAi 2010’ plan as a new initiative focused on achieving important milestones by the end of 2010.”

“A major event for the year was the advancement of our lead program ALN-RSV01, an RNAi therapeutic for the treatment of RSV infection, into Phase II trials and the recent achievement of positive results with statistically significant anti-viral activity. We look forward to presenting the detailed results of the GEMINI study later this month at a clinical meeting,” stated Barry Greene, President and Chief Operating Officer of Alnylam. “In addition, we are very pleased with our continued leadership in the advancement of delivery solutions for RNAi therapeutics and efforts on miRNA therapeutics, as measured by our scientific publications and presentations at scientific meetings. These efforts pave the way for the advancement of RNAi therapeutics with both direct and systemic delivery.”

Cash, Cash Equivalents, and Marketable Securities

At December 31, 2007, Alnylam had cash, cash equivalents, and marketable securities of $455.6 million, compared to $468.4 million at September 30, 2007 and $217.3 million at December 31, 2006. The significant increase in cash from December 31, 2006 was primarily due to $331.0 million of gross proceeds received from the alliance with Roche that closed in August 2007.

Net Income (Loss)

Net income for the fourth quarter of 2007 was $1.7 million, or $0.04 per share on both a basic and diluted basis, as compared to a net loss of ($8.4) million, or ($0.26) per share, for the same period in the previous year. Net income for the fourth quarter of 2007 was primarily a result of strong GAAP revenues, primarily from the Roche alliance and the associated increase in interest income during the quarter as a result of the net proceeds received from the Roche alliance. Expenses for the fourth quarter of 2007 included $2.6 million of non-cash stock-based compensation charges or $0.06 per share on both a basic and diluted basis, compared to $2.6 million or $0.08 per share for the same period in the previous year.

For the year ended December 31, 2007, the net loss was ($85.5) million, or ($2.21) per share, as compared to a net loss of ($34.6) million, or ($1.09) per share, for the prior year. Expenses for the full year 2007 included $14.5 million or $0.37 per share of non-cash stock-based compensation charges, $27.5 million or $0.71 per share of license fees due to licensors incurred as a result of the Roche alliance, and $5.2 million or $0.14 per share of income tax expenses incurred as a result of the sale of the company’s German operations to Roche compared to $8.3 million or $0.26 per share of non-cash stock-based compensation charges for the prior year. The increase in the net loss for 2007 as compared to 2006 is primarily a result of unique transaction-related costs and income tax expenses incurred as a result of the company’s alliance with Roche as well as an increase in stock-based compensation expenses, in addition to the continued investment in the company’s respiratory syncytial virus (RSV) program and pre-clinical pipeline.

Revenues

Revenues in the fourth quarter of 2007 were $18.2 million, as compared to $7.0 million for the same period last year. Revenues for the fourth quarter of 2007 included $11.2 million of net collaboration revenues related to the company’s alliance with Roche and $7.0 million of revenues from Novartis, the National Institutes of Health (NIH), the Department of Defense (DOD), Biogen Idec, InterfeRx™, research reagent and services licensees, and other sources. Revenues for the full year ended December 31, 2007 were $50.9 million as compared to $26.9 million for the prior year. Revenues for the year ended December 31, 2007 included $17.6 million of net collaboration revenues related to the company’s alliance with Roche, $14.7 million of revenues related to the company’s collaborations with Novartis, and $18.6 million of revenues from Biogen Idec, the NIH, the DOD, InterfeRx, research reagent and services licensees, and other sources.

Research and Development Expenses

Research and development (R&D) expenses were $15.6 million in the fourth quarter of 2007, including $1.7 million of non-cash stock-based compensation, as compared to $12.3 million for the same period last year, which included $1.7 million of non-cash stock-based compensation. The increase in R&D expenses in the fourth quarter of 2007 as compared to the prior year period was primarily due to higher external costs in support of the company’s clinical program for RSV infection, as well as the company’s pre-clinical programs for the treatment of hypercholesterolemia and liver cancer. In addition, contributing to the increase were expenses associated with the company’s delivery-related collaborations. R&D expenses were $120.7 million for the year ended December 31, 2007 which included $9.4 million of non-cash stock-based compensation as compared to $49.8 million for the prior year, which included $5.0 million of non-cash stock-based compensation. R&D expenses for the year ended December 31, 2007 increased significantly as compared to the prior year primarily due to $27.5 million of license fees payable to the company’s licensors, primarily Isis, as a result of the company’s alliance with Roche. The increase in R&D expenses was also due to higher external service costs in support of the company’s clinical program for RSV infection as well as the company’s pre-clinical programs for the treatment of hypercholesterolemia and liver cancer. Also contributing to the increase were expenses associated with the company’s delivery-related collaborations. The increase in non-cash stock-based compensation charges in 2007 was primarily related to charges incurred in connection with the sale of the company’s German operations to Roche.

General and Administrative Expenses

General and administrative (G&A) expenses were $5.5 million in the fourth quarter of 2007, which included $0.9 million of non-cash stock-based compensation, as compared to $4.6 million for the same period in 2006, which included $0.9 million of non-cash stock-based compensation. The increase in G&A expenses for the fourth quarter of 2007 was due primarily to higher professional service fees associated with increased business development and intellectual property (IP) activities. G&A expenses were $23.4 million for the year ended December 31, 2007, including $5.1 million of non-cash stock-based compensation, as compared to $16.6 million for the prior year, which included $3.3 million of non-cash stock-based compensation. The increase in G&A expenses for the year ended December 31, 2007 was due primarily to higher professional service fees as a result of increased business activities, including the company’s alliance with Roche, the Regulus Therapeutics joint venture with Isis, and higher costs related to an increase in G&A headcount. The increase in non-cash stock-based compensation charges for the year ended December 31, 2007 was primarily related to charges incurred in connection with the sale of the company’s German operations to Roche.

Regulus Therapeutics; Joint Venture with Isis Pharmaceuticals

During the third quarter of 2007, the company made a $10.0 million investment in Regulus Therapeutics, a joint venture with Isis for the discovery, development, and commercialization of miRNA therapeutics. The company is funding the first $10.0 million of the net spend of Regulus Therapeutics and has capitalized its investment in Regulus Therapeutics on its balance sheet. In its income statement, the company incurred a $0.9 million and $1.1 million equity loss in joint venture related to the company’s share of the net losses incurred by Regulus Therapeutics in the fourth quarter of 2007 and the year ended December 31, 2007, respectively.

Income Tax Expense

Primarily as a result of the company’s sale of its German operations to Roche in August 2007 for $15.0 million, the company recorded income tax expenses of $0.1 million and $5.2 million in the fourth quarter of 2007 and in the year ended December 31, 2007, respectively. The company expects to pay approximately $3.0 million of this amount in early 2008 to the German tax authorities.

2008 Financial Guidance

Alnylam expects that its cash, cash equivalents and marketable securities balance will be greater than $390.0 million at December 31, 2008.

“From a financial perspective, 2007 was a notable year for Alnylam as we realized the benefit of our collaborations in our significant cash position and strong revenue base. In turn, our expenses remained focused on investments in scientific and pipeline advancement,” stated Patricia Allen, Vice President, Finance and Treasurer at Alnylam. “While we achieved a modest net income in the fourth quarter of 2007, we do not view this as a consistent trend due to increased investments in our technology and our growing clinical and pre-clinical pipeline of RNAi therapeutics.”

2007 and Recent Corporate Highlights

Product Pipeline and Scientific Leadership Highlights

Advanced Development of ALN-RSV01 for RSV Infection. Top-line data from the GEMINI study showed that ALN-RSV01 demonstrated statistically significant anti-viral activity and was safe and well tolerated. The full data set from this trial will be presented at the International Symposium of Respiratory Viruses, to be held February 28 – March 2, 2008 in Singapore. Other highlights include the completion of a Phase I study of ALN-RSV01 administered via inhalation. Based on these encouraging clinical study results, the company expects to initiate a Phase II study of ALN-RSV01 in naturally infected adult patients in the first half of 2008.

Announced Two New Development Programs. These new programs included ALN-HTT targeting the huntingtin gene for the treatment of Huntington’s disease, in a partnership with Medtronic, Inc., and ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of liver cancers and potentially other solid tumors.
Advanced Pre-Clinical Programs as Reported at Scientific Meetings. Non-human primate data for the company’s ALN-PCS program demonstrated efficient silencing of PCSK9 and rapid and durable reductions in LDL (“bad”) cholesterol levels by approximately 50 percent. During the fourth quarter, additional data from the company’s pre-clinical programs were presented at a number of peer-reviewed meetings, including:

-- Drugs Affecting Lipid Metabolism, October 2007;
-- Oligonucleotide Therapeutics Society, October 2007;
-- American Association for Cancer Research (AACR),

October 2007;
-- Society for Neuroscience, November 2007; and
-- Drug Delivery to the Lungs, December 2007.

Advanced Platform for Systemic Delivery of RNAi Therapeutics.

Alnylam continued to advance its efforts to develop systemic delivery of RNAi therapeutics through both internal development and collaborations with third parties. Alnylam obtained a worldwide exclusive license to Tekmira’s liposomal delivery formulation technology for the discovery, development, and commercialization of lipid-based nanoparticle formulations for delivery of RNAi therapeutics.
Alnylam also signed an agreement with the MIT Center for Cancer Research to sponsor an exclusive five-year research program focused on the delivery of RNAi therapeutics.
Continued Scientific Leadership. Throughout 2007, Alnylam continued to demonstrate its scientific leadership in the field of RNAi therapeutics as measured by the publication of eight papers in some of the world’s top journals, including Nature, Nature Biotechnology, PNAS, and Cell. During the fourth quarter, the following papers were published:

-- "Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits" DiFiglia et al. PNAS 104: 17204-09 (2007);



-- "Mouse cytomegalovirus microRNAs dominate the cellular small RNAs profile during lytic infection and show features of post-transcriptional regulation" Doelken et al. Journal of Virology 81: 13771-82 (2007);



-- "A viral microRNA functions as an orthologue of cellular miR-155" Gottwein et al. Nature 450: 1096-9 (2007); and



-- "siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells" Hewett et al. Human Molecular Genetics Advance Access doi:10.1093/hmg/ddn032 (2008).



Business Execution Highlights

Formed Major Alliance with Roche, Valued at Over $1 Billion. Alnylam formed an alliance with Roche, which is the largest drug discovery alliance in biotech history and the broadest industry collaboration on RNAi therapeutics to date. Through this alliance, Roche obtained a non-exclusive license to existing Alnylam fundamental, chemistry, and delivery intellectual property for RNAi therapeutics in certain defined fields and acquired Alnylam’s German operations. Alnylam received an aggregate of $331.0 million in upfront cash and equity investment, and may also receive significant milestones and royalties, and additional payments related to field expansion options, valuing the transaction at over $1 billion.

Launched Regulus Therapeutics. Alnylam and Isis Pharmaceuticals created Regulus Therapeutics as a leading company for the discovery, development, and commercialization of miRNA therapeutics. Regulus combines the strengths and assets of Isis’ and Alnylam’s technologies, know-how, and intellectual property in the miRNA therapeutics field. In addition, Regulus was formed with a world-class Scientific Advisory Board chaired by Nobel laureate David Baltimore and includes key pioneers in the miRNA research field. Regulus appointed Kleanthis G. Xanthopoulos, Ph.D., as President and Chief Executive Officer.

Advanced and Revised Medtronic Collaboration. Alnylam and Medtronic advanced and revised their 2005 collaboration agreement into a 50/50 co-development and profit-share relationship for the U.S. market. The collaboration is focused on developing a novel drug-device combination for the treatment of Huntington’s disease, with an RNAi therapeutic targeting the huntingtin gene that is delivered by an implantable infusion pump.

Awarded $38.6 Million Contract from U.S. Government for Alnylam Biodefense Initiative. The 33-month grant from the United States Defense Threat Reduction Agency (DTRA) supports development of a broad spectrum RNAi anti-viral therapeutic for the treatment of viral hemorrhagic fever.

Received Award from Michael J. Fox Foundation. Alnylam and collaborators received a new grant totaling $3.8 million for the development of RNAi therapeutics for the treatment of Parkinson’s disease. The four-year grant, which is part of the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson’s Institute and Clinical Center of Sunnyvale, California.

Terminated Merck Collaboration. Alnylam and Merck terminated their collaboration and Alnylam rescinded all grants of its intellectual property related to current and future Merck development programs, including the collaboration’s former co-development programs.

Continued Leveraging of Intellectual Property. As part of the company’s collaboration with Tekmira, Tekmira received three InterfeRx license options, subject to Alnylam review and third-party obligations, to develop its own RNAi therapeutic products. In addition, Alnylam granted licenses for the research reagent and services market under the “Kreutzer-Limmer” patent family to Bio-Rad, Hayashi-Kasei and Gene Design. The company believes that over 75 percent of industrial sales of siRNAs for research purposes are now made under a license to Alnylam’s intellectual property.
Intellectual Property (IP) Leadership Highlights

Alnylam’s IP estate includes issued, allowed, or granted patents in many of the world’s major pharmaceutical markets, including the following, which have recently advanced through U.S. and EU patent offices.

Tuschl II ’044 patent (EP 1407044). Granted in Europe in September 2007 and exclusively licensed to Alnylam from the Max Planck Society, which broadly covers compositions, methods, and uses of siRNAs.

Kreutzer-Limmer I ’235 patent (DE 10066235). Granted in Germany in January 2008 and owned by Alnylam, which covers methods, uses, and medicaments of siRNAs, with a length between 15 and 49 nucleotides, expressed through a vector.

Kreutzer-Limmer I ’167 patent (DE 10080167). Granted in Germany in October 2007 and owned by Alnylam, which covers pharmaceutical compositions and uses of siRNAs with a length between 15 and 49 nucleotides that target certain broad categories of mammalian genes.

Woppmann et al. ’727 patent (UK 2417727). Granted in the U.K. in January 2008 and owned by Alnylam, which covers siRNA molecules of any length that contain “overhang” and “blunt end” design features, including siRNAs containing chemical modifications and certain novel motifs.

Wheeler patent series (U.S. patent application 09/431,594). Allowed claims in the U.S. in February 2007 and licensed exclusively to Alnylam from Tekmira for the discovery, development, and commercialization of RNAi therapeutics, which covers nucleic acid-lipid compositions, including cationic liposomes, a family of specialized lipid molecules.
Key Patents in the miRNA Field. The USPTO issued claims (U.S. 7,232,806) for the “Tuschl III” patent series for miRNA therapeutics, licensed exclusively to Regulus Therapeutics on a worldwide basis through an agreement with Max-Planck-Innovation GmbH, the licensing agent for the Max Planck Society. In addition, the USPTO allowed claims in the “Sarnow” patent (U.S. patent application 11/122,328) which cover methods for targeting a specific miRNA to inhibit Hepatitis C virus (HCV) replication.
Organizational Highlights

Continued to Expand the Management Team with Key Additions. In 2007, Alnylam announced the appointments of Eric Raichle to Vice President of Human Resources, Jason Rhodes to Vice President of Business Development, Philip Chase to Vice President of Legal, Donna Ward to Vice President of Intellectual Property, and Stuart Pollard to Vice President of Scientific and Business Strategy. In December 2007, Alnylam also announced the promotion of Barry Greene to President, in addition to his existing role as Chief Operating Officer.
Developed the Board of Directors. Alnylam elected Victor Dzau, M.D. to its Board of Directors.
Conference Call Information

Alnylam will host a conference call at 4:30 p.m. ET on February 7, 2008 to discuss these 2007 financial results and recent corporate developments. The call may be accessed by dialing 866-831-6234 (domestic) or 617-213-8854 (international) five minutes prior to the start time and providing the passcode 80945834.

A replay of the call will be available from approximately 6:30 p.m. ET on February 7, 2008 until February 14, 2008. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the passcode 72018193. A live audio webcast of the call will also be available on the “Investors” section of the company’s website, www.alnylam.com. An archived webcast will be available on the company’s website approximately two hours after the event and will be archived for 14 days thereafter.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About RNAi 2010

In January 2008, Alnylam established its “RNAi 2010” outlook for key scientific, clinical, and business initiatives as part of the company’s mission of building a leading biopharmaceutical company founded on RNAi. With RNAi 2010, Alnylam expects to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of miRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

[Fruehrentner]

Alnylam Reports Pre-clinical Progress with RNAi Therapeutics in Neurological Disease

07 Feb 2008

New Paper in Human Molecular Genetics Demonstrates Normalization of Cellular Function with RNAi Therapeutic Targeting Mutant Gene for Dystonia

CAMBRIDGE, MA, USA | February 7, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the publication of new research in the journal Human Molecular Genetics. The new study, performed in collaboration with scientists Xandra Breakefield, Ph.D., Bakhos Tannous, Ph.D., and Jeffrey Hewett, Ph.D., from Massachusetts General Hospital, describes the silencing of a key gene implicated in early onset torsion dystonia, known as mutant torsinA. Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal posture. Early onset torsion dystonia affects approximately 1 in 30,000 - 300,000 persons and, in certain ethnic populations, is prevalent at a frequency of 1 in 10,000.

"We are excited by these new data which demonstrate the ability of RNAi therapeutics to readily discriminate between a disease target of interest, such as mutant torsinA, and a closely related gene, such as wild-type torsinA, thereby providing an important approach for the treatment of genetic disorders," said Dinah Sah, Ph.D., Senior Director of Research at Alnylam. "We are encouraged by these results, as well as results we have seen to date with our other neurological RNAi therapeutic programs, such as Huntington's disease, Parkinson's disease, and others."

Patients with early onset torsion dystonia have a single copy of the wild-type torsinA gene and a single copy of the mutant torsinA gene. TorsinA is implicated in the cellular processing of proteins through the secretory pathway and this cellular function is disrupted by mutant torsinA. The newly published data (Hewett et al., Human Molecular Genetics Advance Access published February 7, 2008 doi:10.1093/hmg/ddn032) show that an siRNA potently and selectively silenced mutant torsinA in vitro, with no effect on the wild-type torsinA gene. The silencing of mutant torsinA by siRNA resulted in normalization of protein secretion. In contrast, siRNAs that suppress both the mutant and normal torsinA genes were not effective in restoring protein secretion, and in fact further impaired secretion. These findings demonstrate that selective inhibition of the mutant torsinA gene only is critical for treatment of dystonia, and that such an approach may be possible with RNAi therapeutics.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

SOURCE: ALNYLAM PHARMACEUTICALS

[Fruehrentner]

11.02.2008 14:00:00

Regulus Therapeutics Appoints Peter S. Linsley, Ph.D. as Chief Scientific Officer

Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY) and Isis Pharmaceuticals, Inc. (Nasdaq:ISIS) formed to discover, develop, and commercialize microRNA therapeutics, announced today the appointment of Peter S. Linsley, Ph.D., as Chief Scientific Officer. Dr. Linsley has been instrumental in advancing the scientific understanding and therapeutic potential of microRNAs.

“I am delighted to welcome Peter, a prominent industry leader and renowned scientist, to the Regulus executive team. Peter’s expertise in microRNA research coupled with his experience in advancing discovery programs into the clinic will be a tremendous asset as we advance our efforts towards developing microRNA therapeutics,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus. “In addition, Peter’s decision to join Regulus is a testament to the unique strengths of Regulus, a company that is positioned with a very strong intellectual property estate and access to advanced RNA-targeted technologies.”

“Regulus has all the necessary components to lead the microRNA therapeutic space, and I am excited to help build an innovative company based on the development of microRNAs for potential new treatment options for a broad range of diseases,” said Peter S. Linsley, Ph.D., Chief Scientific Officer of Regulus. “Regulus has a solid scientific foundation, a notable Scientific Advisory Board and an impressive set of collaborations with leading microRNA scientists at prestigious research institutes. Through its collaborations, Regulus has gained an important understanding of more than 60 microRNAs as potential disease targets in numerous therapeutic areas.”

Before joining Regulus, Dr. Linsley was an Executive Director of Cancer Biology at Merck Research Laboratories. Dr. Linsley joined Merck upon its acquisition of Rosetta Inpharmatics LLC, where he held a variety of positions, most recently Vice President of Research and Development. Prior to joining Rosetta Inpharmatics, Dr. Linsley was a Director of Immunology at Bristol-Myers Squibb, where he co-discovered and aided clinical development of immunomodulatory drugs abatacept (Orencia) and belatacept. Dr. Linsley conducted postdoctoral research in the department of Genetics at the Hospital for Sick Children in Toronto, Canada. He received his Ph.D. at the Molecular Biology Institute of the University of California, Los Angeles, and his B.S. from Auburn University where he graduated magna cum laude. In addition to participating on the editorial board of several scientific research journals, including the Journal of Immunology, Dr. Linsley has published over 220 scientific publications and is an inventor on more than 35 issued U.S. patents.

About microRNAs

microRNAs are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. microRNA therapeutics represent a new approach for the treatment of a wide range of human diseases. The inappropriate absence or presence of specific microRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, and metabolic disorders. Targeting microRNAs with novel therapeutic agents could result in novel and broadly acting treatments for human diseases.

About Regulus

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop and commercialize microRNA therapeutics. The company was created as a joint venture between Alnylam Pharmaceuticals, a leader in RNAi therapeutics, and Isis Pharmaceuticals, a leader in antisense technologies and therapeutics. Isis and Alnylam scientists and collaborators were the first to discover microRNA antagonist strategies that work in vivo in animal studies (Krutzfeldt et al. Nature 438, 685-689 (2005); Esau et al. Cell Metab., 3, 87-98 (2006)). Isis and Alnylam have also created and consolidated key intellectual property (IP) for the development and commercialization of microRNA therapeutics. This IP estate includes over 900 patents and patent applications, including 600 issued patents, owned by Isis and pertaining to chemical modification of oligonucleotides for therapeutic applications. The company, founded in September 2007, maintains facilities in Carlsbad, California. For more information, visit www.regulusrx.com.

About Alnylam Pharmaceuticals, Inc.

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

About Isis Pharmaceuticals, Inc.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. Isis has successfully commercialized the world's first antisense drug and has 18 drugs in development. Isis’ drug development programs are focused on treating cardiovascular and metabolic diseases. Isis’ partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Ibis Biosciences, Inc., Isis’ majority-owned subsidiary, is developing and commercializing the Ibis T5000™ Biosensor System, a revolutionary system to identify infectious organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including our views with respect to the potential for success of Regulus Therapeutics and the potential for the development of microRNA therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

Isis Forward Looking Statements

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Isis’ technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus. Any statement describing Isis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement, including those statements that are described as Isis’ goals. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Isis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis’ programs are described in additional detail in Isis’ annual report on Form 10-K for the year ended December 31, 2006, and its quarterly report on Form 10-Q for the quarter ended September 30, 2007, which are on file with the SEC. Copies of these and other documents are available from the Company.

Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc. Ibis Biosciences and Ibis T5000 are trademarks of Ibis Biosciences, Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics LLC.


Regulus Therapeutics
Investors
Alnylam Pharmaceuticals
Cynthia Clayton, 617-551-8207
or
Media
Isis Pharmaceuticals
Amy Blackley, Ph.D., 760-603-2772


Quelle: BUSINESS WIRE

[Fruehrentner]

12.02.2008 13:00:00

Alnylam Appoints Dr. Edward Scolnick to Board of Directors and Scientific Advisory Board

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today the appointment of Edward Scolnick, M.D., to its Board of Directors and Scientific Advisory Board.
Dr. Scolnick is the director of the Psychiatry Initiative at the Broad Institute. From 1982 to 2003, Dr. Scolnick served in a number of key leadership roles at Merck Research Laboratories, most recently as president. Prior to joining Merck, he worked at the National Cancer Institute and the National Heart Institute.

“We are extremely delighted and honored that Ed has agreed to join the Alnylam board of directors and our scientific advisory board,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “As a leader in the pharmaceutical industry, Dr. Scolnick’s demonstration of scientific excellence and commitment to breakthrough medicines are legendary accomplishments. We believe that his broad and deep expertise in the research and development of innovative medicines will bring a unique dimension to our boards as we build a top-tier biopharmaceutical company founded on RNAi.”

“RNAi creates an entirely new product platform for the discovery and development of high impact medicines,” said Dr. Scolnick. “Alnylam’s progress to date, both in business and scientific excellence, shows promise and I am looking forward to contributing to ongoing efforts as an active member of their boards.”

A graduate of Harvard College, Dr. Scolnick earned an A.B. and then an M.D. from Harvard University Medical School. Dr. Scolnick was elected to the National Academy of Sciences in 1984 and to the American Academy of Arts and Sciences in 1993. He became a member of the Institute of Medicine in 1996. Dr. Scolnick currently serves on the board of directors for Millipore Corporation and served as a member of the Food and Drug Administration Science Board from 2000 to 2002.


Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
or
Yates Public Relations
Kathryn Morris (Media), 845-635-9828

Quelle: BUSINESS WIRE

[Aliberto]

Antwort auf Beitrag Nr.: 33.342.967 von Fruehrentner am 12.02.08 16:00:45

Denke mal, langfristig kann man mit Alnylam nicht viel falsch machen.
Einzig das Mitarbeiter-Optionsprogramm verwässert das Ergebnis doch beträchtlich. Aber die Kröte muss man wohl schlucken.

[Fruehrentner]

19.02.2008 12:54:18

Alnylam Pharmaceuticals Basisinvestment

Kulmbach (aktiencheck.de AG) - Aus Sicht der Experten vom "Biotech-Report" ist und bleibt die Aktie von Alnylam Pharmaceuticals (ISIN US02043Q1076/ WKN A0CBCK) ein Basisinvestment. Die Aktie habe sich trotz der Turbulenzen an den Weltmärkten gut behauptet. Seit Anfang des Jahres liege sie sogar im Plus. Die Gründe dafür seien zahlreiche positive Meldungen. Das Unternehmen habe sich auf die Entwicklung neuartiger Medikamente auf Basis der RNA-Interferenz spezialisiert. Mit dieser preisgekrönten Technologie könnten Gene abgeschaltet werden, die krankmachende Proteine erzeugen würden. Außerdem habe Alnylam Pharmaceuticals die Kooperation mit der Michael J. Fox Stiftung bekannt gegeben. Zusammen mit Partnern wie Mayo Clinic von Jacksonville wolle das Unternehmen in den kommenden vier Jahren an neuen Therapien gegen die Parkinson-Krankheit forschen. Die 3,8 Mio. USD, die sich die Gesellschaft mit ihren Partnern teile, seien zwar nicht mehr als eine Anerkennung. Sollte die Zusammenarbeite jedoch schließlich in vermarktungsfähigen Produkten münden, dürfte ein Vielfaches in Alnylams Kasse fließen. Aus Sicht der Experten hätten wirksame Parkinson-Arzneien Milliarden-Potenzial. Das Unternehmen komme auch bei anderen Projekten planmäßig voran. Alnylam Pharmaceuticals entwickele zurzeit einen experimentellen Wirkstoff der zur Behandlung einer durch ein Virus verursachten Atemwegsinfektion eingesetzt werden solle. Das Präparat ALN-RSV01 habe sich als gut verträglich erwiesen und Ende Januar gute Ergebnisse aus einer klinischen Studie der Phase II geliefert. Es sollten klinische Test zweier weiterer Produktkandidaten durchgeführt werden. ALN-PCS sei ein Medikament zur Behandlung hoher Cholesterinwerte im Blut und ALN-VSP sei ein potenzielles Mittel gegen Leberkrebs. Die Cash-Position zum Jahresende habe 456 Mio. USD betragen. Alnylam Pharmaceuticals gehe davon aus, dass zum Jahresende noch etwa 390 Mio. USD davon übrig sein dürften. Das decke sich in etwa mit den Schätzungen der Analysten. Nach Ansicht der Experten vom "Biotech-Report" ist und bleibt die Alnylam Pharmaceuticals-Aktie ein Basisinvestment. (Ausgabe 02) (19.02.2008/ac/a/a)

Quelle: AKTIENCHECK.DE

[Fruehrentner]

25.02.2008 23:36:00

Alnylam to Webcast Conference Call to Discuss Phase II GEMINI Data for ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today announced that it will host a conference call to discuss the full results from the Phase II GEMINI study of ALN-RSV01, being presented at the International Symposium on Respiratory Viral Infections in Singapore. The webcast will take place on Friday, February 29, 2008 at 8:30 a.m. ET.

To access the call, please dial 888-396-2384 (domestic) or 617-847-8711 (international) five minutes prior to the start time and provide the passcode 86570853. A replay of the call will be available from 10:30 a.m. ET on February 29, 2008 until March 7, 2008. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the passcode 79263826.

A live audio webcast of the call will also be available on the “Investors” section of the company’s website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event and will be archived for 14 days.

About Alnylam

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.


Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Media
For Alnylam Pharmaceuticals, Inc.
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Kathryn Morris, 845-635-9828

Quelle:BUSINESS WIRE

[Fruehrentner]

Alnylam's antiviral drug found effective in Phase II RSV trial

3rd March 2008
By Staff Writer

Alnylam Pharmaceuticals has achieved human proof of concept with an RNAi therapeutic, a first for the industry. Results from the company's Gemini trial with ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus or RSV, showed statistically significant anti-viral efficacy.
In the Phase II experimental infection study, treatment with ALN-RSV01 led to a decreased RSV infection rate, an increase in the number of subjects who remained free of infection, and was safe and well tolerated.

The goal of the Gemini study was to establish the anti-viral activity, safety, and tolerability of ALN-RSV01 in an experimental RSV infection model. Gemini was a double-blind, placebo-controlled study, where a total of 88 adult subjects experimentally infected with RSV was randomized to receive ALN-RSV01 or placebo. ALN-RSV01 or placebo was administered intranasally for five consecutive days - two days prior and three days after viral inoculation. Efficacy measures included infection rate and the effects of treatment on viral dynamics and clinical symptoms. As designed, Gemini had sufficient power to detect a statistically significant difference in infection rate between ALN-RSV01 and placebo.

Akshay Vaishnaw, vice president, clinical research at Alnylam, said: "We believe these findings point to the potential for clinical benefit with ALN-RSV01 in a naturally infected patient population, and we look forward to initiating a Phase II study in naturally infected adult patients in the first half of 2008."

http://www.pharmaceutical-business-review.com/article_news.a…

[aktianer]

Antwort auf Beitrag Nr.: 33.541.131 von Fruehrentner am 04.03.08 09:00:24

@Frührentner,

um das Bild zu vervollständigen, möchte ich noch einige kritische Stimmen zur RSV01-Entwicklung hier einstellen; übrigens ist die Krtik für mich nachvollziehbar und ich bin jetzt etwas
enttäuscht - bleibe aber dennoch investiert - auch wegen der anderen Projekte in der Pipeline - aber ich glaube, Alny-Aktionäre müssen ihren Anlagehorizont nun etwas weiter stecken.

Alnylam Says Drug Study Meets Goal
Friday February 29—2008-- 12:27 pm ET
By Jennifer Sterling, AP Business Writer
Alnylam Gene-Silencing Drug Meets Trial Goal, but Stock Down As Some Analysts Raise Questions

CAMBRIDGE, Mass. (AP) -- Alnylam Pharmaceuticals Inc. reported Friday that its midstage study for experimental drug ALN-RSV01 met its main goal and reduced levels of the respiratory syncytial virus, a highly contagious virus that causes infections in the respiratory tract.

The stock fell, however, as some analysts questioned the drug's true potential effectiveness in a real-world scenario, because patients in the trial took the drug before becoming sick.
......

The Phase II clinical trial of ALN-RSV01 showed "statistically significant" effectiveness, with about a 40 percent reduction in RSV infection rate. Alnylam also said the drug showed an increase in the number of subjects who remained free of infection.

The drug was safe and well-tolerated, the company said.

In an interview with AP, Needham & Co. analyst Alan Carr highlighted potential challenges for the drug in light of the study's design.

He said that while the results were positive, people in the trial were given the drug before they were infected with the virus, meaning the results fail to show a "real-world" scenario.

The numbers were slightly disappointing with respect to viral load and symptom reduction, said Carr, and left him wondering how the drug would work in patients who don't take the drug before infection.

Caris & Co. analyst Douglas Chow told the AP he viewed the results as positive but said the drug still has a long way to go.

"The company will still need further studies before the drug gets commercialized and there are still many questions that remain unanswered," Chow said.

He said the stock also likely fell because some investors may have expected the company to release more trial data.

Alnylam's stock fell 92 cents, or 3.1 percent, to $29 in midday trading, as the broader market declined Friday.

http://biz.yahoo.com/ap/080229/alnylam_study.html?.v=1

[Fruehrentner]

Antwort auf Beitrag Nr.: 33.548.634 von aktianer am 04.03.08 19:03:53

danke für den Text.

Einen Durchmarsch der RNAI-Technologie wirds wohl nicht geben aufgrund der schwierigen Drug Delivey, sprich Transport zum Wirkort.

[Fruehrentner]

20.03.2008 13:00:00

Alnylam Grants Shanghai GenePharma License to Kreutzer-Limmer Patents for the RNA Interference (RNAi) Research Products Market

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, and Shanghai GenePharma Co., Ltd, a leading siRNA supplier in China, announced today that Alnylam has granted Shanghai GenePharma a non-exclusive world-wide license to manufacture and provide RNAi research products and services under the Kreutzer-Limmer patent family. This patent family, owned exclusively by Alnylam, covers fundamental aspects of the structure and uses of RNAi products including their use to mediate RNAi in mammalian cells and of RNAi-related mechanisms.

“The Kreutzer-Limmer patent family is one of the critical components of fundamental intellectual property in the field of RNAi, and we are pleased to grant Shanghai GenePharma a license to manufacture and provide siRNA reagents to its industry and academic customers around the world for research purposes,” said Jason Rhodes, Vice President of Business Development at Alnylam. “Providing this license to Shanghai GenePharma represents our first business transaction in China, which is regarded as having one of the fastest growing life science markets in the world. With more than 16 license agreements with global research product suppliers, we believe the vast majority of industrial sales of RNAi products for research purposes are currently being made under a license from Alnylam.”

“This agreement with Alnylam, a leader in the field of RNAi, reinforces our ability to become a leading global supplier of RNAi reagent products to the pharmaceutical and research community in China and worldwide,” said Peter Zhang, Ph.D., Chairman and Chief Executive Officer of Shanghai GenePharma. “Access to the Kreutzer-Limmer patent estate allows us to augment our RNAi products, thereby strengthening our position in the life sciences marketplace.”

Alnylam’s intellectual property estate includes certain fundamental patents and patent applications, including the Kreutzer-Limmer I and II patents, which claim the broad structural and functional properties of synthetic RNAi products.

[aktianer]

Antwort auf Beitrag Nr.: 33.713.683 von Fruehrentner am 24.03.08 18:01:31

Die Konkurrenz schläft auch nicht (vermutlich deshalb der Kursverfall zu Börsenbegeinn) - kocht aber wohl auch nur mit Wasser (so deute ich die anschließende Kurserholung):

New kind of gene "silencing" drug works in monkeys
Wed Mar 26, 2008 2:12pm EDT
By Ben Hirschler

LONDON (Reuters) - A new class of drug that fine tunes the action of genes has been shown to cut cholesterol in monkeys and may fight a range of ills, including hepatitis C and perhaps cancer, scientists said on Wednesday.

The compound, from Danish biotech firm Santaris Pharma, works by blocking or "silencing" microRNAs -- tiny strands of RNA, or ribonucleic acid, that help turn genes into proteins.

The ground-breaking study is the first demonstration of microRNA silencing in primates and an early endorsement of the technique. Phase I safety trials are now planned in humans.

Unlike other drugs in the hotly pursued RNA interference field, the new designer molecule, known as Locked Nucleic Acid (LNA), can be given as a simple injection rather than having to be delivered direct to affected tissue.

"We think LNA is a one-stop shop for silencing," Santaris Chief Executive Keith McCullagh told reporters.

Scientists from Santaris and the University of Copenhagen lowered total cholesterol in African green monkeys by up to 30 percent, without ill effects, by targeting a microRNA linked to genes in the liver that are involved in cholesterol metabolism.

The results were published in the journal Nature, along with other test-tube research showing that LNA effectively blocks the production of hepatitis C virus in human liver cells.

Santaris intends to test its first LNA compounds in humans by the middle of this year but it will take at least five years before any medicine is ready for submission for approval. Continued...

http://www.reuters.com/article/marketsNews/idUKL264025922008…" target="_blank" rel="nofollow ugc noopener">http://www.reuters.com/article/marketsNews/idUKL264025922008…

[aktianer]

Antwort auf Beitrag Nr.: 33.742.976 von aktianer am 27.03.08 18:26:09

Kursentwicklung sieht heute böse aus:

ALNY 3:31PM ET 24.02 Down 1.49 Down 5.84% 546,581 Stücke

[MrBean07]

Antwort auf Beitrag Nr.: 33.551.943 von Fruehrentner am 04.03.08 23:49:38

da hast du den Nagel aber auf den Kopf getroffen, Frührentner.

In der Tat, gerade deshalb sind fast alle Biotechs mit Oliguncleotid-Therapeutika auf die Nase gefallen. Auch RNAi ist und bleibt nur ein wichtiges diagnostisches und biochemisches Tool.
Ein Drug mit dem angepeilten WEirkstoffmechanismus auf Oligonucleotid-Basis wird es (sag niemals nie!) aber in den nächsten Jahrzehnten nicht geben

[Fruehrentner]

Antwort auf Beitrag Nr.: 33.755.246 von MrBean07 am 28.03.08 21:03:48

Drug Delievery bei RNAI schwierig? Ja, aber unmöglich?

Hast du da tiefere Erkenntnisse, warum das nicht klappen wird?

Warum kaufen sich Big Pharmas dann in diese Technolgie mit viel Geld ein? Die haben doch auch Experten.

[MrBean07]

Hast du da tiefere Erkenntnisse, warum das nicht klappen wird?
Leider ja, würde hier aber zu weit führen. Es reicht aber zu wissen, daß die sogenannte Antisense-Technologie nach 20jähriger Forschung bis auf wenige Ausnahmen einiger Unentwegter gescheitert ist. Die RNAi-Technologie ist nicht grundsätzlich verschieden, aber eben "hipp".

Warum kaufen sich Big Pharmas dann in diese Technolgie mit viel Geld ein? Die haben doch auch Experten.

Sie machen das oft tatsächlich mit mangelnder Expertise. Die Richtung bei Big Pharma wird nicht von den Experten kontrolliert, sondern von Unternehmensberatern, Kaufleuten, etc. Dafür könnte ich dir mehrere Praxisbeispiele nennen, bei denen die Experten abrieten, das Management aber trotzdem mal rasch eine Milliarde in den Sand setzte! Der Prophet gilt sehr wenig im eigenen Lande!Außerdem sagen solche Verträge mit Biotechs erst mal wenig, es wird weit weniger Geld investiert als es aussieht. Pharma hät sich bloß alle Optionen offen, nach dem Motto: man kann es ja nie sicher wissen.

[Fruehrentner]

Alnylam Presents Pre-clinical Data from Hypercholesterolemia, Liver Cancer, Ebola, and Progressive Multifocal Leukoencephalopathy (PML) Programs at RNAi Keystone Symposium

31 Mar 2008

New Data Highlight Broad Applications of RNAi Therapeutics and Continued Progress in Advancing Pipeline of Innovative Medicines

CAMBRIDGE, MA, USA | March 31, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented pre-clinical data at the "RNAi, MicroRNA, and Non-Coding RNA" Keystone Symposium held March 25-30, 2008 in Whistler, British Columbia. Alnylam and its collaborators presented data from Alnylam's therapeutic programs including hypercholesterolemia, liver cancer, Ebola, and PML, as well as an update on delivery approaches for the systemic delivery of RNAi therapeutics.

"Alnylam scientists and collaborators continue to make significant progress with RNAi therapeutics in important areas of unmet medical need. We are encouraged by the data continuing to emerge from our hypercholesterolemia, Ebola, liver cancer, and PML programs which show potent and specific in vivo efficacy mediated by an RNAi mechanism," said Victor Kotelianski, M.D., Ph.D., Vice President, Research at Alnylam. "We are also excited by our progress in optimizing siRNAs for systemic delivery, including our recent data regarding heart and muscle delivery. We believe that these cumulative data demonstrate Alnylam's scientific leadership and commitment in translating the science of RNAi into a new class of innovative medicines."

Hypercholesterolemia

Alnylam is developing a systemically delivered RNAi therapeutic for the treatment of hypercholesterolemia targeting PCSK9, a well-validated gene involved in the metabolism of LDL cholesterol ("bad cholesterol"). In a poster titled "RNAi Therapeutics Targeting PCSK9 Acutely Lower Cholesterol from Mice to Non-Human Primates," Alnylam scientists presented in vivo data demonstrating that an RNAi therapeutic targeting the PCSK9 gene significantly decreased LDL cholesterol in three pre-clinical animal models - mouse, rat and non-human primate.

Data presented at the meeting from studies in rodent models include the following:

-- an RNAi therapeutic targeting PCSK9 demonstrated statistically significant dose- dependent silencing of PCSK9 mRNA and lowered total cholesterol by 40 to 50 percent as compared with control, non-specific siRNAs; and,

-- the effects on cholesterol lowering was mediated by a three to five fold increase in LDL receptor levels with no effect on hepatic triglycerides and hepatic cholesterol; these data further support the belief that RNAi therapeutics targeting PCSK9 are unlikely to result in steatosis (fatty liver).

In non-human primate models, data presented include the following as compared to a control siRNA:

-- RNAi-mediated gene silencing was associated with rapid reductions in LDL cholesterol levels by 40 to 60 percent of pre-dose levels;

-- circulating apolipoprotein B (apoB) levels - a constituent of the LDL particle - decreased by 30 to 40 percent of pre-dose levels;

-- after a single intravenous injection, the RNAi therapeutic showed a durable biological effect with levels of LDL cholesterol decreased for up to three weeks; and,

-- therapeutic efficacy was observed with an overall decreased ratio of total cholesterol to HDL cholesterol ("good cholesterol") - a result which has been shown in humans to correlate with clinical benefit.

Liver Cancer

Alnylam is developing a systemically delivered RNAi therapeutic, ALN-VSP, for the treatment of liver cancers and potentially other solid tumors. ALN-VSP comprises two siRNAs in a lipid particle formulation. These two siRNAs target separate genes involved in the growth and development of tumors: kinesin spindle protein, or KSP, and vascular endothelial growth factor, or VEGF. In a talk titled "Translating RNAi," Muthiah Manoharan, Ph.D., Vice President, Drug Discovery at Alnylam presented in vivo data from its ALN-VSP program which were generated in collaboration with Protiva, using their stable nucleic acid-lipid particles, or SNALP, technology.

Pre-clinical data with ALN-VSP, as compared to a control non-specific siRNA, in a mouse model of liver cancer demonstrated the following:

-- significant dose-dependent silencing of both KSP and VEGF derived from the human tumor;

-- evidence of tumor cell cycle arrest due to KSP silencing documented histologically;

-- reduction in overall tumor growth as measured by quantification of a tumor-specific gene; and

-- marked reduction in the size of liver tumors in VSP-treated animals as observed by gross pathology.

Alnylam BioDefense(TM)/Ebola

Alnylam is developing an RNAi therapeutic directed against the Ebola virus, which can cause a severe, often fatal infection, and poses a potential biological safety risk and bioterrorism threat. In a poster titled "RNAi Therapeutics for the Treatment of Ebola Virus Infection," pre-clinical data were presented on this program, which utilizes an optimized RNAi therapeutic formulated in a lipid particle for systemic delivery. This work was done in collaboration with Tekmira using their lipid particle delivery formulation technology.

Pre-clinical data presented include the following:

-- potent siRNAs with in vitro anti-viral activity have been identified against all genes in the Ebola genome;

-- a greater than 95 percent decrease in viral titer was seen when an RNAi therapeutic targeting one of these genes, VP35, was administered to mice infected with Ebola; and,

-- the VP35 siRNA, as compared with a control non-specific siRNA, was able to protect both mice and guinea pigs from lethal Ebola infection.

Alnylam is working with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), an organization which is uniquely experienced in the handling, safety, and security requirements of specialized biological agents. Alnylam produces drug candidates which are then sent to USAMRIID for in vitro and in vivo testing against the Ebola virus. The National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), is funding this work through a federal contract (No. HHSN266200600012C).

Progressive Multifocal Leukoencephalopathy (PML)

Alnylam is developing an RNAi therapeutic for the potential treatment of PML, in collaboration with Biogen Idec. PML is caused by infection of the central nervous system with a virus called "JC virus" and can occur in certain immune-suppressed patients, including those receiving immunomodulatory therapies. In a poster titled "Developing RNAi Therapeutics Targeting JCV for Treatment of PML," Alnylam scientists presented results showing that potential JCV RNAi therapeutic candidates targeting different JCV transcripts have been identified and showed potent inhibition of secondary PML infection in vitro, both prophylactically and post-infection. Because there is no established animal model of PML, Alnylam is delivering its RNAi therapeutic to normal oligodendrocytes, the primary site of JCV infection in vivo.

Additional pre-clinical data presented from this program included the following:

-- JCV siRNAs are stable in human cerebrospinal fluid (CSF) with half-lives greater than 48 hours, and do not produce unwanted cytokine responses;

-- in a rodent model, siRNAs in vivo were successfully delivered and silenced an endogenous oligodendrocyte target (CNP) in a specific manner as compared with a control non-specific siRNA;

-- direct central nervous system (CNS) delivery of siRNA in the rodent model silenced the CNP mRNA by approximately 75 percent, as compared with a control non-specific siRNA, and was durable for up to one week;

-- CNP silencing was found to be mediated by an RNAi mechanism as measured by 5'RACE; and

-- in a non-human primate model, direct infusion of an siRNA into the CNS silenced the CNP mRNA by 55 percent.

Alnylam believes these findings further support the use of RNAi as a potential therapeutic approach for the treatment of PML.

Delivery

"As we continue to develop novel delivery solutions for RNAi therapeutics, we are excited by the new data around chemical modifications for improved efficacy, safety and delivery," said Muthiah Manoharan, Ph.D., Vice President, Drug Discovery at Alnylam. "In addition, we are also encouraged by the use of simple Intralipid(TM) formulations using cholesterol-conjugated siRNAs and antagomirs which showed promising muscle delivery. Indeed, these data, with our collaborator Markus Stoffel, suggest an exciting convergence of conjugation and formulation approaches for systemic delivery of RNAi therapeutics."

In the talk titled "Translating RNAi," Dr. Manoharan also presented new data related to the effective delivery of RNAi therapeutics. Dr. Manoharan showed that among the numerous carbohydrate modifications to improve the drug-like properties of siRNAs, 2'-Fluoro modifications consistently provided increased target binding affinity, endonuclease stability, and, importantly, reduced immune response. In addition, it is the only modification compared to other carbohydrate modifications, including locked nucleic acid, or LNA, that preserves RISC activity when used in both sense and antisense strands.

Data presented included the following:

-- 2'-Fluoro modified siRNAs are significantly more stable, thermodynamically and to nucleases in biological fluids, and can increase the efficacy of siRNAs approximately 2-fold in vivo; and

-- a 2'-Fluoro modified siRNA targeting Factor VII was found to produce no immuno-stimulatory response, whereas a corresponding unmodified siRNA could stimulate IFN-alpha and TNF-alpha in vitro.

Alnylam has exclusive access to the use of 2'-Fluoro chemistries for RNAi therapeutics through its 2004 agreement with Isis Pharmaceuticals, Inc.

In addition, data were presented related to new delivery approaches for the delivery of RNAi therapeutics. Specifically:

-- a new cationic lipid was developed in collaboration with Tekmira; a substantial increase in potency of siRNA-containing lipid particles containing this lipid was observed suggesting the potential to develop new lipid-based formulations for systemic delivery of siRNAs with markedly improved potency;

-- PEG conjugation can facilitate delivery of siRNAs to the intestine; and

-- Alnylam's new lipid particle formulations with new cationic lipids and PEG modifications continue to improve the therapeutic potential of siRNAs and antagomirs.

Finally, in a talk titled, "RNAi Based Therapy," Markus Stoffel, M.D., Ph.D., Professor for Metabolic Diseases at the Institute of Molecular Systems Biology, Swiss Federal Institute of Technology in Zurich, member of the Alnylam Scientific Advisory Board and long-term collaborator of Alnylam, presented new data utilizing cholesterol-conjugated siRNAs that are co-formulated with commercially available Intralipid(TM). These new cholesterol-conjugated siRNA:Intralipid formulations showed distribution to heart and muscle. Similar results were obtained with single-stranded, cholesterol-conjugated olionucleotides targeting microRNAs, also called "antagomirs," including silencing of microRNAs in heart and muscle.

About RNA Interference (RNAi)

RNAi is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today, and was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans, and prospects, including its views with respect to the robustness, scope, and predictive value of the data presented at the Keystone Symposium, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; Alnylam's ability to fund and the results of further pre-clinical and clinical trials; obtaining, maintaining and protecting intellectual property utilized by its products; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of Alnylam's product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and its short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-K on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

SOURCE: Alnylam Pharmaceuticals, Inc.

http://www.pipelinereview.com/content/view/18588/104/

[aktianer]

Antwort auf Beitrag Nr.: 33.775.757 von Fruehrentner am 01.04.08 11:48:35

@Frührentner, danke für das Einstellen der Infos.

Heute bestätigte King von Rodman seine Empfehlung vom 07.03.08 (wichtiger wäre allerdings, wenn der Alny-kritischen Analyst Alan Carr von Needham eine etwas positivere Analyse schreiben würde):

Rodman Reiterates Alnylam 'Buy'
Tuesday April 1, 1:23 pm ET
Rodman & Renshaw Analyst Reaffirms "Buy" for Alnylam Pharmaceuticals

NEW YORK (AP) -- Rodman & Renshaw reaffirmed a "Buy" rating for biotechnology company Alnylam Pharmaceuticals Inc. Tuesday, citing positive early indicators for its gene-silencing technology.

Cambridge, Mass.-based Alnylam presented a flurry of positive preclinical data on its liver cancer, Ebola, and high blood cholesterol programs at a symposium last week in Whistler, British Columbia.

The company develops RNAi therapeutics, or gene-silencing treatments. The technology is aimed at targeting the gene at the root of a disease or condition and shutting it down, or silencing it.

In laboratory studies, the company's technology showed antiviral activity against all the genes in the Ebola virus genome, resulting in more than a 95 percent drop in the virus. The study used mice as test subjects.

A separate study also showed the technology reduced cholesterol by up to 60 percent in the laboratory model. The RNAi technology also reduced the size of tumors in a liver cancer study.

Analyst Michael G. King Jr. has a $37 price target on the stock.

http://biz.yahoo.com/ap/080401/alnylam_pharmaceuticals_analy…" target="_blank" rel="nofollow ugc noopener">http://biz.yahoo.com/ap/080401/alnylam_pharmaceuticals_analy…

[Salem-]

Die Ribopharma AG fusionierte ja vor Jahren mit Alnylam. Ribopharma galt ja als deutscher Pionier in der "Welt der Antisense". Weis jemand, welche Oligo Projekte oder Wirkstoffkandidaten in die Alnylam Pipeline übergingen?

[Fruehrentner]

aktuelle Meldung aus der RNAi-Branche:

Targeted Genetics Acquires Rights to siRNA Development Program in Huntington's Disease From Sirna Therapeutics

07 Apr 2008

Targeted Genetics Corporation today announced that it has acquired full exclusive rights to its preclinical Huntington's disease program from Sirna Therapeutics, a wholly owned subsidiary of Merck & Co., Inc

SEATTLE, WA, USA | April 7, 2008 | Targeted Genetics Corporation (NASDAQ: TGEN) today announced that it has acquired full exclusive rights to its preclinical Huntington's disease (HD) program from Sirna Therapeutics, a wholly owned subsidiary of Merck & Co., Inc.

In exchange for these rights, which include a license to intellectual property (IP) that Targeted Genetics may find necessary to develop and commercialize an HD product, Targeted Genetics will pay Sirna an undisclosed royalty on future sales. Sirna has also assigned to Targeted Genetics a licensing agreement it has with the University of Iowa that covers certain IP developed by Dr. Beverly Davidson's laboratory related to RNA interference (RNAi) including Adeno-Associated Virus (AAV) expressed RNAi.

In 2005, Targeted Genetics and Sirna Therapeutics formed a collaboration to develop HD therapeutics using an AAV delivered RNAi approach to target the HD gene. This collaboration also involved Dr. Davidson's laboratory and was based on preclinical proof of concept established by University of Iowa researchers. AAV vectors express for long periods of time and allow for infrequent dosing, which is highly desirable when administering a therapeutic directly to the brain.

"This moves all of the key pieces of this program to Targeted Genetics and gives us exclusive rights and direct involvement with the University of Iowa to expedite the program," said H. Stewart Parker, president and chief executive officer of Targeted Genetics. "This program is our primary proof of concept in the area of expressed RNAi, which we believe could present multiple product opportunities to help patients who currently have little hope for treatment, such as those with HD."

"The results we have produced in animal models of HD are very exciting. We have identified and are currently evaluating lead candidates in preclinical studies to move forward into clinical trials," stated Beverly L. Davidson, Ph.D., Roy J. Carver professor of medicine and vice chair of research in the Department of Internal Medicine at the University of Iowa. "Targeted Genetics' approach of using AAV vectors for the delivery of expressed RNAi may have advantages over alternative RNAi delivery approaches due to AAV's proven long-term expression capabilities, stability and safety profile."

HD is a devastating, inherited, neurodegenerative disorder that results from a mutation in the gene that codes for the huntingtin protein. HD generally shows onset in mid-life and, according to the Huntington's Disease Society of America, one of out of every 10,000 Americans has HD and an additional 200,000 are at risk of onset. The disease-causing gene produces a defective huntingtin protein that is toxic to certain brain cells and the subsequent neuronal damage leads to the movement disorders, psychiatric disturbances and cognitive decline that characterize this disease.

"There is a serious unmet medical need for an effective treatment for HD," said Alan Sachs, M.D., Ph.D., vice president RNA therapeutics, Merck Research Laboratories. "This agreement provides Targeted Genetics with the freedom to advance this AAV vector program in the hope of developing a treatment that targets the genetic cause of this devastating condition, not just the symptoms."

About Targeted Genetics

Targeted Genetics Corporation is a biotechnology company committed to the development of innovative targeted molecular therapies for the prevention and treatment of acquired and inherited diseases with significant unmet medical need. Targeted Genetics' proprietary Adeno-Associated Virus (AAV) technology platform allows it to deliver genes that encode proteins to increase gene function or RNAi to decrease or silence gene function. Targeted Genetics' product development efforts target inflammatory arthritis, AIDS prophylaxis, congestive heart failure and Huntington's disease. To learn more about Targeted Genetics, visit Targeted Genetics' website at www.targetedgenetics.com.

SOURCE: Targeted Genetics

[Salem-]

Antwort auf Beitrag Nr.: 33.835.439 von Fruehrentner am 08.04.08 13:24:08

Ist doch PillePalle. Der Deal zwischen Santaris und GlaxoSmithKline ist die Mutter aller Deals. Jedenfalls in der frühen Phase.



GlaxoSmithKline and Santaris Pharma enter global R&D alliance to
discover, develop and commercialise RNA antagonists as novel antivirals

GlaxoSmithKline (GSK) and Santaris Pharma today announced that they have entered into
a worldwide strategic alliance for the discovery, development and commercialisation of novel medicines against viral diseases. The collaboration provides GSK access to
patented RNA antagonist compounds, based on Santaris Pharma’s unique Locked Nucleic
Acid technology, for development as potential new therapies for selected viral diseases.
GlaxoSmithKline will participate in the alliance through its Infectious Diseases Centre of
Excellence for Drug Discovery (ID CEDD). Under the terms of the agreement, Santaris Pharma
will grant GlaxoSmithKline options to drug candidates discovered and developed under the
collaboration in up to four different viral disease programmes. In each of these R&D programmes,
Santaris Pharma will be responsible for the discovery and development of RNA antagonist drug
candidates through to completion of Phase IIa (“Clinical Proof of Concept”), at which point
GlaxoSmithKline has an exclusive option to license each compound for further development and
commercialisation on a worldwide basis. GSK also has an option to include as an additional
programme in the collaboration, SPC3649, Santaris Pharma’s preclinical LNA-antimiR against
microRNA-122, which is being developed by Santaris Pharma as a potential new therapy for
Hepatitis C infection.
Santaris Pharma will receive an upfront fee for the first antiviral programme of $3m (£1.5m) and
GSK will make an equity investment of $5m (£2.5m) in Santaris Pharma. If candidate drugs from
the first viral target programme are successful and reach the market, GSK could make additional
milestone payments to Santaris Pharma of up to $140m (£69.5m) for this first programme.
Similar upfront payments and milestones are payable by GSK to Santaris Pharma in respect of
each of the further 3 antiviral programmes if GSK elects to initiate these additional programmes in
the collaboration. In addition, if GSK exercises its option to further develop and commercialise
SPC3649, it will make a further up front payment of $5m (£2.5m) and additional milestones of up
to $122m (£60.5m) if the drug obtains regulatory approvals in Europe and the USA. Overall,
under the collaboration Santaris Pharma could be eligible to receive in excess of $700m (£347m)
in upfront fees and development and regulatory milestones payments. If a product is successfully
commercialised, Santaris Pharma will receive high single to double-digit royalties on worldwide
sales of alliance products.
Announcing the collaboration, Dr Henrik Ørum, Santaris Pharma’s Chief Scientific Officer and VP
Business Development commented:
”We are delighted that GlaxoSmithKline has chosen to collaborate with Santaris Pharma in the
RNA medicines field. We are confident that the high potency and exquisite precision of RNA
targeting achievable by LNA oligonucleotides has the potential to achieve clinical breakthroughs
in viral infections. I can think of no stronger partner for Santaris Pharma in infectious disease
research than GSK.”
Dr Zhi Hong, Senior Vice President and Head of GlaxoSmithKline’s ID CEDD said:

http://www.santaris.com/filemanager/items/gsksantaris_pr_fin…

Die großen Konzerne gehen vermehrt in die Antisense. Und Girindus stellt für beide die WS unter cGMP her. Auch für Alnylam. Jedenfalls das was von Ribopharma in Pipeline kam. Santaris ist ein heißen Eisen mE, aber leider nicht börsennotiert.

[Salem-]

”We are delighted that GlaxoSmithKline has chosen to collaborate with Santaris Pharma in the
RNA medicines field. We are confident that the high potency and exquisite precision of RNA
targeting achievable by LNA oligonucleotides has the potential to achieve clinical breakthroughs
in viral infections. I can think of no stronger partner for Santaris Pharma in infectious disease
research than GSK.”


Auch ein wichtiges Statement. Nur des gesamte Feld verstehen tue ich nicht unbedingt. Da gibts RNA, mRNA, LNA, DNA als Wirkstoffe.

[Fruehrentner]

09.04.2008 13:00:00

Alnylam Initiates Phase II Trial to Evaluate Safety and Tolerability of ALN-RSV01 in Adult Lung Transplant Patients Naturally Infected with Respiratory Syncytial Virus (RSV) Infection

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today it has initiated a Phase II clinical trial to assess the safety and tolerability of aerosolized ALN-RSV01 versus placebo in adult lung transplant patients naturally infected with RSV. As a secondary objective, this trial will be the first to evaluate the anti-viral activity of ALN-RSV01 in a naturally acquired RSV lower respiratory tract infection.

“There is a significant need for novel therapeutics to effectively treat patients with RSV infection, a prevalent infection in immune-compromised adult populations such as lung transplant patients, and the leading cause of pediatric hospitalization in the U.S. today,” said Akshay Vaishnaw, M.D., Ph.D., Vice President, Clinical Research at Alnylam. “While our primary focus is on developing an RNAi therapeutic for pediatric RSV populations, we see a clear need for new treatments in certain adult patient settings and recognize the importance that comprehensive safety and exploratory efficacy bring to our overall ALN-RSV01 development program.”

RSV infection in lung transplant patients represents a significant unmet medical need. The condition is associated with significant morbidity – up to 15 to 20 percent of infected patients develop acute or chronic lung rejection. These patients are also at risk for an increase in frequency of bronchiolitis obliterans syndrome, a manifestation of chronic rejection that is associated with a high five-year mortality rate.

“I am encouraged by the potential for ALN-RSV01 based on its safety, tolerability, and anti-viral activity to date, and I look forward to working with Alnylam in developing this RNAi therapeutic for the treatment of RSV infection in lung transplant patients,” said Martin Zamora, M.D., Professor of Medicine, and Medical Director, Lung Transplant Program, University of Colorado Health Sciences Center, and Principal Investigator for the trial in the U.S. “These patients have very limited treatment options and pulmonologists are in need for an RSV therapy in this critical disease area. Indeed, morbidities associated with RSV infection in this setting are significant due to the potential for acute and chronic lung rejection and other complications.”

The Phase II trial is a multi-center, multi-national, randomized, double-blind, placebo-controlled study. The primary objective of the study is to assess the safety and tolerability of aerosolized ALN-RSV01 versus placebo in lung transplant patients naturally infected with RSV. Secondary objectives include evaluating the anti-viral activity and pharmacokinetics of ALN-RSV01. Methods for measuring anti-viral activity include nasal swabs to determine level of viral shedding, as well as bronchoalveolar lavage (BAL) sampling in certain patients as determined necessary by the attending physician. BAL is a minimally invasive medical procedure that allows measurement of infection in the lung.

The trial is expected to enroll 21 patients who will be randomized in a two to one, drug to placebo ratio. All patients will receive standard of care, and those receiving ALN-RSV01 will have drug administered as a 0.6 mg/kg dose by inhalation via nebulizer once daily for three days. Results from previous pre-clinical and clinical studies have demonstrated that ALN-RSV01 has a favorable safety profile as well as robust anti-viral activity. Alnylam recently completed its Phase II GEMINI study in experimentally infected adult volunteers where, compared to placebo, intranasally administered ALN-RSV01 demonstrated statistically significant anti-viral efficacy with a 38 percent relative reduction in RSV infection rate and a 95 percent increase in the number of infection-free subjects. In addition and in other studies, ALN-RSV01 was shown to be safe and well tolerated when administered by inhalation via nebulizer in a multi-dose regimen in adult volunteers.

About Respiratory Syncytial Virus (RSV)

RSV is a highly contagious virus that causes infections in both the upper and lower respiratory tract. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems, and others. RSV infection typically results in cold-like symptoms but can lead to more serious respiratory illnesses such as croup, pneumonia, bronchiolitis, and in extreme cases, death. RSV infection in the pediatric and adult populations account for more than 300,000 hospitalizations per year in the U.S. In addition, RSV infection in infants has been linked to the development of childhood asthma. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including without limitation statements concerning the timing and scope of clinical trials and studies, the need for novel RSV therapeutics, its views with respect to the potential for RNAi therapeutics, including ALN-RSV01, and the company’s plans for achievements by the end of 2010, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the “Risk Factors” section of its most recent annual report on Form 10-K on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
(Investors)
or
Yates Public Relations
Kathryn Morris, 845-635-9828
(Media)

Quelle: BUSINESS WIRE

[aktianer]

Hoffentlich ist der gestrige Anstieg nicht wieder nur eine Eintagsfliege:

Analyst comments lift shares of Alnylam Pharmaceuticals
Wednesday April 16, 1:04 pm ET
Alnylam stock rises after analyst praises RNAi technology, strategy and management

NEW YORK (AP) -- Alnylam Pharmaceuticals shares are rising after a Broadpoint analyst praised the company and forecast a strong year for the stock.

Simos Simeonidis says Alnylam is the leader in RNA-interference technology. He compliments Alnylam's management and intellectual property and says the company has had more success in clinical trials and in business than its rivals.

The Cambridge, Mass., company is developing products that treat diseases at the genetic level, "silencing" the genes that cause them.

Simeonidis has a "Buy" rating on the stock with a target price of $38 per share, which implies shares will climb almost 66 percent over the next year. The analyst says the stock is inexpensive.

Alnylam Pharmaceuticals Inc. stock is $1.09, or 4.8 percent, to $24.04.

http://biz.yahoo.com/ap/080416/alnylam_mover.html?.v=1

[aktianer]

Antwort auf Beitrag Nr.: 33.904.744 von aktianer am 17.04.08 08:37:40

scheint doch nur eine Stundenfliege zu sein. Die Analysen kommen anscheinend von Analysten, die (im Moment?) kein Gehör finden.
Auch folgende Meldung zu dem Joint-Venture-Unternehmen mit Isis, der Regulus, scheint den Kürs nicht zu stützen zu können:

GlaxoSmithKline partners with Regulus on gene-silencing tech
Thursday April 17, 9:57 am ET
GlaxoSmithKline partners with Regulus Therapeutics to develop inflammatory-disease treatments

NEW YORK (AP) -- GlaxoSmithKline PLC and Regulus Therapeutics LLC said Thursday they will partner to develop gene-silencing technolgy aimed at treating inflammatory diseases, including rheumatoid arthritis.

Regulus, a joint venture of Alnylam Pharmaceuticals Inc. and Isis Pharmaceuticals Inc., will receive $20 million in upfront payments and is eligible to receive up to $144.5 million in development, regulatory and sales milestone payments. The deal involves product candidates aimed at four gene-silencing targets relevant to inflammatory conditions.

Regulus will be responsible for the discovery and development of the microRNA, or gene silencing, targets through proof of concept. Glaxo will have an exclusive license to drugs developed under each program.

In addition to the potential of nearly $600 million Regulus could receive in option, license and milestone payments, Regulus would also receive tiered royalties up to double digits on worldwide sales.


http://biz.yahoo.com/ap/080417/glaxosmithkline_contract.html…

[Fruehrentner]

Flopmode versucht sich an einer Chartanalyse bei Alnylam:


ALNYLAM - Jetzt wieder hoch?

17.04.2008 - 15:42

Alnylam Pharmaceuticals - Kürzel: ALNY - ISIN: US02043Q1076

Börse: Nasdaq in USD / Kursstand: 24,69 $

Rückblick: Die ALNYLAM Aktie befindet sich in einer mittelfristigen Aufwärtsbewegung, wobei sie ab dem AllTimeHigh bei 37,35 $ im Oktober 2007 grob seitwärts pendelt.

Im Februar 2008 startete schließlich ein deutlicher Kursrutsch bis an den Unterstützungsbereich bei 21,98 - 22,50 $, wo die Aktie nun eine Stabilisierung versucht. In dieser Woche prallt sie erneut nach oben hin ab. Das kurzfristige Chartbild ist neutral zu werten.

Charttechnischer Ausblick: Die ALNYLAM Aktie befindet sich in einer größeren Zwischenkorrektur, wobei sich nun die Chance auf eine Bodenbildung bieten würde. Eine kurzfristige Erholung bis ca. 27,00 - 27,15 $ wäre jetzt bei einem Anstieg über 24,77 $ möglich.

Erst eine nachhaltige Rückkehr über 27,15 $ würde das Chartbild wieder entscheidend aufhellen, größere Käufer könnten dann für einen Kursanstieg bis 35,15 und 37,35 $ sorgen.

Fällt die Aktie hingegen signifikant unter 21,90 $ zurück, trübt sich das mittelfristige Chartbild deutlich ein. Eine durch Stop Loss Orders losgetretene Verkaufswelle könnte die Aktie dann bis 15,06 $ abrutschen lassen.

Kursverlauf vom 04.05.2007 bis 17.04.2008 (log. Kerzenchartdarstellung / 1 Kerze = 1 Tag)

[Fruehrentner]

Es scheint ein wichtiger Meilenstein (systemische Formulierung) erreicht worden zu sein oder zumindest ist man diesbezüglich einen deutlichen Schritt vorangekommen:


Alnylam and Collaborators at MIT Publish Research on the Discovery of 'Lipidoids', a Novel Class of Lipid-Based Molecules for the Delivery of RNAi Therapeutics

28 Apr 2008

New Findings Published in Nature Biotechnology Demonstrate Use of "Lipidoids" to Achieve Systemic Delivery of RNAi Therapeutics in Multiple Pre-Clinical Models

CAMBRIDGE, MA, USA | April 28, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication of a new study in Nature Biotechnology by Alnylam scientists and collaborators from the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT). The new research (Akinc et al., Nature Biotechnology advance online publication, 27 April 2008 (DOI:10.1038/nbt1402)) documents the design and synthesis of a new class of lipid-based molecules called "lipidoids", which were used to form novel nanoparticle formulations for systemic delivery of RNAi therapeutics. The results of the studies showed successful delivery of lipidoid formulations of small interfering RNAs (siRNAs), the molecules that mediate RNAi, in multiple animal species including mice, rats, and non-human primates that together demonstrate potent, specific, and durable effects on gene expression in multiple tissues, including liver, lung, and peritoneal macrophages. Further, the new paper demonstrates applications of the same technology for delivery of microRNA (miRNA) antagonists.

"The successful systemic delivery of RNAi therapeutics remains an important objective in our efforts to bring these innovative medicines to patients. We believe that this new research could pave an entirely new path for efficient delivery of RNAi therapeutics in a broad range of clinical applications," said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. "Further, this new work builds on our existing delivery efforts both in-house, and with collaborators including MIT, Tekmira, Protiva, and others."

"It is clear that more efficient delivery of RNAi therapeutics will require the discovery of new biomaterials and formulations. We believe the lipidoids we have developed greatly expand the collection of available delivery materials, and that they hold significant promise as delivery agents for both siRNA and miRNA therapeutics," said Daniel Anderson, Ph.D. of the David H. Koch Institute for Integrative Cancer Research at MIT. "We're excited about this work and optimistic that our continued collaboration with the team of scientists at Alnylam will lead to additional delivery solutions for RNAi therapeutics."

In the new research, Akinc et al. describe the discovery and synthesis of a novel class of lipid-based molecules called "lipidoids". These lipidoids were used to form entirely new formulations of siRNAs, enabling their delivery to a broad range of tissues in vivo. The lipidoid molecules were created through a new combinatorial synthesis scheme that allows for simple, high-speed production. The rapid synthesis enables the development of a large library of over 1,200 structurally diverse lipidoids, which can ultimately be customized for different RNAi therapies and drug delivery approaches. In an exclusive license agreement with MIT, Alnylam has secured all rights to the lipidoid technology for delivery of RNAi therapeutics for all uses.

In the study, researchers described the discovery of lipidoids and evaluated the delivery of lipidoid formulations with siRNA and anti-miRNA oligonucleotides in multiple animal species including mice, rats, and non-human primates. The lipidoid formulations demonstrated potent, specific, and durable effects on gene expression in multiple tissues, including liver, lung, and peritoneal macrophages.

Specifically:

-- in rats, significant, dose-dependent reductions in liver Factor VII mRNA levels were observed, with > 90% silencing at 5 mg/kg doses;

-- in non-human primates, silencing of apolipoprotein B (apoB) mRNA was observed in a dose-dependent manner, with maximal silencing of apoB liver mRNA of up to 85% corresponding to a maximal reduction in serum apoB reduction of up to 74% relative to pre-dose levels; and

-- in non-human primates, the effects were found to be durable where a single intravenous injection lasted for up to four weeks.

Further, the lipidoid formulations also proved effective for delivery of anti-miRNA oligonucleotides or "antagomirs" that are used to suppress miRNA activity. Also, the delivery technology was used to successfully deliver two different siRNAs at the same time, with no apparent competition between the two siRNAs, demonstrating the potential of a multi-targeting strategy for formulations of RNAi therapeutics.

Alnylam has established multiple industry and academic collaborators in an effort to address delivery of RNAi therapeutics in a comprehensive and systematic manner. In May 2007, Alnylam announced a collaboration with the David H. Koch Institute for Integrative Cancer Research at MIT. As part of this collaboration, Alnylam is sponsoring a five-year research program focused on the delivery of RNAi therapeutics with the exclusive option to license future RNAi technology resulting from the research sponsorship. Additionally, Alnylam has an agreement with Tekmira Pharmaceuticals Corporation related to Tekmira's planned business combination with Protiva Biotherapeutics, Inc. Upon the effective date for the Tekmira-Protiva transaction, the new agreement will expand Alnylam's access to key technology and intellectual property for the delivery of RNAi therapeutics with liposomal delivery technologies.


###

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

About the Koch Institute

The MIT Center for Cancer Research (CCR) has changed its name to the David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute - pronounced "coke") effective March 2008. This name change is linked to generous funding received in support of the creation of a new building and endeavor, to be completed by the year 2010, to house expanded and innovative cancer research at MIT. Note that all CCR facilities and faculty members have been incorporated into the Koch Institute.

SOURCE: Alnylam Pharmaceuticals, Inc.

[Fruehrentner]

06.05.2008 14:00:00

Regulus Therapeutics Exclusively Licenses Intellectual Property from Stanford University Relating to microRNA Antagonists to Treat Inflammatory Diseases

Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY) and Isis Pharmaceuticals, Inc. (Nasdaq:ISIS) formed to discover, develop, and commercialize microRNA (miRNA) therapeutics, announced today that it has obtained exclusive rights from Stanford University to worldwide patent applications covering methods and compositions for antagonizing miR-181a to regulate immune responses. Changes in miR-181a levels have been shown to modify the response of immune cells such as T lymphocytes to specific stimuli and its antagonism could lead to a new way to treat inflammatory diseases.

“We are excited about obtaining exclusive rights to this intellectual property, as it is another step in Regulus’ overall strategy to build a broad and leading platform of technology and intellectual property for the development of miRNA therapeutics, and adds to our already dominant patent position,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus. “At Regulus, we are aggressively exploring a variety of therapeutic areas including viral, metabolic, and inflammatory diseases. Access to this intellectual property allows us to apply our expertise in the biology and potential therapeutic uses of miRNAs to develop novel treatments for inflammatory diseases.”

Data published in 2007 by scientists at Stanford University and Alnylam in the journal Cell (Li et al. (2007) Cell 129, 147-161) demonstrated that modulation of miR-181a levels in an immune cell modified the sensitivity of the cell to specific stimuli. Researchers found that by increasing expression of miR-181a, an increase in the immune cell’s response to an inflammatory stimulus occurred. Conversely, decreasing levels of miR-181a in the immune cell led to a diminution in the cell’s response to an inflammatory stimulus, thereby de-sensitizing the cell to the stimulus. Using a selective miRNA antagonist to inhibit miR-181a function resulted in efficient reduction in the immune cell’s response to a stimulus. These data suggest that controlling miR-181a levels with selective antagonists may lead to a novel approach to treating inflammatory diseases.

###


About microRNAs

microRNAs (miRNAs) are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. miRNA therapeutics represent a new approach for the treatment of a wide range of human diseases. The inappropriate absence or presence of specific miRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, and metabolic disorders. Targeting miRNAs with novel therapeutic agents could result in novel and broadly acting treatments for human diseases.

About Regulus

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop and commercialize miRNA therapeutics. Regulus aspires to successfully translate one of the most important new properties in biology into a novel new approach for innovative medicine and to build the leading microRNA company. Regulus was created as a joint venture between Alnylam Pharmaceuticals, a leader in RNAi therapeutics, and Isis Pharmaceuticals, a leader in antisense technologies and therapeutics. Isis and Alnylam scientists and collaborators were the first to discover miRNA antagonist strategies that work in vivo in animal studies (Krutzfeldt et al. Nature 438, 685-689 (2005); Esau et al. Cell Metab., 3, 87-98 (2006)). Isis and Alnylam have also created and consolidated key intellectual property (IP) for the development and commercialization of miRNA therapeutics. This IP estate includes over 900 patents and patent applications, including 600 issued patents, owned by Isis and Alnylam and pertaining to chemical modification of oligonucleotides for therapeutic applications. In addition, Regulus has collaborations with more than 60 academic researchers to build on the company’s understanding of microRNAs and recently formed a major alliance with GlaxoSmithKline to explore new therapeutic areas for microRNA therapeutics. Regulus, founded in September 2007, maintains facilities in Carlsbad, California. For more information, visit www.regulusrx.com.

About Isis Pharmaceuticals, Inc.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 19 drugs in development. Isis’ drug development programs are focused on treating cardiovascular and metabolic diseases. Isis’ partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Ibis Biosciences, Inc., Isis’ majority-owned subsidiary, is developing and commercializing the Ibis T5000™ Biosensor System, a revolutionary system to identify infectious organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of miRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of miRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Forward-Looking Statement

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Isis’, Alnylam’s and Regulus’ business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus, including statements regarding Regulus’ patent licensing agreement with Stanford University and the potential to develop microRNA antagonists to miR-181a. Any statement describing Isis’, Alnylam’s or Regulus’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement, including those statements that are described as such parties’ goals. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Such parties’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause their results to differ materially from those expressed or implied by such forward-looking statements. Although these forward-looking statements reflect the good faith judgment of the management of each such party, these statements are based only on facts and factors currently known by Isis, Alnylam or Regulus, as the case may be. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis’, Alnylam’s and Regulus’ programs are described in additional detail in Isis’ annual report on Form 10-K for the year ended December 31, 2007 and in Alnylam’s annual report on Form 10-K for the year ended December 31, 2007, which are on file with the SEC. Copies of these and other documents are available from Isis or Alnylam.

Regulus Therapeutics
[e-mail]
or
Isis Pharmaceuticals
Media
Amy Blackley, Ph.D., 760-603-2772
or
Alnylam Pharmaceuticals
Investors
Cynthia Clayton, 617-551-8207

Quelle:BUSINESS WIRE

[aktianer]

erfreuliche Meldung: Novartis übt Optionrecht aus

Novartis buys more Alnylam stock for $5.4 mln
Thu May 8, 2008 8:29am EDT
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Market News


ZURICH, May 8 (Reuters) - Swiss drugmaker Novartis AG (NOVN.VX: Quote, Profile, Research) bought additional shares in Alnylam Pharmaceuticals Inc (ALNY.O: Quote, Profile, Research), a developer of a promising drug technology known as RNA interference, for $5.4 million.

Novartis fully exercised its right to buy more Alnylam stock, snapping up 213,888 shares at $25.29 each, equal to the average closing price for the 20 trading days ending March 28, Alnylam said.

The total cash payment to U.S.-based Alnylam, whose technology involves blocking disease-causing proteins, is $5.4 million and boosts Novartis's stake to about 13.4 percent of its outstanding common stock, from a previous 13 percent.

Alnylam has a partnership with Novartis which gave the Swiss company the right to buy additional shares. (Reporting by Sam Cage; Editing by David Holmes)

http://www.reuters.com/article/marketsNews/idINL089312572008…

[Fruehrentner]

08.05.2008 22:00:00

Alnylam Pharmaceuticals Reports First Quarter 2008 Financial Results

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today reported its consolidated financial results for the first quarter of 2008, and company highlights.

“We have demonstrated significant progress in the first quarter across all dimensions – scientific, clinical, and business,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Most notably in the period, we established human proof of concept for an RNAi therapeutic with the results from our Phase II GEMINI study with ALN-RSV01, representing what we believe is a major ‘de-risking’ event in the advancement of RNAi therapeutics as a whole new class of medicines.”

“Our business development activities also continue to be fruitful, as represented by the recent strategic alliance signed between Regulus Therapeutics, our joint venture with Isis Pharmaceuticals, and GlaxoSmithKline. Our leadership on delivery will be enhanced through the new business combination of Tekmira and Protiva, wherein we expect Alnylam’s access to delivery technology and intellectual property to be strengthened,” said Barry Greene, President and Chief Operating Officer of Alnylam. “We were also pleased to announce this morning that Novartis has exercised their current right to purchase the maximum amount of additional newly issued shares of Alnylam’s common stock as part of our 2005 agreements, which we view as a solid endorsement of our efforts to build a successful company.”

Cash, Cash Equivalents and Marketable Securities

At March 31, 2008, Alnylam had cash, cash equivalents and marketable securities of $443.9 million, compared to $455.6 million at December 31, 2007.

Net Loss

The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the quarter ended March 31, 2008 was $1.2 million, or $0.03 per share (including $3.8 million, or $0.09 per share, of non-cash stock-based compensation expense), compared to $21.6 million, or $0.58 per share (including a one-time non-cash license fee of $7.9 million and a cash license fee of $0.4 million, which totaled $0.22 per share, and $2.2 million, or $0.06 per share of non-cash stock based compensation expense) in the first quarter of 2007.

Revenues

Revenues in the first quarter of 2008 were $22.2 million, compared to $7.2 million during the first quarter of 2007. The significant increase in revenues in the first quarter of 2008 was primarily related to $13.4 million of net collaboration revenues related to the company’s alliance with Roche, which began in the third quarter of 2007. Revenues for the first quarter of 2008 also included $8.8 million of expense reimbursement and amortization revenues from Novartis, the National Institutes of Health (NIH), the Department of Defense (DOD), Biogen Idec, InterfeRx™, research reagent and services licensees, and other sources.

Research and Development Expenses

Research and development (R&D) expenses were $20.3 million in the first quarter of 2008, including $2.3 million of non-cash stock-based compensation, as compared to $26.7 million in the first quarter of 2007, including $1.2 million of non-cash stock-based compensation. The decrease in R&D expenses was primarily due to a first quarter 2007 non-cash license fee of $7.9 million to Tekmira Pharmaceuticals Corporation that the company paid in its common stock as well as a related cash license fee of $0.4 million. R&D expenses in the first quarter of 2008 consisted primarily of external service costs in support of the company’s clinical program for respiratory syncytial virus (RSV) infection as well as the company’s pre-clinical programs for the treatment of hypercholesterolemia, liver cancer, and Huntington’s disease. R&D expenses in the first quarter of 2008 also included costs associated with the company’s delivery-related collaborations. There was also an increase in non-cash stock-based compensation in the first quarter of 2008 as compared to the first quarter of 2007.

General and Administrative Expenses

General and administrative (G&A) expenses were $5.9 million in the first quarter of 2008, including $1.5 million of non-cash stock-based compensation, compared to $4.5 million in the first quarter of 2007, including $1.0 million of non-cash stock-based compensation. The increase in G&A expenses for the first quarter of 2008 was due primarily to higher professional service fees associated with increased business activities and an increase in G&A headcount over the past year to support the company’s growth. There was also an increase in non-cash stock-based compensation in the first quarter of 2008 as compared to the first quarter of 2007.

Regulus Therapeutics LLC; Joint Venture with Isis Pharmaceuticals

During the third quarter of 2007, the company made a $10.0 million investment in Regulus Therapeutics, a joint venture with Isis Pharmaceuticals for the discovery, development, and commercialization of miRNA therapeutics. The company is funding the first $10.0 million of Regulus Therapeutics’ net spend and has capitalized its investment in Regulus Therapeutics on its balance sheet. In its income statement, the company incurred a $1.6 million equity in loss of joint venture related to the company’s share of the net losses incurred by Regulus Therapeutics in the first quarter of 2008.

Interest Income

Interest income was $4.7 million in the first quarter of 2008 as compared to $2.7 million in the first quarter of 2007. The significant increase in interest income was primarily due to $331 million of gross proceeds that the company received from the alliance with Roche that closed in August 2007.

Income Tax Expense

As a result of the company’s alliance with Roche in August 2007, the company recorded income tax expenses of $0.2 million in the first quarter of 2008.

2008 Financial Guidance

Alnylam continues to expect that its cash, cash equivalents and marketable securities balance will be greater than $390.0 million at December 31, 2008.

“The strength of our alliance-based revenues, combined with continued disciplined spending in R&D and G&A, resulted in a modest net loss for the first quarter of 2008,” stated Patricia Allen, Vice President, Finance and Treasurer at Alnylam. “Our strong cash position, along with our expectation for continued funding from our collaborations allows us to invest significantly in advancing our pipeline of proprietary and partnered RNAi therapeutic programs, as well as in our delivery efforts as we continue to build our business.”

First Quarter 2008 and Recent Corporate Highlights

Product Pipeline and Scientific Leadership Highlights

Obtained Human Proof of Concept for RNAi Therapeutics. Alnylam achieved human proof of concept with an RNAi therapeutic, which it believes is a first for the technology and the industry. The company’s Phase II GEMINI study with ALN-RSV01 was a double-blind, randomized, placebo-controlled human clinical study in 88 adult subjects. Data from this study showed that intranasally administered ALN-RSV01 demonstrated statistically significant anti-viral efficacy with a 38% relative reduction in RSV infection rate and a 95% increase in the number of infection-free subjects as compared with placebo. Alnylam believes this represents a major de-risking event for the advancement of RNAi therapeutics, and supports Alnylam’s broad R&D efforts for RNAi therapeutics overall and ALN-RSV01 in particular.

Advanced Development of ALN-RSV01 for RSV Infection. Alnylam initiated a Phase II clinical trial to assess the safety and tolerability of aerosolized ALN-RSV01 versus placebo in adult lung transplant patients naturally infected with RSV. As a secondary objective, this trial will evaluate the anti-viral activity of ALN-RSV01 in patients with a naturally acquired RSV lower respiratory tract infection. The data from this study, in combination with the previous Phase II GEMINI trial and multiple Phase I trials, will comprise a comprehensive safety and efficacy data set with which Alnylam expects to further advance its overall ALN-RSV01 development program aimed toward pediatric RSV populations.
Expanded Development Pipeline. The company is advancing ALN-HTT as a development program, an RNAi therapeutic targeting the huntingtin gene for the treatment of Huntington’s disease. This program is in partnership with Medtronic, Inc., and is structured as a 50/50 co-development/profit share relationship in the U.S. market. In Europe, Medtronic is solely responsible for development and commercialization.

Augmented Platform for Systemic Delivery of RNAi Therapeutics. Alnylam intends to enter into a new agreement with Tekmira Pharmaceuticals Corporation related to Tekmira’s planned business combination with Protiva BioTherapeutics, Inc. Alnylam expects this new agreement will expand its access to key technology and intellectual property for the delivery of RNAi therapeutics with liposomal delivery technologies, including continued exclusive access to the Semple (U.S. Patent No. 6,858,225) and Wheeler (U.S. Patent Nos. 5,976,567 and 6,815,432) patents which the company believes are critical for cationic liposomal delivery of RNAi therapeutics.

Continued Scientific Leadership. Alnylam continued to demonstrate its scientific leadership through publication and presentation of peer-reviewed research, including:

-- publication of data from Alnylam's Phase I clinical trials with intranasally delivered ALN-RSV01 for the treatment of RSV infection (DeVincenzo et al., Antiviral Research 77, 225-231 (2008));

-- data demonstrating normalization of cellular function with RNAi therapeutics targeting a mutant gene for dystonia (Hewett et al., Human Molecular Genetics 17, 1436-1445 (2008));

-- discovery of "lipidoids," a novel biomaterials approach for systemic delivery of RNAi therapeutics as part of a research collaboration with scientists at MIT (Akinc et al., Nature Biotechnology advance online publication, 27 April 2008 (DOI:10.1038/ nbt1402));

-- new research related to defining immunostimulatory properties and mechanisms for siRNAs and methods to screen for and eliminate these properties in defining "drug-like" properties of siRNAs for therapeutic applications (Zamanian-Daryoush et al., Journal of Interferon & Cytokine Research 28, 221-233 (2008)); and,
-- new data at the 2008 Keystone RNAi Symposium highlighting continued progress in advancing pre-clinical programs including those for hypercholesterolemia, liver cancer, Ebola, and progressive multifocal leukoencephalopathy (PML), as well as advancements in systemic delivery of RNAi therapeutics.

Business Execution Highlights

Regulus Therapeutics Formed Major Alliance with GlaxoSmithKline (GSK), Valued at Over $600 Million. GSK and Regulus Therapeutics, Alnylam’s joint venture with Isis Pharmaceuticals, formed a strategic alliance to discover, develop, and market novel microRNA-targeted therapeutics to treat inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. GSK obtained an option to license product candidates directed at four different microRNA targets within inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Regulus Therapeutics received $20.0 million in upfront cash payments, including a $15.0 million option fee and a $5.0 million note, and could also be eligible to receive up to $144.5 million in development, regulatory, and sales milestone payments for each of the four microRNA-therapeutic products discovered and developed as part of the alliance. In addition to the potential of nearly $600 million Regulus Therapeutics could receive in option, license, and milestone payments, Regulus Therapeutics could also receive tiered royalties up to double digits on worldwide sales of products resulting from the alliance.

Continued Leveraging of Intellectual Property for Near-Term Value Creation. Alnylam granted a license to Shanghai GenePharma Co., Ltd under the Kreutzer-Limmer patent family for the research reagent market. This license represents Alnylam’s first business transaction in China, which is regarded as having one of the fastest growing life science markets in the world.
Awarded $3.8 Million LEAPS Grant Funding from Michael J. Fox Foundation for Parkinson’s Disease. Alnylam and collaborators received a new grant totaling $3.8 million for the development of RNAi therapeutics for the treatment of Parkinson’s disease. The four-year grant, which is part of the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson's Institute and Clinical Center of Sunnyvale, California.

Intellectual Property Leadership Highlights

Tuschl II Patent Granted In World’s Top Three Pharmaceutical Markets. Key fundamental patents from Alnylam’s exclusively held Tuschl II patent series were granted by the European Patent Office and the Japanese Patent Office. The European patent (EP 1407044 or “’044 patent”) broadly covers compositions, methods, and uses of small interfering RNAs (siRNAs), the molecules that mediate RNAi. The Japanese patent (JP Application Number 2002/546670) includes 39 claims broadly covering compositions, methods, uses, and systems for siRNAs. The Tuschl II patent series now provides Alnylam exclusivity for RNAi therapeutics in the world’s top three pharmaceutical markets.

United Kingdom Patent Office Granted Patent for Woppmann et al. Series. The United Kingdom Patent Office granted a patent (UK 2417727 or “’727 patent”) for the Woppmann et al. patent series. The newly granted patent includes 32 claims broadly covering compositions and methods, including pharmaceutical compositions, for siRNAs. The claims cover siRNA molecules of any length that contain “overhang” and “blunt end” design features, including siRNAs containing chemical modifications and certain novel motifs.
German Patent Office Granted Patent for Kreutzer-Limmer I Series. The German Patent Office granted a new patent (DE 10066235 or “’235 patent”) in the Kreutzer-Limmer I series broadly covering methods, uses, and medicaments for siRNAs with a length of 15 to 49 nucleotide pairs expressed via vectors.
Regulus Therapeutics Licensed IP from Stanford University. Regulus Therapeutics obtained exclusive license rights from Stanford University to worldwide patent applications covering methods and composition for antagonizing miR-181a to regulate immune responses. Changes in miR-181a levels have been shown to modify the response of immune cells such as T lymphocytes to specific stimuli and its antagonism could lead to a new way to treat inflammatory diseases.

Additional Patents Issued or Granted. Alnylam announced today the issuance or grant of the following patents owned, controlled, or licensed by Alnylam in the RNAi therapeutics field:

-- U.S. Patent No. 7,320,965 titled "Compositions and methods for inhibiting expression of the huntingtin gene" issued on January 22, 2008;

-- U.S. Patent No. 7,348,314 titled "Compositions and methods for inhibiting viral replication" issued on March 25, 2008;

-- U.S. Patent No. 7,361,752 titled "RNAi modulation of MLL-AF4 and uses thereof" issued on April 22, 2008; and,

-- Australian Patent Application No. 2004206255 titled "Lipophilic derivatives of double-stranded ribonucleic acid" has been accepted by the Australian Patent Office.


Organizational Highlights

Expanded Alnylam Board of Directors and Scientific Advisory Board. Edward Scolnick, M.D., was appointed to the Alnylam Board of Directors and Scientific Advisory Board. Dr. Scolnick is the director of the Psychiatry Initiative at the Broad Institute and the former President of Merck Research Laboratories.
Expanded the Regulus Management Team. Regulus Therapeutics announced the appointment of Peter S. Linsley, Ph.D. as Chief Scientific Officer. Dr. Linsley has been instrumental in advancing the scientific understanding and therapeutic potential of microRNAs. Before joining Regulus, Dr. Linsley was an Executive Director of Cancer Biology at Merck Research Laboratories, which he joined upon the acquisition of Rosetta Inpharmatics LLC.
Conference Call Information

Alnylam will host a conference call at 4:30 p.m. ET on May 8, 2008 to discuss the first quarter financial results and recent corporate developments. The call may be accessed by dialing 800-295-4740 (domestic) or 617-614-3925 (international) five minutes prior to the start time and providing the passcode 34498800.

A replay of the call will be available from approximately 6:30 p.m. ET on May 8, 2008 until May 15, 2008. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international) and provide the passcode 32097266. A live audio webcast of the call will also be available on the “Investors” section of the company’s website, www.alnylam.com. An archived webcast will be available on the company’s website approximately two hours after the event and will be archived for 14 days thereafter.

[Fruehrentner]

aus der Branche:

Novosom obtains patents for Smarticles

14th May 2008
By Staff Writer

Germany based Novosom has received patents for both the US and Europe for its drug Delivery technology Smarticles.
Smarticles are fully charge reversible liposomes for the in vivo drug delivery of nucleotides like siRNA or antisense to targeted cells.

Steffen Panzner, founder and chief scientific officer of Novosom, said: "The broad grant of this family of patents in key jurisdictions reflects the originality of our approach in the field of oligonucleotide delivery. Both offices have accepted wide claim language which secures comprehensive protection of the amphoteric liposome concept irrespective of any chemical representation for Novosom and its licensees."

http://www.pharmaceutical-business-review.com/article_news.a…

[Fruehrentner]

21.05.2008 14:00:00

Alnylam and Collaborators Publish In Vivo Research on Validation of a Mammalian Host Gene Involved in Malaria Infection and on the Anti-Parasitic Efficacy of RNAi Therapeutics

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, today announced the publication of a new study in Cell Host & Microbe on the role of a host gene, heme oxygenase-1 (HO-1), in the cause and pathway of malaria parasitic infection. The collaboration was led by scientists at Unidade de Malária in Portugal, and included scientists at Massachusetts Institute of Technology, Roche Kulmbach GmbH (formerly Alnylam Europe AG), and Alnylam. In the new research, in vivo studies demonstrated that HO-1 is a critical host factor involved in the liver stage of malaria infection in a mouse model. Results from the studies showed that RNAi therapeutics that silence HO-1 can significantly inhibit the initial liver stage of malaria infection and completely block the resulting transmission of disease to red blood cells.

“Our new research findings highlight the critical role of certain host-pathogen interactions occurring during malaria infection, in this case the role of HO-1,” said Maria M. Mota, Ph.D., Associate Professor, Instituto de Medicina Molecular. “Our studies also point to the powerful approach of RNAi technology for in vivo validation of key disease-associated genes.”

In the current study, HO-1 was validated as a host gene required for the liver stage of malaria (Plasmodium berghei and Plasmodium yoelii) infection. Liver HO-1 gene expression was significantly increased upon infection of mice with malaria sporozoites, the cells that infect new hosts. Mice lacking the HO-1 gene were found to be resistant to liver infection by malaria. Further, increased expression of HO-1 in transgenic mice was associated with an increased extent of malarial liver infection. RNAi technology using in vivo delivery of siRNAs, the molecules that mediate RNAi, provided validation of the HO-1 genetic data. RNAi treatment resulted in a greater than 60% silencing of HO-1 messenger RNA (mRNA) in the liver of treated mice. Mice treated with a HO-1 specific siRNA showed markedly reduced liver infection and complete attenuation of any detectable red blood cell stage infection, whereas animals treated with a control siRNA developed a normal course of infection. These data point to the potential therapeutic applications of RNAi for the treatment of a major parasitic infection such as malaria and to broader RNAi therapeutic strategies in infectious diseases through the targeting of host factors.

“We are thrilled to publish these new data for this serious global health problem, as RNAi technology and, potentially RNAi therapeutics, could lead to new treatment options,” said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. “The World Health Organization estimates that each year 300 to 500 million cases of malaria occur and that more than 1 million people die of malaria, especially in developing countries. While the specific implications of RNAi therapeutics as a possible treatment for malaria remain to be fully understood, these new data certainly highlight the potential of RNAi in addressing major unmet medical needs.”

[Fruehrentner]

schon älterer Artikel aber DAS kjönnte die Lösung für dad Drug-Delivery Problem für RNAI bzw. SIRNA sein:


Sugar used as 'Trojan Horse' to fight cancer

by Emilie Reymond

15/11/2006- Researchers in Denmark have discovered a new drug delivery method based on sugar nanocapsules that could be a breakthrough to treat cancer, viral diseases and hereditary disorders.

A team of scientists from the Interdisciplinary Nanoscience Center (iNANO) at the University of Aarhus University (http://www.inano.dk)have found that by encapsulating medicine in microscopic sugar cubes, they could induce body cells to absorb pharmaceuticals that could not normally be transported across the cell membrane.
This new technique - which basically involves using sugar nanocapsules as a "Trojan Horse" - could be an alternative to many treatments and in particular chemotherapy, the researchers claim.

While chemotherapy can be administered without difficulty, orally or intravenously, the main drawback is that healthy cells are also affected by the treatment, which leads to a number of side effects, such as hair loss, nausea and a depressed immune system.

However, with the new method, the medicines are encapsulated in microscopic containers - with a diameter of just one hundred thousandth of a millimetre - that can go through the body unnoticed, and finally deliver their load at the point of the illness, which could minimise the side effects and represent major progress in the treatment of cancer, the researchers said.

"Each cell would normally resist the entry of the foreign substance, but this is not the case with the nanocapsules because the cells cannot recognise the pharmaceutical load inside them, but think that a tasty little sugar snack is on its way," said the scientists.

The new drug delivery method has proven effective to treat arthritis in mice during early stage studies, however, arthritis is just one example. Viral infections are also a potential target for the nanocapsules; in such cases though, the treatment is not aimed at the genes in the cells of the body, but at the genome of the disease itself.

The scientists found that by filling the sugar cubes - in this experiment they used a sugar called chitosan - with a DNA copy called small iinterfering RNA (siRNA), the substance can switch off faulty genes selected among thousands of cells and therefore treat the diseases caused by these genes, by means of a mechanism called RNA interference.

"What is so brilliant about this technique called RNA interference is that the body's sick genes are passivated without affecting anything else," said the research team.

"RNA interference is probably the hottest item in biotechnology at present, with loads of high-risk capital to back it up," they added.

Chitosan, the sugar used to encapsulate the siRNA molecules, is therefore very effective in the treatment of arthritis, influenza, hepatitis as well as certain types of cancer, not because the sugar itself cures these diseases, but because it can transport a drug which does. What is more, the researchers found that after delivering the pharmaceutical directly into the cells affected, the chitosan sugar is broken down in the body and disappears without a trace.

"Because chitosan occurs in nature and is completely safe for the body, the capsules can be administered via an oral spray that leads them into the lungs, out into the blood vessels and on to the cells," said the researchers.

The Danish team has tested the new drug delivery method on mice and expects to be able to start the first preclinical trials on humans in three to four years.

The research was published in the peer-reviewed journal Molecular Therapy in October.

http://www.in-pharmatechnologist.com/news/ng.asp?id=72083


Man müsste sich mal schlau machen, wie weit diese dänische Forschungsgruppe mittlereile gekommen ist.

[aktianer]

Heute gleich 2 Meldungen:
1.Zahlung Lizenzgebühren an ISIS und
2.Deal mit Takeda

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Isis to Receive $4.6 Million From Alnylam
Tuesday May 27, 9:50 am ET

CARLSBAD, Calif., May 27 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS - News) announced today that it will receive $4.6 million dollars from Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News) as its portion of the upfront fees in the recently announced transaction between Takeda Pharmaceutical Company Limited and Alnylam. In addition, Isis has the potential to receive portions of future milestone and royalty payments. This transaction further emphasizes the value of Isis' innovation and the leadership role Isis has played in the field of nucleic acid based therapeutics.

ADVERTISEMENT
Isis owns or controls more than 1,500 issued patents, through which it has generated well over $100 million in licensing fees. In 2004, Isis and Alnylam entered into a strategic relationship in which Alnylam obtained an exclusive license to Isis' intellectual property for double-stranded oligonucleotide therapeutics that mediate RNAi. In return, Isis received an upfront payment and financial participation in future transactions supported by Isis' patents.

"Isis' innovation in RNA based drug discovery has created a foundation through our extensive patent position that we have been able to exploit with our unique business strategy. Over the past four years we have enjoyed a productive collaboration with Alnylam. Our technology supports RNA-based drug discovery efforts for both companies, as well as those focused on microRNAs through our joint venture, Regulus Therapeutics. Working together we have made significant advances creating drugs based on the RNAi mechanism. Isis has benefited substantially from Alnylam's business development and financial successes. We look forward to additional successes from this valuable strategic relationship," said Stan Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis Pharmaceuticals, Inc. "Our pioneering efforts in developing nucleic acid based drugs have resulted in a very broad and valuable patent estate. The breadth and depth of our patent estate has allowed us to create a number of strategic relationships such as the one we have with Alnylam that ensure our continued leadership in the field. This transaction further underscores the value of our innovation and strategy."

http://biz.yahoo.com/prnews/080527/latu049.html?.v=101
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Alnylam Pharma, Japan's Takeda sign $1B RNAi deal
Tuesday May 27, 7:38 am ET
Alnylam Pharma signs RNAi drug development deal with Takeda potentially worth $1 billion

CAMBRIDGE, Mass. (AP) -- Biotechnology firm Alnylam Pharmaceuticals Inc. said Tuesday it formed a research partnership with Japan's Takeda Pharmaceutical Co. Ltd. potentially worth more than $1 billion.

The biotech company, which also formed a lucrative $1 billion partnership with Swiss drug maker Roche last year, is developing RNAi, or gene silencing, technology, which uses mechanisms within the body to target and "turn off" certain genes associated with cancer and other diseases.

Takeda will make a $100 million upfront payment, and $50 million in near-term technology transfer payments covering a non-exclusive licenses in two RNAi treatment fields. The companies value the five-year partnership at potentially more than $1 billion in R&D and commercial milestone payments.

Takeda becomes the only Asian company to receive right of first refusal to develop and market Alnylam RNAi therapies for the Asian market, excluding Alnylam's ALN-RSV01 pediatric respiratory syncytial virus program. In addition, Alnylam receives the option to codevelop and co-market Takeda RNAi drug programs in the U.S. market on a 50-50 basis.

The companies said Takeda may opt to expand their partnership to include additional fields, for $50 million each. Alnylam is also eligible to receive research and development funding related to the drug discovery collaboration, and may receive up to $171 million in development and commercial milestone payments and royalties for each product.

Besides its deals with Roche and Takeda, Alnylam also has partnerships with Novartis, Biogen Idec and the National Institutes of Health. The company is among more than a half-dozen biotechnology firms developing RNAi treatments, which involve interfering with messenger-carrying RNA that can trigger disease by delivering genetic information to cells. The technology is designed to ensure a drug reaches its intended target while leaving healthy cells unharmed, unlike blunt approaches such as chemotherapy.

The research stems from a discovery in 1998 by Craig Mello, a researcher at the University of Massachusetts Medical School at Worcester, and Andrew Fire of Stanford University. The pair were honored in 2006 with the Nobel Prize for medicine.

Alnylam's success in forming partnerships with large drugmakers has doubled its share value in the last year. The stock has risen from a 52-week low of $14.87 last July to peak at $37.35 in October following its Roche deal, and closed Friday at $29.45.

Broadpoint Capital analyst Simos Simeonidis said Alnylam's latest deal should silence "non-believers" who didn't think a partner besides Roche would "be willing to dig that deep into its pocket for yet another large upfront fee."

"However, given the non-exclusive nature of the deals, the promise of the RNAi therapeutics field, coupled with large pharma's need for a transformative technology, and the consistency with which Alnylam's management has guided towards a second major deal in 2008, we continued to expect such a deal," Simeonidis wrote in a note to clients.

He backed a "Buy" rating and $38 price target on the stock.

http://biz.yahoo.com/ap/080527/alnylam_pharma_takeda.html?.v…

[Fruehrentner]

Antwort auf Beitrag Nr.: 34.180.697 von aktianer am 27.05.08 16:26:10

Alnylam Pharma, Japan's Takeda sign $1B RNAi deal

Tuesday May 27, 7:38 am ET
Alnylam Pharma signs RNAi drug development deal with Takeda potentially worth $1 billion


hmm, und dann trotzdem heut Kursminus in USA?

[aktianer]

Antwort auf Beitrag Nr.: 34.182.858 von Fruehrentner am 27.05.08 21:09:09

tja, schon seltsamer Kursverlauf. Handelsumsatz war überdurchschnittlich (2,5-fache des Durchschnitts). Fakt ist, daß nur Simeonidis und King jr. positiv gestimmt sind, während
Alan Carr von Needham und Douglas Chow von Caris & Co. der Alnylam-Technik kritisch gegenüberstehen. Nimmt man den Kursverlauf der letzten Monate als Maßstab, dann scheint letzteren größere Kompetenz zugeschrieben zu werden. Also wird ein Kursschub wohl nur erfolgen, wenn eindeutig positive Ergebnisse vorgelegt werden können und wenigstens einer der kritischen Analysten das Lager wechselt. Aber ob die Alnylam-Technik das hergibt? Bin doch ziemlich verunsichert!

Übrigens hat der Kursverfall kurz vor dem Zeitpunkt begonnen, zu dem Santaris Pharma bekanntgab, über ein neues Verfahren (LNA, Locked Nucleid Acid)) zu Abschaltung der Schadgene zu verfügen bzw. bereits erfolgreich an Primaten getestet zu haben; laut Ankündigung vom 26.03.08 sollte bald Phase I angegangen werden. Unternehmen ist zwar noch nicht börsennotiert - aber gut möglich daß Institutionelle bereits umschichten (wäre auch ein trifftiger Grund für die Abgaben).

[aktianer]

Antwort auf Beitrag Nr.: 34.184.572 von aktianer am 28.05.08 09:03:45

einen möglichen Grund für den schwachen Kursvelauf gestern könnte lt. Simeonidis der simple Vergleich des Takeda-Deals mit dem vorjährigen
Roche-Deal sein (woran ich aber nicht glaube, weil ja die Schwäche schon 2 Monate anhält):

Broadpoint Capital analyst Simos Simeonidis thinks the market is getting it wrong. He believes the negative stock reaction comes from a comparison of the deal with Swiss-based Roche last year. Alnylam received $278 million upfront from the Roche deal, but has little say in marketing the drugs later on. Simeonidis believes this is a better deal because Alnylam will have more say with the drugs further down the development line.

http://www.forbes.com/2008/05/27/alnylam-takeda-closer-marke…

[Fruehrentner]

hier nochmal die Alnylam-Takeda-Meldung auf deutsch:

28.05.2008 08:17:00

Alnylam und Takeda bilden eine weltweite strategische Allianz im Bereich der RNAi-Therapeutika

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) und Takeda Pharmaceutical Company Limited (TOKYO: 4502) haben heute bekannt gegeben, dass die beiden Unternehmen eine strategische Allianz in Bezug auf RNAi-Therapeutika insbesondere in den Bereichen der Onkologie und der Stoffwechselkrankheiten gebildet haben. Beide Unternehmen gehen diese Allianz mit der Option ein, ihre Tätigkeiten auch auf andere therapeutische Bereiche zu erstrecken. Diese historische Allianz stellt die erste große Partnerschaft im Bereich der RNAi-Therapeutika zwischen einem japanischen Arzneimittelunternehmen und einem US-amerikanischen Unternehmen für Biotechnologie dar. Gleichzeitig bezeichnet diese Allianz eine neue Vorreiterrolle in Bezug auf die Weiterentwicklung von RNAi-Therapeutika für Patienten auf einer globalen Basis.

Die RNAi stellt einen vollkommen neuen Ansatz zur Entdeckung von bahnbrechenden Medikamenten dar und verwendet einen natürlichen Mechanismus des menschlichen Körpers, um die Arbeit von einzelnen Genen zu hemmen. Indem man sich die Aktivität der RNAi zu Nutze macht, schafft man eine direkte Möglichkeit zur Entwicklung von bestimmten und wirksamen neuen Medikamenten zur Behandlung einer breiten Vielfalt von Krankheiten, einschließlich solcher Krankheiten, die mit den bisherigen Medikamentenansätzen nur schwierig zu behandeln waren. Den Entdeckern des Mechanismus der RNAi wurde im Jahre 2006 der Nobelpreis verliehen, und die Weiterentwicklung der RNAi gilt heute als einer der wichtigsten Vorstöße im Bereich der biomedizinischen Wissenschaften seit Jahrzehnten.

„Wir sind sehr stolz und fühlen uns geehrt, unsere strategische Partnerschaft mit Takeda bekannt geben zu können, einem der weltweit führenden Unternehmen im Bereich der Arzneimittel. Als erste Partnerschaft im Bereich der RNAi-Technologie mit einem Arzneimittelunternehmen mit Sitz in Asien erweitert diese neue Allianz die Weiterentwicklung der RNAi-Therapeutika für Patienten auf einer globalen Basis“, so John Maraganore, Ph.D., CEO von Alnylam. „Über mehrere Dimensionen hinweg stellt diese neue Partnerschaft ein großes Ereignis in Bezug auf die Bemühungen von Alnylam dar, ein weltweit führendes biopharmazeutisches Unternehmen aufzubauen. Ein besonders wichtiges Element dieser neuen Allianz ist die Möglichkeit für Alnylam, Produkte für die RNAi-Therapie zusammen mit Takeda für den US-amerikanischen Markt zu entwickeln und auf diesem zu vertreiben.“

„Wir freuen uns sehr darauf, mit Alnylam zusammenzuarbeiten, dem weltweit führenden Unternehmen im Bereich der RNAi-Therapeutika, das über ein großes Engagement in Bezug auf wissenschaftliche Spitzenleistungen sowie eine beispiellose Position in Bezug auf sein geistiges Eigentum verfügt“, so Yasuchika Hasegawa, Präsident von Takeda. „Wir glauben daran, dass diese Allianz unsere Initiativen in Bezug auf die Schaffung eines Fundaments zur Erforschung von RNAi-Medikamenten mit Hilfe der Technologien und des Know-hows von Alnylam beschleunigen wird. Wir erwarten, dass unser Produktportfolio durch die Hinzufügung der RNAi-Therapeutika zu unseren derzeitigen Forschungsplattformen in Bezug auf Kleinstmoleküle und Antikörper deutlich verbessert wird.“

Durch diese Zusammenarbeit erhält Takeda einen breiten, weltweiten und nicht exklusiven Zugang zu und eine Möglichkeit zur Nutzung der Plattformtechnologie von Alnylam in Bezug auf RNAi-Therapeutika sowie des geistigen Eigentums des Unternehmens im Bereich der Onkologie und der Stoffwechselkrankheiten. Darüber hinaus erhält Takeda das Recht, die Anzahl der therapeutischen Bereiche in der Zukunft noch zu erweitern. Die Vereinbarung erstreckt sich außerdem auf die Übertragung der Plattformtechnologie von Alnylam zu Takeda, eine Zusammenarbeit und gegenseitige Lizenzeinräumung in Bezug auf den Austausch von Technologien zwischen den beiden Unternehmen, sowie die Zusammenarbeit in Bezug auf die Erforschung von Medikamenten für bestimmte RNAi-Therapieziele, die bestimmten Verpflichtungen von Alnylam gegenüber Dritten unterliegen.

Die Vereinbarung zwischen Takeda und Alnylam in Bezug auf die strategische Partnerschaft zwischen beiden Unternehmen gilt zunächst über einen Zeitraum von fünf Jahren. Darüber hinaus wird Takeda durch diese Vereinbarung zum einzigen Unternehmen im asiatischen Raum, das ein Vorverhandlungsrecht in Bezug auf die Entwicklung und Kommerzialisierung von Entwicklungsprogrammen von RNAi-Therapeutika von Alnylam auf dem asiatischen Markt erhält (mit Ausnahme des Programms ALN-RSV01 von Alnylam). Darüber hinaus erhält Alnylam ausdrückliche Optionen in Bezug auf die Co-Entwicklung und die Co-Kommerzialisierung der RNAi-Therapieprogramme von Takeda auf dem US-amerikanischen Markt auf einer 50:50-Basis.

Die Partnerschaft umfasst eine Zahlung von USD 100 Millionen an Vorauszahlungen sowie eine Zahlung von USD 50 Millionen in Bezug auf kurzfristige Technologietransfers für eine nicht exklusive Lizenz in zwei therapeutischen Bereichen; darüber hinaus wird der Wert dieser Partnerschaft bei einer erfolgreichen Kommerzialisierung von verschiedenen Produkten auf eine Summe von möglicherweise über USD 1 Milliarde für zukünftige Meilensteine in Forschung und Entwicklung sowie für Kommerzialisierung einer Reihe von Produkten geschätzt. Auf Wunsch von Takeda kann der Umfang der Partnerschaft mit einer Expansionszahlung von USD 50 Millionen pro Bereich ebenfalls auf zusätzliche Bereiche erweitert werden. Alnylam hat außerdem einen Anspruch auf den Erhalt von finanziellen Mitteln für Forschungs- und Entwicklungszwecke in Bezug auf die Zusammenarbeit zur Medikamentenforschung. Darüber hinaus hat Alnylam einen Anspruch auf den Erhalt einer Summe von bis zu USD 171 Millionen an Zahlungen für Forschungsmeilensteine und kommerzielle Meilensteine sowie erhebliche Lizenzgebühren für jedes Produkt. Alnylam plant die Aktualisierung der finanziellen Steuerung bei der Bekanntgabe der Finanzergebnisse für das zweite Quartal des Jahres 2008.

Informationen in Bezug auf die RNA-Interferenz (RNAi)

Die RNAi (RNA-Interferenz) stellt eine Revolution im Bereich der Biologie dar und ist ein Durchbruch in Bezug auf die Erkenntnis, wie Gene in Zellen aktiviert und gehemmt werden. Darüber hinaus ist die Entdeckung der RNA-Interferenz als ein vollkommen neuer Ansatz für den Bereich der Erforschung und Entwicklung von Medikamenten anzusehen. Die Entdeckung der RNA-Interferenz wurde als ein „herausragender wissenschaftlicher Durchbruch, der so nur einmal in jedem Jahrzehnt geschieht“ angekündigt und stellt eine der meistversprechenden und am schnellsten fortschreitenden Errungenschaften in der Biologie und der Erforschung von Medikamenten der heutigen Zeit dar. Aus diesem Grund wurde den Entdeckern der RNA-Interferenz im Jahre 2006 der Nobelpreis für Physiologie oder Medizin verliehen. Die RNAi ist ein natürlicher Prozess des „Abschaltens“ einzelner Gene, der in allen Organismen von Pflanzen bis zu Säugetieren beobachtet werden kann. Durch die Nutzbarmachung des natürlichen biologischen Prozesses der RNA-Interferenz, der in unseren Zellen abläuft, zeichnet sich die Bildung einer neuen großen Klasse von Arzneimitteln ab, die unter der Bezeichnung RNAi-Therapeutika bekannt sind. RNAi-Therapeutika zielen auf die Ursache von Krankheiten ab, indem sie bestimmte Messenger-RNAs (mRNAs) auf wirksame Art und Weise „abschalten“ bzw. hemmen und somit die Erzeugung von krankheitserregenden Proteinen verhindern. RNAi-Therapeutika verfügen über das Potenzial, Krankheiten wirksam behandeln und Patienten in einer grundlegenden neuen Art und Weise heilen zu können.

[Fruehrentner]

Calando Pharmaceuticals Doses First Patient in siRNA Phase I Clinical Trial

03 Jun 2008

Calando Pharmaceuticals, Inc. Jeremy Heidel, Ph.D., announced today that the first patient has successfully completed the first dosing cycle (four doses over two weeks) of CALAA-01 in the first clinical trial using systemically-delivered siRNA to treat cancer

Pasadena, CA, USA | June 2, 2008 | Calando Pharmaceuticals, Inc. Jeremy Heidel, Ph.D., 626-683-7200 [e-mail]

Calando Pharmaceuticals, a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ:ARWR), announced today that the first patient has successfully completed the first dosing cycle (four doses over two weeks) of CALAA-01 in the first clinical trial using systemically-delivered siRNA to treat cancer. CALAA-01 is a targeted
nanoparticle, comprised of a proprietary, non-chemically-modified siRNA against the M2 subunit of ribonucleotide reductase--a clinically-validated cancer target--formulated with Calando's proprietary RONDEL(TM) (RNAi/Oligonucleotide Nanoparticle Delivery) polymer delivery system. The first patient was enrolled and dosed at South Texas Accelerated Research Therapeutics (START) in San Antonio, Texas.

This open-label, dose-escalation Phase I study in patients with solid tumors which are refractory to standard-of-care therapies is being conducted at the UCLA Jonsson Cancer Center (UCLA) in Los Angeles, California, and at South Texas Accelerated Research Therapeutics (START) in San Antonio, Texas. It is being led by Drs. Antoni Ribas (UCLA) and Anthony Tolcher (START).

"The initiation of this Phase I clinical trial of CALAA-01 is a hallmark for Calando and for the field of RNAi therapeutics," said Calando CSO for siRNA delivery, Jeremy Heidel, Ph.D. "We look forward to the continued treatment of this patient and subsequent patients and the establishment of safety and efficacy profiles for CALAA-01 in humans."


About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally-occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new class of medicines to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Calando Pharmaceuticals Inc.

Calando Pharmaceuticals Inc. (www.calandopharma.com), a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ: ARWR), is a biopharmaceuticals company using proprietary technologies developed at Caltech to create targeted siRNA-based therapeutics. Calando combines its innovative RONDEL(TM) system of polymeric delivery with siRNA to solve the long-standing obstacle of effective delivery and targeting for this revolutionary new field of medicine. Based upon the breakthrough in siRNA delivery enabled by the RONDEL(TM) system, the promise of using siRNA in new systemic therapies may finally be realized.

Calando's RONDEL(TM) technology involves the use of cyclodextrin-containing polymers that form the foundation for its two-part siRNA delivery system. The first component is a linear, cyclodextrin-containing polycation that, when mixed with small interfering RNA (siRNA), binds to the anionic "backbone" of the siRNA. The polymer and siRNA self-assemble into nanoparticles smaller than 100 nm in diameter that fully protect the siRNA from nuclease degradation in serum. The siRNA delivery system has been designed to allow for intravenous injection. When the nanoparticle reaches the target cell, the targeting ligand binds to membrane receptors on the cell surface and the RNA-containing nanoparticle is taken into the cell by endocytosis. There, chemistry built into the polymer functions to unpackage the siRNA from the delivery vehicle.

SOURCE: Calando Pharmaceuticals, Inc.

[Fruehrentner]

02.06.2008 14:00:00

Alnylam Announces Close of Investment and Expanded Agreement Related to the Tekmira-Protiva Business Combination

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced the closing of its investment in and completion of its expanded agreement with Tekmira Pharmaceuticals Corporation as a result of the achievement of Tekmira’s business combination with Protiva Biotherapeutics Inc. which occurred effective May 30, 2008. This agreement expands Alnylam’s access to key technology and intellectual property (IP) for the delivery of RNAi therapeutics with liposomal delivery technologies.

As part of the agreement, Alnylam has made an equity investment of $5.0 million in Tekmira at a price of $2.40 per share. This investment is representative of Alnylam’s continued commitment to pursuing novel delivery strategies for RNAi therapeutics. Alnylam maintains its exclusive license to Tekmira’s rights to the Semple (U.S. Patent No. 6,858,225) and Wheeler (U.S. Patent Nos. 5,976,567 and 6,815,432) patents, which the company believes are required for cationic liposomal delivery. Alnylam also now has obtained expanded rights to IP controlled by Protiva prior to the combination and to new IP generated by the combined entity, the new Tekmira. Alnylam has certain rights to sub-license this Tekmira IP to its strategic partners.

“Our expanded relationship with the new Tekmira significantly solidifies and broadens our access to key technologies and IP related to systemic delivery of RNAi therapeutics,” said Barry Greene, President and Chief Operating Officer of Alnylam. “We have long valued the technology and IP of both Tekmira and Protiva and believe that access to this technology as part of their new merged effort is important as we advance systemic RNAi therapeutics toward the clinic.”

Alnylam has also granted to Tekmira InterfeRx™ licenses to discover, develop, and commercialize RNAi therapeutics towards seven gene targets. In return for these licenses, Alnylam may be eligible to receive milestone fees and royalties. Alnylam also has the option to co-develop and co-commercialize Tekmira’s PLK SNALP program being developed for the treatment of certain cancers. PLK1, the polo-like kinase 1 gene, is one of the seven gene targets for which Tekmira has received an InterfeRx license. It has been shown to be involved in the growth of certain types of solid tumors, and PLK SNALP has been shown in pre-clinical studies to selectively kill cancer cells, while sparing normal healthy cells in the same tissue. Alnylam has the right to exercise its option for this program up until the commencement of Phase II clinical trials.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, and Takeda. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established “RNAi 2010” which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including statements regarding Alnylam’s expectations regarding the success of Tekmira technology and the importance of Tekmira intellectual property, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam’s ability to obtain additional funding to support its business activities; Alnylam’s dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short operating history; as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

Alnylam Pharmaceuticals, Inc.
Investors
Cynthia Clayton, 617-551-8207
or
Yates Public Relations
Media
Kathryn Morris, 845-635-9828

Quelle: BUSINESS WIRE

[Fruehrentner]

First ever patient administered a siRNA cancer treatment

By Nick Taylor

05/06/2008- A patient has completed the first successful dosing cycle with small interfering RNA (siRNA) for the treatment of cancer in a clinical trial.

The patient was administered with four doses of Calando's CALAA-01, a targeted siRNA nanoparticle, over a two week period.

This development is another milestone for siRNA technology, which many people have high hopes for in the treatment of a diverse range of illnesses.

Jeremy Heidel, Calando chief scientific officer for siRNA delivery, said: "The initiation of this Phase I clinical trial of CALAA-01 is a hallmark for Calando and for the field of RNAi therapeutics.

"We look forward to the continued treatment of this patient and subsequent patients and the establishment of safety and efficacy profiles for CALAA-01 in humans."

The siRNA was delivered using Calando's Rondel delivery technology, which the company describes as a "three-part RNAi /Oligonucleotide Nanoparticle Delivery technology".

This entails a polymer binding along the length of the siRNA, with the resulting complex self-assembling into nanoparticles less than 100nm in diameter. This process serves to protect the siRNA from nuclease degradation.

In addition, a molecule in the polymer called cyclodextrin facilitates the attachment of stabilizing agents and targeting ligands to the surface of the siRNA/polymer complex.

These attachments prevent the delivery complexes from aggregating and also enable them to be delivered to specific tissues.

The complexes are delivered intravenously and upon reaching the target cell the targeting ligands bind with receptors on the cell membrane. This allows the RNA-containing nanoparticle to enter the cell whereupon the siRNA is released from the complex.

A week of firsts

In addition to the Calando trial Santaris Pharma has started a Phase I human volunteer trial of the world's first microRNA medicine, Hepatitis C treatment SPC3649.
The treatment targets microRNA-122, a small, liver-expressed RNA which facilitates human Hepatitis C virus replication in liver cells.

Speaking on the launch of the trial Keith McCullagh, president and CEO of Santaris Pharma said: "The mechanism of action of this drug represents a potential breakthrough in medical science.

"The ability to switch off the functions of particular microRNAs may enable clinicians to modulate entire networks of genes associated with disease or ill-health."

Although there is still some way to go in the development of RNA interference technology these two breakthroughs bring it a little closer to reality.

http://www.in-pharmatechnologist.com/news/ng.asp?n=85719-cal…

[Fruehrentner]

19.06.2008 09:00:00

Alnylam und Kyowa Hakko bilden Allianz zur Entwicklung und Vermarktung von ALN-RSV01 in Asien

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY) und Kyowa Hakko Kogyo Co., Ltd. (TSE:4151) meldeten heute die Bildung einer exklusiven Partnerschaft zur Entwicklung und Vermarktung von ALN-RSV01 in Japan und anderen wichtigen Märkten in Asien. ALN-RSV01 ist ein in der klinischen Entwicklung der Phase II befindliches RNAi-Therapeutikum, das von Alnylam zur Behandlung von Infektionen mit dem respiratorischen Synzytial-Virus (RSV) entwickelt wurde.

Gemäß der Vereinbarung leistet Kyowa Hakko Alnylam eine Vorauszahlung von 15 Millionen US-Dollar in bar und bis zu weiteren 78 Millionen US-Dollar beim Erreichen bestimmter Meilensteine in Entwicklung und Verkauf. Nach der Markteinführung erhält Alnylam von Kyowa Hakko Lizenzgebühren in zweistelliger Höhe, basierend auf den Verkäufen von ALN-RSV01 in dieser Region. Die Partnerschaft erstreckt sich auch auf zusätzliche Komponenten für RSV-spezifische RNAi-Therapeutika, die ebenfalls zu dem ALN-RSV-Programm gehören. Alnylam behält alle Entwicklungs- und Vermarktungsrechte weltweit außer für Asien.

,,Wir sind begeistert von dieser neuen Partnerschaft mit Kyowa Hakko, einem japanischen Biotechnologieunternehmen mit einem Schwerpunkt auf der Markteinführung von innovativen neuen Arzneimitteln", so Dr. John Maraganore, Chief Executive Officer bei Alnylam. ,,Diese neue Zusammenarbeit ist ein weiteres Beispiel der Entschlossenheit Alnylams, mit führenden Unternehmen der Biotechnologie- und Pharmabranche zu kollaborieren, um die Entwicklung von RNAi-Therapeutika für Patienten weltweit voranzutreiben. Das ist eine wichtige Partnerschaft im führenden klinischen Programm unseres Unternehmens in einem bedeutenden pharmazeutischen Markt. Zudem ist es bereits die dritte bedeutende Partnerschaft, die wir dieses Jahr eingegangen sind. In unserem bevorstehenden Konferenzgespräch des zweiten Quartals werden wir einen Überblick über unsere aktuellen kurzfristigen Partnerschaftsziele und revidierte Finanzperspektiven zur Verfügung stellen."

,,Wir haben die Fortschritte, die Alnylam mit seinem ALN-RSV01-Programm seit letztem Jahr gemacht hat, genau verfolgt und wir freuen uns sehr über die Partnerschaft mit diesem Programm zum jetzigen Zeitpunkt. Und wir freuen uns auf die Zusammenarbeit mit Alnylam bei der Entwicklung und Markteinführung von ALN-RSV01 in Japan und in anderen wichtigen Märkten in Asien, denn Alnylam ist das Unternehmen, dessen wissenschaftliche Arbeit auf dem Gebiet der RNAi am weitesten fortgeschritten ist", so Dr. Yuzuru Matsuda, Chief Executive Officer bei Kyowa Hakko. ,,Wir benötigen dringend neuartige Arzneimittel, um Patienten mit dem RSV, einer der Hauptursachen für schwere Infektionen bei Kindern und Erwachsenen, wirksam zu behandeln. Wir sind begeistert von der Chance, durch diese Partnerschaft mit Alnylam die Vorteile dieses neuartigen Arzneimittels für Patienten in Asien bereitstellen zu können."

Anfang dieses Jahres gelang Alnylam in der GEMINI-Studie der Phase II der Konzeptnachweis für ALN-RSV01 beim Menschen. In dieser Studie zeigte intranasal verabreichtes ALN-RSV01 eine statistisch signifikante virusbekämpfende Wirksamkeit mit einer 38-prozentigen relativen Verringerung der RSV-Infektionsrate und einer 95-prozentigen Steigerung der Anzahl von infektionsfreien Probanden verglichen mit dem Placebo. Außerdem leitete Alnylam eine klinische Studie der Phase II ein, mit der die Sicherheit und Verträglichkeit von ALN-RSV01 in Sprayform im Vergleich zum Placebo bei erwachsenen Lungentransplantatempfängern, die auf natürliche Weise mit RSV infiziert wurden, überprüft werden soll. Als Sekundärziel soll mit der Studie ferner die virusbekämpfende Wirkung von ALN-RSV01 ermittelt werden. Die Daten aus dieser Studie werden in Kombination mit der früheren Phase-II-GEMINI-Studie und mehreren Phase-I-Studien einen umfassenden Datensatz über Sicherheit und Wirksamkeit ergeben, mit dem Alnylam sein gesamtes ALN-RSV-Entwicklungsprogramm weiter voranzutreiben gedenkt.

Informationen über RNA-Interferenz (RNAi)

Die RNAi (RNA-Interferenz) stellt eine Revolution im Bereich der Biologie dar und ist eine bahnbrechende Erkenntnis, wie Gene in Zellen aktiviert und gehemmt werden. Darüber hinaus ist die Entdeckung der RNA-Interferenz ein vollkommen neuer Ansatz in der Erforschung und Entwicklung von Arzneimitteln. Diese Entdeckung wurde als „herausragender wissenschaftlicher Durchbruch" begrüßt, der ,,vielleicht alle 10 Jahre einmal auftritt“. Sie ist eine der vielversprechendsten und am schnellsten fortschreitenden Errungenschaften in der Biologie und Arzneimittelforschung der heutigen Zeit. Die Entdecker der RNA-Interferenz erhielten 2006 den Nobelpreis für Physiologie oder Medizin. Die RNAi ist ein natürlicher Prozess des „Stilllegens“ einzelner Gene, der in allen Organismen von Pflanzen bis zu Säugetieren auftritt. Mit der Nutzbarmachung des natürlichen biologischen Prozesses der RNA-Interferenz, der in unseren Zellen abläuft, zeichnet sich die Bildung einer neuen bedeutenden Klasse von Arzneimitteln ab, den sogenannten RNAi-Therapeutika. RNAi-Therapeutika zielen auf die Ursache von Erkrankungen ab, indem sie bestimmte Messenger-RNAs (mRNAs) effektiv „abschalten“ und somit die Erzeugung von krankheitserregenden Proteinen verhindern. Mit RNAi-Therapeutika lassen Krankheiten sich potenziell wirksam behandeln, so dass den Patienten in einer ganz neuen Art und Weise geholfen werden kann.

Über Alnylam Pharmaceuticals

Alnylam ist ein biopharmazeutisches Unternehmen, das mit der Entwicklung neuartiger Therapeutika auf der Basis der RNA-Interferenz bzw. RNAi befasst ist. Das Unternehmen wendet seine therapeutischen Kenntnisse im Bereich der RNAi an, um Lösungen für signifikante medizinische Bedürfnisse zu finden, die in vielen Fällen auf Kleinstmoleküle oder Antikörper, die derzeit größten Arzneimittelklassen, nicht wirksam ansprechen. Alnylam ist führend im Bereich der Umsetzung der RNAi in eine neue Klasse von innovativen Arzneimitteln und veröffentlicht seine von Fachkollegen begutachteten Forschungsergebnisse in den weltweit renommiertesten wissenschaftlichen Fachzeitschriften, wie Nature, Nature Medicine und Cell. Das Unternehmen nutzt diese Fähigkeiten dazu, eine umfangreiche Pipeline an RNAi-Therapeutika aufzubauen. Sein am weitesten entwickeltes Programm befindet sich in der Phase II der humanmedizinischen, klinischen Studien zur Therapie von Infektionen mit dem respiratorischen Synzytial-Virus (RSV). Darüber hinaus entwickelt das Unternehmen derzeit RNAi-Therapeutika für die Behandlung einer Vielzahl von Erkrankungen, beispielsweise Hypercholesterinämie, Leberkrebs und Chorea Huntington. Dank seiner führenden Position im Bereich von grundlegenden Patenten, Technologien und Knowhow in Bezug auf die RNA-Interferenz war das Unternehmen in der Lage, bedeutende Allianzen mit führenden Unternehmen zu bilden, darunter Medtronic, Novartis, Biogen Idec, Roche, Takeda und Kyowa Hakko Kogyo. Da Alnylam ständig nach wichtigen wissenschaftlichen, klinischen und geschäftlichen Initiativen Ausschau hält, wurde das Programm ,,RNAi 2010” eingeführt. Dieses Programm schließt die Pläne des Unternehmens ein, den Umfang von Lieferlösungen für RNAi-Therapeutika erheblich auszuweiten, über vier oder mehr Programme in der klinischen Entwicklung zu verfügen und vier oder mehr neue, bedeutende Geschäftspartnerschaften zu bilden. Und all das soll bis Ende 2010 erreicht sein. Alnylam ist Miteigentümer von Regulus Therapeutics LLC, einem Joint Venture mit Schwerpunkt auf der Erforschung, Entwicklung und Vermarktung von microRNA-Therapeutika. Das Unternehmen wurde im Jahre 2002 gegründet und hat seinen Hauptsitz in Cambridge, Massachusetts (USA). Weitere Informationen erhalten Sie auf der Website des Unternehmens unter www.alnylam.com.

Über Kyowa Hakko

Kyowa Hakko (TSE:4151) ist ein biotechnologisch ausgerichtetes Pharmaunternehmen mit Schwerpunkt auf Forschung und Entwicklung, Herstellung und Vermarktung von verschreibungspflichtigen Arzneimitteln. Kyowa Hakko vermarktet Arzneimittel für zahlreiche Erkrankungen, beispielsweise Allergien, Bluthochdruck, Angina pectoris und Krebs. Mit dem Ziel in den Weltmarkt einzudringen, unterhält Kyowa Hakko Entwicklungsstandorte in den USA (Kyowa Pharmaceutical, Inc. und BioWa, Inc.) und in Großbritannien (Kyowa Hakko U.K. Ltd.). In den USA, Großbritannien und China treibt Kyowa Hakko die klinische Entwicklung von neuen Arzneimittelkandidaten voran. Außerdem verfügt das Unternehmen über einen Geschäftsbereich für therapeutisch genutzte Antikörper auf der Basis der unternehmenseigenen Technologie zur Förderung der Aktivität bestimmter Antikörper.

Im Oktober 2007 meldete Kyowa Hakko die Vereinbarung einer strategischen Allianz zwischen der Kyowa-Hakko-Gruppe und der Kirin-Gruppe. Im Rahmen dieser strategischen Partnerschaft sind die beiden Konzerne bestrebt, ein weltweit führendes Unternehmen auf dem Gebiet der biowissenschaftlichen Forschung und Entwicklung in Japan aufzubauen. Der Schwerpunkt soll dabei auf einer biotechnologischen Ausrichtung in der Pharmabranche liegen. Das neue Unternehmen wird seinen Betrieb am 1. Oktober 2008 unter dem Namen ,,Kyowa Hakko Kirin Co., Ltd.” aufnehmen.

Weitere Informationen zu Kyowa Hakko finden Sie unter http://www.kyowa.co.jp/eng/index.htm.

Alnylam zum Thema zukunftsgerichtete Aussagen

Bei diversen Aussagen in dieser Pressemitteilung zu den künftigen Erwartungen, Plänen und Aussichten von Alnylam handelt es sich um zukunftsgerichtete Aussagen im Sinne der Safe-Harbor-Bestimmungen des US-amerikanischen Private Securities Litigation Reform Act von 1995. Die tatsächlichen Ergebnisse können infolge von diversen wichtigen Faktoren erheblich von den in den zukunftsgerichteten Aussagen zum Ausdruck gebrachten Erwartungen abweichen. Zu derartigen Faktoren gehören beispielsweise Risiken im Zusammenhang mit dem Ansatz von Alnylam bei der Erforschung und Entwicklung neuartiger Medikamente, der unerprobt ist und eventuell nicht zu marktfähigen Produkten führt; mit Erhalt, Wahrung und Schutz von geistigem Eigentum; mit der Fähigkeit von Alnylam, seine Patente bei Verletzungen durchzusetzen und sein Patentportfolio gegen Anfechtungen zu verteidigen; mit der Fähigkeit von Alnylam, zusätzliche finanzielle Mittel zur Unterstützung der Geschäftstätigkeiten des Unternehmens zu erlangen; mit der Fähigkeit von Alnylam, künftige Meilensteine und Lizenzgebühren zu realisieren; mit der Abhängigkeit von Alnylam von Dritten bei der Entwicklung, Herstellung, Vermarktung, dem Vertrieb und der Verbreitung von Produkten; mit dem Erhalt von behördlichen Genehmigungen für Produkte; mit dem Wettbewerb seitens anderer Unternehmen, die ähnliche Technologien wie die von Alnylam verwenden, sowie seitens Unternehmen, die Produkte für ähnliche Verwendungszwecke entwickeln; mit der Abhängigkeit von Alnylam von Geschäftspartnern; sowie mit der relativ kurzen Geschäftshistorie von Alnylam. Hinzu kommen die Risiken, die im Abschnitt ,,Risk Factors" (Risikofaktoren) des zuletzt bei der US-amerikanischen Börsenaufsichtsbehörde (SEC) auf Formblatt 10-Q eingereichten Quartalsberichts näher erläutert werden. Außerdem geben zukunftsgerichtete Aussagen lediglich die Ansichten von Alnylam zum heutigen Zeitpunkt wieder und sollten nicht als Darstellung der Ansichten des Unternehmens zu einem späteren Zeitpunkt betrachtet werden. Alnylam übernimmt keinerlei Verpflichtung, zukunftsgerichtete Aussagen zu aktualisieren.

Die Ausgangssprache, in der der Originaltext veröffentlicht wird, ist die offizielle und autorisierte Version. Übersetzungen werden zur besseren Verständigung mitgeliefert. Nur die Sprachversion, die im Original veröffentlicht wurde, ist rechtsgültig. Gleichen Sie deshalb Übersetzungen mit der originalen Sprachversion der Veröffentlichung ab.


Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207 (Investoren)
oder
Yates Public Relations
Adriana Jenkins, 617-551-8252 (Medien)
oder
Kyowa Hakko Kogyo Co., Ltd.
Tetsuro Kuga, [phone]
Corporate Communications Dept.
Fax: [phone]


Quelle: BUSINESS WIRE

[Fruehrentner]

News vom Wettbewerber:

FDA approves Quark IND for DGFi, an siRNA therapeutic based on Silence Therapeutics’ Unique Proprietary Chemistry
25 Jun 2008

Silence Therapeutics announces FDA grants IND to Quark for AtuRNAi based siRNA product.Quark Pharmaceuticals to develop drug candidate for prevention and treatment of delayed graft function in kidney transplantation

London, UK | June 25, 2008 | Silence Therapeutics plc (London AIM: SLN) today announces that the U.S. Food and Drug Administration (FDA) has approved a Quark Pharmaceuticals Inc (“Quark”) Investigational New Drug application (IND) for an siRNA therapeutic product based on Silence’s unique proprietary chemistry. The product, DGFi, was discovered and is being developed by Quark for use in kidney transplantation. Rights to the AtuRNAi structure of DGFi were licensed to Quark by Silence Therapeutics.

DGFi is being investigated for the prevention and treatment of Delayed Graft Function (“DGF”) associated with renal transplantation. DGF is a syndrome caused by ischemia and reperfusion injury, which frequently occurs in kidneys once they are removed from a donor and transplanted into the patient. In patients with DGF, the transplanted kidney does not function properly and requires intervention by dialysis. DGFi is designed to temporarily inhibit the activity of the p53 gene, which is associated with apoptosis, also known as programmed cell death, and is believed to be critical in the ischemia and reperfusion injury process. DGFi uses the same active AtuRNAi molecule as AKIi-5, which Quark is developing for treatment of Acute Kidney Injury.

Jeff Vick, Chief Executive Officer of Silence Therapeutics, said “We are very excited by this news, as it is the third IND approved for a product based upon our proprietary AtuRNAi chemistry and confirms our leading position in this revolutionary field of technology.”

SOURCE: Silence Therapeutics plc

[aktianer]

Antwort auf Beitrag Nr.: 34.380.036 von Fruehrentner am 26.06.08 13:43:22

Meldung zur Joint-Venture mit ISIS, der Regulus:

Regulus Therapeutics Selected for Fierce 15 Top Biotech Companies
Tuesday June 24, 11:00 am ET

CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS - News) formed to discover, develop, and commercialize microRNA (miRNA) therapeutics, announced today that it has been named to the annual FierceBiotech “Fierce 15” list, designating it as one of the top privately held biotech companies of 2008.

ADVERTISEMENT
“Spawned by two powerhouses in the RNA-targeted therapeutics field – Isis and Alnylam Pharmaceuticals – Regulus got started at an advanced stage in the microRNA field,” said John Carroll, Editor of FierceBiotech. “The company was quick to capitalize on its hefty IP with an up to $600 million pact with GlaxoSmithKline. Anyone tracking microRNA drug development should pay close attention.”

“Regulus is honored to be recognized by FierceBiotech as a ‘Fierce 15’ chosen from among so many innovative companies in our industry,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus. “With our broad and dominant intellectual property position, expertise in microRNAs, world-class Scientific Advisory Board and the support of Isis and Alnylam, we are positioned to quickly translate the therapeutic potential of microRNAs into new treatment options for many diseases, including oncology, viral infections and inflammatory diseases.”

About “Fierce 15”

The editors of FierceBiotech evaluate hundreds of privately held firms based on company vision, revenue potential, quality of deals, strength of technology, partnerships, and competitive market position each year. The Fierce 15 celebrates the spirit of being “fierce” – championing innovation and creativity, even in the face of intense competition. Regulus Therapeutics was determined to be one of the “fiercest,” proven by the Company’s creativity and innovations in the industry.

About miRNAs

miRNAs are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. miRNA therapeutics represent a new approach for the treatment of a wide range of human diseases. The inappropriate absence or presence of specific miRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, metabolic disorders and inflammatory disease. Targeting miRNAs with novel therapeutic agents could result in novel and broadly acting treatments for human diseases.

About Regulus

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop, and commercialize miRNA therapeutics. Regulus aspires to translate one of the most important new discoveries in biology into a novel new approach for innovative medicine and to build the leading miRNA company. Created as a joint venture by Alnylam Pharmaceuticals and Isis Pharmaceuticals, Regulus benefits from oligonucleotide drug discovery expertise, an established technology, and a broad intellectual property estate created and consolidated by its parent companies for the development and commercialization of miRNA therapeutics. Regulus’ patent estate includes over 600 patents and more than 300 pending patent applications, pertaining primarily to chemical modifications of oligonucleotides targeting miRNA for therapeutic applications. In addition, Regulus has collaborations with academic researchers to build on the company’s understanding of more than 60 miRNAs. In April 2008, Regulus formed a major alliance with GlaxoSmithKline to explore miRNA therapeutics for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Regulus, founded in September 2007, maintains facilities in Carlsbad, California.

http://biz.yahoo.com/bw/080624/20080624005589.html?.v=1

[Fruehrentner]

Breaking News on Pharmaceutical Technology

Researchers improve siRNA delivery

By Nick Taylor

03/07/2008- The delivery of siRNA into cells has taken a step forward according to research published in the Journal of the American Chemical Society.

Researchers from the University of Washington and Emory University believe that by utilising nanotechnology known as quantum dots they have made the delivery 10 to 20 times more effective than existing methods.

This technique could pave the way for more effective, targeted delivery of siRNA or small interfering RNA - used to selectively switch off target genes via a process known as gene silencing - into cells.

Shuming Nie, co-author of the research, said: "This work helps to overcome the longstanding barrier in the siRNA field: How to achieve high silencing efficiency with low toxicity."

siRNA does not easily cross cell membranes but the researchers overcame this by using quantum dots as a chaperone. Quantum dots are 6nm wide fluorescent balls of semiconductor material, which emit different colours of light depending on their size. They are already a well-established technology in drug discovery, where they are used as reagents in assays and screening.

Each quantum dot is surrounded by a positively charged proton sponge, which enables the negatively charged siRNA to traverse the cell membrane.

Once inside the cell the siRNA is released from the endosome and acts to achieve the desired therapeutic effect through disruption of protein production.

This technique resulted in production of a test protein falling to just 2 per cent, in comparison with 13 to 51 per cent when the experiment was run using one of three commercial reagents commonly used in laboratories.

Another advantage is that this delivery method is five to 10 times less toxic to the cell than currently available techniques.

The researchers are now planning on trying to achieve the same results without the use of quantum dots, which have not been approved for use in humans. Nontoxic iron oxide or biodegradable polymeric carriers are two potential alternatives as the research team seeks to advance the work.

This could eventually lead to the technologies use in the treatment of a wide range of ailments, from cancer to deteriorating eyesight.

Research into the use of siRNA is continuing apace, with the first clinical trial for the treatment of cancer using the technology commencing recently.

Improvements to the targeting and efficiency of siRNA delivery could play an important role in ensuring the widespread adoption of the technology.

http://www.in-pharmatechnologist.com/news/ng.asp?n=86298-jou…

[Fruehrentner]

Alnylam Announces Extension of RNAi Therapeutics Collaboration with Novartis

16 Jul 2008

Alnylam Pharmaceuticals announced today that Novartis has elected to extend the company's RNAi therapeutics collaboration for an additional year, through October 2009

CAMBRIDGE, MA, USA | Juyl 16, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that Novartis has elected to extend the company's RNAi therapeutics collaboration for an additional year, through October 2009. The landmark alliance was initiated in October 2005 and is focused on the discovery, development, and commercialization of RNAi therapeutics toward a defined number of Novartis-selected disease gene targets.

"Our efforts with Novartis have been very productive over the past three years, and we are delighted that Novartis has elected to extend our alliance for another year," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "Novartis was a pioneer in recognizing the potential of RNAi therapeutics as a new class of medicines, and we look forward to continuing our work with them as we advance this innovation to patients."

In the Novartis-Alnylam collaboration, both companies are jointly responsible for RNAi discovery activities and Novartis is generally responsible for development and commercialization of RNAi therapeutic products. With the extension of the alliance term, Novartis will continue to fund collaboration research and development efforts conducted by Alnylam. Further, Novartis retains its right to exercise a non-exclusive platform license from Alnylam in exchange for an undisclosed payment and future milestones and royalties. In addition, Novartis has the option to extend the collaboration for one additional one-year term through 2010. Finally, Novartis retains certain rights to purchase Alnylam equity up to 19.9%; current Novartis ownership is approximately 13.4%.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, and Kyowa Hakko Kogyo. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals, Inc.

http://www.pipelinereview.com/content/view/20981/104/

[Fruehrentner]

12.07.2008 01:10:00

Silence Therapeutics gibt erfolgreichen Einspruch gegen Glover-Patent bekannt

LONDON, July 12 /PRNewswire/ --

Silence Therapeutics plc (London AIM: SLN), ein führendes, europäisches, auf RNA-Interferenz (RNAi) ausgerichtetes Biotechnologie-Unternehmen, gab heute den erfolgreichen Einspruch gegen ein grundlegendes, europäisches Patent von Alnylam Pharmaceuticals, Inc. bekannt, der dazu führte, dass das Patent insgesamt widerrufen wurde.

Die Einspruchsabteilung des Europäischen Patentamts gab nach einer dreitägigen Anhörung seine Entscheidung bekannt, das europäische Patent EP 1 230 375, das exklusiv an Alnylam Pharmaceuticals von Cancer Research Technology, Ltd. (Grossbritannien) erteilt worden war, zu widerrufen. Das Patent, das allgemein unter der Bezeichnung "Glover"-Patent bekannt ist, bezieht sich generell auf Medikamente, die RNA-Interferenz vermittelnde RNA-Moleküle enthalten.

Die Schriftsätze zum Einspruch gegen das Glover-Patent wurden von Silence Therapeutics AG, Sanofi-Aventis Deutschland GmbH, Quark Biotech, Inc., Sirna Therapeutics und Nucleonics, Inc. eingereicht. Im Verlauf der mündlichen Anhörung, die vom 8. bis zum 10. Juli 2008 stattfand, reichte Cancer Research Technology Ltd. insgesamt sieben Hilfsanträge ein, um das Patent zumindest in Teilen zu verteidigen. Doch konnte keiner dieser Anträge die Bedenken der Einspruchsabteilung ausräumen, die das Patent für rechtlich ungültig hielt. Cancer Research Technology und Alnylam werden voraussichtlich Berufung gegen die Entscheidung einlegen.

Jeff Vick, Chief Executive Officer von Silence Therapeutics, sagte: "Das Glover-Patent war wohl Alnylams umfassendstes Patent und der erfolgreiche Einspruch stellt für uns einen wichtigen Sieg dar, der es uns ermöglicht, unsere Handlungsfreiheit aufrechtzuerhalten. Wir sind seit Langem davon überzeugt, dass dieses Patent widerrufen werden müsste und sind über das Ergebnis sehr erfreut. Die Entscheidung des Europäischen Patentamtes baut unsere führende Position im Bereich der RNA-Interferenz noch weiter aus."

Redaktionelle Hinweise

Informationen zu Silence Therapeutics plc (http://www.silence-therapeutics.com)

Silence Therapeutics plc (AIM: SLN) ist ein führendes, europäisches, auf RNAi ausgerichtetes Biotechnologie-Unternehmen. Mithilfe von RNAi können Gene, die mit dem Ausbruch von Krankheiten in Verbindung stehen, selektiv "abgeschaltet" werden. RNAi wurde als Verfahren mit dem Nobelpreis ausgezeichnet und ist derzeit eines der am meisten versprechenden Bereiche für die Entdeckung und Entwicklung neuer Medikamente.

Silence Therapeutics hat AtuRNAi, eine Plattform neuartiger, kurz interferierender RNA-Moleküle ("siRNA" - short interfering RNA) entwickelt, die gegenüber herkömmlichen siRNA-Molekülen eine Reihe von Vorteilen aufweisen, u.a. eine höhere Stabilität gegen den Nuklease-Abbau. Darüber hinaus hat das Unternehmen AtuPLEX, ein firmeneigenes systemisches Verabreichungssystem entwickelt. Dies ermöglicht die funktionale Zuführung von siRNA-Molekülen direkt in krankes Zielgewebe bzw. in Zielzellen und erhöht auf diese Weise die Bioverfügbarkeit und die intrazelluläre Aufnahme.

Bei Atu027, dem führenden internen Produkt von Silence, handelt es sich um ein firmeneigenes AtuRNAi-Molekül, das sich in der vorklinischen Entwicklung für systemische Krebsindikationen befindet. Toxologiestudien mit Atu027 bei Einzel- und Wiederholungsdosierungen sowie eine 28-tägige toxologische Untersuchung mit verschiedenen Dosierungen wurden erfolgreich abgeschlossen. Silence beabsichtigt, den Zulassungsantrag für den Beginn der klinischen Untersuchungen mit Atu027 noch im Jahre 2008 einzureichen.

Im März 2008 gab Silence Therapeutics eine Kooperation mit AstraZeneca (LSE: AZN) bekannt, die sich auf die Entwicklung einer Reihe neuartiger Verabreichungsansätze für siRNA-Moleküle konzentriert. Die Vertragsbedingungen sehen dabei vor, dass sowohl Silence Therapeutics als auch AstraZeneca die von beiden Partnern gemeinsam entwickelten, tatsächlich neuartigen Verabreichungssysteme vermarkten dürfen.

Im Juli 2007 ging Silence Therapeutics seine erste Forschungs- und Entwicklungskooperation mit AstraZeneca ein, um neuartige AtuRNAi-Therapeutika gegen fünf spezifische Ziele, darunter solche bei Atemwegsindikationen, zu entwickeln. Diese Zusammenarbeit stellte die erste Anerkennung der potenziellen Anwendungsmöglichkeit des firmeneigenen AtuRNAi-Moleküls von Silence Therapeutics durch die Branche dar und festigte die führende Position des Unternehmens im Bereich der RNAi-Therapeutika.

Eine Unterlizenz für das AtuRNAi-Verfahren des Unternehmens wurde für die Verbindung RTP-801i-14 zur Behandlung der altersbedingten Makuladegeneration und mehrerer anderer Indikationen über die Quark-Lizenz auch an Pfizer vergeben. Die Verbindung kam Anfang 2007 in die klinische Phase. Silence Therapeutics hat darüber hinaus an Quark auch eine Lizenz für die AtuRNAi-Struktur der firmeneigenen Verbindung AKIi-5 erteilt, die sich in Phase I einer klinischen Studie am Menschen zur Behandlung akuter Nierenschäden befindet. Im Mai 2008 gab die US-amerikanische FDA (Food and Drug Administration) dem IND-Antrag (Investigational New Drug Application) von Quark für ein anderes, auf Silences einzigartiger, firmeneigener Chemie basierendes siRNA-Produkt statt. Dieser Wirkstoff namens DGFi, bei dem dasselbe AtuRNAi-Molekül wie bei AKIi-5 zum Einsatz kommt, wurde von Quark entdeckt und wird zur Vorbeugung bzw. Behandlung einer verzögerten Funktionsübernahme nach Nierentransplantationen entwickelt.

Silence Therapeutics ist in London (Grossbritannien) und Berlin (Deutschland) ansässig und wird am AIM notiert.

Informationen zu RNAi

RNA-Interferenz (RNAi) ist ein mit dem Nobelpreis ausgezeichnetes Verfahren und derzeit eines der interessantesten Gebiete der Wirkstoffentdeckung. Das Verfahren stellt einen völlig neuen Ansatz zur selektiven "Abschaltung" bzw. Deaktivierung krankheitsrelevanter Gene dar und hat daher das Potenzial, zur Entwicklung einer ganz neuen Klasse therapeutischer Produkte zu führen. RNAi könnte auf diese Weise einen therapeutischen Ansatz zur Behandlung einer ganzen Reihe, bisher als unheilbar geltender Krankheiten (Krebs, Infektionskrankheiten, Erbkrankheiten) bieten, für die derzeit keine Therapeutika zur Verfügung stehen. Die Marktaussichten sind daher entsprechend gross.

Zukunftsweisende Aussagen

Die vorliegende Pressemitteilung enthält zukunftsweisende Aussagen, die Risiken, Unwägbarkeiten und anderen Umständen unterliegen. Diese Risiken und Unwägbarkeiten können dazu führen, dass die tatsächlich eintretenden Ergebnisse wesentlich von den in den zukunftsweisenden Aussagen vorweggenommenen abweichen. Alle zukunftsweisenden Aussagen beruhen auf den Silence Therapeutics derzeit zur Verfügung stehenden Informationen und Silence Therapeutics übernimmt keinerlei Verpflichtung, derartige zukunftsweisende Aussagen zu aktualisieren.

Website: http://www.silence-therapeutics.com

Quelle: PR NEWSWIRE

[aktianer]

Antwort auf Beitrag Nr.: 34.528.600 von Fruehrentner am 17.07.08 13:24:31

8:11AM Alnylam Pharmaceuticals: Novartis extends alliance agreement;
a postive indicator - Cantor (ALNY) 28.85 : Cantor notes that Yesterday, ALNY announced that Novartis extended their RNAi collaboration through 2009 - significant in that a decision was not required until October of this year - a positive indicator of commitment, in their view. They believe the current pharma environment - stepped-up demand for innovation, in particular, access to intra-cellular targets and condensed development timelines - favors ALNY's licensing and collaboration focus and will continue to drive demand for ALNY's RNAi technology, plus Regulus' miRNA technology. They expect ALNY to consummate a major alliance in 2008.

http://finance.yahoo.com/marketupdate/inplay#alny

[Fruehrentner]

news vom Wettbewerber SILENCE THERAPEUTICS, was eine starke Kursgegenreaktion bei Silence ausgelöst hat:

18.07.2008 00:56:00

Organisatorische Veränderungen bei Silence Therapeutics

LONDON, July 17 /PRNewswire/ --

Silence Therapeutics plc (London AIM: SLN), ein führendes, europäisches, auf RNA-Interferenz (RNAi) ausgerichtetes Biotechnologie-Unternehmen, gab heute bekannt, dass Jeffery Vick aus persönlichen Gründen als Group CEO zurückgetreten ist und das Unternehmen verlassen hat.

Der Vorstand hat Iain Ross, dem derzeitigen nebenamtlichen Chairman, mit sofortiger Wirkung zum hauptamtlichen Chairman und Group CEO ernannt. Jeremy Curnock Cook, ein nebenamtlicher Direktor des Unternehmens, wurde zum leitenden unabhängigen nebenamtlichen Direktor ernannt.

Jeremy Curnock Cook sagte im Auftrag des Vorstands von Silence Therapeutics plc:

"Iain Ross war für die Trendwende des Finanz- und operativen Geschäfts des Unternehmens zwischen Juli 2004 und Juli 2007 verantwortlich, und der Vorstand von Silence ist zuversichtlich, dass der Wert des Unternehmens für Aktionäre unter seiner Leitung beträchtlich erhöht werden kann. Iain ist ein erfahrener Verhandlungsführer, und wir sind davon überzeugt, dass er eine Reihe von Transaktionen und Partnerschaften, die derzeitig im Gespräch sind, erfolgreich zum Abschluss bringen kann."

Iain Ross, Chairman & CEO, fügte hinzu:

"Ich bin der Überzeugung, dass wir unter Einsatz eines konzentrierteren und aggressiveren Ansatzes sowie mit der anhaltenden Unterstützung eines Leitungsteams der Weltspitze in der Lage sein werden, in den kommenden 12 Monaten bedeutende technische und kommerzielle Meilensteine zu erreichen.

Wir verfügen über eine einzigartige proprietäre Position auf RNAi-Markt, und ich bin zuversichtlich, dass wir diese Stellung in den kommenden Monaten weiter stärken werden und darauf aufbauend ein wachsendes Interesse sowohl von Investoren als auch von pharmazeutischen Partnern an unserem Unternehmen verzeichnen werden.

Produkte, die auf der AtuRNAi-Technologie des Unternehmens basieren, befinden sich derzeit im Rahmen laufender Lizenzvereinbarungen im klinischen Stadium. Wir planen noch vor Ende des Jahres 2008 die Einreichung eines Zulassungsantrags bei den Aufsichtsbehörden, um mit den klinischen Prüfungen für unser führendes internes Entwicklungspräparat Atu027 zu beginnen. Nach dem Interesse an diesem Entwicklungsprogramm, dass von einer Reihe von Fremdunternehmen bekundet wurde, beabsichtige ich die Aufnahme von Diskussionen mit Partnerunternehmen."

Redaktionelle Hinweise:

Informationen zu Silence Therapeutics plc (http://www.silence-therapeutics.com)

Silence Therapeutics plc (London AIM: SLN) ist ein führendes, europäisches, auf RNAi ausgerichtetes Biotechnologie-Unternehmen. Mithilfe von RNAi können Gene, die mit dem Ausbruch von Krankheiten in Verbindung stehen, selektiv "abgeschaltet" werden. RNAi wurde als Verfahren mit dem Nobelpreis ausgezeichnet und ist derzeit einer der vielversprechendsten Bereiche für die Entdeckung und Entwicklung neuer Medikamente.

Silence Therapeutics hat AtuRNAi, eine Plattform neuartiger, kurz interferierender RNA-Moleküle ("siRNA" - Short Interfering RNA) entwickelt, die gegenüber herkömmlichen siRNA-Molekülen eine Reihe von Vorteilen aufweisen, u.a. eine höhere Stabilität gegen den Nuklease-Abbau. Darüber hinaus hat das Unternehmen AtuPLEX, ein firmeneigenes systemisches Verabreichungssystem, entwickelt. Dieses System ermöglicht die funktionale Zuführung von siRNA-Molekülen direkt in kranke Zielgewebe bzw. -zellen und erhöht auf diese Weise die Bioverfügbarkeit und die intrazelluläre Aufnahme.

Bei Atu027, dem führenden internen Produkt von Silence, handelt es sich um ein firmeneigenes AtuRNAi-Molekül, das sich in der vorklinischen Entwicklung für systemische Krebsindikationen befindet. Toxikologiestudien mit Atu027 bei Einzel- und Wiederholungsdosierungen sowie eine 28-tägige toxikologische Untersuchung mit verschiedenen Dosierungen wurden erfolgreich abgeschlossen. Silence beabsichtigt, den Zulassungsantrag für den Beginn der klinischen Untersuchungen mit Atu027 noch im Jahre 2008 einzureichen.

Im März 2008 gab Silence Therapeutics eine Kooperation mit AstraZeneca (LSE: AZN) bekannt, die sich auf die Entwicklung einer Reihe neuartiger Verabreichungsansätze für siRNA-Moleküle konzentriert. Die Vertragsbedingungen sehen dabei vor, dass sowohl Silence Therapeutics als auch AstraZeneca die von beiden Partnern gemeinsam entwickelten, tatsächlich neuartigen Verabreichungssysteme vermarkten dürfen.

Im Juli 2007 ging Silence Therapeutics seine erste Forschungs- und Entwicklungskooperation mit AstraZeneca ein, um neuartige AtuRNAi-Therapeutika gegen fünf spezifische Ziele, darunter solche bei Atemwegsindikationen, zu entwickeln. Diese Zusammenarbeit stellte die erste Anerkennung der potenziellen Anwendungsmöglichkeit des firmeneigenen AtuRNAi-Moleküls von Silence Therapeutics durch die Branche dar und festigte die führende Position des Unternehmens im Bereich der RNAi-Therapeutika.

Eine Unterlizenz für das AtuRNAi-Verfahren des Unternehmens wurde für die Verbindung RTP-801i-14 zur Behandlung der altersbedingten Makuladegeneration und mehrerer anderer Indikationen über die Quark-Lizenz auch an Pfizer vergeben. Die Verbindung kam Anfang 2007 in die klinische Phase. Silence Therapeutics hat darüber hinaus an Quark auch eine Lizenz für die AtuRNAi-Struktur der firmeneigenen Verbindung AKIi-5 erteilt, die sich in Phase I einer klinischen Studie am Menschen zur Behandlung akuter Nierenschäden befindet.

Silence Therapeutics ist in London (Grossbritannien) und Berlin (Deutschland) ansässig und ist am AIM notiert.

Informationen zu RNAi

RNA-Interferenz (RNAi) ist ein mit dem Nobelpreis ausgezeichnetes Verfahren und derzeit eines der interessantesten Gebiete der Wirkstoffentdeckung. Das Verfahren stellt einen völlig neuen Ansatz zur selektiven "Abschaltung" bzw. Deaktivierung krankheitsrelevanter Gene dar und hat daher das Potenzial, zur Entwicklung einer ganz neuen Klasse therapeutischer Produkte zu führen. RNAi könnte auf diese Weise einen therapeutischen Ansatz zur Behandlung einer ganzen Reihe, bisher als unheilbar geltender Krankheiten (Krebs, Infektionskrankheiten, Erbkrankheiten) bieten, für die derzeit keine Therapeutika zur Verfügung stehen. Die Marktaussichten sind daher entsprechend gross.

Zukunftsweisende Aussagen

Die vorliegende Pressemitteilung enthält zukunftsweisende Aussagen, die Risiken, Unwägbarkeiten und anderen Umständen unterliegen. Diese Risiken und Unwägbarkeiten können dazu führen, dass die tatsächlich eintretenden Ergebnisse wesentlich von den in den zukunftsweisenden Aussagen vorweggenommenen abweichen. Alle zukunftsweisenden Aussagen beruhen auf den Silence Therapeutics derzeit zur Verfügung stehenden Informationen und Silence Therapeutics übernimmt keinerlei Verpflichtung, derartige zukunftsweisende Aussagen zu aktualisieren.

Website: http://www.silence-therapeutics.com

Quelle: PR NEWSWIRE

[-Salem-]

Antwort auf Beitrag Nr.: 34.528.600 von Fruehrentner am 17.07.08 13:24:31

Alnylam, Santaris S.A. und Isis sind für mich die Leitochsen der Antisense. Alle dieser Unternehmen verfügen über WS-Kandidaten, die gewaltiges Potential haben. Und das sehen die "Großen" Konzerne ähnlich. Während ALNY sich mit Novartis´ 700Mios abfinden muß, sind es bei Santaris schon 900 Mio von GlaxoSmithHolzbein. Die Antisense erleben so langsam das Interesse der Konzerne, welches ihnen ohne Zweifel zusteht. Auch Roche mit den Übernahmen hält den Fuß in der Türe.

Auf das es gelinge!

[Aliberto]

Freitag, 8. August 2008
In Versuchen mit Mäusen
HIV-Ausbreitung gestoppt

­Einen neuen Ansatz zur Bekämpfung der Immunschwächekrankheit Aids haben Forscher in Mäusen erfolgreich getestet. Sie schleusten winzige Erbgutmoleküle in die infizierten Zellen, die dort bestimmte Gene lahmlegten. Auf diese Weise bremsten sie die Vermehrung und Ausbreitung der Viren. Das Verfahren der "RNA- Interferenz" (RNAi) ist noch relativ jung und wird derzeit für die Behandlung zahlreicher Krankheiten erprobt. Die Forscher stellen ihre Arbeit im Fachmagazin "Cell" vor.

Mit Hilfe der RNAi lassen sich schnell einzelne Gene zielgenau abschalten, zum Beispiel solche, die mit der Entstehung von Krankheiten oder eben der Vermehrung von Viren in Verbindung stehen. Dazu bringen die Wissenschaftler winzige Abschnitte des Erbgutmoleküls RNA (siRNA) in die Zellen, die in ihrem Aufbau genau zu den Genen passen, deren Funktion unterdrückt werden soll. Experten sprechen davon, die Gene "stummzuschalten".

Moleküle an Antikörper angehaftet

Eines der Hauptprobleme bei der Anwendung besteht darin, die siRNA-Moleküle in die Zellen hineinzubringen. Den Forschern um Premlata Shankar von der Harvard Medical School in Boston (US-Staat Massachusetts) gelang das nun, indem sie die Moleküle an einen Antikörper koppelten. Dieser Antikörper bindet sich an die T-Zellen des Körpers das sind genau die Zellen, die bevorzugt von dem Aidsvirus befallen werden. Sie testeten ihr Transportsystem an "vermenschlichten" Mäusen. Durch die Gefäße dieser Tiere floss Blut mit menschlichen Blutzellen. Die Wissenschaftler injizierten nun den Antikörper mit dem daran hängenden siRNA-Molekül direkt in die Blutbahn der Tiere

Der Antikörper lagerte sich an die Zellmembran der menschlichen Blutzellen an, die ihn daraufhin samt des angekoppelten siRNA- Moleküls - "verschluckten". In den Zellen schaltete das siRNA-Molekül das zu ihm passenden Gen stumm. Dieses Gen bildet normalerweise ein Eiweiß, das auf der Oberfläche der T-Zellen sitzt und ist für das Eindringen der Viren in die Zellen nötig. Nun infizierten die Forscher die Mäuse mit HIV.

Auf Mutationen eingestellt

Das Ergebnis: Die ansonsten übliche Zerstörung der T-Zellen wurde gebremst, die Ausbreitung der Viren verhindert. "Infizierte Mäuse, die mit dem siRNA-Mix behandelt wurden, sahen nahezu aus wie die nicht-infizierten Kontrolltiere", fasst Premelata Shankar die Ergebnisse zusammen. "Sie hatten zu vernachlässigende Viren-Titer und ihre CD4-T-Zellen blieben erhalten", sagte die Forscherin dem Magazin "Cell". In einem zweiten Versuch behandelten die Wissenschaftler bereits infizierte Mäuse mit dem Gemisch der siRNA-Moleküle. Auch dabei drosselte die Behandlung die Vermehrung der Viren und die Zerstörung der CD4-Zellen.

Ein besonderer Vorteil des Verfahrens liege darin, dass man damit auf die ständigen Veränderungen des Virus reagieren könne, so die Forscher weiter. Verändert sich nun eines der stumm geschalteten Gene durch Mutationen, brauche man nur das siRNA-Molekül dementsprechend anzupassen.
Adresse:
http://www.n-tv.de/1005711.html

[Fruehrentner]

Alnylam obtains continued funding from NIAID for anti-viral program

7th August 2008

Alnylam Pharmaceuticals has announced that the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, has committed to $7.5 million of continued funding related to the 2006 contract for the development of a broad spectrum RNAi anti-viral therapeutic against hemorrhagic fever virus, including Ebola virus.
In September 2006, Alnylam was awarded a federal contract providing the company with up to $23 million in funding over a four-year period to develop small interfering RNAs (siRNAs), the molecules that mediate RNAi, as anti-viral drugs targeting Ebola virus.

To date, the government has committed to paying Alnylam up to $14.2 million for the first two years of the contract. As a result of the continued progress of this program, the government has committed to fund an additional $7.5 million over year three of the contract.

Antonin de Fougerolles, senior director of research at Alnylam, said: "We are encouraged by the data we have seen with the Ebola program. These data have demonstrated potent and specific in vivo efficacy mediated by an RNAi mechanism. This funding from the National Institute of Allergy and Infectious Diseases (NIAID) allows us to continue to develop our technology as we advance our pipeline programs."

[Fruehrentner]

Tekmira's partner Alnylam to file IND application for tumor drug

7th August 2008

By Staff Writer

Tekmira Pharmaceuticals has reported that Alnylam Pharmaceuticals, one of the company's collaboration partners, is on track to file an investigational new drug application before the end of 2008 for a product candidate that includes Tekmira's SNALP delivery technology.
The Alnylam product candidate, ALN-VSP, is being developed as a treatment for liver cancers and potentially other solid tumors. ALN-VSP comprises small interfering RNA (siRNA) molecules delivered systemically using Tekmira's stable nucleic acid-lipid particles (SNALP) technology. Tekmira is responsible for manufacturing ALN-VSP drug product and has conducted preclinical work in support of Alnylam's investigational new drug (IND) application.

Tekmira is eligible to receive a milestone payment upon the dosing of the first patient in a ALN-VSP Phase I clinical trial. In aggregate, Tekmira is eligible to receive up to $16 million in milestones on each and every RNAi therapeutic advanced by Alnylam or its partners that utilizes Tekmira's technology, as well as royalties on product sales.

Alnylam has provided access to Tekmira's technology to certain of its partners, including Roche, Regulus Therapeutics and most recently, Takeda Pharmaceutical Company.

Mark Murray, Tekmira's president and CEO, said: "Alnylam's progress towards an IND filing for ALN-VSP represents further validation of our technology and will enable the first human clinical trial using SNALP for an siRNA therapeutic product."

[Latinl]

a ist heute in der Bams, nicht wundern abonneten kriegen sie schon am samstag per post

[Fruehrentner]

news aus der Branche bzw. Wettbewerb:

Calando Pharmaceuticals Announces Next siRNA Therapeutic Candidate for Oncology
15 Sep 2008

Calando Pharmaceuticals announces development of a second siRNA oncology therapeutic, CALAA-02, targeting HIF-2alpha

PASADENA, CA, USA | September 15, 2008 | Calando Pharmaceuticals, a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ:ARWR), announced today that pre-clinical development of a second siRNA oncology therapeutic, CALAA-02, is underway. The intracellular target for CALAA-02 is HIF-2alpha, or Hypoxia Inducible Factor-2 alpha. HIF-2alpha is overexpressed in a number of solid tumors and is critical for many aspects of tumorigenesis, such as metastasis, angiogenesis, tumor cell proliferation, and tumor response to radiation. HIF-2alpha has been difficult to target using traditional drugs but is effectively targeted by the proprietary siRNA in CALAA-02.

“We are encouraged by the results obtained thus far with our proprietary anti-HIF-2alpha siRNA and are excited to pursue pre-clinical development of CALAA-02,” said Calando CSO for siRNA delivery, Jeremy Heidel, Ph.D. “We expect our experience with CALAA-01 will simplify and accelerate CALAA-02 development.”

Calando’s first siRNA therapeutic, CALAA-01, which targets the M2 subunit of ribonucleotide reductase, is currently in a Phase I clinical trial. Calando intends to move CALAA-02 into the clinic in 2009 to demonstrate the ability of the RONDEL(TM) delivery system to rapidly enable the pathway from target identification through pre-clinical development to clinical application of siRNA therapeutics.

About Calando Pharmaceuticals Inc.

Calando Pharmaceuticals Inc. (www.calandopharma.com), a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ:ARWR), is a biopharmaceuticals company using proprietary technologies developed at Caltech to create targeted siRNA-based therapeutics and small molecule nanoparticle drug conjugates. Calando uses its innovative Cyclosert(TM) and RONDEL(TM) nanoparticle systems to solve the long-standing obstacle of effective delivery and targeting for oligonucleotide and small molecule therapeutics.

Calando’s Cyclosert(TM) technology uses cyclodextrins as building blocks to create an entirely new class of biocompatible materials - linear cyclodextrin-containing polymers that are non-toxic and non-immunogenic at therapeutic doses. The Company leverages Cyclosert(TM) to design, develop and commercialize drug-delivery-enhanced small-molecule therapeutics. IT-101 is Calando’s lead small molecule Cyclosert conjugate, which recently completed a phase I study in solid tumors at City of Hope Comprehensive Cancer Center.

Calando’s RONDEL(TM) technology involves the use of cyclodextrin-containing polymers that form the foundation for its two-part siRNA delivery system. The first component is a linear, cyclodextrin-containing polycation that, when mixed with small interfering RNA (siRNA), binds to the anionic “backbone” of the siRNA. The polymer and siRNA self-assemble into nanoparticles smaller than 100 nm in diameter that fully protect the siRNA from nuclease degradation in serum. The siRNA delivery system has been designed to allow for intravenous injection. Upon delivery to the target cell, the targeting ligand binds to membrane receptors on the cell surface and the RNA-containing nanoparticle is taken into the cell by endocytosis. There, chemistry built into the polymer functions to unpackage the siRNA from the delivery vehicle. Based upon this breakthrough in siRNA delivery enabled by the RONDEL(TM) system, the promise of using siRNA in new systemic therapies may finally be realized.

SOURCE: Calando Pharmaceuticals Inc.

[aktianer]

Antwort auf Beitrag Nr.: 35.129.077 von Fruehrentner am 16.09.08 13:21:49

Interessantes Interview mit Dr.Tuschl heute in Spiegel-online:

http://www.google.de/search?q=Der+Mann%2C+der+die+Gene+zum+S…

[aktianer]

Antwort auf Beitrag Nr.: 35.208.020 von aktianer am 21.09.08 20:01:37

pardon, versehentlich falscher Link und zudem auch noch unbeabsichtigtes Emoticon im vorigen Posting; jetzt alos der zweite Versuch "Interview mit Dr.Tuschl" in Spiegel-online:

http://www.spiegel.de/wissenschaft/mensch/0,1518,576090,00.h…

[-Salem-]

http://biz.yahoo.com/bw/081015/20081015006224.html?.v=1

Alnylam Scientists Present Data from Multiple Programs at the 4th Annual Meeting of the Oligonucleotide Therapeutics Society

Na da bin ick ja mal jespannt. Wird auf alle Fälle ein Highlight für die Oligo Branche in 2008.

[Fruehrentner]

Alnylam Presents Pre-clinical Data from TTR Amyloidosis Development Program

20 Nov 2008

Results Demonstrate In Vivo Silencing of Mutant and Wild-Type Transthyretin Gene with an RNAi Therapeutic in Transgenic Mice and Non-Human Primates

CAMBRIDGE, MA, USA | November 20, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented new pre-clinical data from its TTR amyloidosis development program at Cambridge Healthtech Institute's Drug Formulation conference held in Philadelphia, November 19-20, 2008. These data demonstrate the potential therapeutic benefit of an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR amyloidosis, including familial amyloidotic polyneuropathy (FAP).

"Based on Alnylam's success in achieving systemic delivery of RNAi therapeutics, we are excited to be advancing an RNAi therapeutic targeting the TTR gene for the treatment of TTR amyloidosis," said Dinah Sah, Ph.D., Vice President, Research, CNS, and Oncology. "We are very encouraged by these promising pre-clinical data and look forward to next steps with this program, which is one of our investigational new drug (IND) candidates for 2009. TTR amyloidosis is an example of a larger number of orphan-like indications that Alnylam intends to advance to the market where there is a very significant unmet medical need, the potential for early biomarker data in clinical studies that enables rapid proof-of-concept, and a clear opportunity for a large therapeutic impact for patients."

"I am excited to be working with Alnylam on this novel program that represents an opportunity to make a profound difference in the lives of patients afflicted with this tragic disease," said Maria Joao Saraiva, Ph.D., Professor of Biochemistry, Molecular Neurobiology Group, Institute for Molecular and Cellular Biology in Portugal. "TTR amyloidosis, which has severe manifestations in FAP, is an orphan disease estimated to affect approximately 10,000 people worldwide. The debilitating disease is associated with significant morbidity, such as intractable peripheral sensory neuropathy and disabling dysfunction of the autonomic nervous system, including severe gastrointestinal symptoms. Based on this encouraging pre-clinical data with ALN-TTR, I am excited about the advancement of this promising new RNAi therapeutic towards clinical trials."

The new data demonstrated that highly potent RNAi therapeutics targeting TTR dramatically reduced the levels of target messenger RNA (mRNA) in the liver and TTR protein in circulation. Using Alnylam's proprietary lipid nanoparticle formulation, studies were performed in a transgenic mouse model where human TTR (hTTR) with a certain mutation known as V30M is over-expressed. Studies were also performed in non-human primates using lipid nanoparticle formulations from Tekmira Pharmaceuticals Corp. Specifically, data from these studies showed that administration of ALN-TTR resulted in:

-- dose-dependent silencing of TTR in vitro and absence of any immune stimulatory effects;

-- reduced TTR plasma levels and liver TTR mRNA by greater than 90% in the V30M-hTTR transgenic mouse model; and

-- reduced liver TTR mRNA levels by approximately 80% in non-human primates.

For most patients with TTR amyloidosis, liver transplantation is the only treatment option. These data suggest that treatment of TTR amyloidosis with an RNAi therapeutic may represent a promising alternative medical strategy, including the ability to simultaneously reduce the expression of mutant as well as wild-type TTR.

About TTR Amyloidosis

TTR amyloidosis is a hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest form, TTR amyloidosis represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; FAP (familial amyloidotic polyneuropathy) affects approximately 10,000 people worldwide with additional patients affected by FAC (familial cardiac amyloidosis). TTR amyloidosis patients with FAP have a mean life expectancy of nine to eleven years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene.

[Fruehrentner]

Alnylam Advances RNAi Therapeutics Pipeline and Files Company's First Systemic Delivery IND

23 Dec 2008

Company Files IND for ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers
ALN-VSP Represents Industry's First Dual Targeting RNAi Therapeutic to Advance to IND Stages

CAMBRIDGE, MA, USA | December 23, 2008 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for ALN-VSP, an RNAi therapeutic for the treatment of liver cancers, including hepatocellular carcinoma and other solid tumors with liver involvement. ALN-VSP contains two small interfering RNAs (siRNAs), the molecules that mediate RNAi, formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation. ALN-VSP is designed to target two genes critical in the growth and development of cancer: kinesin spindle protein, or KSP, required for tumor proliferation; and vascular endothelial growth factor, or VEGF, required for tumor growth. Pre-clinical data in mouse tumor model studies have demonstrated robust efficacy of ALN-VSP, including suppression of these targeted genes, demonstration of an RNAi mechanism of action, tumor reduction, and extension of survival.

"ALN-VSP represents Alnylam's first IND for a systemically delivered RNAi therapeutic, which is a testament to the very strong progress we've made in achieving systemic delivery of siRNAs, including our efforts with Tekmira," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "We're also pleased, with this IND filing, to have met one of our key pipeline goals for 2008. Following FDA review of our submission, we expect to initiate patient dosing in the first half of 2009, which positions us solidly on track to meet our goal of having three programs in clinical trials next year."

"Based on the encouraging pre-clinical data we've seen to date with this program, we believe our strategy of using an RNAi therapeutic targeting two well-validated genes critical for tumor proliferation and survival has the potential of achieving meaningful clinical benefit for patients with liver cancer," said Dinah Sah, Ph.D., Vice President, Research, CNS and Oncology, at Alnylam. "We believe that this is the first dual targeting RNAi therapeutic program to advance to this stage of development across the entire industry. This is an important milestone, as we view the ability to design and formulate siRNAs that achieve dual targeting as a very attractive feature of our RNAi therapeutics platform, especially in the setting of oncology drug discovery."

"Cancer affecting the liver, either as primary disease or as metastatic spread from cancer originating at another site, represents a major cause of death and a major unmet medical need affecting a large number of patients in the U.S. and across the world," said George D. Demetri, M.D., director of the Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical School, a collaborating investigator in this work. "Many common cancers, such as breast cancer and colorectal cancer, spread to the liver, where the metastatic disease is life threatening. Additionally, primary liver cancer, known as hepatocellular carcinoma, is one of the most common solid tumors in the world overall, and is associated with one of the poorest survival rates in cancer. The ALN-VSP clinical development program will have great impact in this area, if the pre-clinical testing can be translated into similar benefits for patients with liver involvement from cancer."

The proposed Phase I study is a multi-center, open label, dose escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous ALN-VSP in patients with advanced solid tumors with liver involvement. Additional study design details will be provided upon initiation of the Phase I trial.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington's disease, and TTR amyloidosis. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, and Kyowa Hakko. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established "RNAi 2010" in January 2008 which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals, Inc

[Fruehrentner]

Alnylam Receives Clearance from FDA to Initiate Phase I Study with ALN-VSP for the Treatment of Liver Cancers

23 Jan 2009

ALN-VSP Represents Industry's First Dual Targeting RNAi Therapeutic to Advance to Clinical Studies
Company on Track to Begin Dosing Patients in the First Half of 2009

CAMBRIDGE, MA, USA | Jan. 23, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that its investigational new drug (IND) application for ALN-VSP has been cleared by the U.S. Food and Drug Administration (FDA) to begin enrolling patients. ALN-VSP, an RNAi therapeutic for the treatment of liver cancers including hepatocellular carcinoma and other solid tumors with liver involvement, contains two small interfering RNAs (siRNAs, the molecules that mediate RNAi), formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation. ALN-VSP is designed to target two genes critical in the growth and development of cancer: kinesin spindle protein, or KSP, required for tumor proliferation; and vascular endothelial growth factor, or VEGF, required for tumor growth. Pre-clinical data in mouse tumor model studies have demonstrated robust efficacy of ALN-VSP, including suppression of targeted genes, demonstration of an RNAi mechanism of action, tumor reduction, and extension of survival.

"ALN-VSP represents Alnylam's first IND for a systemically delivered RNAi therapeutic, which is a testament to the very strong progress we have made in achieving delivery of siRNAs," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "We are very excited about reaching yet another important milestone in this program and in our overall efforts. As planned, we expect to initiate patient dosing in the first half of this year, which positions us solidly on track to meet our goal of having three programs in clinical trials in 2009."

The proposed Phase I study is a multi-center, open label, dose escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous ALN-VSP in patients with advanced solid tumors with liver involvement. Additional study design details will be provided upon initiation of the clinical study.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington's disease, and TTR amyloidosis. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established "RNAi 2010" in January 2008 which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals, Inc.

[Fruehrentner]

Alnylam and Collaborators Publish New Pre-Clinical Research Demonstrating In Vivo Efficacy of Systemically Delivered RNAi Therapeutics in Ovarian Cancer

11 Feb 2009

New Findings Published in the Proceedings of the National Academy of Sciences Demonstrate Suppression of Ovarian Tumor Growth in Three Different Animal Models

CAMBRIDGE, MA, USA | February 11, 2009 |

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication of new research in the Proceedings of the National Academy of Sciences (PNAS) by Alnylam scientists and collaborators from the Lankenau Institute for Medical Research and the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT).

These new findings (Huang et al. (February 10, 2009) Proc. Natl Acad. Sci. USA, 10.1073/pnas.0813348106) demonstrate that RNAi silencing of the claudin-3 protein using lipidoid formulations of small interfering RNAs (siRNAs, the molecules that mediate RNAi) results in the suppression of ovarian tumor growth and metastases. Claudin-3 is a tight junction protein that is highly over-expressed in approximately 90% of ovarian tumors. Previous in vitro studies have shown that the over-expression of claudin-3 promotes migration, invasion, and increased survival of ovarian cancer cells.

“We are encouraged by the findings published today in PNAS, as they represent a promising therapeutic approach that could significantly slow the progression of disease in patients with advanced-stage ovarian cancer,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “Clearly, these results reflect the continued progress that Alnylam and our collaborators are making in advancing systemic delivery solutions for RNAi therapeutics, as well as our commitment to scientific excellence through publication of our research data. At the same time, we are making substantial progress in advancing our therapies to patients, as evidenced by the FDA clearance of our IND filing for ALN-VSP, an RNAi therapeutic for the treatment of liver cancers.”

“I am excited by these new data as there is a very significant need for novel therapies to treat patients with ovarian cancer – a devastating disease that affects more than 20,000 women and results in more than 15,000 deaths each year in the U.S. alone,” said Janet Sawicki, Ph.D., Professor at the Lankenau Institute for Medical Research. “Advanced-stage ovarian cancer is extremely difficult to treat with today’s medicines, and these new data suggest that an RNAi therapeutic targeting claudin-3 may represent a novel treatment option in the future.”

“These data further illustrate the broad potential of RNAi therapeutics in medicine,” said Daniel Anderson, Ph.D., of the David H. Koch Institute for Integrative Cancer Research at MIT. “We are excited by the pre-clinical efficacy of these siRNA formulations, as demonstrated in multiple animal models of ovarian cancer, and I am optimistic that the delivery systems described here will provide new avenues for the treatment of cancer and other diseases.”

The published data showed that lipidoid-mediated delivery of siRNAs targeting claudin-3 in ovarian tumor tissue resulted in the dramatic silencing of the gene and a substantial reduction in tumor growth and metastases as compared to controls in three different mouse tumor models.

Specifically, data with lipidoid-formulated claudin-3-specific siRNAs showed:

* in an ovarian cancer cell xenograft model with intratumoral injection, a significant silencing of claudin-3, a reduction in cell proliferation and tumor growth, and a significant increase in the number of apoptotic cells;

* in an ovarian tumor-bearing transgenic mouse model with intraperitoneal dosing, an approximately 40% suppression of tumor growth rate, including tumor regression in some mice, compared to controls, and a significant reduction of malignant ascites (fluid in the abdominal cavity that contains cancer cells), where only 22% of mice treated with the claudin-3 siRNA developed ascites compared to 75% of control-treated animals;

and,

* in a mouse ovarian surface epithelial cell model with intraperitoneal dosing, a survival rate of 50% for siRNA-treated mice compared to 0% survival in control-treated animals.

In addition to ovarian tumors, claudin-3 is over-expressed in other tumor types, including breast and prostate, and therefore lipidoid-mediated delivery of siRNAs targeting this protein may also be effective in the treatment of other cancers.

‘Lipidoids’ are a new class of lipid-based molecules which are used to form novel nanoparticle formulations for systemic delivery of RNAi therapeutics. A previous study by Alnylam scientists in collaboration with scientists from MIT (Akinc et al., Nature Biotechnology 26, 561-569 (01 May 2008)), showed successful delivery of siRNAs encapsulated in lipidoid formulations when administered in multiple animal species including mice, rats, and non-human primates. Together, these data demonstrated potent, specific, and durable effects on gene expression in multiple tissues, including liver, lung, and peritoneal macrophages. Further, the Akinc et al. paper demonstrated applications of the same technology for delivery of microRNA antagonists.

About Ovarian Cancer

Ovarian cancer is the fourth most common cancer in women, and has the highest mortality rate among gynecologic malignancies in the United States. Treatment of early-stage ovarian carcinoma improves the survival rate up to 90%. However, due to the lack of effective screening tests and the asymptomatic nature of the disease in its early stages, most women are not diagnosed until the cancer has reached more advanced stages. There are currently no treatments available for those women with advanced-stage ovarian cancer who either do not respond to initial therapy or develop recurrent disease.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington’s disease, and TTR amyloidosis. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com.

About Lankenau Institute for Medical Research

Founded in 1927, the Lankenau Institute for Medical Research (LIMR) is an independent, nonprofit biomedical research center located in suburban Philadelphia on the campus of the Lankenau Hospital. As part of the Main Line Health System, LIMR is one of the few freestanding, hospital-associated medical research centers in the nation. The faculty and staff at the Institute are dedicated to advancing an understanding of the causes of cancer and heart disease. They use this information to help improve diagnosis and treatment of these diseases as well as find ways to prevent them. They are also committed to extending the boundaries of human health and well-being through technology transfer and education directed at the scientific, clinical, business and lay public communities. For more information visit: www.limr.org.

About the Koch Institute

The MIT Center for Cancer Research (CCR) has changed its name to the David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute – pronounced “coke”) effective March 2008. This name change is linked to generous funding received in support of the creation of a new building and endeavor, to be completed by the year 2010, to house expanded and innovative cancer research at MIT. Note that all CCR facilities and faculty members have been incorporated into the Koch Institute.

SOURCE: Alnylam Pharmaceuticals, Inc.

[Fruehrentner]

Rückschlag beim Patentportfolio für Alnylam:

21.01.2009 08:00:00

SILENCE THERAPEUTICS PLC - Statement re Patent Update


Silence Therapeutics announces its successful opposition to second European Patent in Kreutzer-Limmer patent family.

London, UK, 21 January 2009 -

Silence Therapeutics plc (London AIM: SLN), the
leading European biopharmaceutical company focused on RNA interference (RNAi), welcomes the announcement today that a second member of the Kreutzer-Limmer patent family has been revoked in its entirety.

Following an oral hearing, the Opposition Division of the European Patent Office announced its decision yesterday to revoke European Patent EP 1 214 945 in its entirety. This patent, which is held by Alnylam Europe AG, is a divisional of European patent EP 1 144 623, which was itself revoked in its entirety by the Technical Board of Appeal on December 09, 2008.

The patent was opposed by Silence Therapeutics AG, Sirna Therapeutics, Quark
Biotech Inc. and Abbott Laboratories.

Dr. John Lucas, General Counsel & Vice President, Intellectual Property, at Silence Therapeutics, said: "The decision of the Opposition Division confirms our view that the entire Kreutzer-Limmer RNAi patent family is vulnerable and may be successfully challenged. This is now the second European patent of this
family to be revoked. As all of the members of the Kreutzer-Limmer RNAi patent family suffer from the same shortcomings in terms of disclosure, we expect the European Patent Office will take the same position with any further patents in
this patent family"

- Ends -

For further information, please contact the following:

Silence Therapeutics plc Powerscourt

[phone] [phone]

Iain Ross, Chairman & CEO Paul Durman

John Lucas, General Counsel & Vice Kay Larsen
President Intellectual Property

Nominated Advisers

Nomura Code Securities Limited

[phone]

Richard Potts


Notes to Editors:

About Silence Therapeutics plc (www.silence-therapeutics.com )

Silence Therapeutics plc (AIM: SLN) is a leading European RNAi-focused
biotechnology company.

RNA interference (RNAi), is a Nobel Prize winning technology and one of the
most exciting areas of drug discovery today. It represents a completely new
approach to selectively 'silence' or inactivate disease relevant genes and as
such it has the potential to create a new class of therapeutic products. RNAi
could therefore offer a therapeutic approach to a broad range of diseases
(cancer, infectious diseases, inherited diseases), many of which have been
regarded as incurable and are not addressed by current therapeutics, therefore
providing a large market opportunity.

Silence Therapeutics has developed a platform of novel short interfering RNA

('siRNA') molecules, AtuRNAi, which provide a number of advantages over
conventional siRNA molecules, including increased stability against nuclease
degradation. In addition, the Company has developed a proprietary systemic
delivery system, AtuPLEX. This system enables the functional delivery of siRNA
molecules to targeted diseased tissues and cells, while increasing their
bioavailability and intracellular uptake.

Following the granting of its patents in Europe, the USA and Australia, Silence
Therapeutics is one of only two companies worldwide with a proprietary position
on composition of matter for siRNA therapeutics.

Silence's lead internal product, Atu027, is a proprietary AtuRNAi molecule in
preclinical development for systemic cancer indications. Atu027 has
successfully completed single and repeat dose toxicology and geno-toxicology
studies, as well as a 28-day toxicology study using multiple dosing regimens.
Silence made a regulatory filing in 2008 and expects to commence clinical
trials for Atu027 in 2009.

In March 2008 Silence Therapeutics announced a collaboration with AstraZeneca

(LSE: AZN) focused on the development of a range of novel delivery approaches
for siRNA molecules. Under the terms of the agreement both Silence Therapeutics
and AstraZeneca will be allowed to commercialize the truly novel delivery
systems that the two partners develop together.

Silence Therapeutics has granted a licence to AstraZeneca to develop novel
AtuRNAi therapeutics against five specific targets. This collaboration was the
first industry validation of the potential application of Silence Therapeutics'
proprietary AtuRNAi molecules and solidified the Company's leadership position
in field of RNAi therapeutics.

The Company's AtuRNAi technology also has been sublicensed to Pfizer via
Quark's license to them of the compound RTP-801i-14 for the treatment of
age-related macular degeneration (AMD) and a number of other indications. This
compound entered a phase II clinical study in July 2008. Silence Therapeutics
also has licensed to Quark rights to the AtuRNAi structure for Quark's
proprietary compound, AKIi-5, which is in a Phase I human clinical study for
treatment of acute kidney injury.

Forward-Looking Statements

This press release includes forward-looking statements that are subject to
risks, uncertainties and other factors. These risks and uncertainties could
cause actual results to differ materially from those referred to in the
forward-looking statements. All forward--looking statements are based on
information currently available to Silence Therapeutics and Silence
Therapeutics assumes no obligation to update any such forward-looking
statements.

Silence Therapeutics is based in London, UK, and Berlin, Germany, and is listed
on AIM.

END
Quelle:PR NEWSWIRE

[Fruehrentner]

!

Dieser Beitrag wurde vom System automatisch gesperrt. Bei Fragen wenden Sie sich bitte an [e-mail]

[aktianer]

Umstz und Verlust lagen für das 4.Quartal 2008 etwas unter den Schätzungen; mal sehen, wie sich das heute auswirkt, Zahlen kamen nämlich erst nach Börsenschluß:

* Q4 loss/shr 23 cents vs est loss/shr 15 cents
* Q4 revenue $24.4 mln vs est $26.1 mln

http://finance.yahoo.com/news/Alnylam-Pharmaceuticals-bw-144…

[aktianer]

Ein upgrade durch Needham, von "underperform" auf "hold" sorgt heute wohl für etwas Auftrieb.

http://finance.yahoo.com/q/ud?s=ALNY

Needhams Analyst Carr hatte vor einem Jahr folgendes Urteil abgegeben:

"Still, Carr said, there is some uncertainty in the company's RSV development program and he remained cautious with a "Underperform" rating."

Das scheint er nun zumindest teilweise zurückgenommen haben!

[[KERN]Codex]

[[KERN]Codex]

schaltet mal zdf doku ein, da läuft gerad was darüber

[Fruehrentner]

Alnylam Initiates Phase I Clinical Study of ALN-VSP in Patients with Liver Cancer

03 Apr 2009

ALN-VSP Represents Company's First Clinical Program with a Systemically Delivered RNAi Therapeutic

CAMBRIDGE, MA, USA | April 3, 2009 |

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it has initiated a Phase I human clinical trial of ALN-VSP to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced liver cancers, including hepatocellular carcinoma and other solid tumors with liver involvement.

ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs (or siRNAs, the molecules that mediate RNAi) formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation and designed to target two genes critical in the growth and development of cancer cells: kinesin spindle protein, or KSP, required for tumor proliferation; and vascular endothelial growth factor, or VEGF, required for tumor growth.

Pre-clinical data in mouse tumor model studies have demonstrated robust efficacy of ALN-VSP, including suppression of targeted genes, demonstration of an RNAi mechanism of action, tumor reduction, and extension of survival.

"We are excited to have initiated this Phase I trial as it represents an important milestone in Alnylam's efforts to advance RNAi therapeutics for the treatment of cancer. ALN-VSP is also Alnylam's first clinical program employing systemic delivery. Moreover, in this program we are targeting two well-validated genes critical for tumor proliferation and survival, an attractive strategy for the advancement of novel anti-cancer medicines," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "More than one million liver cancer patients are diagnosed annually, and currently have limited therapeutic options and extremely poor survival rates. Over time and as we aim to demonstrate safety and efficacy for ALN-VSP, we hope that our efforts will provide patients a meaningful treatment option for their disease."

The Phase I trial, conducted in the U.S., is a multi-center, open label, dose escalation study designed to enroll approximately 55 patients with advanced solid tumors with liver involvement, who have failed to respond to or have progressed after standard treatment. The primary objective is to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP, including demonstration of the maximum tolerated dose. Other exploratory objectives include the assessment of tumor response through Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients' disease improves, stabilizes or progresses during treatment; change in tumor blood flow or vascular permeability measured by DCE-MRI; and, change in plasma biomarkers of angiogenesis. In addition, the analysis of pharmacodynamic effects of ALN-VSP on tumors will be measured in patients electing to proceed with voluntary pre- and post-treatment biopsies.

"RNAi therapeutics represent an encouraging new modality that has the potential to create a new benchmark in the treatment of cancer," said Charles Fuchs, M.D., M.P.H., Director for the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute in Boston. "The ALN-VSP pre-clinical data have demonstrated the ability of an RNAi therapeutic to simultaneously target two key disease pathway genes implicated in primary and secondary liver cancer. The application of this RNAi-based approach may hold promise for other cancers as well."

About Liver Cancers

Cancer affecting the liver, known as either primary or secondary liver cancer, is associated with one of the poorest survival rates in oncology and represents a major unmet medical need affecting a large number of patients worldwide. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 600,000 people diagnosed each year. Secondary liver cancer, also known as metastatic liver cancer, is cancer that spreads to the liver from another part of the body due to other common cancers like colon, lung, or breast cancer. Worldwide, more than 500,000 people are diagnosed with secondary liver cancer each year.

For more information, please visit www.alnylam.com.

[Fruehrentner]

Alnylam obtains notice of allowance for new European patent

Published: 22-April-2009

Grant of Tuschl I patent consists of 19 claims

Alnylam Pharmaceuticals, an RNAi therapeutics company, has reported that the European Patent Office has issued a notification of intent to grant for a patent in the Tuschl I patent series.

The new patent is the first to be granted in the EU from the Tuschl I patent series, and includes 19 claims broadly covering the use of double stranded RNAs (dsRNAs) for RNAi, said Alnylam. This new patent grant extends the scope and breadth of Alnylam's fundamental intellectual property (IP) estate that comprises numerous issued or granted patents and a large number of pending patent applications that together broadly cover RNAi therapeutics, including small interfering RNAs, or siRNAs, the molecules that mediate RNAi.

The current grant of the Tuschl I patent consists of 19 claims broadly covering RNAi methods, including methods of reducing the expression of a gene, including those of mammalian or viral origin, with dsRNAs between 21 and 23 nucleotides in length. In addition, the patent also includes claims covering methods of examining the function of a gene, as well as the use of both unmodified and chemically modified dsRNAs.

Upon completion of certain formalities, the patent will be granted in approximately four months. Alnylam said that it is the exclusive licensee of the ownership interests of the Max Planck Society, the Massachusetts Institute of Technology, and Whitehead Institute for Biomedical Research, in the Tuschl I patent series for RNAi therapeutics.

Barry Greene, president and COO of Alnylam, said: "This is the first patent of the Tuschl I patent series to be granted in the EU, and expands the scope of our fundamental IP that also includes issued or granted patents from the Crooke, Kreutzer-Limmer, Tuschl II, and Kay & McCaffrey patent estates, amongst other patent applications pending.

"We have demonstrated a clear track record of leveraging our patent portfolio to enable the field in developing RNAi therapeutics, as evidenced by more than 25 licensing agreements which have yielded over $660 million in realized cash funding for Alnylam. With this new patent grant, and the continued expansion of our IP estate, we expect our business development execution to only continue in the future."


http://regulatoryaffairs.pharmaceutical-business-review.com/…

[Fruehrentner]

Isis and Alnylam Form New Collaboration to Develop Single-Stranded RNAi Technology

29 Apr 2009

Single-Stranded RNAi Represents a Novel Strategy of Harnessing the RNAi Pathway for Gene Silencing Isis Co-Exclusively Licenses Intellectual Property and Technology to Alnylam Companies to Host Conference Call Webcast to Discuss Isis-Alnylam Collaboration on April 29, 2009 at 9:00 a.m. ET (6:00 a.m. PT)

CAMBRIDGE, MA. & CARLSBAD, CA, USA | April. 29, 2009 |

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that they have formed a new collaboration focused on the development of single-stranded RNAi (ssRNAi) technology. As part of the collaboration, Isis has co-exclusively licensed its ssRNAi technology to Alnylam in exchange for upfront payments, research and development milestone payments, and royalties. The alliance provides Alnylam with access to Isis’ intellectual property and expertise regarding the development of ssRNAi antisense drugs, while both companies will have the opportunity to discover and develop drugs employing the new technology. In addition to the new collaboration, Isis and Alnylam also agreed to extend their broad cross-licensing arrangement regarding double-stranded RNAi that was established in 2004.

As it is known to occur in nature, the RNAi pathway is mediated by short double-stranded RNA oligonucleotides called “small interfering RNAs” or “siRNAs.” To date, efforts aimed at harnessing this pathway to silence disease-causing proteins have used double-stranded siRNAs. Using its expertise in oligonucleotide chemistry and design, Isis has discovered strategies for designing single-stranded oligonucleotides that act through the RNAi mechanism. With further development, these chemically modified, single-stranded, RNA-like oligonucleotides could have improved properties for systemic administration while harnessing certain advantages of the RNAi mechanism.

“At Isis, we have made significant breakthroughs showing that chemically modified single-stranded oligonucleotides can activate the RNAi pathway. It is now time to expand upon our efforts and broaden the applications of these inventions. We believe that Alnylam, the leading company in the field of RNAi therapeutics, is the perfect partner to work with in advancing this exciting effort,” said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. “Since we began our collaborative efforts in 2004, Alnylam has been a great partner and has made excellent progress in its RNAi therapeutic programs. We are confident that working together in RNAi gives ssRNAi technology the best chance for success.”

“We are committed to advancing RNAi therapeutics as a new class of innovative medicines for patients, and we continue to make significant progress in the advancement of double-stranded siRNA-based drugs. As we continue our primary focus on double-stranded siRNAs, we believe that ssRNAi technology and this new collaboration with Isis can strengthen our overall efforts,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “We’ve recognized since Alnylam’s beginning that Isis is the leader in all aspects of antisense technology. We’ve had a mutually beneficial collaboration based on their innovation and patents in the field of double-stranded RNAi drugs, and we’ve been impressed with their continued expansion of this innovation to single-strand RNAi approaches. While there’s more to do, we are excited to combine our expertise with theirs in advancing this promising technology.”

Under the terms of the licensing and collaboration agreement, Alnylam will potentially pay Isis up to $31 million in license fees payable in four tranches that include $11 million on signing, $10 million in 18 months or earlier if in vivo efficacy in rodents is demonstrated sooner, $5 million upon achievement of in vivo efficacy in non-human primates, and $5 million upon initiation of the first clinical trial with an ssRNAi drug. Alnylam will fund research activities at a minimum of $3 million each year for three years with research development activities conducted both at Isis and Alnylam. If Alnylam develops and commercializes drugs utilizing ssRNAi technology on its own or with a partner, Isis will receive milestones and royalties. Also, initially Isis is eligible to receive up to 50 percent of any sublicense payments due to Alnylam based on Alnylam partnering of ssRNAi products, which will decline over time as Alnylam’s investment in the technology and drugs increases. In turn, Alnylam is eligible to receive up to 5 percent of any sublicense payments due to Isis based on Isis’ partnering of ssRNAi products. Both Isis and Alnylam are eligible to receive royalties from each other on any ssRNAi products developed by the other company.

SOURCE: Alnylam Pharmaceuticals, Inc.

[Fruehrentner]

aus der RNAi Branche:

RXi Pharmaceuticals Announces Publication in Nature of Positive Pre-clinical Data Demonstrating that Oral Administration of RNAi Therapeutics Effectiv

30 Apr 2009

RXi Pharmaceuticals announced the publication of an article in the journal Nature that presents new pre-clinical data demonstrating that low dose (20 μg/kg) oral administration of RNAi therapeutics resulted in a significant reduction of a systemic inflammatory response in an established mouse model of inflammation

WORCESTER, MA, USA | April 30, 2009 |

RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced the publication of an article in the journal Nature that presents new pre-clinical data demonstrating that low dose (20 μg/kg) oral administration of RNAi therapeutics resulted in a significant reduction of a systemic inflammatory response in an established mouse model of inflammation.

This important work on oral delivery of RNAi compounds was published by Michael Czech, Ph.D., co-founder of, and Scientific Advisor to, RXi Pharmaceuticals and Professor and Chair of Molecular Medicine and Professor of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School (UMMS) (Aouadi, et al, Nature, Vol. 458 (7242), pp. 1180-1184). RXi Pharmaceuticals has the exclusive worldwide rights to certain patent applications claiming aspects of the technology behind the oral delivery of RNAi therapeutics upon which this work was based under a license agreement entered with UMMS in October 2008.

Commenting on today’s news, Tod Woolf, Ph.D., President and Chief Executive Officer of RXi Pharmaceuticals, noted, “Oral administration of RNAi therapeutics using this particular technology is a major scientific breakthrough that was not previously thought practical. As a result of the publication of Dr. Czech’s data in Nature, one of the premier scientific journals, it now appears that this method may constitute a significant advance in RNAi delivery. This new orally available, low dose RNAi therapy may be able to control many severe inflammatory diseases without the need for more invasive types of administration such as injection, which is the current standard of care for approved non-RNAi therapeutics. We believe that oral RNAi therapeutics, if successfully developed, could address the multi-billion dollar markets of rheumatoid arthritis, Crohn’s disease, atherosclerosis, inflammatory bowel disease and diabetes. As a result, this new technology provides many potential scientific and commercial opportunities for RXi Pharmaceuticals, and we are focusing our resources on this exciting therapeutic area.”

In the published work, which was funded by UMMS and the National Institutes of Health, oral delivery of micron sized RNAi encapsulation vehicles made of beta 1,3 D glucan (called “GeRPs”) target macrophages in the gut that then migrate to tissues throughout the body. Gene silencing of the cytokine TNF-alpha or the protein kinase MAP4K4 that controls TNF-alpha expression was observed in isolated immune cells of treated mice, as compared to controls, after oral administration of the respective GeRP-encapsulated RNAi compound. Silencing of the MAP4K4 target gene mRNA level was observed in macrophages isolated from spleen, liver and lung tissues. Additional experiments featured in the publication showed that the gene silencing with this technology and delivery of unmodified siRNAs lasted about eight days following the termination of oral administration.

The data presented in Nature shows that the GeRPs efficiently target immune cells and that efficient gene silencing can be observed specifically in macrophages. In addition, the work revealed that MAP4K4 is a novel mediator of cytokine expression, providing an opportunity to use this target to attenuate the inflammatory response in human diseases.

Michael Czech, Ph.D., noted, “Macrophages are key cells which orchestrate immune responses in man. Our collaboration with Gary Ostroff, Ph.D., Professor of Molecular Medicine, and my colleague here at UMMS, has led to encouraging results that show oral delivery of RNAi compounds is feasible for reducing inflammatory gene expression in these cell types. We are very excited about this technology and the potential to move it forward in collaboration with RXi Pharmaceuticals.”

Earlier this year, a collaboration between RXi Pharmaceuticals and the UMMS research team received funding from a Massachusetts Life Sciences Center Cooperative Research Grant to further develop this technology. The three-year grant of up to $250,000 per year, which is part of the state’s $1 billion, 10-year life-science initiative, will help fund the use of RXi Pharmaceutical’s rxRNA™ compounds to advance the progress of oral administration of RNAi therapeutics.

RXi Pharmaceuticals has an agreement with UMMS whereby UMMS has granted RXi an exclusive license to certain patent applications to this technology and co-exclusive options to other underlying technology. UMMS and inventors of this intellectual property may receive developmental milestones and/or royalty payments pursuant to the agreement.

The journal article can be accessed on-line at www.nature.com.

---------------------------------------------------------


About GeRPs

The GeRP delivery system uses hollow, porous, micron-sized shells filled with RNAi compounds that may be taken up by M (microfold) cells in the intestinal wall and are then transferred to the underlying GALT (gut associated lymphatic tissue) where they are then taken up by macrophages and other phagocytic cell types. The RNAi compounds are presumed to be released into the cytoplasm of the macrophage where they will start silencing genes by an RNAi mechanism, while the macrophages traffic throughout the body. The GeRP delivery system appears to be 5 to 250 times more potent than previous generally known methods used for systemic delivery of RNAi therapeutics by intravenous injection. The loading capacity of the shells would also potentially allow co-delivery of RNAi, DNA, protein and small molecule combinations.

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals is a discovery-stage biopharmaceutical company pursuing the development and potential commercialization of proprietary therapeutics based on RNA interference (RNAi) for the treatment of human diseases. RXi has a comprehensive RNAi platform that includes both RNAi compounds and delivery methods. RXi Pharmaceuticals’ rxRNA™ compounds are distinct from the siRNA compounds used by many other companies developing RNAi therapeutics and are very active and potent (10-100pM activity in cell culture) based on the company’s internal research, in addition to being nuclease resistant and readily manufactured. RXi Pharmaceuticals believes it is well positioned to compete successfully in the RNAi-based therapeutics market with its accomplished scientific advisors, including Dr. Craig Mello, recipient of the 2006 Nobel Prize for his co-discovery of RNAi; a management team that is experienced in developing RNAi products; and a strong early intellectual property position in RNAi chemistry and delivery. www.rxipharma.com.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $193 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.

SOURCE: RXi Pharmaceuticals

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 37.099.569 von Fruehrentner am 05.05.09 15:43:38

Alnylam lässt seine Wirkstoffe von der deutschen Solvay SA Tochter ,Girindus AG, entwickeln und synthetisieren.

Also ein gerade mal noch 6 Mio€ MK Unternhemen aus DL, Tochter eines 10 Mrd Umsatz und 450 Gewinn starken Unternehmens aus Belgien, macht das alles für ALNY. Da sieht man, dass Antisense oder Oligos, in DL bei Investoren kaum einen Stellenwert haben. Noch....

[Fruehrentner]

Antwort auf Beitrag Nr.: 37.103.623 von Berliner_Landstreicher am 05.05.09 22:38:50

Alnylam lässt seine Wirkstoffe von der deutschen Solvay SA Tochter , Girindus AG, entwickeln und synthetisieren.

Hast du dazu eine Quellenangabe/link? Danke.

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 37.103.635 von Fruehrentner am 05.05.09 22:41:15

http://www.sec.gov/Archives/edgar/data/1178670/0000950135070…,


Einfach nach Girindus suchen! Alnylam Europa ist ehem. Ribopharma und die pflegen und pflegten intensive Geschäftbeziehungen mit GIR.

Es gibt noch ne andere Quelle.

Der Chef für Mnufacturing von Alnylam Dr. Konys war auch auf dem Girindus GLOS in Cincinnati, wo die Antisense sythetisiert werden.

http://www.girindusglos.com/

Ist sogar mit auf deem Foto.

[Fruehrentner]

Heute geht's aber kräftig abwärts! Was ist los?

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 37.109.427 von Fruehrentner am 06.05.09 15:47:25

Ist doch alles im Lot.

Zugegeben ALNY hat die Monate etwas leiden müssen, aber iM laufen bis auf DNDN die Biotechs eher schwerfällig.

Hier ist noch ne Präsentation von Dr. Konys von Alnylam auf dem Giridnus Symposium.

http://www.girindusglos.com/resources/GLOS2009Day2/GirindusM…

[Berliner_Landstreicher]

http://finance.yahoo.com/news/Novartis-Exercises-its-Right-b…

Na ob Novartis hier nicht die Übernahme plant? Es ist iM ein totaler Run auf Unternehmen mit vielversprechenden Antisense Wirkstoffen. Da will keiner der Großen zurück stecken.

Bsp.

-Pfizer übernimmt Coley GmbH aus Düsseldorf.
-Wyeth kauft sich mit bis zu 1 Mrd$ ind die Santaris Pipeline ein.
-GlaxoSmithKline kauft sich mit bis zu 900 Mio$ in Antisenseprojekte von Santaris ein.
-Enzon kauft sich in die Santaris Pipeline ein.
-Solvay übernimmt Girindus, eine Lead-Supplier für Antisense, mit einzigartigen Technologien.
-Roche hat glaub ich auch was übernommen.
-Die gesamte Isis Pipeline ist verteilt.
-Novartis und Alnylam!?!?!?!??!
usw.

[Berliner_Landstreicher]

Sagt mal, wie kommt denn Alnylam eigentlich auf 96 Mio Umsatz? Bis auf Isis kenne ich kein Unternehmen mit zugelssenen Antisense Wirkstoffen. Es soll aber noch ein 2. oder 3. geben.

Und ALNY ist auch gerade mal in p2. Scheinbar bekommen die mega viele Royalties ihrer Partner. Die Pipeline von Alny ist schon dufte. Heute kommen wieder Zahlen bei ALNY.

[Fruehrentner]

news aus der RNAi-Branche:


Roche Partners With Tekmira Pharmaceuticals to Advance RNAi Product Candidates

11 May 2009

Tekmira Pharmaceuticals announced today that it has entered into a product development agreement with global healthcare company Roche to advance Roche's first two RNA interference (RNAi) product candidates into human clinical testing. Both of the product candidates will be based on Tekmira's stable nucleic acid-lipid particle (SNALP) technology

VANCOUVER, BRITISH COLUMBIA, CANADA | May 11, 2009 |

Tekmira Pharmaceuticals Corporation (TSX: TKM.TO) announced today that it has entered into a product development agreement with global healthcare company Roche (SWX: ROG-VX.SW)(SWX: RO-S.SW)(OTCQX: RHHBY) to advance Roche's first two RNA interference (RNAi) product candidates into human clinical testing. Both of the product candidates will be based on Tekmira's stable nucleic acid-lipid particle (SNALP) technology.

Under the terms of the product development agreement, Roche will pay Tekmira up to US$18.4 million to support the advancement of the product candidates to the filing of Investigational New Drug (IND) applications. Tekmira is also eligible to receive up to US$32 million in milestones plus royalties on product sales as the first two products are advanced through development and commercialization based on Roche's access to Tekmira's intellectual property under previously announced agreements.

Dr. Mark J. Murray, Tekmira's President and CEO, said "We are extremely pleased to be working with Roche, a global pioneer in the development of important therapeutic products and a leader in the RNAi field. This agreement is consistent with our strategy of working with leading pharmaceutical companies to help them advance products based on our SNALP technology, and to leverage this work in order to advance our own products."

"At the same time, the funding from Roche will further strengthen our balance sheet and extend our cash resources as we execute on our business plan of advancing novel RNAi products," said Dr. Murray.

Dr. Louis Renzetti, Head of RNA Therapeutics at Roche, said "We are enthusiastic about the potential of RNAi therapeutics for patients with hard-to-treat diseases. We believe Tekmira's SNALP is the leading lipid nanoparticle delivery technology and we are confident that Tekmira's research and manufacturing capabilities will help us to meet our product development objectives."

Roche will use Tekmira's SNALP technology for two RNAi product candidates. Each of the product candidates will be comprised of Roche proprietary small interfering RNAs (siRNAs) encapsulated in a Tekmira proprietary SNALP formulation. Roche and Tekmira expect an IND for the first product candidate to be filed before the end of 2010.

Tekmira will develop and manufacture the drug product for use in all preclinical studies and both companies will collaborate on the preclinical testing. The agreement also provides that Tekmira will manufacture one batch of clinical product for a phase 1 clinical trial.

About RNAi and SNALP

RNAi drugs have the potential to treat human diseases by "switching-off" disease causing genes. The technology, representing one of the most promising and rapidly advancing frontiers in biology and drug discovery, was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi drugs, such as siRNA, require delivery technology to be administered systemically. In preclinical studies, Tekmira's SNALP (stable nucleic acid-lipid particles) technology has been shown to be a safe and effective way to deliver RNAi drugs to disease sites. Tekmira believes it has a leading intellectual property position in the field of siRNA delivery.

About Tekmira

Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle delivery technology to pharmaceutical partners. Further information about Tekmira can be found at www.tekmirapharm.com. Tekmira is based in Vancouver, B.C.

SOURCE: Tekmira Pharmaceuticals Corporation

[Fruehrentner]

Antwort auf Beitrag Nr.: 37.153.243 von Fruehrentner am 12.05.09 13:06:29

TEKMIRA Chart

Auf WO gibts noch keine thread zu TEKMIRA.

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 37.153.261 von Fruehrentner am 12.05.09 13:08:10

Vermutlich weil die deutsche Anlegerschaft mit Antisense nix am Hut hat. Leider muss man sagen, dann im Gegensatz zu den deutschen Schrottbios (durch die Bank), werden hier Partnerschaften am laufenden Band gegründet. Und zugegeben, in DL gibt es auch wenig zum investieren in Antisense. Und es gibt bereits zahlreiche zugelassene WS bei den Antisense. Das Prinzip funktioniert also. Probleme bilden die Carrier, die aber gelöst werden.

[aktianer]

50%-Joint-Venture Tochter (andere 50% asn Regulus hält ISIS), erhält Meilensteinzahlung von Glaxo:

On Thursday May 14, 2009, 7:00 am EDT
Regulus Therapeutics Achieves Initial Milestone in its Inflammatory Diseases Collaboration with GlaxoSmithKline

First demonstration of a target-specific pharmacological effect for a microRNA antagonist in immune cells

CARLSBAD, Calif.--(BUSINESS WIRE)--Regulus Therapeutics Inc. today announced that it achieved the initial milestone with GlaxoSmithKline (GSK) as part of their ongoing worldwide strategic alliance established to discover, develop and market novel microRNA-based therapeutics to treat inflammatory diseases. The two companies are working to identify drugs directed at four different microRNA targets related to inflammatory disease. Regulus has now reached an important discovery milestone, which triggered a payment, concurrent with the first demonstration of a pharmacological effect in immune cells by specific microRNA inhibition. Scientists successfully delivered specific microRNA inhibitors, known as anti-miRs, to mice and clearly identified changes in expression of the genes regulated by the microRNA in immune cells.

“This milestone is further evidence that microRNAs represent disease targets whose therapeutic modulation could revolutionize the way we treat immune diseases,” said Peter S. Linsley, Ph.D., Chief Scientific Officer at Regulus. “We believe that we are the leaders in microRNA and are delighted to have such a good partner as GSK supporting the translation of our groundbreaking research into therapeutic opportunities. We are particularly pleased that this has been achieved in the first year of the collaboration.”

The Regulus-GSK alliance, which has a potential value of nearly $600 million, was established in April 2008 to focus on inflammatory diseases. Regulus is responsible for the development of antagonists to four microRNA targets from discovery through completion of clinical proof of concept. GSK has an exclusive license for worldwide development and commercialization of drugs developed by Regulus under each program for the relevant microRNA. The alliance combines Regulus’ unique expertise and comprehensive intellectual property estate in the microRNA therapeutics field with GSK’s extensive inflammatory disease expertise.

http://finance.yahoo.com/news/Regulus-Therapeutics-Achieves-…

[Fruehrentner]

News aus der RNAi-Branche:


RXi Pharmaceuticals Reports Financial Results for the First Quarter of 2009

WORCESTER, Mass.--(BUSINESS WIRE)--May. 15, 2009--

RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today reported results for the quarter ended March 31, 2009.

Tod Woolf, Ph.D., President and Chief Executive Officer of RXi, commented, “We have begun 2009 with two significant external validations of our RNAi therapeutic platform; the publication of our in-licensed oral delivery technology in Nature by our founder Michael Czech, Ph.D., and the award of a RXi/UMass grant from the Massachusetts Life Sciences Center to further support this breakthrough research that has the potential to address multiple multi-billion dollar anti-inflammation therapeutic markets. Additionally, our internal research team has made dramatic breakthroughs with our self-delivering rxRNA™ compounds, which we believe have the potential to help us realize our goal of becoming the technology leaders in the RNAi therapeutics space.”

Corporate Highlights:

Ramani Varanasi, MS, MBA joined RXi as Vice President of Business Development - Ms. Varanasi was most recently the Head of Business Development at Archemix Corporation, where she was responsible for and led a $600 million partnership between Merck Serono and Archemix, prior to which she held senior management/Business Development positions at Momenta and Millennium. Ms. Varanasi has more than 15 years of experience in executing strategic alliances and in providing business development and strategic leadership in the biopharmaceutical industry.
RXi added two more members to its Board of Directors, Richard Chin, M.D. and Rudolph Nisi, M.D.
Dr. Chin brings experience from some of the world’s leading drug development companies, including Genentech, Procter and Gamble Pharmaceuticals, Elan Pharmaceuticals and The Institute for OneWorld Health, a nonprofit pharmaceutical company developing drugs for neglected diseases in developing countries. He has overseen over 40 programs bringing new drugs into the clinic and 8 new drug applications/biologic license applications. Dr. Chin received a law degree with honors from Oxford University under a Rhodes Scholarship and holds a B.A. in Biology and a Medical Degree from Harvard University.
Dr. Nisi is a prominent cardiologist and the Chairman of the Board of New York Westchester Square Medical Center. He co-founded Medco Research, which was later acquired by King Pharmaceuticals, based on the widely used ambulance drug, Adenocard®. He has extensive experience in healthcare as a practicing physician and hospital board member and will contribute significantly to RXi and the application of our technology to medicine.
The Massachusetts Life Science Center awarded a Collaborative Research Grant – The funds will be used for research studies using RXi’s rxRNA™ compounds and our in-licensed oral delivery technology developed by the University of Massachusetts Medical School (UMMS) and published in Nature that encapsulates the rxRNA™ compounds with micron-sized particles.
RXi secured a $25 million committed standby equity agreement with YA Global Investments – This agreement provides RXi the ability to raise capital on terms that we believe are favorable, while giving us the financial flexibility to move our product programs towards the clinic.
Scientific Achievements:

RXi announced a publication in Nature of positive pre-clinical data demonstrating that administration of RNAi therapeutics effectively reduces systemic inflammatory response - In this publication, low dose (20 μg/kg) oral administration of RNAi therapeutics resulted in a significant reduction of a systemic inflammatory response in an established mouse model of inflammation (Aouadi, et al, Nature, Vol. 458 (7242), pp. 1180-1184). RXi has the exclusive worldwide rights to certain patent applications relating to this delivery technology based on a license agreement entered into with UMMS in October 2008.
RXi presented more data on its solo-rxRNA™ and self delivering-rxRNA™ compounds at the BioCentury Future Leaders in the Biotech Industry conference.
Solo-rxRNA™ compounds work via the RNAi mechanism but use a single sequence to achieve the same efficacy in pre-clinical models as traditional RNAi compounds. They are proprietary to RXi and we believe they are distinct from other intellectual property in the field, giving RXi novel scaffolding from which to develop new potential therapies.
Our proprietary self-delivering-rxRNA™ technology may enable the development of RNAi therapeutics to a variety of gene targets without the use of a delivery vehicle, potentially resulting in greater efficacy along with lower costs and side effects. Additionally, RXi believes that self-delivering rxRNA™ should support subcutaneous versus IV administration, which is a necessity for many clinical applications.
Multiple patent applications were filed encompassing the breakthrough discoveries of RXi’s research team relating to novel rxRNA™ compound chemistries and RNAi delivery technologies, further enhancing RXi’s intrinsic value and laying the foundation for technology platforms that we believe can lead the RNAi therapeutic space in the years ahead.
RXi scientists presented “Delivery to Macrophages and Efficacy of Glucan Particle Administered RNAi Compounds”, at the Keystone Symposia on Molecular and Cellular Biology conference “The Biology of RNA Silencing”, reproducing and building on the work published in the April 30th Nature publication.
A keynote address at this scientific conference was delivered by RXi’s founder and Scientific Advisory Board Chairman, Dr. Craig Mello, the recipient of the 2006 Nobel Prize in Medicine for his co-discovery of RNAi. Other key members of RXi’s management and scientific advisory team also presented at the conference.
RXi scientists and advisors have also presented at many other scientific conferences this quarter often being invited to give keynote addresses or contribute as chairpersons or scientific advisors.

Financial Highlights:

The Company reported a net loss of $4.2 million, or $0.30 per share, for the three months ended March 31, 2009, compared to a net loss of $2.6 million, or $0.21 per share, for the same period in 2008. The Company had 13,821,629 common shares outstanding at March 31, 2009, as compared to 12,684,432 common shares outstanding at March 31, 2008.

Research and development expenses for the three months ended March 30, 2009 were $1.4 million, including approximately $0.2 million in stock based compensation, compared to $1.1 million including $0.2 million in stock based compensation, for the three months ended March 30, 2008. The increase of $0.3 million, or 30.0%, was primarily due to higher employee compensation costs, as well as an increase in legal expenses related to patent applications on internal discoveries. General and administrative expenses for the three months ended March 30, 2009 were $2.8 million, including $1.5 million in stock based compensation, compared to $1.6 million, including $0.4 million in stock based compensation, for the three months ended March 30, 2008. The increase of $1.2 million, or 69.0%, was primarily due to non-cash costs associated with warrants issued for business advisory services.

As of March 30, 2009, cash and cash equivalents totaled $7.2 million, compared to cash, cash equivalents, and short term investments of $9.9 million at December 31, 2008. This decrease is due primarily due to cash used in operations of $2.7 million for the three months ended March 30, 2008.

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals is a discovery-stage biopharmaceutical company pursuing the development and potential commercialization of proprietary therapeutics based on RNA interference (RNAi) for the treatment of human diseases. RXi Pharmaceuticals has a comprehensive RNAi platform that includes both RNAi compounds and delivery methods. RXi Pharmaceuticals' rxRNA™ compounds are distinct from the siRNA compounds used by many other companies developing RNAi therapeutics and are very active and potent (10-100pM activity in cell culture) based on the company’s internal research, in addition to being nuclease resistant and readily manufactured. RXi Pharmaceuticals believes it is well positioned to compete successfully in the RNAi-based therapeutics market with its accomplished scientific advisors, including Dr. Craig Mello, recipient of the 2006 Nobel Prize for his co-discovery of RNAi; a management team that is experienced in developing RNAi products; and a strong early intellectual property position in RNAi chemistry and delivery. www.rxipharma.com

[Fruehrentner]

News aus der RNAi-Branche:


MDRNA Reports Its Proprietary RNAi-Based Compounds Are Well Tolerated and Demonstrate High Potency Against Multiple Targets in Preclinical Studies

19 May 2009

Data Confirm 90% Knockdown of Factor VII at 1 mg/kg With Duration of Effect up to 28 Days

BOTHELL, WA, USA | May 19, 2009 |

MDRNA, Inc. (NASDAQ: MRNA) announced today positive in vivo efficacy data showing that its proprietary UsiRNA constructs are highly potent and highly specific against ApoB and Factor VII message. The data are being presented today by Michael V. Templin, Ph.D., Vice President, Discovery Research and Pharmaceutical Development of MDRNA, at the TIDES Oligonucleotide and Peptide(R) Technology and Product Development Conference in Las Vegas, Nevada.

"Data from recent in vivo studies using our UsiRNAs targeting ApoB message confirm that RNA interference is the mechanism of action by which knockdown occurs, giving us high confidence that our UsiRNAs work by a sequence-specific mechanism," stated Barry Polisky, Ph.D., Chief Scientific Officer of MDRNA. "Data from the Factor VII studies indicate that a siRNA in our lead formulation achieved greater than 90% knockdown at 1 mg/kg with duration of effect of up to 28 days. This level of inhibition and duration of effect meets or exceeds published data for Factor VII."

Dr. Polisky added, "Data from rodent studies with our DiLA2 delivery system also continue to show encouraging results, with potency, specificity and duration of effect data now achieved for four independent liver targets, including ApoB, PCSK9, DGAT2 and Factor VII. The absence of histological changes in the liver with doses up to 9 mg/kg in rodents confirms that our DiLA2 liposomes are well tolerated."


About UsiRNAs

UsiRNAs are duplex siRNAs that are modified with non-nucleotide acyclic monomers, termed unlocked nucleobase analogs (UNA), in which the bond between two adjacent carbon atoms of ribose is removed. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity. Placement of UNA within UsiRNA minimizes the potential for off-target effects by the guide strand as well as undesired activity of the passenger strand. Further, the change in sugar structure renders this unlocked nucleobase analog conformationally flexible. The flexibility of the monomer escapes the body's surveillance mechanisms associated with cytokine induction, as well as providing protection from nuclease degradation.

About the DiLA2 Delivery Platform

DiLA2 is MDRNA's proprietary platform technology for creating novel liposomal delivery systems from amino acids. The platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids in order to optimize the liposome for delivery to the target tissue of interest. In addition, the platform is designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics. In addition, MDRNA is utilizing peptides for nanoparticle formulations to increase cellular uptake and endosomal release.

About MDRNA, Inc.

MDRNA is a biotechnology company focused on the development and commercialization of therapeutic products based on RNA interference (RNAi). Our goal is to improve human health by combining novel RNAi-based compounds and proprietary peptide- and liposomal-based drug delivery technologies to provide superior therapeutic options. Our multi-disciplinary portfolio of capabilities includes molecular biology, cellular biology, formulation expertise, peptide and alkylated amino acid chemistry, pharmacology, toxicology and bioinformatics. We are applying this expertise to a single, integrated drug discovery platform that will be the engine for our clinical pipeline and a versatile platform for establishing broad therapeutic partnerships. We are also building on new technologies, such as UsiRNAs that incorporate the non-nucleotide moiety Unlocked Nucleobase Analog (UNA) within the siRNA molecule, that we expect to lead to safer and more effective RNAi-based therapeutics. By combining broad expertise in siRNA science with proven delivery platforms and a strong and growing IP position, MDRNA is well positioned as a leading RNAi therapeutics company and value-added collaborator for our research partners. Additional information about MDRNA, Inc. is available at http://www.mdrnainc.com.

SOURCE: MDRNA, Inc.

[Fruehrentner]

news aus der RNAi Branche:


RXi Pharmaceuticals Presented Breakthrough RNAi Delivery

Technologies at the TIDES(R) 2009 Conference

WORCESTER, Mass.--(BUSINESS WIRE)--May. 21, 2009--

RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced that the Company’s Chief Scientific Officer, Anastasia Khvorova, Ph.D., presented new pre-clinical data on novel RNAi therapeutic approaches at IBC’s TIDES Oligonucleotide and Peptide® Technology and Product Development Conference in Las Vegas, Nevada. This conference is one of the longest-running, most prestigious conferences on oligonucleotide-based therapeutics, a field of drug development that includes RNAi. The conference was not webcasted.

Regarded as a revolutionary discovery in biology, RNA interference (RNAi) is a naturally occurring mechanism whereby short, double-stranded RNA molecules interfere with the expression of genes in living cells. RXi’s world-leading scientists have made significant advancements in this technology and Dr. Khvorova presented new forms of potential RNAi drugs with improved therapeutic properties.

Tod Woolf, Ph.D., President and CEO of RXi Pharmaceuticals commented: “Our research team is making significant progress, and I am very impressed with the amount of robust scientific data generated by our laboratory. The breakthrough technologies presented yesterday by Dr. Khvorova have the potential to address multiple multi-billion dollar therapeutic markets, may lead to improved therapeutics for many currently untreatable diseases and will help RXi realize its goal of becoming the technology leaders in the RNAi therapeutics space.”

RXi presented data on the following therapeutically advanced RNAi compounds and delivery technologies:

Glucan Encapsulated RNAi Particles (GeRPS) – The GeRP technology delivers RNAi compounds directly to macrophages. RXi has been building on the work published in an April 30th Nature article reporting positive pre-clinical data demonstrating that administration of RNAi therapeutics effectively reduces systemic inflammatory response. RXi has brought the GeRP technology in-house, established manufacturing in its own laboratory and has advanced the technology to the level necessary for further pre-clinical development.
Self-delivering RNA (sdRNA) – The proprietary self-delivering-rxRNA™ technology promotes spontaneous cellular uptake of the RNAi therapeutic, which is similar to the uptake of traditional small molecule drugs. Without the use of an additional delivery vehicle, this RNAi delivery technology potentially results in greater efficacy along with lower costs and side effects attributed to a delivery formulation. RXi believes that self-delivering rxRNA™ should support direct application or subcutaneous administration, opening the door for many clinical areas of RNAi therapeutic development.
Advancements to rxRNA™ compounds – Improvements have been made to rxRNA™ compounds allowing them to work in concert with the new delivery technologies. Efficient cellular uptake is critical for an effective therapeutic and advancements have been made to minimize rxRNA™ compounds to improve delivery. These minimized compounds also reduce the immune response and are easier and less costly to manufacture. These advancements are proprietary to RXi and encompass novel and unconventional chemistries when compared to the current siRNA molecules.
The combination of these new advanced technologies may enable RXi to discover and develop drugs for multiple indications and to build a sustainable pipeline of products for unmet medical needs.

http://www.rxipharma.com/news_press_releases.html

[Berliner_Landstreicher]

Oh das ist gut. Aber trotzdem noch nicht zu den Schnapsgläsern greifen.

Delivery ist noch eine der größten Herausforderungen, der sich die gesamte Branche stellen muss. Wie ich sehe ist der ALNY Thread auch gleichzeitig der deutschsprachige Anbtisense Thread. Bisher dachte immer der Girindus Thread erfüllt diese Aufgabe. Werde diese Info mal auch in den GIR Thread stellen.

[Fruehrentner]

news vom Wettbewerber:


03.06.2009 13:05:00

SILENCE THERAPEUTICS PLC - Statement re Approval for Clinical Trial

Silence Therapeutics receives approval to initiate Phase I clinical trials on Atu027 for treatment of patients with advanced solid tumours

London - June 3, 2009 - Silence Therapeutics plc (AIM: SLN) ("Silence" or "the
Company"), the leading European biopharmaceutical company focused on RNA
interference (RNAi), announces that its Clinical Trial Application (CTA) for
Atu027, its lead drug candidate, has been cleared by the German regulator
Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM).

The planned trial will be a prospective, open-label, single-centre,
dose-finding Phase I study with Atu027 in patients with advanced solid
(malignant) tumours involving single as well as repeated intravenous
administration.

The trial will be conducted at the clinical study centre of the Cancer Hospital
SanaFontis in Freiburg, Germany and will address safety, tolerability and
pharmacokinetics. Silence has already received approval from the Ethics
Committee and the trial, which is expected to take approximately 18 months to
complete, will commence immediately following successful patient enrolment.

Atu027 specifically targets PKN3, a molecule involved in cancer growth and
metastasis formation. Atu027 is Silence's most advanced clinical candidate for
a systemically delivered short interfering RNA (siRNA) using the Company's
proprietary AtuPLEX delivery technology. The compound is a potential new
therapeutic option for patients with advanced solid tumours that do not
adequately respond to standard therapy.

Iain Ross, chairman and chief executive of Silence Therapeutics, said:

"We welcome the decision by the German regulator to allow Silence to take
Atu027 forward into Phase I clinical testing. This marks a further step in the
development of Silence's science towards commercialisation and underscores the
company's strength in the field of RNAi."

Klaus Giese, Chief Scientific Officer of Silence Therapeutics, added:

"We are very excited at the prospect of commencing Phase I testing of Aut027 in
subjects with advanced solid tumours. We believe that our AtuPLEX delivery
system can be applied for the delivery of different siRNAs for several targets
in indications that are connected with angiogenesis, which is key to tumour
growth and metastasis."

- Ends -

Enquiries:

For further information, please contact the following:

Silence Therapeutics plc Powerscourt

44 (0) 20 7491 6520 [phone]

Iain Ross, Chairman & CEO Paul Durman

Kay Larsen

Nominated Advisers

Nomura Code Securities Limited

[phone]

Richard Potts

Notes to editors

About Atu027

Atu027 is Silence's lead internal product. It specifically targets PKN3, a
molecule involved in cancer growth and metastasis formation. Silence's
liposomal complex (siRNA-lipoplex) targets the vascular endothelial cell
compartment delivering PKN3-siRNA into the cytoplasm of endothelial cells,
where it acts catalytically on PKN3 mRNA via the gene silencing mechanism.

Silence submitted the Clinical Trial Application for Atu027 in December 2008
having successfully completed single and repeat dose toxicology and
geno-toxicology studies, as well as a 28-day toxicology study using multiple
dosing regimens.

About the trial

The trial will be conducted at the clinical study centre of the Cancer Hospital
SanaFontis in Freiburg, Germany. The Cancer Hospital SanaFontis is an
international centre for holistic cancer therapy and clinical cancer research.
Both out- and in-patients of the hospital have the option to participate in
studies that investigate innovative therapies, provided the patients can be
expected to benefit from the treatment and there are no further therapy options
open to them.

The trial will be an open-label , single-centre, dose-finding Phase I study
with Atu027 in subjects with advanced solid tumours involving single as well as
repeated intravenous administration. An open-label trial is a trial in which in
which both the researchers and participants know which treatment is being
administered.

The trial will address safety, tolerability and pharmacokinetics.
Pharmacokinetics is the study of the way the body interacts with a particular
drug, including the mechanisms of absorption and distribution, the rate at
which a drug action begins and the duration of the effect, the chemical changes
of the substance in the body and the effects and routes of excretion of the
metabolites of the drug.

About Silence Therapeutics plc (www.silence-therapeutics.com )

Silence Therapeutics plc (AIM: SLN) is a leading European RNAi-focused
biotechnology company.

RNA interference (RNAi), is a Nobel Prize winning technology and one of the
most exciting areas of drug discovery today. It represents a completely new
approach to selectively 'silence' or inactivate disease relevant genes and as
such it has the potential to create a new class of therapeutic products. RNAi
could therefore offer a therapeutic approach to a broad range of diseases
(cancer, infectious diseases, inherited diseases), many of which have been
regarded as incurable and are not addressed by current therapeutics, therefore
providing a large market opportunity.

Silence Therapeutics has developed a platform of novel short interfering RNA

('siRNA') molecules, AtuRNAi, which provide a number of advantages over
conventional siRNA molecules, including increased stability against nuclease
degradation. In addition, the Company has developed a proprietary systemic
delivery system, AtuPLEX. This system enables the functional delivery of siRNA
molecules to targeted diseased tissues and cells, while increasing their
bioavailability and intracellular uptake.

Following the granting of its patents in Europe, the USA and Australia, Silence
Therapeutics is one of only two companies worldwide with a proprietary position
on composition of matter for siRNA therapeutics.

In March 2008 Silence Therapeutics announced a collaboration with AstraZeneca

(LSE: AZN) focused on the development of a range of novel delivery approaches
for siRNA molecules. Under the terms of the agreement both Silence Therapeutics
and AstraZeneca will be allowed to commercialize the truly novel delivery
systems that the two partners develop together.

Silence Therapeutics has granted a licence to AstraZeneca to develop novel
AtuRNAi therapeutics against five specific targets. This collaboration was the
first industry validation of the potential application of Silence Therapeutics'
proprietary AtuRNAi molecules and solidified the Company's leadership position
in field of RNAi therapeutics.

The Company's AtuRNAi technology also has been sublicensed to Pfizer via
Quark's license to them of the compound RTP-801i-14 for the treatment of
age-related macular degeneration (AMD) and a number of other indications. This
compound entered a phase II clinical study in July 2008. Silence Therapeutics
also has licensed to Quark rights to the AtuRNAi structure for Quark's
proprietary compound, AKIi-5, which is in a Phase I human clinical study for
treatment of acute kidney injury.

Forward-Looking Statements

This press release includes forward-looking statements that are subject to
risks, uncertainties and other factors. These risks and uncertainties could
cause actual results to differ materially from those referred to in the
forward-looking statements. All forward--looking statements are based on
information currently available to Silence Therapeutics and Silence
Therapeutics assumes no obligation to update any such forward-looking
statements.

Silence Therapeutics is based in London, UK, and Berlin, Germany, and is listed
on AIM.

END

Quelle:PR NEWSWIRE

[Berliner_Landstreicher]

Alnylam, Cubist: Drug meets midstage safety goals

http://finance.yahoo.com/news/Alnylam-Cubist-Drug-meets-apf-…

[aktianer]

Antwort auf Beitrag Nr.: 37.346.759 von Berliner_Landstreicher am 08.06.09 20:08:46

Ergebnis wird an der Börse ziemlich negativ aufgenommen wegen Zweifel, ob der Wirkstoff tatsächlich effizient ist.


Nach einer Morgan Stanley-Einschätzung der Resultate und Übersicht über den weiteren Gang des RSV-Programms durch den Partner Cubist hat sich der Kurs dann etwas gefangen.

Aber hier dier Morgan Stanley - Einschätzung (aus Investorvillage)


Morgan Stanley view

Alnylam Pharmaceuticals

RSV Data Further Validates

Technology Potential but Path Forward Needs Clarity

Impact on our views: Our take on the Phase II RSV data is positive as it further validates the potential of the RNAi technology platform, the key driver of our Overweight thesis. The data shows that ALN-RSV01 can be given very safely to a complicated patient population, which we view as a significant de-risking step in developing RNAi as a drug class. Additionally, it increases the attractiveness of the technology for partners – we continue to expect two deals in 2009.

However, the data does little to define the path forward in the RSV program itself. While the study
met the primary endpoint of safety and tolerability, the lack of clarity on the efficacy data makes it hard to gauge how the program moves forward. Based on our research and discussions with Management, we believe that four more sets of data are likely needed (see below) before the potential of ALN-RSV01 is understood.

What is needed to define the next steps? The data sets which are needed are:

1) 90-day data from the current lung transplant trial to better understand safety,
2) a larger Phase II study in adults to understand efficacy,
3) data from the ongoing dosing study in adults (multiple doses and longer exposures) and
4) a safety study in pediatrics – before conducting a larger efficacy trial.

We expect greater visibility by year-end 2009,
based on the 90 day follow up and dosing study data.

What's new: Preliminary Phase II data from the inhaled ALN-RSV01 trial in 24 adult
lung transplant patients (16 active, 8 placebo – treated for 3 days) with RSV infection.

Data summary in Exhibits 1 and 2.
Key milestones:
1) full lung transplant and dosing study data in 2H09,
2) updates on development strategy for RSV program, and
3) potential partnerships.

http://www1.investorvillage.com/smbd.asp?mb=569&mn=20074&pt=…

[aktianer]

Antwort auf Beitrag Nr.: 37.347.056 von aktianer am 08.06.09 20:31:17

auch zum Hypercholesterolprogramm scheint nun zumindest ein Konkurrenzverfahren von Amgen bei Mäusen erfolgreich zu sein; dennoch wird auch dem Ansatz Alny's als auch dem von ISIS Potential zugebilligt.

http://www.nature.com/scibx/journal/v2/n22/full/scibx.2009.8…

[Fruehrentner]

Alnylam and Collaborators Present New Pre-Clinical Research Findings on RNAi Therapeutics Targeting PCSK9, a Genetically Validated Regulator of LDL Metabolism

18 Jun 2009

New Data Include Use of Novel Lipid Nanoparticles with Markedly Improved Potency, Achieving a New Benchmark for Systemically Delivered RNAi Therapeutics

CAMBRIDGE, MA, USA | June 18, 2009 |
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the presentation of new pre-clinical data from its hypercholesterolemia program, performed in collaboration with the University of Texas Southwestern Medical Center at Dallas, at the XV International Symposium on Atherosclerosis 2009 held in Boston, Mass. from June 14-18, 2009. Alnylam’s ALN-PCS program is focused on using RNAi therapeutics targeting proprotein convertase subtilisin/kexin type 9, or PCSK9, as a novel strategy for reducing LDL (or “bad”) cholesterol. The newly presented data include results with novel lipid nanoparticles (LNPs), developed in collaboration with Tekmira Pharmaceuticals Corporation and University of British Columbia and exclusively licensed to Alnylam, that show significantly improved in vivo potency and the use of certain optimized dosing regimens that also improve potency and enhance durability. Further, the new research findings show that silencing PCSK9 with RNAi therapeutics results in no measurable decrease in HDL (or “good”) cholesterol.

“We are excited about the progress we’re making in our development efforts for ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. We remain convinced that this is an ideal target for the advancement of new medicines in this significant clinical indication,” said Kevin Fitzgerald, Ph.D., Director of Research of Alnylam. “A key highlight from our presentation is new data with a novel LNP that markedly improves efficacy for systemically administered RNAi therapeutics with effective doses for gene silencing at approximately 0.1 mg/kg. We believe that these LNPs achieve a new benchmark for the systemic delivery of RNAi therapeutics.”

The new research findings presented at the meeting include the following:

* in vitro data on the selectivity of PCSK9-specific siRNAs (or small interfering RNAs, the molecules that mediate RNAi), with no apparent silencing of likely off-target genes within the same cell line;
* in vivo rodent data on novel LNPs, showing improved efficacy with an approximately 50% gene silencing effect at doses of approximately 0.1 mg/kg;
* in vivo rodent data on sustained durability for PCSK9 silencing with reduction in total cholesterol levels of approximately 50% using an optimized maintenance dosing regimen; and,
* in vivo non-human primate data showing the absence of any measureable decrease in HDL cholesterol with PCSK9 RNAi therapeutics.

“I am very encouraged by these new data, which offer further support for an RNAi therapeutic strategy of targeting PCSK9 for the treatment of hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. “An RNAi therapeutic targeting this genetically validated gene has the potential to rapidly and durably lower LDL cholesterol, while preserving HDL cholesterol, and may also function synergistically with statins for the treatment of hypercholesterolemia.”

Human genetic studies have correlated increased levels of PCSK9 with an increased risk of cardiovascular disease (Abifadel et al., Nature Genetics, 34 (2): 154-6; 2003). Conversely, human genetic studies have confirmed a nearly 88% reduced risk of cardiac events in subjects with decreased levels of PCSK9 (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006). Alnylam is developing ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-PCS is a systemically delivered RNAi therapeutic comprised of an optimized siRNA encapsulated in an LNP.

Alnylam expects to file one additional investigational new drug (IND) application in 2009 from its development pipeline, with candidates including ALN-PCS, ALN-HTT for the treatment of Huntington’s disease, and ALN-TTR for the treatment of transthyretin (TTR) amyloidosis.


SOURCE: Alnylam Pharmaceuticals, Inc

[Popeye82]

[Fruehrentner]

Alnylam Joins GSK In Patent Pool For Neglected Tropical Diseases

Published:08-July-2009

RNAi technology could lead to new targets and treatments

Alnylam shall contribute more than 1500 issued or pending patents on its RNA interference (RNAi) technology patent estate, to the patent pool established by GlaxoSmithKline (GSK).

Alnylam to add its patents to approximately 800 patent filings that GSK provided to populate the pool in March. The company’s RNAi platform provides an approach to drug discovery and development through gene silencing.

Andrew Witty, Chief Executive Officer, GSK, said: “We are delighted that Alnylam will join GSK in this important programme by adding their unique RNAi technology to the patent pool.”

“The key objective of the pool is to make it easier for researchers across the world to access intellectual property that may be useful in the search for new medicines to treat neglected tropical diseases. The more companies, academic institutions and foundations that join the pool, the more effective it will be. Alnylam’s announcement today is therefore a welcome and significant step forward.”

The patent pool was formed to aid in the discovery and development of new medicines for the treatment of 16 neglected tropical diseases, as defined by FDA.

[Fruehrentner]

Alnylam and Cubist Announce Complete Data from Phase II Study of ALN-RSV01 in Lung Transplant Patients Naturally Infected with Respiratory Syncytial Virus

20 Jul 2009

90 Day Data Confirm ALN-RSV01 Meets Primary Study Objective of Safety and Tolerability

CAMBRIDGE, MA. & LEXINGTON, MA, USA | Jul 20, 2009 |

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and Cubist Pharmaceuticals, Inc. (Nasdaq: CBST), an acute care focused therapeutics company, today reported complete data from their Phase II study of ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection. Data were presented at the BIT Life Science's 2nd Annual Summit of Antivirals held in Beijing, China from July 18 - 25, 2009. The Phase II study was a randomized, double-blind study of inhaled ALN-RSV01 or placebo in adult lung transplant patients naturally infected with RSV. Clinical evaluations at 90 days confirmed that the primary objective of safety and tolerability was achieved.

In the Phase II study, conducted at 11 sites in 4 countries, 24 lung transplant patients with confirmed RSV infection were randomized to receive inhaled ALN-RSV01 (N=16) or placebo (N=8) once daily for three consecutive days. Overall, the study achieved its primary objective of demonstrating safety and tolerability of ALN-RSV01. In particular, there were no drug-related serious adverse events or discontinuations, and there were no clinically significant differences in the overall adverse event profile between ALN-RSV01 and placebo. Importantly, there was no evidence of disease exacerbation related to ALN-RSV01 treatment. At the 90 day endpoint, all patients survived and the incidence of intubation, new respiratory infection, or acute rejection was comparable across ALN-RSV01 and placebo groups.

In addition, new 90 day clinical data were collected, although the study was not powered for these outcomes due to the small sample size, and they were therefore considered exploratory. Related to these 90 day data, key prospectively defined clinical secondary endpoints included recovery of lung function (forced expiratory volume in the first second, or FEV1) as measured by spirometry and clinical determination of new or progressive bronchiolitis obliterans syndrome, or BOS. Baseline measurements of FEV1 were obtained from patient records prior to their RSV infection. In the study, FEV1 measurements were obtained at screening and at day 90 in order to determine the percentage of patients with FEV1 at least 20% below baseline at those time points. Thirty-eight percent of placebo patients had an FEV1 at least 20% below baseline at day 90 compared to only 14% of ALN-RSV01-treated patients (p=NS). BOS scoring was based on the decline in FEV1 during the study as well as the physicians' determination of whether there was a cause other than BOS responsible for a change in FEV1. In the study, ALN-RSV01 treatment was associated with a statistically significant decrease in the total incidence of new or progressive BOS at 90 days compared to placebo (p=0.02); 50% of placebo patients showed new or progressive BOS as compared with only 7.1% of ALN-RSV01-treated patients.

"We are very pleased with the outcome of this study, which demonstrated for the first time the safety and tolerability of inhaled ALN-RSV01 in naturally infected patients," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research of Alnylam. "As such, these data provide important de-risking for the advancement of our overall ALN-RSV program. While the study was not powered for efficacy and is too small to make firm conclusions, we are encouraged by the 90 day clinical endpoint data, including improvement in lung function and a statistically significant reduction in new or progressive BOS in patients receiving ALN-RSV01 as compared with placebo."

"We are encouraged by these important safety results and other findings in this program in support of the continued advancement of our overall ALN-RSV program," said Steven C. Gilman, Ph.D., Senior Vice President, Chief Scientific Officer, for Cubist Pharmaceuticals. "We are in the process of reviewing data from these and other studies related to specific plans for the advancement of our RSV program and look forward to providing further guidance on our specific plans later this year."

Key 90 day safety and clinical data are provided in the table below:


Day 90 Outcomes: ALN-RSV01 vs. Placebo
Day 90 Outcome ALN-RSV01 Placebo P-value
(N=15) (N=8)

Survival 100.0% 100.0% NS
Intubation 0.0% 0.0% NS
Acute Rejection 13.3% 12.5% NS
Respiratory Infections After Day 30 26.7% 12.5% NS
Patients with FEV1 at least 20% below baseline*
Screening 33.0% 29.0%
Day 90 14.0% 38.0% NS
Change in BOS from Baseline:
Total New Onset or Progressive 7.1% 50.0% 0.02
*Baseline data are pre-infection FEV1 values for each patient

"The full data set confirms that ALN-RSV01 is safe and well tolerated in a naturally infected patient population with RSV and, specifically, in lung transplant patients," said Professor Allan Glanville, M.B., B.S., M.D., FRACP, Director of Thoracic Medicine, St. Vincent's Hospital, Sydney, and Principal Investigator for the trial in Australia. "RSV infection remains a significant cause of morbidity and even mortality in lung transplant patients due to the potential for severe pneumonia and both acute and chronic lung rejection. Specifically, RSV infection is linked to the development or progression of BOS, an irreversible disease of the transplanted lung resulting in approximately 50% mortality within three to five years of onset. Clearly, new medicines for the treatment of RSV infection are greatly needed for these patients."

The companies plan to evaluate these and additional data from the broader ALN-RSV program, including its second-generation compounds, to determine the optimal development strategy and specific plans for all RSV indications.

Alnylam's partnership with Cubist is a 50-50 co-development and profit share arrangement in North America, and a milestone- and royalty-bearing license arrangement in the rest of the world outside of Asia, where ALN-RSV is partnered with Kyowa Hakko Kirin.

[mitleser3108]

Glaube ich zwar nicht, dennoch interresant:

[http://boston.bizjournals.com/boston/blog/bottom_line/2009/0…

[mitleser3108]

Antwort auf Beitrag Nr.: 37.938.016 von mitleser3108 am 08.09.09 14:06:42

http://boston.bizjournals.com/boston/blog/bottom_line/2009/0…

[Fruehrentner]

Antwort auf Beitrag Nr.: 37.938.016 von mitleser3108 am 08.09.09 14:06:42

http://boston.bizjournals.com/boston/blog/bottom_line/2009/0…


so ist's richtig

[mitleser3108]

Antwort auf Beitrag Nr.: 37.938.457 von Fruehrentner am 08.09.09 14:59:04

bitte um aufklärung: wie bindet man einen link richtig ein?

[aktianer]

Antwort auf Beitrag Nr.: 37.939.755 von mitleser3108 am 08.09.09 16:56:06

Hallo,

Link kopieren, anschließend diesen einfügen in Deinen Post, danach die eingefügte Adresse mit der Maus markieren und dann Button "URL einfügen" (den Button findest du links unter den Werkzeugen) drücken. Fertig!

[mitleser3108]

Antwort auf Beitrag Nr.: 37.940.077 von aktianer am 08.09.09 17:32:47

Danke, dafür noch einen Link, meiner Meinung nach eine der besten Quellen zum Thema, hat fast ein Jahr Pause gemacht, jetzt aber wieder zurück.

http://rnaitherapeutics.blogspot.com/

[mitleser3108]

Alnylam Announces Allowance in Europe of New Fundamental Patent Broadly Covering RNAi Therapeutics in Oncology

http://www.reuters.com/article/pressRelease/idUS117135+09-Se…

[dottore]

10. September 2009 06:39
Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, announced today that the European Patent Office (EPO) has issued a notification of intent to grant for a patent in the Kreutzer-Limmer III patent series (EP Application No 02702247.4).

Ich bin nicht investiert. Da der Kurs sich in diesem Jahr schon verdreifacht hat, werde ich vom her zusehen.
Good luck

[mitleser3108]

Antwort auf Beitrag Nr.: 37.953.743 von dottore am 10.09.09 12:49:44

verdreifacht ???????????????
30.12.2008: 16,47 €
heute: 14,96 €

[mitleser3108]

In Ongoing Tuschl IP Row, USPTO OKs Planck’s Request to Pull Power of Attorney from Whitehead
September 14, 2009
By Doug Macron

Although Alnylam Pharmaceuticals and the Max Planck Institute suffered a setback earlier this month in their lawsuit over rights to certain RNAi-related intellectual property, the two scored a victory last week when one of their gambits to stymie the prosecution of disputed patent applications succeeded.

In their suit, they allege that the University of Massachusetts, the Massachusetts Institute of Technology, and the Whitehead Institute for Biomedical Research have been inappropriately trying to incorporate certain RNAi inventions from the Tuschl-II patent estate into Tuschl-I patent applications.

In an effort to prevent the issuance of any Tuschl-I patents containing the disputed inventions, Max Planck asked the US Patent and Trademark Office to revoke the power of attorney it gave Whitehead for each patent application from that family, according to court documents. Whitehead has had this power since 2001.

If granted by the USPTO, Max Planck’s petition would allow it to “unilaterally … stop the ongoing prosecution of the jointly owned applications,” UMass last month told the US District Court hearing the case.

Now, it seems, the USPTO has done just that after deciding that it should not become an arbiter in the controversy.

According to a letter Alnylam and Max Planck’s attorneys filed with the court, “Max Planck filed petitions with the [USPTO] seeking permission to revoke each power of attorney that it had executed in favor of [Whitehead’s chosen law firm] to allow that firm to represent Max Planck’s interests in the prosecution of each of the [US] Tuschl-I patent applications pending.

“Max Planck learned … that the USPTO has granted each of these petitions,” the letter noted.

The litigation began in June when Alnylam and Max Planck sued UMass, MIT, and Whitehead for allegedly incorporating various features of the Tuschl-II IP, namely the use of 3’ overhangs on siRNAs, into Tuschl-I patent applications (see RNAi News, 7/9/2009).

Alnylam holds the exclusive rights to the Tuschl-II estate through a license from the IP's sole owner, Max Planck. However, the company shares therapeutic rights to the Tuschl-I estate — invented at Max Planck, Whitehead, MIT, and UMass — with Merck subsidiary Sirna Therapeutics (see RNAi News, 9/13/2003) and, to a limited degree, CytRx spinout RXi Pharmaceuticals.

The plaintiffs charged that if any Tuschl-II inventions are included in Tuschl-I patents, companies with access to Tuschl-I will "unfairly gain access to the Tuschl-II property without paying consideration for a license,” and said that the US Patent and Trademark Office was poised to grant a Tuschl-I patent.

In a bid to prevent that patent issuance, the plaintiffs asked the court for a preliminary injunction preventing the payment of issuance fees on any Tuschl-I application unless all the IP's co-assignees, including Max Planck, agree that the fee shall be paid — a move calculated to effectively halt the prosecution of Tuschl-I IP in the US (see RNAi News, 7/16/2009).


That effort failed earlier this month when the court denied the injunction request. In its response, the court said that Alnylam and Max Planck have “not shown a substantial likelihood of success” on the merits of their case, especially since Max Planck had previously authorized the inclusion of the dispute data in Tuschl-I filings (see RNAi News, 9/3/2009).

But Alnylam and Max Planck had another trick up their sleeves and asked petitioned the USPTO to pull the authorization Max Planck had given Whitehead to use the attorney of its choice in prosecuting Tuschl-I applications, which the patent office did earlier this month (see RNAi News, 8/27/2009).

Both UMass and Whitehead have asked the court to order Max Planck to withdraw its petitions to revoke power of attorney, but it is unclear whether the court can or will act. Meanwhile, the USPTO has sided with Max Planck on the issue.

According to a letter from the USPTO and provided to the court by the plaintiffs, “speculation that Max Planck is motivated by nefarious purposes and should not be able to appoint counsel of its choosing is not relevant since a party’s future intent is not considered by the USPTO in this situation.”

The patent office wrote that it is not “the best forum in which to determine a party’s intent. Such intent is best determined when the trier of facts can observe [the] demeanor of witnesses subjected to cross-examination … [and] a court, with subpoena power, is presently the best forum to consider such an issue.”

The USPTO noted that since the co-assignees of the Tuschl-I IP “have divergent interests, no one side can reasonably expect or be permitted to control the prosecution of [the] patent application [at issue] to the exclusion of the others. Furthermore, denying Max Planck the ability to choose its own counsel and requiring [it] to have its interests represented by an opposing party in litigation would not be appropriate for the USPTO.

“The ongoing disputes, including litigation … provide sufficient cause for Max Planck to revoke a power of attorney that it previously gave and an extraordinary situation where justice requires waiver of” existing USPTO regulations, the office added.

The patent office noted that further correspondence related to Tuschl-I applications must be signed by “registered practitioners” representing both Max Planck and the other co-assignees of the IP “in order to assure that all interests are properly and effectively represented.”

In its own letter to the court, Alnylam and Max Planck added that Whitehead and possibly the other defendants in the lawsuit are expected to appeal the USPTO’s decisions.

http://www.genomeweb.com/rnai/ongoing-tuschl-ip-row-uspto-ok…

[mitleser3108]

http://pubs.acs.org/cen/coverstory/87/8736cover.html

Delivering The Promise
Developing drugs based on RNA interference hinges on finding better ways to safely and potently get molecules into cells
Lisa M. Jarvis

[mitleser3108]

http://finance.yahoo.com/news/Alnylam-and-Medtronic-Present-…

[Fruehrentner]

Antwort auf Beitrag Nr.: 37.980.695 von mitleser3108 am 15.09.09 11:33:56

Danke für den link, auch wenn's etwas ernüchternd klingt, aber die problematik war ja schon länger bekannt.

[mitleser3108]

Antwort auf Beitrag Nr.: 37.981.645 von Fruehrentner am 15.09.09 13:19:10

ernüchternd einerseits schon, andererseits zeigt es auch wie überlegt alnylam hier vorgeht, d. h.

- RSV: Inhalation, kein "systemic delivery" notwendig
- Krebs und Cholesterin: Leber, relativ "einfach" für systemic delivery
- Huntington: Medtronic Pumpe für CNS

des weiteren die ganzen Kooperationen, z.B mit Tekmira oder dem Langer-Lab, so dass eventuell, wenn eines Tages bei systemischen Anwendungen mehr Organe erreichbar sind, auch hier wieder (wie in der RNAI selbst), ein breites Patentportfolio bei alny liegt

[Fruehrentner]

Heutige Meldung aus der RNAi-Branche:

RXi Pharmaceuticals' Self-delivering rxRNAs Demonstrate Superior Drug Properties Compared to Classic RNAi Compounds in Animal Studies

WORCESTER, Mass.--(BUSINESS WIRE)--Sep. 15, 2009

RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced that it will be presenting new in vivo data on its self-delivering rxRNA™ compounds at a number of upcoming scientific conferences, detailed below.

mehr: http://www.rxipharma.com/news_press_releases.html

[mitleser3108]

Antwort auf Beitrag Nr.: 37.986.631 von Fruehrentner am 15.09.09 22:38:30

danke für den Link, sehr interresant, habe auf deren Internet-Seite ein bisschen gestöbert, damit macht für mich "Alnylam and RXi: A match made in heaven?" auch mehr Sinn, nicht wegen der Manager/Targets/etc., aber wenn die "self delivery" technologie wirklich so gut ist, wie hier beschrieben: http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9M…, wäre das für Alnylam sicher interresant

[mitleser3108]

neues von Dirk Haussecker über ALNY:

Alnylam: As the bellwether of RNAi Therapeutics due to its IP position, maturing pipeline, strong balance sheet and a generally broad outlook on RNAi Therapeutics, a must for those (institutional) investors with significant funds to invest in the RNA Therapeutics space. Data from Alnylam’s Huntington’s Disease and RSV programs suggest that they have potential on their own, independent of how they contribute to the learning of RNAi for CNS and lung disorders in general. Surely, the hiring pattern of Big Pharma argues that the perception of RNAi as a therapeutic modality has not gone out of fashion there, immediately adding potential licensees to Alnylam’s leading RNAi trigger portfolio.


However, as it is delivery that potential licensees and investors are increasingly paying attention to and even cash-rich Big Pharma/Biotech will question whether it should spend $300M for an RNAi trigger license now that there have been a few decisions that did not go in Alnylam’s favor, I am not sure whether we will see a simple pre-packaged RNAi trigger platform deal. Rather, such IP access may be packaged with access to Alnylam’s know-how on the delivery, chemistry, and safety of RNAi Therapeutics, somewhat reminiscent of the Roche deal and the Kulmbach component. To set up such deals may take longer, but ultimately provide more value not only for the licensee, but also for Alnylam. Certainly, positive SNALP clinical data should prove as a catalyst for these negotiations and the stock.

für alle, die auch den Rest, über die anderen RNAI(und-related) Firmen lesen möchten:
http://rnaitherapeutics.blogspot.com/2009/09/run-down-of-com…

[mitleser3108]

http://rnaitherapeutics.blogspot.com/2009/09/important-decis…

News vom Wettbewerb, kommentiert von DH:

Important Decision for Silence Therapeutics Looms

In another sign that deal activity is also picking up in the RNAi Therapeutics space, Silence Therapeutics announced this morning that trading has been suspended awaiting the outcome of M&A talks with a private US investor group. It is not the first time that rumors around Silence Therapeutics have had a major influence on the trading of the stock. This time, however, there appears to be a factual basis for the rumors and if the deal materialized it would qualify as a reverse takeover according to the company.


It will be interesting to see whether the deal was negotiated from a position of strength or weakness, and whether there will be a change of scientific direction or IP strategy of Silence Therapeutics, one of the older players in the field. Clearly, their position should have been hampered due to their unfavorable cash and uncertain IP positions. A reverse takeover may thus allow the rumored private investor group from the US to access the public equity markets through Silence Therapeutics and at the same time re-capitalize the company. This may also mean that AtuRNAi will be replaced by another biotechnology as the company’s scientific foundation.


On the other hand, events over the last year may have given Silence Therapeutics investors increased confidence in their freedom-to-operate, and given that the phase I trial for solid cancers has just commenced, they may not want to give up their technology hopes just yet. The US investor group may thus gain access to Silence Therapeutics’ scientific and IP portfolio, although the money they would infuse into the company would mean that they are now the majority owners. A third scenario may be that the US investor group brings with it a complementary RNA Therapeutics asset, be it another set of RNAi triggers, targets (e.g. microRNAs) or delivery technology.


In any case, I am very curious to hear about the news as it should provide for some tantalizing insight into some of the dynamics moving the RNAi Therapeutics financial market. Tomorrow, at the latest, we should know more as the company was to announce its half-year report then.

[mitleser3108]

http://www.genomeweb.com/rnai/roche-using-snalps-first-rnai-…

Roche Using SNALPs with First RNAi Rx Candidate, Optimizing Internal Delivery Tech
September 29, 2009
By Doug Macron

A top Roche official confirmed this week that the company will file its first investigational new drug application for an siRNA therapeutic in 2010, and that the agent will be delivered using Tekmira Pharmaceuticals' stable nucleic acid lipid particles, rather than an in-house delivery technology.

Meanwhile, the Swiss drugs and diagnostics giant is taking a measured approach to the related but nascent microRNA field, exploring partnerships with key miRNA companies and doing a certain amount of research on its own, yet keeping most of its attention focused on RNAi, Lou Renzetti, global head of RNA therapeutics for Roche, told RNAi News.

One of the biggest pharmas playing in the RNAi space, Roche has long expected to advance its first drug based on the gene-silencing technology into human trials next year (see RNAi News, 2/14/2008).

Having acquired in 2007 the Kulmbach, Germany-based operations of Alnylam Pharmaceuticals — another Tekmira partner — as part of a broad drug-discovery and -development deal (see RNAi News, 7/12/2007), it was not unexpected that Roche's first RNAi drug would be siRNA-based.

Although Roche licensed Tekmira's SNALPs less than a year later (see RNAi News, 4/3/2008), its $125 million acquisition of Mirus Bio and its dynamic polyconjugate delivery technology in July 2008 suggested that the company was making its in-house portfolio of delivery solutions a priority.

And while Roche is focused on its own delivery technologies, being "first and best in class" is a top goal, Renzetti said. Using SNALPs with its first siRNA drug "would give us a chance to get a first-in-human study [underway], monitor target knockdown," and examine pharmacokinetics and pharmacodynamics.

Indeed, with SNALPs having already been administered, albeit to a limited degree, to humans — Tekmira recently began a phase I study of a SNALP-delivered siRNA drug for hypercholesterolemia (see RNAi News, 7/9/7009), just a few months after Alnylam began a phase I study of a liver cancer drug that incorporates the technology (see RNAi News, 4/9/2009) — the trail to the clinic has already been blazed for Roche.

The company could still evaluate the DPCs in humans in the relatively near future, possibly even with its lead RNAi drug candidate, but as it stands now, it is in the process of optimizing the delivery technology, since "we do not wish to take a first-generation DPC into the clinic," he noted.

At the same time, with DPCs, "we have evidence … of active targeting," Renzetti added. "So the question becomes, 'Which target cells would we like to go after for proof of concept?'" The additional optimization work would help establish that, he said.


Overall, Roche believes that the development of multiple RNAi drugs will require multiple delivery approaches, and "one challenge we're all going to face is the extrapolation to humans with these different delivery modules," Renzetti said. As such, just getting into the clinic is key because the data, "even if they were something that were not quite optimal … will be critical."

Renzetti noted that Roche is currently preparing for a pre-IND meeting with the US Food and Drug Administration, but declined to provide specific details about the siRNA drug candidate or its clinical-development plan.

He also declined to comment on additional RNAi programs in the pipeline, but noted that Roche's interests in the space continue to center around liver-associated metabolic diseases, respiratory disorders, and cancer.

microRNAs?

In early 2008, Lee Babiss, Roche's global head of pharma research, told RNAi News that the company was in talks about a possible miRNA drugs collaboration with an undisclosed company and that it was conducting "preliminary" research on agents targeting the small, non-coding RNAs.

This week, Renzetti said that Roche continues to monitor the field, and while it may not have actually consummated any kind of alliance, it did recently hold a partnering meeting with "several" unnamed miRNA companies.

"It's an exciting, evolving area … you just have to decide when to jump in," Renzetti said. "We also have to be careful that we don't distract ourselves from our primary effort right now in the siRNA space.

"There is going to be a time when we place a bet" on miRNA therapeutics, he added. Still, "we already placed one bet in the siRNA and delivery area," and the trick will be balancing the two.

Leading Roche to be a little cautious about miRNAs is the fact that their effects are so widespread, he noted.

With siRNAs, "you're looking at modulation of a single gene product or modulating several gene products very selectively," Renzetti explained. But with miRNAs, "when you modulate one, whether [with] agonists or antagonists, the consequences are not really known … [and] that's always the concern."

And that concern also extends to the diagnostic space, where miRNAs have already proven themselves to a certain degree with the commercialization of tests by Rosetta Genomics and Asuragen.

As one of the biggest diagnostic firms in the world, Roche is also weighing the potential to use miRNAs as biomarkers in various contexts, Renzetti said. "But again, when these things are changed within the cellular environment, do we understand enough about these that we can then make those claims?"

[mitleser3108]

http://www.xconomy.com/boston/2009/10/07/alnylam-chief-fores…
http://www.genomeweb.com/rnai/two-rnai-rx-shops-see-strong-g…

[Fruehrentner]

RXi Pharmaceuticals Presented New Pre-Clinical Animal Data at its Annual Investor Day

New Data Include Use of Novel sd-rxRNA™ with Improved Pharmacology with Both Local and Systemic Administration

WORCESTER, Mass.--(BUSINESS WIRE)--Oct. 8, 2009--

RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced the presentation of new preclinical data from its advanced RNAi therapeutic platform at its Annual Investor Event held in New York City on Monday, October 5, 2009.

The presented data include results with novel self-delivering (sd-rxRNA™) RNAi compounds, which do not require an additional delivery vehicle to enter cells. The data show significantly improved pharmacological properties of these molecules, with applicability in a broad range of therapeutic applications.

“We are excited about the progress we are making in our sd-rxRNA™ research efforts,” said Tod Woolf, Ph.D. President and CEO of RXi Pharmaceuticals. “A key highlight from our presentation was that recently obtained data with our proprietary sd-rxRNA™ markedly improves the delivery of systemically and locally administered RNAi compounds. RXi and our collaborators in RNAi consider advances in the delivery to be the most important factor for the successful commercialization of RNAi therapeutics. ”

RXi’s therapeutic platform leverages its Next Generation rxRNA™ compounds and advanced delivery technologies to enable its internal programs and external collaborations. This provides RXi with multiple opportunities for the potential development of a sustainable pipeline of RNAi based products for unmet medical needs.

Key findings and highlights from the event include the following:

* Dr. Craig Mello, Nobel Laureate and RXi’s co-founder and Chairman of its Scientific Advisory Board, provided novel insights into the RNAi mechanism which have aided in the design of RXi’s novel rxRNA™ compounds.
* Data presented on the length of compounds showed that reducing the size of RNAi compounds could be important for cellular uptake.
* sd-rxRNA™ compounds were shown to have improved pharmacological and drug-like properties compared to unmodified classic siRNA (short interfering RNA). Research findings on sd-rxRNAs show:
o Increased serum stability
o Improved retention in the circulation
o Minimal immune response activation
o Efficient cellular uptake and internalization to many diverse cell types
o Systemic delivery to the liver with effective gene silencing
o Local delivery via intradermal injection with effective gene silencing
* An update to the status of indications currently being pursued by RXi was provided:
o Compromised skin – RXi is performing animal studies based on positive data showing spontaneous uptake and enhanced tissue penetration with sd-rxRNA compounds.
o Inflammatory diseases – RXi is working with researchers from the University of Massachusetts to deliver rxRNA™ compounds using an advanced delivery vehicle that targets macrophage cells.
o Liver diseases – RXi is exploring sd-rxRNA™ delivery to the liver upon subcutanteous administration to animal models without the use of an additional delivery vehicle. Delivery to the liver may have many applications such as controlling hypercholesterolemia as well as several other metabolic indications.
o Ocular diseases – RXi has shown spontaneous cellular uptake of its sd-rxRNA™ compounds by retinal cells and is working with an academic collaborator to further address retinal diseases.
o Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) – RXi has established an academic collaboration with one of the leading ALS researchers to explore delivery of sd-rxRNA compounds to the spinal cord.
o Oncology – RXi has an active pharmaceutical collaboration to explore the potential of using the rxRNA™ therapeutic platform in this area.

* RXi summarized its intellectual property position including its alternative path to RNAi based on the length of rxRNA™ duplexes and distinct end-structures and multiple layers of patent protection for both rxRNA™ compounds and delivery vehicles.

http://www.rxipharma.com/news_press_releases.html

[mitleser3108]

ups, jetzt verliert sogar DH seine positive sicht auf alnylam, oder schränkt sie zumindest stark ein, interresant wie immer bei ihm, fände es interresant eure Meinung dazu auch zu hören

http://rnaitherapeutics.blogspot.com/2009/10/refocusing-on-f…

[Fruehrentner]

Bin zwar nicht investiert, aber warum schmiert ALNYLAM so ab?

[mitleser3108]

Antwort auf Beitrag Nr.: 38.264.938 von Fruehrentner am 27.10.09 20:21:54

führe ich auf das allgemeine Marktumfeld für "gewisse" Biotechs, d.h. noch keine Produkte auf dem Markt, oder solche, die noch nicht genug Cash generieren, um die Firma am Leben zu halten,

sieht nicht jeder so, muss auch nicht zwingend so sein

mehr Details der Diskussion hier:

http://www.wallstreet-online.de/diskussion/1141290-15051-150…

Beitrag Nr.: 38.266.611
Beitrag Nr.: 38.263.741
Beitrag Nr.: 38.263.372

[traumstrand]

Antwort auf Beitrag Nr.: 38.264.938 von Fruehrentner am 27.10.09 20:21:54

wundert mich auch, konnte keine wirklich ausschlaggebende Info finden:

[Fruehrentner]

Alnylam Presents New Pre-Clinical Data on ALN-TTR, an RNAi Therapeutic for the Treatment of Transthyretin-Mediated Amyloidosis

02 Nov 2009

New Data Demonstrate Durable In Vivo Efficacy for ALN-TTR

CAMBRIDGE, MA, USA | November 2, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented new pre-clinical research findings from its transthyretin (TTR)-mediated amyloidosis (ATTR) program at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (“The Liver Meeting”). Alnylam is developing ALN-TTR, a systemically delivered RNAi therapeutic targeting the TTR gene for the treatment of ATTR, including familial amyloidotic cardiomyopathy (FAC) and familial amyloidotic polyneuropathy (FAP). There are more than 100 mutations that have been identified in the TTR gene. ALN-TTR targets a region of the gene common to wild-type and all known mutant forms of TTR, and therefore, has potential as a therapeutic for all patients with FAC and FAP.

“We are very encouraged by these significant and important pre-clinical findings, which continue to validate the potential benefit of an RNAi therapeutic targeting TTR for the treatment of ATTR,” said Dinah Sah, Ph.D., Vice President, Research, CNS and Oncology at Alnylam. “Our new in vivo studies represent a significant step forward as they demonstrate the ability of ALN-TTR to silence the TTR gene for a period of weeks after a single dose administration. These data provide continued validation of our RNAi therapeutics strategy, and we are looking forward to advancing this program towards the clinic.”

The new pre-clinical research findings presented at the meeting demonstrated dose-dependent ALN-TTR reduction of liver TTR messenger (mRNA) and serum TTR protein levels by greater than 80% in transgenic mice and non-human primates, with gene silencing effects found to be durable for more than three weeks following a single dose administration.

“I am quite excited by these new data, which strongly support the advancement of this program towards patients who have extremely limited therapeutic options,” said Maria Joao Saraiva, Ph.D., Professor of Biochemistry, Molecular Neurobiology Group, Institute for Molecular and Cellular Biology in Portugal. “ATTR, which presents severe manifestations in both FAP and FAC, is estimated to affect approximately 50,000 people worldwide and is associated with significant morbidity, including intractable peripheral sensory neuropathy, disabling dysfunction of the autonomic nervous system that leads to severe intestinal dysfunction, and in many cases severe cardiomyopathy.”

Alnylam expects to file regulatory applications for ALN-TTR by the end of 2009 with a goal of initiating a Phase I clinical trial in early 2010. ALN-TTR is being advanced using stable nucleic acid-lipid particles (SNALP) delivery technology in collaboration with Tekmira Pharmaceuticals Corporation.

About TTR-mediated Amyloidosis

TTR-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest form, ATTR represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; FAP (familial amyloidotic polyneuropathy) affects approximately 10,000 people worldwide with additional patients affected by FAC (familial amyloidotic cardiomyopathy). ATTR patients with FAP have a mean life expectancy of five to fifteen years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene.

[Fruehrentner]

Aus der Branche bzw. vom Wettbewerb:


RXi Pharmaceuticals to Present Data Demonstrating the Robust Performance of its RNAi Therapeutics Platform at Upcoming Scientific Conference

WORCESTER, Mass.--(BUSINESS WIRE)--Nov. 3, 2009-- RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced that Dmitry Samarsky, Ph.D., Vice President of Technology Development, will be presenting at the Discovery on Target scientific conference in Boston, MA tomorrow, November 4, 2009. The presentation will not be webcasted.

The presentation will describe RXi’s therapeutic platform, including RXi’s next generation rxRNA™ compounds and advanced delivery approaches. The talk will focus on self-delivering rxRNA (sd-rxRNA™) compounds. Dr. Samarsky will present data exemplifying the robust performance of RXi’s self-delivering rxRNAs across multiple genes, cell types, target tissues and animal species.

Craig Mello, Ph.D., Chairman of RXi’s Scientific Advisory Board and Noble Laureate noted, “The results presented by Dr. Samarsky demonstrate the robustness and potential for broad-based applications of self-delivering rxRNA to multiple therapeutic areas. Scientists are seeking RNAi-delivery solutions to disease tissues, and RXi’s results represent some of the most impressive delivery data in the field”.

RXi is leveraging its therapeutic platform for both internal programs and external collaborations and partnerships to create a sustainable pipeline of RNAi based products for unmet medical need.

About RNA Interference (RNAi) and Self-delivering rxRNA™ (sd-rxRNA™)

Regarded as a revolutionary discovery in biology, RNA interference (RNAi) is a naturally occurring mechanism whereby short, double-stranded RNA molecules interfere with the expression of genes in living cells. This mechanism has the potential to be harnessed to “silence” or specifically block the production of disease-causing proteins before they are made. This technology can potentially be used to treat human diseases by “turning-off” genes that lead to disease in the first place. RXi Pharmaceuticals is using RNAi technology to develop RNA-derived molecules targeting disease-causing genes.

Self-delivering rxRNA™ (sd-rxRNA™) is a proprietary technology recently developed at RXi which enables the efficient delivery of RNAi compounds without the requirement of an additional delivery vehicle.

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals is a discovery-stage biopharmaceutical company pursuing the development and potential commercialization of proprietary therapeutics based on RNA interference (RNAi) for the treatment of human diseases. RXi has a comprehensive therapeutic platform that includes both RNAi compounds and delivery methods. RXi uses its own version of RNAi compounds -- rxRNA™ -- that provide an advanced alternative to conventional small interfering RNAs (siRNAs) and define the next generation of RNAi technology. rxRNA™ compounds are designed specifically for therapeutic use and contain many of the properties needed to move RNAi based drugs into the clinic. RXi Pharmaceuticals believes it is well positioned to compete successfully in the RNAi-based therapeutics market with its accomplished scientific advisors, including Dr. Craig Mello, recipient of the 2006 Nobel Prize for his co-discovery of RNAi; a management team that is experienced in developing RNAi products; and a strong early intellectual property position in RNAi chemistry and delivery. www.rxipharma.com

Source: RXi Pharmaceuticals Corporation

[mitleser3108]

http://phx.corporate-ir.net/preview/phoenix.zhtml?c=148005&p…

Alnylam and Roche Advance RNAi Therapeutic Collaboration Phase of Landmark 2007 Alliance

– Partners to Co-Develop and Co-Commercialize Certain RNAi Therapeutic Products in U.S. Market –

– Collaboration to Include Alnylam Lipid Nanoparticle and Roche Dynamic Polyconjugate Delivery Technologies –

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 4, 2009-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has advanced to the RNAi therapeutic collaboration stage of its landmark alliance with Roche formed in 2007. In this phase of the collaboration, the partners will jointly collaborate on the discovery and development of specific RNAi therapeutic products and each will contribute key delivery technologies in the new disease target-focused effort. New delivery technologies include Alnylam lipid nanoparticles and Roche Madison dynamic polyconjugate delivery technologies. Alnylam and Roche will co-develop and co-commercialize RNAi therapeutic products in the U.S. market and Alnylam is eligible to receive additional milestone and royalty payments for products developed in the rest of world.

“We are excited to advance to this phase of our 2007 agreement, as our joint efforts combine many strengths of the Alnylam and Roche platforms on specific disease target programs,” said Barry Greene, President and Chief Operating Officer of Alnylam. “Our partnership with Roche remains very strong and we look forward to working together to bring our innovation to patients.”

“Since the formation of our alliance with Alnylam and the establishment of Roche Kulmbach and Roche Madison as Centers of Excellence for RNA therapeutic research, we have made significant progress in advancing this technology as a potential new class of innovative medicines,” said Louis Renzetti, Ph.D., Vice President of RNA Therapeutics Research of Roche. “We continue to view RNAi as having true potential as a whole new class of differentiated drugs to benefit patients.”

In July 2007, Alnylam granted to Roche a non-exclusive license providing access to broad Alnylam intellectual property (IP) and know-how, including fundamental, chemistry and delivery IP, in the fields of oncology, respiratory disease, metabolic disease, and certain liver diseases. In addition, Alnylam and Roche agreed to collaborate on RNAi therapeutics drug discovery for a defined number of disease targets, subject to certain Alnylam third party obligations. As part of the agreement, Roche also acquired Alnylam’s Kulmbach-based research & development (R&D) organization which has now become Roche Kulmbach, a Roche Centre of Excellence for RNA therapeutics. In July 2008, Roche acquired Madison, WI-based Mirus Technologies, Inc., a pioneer in the discovery of a novel RNAi delivery technology known as dynamic polyconjugates. Mirus has become Roche Madison, an additional Roche Centre of Excellence for RNA therapeutics.

[Fruehrentner]

Alnylam and Roche Advance RNAi Therapeutic Collaboration Phase of Landmark 2007 Alliance

04 Nov 2009

– Partners to Co-Develop and Co-Commercialize Certain RNAi Therapeutic Products in U.S. Market

– Collaboration to Include Alnylam Lipid Nanoparticle and Roche Dynamic Polyconjugate Delivery Technologies

CAMBRIDGE, MA, USA | November 4, 2009 |

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has advanced to the RNAi therapeutic collaboration stage of its landmark alliance with Roche formed in 2007. In this phase of the collaboration, the partners will jointly collaborate on the discovery and development of specific RNAi therapeutic products and each will contribute key delivery technologies in the new disease target-focused effort. New delivery technologies include Alnylam lipid nanoparticles and Roche Madison dynamic polyconjugate delivery technologies. Alnylam and Roche will co-develop and co-commercialize RNAi therapeutic products in the U.S. market and Alnylam is eligible to receive additional milestone and royalty payments for products developed in the rest of world.

“We are excited to advance to this phase of our 2007 agreement, as our joint efforts combine many strengths of the Alnylam and Roche platforms on specific disease target programs,” said Barry Greene, President and Chief Operating Officer of Alnylam. “Our partnership with Roche remains very strong and we look forward to working together to bring our innovation to patients.”

“Since the formation of our alliance with Alnylam and the establishment of Roche Kulmbach and Roche Madison as Centers of Excellence for RNA therapeutic research, we have made significant progress in advancing this technology as a potential new class of innovative medicines,” said Louis Renzetti, Ph.D., Vice President of RNA Therapeutics Research of Roche. “We continue to view RNAi as having true potential as a whole new class of differentiated drugs to benefit patients.”

In July 2007, Alnylam granted to Roche a non-exclusive license providing access to broad Alnylam intellectual property (IP) and know-how, including fundamental, chemistry and delivery IP, in the fields of oncology, respiratory disease, metabolic disease, and certain liver diseases. In addition, Alnylam and Roche agreed to collaborate on RNAi therapeutics drug discovery for a defined number of disease targets, subject to certain Alnylam third party obligations. As part of the agreement, Roche also acquired Alnylam’s Kulmbach-based research & development (R&D) organization which has now become Roche Kulmbach, a Roche Centre of Excellence for RNA therapeutics. In July 2008, Roche acquired Madison, WI-based Mirus Technologies, Inc., a pioneer in the discovery of a novel RNAi delivery technology known as dynamic polyconjugates. Mirus has become Roche Madison, an additional Roche Centre of Excellence for RNA therapeutics.

[Fruehrentner]

Alnylam Presents New Pre-clinical Data on ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancer

18 Nov 2009

New Results Demonstrate Robust Anti-Tumor Activity in Multiple Models, Including Extra-Hepatic Tumors

CAMBRIDGE, MA, USA | November 18, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced new pre-clinical data from its ALN-VSP program presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International conference being held November 15 - 19, 2009 in Boston, Mass. ALN-VSP is an RNAi therapeutic currently in a Phase I clinical trial for the treatment of liver cancers, including hepatocellular carcinoma (HCC) and other solid tumors with liver involvement. The new data demonstrated robust anti-tumor activity in orthotopic liver tumor models comprised of both HCC- and colorectal cancer-derived cell lines. ALN-VSP was also shown to act on disseminated tumors outside of the liver. Further, in addition to anti-proliferative effects, studies showed that ALN-VSP exerts a potent anti-angiogenic effect on tumors.

“ALN-VSP is Alnylam’s first systemic RNAi program, as well as our first clinical program in an oncology indication,” said Dinah Sah, Ph.D., Vice President Research, CNS and Oncology at Alnylam. “This RNAi therapeutic targets two well-validated genes critical for tumor cell proliferation and survival, an attractive strategy supported by these current data for the advancement of novel anti-cancer medicines. Meanwhile, we are making continued progress in our Phase I clinical trial with ALN-VSP having now enrolled a significant portion of the study across multiple dose cohorts, and look forward to sharing preliminary results in mid-2010.”

ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs (siRNAs) formulated in a lipid nanoparticle (LNP) and designed to target two genes critical in the growth and survival of cancer cells: kinesin spindle protein, or KSP, required for tumor cell proliferation; and vascular endothelial growth factor, or VEGF, required for blood vessel formation to sustain tumor growth. The pre-clinical studies were performed using ALN-VSP in an orthotopic liver tumor model utilizing either human HCC cells or human colorectal carcinoma cells. In a poster titled “Development of ALN-VSP: an RNAi Therapeutic for Liver Malignancies,” Alnylam scientist Dr. Iva Toudjarska, presented the following data:

* ALN-VSP-mediated silencing of KSP in both HCC and colorectal carcinoma models, resulting in the accumulation in tumor cells of aberrant mitotic figures, also known as monoasters, a hallmark of KSP inhibition;
* monoaster formation in tumor cells within lymph node metastases derived from the orthotopic liver tumors, demonstrating the ability of LNPs in general, and ALN-VSP in particular, to achieve effective delivery in extra-hepatic tumor sites;
* marked anti-angiogenic effects resulting from ALN-VSP treatment, including reductions in both tumor microvessel density and intratumoral hemorrhage; and
* similar anti-angiogenic results with an LNP containing only the VEGF siRNA, demonstrating that the vascular effects are due to VEGF silencing.

“We are very encouraged by these new results, as they show anti-tumor activity for ALN-VSP in both primary and metastatic disease settings,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “Importantly, these new studies demonstrate anti-tumor activity in extra-hepatic tumors, highlighting the potential for effective delivery of siRNAs to sites beyond the liver. These new results also confirm the anti-angiogenic effects of ALN-VSP, providing continued support for our dual-targeting strategy.”

ALN-VSP is currently in a Phase I multicenter, open-label, dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALN-VSP in patients with advanced solid tumors with liver involvement, including HCC. Alnylam has enrolled a significant number of patients across multiple dose cohorts in the Phase I trial, and expects to present preliminary data from the Phase I trial in mid-2010. ALN-VSP is formulated in an LNP, also known as SNALP, in collaboration with Tekmira Pharmaceuticals Corporation.

[Fruehrentner]

Alnylam Presents New Pre-clinical Data on ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancer

18 Nov 2009

New Results Demonstrate Robust Anti-Tumor Activity in Multiple Models, Including Extra-Hepatic Tumors

CAMBRIDGE, MA, USA | November 18, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced new pre-clinical data from its ALN-VSP program presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International conference being held November 15 - 19, 2009 in Boston, Mass. ALN-VSP is an RNAi therapeutic currently in a Phase I clinical trial for the treatment of liver cancers, including hepatocellular carcinoma (HCC) and other solid tumors with liver involvement. The new data demonstrated robust anti-tumor activity in orthotopic liver tumor models comprised of both HCC- and colorectal cancer-derived cell lines. ALN-VSP was also shown to act on disseminated tumors outside of the liver. Further, in addition to anti-proliferative effects, studies showed that ALN-VSP exerts a potent anti-angiogenic effect on tumors.

“ALN-VSP is Alnylam’s first systemic RNAi program, as well as our first clinical program in an oncology indication,” said Dinah Sah, Ph.D., Vice President Research, CNS and Oncology at Alnylam. “This RNAi therapeutic targets two well-validated genes critical for tumor cell proliferation and survival, an attractive strategy supported by these current data for the advancement of novel anti-cancer medicines. Meanwhile, we are making continued progress in our Phase I clinical trial with ALN-VSP having now enrolled a significant portion of the study across multiple dose cohorts, and look forward to sharing preliminary results in mid-2010.”

ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs (siRNAs) formulated in a lipid nanoparticle (LNP) and designed to target two genes critical in the growth and survival of cancer cells: kinesin spindle protein, or KSP, required for tumor cell proliferation; and vascular endothelial growth factor, or VEGF, required for blood vessel formation to sustain tumor growth. The pre-clinical studies were performed using ALN-VSP in an orthotopic liver tumor model utilizing either human HCC cells or human colorectal carcinoma cells. In a poster titled “Development of ALN-VSP: an RNAi Therapeutic for Liver Malignancies,” Alnylam scientist Dr. Iva Toudjarska, presented the following data:

* ALN-VSP-mediated silencing of KSP in both HCC and colorectal carcinoma models, resulting in the accumulation in tumor cells of aberrant mitotic figures, also known as monoasters, a hallmark of KSP inhibition;
* monoaster formation in tumor cells within lymph node metastases derived from the orthotopic liver tumors, demonstrating the ability of LNPs in general, and ALN-VSP in particular, to achieve effective delivery in extra-hepatic tumor sites;
* marked anti-angiogenic effects resulting from ALN-VSP treatment, including reductions in both tumor microvessel density and intratumoral hemorrhage; and
* similar anti-angiogenic results with an LNP containing only the VEGF siRNA, demonstrating that the vascular effects are due to VEGF silencing.

“We are very encouraged by these new results, as they show anti-tumor activity for ALN-VSP in both primary and metastatic disease settings,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “Importantly, these new studies demonstrate anti-tumor activity in extra-hepatic tumors, highlighting the potential for effective delivery of siRNAs to sites beyond the liver. These new results also confirm the anti-angiogenic effects of ALN-VSP, providing continued support for our dual-targeting strategy.”

ALN-VSP is currently in a Phase I multicenter, open-label, dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALN-VSP in patients with advanced solid tumors with liver involvement, including HCC. Alnylam has enrolled a significant number of patients across multiple dose cohorts in the Phase I trial, and expects to present preliminary data from the Phase I trial in mid-2010. ALN-VSP is formulated in an LNP, also known as SNALP, in collaboration with Tekmira Pharmaceuticals Corporation.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko Kirin. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington’s disease, and TTR amyloidosis. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals

[Fruehrentner]

News vom Wettbewerb:


MDRNA Expands RNAi Bladder Cancer Program With the Vancouver Prostate Centre

24 Nov 2009

Decision to Expand Based Upon Promising Pre-Clinical Results

BOTHELL, WA, USA | November 24, 2009 | MDRNA, Inc. (NASDAQ: MRNA), a leading RNAi-based drug discovery and development company, today announced the extension and expansion of its collaboration with the Vancouver Prostate Centre (VPC), covering the discovery and development of RNAi-based therapeutics for the treatment of bladder cancer. Research conducted by scientists and surgeons from both institutions demonstrated that MDRNA's UsiRNA targeting human survivin and delivered via DiLA2 liposomes achieved up to 90% target knockdown in a mouse model of orthotopic bladder cancer. The effects of UsiRNA persisted for the duration of the three week study, and the level of survivin mRNA knockdown was associated with a significant reduction in tumor growth as measured by fluorescence from luciferase-expressing tumor cells.

"Intravesical delivery of the survivin UsiRNA using MDRNA's DiLA2 liposome formulation specifically targeted to a bladder tumor has yielded encouraging results that could lead to the development of useful therapies in patients with bladder cancer," said Dr. Alan So, an Assistant Professor in the Department of Urologic Sciences at the University of British Columbia, Research Scientist at the Vancouver Prostate Centre, and the study's principal investigator. "We are looking forward to expanding our current studies as the success of RNAi cancer therapeutics will be dependent upon the development of safe and efficacious delivery systems such as those being developed by MDRNA."

The collaboration with VPC's world-renowned clinical cancer research lab was formed in 2008 to investigate MDRNA's UsiRNAs and DiLA2 delivery platform in one of the Centre's well-validated bladder cancer models. The VPC is a National Centre of Excellence for translational research located at the University of British Columbia and the Vancouver General Hospital. In light of current results demonstrating efficient delivery and high potency for RNAi, the program will expand to evaluate UsiRNAs targeting other critical pathways in cancer, the impact on tumor biology, tumor growth, and survival rates. These studies are considered essential to identify the most effective target and dosing regimens for clinical intervention. MDRNA recently presented detailed results of the initial research at the International Society for Biological Therapy of Cancer.

"The encouraging data gathered so far supports our decision to add bladder cancer to our internal pipeline and provides further validation of the value of our RNAi drug discovery platform to potential pharmaceutical partners," said Dr. Barry Polisky, Chief Scientific Officer of MDRNA. "The expansion of this program reflects the value of VPC's world-class clinical research laboratory and the rewarding relationship that exists between MDRNA and VPC's outstanding scientific and medical teams. Together we are making progress to discover and develop novel treatments for this important unmet medical need."

**************************************************************




About UsiRNAs and Unlocked Nucleobase Analogs

A UsiRNA is a duplex siRNA containing at least one Unlocked Nucleobase Analog (UNA). In a UsiRNA, UNAs are non-nucleotide monomers and synthesized much like RNA in the construction of a double-stranded oligonucelotide for use as an RNAi-based therapeutic. In the case of the UsiRNA, UNA is substituted for specific nucleotides in both the guide and passenger strands. UsiRNAs are fully recognized by the cellular RNAi machinery, as demonstrated by their potent activity. MDRNA has also shown that substitution of UNA for specific RNA increases stability to nucleases, substantially reduces cytokine induction, and reduces passenger and guide strand-mediated offtarget effects. The high potency, and improved drug-like properties, associated with UsiRNAs provide the potential to greatly enhance RNAi-based therapeutics.

About the DiLA2 Delivery Platform

The DiLA2 Delivery Platform is MDRNA's proprietary platform for creating novel liposomal delivery systems based on di-alkylated amino acids (DiLA2). The DiLA2 Platform enables MDRNA to tailor the charge, linker length, and acyl chain characteristics to improve delivery of the liposomes to target tissue of interest. In vivo studies have demonstrated effective delivery in models of metabolic disease, cancer, and other diseases. DiLA2 based liposomes are well tolerated for repeat dose, and systemic and local administration. MDRNA is also utilizing condensing peptides to form peptide-siRNA nanoparticles to further increase the delivery efficiency of its DiLA2 delivery systems. In addition, the platform is designed to permit attachment of peptides and other targeting molecules for delivery to a variety of tissues, and thus provide for a diverse therapeutic portfolio.

About MDRNA, Inc.

MDRNA is a biotechnology company focused on the development and commercialization of therapeutic products based on RNA interference (RNAi). Our goal is to improve human health through the development of RNAi-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Over the past decade, we have developed substantial capabilities in molecular biology, cellular biology, lipid chemistry, peptide chemistry, pharmacology and bioinformatics, which we are applying to a wide range of RNAi technologies and delivery approaches. These capabilities plus the in-licensing of key RNAi-related intellectual property have rapidly enabled us to become a leading RNAi-based therapeutics company with a pre-clinical pipeline in oncology. Through our capabilities, expertise and know-how, we are incorporating multiple RNAi technologies as well as peptide- and lipid-based delivery approaches into a single integrated drug discovery platform that will be the engine for our clinical pipeline as well as a versatile platform for establishing broad therapeutic partnerships with biotechnology and pharmaceutical companies. We are also investing in new technologies that we expect to lead to safer and more effective RNAi-based therapeutics while aggressively building upon our broad and extensive intellectual property estate. By combining broad expertise in siRNA science with proven delivery platforms and a strong IP position, MDRNA is well positioned as a leading RNAi-based drug discovery and development company. Additional information about MDRNA, Inc. is available at http://www.mdrnainc.com.

SOURCE: MDRNA

[Fruehrentner]

News vom Wettbewerber:


Silence Therapeutics to Merge with Intradigm Corp to Create Leading RNAi Therapeutics Company Print E-mail
16 Dec 2009

The Boards of Silence Therapeutics and Intradigm Corporation are delighted to announce the merger of their businesses to form a leading company in the field of RNAi (RNA interference)

PALO ALTO, CA, USA | Decembre 16, 2009 | The Boards of Silence Therapeutics plc (AIM: SLN) and Intradigm Corporation are delighted to announce the merger of their businesses to form a leading company in the field of RNAi (RNA interference). The enlarged company, to be called Silence Therapeutics, will have multiple RNAi discovery, development and delivery technologies, a broad internal and partnered product pipeline and a broad portfolio of intellectual property.

The Directors believe the merger will enable Silence Therapeutics to build a competitive offering and facilitate more deals of greater value with the pharmaceutical industry. In particular, the combined business will be able to offer potential partners a choice of technologies to deliver RNAi molecules to diseased tissue, one of the main challenges in the emerging field of RNAi therapeutics. In addition, the enlarged Silence Therapeutics will have the financial strength to exploit its technology by developing its own therapeutic candidates.

Silence Therapeutics will issue 79,640,668 of its Ordinary Shares to acquire the entire share capital of Intradigm. Upon completion of the transaction, Intradigm's shareholders and management will own 36.6 percent of the enlarged group. The completion of the proposed acquisition is contingent upon approval by Silence Therapeutics' shareholders.

In parallel with the merger, Silence Therapeutics has raised 15 million pounds Sterling through a placing and subscription of shares at a price of 23 pence per share. Existing shareholders of Intradigm, including Alta Partners, Frazier Healthcare, Lilly Ventures, Roche Finance and Astellas Venture have committed over 5 million pounds of new funds by way of subscription. The placing has been underwritten by Nomura Code Securities Limited, who also advised Silence Therapeutics on the merger with Intradigm.

Iain Ross, currently chairman of Silence Therapeutics, will remain as Chairman of the enlarged company. Philip Haworth, Chief Executive of Intradigm, will become CEO of Silence Therapeutics and Klaus Giese will continue as Chief Scientific Officer of Silence Therapeutics.

The transaction will bring five strategic benefits:

* A broad platform of technologies capable of addressing the discovery, development and delivery of RNAi therapeutics. The combined companies' capabilities extend to all essential areas for short interfering RNA (siRNA) product development and in particular delivery, but also structure, chemistry and a diverse library of therapeutic siRNA sequences.
* An advancing pipeline of internal and partnered product candidates. Four of the nine siRNA candidates currently in clinical development globally utilize Silence's technology.
* A broad intellectual property portfolio, with protection covering all essential areas of RNAi therapeutic development, including target sequences, delivery and siRNA structural features.
* An expanded scientific team and an experienced group of senior executives and board of directors.
* Expanded financial support and stability to facilitate new growth opportunities. International shareholder base offers broader access to capital to enable internal growth and provide additional strength for the purpose of negotiating favorable strategic transactions in the sector.

Iain Ross, Chairman of Silence Therapeutics, said: "By bringing together a comprehensive platform of siRNA delivery and development technologies, we believe Silence Therapeutics will be a partner of choice for those seeking to develop RNAi therapeutics. With a strengthened balance sheet, experienced management and extended research capability, Silence Therapeutics is well placed to strike the development deals that will deliver value for shareholders."

Philip Haworth, Chief Executive of Intradigm, said: "We are excited to join forces with Silence Therapeutics and look forward to continuing our pursuit of valuable RNAi therapeutics as part of this new team. Perhaps most exciting about the merger is the powerful range of RNAi delivery technology solutions possessed by the new company. The most significant hurdle to be overcome in realizing the vast potential of RNAi therapeutics is that of enabling safe and effective delivery of siRNA payloads. By combining the impressive expertise of both Intradigm and Silence, we now have one of the industry's most comprehensive and versatile delivery technology platforms, providing the enlarged company with an unparalleled potential to develop delivery solutions that can be tailored to address various therapeutic requirements."

The board of the enlarged company will have eight members. Five of the nominated directors currently sit on the Board of Silence Therapeutics: Iain Ross, Jerry Randall, Annette Clancy, David U'Prichard and Melvyn Davies. The remaining three Board members are directors of Intradigm: James Topper, David Mack and Philip Haworth.

Documentation describing the transaction and share placing will be posted to Shareholders later today. More information about the proposed acquisition is also available from Silence Therapeutics and from the company website: www.silence-therapeutics.com.

An Extraordinary General Meeting of shareholders to approve the transaction and share placing will be held on January 4, 2010 at 10:00am.

The suspension of trading in Silence Therapeutics shares is expected to be lifted later today.

About Silence Therapeutics plc (www.silence-therapeutics.com)

Silence Therapeutics plc (AIM: SLN) is a leading European RNAi-focused biotechnology company.

RNA interference (RNAi) is a Nobel Prize winning technology and one of the most exciting areas of drug discovery today. It represents a completely new approach to selectively 'silence' or inactivate disease relevant genes and as such it has the potential to create a new class of therapeutic products. RNAi could therefore offer a therapeutic approach to a broad range of diseases (cancer, infectious diseases, inherited diseases), many of which have been regarded as incurable and are not addressed by current therapeutics, therefore providing a large market opportunity.

Silence Therapeutics has developed a platform of novel short interfering RNA (siRNA) molecules, AtuRNAi, which provide a number of advantages over conventional siRNA molecules, including increased stability against nuclease degradation. In addition, the Company has developed a proprietary systemic delivery system, AtuPLEX. This system enables the functional delivery of siRNA molecules to targeted diseased tissues and cells, while increasing their bioavailability and intracellular uptake.

Following the granting of its patents in Europe, the USA and Australia, Silence Therapeutics is one of only two companies worldwide with a proprietary position on composition of matter for siRNA therapeutics.

Silence's lead internal product, Atu027, is a proprietary AtuRNAi molecule in clinical development for systemic cancer indications. Atu027 has successfully completed single and repeat dose toxicology and geno-toxicology studies, as well as a 28-day toxicology study using multiple dosing regimens. In June 2009, the Company started an open-label, single-centre, dose-escalation Phase I study with Atu027 in patients with advanced solid (malignant) tumors involving single as well as repeated intravenous administration. Atu027 specifically targets PKN3, a molecule involved in cancer growth and metastasis formation. Atu027 is Silence's most advanced clinical candidate for a systemically delivered siRNA using the Company's proprietary AtuPLEX delivery technology.

In March 2008 Silence Therapeutics announced a collaboration with AstraZeneca (LSE: AZN) focused on the development of a range of novel delivery approaches for siRNA molecules. Under the terms of the agreement both Silence Therapeutics and AstraZeneca will be allowed to commercialize the truly novel delivery systems that the two partners develop together.

Silence Therapeutics has granted a license to AstraZeneca to develop novel AtuRNAi therapeutics against five specific targets. This collaboration was the first industry validation of the potential application of Silence Therapeutics' proprietary AtuRNAi molecules and solidified the Company's leadership position in field of RNAi therapeutics.

The Company's AtuRNAi technology also has been sublicensed to Pfizer via Quark's license to it of the compound RTP-801i-14 for the treatment of age-related macular degeneration (AMD) and a number of other indications. This compound entered a phase II clinical study in July 2008. Silence Therapeutics also has licensed to Quark rights to the AtuRNAi structure for Quark's proprietary compound, AKIi-5 and DGFi, which are both in Phase I human clinical studies for treatment of acute kidney injury and delayed graft function in kidney transplantation respectively.

Silence Therapeutics is based in London, UK, and Berlin, Germany, and is listed on AIM.

About Intradigm

Intradigm is a private biotechnology company committed to the discovery, development and delivery of targeted, systemic RNA interference (RNAi) therapeutics for the treatment of serious diseases with an initial focus on oncology. Intradigm is unique among private companies, with its comprehensive RNAi therapeutics platform consisting of structural features for a next generation of RNAi molecules, biodegradable polycationic polymers for the delivery of RNAi therapeutics and proprietary siRNA sequences. Intradigm's proprietary delivery technology is unique in its potential to offer safe and effective systemic administration using a library of novel peptide-based biodegradable polymers.

Intradigm has established an impressive proprietary portfolio of siRNA sequences against more than 50 highly valued oncology and other disease targets. In addition, Intradigm has secured an exclusive license to the Zamore patent family from the University of Massachusetts, which covers broad structural features of siRNA design for more potent next generation siRNA sequences.

SOURCE: Intradigm

[Fruehrentner]

Alnylam, Collaborators At MIT Publish New Pre-clinical Research On Lipidoid Formulations for the systemic delivery of RNAi therapeutics

Published: 29-Dec-2009

Alnylam Pharmaceuticals (Alnylam) and collaborators from the David Koch Institute for Integrative Research at the Massachusetts Institute of Technology (MIT) have published new data in the journal Proceedings of the National Academy of Sciences (PNAS). The publication describes further advancements in discovery and development of lipidoid formulations for the systemic delivery of RNAi therapeutics.

Lipidoids are lipid-like materials discovered for the delivery of RNAi therapeutics, and were originally described by Alnylam and MIT collaborators. In particular, the new research findings demonstrate the discovery of new lipidoid materials that facilitate improved in-vivo potency for RNAi therapeutics.

The new pre-clinical data describe a formulation based on a lipidoid known as C12-200, that was shown to enable gene silencing in-vivo in rodents at doses below 0.01mg/kg. It demonstrate complete, rapid, and durable gene silencing in rodents as soon as 24 hours with protein levels returning to baseline within 20 to 35 days.

Specifically inhibit expression of as many as five target genes simultaneously after a single injection of an LNP formulation in rodents and demonstrate potent and selective silencing of the clinically relevant gene transthyretin (TTR) at doses as low as 0.03mg/kg in non-human primates.

Victor Kotelianski, senior vice president of Alnylam, said: “We are very encouraged with the substantial progress we and our collaborators have made with lipid nanoparticles (LNPs) based on novel lipid-like materials such as lipidoids. To our knowledge, these new LNP formulations facilitate endogenous liver gene silencing at doses that are orders-of-magnitude lower than those required by previously described siRNA delivery approaches, thereby setting a new standard in potency for the systemic delivery of RNAi therapeutics.

“In addition, the current study is the first to report on the simultaneous and specific RNAi-mediated silencing of as many as five liver targets in-vivo, serving as proof of principle that multiple genes involved in similar or divergent biological pathways can be silenced with a single administration of a single drug product. From a therapeutic standpoint, this could enable novel pharmaceutical strategies, where silencing of multiple targets could achieve an enhanced level of efficacy.”

[Fruehrentner]

aus der RNAi-Branche:

Benitec Licensee Achieves Milestone With Pfizer

Published: 05-Feb-2010

Benitec licensee company, Tacere Therapeutics said that Pfizer has exercised the option, granted in a collaboration and license agreement announced in January 2008, to further develop and commercialise Tacere’s hepatitis C virus (HCV) compounds.

The clinical candidate is a new class of agent containing three separate RNAi elements, simultaneously targeting three different sites of the hepatitis C virus, and encapsidated in an adeno-associated virus (AAV) protein coat.

In preclinical animal studies, Tacere have demonstrated that a single intravenous injection of the agent results in penetration of hepatocytes at sufficiently high levels to potentially eradicate HCV. Tacere have been collaborating with Pfizer for two years to demonstrate that this agent has an excellent safety profile in both mice and non-human primates.

Sue MacLeman, chief executive officer of Benitec, said: “The triggering of this option by Pfizer is a validation of the Benitec ddRNAi 'expressed' approach to treating chronic diseases from the world’s biggest pharmaceutical company.”

Tacere and Pfizer will continue to work together for the next 12 months to complete regulatory toxicology studies, with Pfizer maintaining funding for all aspects of this collaboration. Benitec possesses and retains rights to all human therapeutic applications of its ddRNAi technology and continues to explore licensing and other growth opportunities.
----------------------------------------------------


Benitec ist übrigens auch börsennnotiert.

[Fruehrentner]

Antwort auf Beitrag Nr.: 38.890.211 von Fruehrentner am 05.02.10 15:14:27

About BENITEC:

Company Overview

Benitec Limited is an international biotechnology company listed on the Australian Stock Exchange (ASX:BLT). Benitec is a leading company in the area of RNA interference (RNAi) technology, which utilises the body’s own mechanism to turn off the expression of defective genes, thus opening up potential new therapies for a range of serious life-threatening diseases. The discovery of this science won two US researchers the Nobel Prize in 2006.

Benitec's core patents and licenses provide it with key technologies to turn off target genes using DNA-directed RNAi (ddRNAi) or vector expressed technology in human cells and in live animals. Benitec holds exclusive worldwide rights for development and commercialization for all therapeutic human applications of this technology.

The corporate goal of Benitec is to develop RNAi-based therapeutics for serious diseases such as infectious diseases, cancers and autoimmune disorders through co-investment and out-licensing. Benitec is now well advanced along this path, with three projects underway - two in infectious disease and one in cancer:

1.
HIV/AIDS. The first is Benitec's RNA-based HIV therapeutic, co-developed with the City of Hope in Duarte, California, which has entered human clinical trials with promising interim results.
2.
Hepatitis B. Benitec has commenced a research project aimed at using RNAi to treat another infectious disease, Hepatitis B, in collaboration with Biomics Biotechnologies Inc., a biotechnology company located in China with RNAi expertise. The RNAi is targeted at turning off a gene vital to the growth of the hepatitis B virus.
3.
Lung cancer. In collaboration with researchers in the Children’s Cancer Institute, at the University of New South Wales (UNSW), Benitec is undertaking a project to validate preliminary findings that turning off a gene in human lung cancer cells using Benitec’s technology can make those cancer cells much more sensitive to current anti-cancer drugs.

Benitec derives revenues from out-licensing its proprietary ddRNAi technology to life sciences companies in various fields. The Company's proprietary ddRNAi technology provides unique capability and significant competitive advantages for:

* Developing RNAi-based treatments for chronic life threatening diseases;
* Disease modeling in vitro and in vivo;
* Target validation in vitro and in vivo; and
* RNAi enabling research agents.

http://www.benitec.com/about.php

[Fruehrentner]

Alnylam Initiates Phase IIb Clinical Trial For RSV Infection

Published: 22-Feb-2010

Alnylam Pharmaceuticals has initiated a Phase IIb trial in adult lung transplant patients with ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection.

The Phase IIb trial is a multi-center, global, randomized, double-blind, placebo-controlled study in RSV-infected lung transplant patients with a primary endpoint of a reduction in incidence of new or progressive BOS.

Secondary endpoints include assessments for safety and additional measurements of efficacy, including: anti-viral activity; recovery of lung function, as monitored by the proportion of patients with forced expiratory volume in the first second (FEV1), of greater than 80% of their pre-infection baseline value; and, improvement in RSV symptoms as measured by mean cumulative daily total symptom score.

The trial is expected to enroll 76 patients who will be randomized in a one to one, drug to placebo ratio. All patients will receive standard of care, and those receiving ALN-RSV01 will have drug administered as a 0.6mg/kg dose by inhalation using an investigational eFlow Nebulizer System (PARI Pharma) once daily for five days.

Results from previous pre-clinical and clinical studies with ALN-RSV01 have documented the drug’s safety profile and anti-viral activity. In 2009, Alnylam completed a Phase IIa study of ALN-RSV01 in RSV-infected adult lung transplant patients. In this small study of 24 patients, ALN-RSV01 was safe and well tolerated, which was the primary study objective.

Interpretation of secondary study objectives, including anti-viral activity, was confounded by certain imbalances, for example baseline viral loads, that occurred by chance. By day 14, there was a greater reduction in cumulative symptoms scores in the ALN-RSV01 group. At the 90 day endpoint, ALN-RSV01 treatment was associated with evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS.

In 2008, the anti-viral activity of ALN-RSV01 was demonstrated in the company’s Phase II GEMINI study, which was a randomized, double-blind, placebo-controlled study of intranasal ALN-RSV01 in 88 adult volunteers experimentally infected with RSV.

In this study, ALN-RSV01 treatment was associated with a decrease in the incidence of RSV infection as compared with placebo. Finally, pre-clinical studies have documented the anti-viral activity of ALN-RSV01 in rodent models (Alvarez et al., Antimicrob Agents Chemother. 53(9):3952-62, 2009).

The ALN-RSV program is partnered with Kyowa Hakko Kirin Co in Asia, and Cubist Pharmaceuticals worldwide except Asia. In parallel with Alnylam’s development of ALN-RSV01 for the treatment of RSV in lung transplant patients, Alnylam and Cubist are developing a second-generation compound, ALN-RSV02, which will be focused on the pediatric patient population.

Akshay Vaishnaw, senior vice president of clinical research at Alnylam, said: “RSV is a major infectious disease in both adult and pediatric populations and there are no effective treatments used widely today. It is an especially dangerous infection in immuno-suppressed patients, such as lung transplant patients.

“Alnylam’s new Phase IIb study aims to repeat and extend the results we saw in our previous Phase IIa study in the same patient population. In that small study, treatment with ALN-RSV01 fulfilled the primary study objective of safety and tolerability, and showed preliminary evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS.”

[mitleser3108]

et jibt Jeld:

http://phx.corporate-ir.net/phoenix.zhtml?c=148005&p=irol-ne…

wenn dann noch die 100 Mio von Novartis wg. Platform Lizenz und gute Daten aus der Leberkrebs-Studie

(analog zu dem was der wettbewerb liefert: http://rnaitherapeutics.blogspot.com/2010/03/calaa-01-result…) gibt,

dann ist 2010 zumindest "Alnylamtechnisch" gerettet

[Fruehrentner]

aus der Branche bzw. Wettbewerb:


RXi Pharmaceuticals to Present New Preclinical Data Demonstrating the Robust Performance of its RNAi Therapeutics Platform

WORCESTER, Mass., Mar 25, 2010 (BUSINESS WIRE) -- RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), announced that Pamela Pavco, Ph.D., Vice President of Pharmaceutical Development, will be presenting at the 3rd International Scar Club Meeting in Montpellier, France on March 26, 2010. The presentation will not be webcast.

Dr. Pavco's presentation describes new preclinical data exemplifying the performance of RXi's proprietary self-delivering rxRNA (sd-rxRNA(TM)) compounds in an in vivo model of compromised skin. Data generated using a fluorescently-tagged sd-rxRNA(TM) compound demonstrate spontaneous cellular uptake into dermal cells and a significant, sustained and reproducible silencing of the targeted mRNA. The data presented establish the efficacy of locally-administered sd-rxRNA(TM) in animal models and support the potential use of these novel compounds for clinical applications where direct or local administration is possible.

"We are very encouraged with the substantial progress we have made with our therapeutic platform, especially our proprietary sd-rxRNA(TM)," said Noah D. Beerman, President and Chief Executive Officer of RXi. "Delivery remains one of the most important objectives in our efforts to advance RNAi therapeutics into patients. Our demonstration that sd-rxRNA(TM) compounds efficiently enter cells in vivo and effect significant gene silencing without the need for an additional delivery vehicle is an important advancement for RXi in its progression toward the clinic."

About RNAi and sd-rxRNA(TM)

Regarded as a revolutionary discovery in biology, RNAi is a naturally occurring mechanism whereby short, double-stranded RNA molecules interfere with the expression of genes in living cells. This mechanism has the potential to be harnessed to "silence" or specifically block the production of disease-causing proteins before they are made. This technology can potentially be used to treat human diseases by "turning-off" genes that lead to disease in the first place. RXi Pharmaceuticals is using RNAi technology to develop RNA-derived molecules targeting disease-causing genes.

sd-rxRNA(TM) is a proprietary technology recently developed at RXi which enables the efficient delivery of RNAi compounds without the requirement of an additional delivery vehicle.

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals is a discovery-stage biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi) for the treatment of human diseases. RXi has a comprehensive therapeutic platform that includes both RNAi compounds and advanced delivery methods. RXi uses its own version of RNAi compounds -- rxRNA(TM) -- that provide an advanced alternative to conventional small interfering RNAs (siRNAs) and define the next generation of RNAi technology. rxRNA compounds are designed specifically for therapeutic use and contain many of the properties required to progress RNAi based drugs into the clinic. RXi Pharmaceuticals believes it is well positioned to compete successfully in the RNAi-based therapeutics market with its accomplished scientific advisors, including Dr. Craig Mello, recipient of the 2006 Nobel Prize for his co-discovery of RNAi; a management team that is experienced in developing RNAi products; and a strong early intellectual property position in RNAi chemistry and delivery. http://www.rxipharma.com

http://www.rxipharma.com/news_press_releases.html

[mitleser3108]

Alnylam Announces Grant of New United States Patent Broadly Covering RNAi Therapeutics

Press Release Source: Alnylam Pharmaceuticals, Inc. On Wednesday April 7, 2010, 8:00 am

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that the United States Patent Office (USPTO) has allowed a patent (Application No. 10/560,336) for the Woppmann et al. patent series, entitled “Double-stranded ribonucleic acid with increased effectiveness in an organism.” The newly allowed patent includes 31 claims broadly covering compositions and methods, including pharmaceutical compositions, for small interfering RNAs (siRNAs), the molecules that mediate RNAi.

The Woppmann patent stems from the early research performed at Ribopharma AG, the world’s first-ever RNAi therapeutics company founded in June, 2000. Alnylam acquired Ribopharma in 2003, which then became Alnylam Europe AG. The operations of Alnylam Europe AG were acquired by Roche in 2007 as part of their broad RNAi therapeutics alliance with Alnylam.

“We are pleased with the decision by the USPTO to allow these new claims from the Woppmann et al. patent series, which we believe covers important design features for the development of RNAi therapeutics. This patent derives from the early and comprehensive research performed at Ribopharma AG that characterized design, length, and motif features of siRNAs,” said Barry Greene, President and Chief Operating Officer of Alnylam. “This new U.S. patent continues to broaden the scope of our intellectual property portfolio covering compositions, methods, and uses of RNAi therapeutics.”

The claims for the newly allowed patent cover compositions and methods for siRNAs, including:


a double-stranded RNA (dsRNA) of any length having effectiveness in inhibiting a target gene by RNAi;

“overhang” and “blunt-end” design features and certain nucleotide pair motifs; and,

a 19-28 nucleotide region of the antisense strand that is complementary to the target gene.

[mitleser3108]

Antwort auf Beitrag Nr.: 39.287.164 von mitleser3108 am 07.04.10 14:14:45

dirk haussecker sieht das wesentlich kritischer als ich gestern, seine vollständige analyse hier:

http://rnaitherapeutics.blogspot.com/2010/04/alnylam-with-do…

besonderst interresant:

Alnylam is considered the 800-pound gorilla when it comes to RNAi trigger IP, and rightly so.

In fact, most competitors would give an arm and a leg for such a patent that gives broad freedom to design effective siRNAs. It is therefore difficult to understand why the company characterizes the patent in the press release as if it had broad power to exclude, while the actual claims are much more specific than that.

By this, it risks to lose the trust of an already wary investor base, quite confused anyway by the barrage of press releases.

Worse than that would be if Woppmann would be considered to substitute for the Tuschl patents should the lawsuit not end in Alnylam’s favor.

This is not to say that it is any worse than the PR policies of a number of other competing companies in the space.

However, to maintain its leadership position in RNAi Therapeutics, it is important to maintaining the credibility of a company that has suffered recently.[/i]

[mitleser3108]

Antwort auf Beitrag Nr.: 39.293.283 von mitleser3108 am 08.04.10 11:13:33

http://www.nature.com/mt/journal/vaop/ncurrent/abs/mt201085a…

http://alnylam.com/Files/Presentations/ALN-TTR_AmyloidosisSy…

[mitleser3108]

http://abstract.asco.org/AbstView_74_51118.html

Interim safety and pharmacodynamic results for ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement.


Sub-category: Antiangiogenic Agents
Category: Developmental Therapeutics - Experimental Therapeutics
Meeting: 2010 ASCO Annual Meeting
Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 3042)
Type: General Poster Session
Time: Monday June 7, 8:00 AM to 12:00 PM

Author(s): J. Gollob, J. R. Infante, G. Shapiro, P. LoRusso, B. J. Dezube, J. Heymach, J. Cehelsky, R. Falzone, A. Vaishnaw, H. A. Burris III; Alnylam Pharmaceuticals, Cambridge, MA; Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Dana-Farber Cancer Institute, Boston, MA; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Beth Israel Deaconess Medical Center, Boston, MA; University of Texas M. D. Anderson Cancer Center, Houston, TX; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN

Abstract:
Background: Malignancies involving the liver represent a significant unmet medical need. ALN-VSP02 is a novel RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs (siRNAs) targeting the expression of vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP).
Methods: A multicenter, open label, phase 1 dose escalation trial of ALN-VSP02 administered as a 15-minute iv infusion every two weeks was initiated in March 2009. Patients with advanced solid tumors are eligible if they have at least one measurable liver lesion and adequate liver function. The study uses a 3+3 design with 8 potential dose levels: 0.1, 0.2, 0.4, 0.7, 1.0, 1.25, 1.5, and 1.7 mg/kg. The primary objective is evaluation of safety and tolerability. Secondary objectives include assessment of PK and pharmacodynamic (PD) activity through DCE-MRI, biomarkers of angiogenesis, tumor biopsies, and response rate. Results: As of December 2009, 12 patients (most with colorectal cancer) have been treated on the first 4 dose levels. Forty-one doses have been administered; 0.1-0.4 mg/kg ALN-VSP02 was well- tolerated, with no hepatotoxicity. The only significant adverse event (AE) was a grade 2 infusion reaction in one patient at 0.4 mg/kg that responded to slowing of the infusion. At 0.7 mg/kg, a patient with pancreatic neuroendocrine tumor extensively involving both lobes of the liver died of hepatic failure following the second dose; this was deemed possibly related to study drug. Two additional patients treated at 0.7 mg/kg did not exhibit hepatotoxicity or any other significant AEs. PK showed Cmax and AUC that were dose proportional with no accumulation. Serial DCE-MRI scans performed 2-9 days after the first dose on 8 of the 12 patients showed a ≥40% decline in Ktrans in 12 of 15 liver tumors (80%) evaluated. This decline in blood flow was associated with extensive tumor necrosis in the patient with the neuroendocrine tumor.
Conclusions: ALN-VSP02 was well-tolerated by the majority of patients across the first 4 dose levels. DCE-MRI results show preliminary evidence of an anti-VEGF effect. Accrual is continuing, and additional safety and PD data will be forthcoming.

und DH dazu:
http://rnaitherapeutics.blogspot.com/2010/05/aln-vsp02-inter…

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Alnylam and Collaborators Publish New Pre-clinical Research on Therapeutic Silencing of Parkinson's Disease Gene

23 Aug 2010

– New Research Published in Journal “PLoS” Shows Silencing of Alpha-Synuclein in the Substantia Nigra of Non-Human Primates with an RNAi Therapeutic

CAMBRIDGE, MA, USA | August 23, 2010 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, and collaborators at The Parkinson’s Institute and the Mayo Clinic have published new research findings in the journal Public Library of Science (PLoS). The new data show effective silencing of the alpha-synuclein gene with an RNAi therapeutic administered directly to the substantia nigra in the CNS of non-human primates. Alpha-synuclein is widely believed to play a central role in the development of Parkinson’s disease, where the accumulation of excess alpha-synuclein protein in the substantia nigra has been associated with the cause and/or progression of the disease.

“These new findings add to a growing body of data on the applications of RNAi therapeutics for the treatment of neurodegenerative disorders, such as Parkinson’s disease. Indeed, direct delivery of RNAi therapeutics in the CNS represents an important component of our overall product development strategy,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “We remain committed to advancing this promising therapeutic modality to patients.”

Parkinson’s disease is a chronic, degenerative neurological disorder that affects dopaminergic neurons in the brain involved in the control of movement. Symptoms include tremor, slowed movement, and rigid muscles. Recent research indicates that at least one million people in the United States, and more than five million worldwide, suffer from Parkinson’s disease. There exists a significant need for disease modifying therapies for the treatment of Parkinson’s disease as no such treatments are currently available.

“A wide range of genetic, epidemiologic, and laboratory data support the hypothesis that reducing levels of alpha-synuclein in the brain may slow or even halt the progression of Parkinson’s disease and its associated symptoms,” said Donato A. Di Monte, M.D., Professor & Senior Research Group Leader at the German Center for Neurodegenerative Diseases (DZNE) in Bonn, and previously with The Parkinson’s Institute. “Accordingly, we are encouraged by these important results, which for the first time demonstrate RNAi-mediated silencing of alpha-synuclein in the substantia nigra of non-human primates. To date, no drugs have been identified that are capable of lowering alpha-synuclein levels, and these data certainly support further development of an RNAi-based approach for the treatment of Parkinson’s disease.”

The published data (McCormack et al., PloS ONE, 5: e12122, 2010) demonstrated that direct delivery of chemically modified siRNAs specific for alpha-synuclein resulted in significant silencing of the target gene in the substantia nigra in the non-human primate brain. A significant 40-50% suppression of both alpha-synuclein mRNA and protein levels was observed in treated animals, as compared to controls. In these preliminary studies, the siRNA was found to be well tolerated after direct CNS administration; no complications or adverse events were observed, including the absence of detectable microglial activation or change in the number of nigral dopaminergic neurons. These results suggest that RNAi therapeutics may be useful in reducing the pathogenic burden of alpha-synuclein in patients with Parkinson’s disease.

The study was conducted in collaboration with scientists at Mayo Clinic and The Parkinson’s Institute, and funded by a “LEAPS” (Linked Efforts to Accelerate Parkinson’s Solutions) award from The Michael J. Fox Foundation for Parkinson’s Research. Alnylam has an agreement with the Mayo Clinic whereby Mayo has granted Alnylam an exclusive license to certain patents and know-how related to alpha-synuclein.

[Fruehrentner]

Ganz schön abgesackt der Kurs

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Alnylam Publishes Results from Phase IIa Study of ALN-RSV01 in the Treatment of Respiratory Syncytial Virus Infection in Lung Transplant Patients

29 Sep 2010

Alnylam Pharmaceuticals announced that it has published results in the American Journal of Respiratory and Critical Care Medicine from its double-blind, placebo-controlled, randomized Phase IIa study of ALN-RSV01 in lung transplant patients naturally infected with respiratory syncytial virus (RSV)

CAMBRIDGE, MA, USA | September 29, 2010 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company announced today that it has published results in the American Journal of Respiratory and Critical Care Medicine (Zamora et al., Am. J. Respir. Crit. Care Med., doi:10.1164/rccm.201003-0422OC, 2010) from its double-blind, placebo-controlled, randomized Phase IIa study of ALN-RSV01 in lung transplant patients naturally infected with respiratory syncytial virus (RSV). These data, presented previously at the BIT Life Science’s 2nd Annual Summit of Antivirals held in Beijing, China in July 2009, documented for the first time safety and tolerability of inhaled ALN-RSV01 in a naturally infected patient population. The results also demonstrated statistically significant improvements in clinical symptom scores and reductions in the incidence of bronchiolitis obliterans syndrome (BOS), an irreversible and life-threatening complication of RSV infection in lung transplant patients resulting in approximately 50% mortality within three to five years of onset.

“Our Phase IIa study of ALN-RSV01 demonstrated safety and tolerability in a naturally infected patient population. The study also demonstrated statistically significant effects on certain clinical endpoints that warrant verification in a larger study such as our current Phase IIb study which is actively enrolling,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President of Clinical Research. “We are also pleased with the continued and growing track record of Alnylam publications regarding our clinical trial results, as these importantly demonstrate our translation of RNAi therapeutics to patients.”

The Phase IIa study was conducted at 11 sites in four countries, where 24 lung transplant patients with confirmed RSV infection were randomized to receive inhaled ALN-RSV01 or placebo once daily for three consecutive days. Overall, the study achieved its primary objective of demonstrating safety and tolerability of ALN-RSV01. Interpretation of anti-viral effects for ALN-RSV01 was confounded by an imbalance in certain baseline patient characteristics. There was a statistically significant improvement in clinical symptom scores in patients receiving ALN-RSV01. Further, although the study was not powered for efficacy due to the small sample size, data at 90 days showed preliminary evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS, as compared with placebo (p=0.02).

“RSV infection in lung transplant patients is a cause of significant morbidity and even mortality due to the potential for both acute and chronic lung rejection,” said Martin Zamora, M.D., Professor of Medicine, and Medical Director, Lung Transplant Program, University of Colorado Health Sciences Center, and Principal Investigator for the trial in the U.S. “The results from this Phase IIa study with ALN-RSV01 are encouraging and support the continued development of an RNAi therapeutic for the treatment of RSV infection, a major unmet medical need with no effective treatments. I am pleased to be involved in the ongoing Phase IIb in the adult lung transplant patient population and look forward to continuing enrollment in this trial.”

As a result of this study, Alnylam initiated earlier this year a multi-center, global, randomized, double blind, placebo-controlled Phase IIb trial for ALN-RSV01 in RSV-infected adult lung transplant patients. This new study aims to repeat and extend the results of the Phase IIa study. The primary endpoint is the incidence of new or progressive BOS. Secondary endpoints include assessments for safety and additional measurements of efficacy, including: anti-viral activity; recovery of lung function, as monitored by the proportion of patients with forced expiratory volume in the first second (FEV1); and, improvement in RSV symptoms as measured by mean cumulative daily total symptom score. The Phase IIb study is expected to enroll up to 76 patients.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington’s disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals, Inc.

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Alnylam Presents Additional Interim Phase I Data for ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancer

12 Nov 2010

- 28 Patients Treated to Date with 127 Total Number of Doses as High as 1.25 mg/kg with Dose Escalation Continuing
– Results to Date Demonstrate Tolerability and Evidence for Pharmacodynamic Activity, Providing Key Human Data for Alnylam Systemic Delivery Platform

CAMBRIDGE, MA, USA | November 12, 2010 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today presented additional interim data from its ongoing Phase I trial with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The data were presented at the Chemotherapy Foundation Symposium being held in New York City. Data from pharmacodynamic measurements shown earlier this year provided preliminary evidence of clinical activity, and new results from the initial 28 patients in the first six dose cohorts demonstrate that ALN-VSP is generally well tolerated. The study has not yet reached a maximum tolerated dose (MTD) and the trial continues to enroll patients with dose escalation. Importantly, the safety results from this study provide a significant human experience database applicable to broader elements of the Alnylam systemic delivery pipeline, including ALN-TTR01, an RNAi therapeutic for the treatment of transthyretin-mediated amyloidosis (ATTR) which is also in a Phase I clinical trial.

“We continue to be encouraged by the data emerging from our ALN-VSP program, as they represent key clinical results from our most advanced systemically delivered RNAi therapeutic. Indeed, these data are not only important for the continued advancement of our ALN-VSP program, but they also significantly increase our confidence in our entire platform of systemically delivered RNAi therapeutics, including ALN-TTR01 which is in a Phase I study for ATTR,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research. “In our ALN-VSP Phase I study, the MTD has not yet been reached and we continue to enroll patients in a dose-escalating manner. In addition, several patients with stable disease have advanced to an extension study. The next steps in this program include continued patient accrual to determine MTD, and further assessment of safety and activity in the MTD expansion phase of the study. We have also obtained a significant number of human biopsy samples in this study with which we intend to perform molecular analyses for RNAi delivery and pharmacology. We expect to further update these results at the annual ASCO meeting in 2011.”

“Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed. These interim data with multiple doses of ALN-VSP, combined with the data presented earlier in the year, are encouraging and we look forward to continued dose escalation to explore tolerability and potential for tumor response,” said Howard A. (Skip) Burris, III, M.D., Chief Medical Officer; Director, Drug Development of the Sarah Cannon Research Institute in Nashville, Tennessee, and a Principal Investigator for the ALN-VSP Phase I study. “To our knowledge, ALN-VSP is the most advanced RNAi therapeutic for the treatment of cancer, and the clinical experience to date represents the most extensive experience in advancing this promising approach to patients.”

Data presented today demonstrate that ALN-VSP is well tolerated in most patients. The maximum tolerated dose has not yet been reached and enrollment in the trial is continuing in a dose escalating manner. A total of 127 doses of ALN-VSP ranging from 0.1 to 1.25 mg/kg have been administered to 28 patients, with two to 13 doses administered per patient. The majority of these patients have colorectal cancer, a primary tumor that often metastasizes to the liver.

Several patients enrolled in the higher dose groups have achieved stable disease. Patients who achieved stable disease have been enrolled in a dose extension study which continues to actively enroll. This trial is designed to enroll patients that have completed four months of dosing cycles and achieved designation of at least stable disease.

No dose-dependent trends have been observed in clinical or laboratory adverse events, including liver function tests (LFT). As previously presented at the ASCO 2010 meeting, a patient with advanced pancreatic neuroendocrine cancer with extensive involvement of the liver developed hepatic failure five days following the second dose at 0.7 mg/kg, and subsequently died; this was deemed possibly related to study drug. At 1.25 mg/kg, a patient experienced grade three thrombocytopenia after the first dose; this was deemed related to study drug and was resolved within five days. There have been three acute infusion reactions at 0.4, 0.7, and 1.25 mg/kg; all three patients tolerated further treatment with prolongation of infusion duration. None of these events preclude further dose-escalation.

This Phase I trial is also designed to obtain tumor biopsies from patient volunteers. To date, 17 biopsies have been obtained from nine patients. These include liver and extrahepatic tumors biopsies that have been obtained in patients who have received ALN-VSP at doses ranging from 0.4 to 1.25 mg/kg. Histopathological and molecular analyses are ongoing to assess drug delivery, RNAi mediated activity, and mRNA target engagement. Alnylam anticipates obtaining multiple additional biopsies as the study progresses.

As previously presented at the ASCO 2010 meeting, DCE-MRI results from patients treated at the 0.1 to 0.7 mg/kg dose levels were suggestive of an anti-VEGF effect in the majority of treated patients. In 62% of evaluable liver tumors, there was a greater than 40% decline in Ktrans (measure of blood flow), an effect that is comparable to what has been observed with other anti-VEGF drugs in solid tumors (Cannistra et al., Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S, 2006; and Siegel et al., Journal of Clinical Oncology, Vol 26, No 18: pp. 2992-2998, 2008). Also, as previously presented at ASCO 2010, pharmacokinetic data shows that Cmax (peak serum concentration of drug) and area under the curve (AUC) were dose proportional with no evidence of drug accumulation.

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Alnylam reveals new data on applications of RNAi technology

Published 18 November 2010

Alnylam Biotherapeutics has revealed new data from its platform efforts aimed at developing RNAi technologies for applications in biologics manufacturing at the MIT Center for Biomedical Innovation's Biomanufacturing Summit.


The new studies show that siRNAs designed to target a virus known to infect CHO cells - cells that are commonly used to produce recombinant proteins and monoclonal antibodies - can potently block infection and viral replication.

Alnylam said that RNAi technologies to prevent or treat viral infection of manufacturing cell lines could provide a novel strategy to ensure product quality of biotherapeutic products for patients.

In the new study, performed in collaboration with Ian Goodfellow from Imperial College London, siRNAs were designed and synthesised toward vesivirus.

Alnylam chief scientific officer Ken Koblan said that they remain excited about the Alnylam Biotherapeutics platform and how this application of RNAi technology has the potential to transform the manufacturing of biotherapeutic products.

"These new data describe applications of RNAi technologies to block viral infection of CHO cells - an approach that could preserve quality in biologics manufacturing and also maintain consistency of product supply, Koblan said.

"By all accounts, these encouraging new findings are representative of the rapid progress we are making in this overall effort, and highlight important new applications of our biotherapeutics platform."

[Aliberto]

Alnylam Caught Off - Guard by Roche Decision to Drop Alliance
by: The Burrill Report November 21, 2010


By Michael Fitzhugh

Roche (RHHBY.PK) will cut thousands of jobs and end a closely watched gene silencing partnership with Alnylam Pharmaceuticals (ALNY) as part of a deep cost-cutting and reorganization plan.

The Swiss drug giant will trim and outsource 6,300 U.S. and European positions altogether, mostly in sales, marketing, and manufacturing. The job and program cuts have been anticipated ever since the company announced plans to reorganize in September.

But Roche’s decision to abandon Alnylam caught even Alnylam off-guard, prompting CEO John Maraganore to say the company is “disappointed and surprised to hear of their portfolio decision given the progress being made in the RNAi field.” The decision would not fundamentally impact Alnylam’s financial position or its current or future plans, Maraganore added.

Alnylam has long benefited from its relationship with Roche and fevered industry interest in the Nobel-winning potential of gene silencing methods, a fire Merck (MRK) helped fuel with its $1.1 billion cash acquisition of Sirna Therapeutics in 2006.

Since 2007 Roche and Alnylam have worked on four major therapeutic areas, including oncology, respiratory diseases, metabolic diseases and certain liver diseases. Roche invested $331 million upfront to jumpstart the partnership and even bought Alnylam’s European research site in Kulmbach, Germany, making it Roche’s Center of Excellence for RNAi therapeutics discovery.

Now the Kulmbach site will close, as will RNA interference research operations in Nutley, New Jersey, and Madison, Wisconsin, impacting about 600 jobs altogether.

Fall hasn’t been kind to Alnylam, which came to the end of a five-year partnership with Novartis (NVS) in September, a loss that prompted it to cut 25 to 30 percent of its workforce. But the company remains confident. Its technology platform holds the potential to leverage a naturally occurring biological pathway within cells to selectively silence and regulate gene expression. That could open up a whole new class of drugs for treating a wide range of diseases that current drugs can’t touch. It also has a host of other alliances with companies such as Cubist Pharmaceuticals (CBST), Medtronic (MDT), Takeda Pharmaceuticals (TKPHF.PK), Biogen Idec (BIIB), and Sanofi-Aventis (SNY).

“We believe we are on the frontier of demonstrating human proof-of-concept for these and other programs in the near term, and we are confident that these data will provide a strong foundation for continued execution on our business model and value creation strategy,” says Maraganore.

Tekmira Pharmaceuticals, a Vancouver company with an exclusive manufacturing relationship with Alnylam, will also lose some business due to Roche’s cutbacks, but says that it doesn’t expect Roche’s decision to have a “substantive impact” on its business going forward.

[Fruehrentner]

RNA-Interferenz

Einfach stillgelegt
Die Technik der RNA-Interferenz birgt für die Medizin große Möglichkeiten. Deutsche Forscher erkannten das früh. Doch jetzt stoppen Wirtschaftsstrategien die Umsetzung der Idee.

Von Sascha Karberg

http://www.faz.net/s/Rub7F74ED2FDF2B439794CC2D664921E7FF/Doc…

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Alnylam Demonstrates RNAi in Man with Systemically Delivered RNAi Therapeutics
04 Jan 2011

– Analysis of Liver Biopsy Samples from Patients in ALN-VSP Phase I Trial Shows Achievement of Pharmacologically Relevant Tissue Drug Levels and Specific RNAi-Mediated Cleavage of Target mRNA –

CAMBRIDGE, MA, USA | January 4, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, today presented new clinical data from its ALN-VSP Phase I liver cancer trial in a presentation at the Dana-Farber Cancer Institute in Boston. Results from molecular analysis of human biopsy samples showed achievement of pharmacologically relevant siRNA drug levels in tissues. In addition, using a highly precise polymerase chain reaction (PCR)-based technique known as 5’- rapid amplification of cDNA ends (5’-RACE), analysis of human tissue samples showed proof of RNAi-mediated target mRNA cleavage, and thus RNAi in man with the systemically delivered RNAi therapeutic. These results provide significant human proof of concept for Alnylam’s efforts in advancing RNAi therapeutics to patients.

“These data provide conclusive evidence that RNAi can be harnessed in man and, as such, represent a notable and important milestone in the advancement of RNAi therapeutics as a potential new class of medicines,” said Phillip Sharp, Ph.D., Institute Professor, The Koch Institute for Integrative Cancer Research, MIT, and Chairman of Alnylam Scientific Advisory Board and Alnylam Director. “I applaud Alnylam scientists, clinicians, and their collaborators for reaching this important achievement and I look forward to the results of their continued efforts.”

Post-treatment tumor biopsies from eight patients were analyzed for ALN-VSP drug levels. All biopsy samples were obtained on a voluntary basis using a CT-guided procedure. Five of these biopsy samples were obtained from tumor in the liver and three were taken from tumor located outside the liver in patients receiving doses of ALN-VSP ranging from 0.4 to 1.25 mg/kg. The two siRNAs targeting VEGF and KSP that comprise ALN-VSP were detected in almost all of these biopsy samples at concentrations ranging from 0.3 to 142 ng/g tissue. These levels of siRNA are pharmacologically relevant since in pre-clinical studies with systemically delivered siRNAs, a tissue level of 1 ng/g has been shown to be associated with 50% target gene silencing (Landesman et al., Silence, 1:16, 2010).

RNAi is an endogenous cellular enzymatic process whereby siRNAs mediate sequence-dependent cleavage of target mRNAs; cleavage of the target mRNA is highly precise, occurring exactly 10 nucleotide positions from the 5’-end of the siRNA antisense strand. In order to establish RNAi-mediated effects in vivo, 5’RACE has been established as a robust method for detecting the specific cleavage products of siRNA pharmacology in pre-clinical animal models (Soutschek et al., Nature, 432: 173-8, 2004; Zimmermann et al., Nature, 441: 111-4, 2006). As a PCR-based technique, 5’RACE is not a quantitative measurement; a positive result simply confirms that there is evidence of RNAi-mediated target mRNA cleavage.

As currently analyzed, three patients had biopsies that were of sufficient quality to permit blinded 5’ RACE analysis for the VEGF target mRNA following the first dose of ALN-VSP; additional analyses are ongoing. All three biopsy samples were from the 0.4 mg/kg dose group, and post-treatment biopsy samples were comprised of 80% to 100% normal liver. In two patients whose post-treatment biopsies were performed two days after dosing, the 5’ RACE assay combined with deep sequencing showed that approximately 27% and 29% of all VEGF-derived mRNA fragments corresponded exactly to the predicted RNAi-mediated cleavage product based on the VEGF siRNA sequence. By contrast, a pre-dose biopsy available for one of those patients contained only approximately 1% predicted VEGF cleavage product, and analysis of banked normal liver and tumor samples from untreated patients showed a background level of only 0.1% to 0.7%. Compared to these low background levels, the amount of predicted VEGF cleavage product in the two post-treatment biopsies was highly statistically significant (p<0.0001). In the third patient at 0.4 mg/kg whose post-treatment biopsy was obtained 7 days post-dose, there was no detectable increase in the predicted VEGF cleavage product compared to the pre-dose biopsy. These positive 5’ RACE data from human biopsies provide clear evidence for RNAi in man following systemic administration of lipid nanoparticle (LNP)-formulated siRNA.

“Achievement of these results is very important for Alnylam’s overall RNAi therapeutics efforts, and has many implications. First, we have been able to quantify significant human tissue levels of siRNAs at concentrations that exceed our 1 ng/g target level that is associated with effective target gene silencing in pre-clinical animal models. More importantly, we have demonstrated proof of RNAi mechanism in man with LNP delivery of siRNAs, an important milestone in overall human translation of RNAi therapeutics,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “As this systemic delivery platform is employed in our pipeline of clinical and development-stage programs, we believe that we have now made a major leap forward in advancing RNAi therapeutics to patients.”

About ALN-VSP Clinical Program

ALN-VSP is Alnylam’s first systemic RNAi program and represents the company’s first clinical program in oncology. ALN-VSP is a systemically delivered RNAi therapeutic comprising two siRNAs designed to target two genes critical for the growth and survival of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), also known as eglin 5 (Eg5). The drug is formulated in a first generation LNP developed by Tekmira Pharmaceuticals Corporation. The ongoing Phase I trial is a multi-center, open label, dose escalation study designed to enroll approximately 55 patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective is to evaluate safety and tolerability of eight potential dose levels ranging from 0.1 to 1.7 mg/kg. Secondary objectives include characterization of pharmacokinetics, and assessment of pharmacodynamic effects and tumor response through Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients’ disease improves, stabilizes, or progresses during treatment; change in tumor blood flow or vascular permeability as measured by Dynamic Contrast - Enhanced Magnetic Resonance Imaging (DCE-MRI); change in plasma biomarkers of angiogenesis; and, molecular and cellular analyses of tumor biopsy samples.

Prior data presented at the November 2010 Chemotherapy Foundation Symposium showed that 127 doses of ALN-VSP at dose levels of 0.1 to 1.25 mg/kg had been administered to 28 patients and was generally well tolerated. A total of two dose limiting toxicites were reported to be possibly or probably related to drug treatment. The maximum tolerated dose had not yet been reached and dose escalation was continuing. In addition to the data presented in November, DCE-MRI results were previously presented at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. DCE-MRI results from patients treated at the 0.1 to 0.7 mg/kg dose levels were found to be suggestive of an anti-VEGF effect in the majority of treated patients. In 62% of evaluable liver tumors, there was a greater than 40% decline in Ktrans (measure of blood flow), an effect that is comparable to what has been observed with other anti-VEGF drugs in solid tumors (Cannistra et al., Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S, 2006; and Siegel et al., Journal of Clinical Oncology, Vol 26, No 18: pp. 2992-2998, 2008).

About Liver Cancers

Cancer affecting the liver, known as either primary or secondary liver cancer, is associated with one of the poorest survival rates in oncology and represents a major unmet medical need affecting a large number of patients worldwide. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 600,000 people diagnosed each year. Secondary liver cancer, also known as metastatic liver cancer, is cancer that spreads to the liver from another part of the body due to other common cancers like colon, lung, or breast cancer. Worldwide, more than 500,000 people are diagnosed with secondary liver cancer each year.

[Fruehrentner]

Alnylam ALN-TTR01 gets COMP positive opinion for orphan drug status

Published 26 January 2011

Alnylam has received positive opinion from the European Medicines Agency's (EMA) Committee for Orphan Medicinal Products (COMP) regarding orphan drug status for ALN-TTR01, as a treatment for familial amyloidotic polyneuropathy (FAP).


ALN-TTR01 is a systemically delivered RNAi therapeutic being developed for the treatment of all forms of ATTR, which includes FAP and familial amyloidotic cardiomyopathy (FAC).

Alnylam Regulatory Affairs vice president Saraswathy Nochur said they believe that RNAi therapeutics targeting transthyretin could represent a major advance for the treatment of ATTR - a significant unmet medical need where breakthrough therapies are needed.

"Our ongoing Phase I trial is actively enrolling patients and is focused on demonstrating safety and tolerability of ALN-TTR01; importantly, it is also designed to capture key data on clinical activity through measurements of serum TTR levels," Nochur said.

"We are on track to complete enrollment in this study by the end of the first half of this year and to report data in the third quarter."

[Aliberto]

Aus der FTD vom 22.02.2011:

Spektakuläre Erfindung

Pharma lässt Nobelpreis-Technologie sausen
Die Entdeckung der RNA-Interferenztechnik löste vor wenigen Jahren Milliardeninvestitionen aus. Doch noch immer warten Pharmakonzerne vergeblich auf lukrative Produkte – und wenden sich von der Wunderendeckung ab. von Ruth Fend
Der größte Pharmakonzern der Welt lässt eine nobelpreisgekrönte Technologie fallen - und kaum einer guckt hin. Kein Wunder. Pfizer kündigt Anfang des Monats an, seine Forschungsausgaben von über 9 Mrd. Dollar mal eben auf 6,5 Mrd. Dollar zu kürzen. Was ist da schon ein gestrichener Forschungsstandort mit 100 Mitarbeitern? Nun, für einen der größten Medizinhypes der letzten Jahre ist es ein weiterer Hieb in einer ganzen Serie von Rückschlägen. Die nobelpreisgekrönte RNA-Interferenz-Technik (RNAi), so scheint es, fällt dem Sparzwang von Big Pharma zum Opfer.

2006 gewinnen Andrew Fire und Craig Mello den Nobelpreis für ihre Entdeckung, dass der mit DNA verwandte Botenstoff RNA Gene ein- und ausschalten kann. Theoretisch könnten sämtliche mit Krankheiten verbundene Gene mit einem Schnipsel doppelsträngiger RNA ausgeschaltet werden. Die großen Pharmakonzerne sind elektrisiert: Roche baut in Kulmbach einen Technologiepark und steckt 1 Mrd. Dollar in eine Kooperation mit der RNAi-Firma Alnylam. Novartis investiert 700 Mio. Dollar in das US-Biotechunternehmen. Merck kauft für über 1 Mrd. Dollar Sirna; auch Pfizer, GlaxoSmithKline und AstraZeneca machen dreistellige Millionendeals.
Doch bisher ist die erhoffte Fülle vermarktbarer Medikamente ausgeblieben, der Enthusiasmus der großen Pharmafirmen verfliegt. Roche verkündet im November 2010, das Zentrum in Kulmbach zu schließen. Novartis lässt das Kooperationskommen mit Alnylam still auslaufen. Nun zieht sich sogar Pfizer zurück.

Die Forschergemeinde ist schockiert. "Gerade in den letzten ein, zwei Jahren dachten wir: Jetzt werden endlich die entscheidenden Fortschritte gemacht", sagt Jörn Erselius, Geschäftsführer der Technologie-Transfer-Gesellschaft Max-Planck-Innovation, die auch für Alnylam forscht. Zu lösen gilt es vor allem ein Problem: die Botenstoffe an die Stelle im Körper zu bringen, wo sie wirken sollen.
"Wenn man etwas so Umwälzendes entdeckt, träumen die Leute manchmal von zu großen Dingen", erklärt sich Andrés McAllister, Forschungsvorstand beim Schweizer Pharmaunternehmen Debiopharm, die Wende. Seine Firma hat vorletzte Woche den Kauf der RNAi-Firma Marina Biotech verkündet. Debiopharm will sich auf ein einzelnes Feld konzentrieren, bei dem sich der Transport der Wirkstoffe erübrigt: die Behandlung von oberflächlichem Blasenkrebs. Ist der Tumor erst operativ entfernt, soll das Präparat direkt in die Blase gegeben werden. "So etwas in der Art machen auch andere, die an RNAi noch dran sind", so McAllister.
Den großen Konzernen sind solche Nischen offenbar nicht genug, um hohe Investitionen zu rechtfertigen. Man konzentriere sich nun "auf die größten Hoffnungsträger und Therapiegebiete mit dem größten medizinischen Bedarf", sagt ein Pfizer-Sprecher. Im Fall des Schweizer Konzerns Roche, der Tausende Stellen streicht, mutmaßt Erselius: "RNAi könnte schon der Strategie der Pharmaunternehmen zum Opfer gefallen sein, sich auf Entwicklungen in späteren Phasen zu konzentrieren."

Für Anton Gueth, Analyst bei Life-Science-Spezialist Burrill & Company, wiederholt sich gerade die Geschichte. Ab Mitte der 70er-Jahre hätten die Konzerne von patentgeschützten Blockbuster-Medikamenten profitiert und viel in eigene Forschung investiert. "Dieser Zyklus kommt jetzt ans Ende, und wir sind wieder da, wo wir damals waren. Die Grundlagenforschung wandert zu einem größeren Teil wieder in die Universitäten", sagt Gueth. Am Ende sieht er die RNAi-Technologie damit aber noch nicht - ebenso wenig wie Erselius. Der Wissenschaftler sorgt sich zwar, dass die Abnehmer für seine Technologien wegbrechen. Er gesteht aber zu: "Alle großen Pharmafirmen denken über neue Formen der Kooperation mit akademischen Forschungseinrichtungen nach und wollen da auch mehr Geld reingeben." Außerdem sei die Industrie selbst viel offener geworden, was ihre eigene Forschung angehe.
Roche bestreitet gar, überhaupt zu sparen. "Unser Gesamtinvestment für Forschung und Entwicklung wird dieses Jahr nicht wesentlich unter dem letztem Jahr liegen", sagt eine Sprecherin. Auch frühen Forschungsphasen wolle man sich verstärkt widmen - nur eben nicht selbst, sondern über Lizenzvereinbarungen mit Biotechfirmen und wissenschaftlichen Zentren. Und was RNAi betrifft: "Das werden wir sorgfältig beobachten und könnten dort auch wieder aktiv werden."

Was das medizinische Potenzial angeht, ist Erselius weiter optimistisch. "RNAi könnte Behandlungen so revolutionieren wie einst monoklonale Antikörper die Krebstherapien. Das hat auch 20 Jahre gedauert." Auch damals erlosch die Begeisterung von Pharmakonzernen nach einer frühen Investitionsphase wieder, Biotechfirmen hingegen machten weiter. Alnylam-Chef John Maraganore drückte es in der "New York Times" ähnlich aus: "Viele Leute denken, dass für RNAi Winter ist. Ich denke, es ist Frühling."
Die Frage ist, ob die Durchbrüche je kommen - oder den forschenden Unternehmen und der Wissenschaft ob nicht gerade Biotechfirmen vorher das nötige Geld ausgeht. "In frühe und riskante Technologien zu gehen hat sich für kleinere Firmen auf Dauer nicht gerechnet. Sie standen zu sehr unter dem Druck der Pharmaindustrie, sich auch auf aussichtsreichere Dinge zu konzentrieren", so Erselius. Der Wissenschaftler sieht Biotech als möglichen Verlierer des Trends. Denn auch Wagniskapital kann nicht alle Lücken füllen, die Pharma reißt. Seit der Wirtschaftskrise fließt es spärlicher. Für Anton Gueth ist deshalb klar, wer Instituten und Biotech mit höherer Förderung beistehen muss: der Staat.

[Fruehrentner]

Alnylam Pharma gets $10m under Takeda alliance

Published 29 March 2011

Alnylam Pharmaceuticals has got $10m from Takeda Pharmaceutical, under the agreement signed between the two parties in May 2008.

The payment triggers from the transferring of Alnylam's RNA interference drug technology to Takeda Pharma for the development of RNAi therapeutics.

Earlier, Alnylam has obtained $140m in upfront and technology transfer payments from Takeda.

Further, Anylam is also entitled to receive milestones and royalties related to the Takeda's advancement of RNAi therapeutic products, and has retained certain product opt-in rights in the US market.

Alnylam president and chief operating officer Barry Greene said they look forward to their continued work with them in developing RNAi therapeutics on a global basis, which includes Alnylam's opt-in right to co-develop and co-commercialize certain Takeda RNAi therapeutic products in the US market.

[Fruehrentner]

Precision NanoSystems and Alnylam Form New Delivery Collaboration

19 Apr 2011

Precision NanoSystems and Alnylam Pharmaceuticals announced that the two companies have formed an exclusive collaboration focused on the discovery and development of novel lipid nanoparticles, known as small lipid nanoparticles (“sLNPs”), using microfluidics technology

VANCOUVER, British Columbia, CANADA & CAMBRIDGE, MA, USA | April 19, 2011 | Precision NanoSystems, Inc. and Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, announced today that the two companies have formed an exclusive collaboration focused on the discovery and development of novel lipid nanoparticles, known as small lipid nanoparticles (“sLNPs”), using microfluidics technology. Based on their small particle size of approximately 20 nanometers, sLNPs have the potential for broadened biodistribution beyond liver delivery.

“We look forward to working with Precision NanoSystems to support research efforts around the discovery of novel sLNPs that we believe have the potential to significantly improve and broaden biodistribution,” said Kenneth Koblan, Ph.D., Chief Scientific Officer at Alnylam. “sLNPs represent an exciting and innovative approach in Alnylam’s advancement of proprietary LNPs for RNAi therapeutics.”

“We are excited to have formed this exclusive collaboration with Alnylam focused on the discovery and development of novel sLNPs using microfluidics technology,” said James Taylor, Ph.D., Chief Executive Officer of Precision NanoSystems. “Alnylam is leading the translation of RNAi technology into human therapeutics, and we look forward to working with them.”

[Fruehrentner]

Molecular Templates Announces RNAi Drug-Delivery Research Collaboration with Alnylam Pharmaceuticals

04 May 2011

Molecular Templates announced that it has entered into a research collaboration with Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, to evaluate and develop Molecular Templates’ proprietary technology for targeted delivery of RNAi therapies

GEORGETOWN, TX, USA | MAy 4, 2011 | Molecular Templates, Inc., a biopharmaceutical company focused on the discovery and development of a new class of small biologic therapies called Engineered Toxin Bodies (ETB), announced today that it has entered into a research collaboration with Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, to evaluate and develop Molecular Templates’ proprietary technology for targeted delivery of RNAi therapies. No financial terms were disclosed.

ETBs represent a new class of biologic therapies evolved from a toxin scaffold that have been engineered with a unique targeting domain and designed for reduced immunogenicity. ETBs retain the predictable pharmacokinetics, mechanism-of-action, ability to induce internalization, and intracellular self-routing capabilities of the parent scaffold. Molecular Templates has created vast libraries of ETBs that can be rapidly screened on functionality where the target may or may not be known a priori. These unique properties allow ETBs to target cell surface or intracellular targets that may be intractable to antibody or small molecule approaches.

“We look forward to working closely with Alnylam, the leader in the RNAi space, to capitalize on some of the unique capabilities of our ETB platform,” said Eric Poma, Ph.D., President and Chief Executive Officer of Molecular Templates. “ETBs represent a new class of targeted biologics that possess active intracellular properties that uniquely positions us to address delivery of RNAi drugs in a target directed manner.”

[Fruehrentner]

Tekmira secures licenses from Alnylam under InterfeRx program

Published 03 June 2011

Tekmira Pharmaceuticals has secured licenses from Alnylam Pharmaceuticals under its InterfeRx program to develop a new RNAi therapeutic targeting two validated oncology targets - WEE1 and CSN5.

Gene expression data from human tumor samples indicate that both CSN5 and WEE1 genes promote tumor cell growth and cancer pathogenesis.

WEE1 is a tyrosine kinase that regulates cell cycle progression and the response to DNA damage by its control of a cell cycle checkpoint that precedes entry into cell division.

Inhibiting WEE1 increases cancer cell sensitivity to DNA damaging agents and other therapies.

CSN5 is the catalytic center of the COP9 signalosome, a multi-protein complex involved in regulating protein degradation via the ubiquitin proteasome pathway. CSN5 regulates protein turnover and other protein interactions that affect many stages of tumorigenesis.

Silencing of CSN5 causes molecular changes that inhibit tumor cell growth and increases apoptosis (programmed cell death).

Lipid nanoparticle (LNP) delivery of siRNA targeting WEE1 effectively suppresses tumor growth and increases the survival of treated animals in preclinical models of human hepatocellular carcinoma (HCC or liver cancer) in a dose-dependent manner.

LNP delivery of siRNA against CSN5 resulted in 80% inhibition of tumor cell growth in vitro and significant reduction in tumor growth in preclinical models of human liver cancer.

A combination RNAi approach that depletes both WEE1 and CSN5 may be ideal for inactivating multiple pathways that promote cancer, and to avoid cellular resistance.

Combinations of WEE1 and CSN5 siRNA resulted in a significant increase in apoptosis in human liver cancer cells in vitro, relative to the action of each siRNA alone.

Tekmira is conducting additional preclinical work on a WEE1/CSN5 product candidate including the evaluation of a number of tumor specific LNP formulations prior to initiating formal toxicology studies required for filing an Investigational New Drug application.

Tekmira has access to eight InterfeRx licenses at pre-negotiated financial terms and has identified the first five targets, including ApoB, PLK1, Ebola, WEE1 and CSN5

[Fruehrentner]

Alnylam Presents Phase I Data for ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers, at American Society of Clinical Oncology (ASCO) Meeting

05 Jun 2011

RNAi Therapeutic Demonstrates Evidence for Anti-Tumor Activity in Advanced Malignancy Patients Biopsy Samples Show Drug Delivery and Proof of RNAi Mechanism in Both Hepatic and Extra-Hepatic Tumors

CAMBRIDGE, MA, USA | June 4, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, announced today the results from its Phase I clinical trial with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The data are being presented at the ASCO meeting in a poster titled “Phase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement,” in the Developmental Therapeutics – Experimental Therapeutics poster discussion session being held on Saturday, June 4, 2011 from 2:00 to 6:00 p.m. CDT. In this Phase I study, ALN-VSP was generally well tolerated, demonstrated evidence for anti-tumor activity, and was found to mediate RNAi activity in both hepatic and extra-hepatic tumors.

“We are very pleased with the Phase I results with ALN-VSP which include safety and tolerability of multiple doses of ALN-VSP, as well as evidence for anti-tumor activity in this very advanced, heavily pre-treated cancer patient population. In particular, we have seen multiple patients achieve stable disease or better, including a patient with endometrial cancer metastatic to the liver who has achieved 70% tumor regression so far and continues on study after having been on drug for over one full year,” said Jared Gollob, M.D., Senior Director of Clinical Research at Alnylam. “It is also notable that DCE-MRI results appear to show an anti-VEGF effect with ALN-VSP in approximately 50% of evaluable patients, including those who have been previously exposed to anti-VEGF drugs. Finally, analysis of tumor biopsy samples has demonstrated siRNA delivery and proof of RNAi mechanism in both hepatic and extra-hepatic tumors.”

Results from this Phase I study show that ALN-VSP was generally well tolerated. ALN-VSP was administered to 41 patients at doses ranging from 0.1 to 1.5 mg/kg; a total of 182 doses have been administered, including to one patient who has received 24 doses at 0.7 mg/kg over the course of more than one full year, and continues to receive treatment in the study. The most common adverse events were grade 1-2 fatigue (24% of patients), nausea (17% of patients) and fever (15% of patients), with no clear dose dependence. There were also no dose-dependent changes in liver function tests. Grade 2 infusion-related reactions were observed in 15% of patients, or 3% of total doses administered; these reactions responded to slowing of the infusion of drug, and no patients discontinued therapy because of an infusion reaction. Dose-limiting toxicities included: liver failure and death in one patient with extensive hepatic metastases and prior splenectomy/partial hepatectomy at 0.7 mg/kg which was deemed possibly related to study drug; transient grade 3 thrombocytopenia in two patients at 1.25 mg/kg; and grade 3 hypokalemia in one patient at 1.5 mg/kg. Based on these safety data, the recommended dose for advancement of ALN-VSP into Phase II studies is 1.0 mg/kg.

ALN-VSP demonstrated evidence of anti-tumor activity in advanced malignancy patients. Patients participating in the study were heavily pre-treated, having received an average of 4.3 prior treatment regimens for their metastatic cancer, including both chemotherapy and anti-angiogenic drugs. Fifty percent (12 of 24) of patients evaluable for response attained stable disease (SD) or better with ALN-VSP doses greater than or equal to 0.7 mg/kg, compared to only 8% (1 of 13) at doses less than or equal to 0.4 mg/kg. Results include one major ongoing response in a patient with endometrial cancer and multiple liver metastases treated at 0.7 mg/kg. This patient, whose treatment is ongoing after over one full year, has so far had a partial response (PR) with an approximately 70% reduction in tumor burden. Sixty four percent (7 of 11) of patients achieved SD at the recommended Phase II dose of 1.0 mg/kg and 45% (5 of 11) continue to receive drug on study. In addition, DCE-MRI results were suggestive of an anti-VEGF effect. In approximately 50% of evaluable patients, the average decline in Ktrans (measure of blood flow) in liver tumors where this parameter was measured was greater than or equal to 40%, an effect that is comparable to what has been observed with other anti-VEGF drugs in solid tumors (Cannistra et al., Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S, 2006; and Siegel et al., Journal of Clinical Oncology, Vol 26, No 18: pp. 2992-2998, 2008).

“Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed,” said Dr. Patricia LoRusso, D.O., Professor of Medicine, Director of the Phase I Clinical – Pharmacology Team at the Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine. “This Phase I study with ALN-VSP currently represents, to our knowledge, one of the most comprehensive clinical trials of a systemically delivered RNAi therapeutic and also one of the most extensive experiences with RNAi therapeutics in cancer. The safety data and anti-tumor activity with ALN-VSP are encouraging and I look forward to the further development of this promising agent.”

In this study, 29 tumor biopsies were obtained voluntarily from 15 patients across multiple dose levels (from 0.4 to 1.5 mg/kg) using a CT-guided procedure; these included hepatic (liver) tumor biopsies from 11 patients and extra-hepatic tumor biopsies from four patients. The two siRNAs targeting VEGF and KSP that comprise ALN-VSP were detected in nearly all of the biopsy samples evaluable for drug levels at siRNA concentrations ranging from 0.3 to 142 ng/g tissue. These levels of siRNA are pharmacologically relevant since pre-clinical studies have shown that siRNA tissue levels of 1 ng/g are associated with 50% target gene silencing (Landesman et al., Silence, 1:16, 2010). While there was no dose-dependence to the levels of VEGF and KSP siRNAs detected in biopsy samples, this finding was consistent with the high degree of variability in proportion of tumor, fibrotic/necrotic tissue, and normal tissue in biopsy samples, which impacts the quantitative interpretations of molecular results. Using a highly precise polymerase chain reaction (PCR)-based technique known as 5’ rapid amplification of cDNA ends (5’ RACE), blinded analysis of human tissue samples showed proof of RNAi-mediated target mRNA cleavage. Specifically, three of 15 biopsy samples showed VEGF-derived mRNA fragments corresponding exactly to the predicted RNAi-mediated cleavage product based on the VEGF siRNA sequence (p<0.001) in the post-treatment biopsy sample. The samples that were positive for VEGF 5’ RACE included liver tumor biopsies obtained from two patients dosed at 0.4 mg/kg and an extra-hepatic tumor biopsy from one patient dosed at 1.25 mg/kg. KSP 5’ RACE assay development is in progress, with further optimization required due to low expression of KSP mRNA in tissue samples.

Pharmacokinetic data from this study showed that Cmax (peak serum concentration of drug) and area under the curve (AUC) were dose proportional with no evidence of drug accumulation. Pre-clinical animal pharmacokinetic data were predictive for the observed results in man.

“We believe the results from our ALN-VSP Phase I trial represent an important milestone in the advancement of RNAi therapeutics. Indeed, our data demonstrate for the first time both clinical activity and RNAi mechanism for an RNAi therapeutic,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Clearly, these data are not only important for the continued advancement of our ALN-VSP program, but they also significantly increase our confidence in our entire pipeline of systemically delivered RNAi therapeutics, including ALN-TTR01 which is in a Phase I study for the treatment of transthyretin mediated amyloidosis, and ALN-PCS, which will soon enter clinical trials for the treatment of severe hypercholesterolemia.”

About ALN-VSP

ALN-VSP is a systemically delivered RNAi therapeutic comprising two siRNAs designed to target two genes critical for the growth and development of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), also known as eglin 5 (Eg5). ALN-VSP is Alnylam’s first systemic RNAi program and represents the company’s first clinical program in oncology. The drug is formulated using a first generation lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation. The company expects to partner its ALN-VSP program prior to initiating a Phase II clinical study, with the goal of initiating this study in 2012.

About ALN-VSP Phase I Study Design

The Phase I trial was designed as a multi-center, open label, dose escalation study in patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective was to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP. Other secondary and exploratory objectives included:

* assessment of tumor response using Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients’ disease improves, stabilizes or progresses during treatment;
* quantitation of change in tumor blood flow and vascular permeability as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and,
* analysis of pharmacodynamic effects of ALN-VSP on tumors as measured in patients electing to proceed with voluntary pre- and post-treatment biopsies.

About Liver Cancers

Cancer affecting the liver, known as either primary or secondary liver cancer, is associated with one of the poorest survival rates in oncology and represents a major unmet medical need affecting a large number of patients worldwide. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 600,000 people diagnosed each year. Secondary liver cancer, also known as metastatic liver cancer, is cancer that spreads to the liver from another part of the body due to other common cancers like colon, lung, or breast cancer. Worldwide, more than 500,000 people are diagnosed with secondary liver cancer each year.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, and ALN-HPN for the treatment of refractory anemia. As part of its “Alnylam 5x15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntington’s disease. The company’s leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and sanofi-aventis. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world’s top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

SOURCE: Alnylam Pharmaceuticals, Inc.

[aktianer]

Leider mal wieder schlechte Nachrichten von Alnylam.
Anstatt des unsäglichen und unfähigen CEO John Maraganore, seines Zeichens vor allem Abzocker, geht nun mal wieder ein CSO.

Alnylam chief scientific officer jumps ship
Boston Business Journal - by Galen Moore
Date: Wednesday, June 8, 2011, 11:58am EDT
Related:
Health Care

Alnylam Pharmaceuticals Inc. (Nasdaq: ALNY) has announced that its chief scientific officer, Kenneth Koblan, is leaving the Cambridge, Mass. RNAi therapeutics company for personal reasons.

"Ken has decided to return to big pharma, and leave Alnylam. We wish him well in his future endeavors,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam, in a statement issued as part of a press release late Tuesday. He expressed confidence in the company's future research endeavors.

The press release did not specify where Koblan is headed.

Read more: Alnylam chief scientific officer jumps ship | Boston Business Journal

http://www.bizjournals.com/boston/news/2011/06/08/alnylam-cs…

Das einzig gute Alnylam ist 50%-Anteil am Joint-Venture-Unternehmen Regulus, dort wird im Gegensatz zur Mutter scheinbar etwas erfolgreicher entwickelt. Ist alledings auch kein Wunder, denn dort gute Maganore nicht all zuviel zu sagen!
Wenn ich jemand feuern könnte, dann wäre es John Maraganore!

[aktianer]

so, und jetzt muss sich Abzocker-CEO Maraganore angesichts des gedrittelten Kurses mal eine Erhöhung des Fixgehaltes gönnen; eigentlich ist es unbegreiflich, dass die mehrheitlich institutionellen Anleger bei Alny derartige Faxen bei nachgewiesener Erfolgslosigkeit des CEO dies mitmachen:


"Grrrrrr -- JM got a pay raise.
Item 5.02. Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.
On June 9, 2011, the Compensation Committee of the Board of Directors (the “Board”) of Alnylam Pharmaceuticals, Inc. (the “Company”) approved an increase in annual base salary for John M. Maraganore, Ph.D., the Company’s Chief Executive Officer, from $525,000 to $650,000, effective immediately. Dr. Maraganore’s annual base salary had not been increased since January 2008 and was increased at this time to be more competitive with salaries within the 50 th and 60 th percentiles for similar positions in the Company’s industry peer group. "

http://www.investorvillage.com/smbd.asp?mb=569&mn=28280&pt=m…

[Fruehrentner]

aktianer,

danke für die Infos.

Biotechs erweisen sich zunehmend als Non-Investments, die man meiden sollte.

Jüngstes Beispiel: Intercell

Man kann besser in eine Spielbank gehen, ist unterhaltsamer.

[Aliberto]

Antwort auf Beitrag Nr.: 41.672.013 von Fruehrentner am 20.06.11 16:31:52

Neutral on Alnylam
By: Zacks Equity Research
June 23, 2011 | Comments: 0
Recommended this article (2)
RHHBY | MDT | SNY | ISIS | CBST | NVS | GSK | ALNY | BIIB

We have maintained a Neutral rating on Alnylam Pharmaceuticals Inc. (ALNY - Analyst Report) with a target price of $9.50 per share.

Alnylam Pharmaceuticals Inc. is a biopharmaceutical company developing novel therapeutics based on a biological breakthrough known as RNA (Ribo Nucleic Acid) interference (RNAi). Alnylam is currently utilizing this technology to build a pipeline of drug candidates for the treatment of a wide array of diseases.

Alnylam Pharmaceuticals Inc.’s first quarter loss of 38 cents per share was wider than the Zacks Consensus Estimate of 32 cents per share and also the year-ago loss of 29 cents. Lower revenues and higher research and development expenses led to the greater loss. Revenues for the reported quarter fell 15% from the prior year to $20.9 million but were in line with the Zacks Consensus Estimate of $21 million.

We like the company’s newly launched “5X15” initiative and are pleased with the progress of the company’s pipeline. Alnylam’s core product strategy, Alnylam 5x15, is aimed at developing RNAi therapeutic products for the treatment of genetically defined diseases addressing major unmet medical needs. Under this strategy, the company aims to move five RNAi therapeutic programs into clinical development by 2015. These include among others ALN-PCS (for hypercholesterolemia), second generation ALN-TTR (a hepatitis C compound), and ALN-HPN (refractory anemia).

Furthermore, the company is developing ALN-RSV01 for the treatment of respiratory syncytial virus, or RSV, infection; ALN-VSP for the treatment of liver cancers; and ALN-HTT for the treatment of Huntington's disease, or HD, through existing or future partnerships.

We believe 2011 will be an important year for the company as it expects to report data from several of the above pipeline programs. Data from an early stage trial of ALN-TTR01 (a systemically delivered RNAi therapeutic that employs a first-generation LNP formulation) to treat transthyretin (TTR) mediated amyloidosis is expected to be presented in the third quarter of 2011. An Investigational New Drug (IND) for ALN-PCS is expected to be filed in the second quarter of 2011 with data presentation by the end of 2011. Data from a phase IIb study of ALN-RSV01 in RSV-infected lung transplantations is expected in 2012.

Alnylam also generates revenues from research collaborations, grants, and licensing of the RNAi technology outside its core focus area. Alnylam has partnerships with several large pharmaceutical companies, such as Biogen Idec (BIIB - Analyst Report), Medtronic (MDT - Analyst Report), Takeda, Kyowa Hakko Kirin, Cubist Pharmaceuticals (CBST - Snapshot Report) and Isis Pharmaceuticals (ISIS - Analyst Report), to help fund preclinical and clinical work. The partnerships with major players further validate the potential and viability of the RNAi approach. Alnylam has a 45% stake in Regulus, which is engaged in research in microRNA and has entered into major partnerships with GlaxoSmithKline (GSK - Analyst Report) and Sanofi Aventis (SNY - Analyst Report).

We are also comfortable with the company’s current cash position, which allays concerns regarding its cash-burn rate.

In September 2010, Alnylam’s long time collaborator, Novartis (NVS - Snapshot Report), opted to end a five-year alliance with Alnylam. The end of the Novartis collaboration in turn reduced the company’s need for service-based activities. As a result Alnylam announced a corporate restructuring with an approximate 25% reduction in the overall workforce. Further, in November 2010, Roche (RHHBY) also ended research efforts in RNAi, including activities in Madison, Wisconsin and at the Kulmbach, Germany facility it acquired from Alnylam. Until September 2010, a substantial portion of Alnylam’s total net revenues comprised collaboration revenues from its strategic alliances with Roche, Takeda and Novartis. Though without any immediate effect, we believe the end of the Roche and Novartis deal robs Alnylam of two very big co-development partners and potential future milestones and royalties.

We prefer to remain on the sidelines and await further visibility on the clinical progress of the pipeline as well as the company’s ability to enter into new large partnerships to make up for the loss of Novartis and Roche deals.

[Fruehrentner]

Alnylam Presents New Data from ALN-TTR Program at Peripheral Nerve Society Meeting

28 Jun 2011

2011 Peripheral Nerve Society Meeting

CAMBRIDGE, MA, USA | June 28, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it is presenting new data from its ALN-TTR program at the 2011 Peripheral Nerve Society Meeting being held in Potomac, Maryland. The company is reporting results from a natural history study which was designed to measure blood levels of wild-type and mutant transthyretin (TTR) over time in both transthyretin-mediated amyloidosis (ATTR) patients and gene carriers. The study was performed at Boston Medical Center under the direction of John Berk, M.D., who leads the Amyloid Clinical Program at Boston University School of Medicine. ALN-TTR01 is currently in a Phase I clinical trial for the treatment of ATTR.

“a major scientific breakthrough that happens once every decade or so”

“We are pleased with the progress we are making in our ALN-TTR program and remain on track to report data from our Phase I trial in the third quarter of this year. The new data presented at the Peripheral Nerve Society Meeting define blood levels of circulating transthyretin in ATTR patients and gene carriers, and are informative in our efforts to develop our RNAi therapeutic for this devastating disease,” said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “In addition to progress in our ALN-TTR program, we remain on track in our other ‘Alnylam 5x15™’ programs. Specifically, we expect to file our regulatory documents in the coming weeks to begin a Phase I trial with ALN-PCS for the treatment of severe hypercholesterolemia, and we remain on track to report human proof-of-concept data from the ALN-PCS program by year end.”

ATTR is caused by mutations in the TTR gene, which is expressed predominantly in the liver, and is characterized by the abnormal accumulation of mutant and wild-type TTR protein deposits in multiple extra-hepatic tissues, including the peripheral nervous system, heart, and gastrointestinal tract. Although it is known that serum TTR concentrations in ATTR patients and gene carriers are below the normal range, little is known about temporal changes in TTR levels in either patients or carriers. Accordingly, Alnylam conducted a natural history study to measure serial TTR levels over a four week period in ATTR patients and gene carriers, and to determine the intra- and inter-patient variability in serum TTR. The study enrolled 26 patients and gene carriers with seven different amyloidogenic TTR mutations, the most common being the Val30Met mutation that is the primary cause of familial amyloidotic polyneuropathy (FAP). The data from this study showed that TTR levels were stable over time in patients and carriers. The average serum TTR concentration was approximately 200 micrograms/mL with 10 to 20% intra-subject variability over the 28-day observation period. Results showed that inter-subject TTR variability was approximately 25%.

Alnylam scientists and collaborators also presented pre-clinical data from its ALN-TTR program, including new data demonstrating improved potency with ALN-TTR01 using a loading dose/maintenance dose regimen.

About ALN-TTR Phase I Study

ALN-TTR01 is currently in a blinded, randomized, placebo-controlled, single dose escalation Phase I clinical trial in patients with ATTR. The primary objective of this trial is to evaluate the safety and tolerability of a single dose of ALN-TTR01, with patients being enrolled into sequential cohorts of increasing doses. Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-TTR01 and assessment of pharmacodynamic activity based on serial measurements of circulating TTR serum levels. The European Commission has designated ALN-TTR01 as an orphan medicinal product for the treatment of familial amyloidotic polyneuropathy (FAP). In parallel, Alnylam is also advancing ALN-TTR02, which utilizes proprietary second-generation delivery technology, and is on track to file an investigational new drug (IND) or IND equivalent application in the second half of 2011.

About TTR-Mediated Amyloidosis

TTR-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest form, ATTR represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; combined, FAP (familial amyloidotic polyneuropathy) and FAC (familial amyloidotic cardiomyopathy) affect approximately 50,000 people worldwide. ATTR patients with FAP have a mean life expectancy of five to 15 years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene.

About “Alnylam 5x15™”

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylam’s clinical progress on siRNA delivery, including definitive human proof-of-concept data for systemic delivery. By the end of 2015, the company expects to have five such RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and two additional programs from the company’s ongoing discovery efforts that will be designated and advanced into development later in 2011. Alnylam intends to commercialize the products arising under the “Alnylam 5x15” strategy itself in the United States and potentially certain other countries; the company will seek development and commercial partners in other global territories.

[Fruehrentner]

Alnylam Files Clinical Trial Application (CTA) for ALN-PCS, an RNAi Therapeutic Targeting PCSK9 for the Treatment of Severe Hypercholesterolemia

11 Jul 2011

– Company Achieves Important Milestone in Alnylam 5x15™ Product Strategy by Advancing Second Generation Lipid Nanoparticles to Clinical Stage, with Data Expected by Year’s End –

CAMBRIDGE, MA, USA | July 11, 2011 |

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, announced today that it has filed a Clinical Trial Application (CTA) with the Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase I clinical trial with ALN-PCS, an RNAi therapeutic for the treatment of severe hypercholesterolemia. Upon receiving clearance of the CTA, Alnylam plans to initiate the Phase I trial and expects to present initial safety, tolerability, and clinical activity data from this study by the end of this year.

“The filing of this CTA marks an important milestone in our Alnylam 5x15 product efforts, as it is the first program using our second generation lipid nanoparticle technology to enter clinical testing, where we aim to have important safety, tolerability, and clinical activity data by year’s end. Moreover, we are excited about the potential for ALN-PCS to make an impact in the treatment of severe hypercholesterolemia as this RNAi therapeutic targets both intracellular and extracellular PCSK9, a target validated by human genetics that is known to play a central role in LDL cholesterol metabolism,” said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “We continue to execute on our Alnylam 5x15 initiative, which is focused on advancing innovative RNAi therapeutics that address genetically defined targets and diseases with high unmet medical need. ALN-PCS represents the second of such programs, following ALN-TTR01 which is currently in a Phase I trial with data expected later this quarter.”

ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene proprotein convertase subtilisin/kexin type 9, or PCSK9, a target validated by human genetics that is involved in the metabolism of low-density lipoprotein cholesterol (LDLc, or “bad” cholesterol). ALN-PCS targets both intracellular and extracellular PCSK9, thereby phenocopying the human genetics observed in loss of function or null human PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am. J. Hum. Genet. (2006) 79: 514-523), without any adverse effects on high-density lipoprotein (HDL, or “good” cholesterol) levels. An RNAi therapeutic targeting PCSK9 has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher LDL receptor levels in the liver, and subsequently lower LDLc levels. Lower LDLc is associated with a decreased risk of cardiovascular disease, including myocardial infarction. Pre-clinical data from the ALN-PCS program have shown specific silencing of PCSK9 mRNA in the liver, and plasma PCSK9 protein levels of up to 90%, with an ED50 (the dose that provides a 50% silencing effect) of approximately 0.06 mg/kg for both mRNA and protein reduction. These studies have also demonstrated a greater than 50% reduction in levels of LDLc, which is rapid and durable, lasting for weeks after a single dose.

As per the filed CTA, the Phase I trial of ALN-PCS is expected to be conducted in the U.K. as a randomized, single-blind, placebo-controlled, single ascending dose study, enrolling approximately 32 healthy volunteer subjects with elevated baseline LDLc (>116mg/dL). The primary objective of the study is to evaluate the safety and tolerability of a single dose of ALN-PCS, with patients being enrolled into five sequential cohorts of increasing doses ranging from 0.015 to 0.25 mg/kg. Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-PCS, and assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein and LDLc levels measured from serial blood samples prior to and following dosing.

ALN-PCS is an RNAi therapeutic that utilizes proprietary Alnylam second-generation lipid nanoparticle (LNP) technology, specifically that using the MC3 lipid.

[Fruehrentner]

Alnylam and MIT Collaborators Publish Data on Novel Lipid Nanoparticles for Systemic Delivery of RNAi Therapeutics

19 Jul 2011

New Pre-clinical Findings Demonstrate that Binary Combinations of Novel “Lipidoids” Result in Synergistic Effects on Target Gene Silencing

CAMBRIDGE, MA, USA | July 19, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, together with collaborators at the Massachusetts Institute of Technology (MIT), announced today the publication of new data describing a novel approach for systemic delivery of RNAi therapeutics using synergistic combinations of novel lipid-like materials called “lipidoids.”

“These new data reflect our continued and broad-based commitment to developing novel approaches for the systemic delivery of RNAi therapeutics. In working with world-renowned academic leaders in the field of drug delivery at MIT, we continue to expand our understanding and knowledge about innovative delivery approaches,” said Kevin Fitzgerald, Ph.D., Senior Director of Research at Alnylam. “These recently published data show that binary combinations of specific lipidoids can result in optimized lipid nanoparticle formulations with synergistic siRNA delivery properties.”

“Our long-standing collaborative efforts with Alnylam continue to be very productive as evidenced by this current publication, marking the 12th peer-reviewed paper we have co-authored together,” said Dan Anderson, Ph.D., of the David H. Koch Institute for Integrative Research at MIT. “As we continue in these joint efforts, we see boundless opportunities for novel delivery strategies for RNAi therapeutics and we look forward to continued progress.”

The new research results, which were published in the journal Molecular Therapy (Whitehead et al., MolTher, 2011 July 12, doi:10.1038/mt.2011.141), established that binary combinations of lipidoids can be formulated together in a single lipid nanoparticle (LNP) formulation to achieve synergistic gene silencing effects both in vitro and in vivo. In the current study, more than 3,500 novel LNP formulations were prepared and then evaluated for effects on gene silencing. Results demonstrated achievement of synergistic gene silencing when utilizing materials that, when combined, mediated both efficient cellular uptake and productive endosomal escape. The pre-clinical data showed that ineffective single lipidoids could be formulated together to induce robust silencing of the luciferase mRNA in vitro and the Factor VII mRNA in vivo. Importantly, it is anticipated that this binary formulation strategy could be applicable to any siRNA delivery material in any target cell population that utilizes combinations of unique components to mediate distinct steps in the delivery process, for example lipids, polymers, and siRNA conjugates.

[Fruehrentner]

Alnylam and MIT Collaborators Discover Novel “Core-Shell” Nanoparticles for Systemic Delivery of RNAi Therapeutics

25 Jul 2011

Alnylam Pharmaceuticals announced the publication of new paper describing discovery of “core-shell” nanoparticles for systemic delivery of RNAi therapeutics

CAMBRIDGE, MA, USA | July 25, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY - News), a leading RNAi therapeutics company, together with collaborators at the Massachusetts Institute of Technology (MIT), announced today the publication of new paper describing discovery of “core-shell” nanoparticles for systemic delivery of RNAi therapeutics. The core-shell nanoparticles were generated using a high-throughput polymer synthesis strategy and screened for intracellular delivery applications including siRNA delivery. These findings, published in the Proceedings of the National Academy of Sciences (Siegwart et al., PNAS, 2011, doi: 10.1073/pnas.1106379108) allow for the development of novel nanoparticles that have optimal chemical and physical properties for effective intracellular delivery of RNAi therapeutics.

“Continued progress in delivery of RNAi therapeutics requires broad-based efforts around novel lipids, conjugates, and polymers. In the current study, core-shell nanoparticles were discovered using combinatorial approaches to identify novel materials for siRNA delivery,” said Kevin Fitzgerald, Ph.D., Senior Director of Research at Alnylam. “These findings further expand our systemic delivery platform to achieve the broadest applications of RNAi therapeutics.”

“Together with our collaborators at Alnylam, we continue to make exciting progress on delivery of RNAi therapeutics,” said Dan Anderson, Ph.D., of the David H. Koch Institute for Integrative Research at MIT. “Importantly, these new data on core-shell nanoparticles highlight non-lipid approaches for siRNA delivery with opportunities for further optimization.”

Specifically, this study evaluated a library of over 1,500 chemically diverse nanoparticles as drug delivery vehicles, with precise control over particle size, chemical composition and architecture. The physical and chemical properties of materials can have controlling effects on their utility as nanotherapeutics and the findings revealed that certain chemical functionalities may be advantageous for polymer-based delivery. Initial in vivo studies on one of these novel nanoparticles showed silencing of hepatocyte-specific Factor VII in a pre-clinical model. The ability to control and modify the chemical nature of the core and shell of the nanoparticle may afford utility of these materials in a wide range of drug delivery applications.

[Fruehrentner]

Alnylam Initiates Phase I Clinical Study of ALN-PCS, an RNAi Therapeutic Targeting PCSK9 for the Treatment of Severe Hypercholesterolemia

26 Sep 2011

– Study Provides Opportunity to Assess Human Proof of Concept with Second Generation Lipid Nanoparticles; Data Expected at Year’s End –

CAMBRIDGE, MA, USA | September 26, 2011 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has initiated dosing in its Phase I clinical trial with ALN-PCS, an RNAi therapeutic targeting proprotein convertase subtilisin/kexin type 9, or PCSK9, for the treatment of severe hypercholesterolemia. The study is aimed at evaluating the safety and tolerability of ALN-PCS in subjects with elevated low-density lipoprotein cholesterol (LDLc, or “bad” cholesterol). In addition, the study will evaluate clinical activity of ALN-PCS based on measurements of plasma PCSK9 protein and serum LDLc levels. Alnylam expects to present data from this study at year’s end.

“We look forward to results from this new Phase I study at year’s end as it defines an important data point for broader execution on our ‘Alnylam 5x15’ product strategy, including our programs in transthyretin-mediated amyloidosis, refractory anemia, and hemophilia.”

“We believe ALN-PCS has the potential to make a significant impact in the treatment of severe hypercholesterolemia, as this RNAi therapeutic targets both intracellular and extracellular PCSK9, a target validated by human genetics that is known to play a central role in LDLc metabolism. The primary objective of this Phase I study is to demonstrate safety and tolerability of ALN-PCS in subjects with elevated baseline LDLc. In addition, we also believe we have an opportunity to assess preliminary human proof of concept based on blood measurements of PCSK9 protein and LDLc levels,” said Akshay Vaishnaw, Ph.D., M.D., Senior Vice President, Chief Medical Officer of Alnylam. “The start of this trial also marks an important milestone in our Alnylam 5x15 product efforts, as it is the first program using our second generation lipid nanoparticle technology to enter clinical testing, where we aim to have important safety, tolerability, and clinical activity data by this year’s end.”

ALN-PCS is a systemically delivered RNAi therapeutic targeting PCSK9, a disease gene validated by human genetics that is involved in the metabolism of LDLc. By targeting the PCSK9 mRNA, ALN-PCS depletes both intracellular and extracellular PCSK9 protein, thereby phenocopying the human genetics observed in loss of function PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am. J. Hum. Genet. (2006) 79: 514-523). An RNAi therapeutic targeting PCSK9 has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher LDL receptor levels in the liver, and subsequently lower LDLc levels, without any change in high-density lipoprotein (HDL, or “good” cholesterol) levels. Lower LDLc is associated with a decreased risk of cardiovascular disease, including myocardial infarction. Pre-clinical data from the ALN-PCS program have shown specific silencing of PCSK9 mRNA in the liver and reduced plasma PCSK9 protein levels of up to 90%, with an ED50 (the dose that provides a 50% silencing effect) estimated at approximately 0.06 mg/kg for both mRNA and protein reduction. These studies have also demonstrated a greater than 50% reduction in levels of LDLc, which is rapid and durable, lasting for weeks after a single dose.

“Cardiovascular disease is the leading cause of mortality worldwide, with elevated LDLc remaining the major risk factor. It is clear that new therapeutic options are needed for patients who cannot achieve target LDL levels with current drugs. As a key regulator of LDL receptor levels, PCSK9 is arguably one of the most important targets for development of molecular medicines for hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal Medicine – Digestive and Liver Diseases, University of Texas Southwestern Medical Center. “An RNAi therapeutic targeting this genetically validated gene has the potential to rapidly and durably lower LDL cholesterol - while preserving HDL cholesterol - and may also function synergistically with statins.”

The Phase I trial of ALN-PCS is being conducted in the U.K. as a randomized, single-blind, placebo-controlled, single-ascending dose study, enrolling approximately 32 healthy volunteer subjects with elevated baseline LDLc (>116mg/dL). The primary objective of the study is to evaluate the safety and tolerability of a single dose of ALN-PCS, with patients being enrolled into five sequential cohorts of increasing doses ranging from 0.015 to 0.25 mg/kg. Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-PCS, and assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein and LDLc levels measured from serial blood samples prior to and following dosing. ALN-PCS is an RNAi therapeutic that utilizes proprietary Alnylam second-generation lipid nanoparticle (LNP) technology, specifically the MC3 lipid.

“ALN-PCS is Alnylam’s fourth RNAi therapeutic to enter clinical development, highlighting our continued commitment and focus on advancement of breakthrough medicines to patients. This milestone also exemplifies our ongoing transition from ‘platform company’ to ‘product company’,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “We look forward to results from this new Phase I study at year’s end as it defines an important data point for broader execution on our ‘Alnylam 5x15’ product strategy, including our programs in transthyretin-mediated amyloidosis, refractory anemia, and hemophilia.”

About Severe Hypercholesterolemia

Severe hypercholesterolemia affects more than 500,000 people worldwide and is characterized by very high levels of cholesterol in the blood which is known to increase the risk of coronary artery disease, the leading cause of death in the U.S. Most forms of hypercholesterolemia can be treated through dietary restrictions and medicines such as statins. However, a large proportion of patients with hypercholesterolemia are not achieving low-density lipoprotein cholesterol (LDLc, or “bad” cholesterol) goals by statin therapy including genetic familial hypercholesterolemia patients, acute coronary syndrome patients, high risk cardiovascular patients, and other patient populations that are statin intolerant or statin resistant. As a result, there is a significant need for novel therapeutics to treat patients with severe hypercholesterolemia whose disease is inadequately managed by existing therapies.

About ‘Alnylam 5x15’

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylam’s clinical progress on siRNA delivery, including definitive human proof-of-concept data for systemic delivery. By the end of 2015, the company expects to have five such RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, ALN-APC for the treatment of hemophilia, and one additional program from the company’s ongoing discovery efforts that will be designated and advanced into development later in 2011. Alnylam intends to commercialize the products arising under the “Alnylam 5x15” strategy itself in the United States and potentially certain other countries; the company will seek development and commercial partners in other global territories.

[Fruehrentner]

Alnylam and GlaxoSmithKline Form Collaboration on RNAi Technology for Vaccine Production

01 Nov 2011

Alnylam VaxiRNATM Platform Applies RNAi to Enhance Vaccine Production for Influenza and Other Pathogens

CAMBRIDGE, MA, USA I November 1, 2011 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today it has formed a collaboration with GlaxoSmithKline (GSK) focused on Alnylam’s VaxiRNATM technology for certain GSK vaccine products, including influenza. VaxiRNA is a new RNAi technology for the enhanced production of viruses used in the manufacture of vaccine products. GSK, a leading vaccine manufacturer, is the first company to form a collaboration accessing this new platform.

“At Alnylam, we continue to pioneer innovative opportunities for our RNAi platform that could have transformative impact in medicine and the biopharmaceutical industry. This is exemplified with VaxiRNA, where siRNA technology is being used to increase virus titers in the production of vaccine products. Since production of vaccines can be limiting for the scale and speed of global immunization against many pathogens, including influenza, we believe that VaxiRNA can become an enabling technology for the broader vaccine industry,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “As we advance our VaxiRNA effort, we are excited to form a new collaboration with GSK, a global leader and innovator in vaccine development and manufacturing. With GSK, we aim to apply VaxiRNA technology to enhance influenza vaccine production in cell culture, where Alnylam will receive research funding, in addition to potential milestones and payments on unit sales of commercialized vaccine product.”

Alnylam’s VaxiRNA platform applies siRNAs for the silencing of specific genes that limit or prevent efficient growth of viruses in vaccine manufacturing systems, including those in cell culture and also in eggs. The VaxiRNA platform stems from work Alnylam has performed as part of its Alnylam Biotherapeutics efforts, where RNAi technology has been applied to improve the manufacture of biotherapeutic products, such as recombinant proteins and monoclonal antibodies. This new platform addresses the significant unmet commercial need for innovative technologies that can improve the manufacture of vaccine products, especially where vaccine production is a limiting factor for the scale and speed of global immunization needs.

The GSK collaboration is focused initially on influenza vaccine production in cell culture systems. Under the terms of the agreement, GSK will provide funding and certain milestone payments to Alnylam. If successfully applied in the manufacture of commercial product, Alnylam will receive payments on unit product sales. In addition, GSK has obtained an option for VaxiRNA applications toward two additional vaccine products.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About VaxiRNA™

Alnylam is applying RNAi technology to improve the manufacturing processes for vaccines in an effort called VaxiRNA. With VaxiRNA, Alnylam is using siRNAs that silence specific genes in vaccine production systems, such as cells or eggs, which limit or prevent the efficient growth of viruses used in the manufacture of vaccine products. New innovations in vaccine manufacturing are needed to enable the scale and speed of global immunization for a number of pathogens. In 2011, Alnylam formed a VaxiRNA partnership with GlaxoSmithKline for influenza vaccine production.

[Fruehrentner]

Affymetrix strikes deal with Genisphere for miRNA reagents

18 November 2011

Affymetrix has entered an agreement with Genisphere to provide miRNA reagents including FlashTag Biotin HSR Reagents designed for Affymetrix.

The miRNA reagents provide streamlined, high-fidelity target preparation methods yielding better data reproducibility in combination with the Affymetrix GeneChip Arrays.

The reagents by Genisphere are said to be compatible with varied sample types including formalin-fixed, paraffin-embedded (FFPE) fresh frozen samples and blood.

The solution will help researchers study the role of miRNAs in biological processes such as mRNA degradation, transcriptional gene silencing, translational repression, and in biomarker discovery in translational and cancer research.

Furthermore, these reagents provide ultrasensitive miRNA labeling in just 45 minutes, eliminating the need for purification steps to go from sample to target for microarray hybridization.

[Fruehrentner]

Alnylam Completes Enrollment in Phase IIb Study of ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection

30 Nov 2011

On Track to Report Data from Completed Trial in Mid-2012 –

CAMBRIDGE, MA, USA I November 29, 2011 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has completed patient enrollment in its Phase IIb study with ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection. The Phase IIb trial was designed as a multi-center, randomized, double-blind, placebo-controlled study in RSV-infected lung transplant patients. The global study is being conducted at 33 lung transplant centers in six countries around the world. Results are expected to be reported mid-2012.

“In the meanwhile, Alnylam remains focused on its core ‘5x15’ strategy advancing RNAi therapeutics for the treatment of genetically defined targets and diseases, exemplified by our recent positive results in our ALN-TTR01 clinical study.”

“ALN-RSV01 represents Alnylam’s most advanced partner-based program and is aimed at the treatment of RSV infection in high-risk adult populations. In an earlier small Phase IIa study, we showed promising clinical activity in RSV-infected lung transplant patients that we have aimed to reproduce in this current Phase IIb study. We look forward to reporting on data from this trial in mid-2012, and then evaluating next steps for this program together with our partners Cubist and Kyowa Hakko Kirin,” said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “In the meanwhile, Alnylam remains focused on its core ‘5x15’ strategy advancing RNAi therapeutics for the treatment of genetically defined targets and diseases, exemplified by our recent positive results in our ALN-TTR01 clinical study.”

The Phase IIb study was designed to repeat and extend findings from a previous small Phase IIa study of ALN-RSV01 in RSV-infected lung transplant patients (Zamora et al., Am. J. Respir. Crit. Care Med., Feb 2011, Vol 183, No 4: pp 531-538), where the drug was shown to significantly decrease the incidence of bronchiolitis obliterans syndrome (BOS), a life-threatening complication of RSV infection, at 90 days in ALN-RSV01 recipients compared to placebo (6.3% vs.50%; ALN-RSV01 N=16, placeboN=8; p=0.027). In the current Phase IIb study, the primary endpoint was designed as a reduction in the incidence of new or progressive BOS at 180 days. The trial enrolled approximately 90 patients who were randomized in a 1:1 ratio of drug to placebo. All patients received standard of care, and those receiving ALN-RSV01 had drug administered as a 0.6 mg/kg dose by inhalation using an investigational eFlow Nebulizer System (PARI Pharma) once daily for five days. A planned interim analysis was recently performed by an Independent Study Biostatistical Committee to determine whether an increase in sample size up to a maximum of 120 patients was warranted. Alnylam was informed that the study should be completed with the current sample size; because the study remains blinded to all parties, the interim analysis results cannot be interpreted to suggest either a positive or negative outcome.

The RSV program is partnered with Cubist Pharmaceuticals in North America and the rest of the world outside of Asia, where the program is partnered with Kyowa Hakko Kirin Co., Ltd. These partners maintain opt-in rights for the development of ALN-RSV01.

About RSV

Respiratory syncytial virus (RSV) is a highly contagious virus that causes infections in both the upper and lower respiratory tract. RSV infection typically results in cold-like symptoms but can lead to more serious respiratory illnesses such as croup, pneumonia, bronchiolitis, and in extreme cases, death. In the pediatric and adult populations, it account for more than 300,000 hospitalizations per year in the U.S. RSV infection in lung transplant patients represents an important unmet medical need; the condition is associated with significant morbidity, including the development of acute lung transplant rejection in up to 20% of infected patients. Lung transplant patients infected with RSV are also at risk for an increase in frequency of chronic allograft dysfunction, which manifests as bronchiolitis obliterans syndrome (BOS), a life-threatening complication representing an irreversible disease of the transplanted lung resulting in approximately 50% mortality within three to five years of onset. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems, and others. In addition, RSV infection in infants has been linked to the development of childhood asthma. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.

[Fruehrentner]

Alnylam Scientists Present New Data on RNAi Therapeutics at 53rd ASH Annual Meeting

14 Dec 2011

– Research Highlights Include Pre-Clinical Data from “Alnylam 5x15” Programs in Hemophilia and Refractory Anemia and New Candidate Programs in Beta-Thalassemia and Erythropoiesis –

CAMBRIDGE, MA, USA I December 13, 2011 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today that it presented multiple posters and presentations at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition held in San Diego, CA between December 10 – 13, 2011. At the meeting, research was presented from programs in the company’s “Alnylam 5x15” product pipeline, including pre-clinical data from ALN-APC, an RNAi therapeutic targeting protein C for the treatment of hemophilia, and ALN-HPN, an RNAi therapeutic targeting the hepcidin pathway for the treatment of refractory anemia. In addition, pre-clinical research was also presented from candidate programs in beta-thalassemia and erythropoiesis.

“The research we presented at this meeting highlights the significant progress we are making in translating RNAi therapeutics toward an innovative class of medicines for a broad range of human disease,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “Specifically, we were pleased to present additional updates from some of our ‘Alnylam 5x15’ programs, including ALN-APC for the treatment of hemophilia and ALN-HPN for the treatment of refractory anemia in addition to candidate programs in beta-thalassemia and erythropoiesis. Importantly, all four programs are focused on genetically defined targets expressed in the liver, where we have recently proven safe and effective delivery in man, with target and/or disease biomarkers measureable in early clinical studies. We remain on track to nominate our fifth ‘Alnylam 5x15’ program at or around year’s end from these and other candidate programs.”

Presentations and posters from Alnylam scientists at the ASH Meeting included a poster titled “RNAi-Mediated Inhibition of Activated Protein C. A New Approach for Hemophilia Treatment,” where Alnylam scientists presented pre-clinical data from its ALN-APC program. These data demonstrate dose-dependent silencing of protein C mRNA with silencing of greater than 90% and an ED50 of approximately 0.02 mg/kg. When administered as a single dose of 0.3 mg/kg, the lipid nanoparticle (LNP)-formulated siRNA achieved greater than 75% silencing of protein C mRNA with effects lasting for over two weeks. Based on Western blot analysis, the reduction of protein C mRNA led to virtually undetectable levels of circulating protein C protein levels in plasma. By reducing levels of protein C, ALN-APC is expected to increase thrombin generation in hemophilia.

A presentation titled “Targeting the Hepcidin Pathway with RNAi Therapeutics for the Treatment of Anemia,” showed new pre-clinical data from the company’s ALN-HPN program for the treatment of refractory anemia. New data was shown highlighting the ability of an RNAi therapeutic to silence the hepcidin pathway in pre-clinical models, resulting in associated dose-dependent increases in serum iron and transferrin saturation, a measure of effective iron mobilization in vivo. New data also revealed transferrin receptor type 2 (TFR2) as the optimal target in the hepcidin pathway, as TFR2 silencing was associated with marked decreases in hepcidin expression and greater levels of transferrin saturation as compared with direct targeting of the hepcidin mRNA itself. TFR2 silencing was also found to be more effective than direct silencing of hepcidin in animal models, including correction of hemoglobin levels in a model of inflammatory anemia. TFR2 is a genetically validated target as loss of function human mutations are associated with a hereditary form of hemochromatosis. Further efforts on ALN-HPN will focus on TFR2 as the molecular target.

In a poster titled “RNAi-Mediated Inhibition of Tmprss6 Elevates Hamp1 [Hepcidin] Expression and Reduces Serum Iron Levels in Mice,” Alnylam scientists and collaborators from Children’s Hospital Boston showed that the systemic administration of an LNP-formulated siRNA targeting Transmembrane protease, serine 6 (Tmprss6) represents a potential novel approach to treat congenital iron overload disorders. In a pre-clinical model of iron overload in beta-thalassemia, potent and dose dependent silencing of Tmprss6 was achieved, resulting in a concomitant induction of hepcidin mRNA. As a result of increased hepcidin levels, treatment with the Tmprss6 siRNA resulted in significant decreases in serum iron concentration and transferrin saturation. Moreover, Tmprss6 silencing with a single dose of the RNAi therapeutic was associated with a dramatic normalization of multiple hematological parameters including hemoglobin, normalization of splenic iron levels and tissue histology, and reductions in splenomegaly. These findings suggest that iron restriction via Tmprss6 silencing can correct the disease phenotype of beta-thalassemia intermedia in a pre-clinical model.

Lastly, in a poster titled “Liver Specific Delivery of siRNA Targeting EGLN Prolyl Hydroxylases Activates Hepatic Erythropoietin Production and Stimulates Erythropoiesis,” Alnylam scientists and collaborators at the Dana-Farber Cancer Institute and the Massachusetts Institute of Technology (MIT) highlighted the potential of RNAi therapeutics targeting liver-expressed egl nine homolog (EGLN) prolyl hydroxlase genes to promote effective and durable erythropoiesis. Pre-clinical data demonstrated that LNP-formulated EGLN siRNA induced hepatic erythropoietin (EPO) mRNA activation leading to increased serum EPO levels and stimulation of erythropoiesis. Following a single dose, increases in serum EPO and hematocrit were durable for approximately two weeks and one month, respectively. Treatment with EGLN siRNAs corrected anemia in both renal failure and inflammatory anemia pre-clinical disease models.

[Fruehrentner]

Alnylam reports encouraging pre-clinical results with ALN-HTT program

29 December 2011

Alnylam Pharmaceuticals has reported promising pre-clinical results related to its ALN-HTT program, an RNAi therapeutic drug-device combination for the treatment of Huntington's disease.

The findings were the result of research partnership between Alnylam and Medtronic and supported by CHDI.

The results demonstrated that a small interfering RNA (siRNA) targeting huntingtin gene, when administered by intrastriatal infusion with convection-enhanced delivery (CED), results in widespread distribution of the siRNA.

The results also demonstrated significant silencing of the huntingtin mRNA throughout the striatum and administration of the RNAi therapeutic was well tolerated in these studies.

Alnylam research vice president Dinah Sah said the pre-clinical results extend earlier data on siRNA biodistribution in the central nervous system and degree and scope of therapeutic huntingtin gene silencing.

[Fruehrentner]

Alnylam Reports Positive Preliminary Clinical Results for ALN-PCS, an RNAi Therapeutic Targeting PCSK9 for the Treatment of Severe Hypercholesterolemia

04 Jan 2012

RNAi Therapeutic Achieves Robust Silencing of PCKS9 and Reductions of Over 50% in LDL Cholesterol, a Validated Clinical Endpoint
Results Highlight Major Potency Improvements of Second-Generation Lipid Nanoparticle Platform in Man
Alnylam to Host Conference Call Today, January 4 @ 8:30 a.m. ET to Discuss Results

CAMBRIDGE, MA, USA I January 4, 2011 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today the achievement of positive preliminary results from its ongoing clinical trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia. ALN-PCS demonstrated statistically significant RNAi silencing of PCSK9 of up to 66% and reductions of up to over 50% in levels of low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, a clinically validated endpoint. Alnylam believes that the preliminary results of this study, presented today at the Brigham and Women’s Hospital in Boston, also document for the first time major advances in delivery of RNAi therapeutics with second generation lipid nanoparticles (LNPs) in human studies. This Phase I study continues with planned dose escalation, given the favorable safety profile and positive efficacy achieved to date. Additional results of the study are expected to be reported in the first half of 2012.

“We are extremely pleased with these data from our ALN-PCS trial which represent what we believe is the first ever demonstration of efficacy for an RNAi therapeutic toward a clinically validated endpoint, namely LDL-C, a defined risk factor for coronary artery disease and acute myocardial infarction. Indeed, preliminary results from our ongoing study show robust, statistically significant, and dose-dependent lowering of both PCSK9 and LDL-C levels,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “The RNAi effects were rapid and durable after a single dose, exemplifying a compelling profile for RNAi therapeutics that we have now established in man for two disease programs.”

This Phase I ALN-PCS study is being conducted as a randomized, single-blind, placebo-controlled, single-ascending dose study in healthy volunteer subjects with elevated baseline LDL-C (>116mg/dL). The primary objective of the study is to evaluate the safety and tolerability of a single dose of ALN-PCS, with subjects being enrolled into sequential cohorts of increasing doses. Secondary objectives of the study include characterization of plasma and urine pharmacokinetics of ALN-PCS, assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein levels, and evaluation of clinical efficacy as measured by LDL-C levels. This trial is being performed in the absence of statins or other lipid lowering therapy. The findings presented today describe results from the initial 20 subjects enrolled in five sequential dose cohorts ranging from 0.015 to 0.250 mg/kg in a 3:1 randomization of drug to placebo.

In this study, administration of ALN-PCS resulted in a rapid, dose-dependent, and durable silencing of PCSK9 protein levels in plasma of up to 66% relative to baseline, with a statistically significant mean reduction of 60% at day four in the current high dose group of 0.250 mg/kg (p<0.001). In addition, administration of ALN-PCS resulted in dose-dependent reductions in LDL-C of up to 50% relative to baseline, with a statistically significant mean reduction of 39% at day four (p<0.05) at the 0.250 mg/kg dose level. Nadir effects on PCSK9 and LDL-C were achieved rapidly and occurred approximately four days after administration of a single dose. There was also a dose-dependent increase in the proportion of subjects who achieved “target” levels of LDL-C of less than 100 mg/dL (p<0.05), with 100% (6/6) of subjects in the two highest dose groups achieving target and a mean LDL-C of 84.0 mg/dL, as compared with 21.4% (3/14) of subjects achieving target in any other group. Moreover, the effects of a single dose were durable, supporting a once-monthly dose administration regimen expected in future studies. Further, there was no significant decrease in high-density lipoprotein (HDL), or “good” cholesterol levels, consistent with the phenotype observed in human loss-of-function mutations in PCSK9.

To date, ALN-PCS has been shown to be safe and well tolerated in this study and there have been no serious adverse events related to study drug administration. There have been no drug-related discontinuations from the study and no liver enzyme elevations. A mild, transient rash was observed in five subjects, including two who received placebo. The study is ongoing; based on the favorable safety profile and positive clinical activity to date, the company plans to continue dose escalation.

“Cardiovascular disease remains the leading cause of mortality worldwide, with elevated LDL-C defining the major risk factor. It is clear that new therapeutic options are needed for patients who cannot achieve target LDL levels with current drugs,” said Christopher Cannon, M.D., Professor of Medicine, Harvard Medical School. “As a key regulator of the LDL receptor, PCSK9 is one of the most important targets in molecular medicine for the treatment of hypercholesterolemia. An RNAi therapeutic targeting this genetically validated gene has the potential to rapidly and durably lower LDL cholesterol, thereby reproducing the effects observed in loss-of-function human mutations associated with significant clinical benefit.”

ALN-PCS is an RNAi therapeutic that utilizes proprietary second-generation LNP technology with the MC3 lipid; this study represents the first human results with this delivery platform. The same RNAi delivery formulation is being used for Alnylam’s program on ALN-TTR02, an RNAi therapeutic for the treatment of transthyretin (TTR)-mediated amyloidosis (ATTR).

“These data mark an important milestone in our overall ‘Alnylam 5x15’ efforts, as they are the first to demonstrate safety, tolerability, and clinical efficacy of an RNAi therapeutic utilizing our second generation lipid nanoparticle delivery technology. In this regard, these data strongly support advancement of our ALN-TTR02 program for the treatment of transthyretin-mediated amyloidosis, where we expect to start clinical studies shortly,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “It is also notable that these new data round out a remarkable year of clinical achievement, where we demonstrated RNAi proof of mechanism in biopsy samples from our ALN-VSP liver cancer program, showed human proof of concept with robust TTR lowering in our ALN-TTR01 Phase I study, and now demonstrated human clinical efficacy with LDL-C reductions with ALN-PCS. To say the least, we believe these data provide very strong support for our future efforts in developing RNAi therapeutics as a new class of innovative medicines.”

The presentation of these data can be found on Alnylam’s website at www.alnylam.com/capella.

Conference Call Information

Alnylam will host a conference call on Wednesday, January 4 at 8:30 a.m. ET to discuss the preliminary Phase I results of its ALN-PCS clinical trial. To access the call, please dial 800-901-5217 (domestic) or 617-786-2964 (international) five minutes prior to the start time and provide the passcode 78688967. A replay of the call will be available beginning at 10:30 a.m. ET on January 4, 2012. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the passcode 52686639. A live audio webcast of the call will also be available on the News & Investors page of the company’s website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event.

About Severe Hypercholesterolemia

Severe hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood which is known to increase the risk of coronary artery disease, the leading cause of death in the U.S. Most forms of hypercholesterolemia can be treated through dietary restrictions, lifestyle modifications (e.g., exercise and smoking cessation) and medicines such as statins. However, a large proportion of patients with hypercholesterolemia are not achieving target LDL-C goals with statin therapy, including genetic familial hypercholesterolemia patients, acute coronary syndrome patients, high-risk patient populations (e.g. diabetics, symptomatic carotid artery disease, etc.) and other patients that are statin intolerant. Severe hypercholesterolemia is estimated to affect more than 500,000 patients worldwide, and as a result, there is a significant need for novel therapeutics to treat patients with severe hypercholesterolemia whose disease is inadequately managed by existing therapies.

About ALN-PCS

ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene proprotein convertase subtilisin/kexin type 9, or PCSK9, a target validated by human genetics that is involved in the metabolism of low-density lipoprotein cholesterol (LDL-C, or “bad” cholesterol). ALN-PCS targets both intracellular and extracellular PCSK9, thereby phenocopying the human genetics observed in loss of function or null human PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am. J. Hum. Genet. (2006) 79: 514-523), without any adverse effects on high-density lipoprotein (HDL, or “good” cholesterol) levels. An RNAi therapeutic targeting PCSK9 has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher LDL receptor levels in the liver, and subsequently lower LDL-C levels. Lower LDL-C is associated with a decreased risk of cardiovascular disease, including myocardial infarction and stroke. Pre-clinical data from the ALN-PCS program have shown specific silencing of PCSK9 messenger RNA (mRNA) in the liver, and plasma PCSK9 protein levels of up to 90%, with an ED50 (the dose that provides a 50% silencing effect) of approximately 0.06 mg/kg for both mRNA and protein reduction. These studies have also demonstrated a greater than 50% reduction in levels of LDL-C, which is rapid and durable, lasting for several weeks after a single dose.

About “Alnylam 5x15™”

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylam’s clinical progress on siRNA delivery, including definitive human proof-of-concept data for systemic delivery. By the end of 2015, the company expects to have five such RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, ALN-APC for the treatment of hemophilia, and one additional program from the company’s ongoing discovery efforts that will be designated at or around the end of 2011. Alnylam intends to focus on developing and commercializing certain products arising under the “Alnylam 5x15” strategy itself in the United States and potentially certain other countries; the company will seek development and commercial partners for other core products both in the United States and in other global territories.

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Alnylam presents positive Phase I ALN-PCS trial data

23 April 2012

Alnylam Pharmaceuticals has reported positive clinical results from Phase I trial of ALN-PCS, which utilizes Tekmira's lipid nanoparticle (LNP) technology.

The RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia utilized Tekmira's lipid nanoparticle (LNP) technology.

Tekmira president and CEO Mark Murray said the new data from the ALN-PCS human clinical trial continues to demonstrate that Tekmira's LNP technology is well tolerated and enables RNAi activity in humans.

The study has demonstrated that administration of a single dose of ALN-PCS, in the absence of concomitant lipid-lowering agents such as statins, resulted in durable reductions of PCSK9 plasma levels of up to 84% and lowering of low-density lipoprotein cholesterol of up to 50%.

ALN-PCS was shown to be safe and well tolerated in the study.

"As the evidence of positive data within the RNAi field continues to grow, we believe that Tekmira's LNP technology is a key driver advancing the field towards the commercialization of RNAi therapeutics for a variety of clinical indications," Murray added.

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Alnylam ALN-TTR01 drug shows efficacy in Phase I study

Published 11 May 2012

Alnylam Pharmaceuticals has reported results from the Phase I clinical trial with ALN-TTR01, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR).


The randomized, placebo-controlled single-dose escalation Phase I study enrolled patients with ATTR into seven sequential cohorts of increasing doses ranging from 0.01 to 1.0mg/kg.

Patients administered with ALN-TTR01 showed significant reductions in serum TTR protein levels, including both wild-type and mutant TTR protein.

ALN-TTR01 also demonstrated a dose-dependent reduction in serum TTR levels with a mean reduction of 38% at approximately day 7 to 10 in the 1mg/kg group.

Alnylam Pharmaceuticals Clinical Research senior director Jared Gollob said the Phase I data from the ALN-TTR01 clinical study demonstrate rapid, dose-dependent, and durable lowering of TTR protein levels after a single dose in ATTR patients.

"We believe these data with ALN-TTR01 provide key human proof of concept as we advance ALN-TTR02 as our 'go-to-market' RNAi therapeutic for the treatment of ATTR, a debilitating orphan genetic disease," Gollob added.

The company plans to commence a Phase II multi-dose study of ALN-TTR02 in the second half of 2012.

[aktianer]

Und noch 'n Versuch die Liefer- und Nebenwirkungsproblematik in den Griff zu bekommen, die Zweifel bleiben, zu oft hat Maganore schon den Durchbruch angekündigt, aber die Hoffnung stirbt zuletzt:

Researchers achieve RNA interference, in a lighter package
Pared-down nucleic acid nanoparticle poses less risk of side effects, offers better targeting.
Anne Trafton, MIT News Office

June 4, 2012

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Using a technique known as “nucleic acid origami,” chemical engineers have built tiny particles made out of DNA and RNA that can deliver snippets of RNA directly to tumors, turning off genes expressed in cancer cells.

To achieve this type of gene shutdown, known as RNA interference, many researchers have tried — with some success — to deliver RNA with particles made from polymers or lipids. However, those materials can pose safety risks and are difficult to target, says Daniel Anderson, an associate professor of health sciences and technology and chemical engineering, and a member of the David H. Koch Institute for Integrative Cancer Research at MIT.

The new particles, developed by researchers at MIT, Alnylam Pharmaceuticals and Harvard Medical School, appear to overcome those challenges, Anderson says. Because the particles are made of DNA and RNA, they are biodegradable and pose no threat to the body. They can also be tagged with molecules of folate (vitamin B9) to target the abundance of folate receptors found on some tumors, including those associated with ovarian cancer — one of the deadliest, hardest-to-treat cancers.

Anderson is senior author of a paper on the particles appearing in the June 3 issue of Nature Nanotechnology. Lead author of the paper is former MIT postdoc Hyukjin Lee, now an assistant professor at Ewha Womans University in Seoul, South Korea.

Genetic disruption

RNA interference (RNAi), a natural phenomenon that cells use to control their gene expression, has intrigued researchers since its discovery in 1998. Genetic information is normally carried from DNA in the nucleus to ribosomes, cellular structures where proteins are made. Short interfering RNA (siRNA) disrupts this process by binding to the messenger RNA molecules that carry DNA’s instructions, destroying them before they reach the ribosome.

siRNA-delivering nanoparticles made of lipids, which Anderson’s lab and Alnylam are also developing, have shown some success in turning off cancer genes in animal studies, and clinical trials are now underway in patients with liver cancer. Nanoparticles tend to accumulate in the liver, spleen and lungs, so liver cancer is a natural target — but it has been difficult to target such particles to tumors in other organs.

“When you think of metastatic cancer, you don’t want to just stop in the liver,” Anderson says. “You also want to get to more diverse sites.”

Another obstacle to fulfilling the promise of RNAi has been finding ways to deliver the short strands of RNA without harming healthy tissues in the body. To avoid those possible side effects, Anderson and his colleagues decided to try delivering RNA in a simple package made of DNA. Using nucleic acid origami — which allows researchers to construct 3-D shapes from short segments of DNA — they fused six strands of DNA to create a tetrahedron (a six-edged, four-faced pyramid). A single RNA strand was then affixed to each edge of the tetrahedron.

“What’s particularly exciting about nucleic acid origami is the fact that you can make molecularly identical particles and define the location of every single atom,” Anderson says.

To target the particles to tumor cells, the researchers attached three folate molecules to each tetrahedron. Short protein fragments could also be used to target the particles to a variety of tumors.

Using nucleic acid origami, the researchers have much more control over the composition of the particles, making it easier to create identical particles that all seek the right target. This is not usually the case with lipid nanoparticles, says Vinod Labhasetwar, a professor of biomedical engineering at the Lerner Research Institute at the Cleveland Clinic. “With lipid particles, you’re not sure what fraction of the particles are really getting to the target tissue,” says Labhasetwar, who was not involved in this study.

Circulate and accumulate

In studies of mice implanted with human tumors, the researchers found that once injected, the nucleic acid nanoparticles circulated in the bloodstream with a half-life of 24 minutes — long enough to reach their targets. The DNA tetrahedron appears to protect the RNA from rapid absorption by the kidneys and excretion, which usually happens with RNA administered on its own, Anderson says.

“If you take a short interfering RNA and inject it into the bloodstream, it is typically gone in six minutes. If you make a bigger nanoparticle using origami methods, it increases its ability to avoid excretion through the kidneys, thereby increasing its time circulating in the blood” he says.

The researchers also showed that the nucleic acid nanoparticles accumulated at the tumor sites. The RNA delivered by the particles was designed to target a gene for luciferase, which had been added to the tumor cells to make them glow. They found that in treated mice, luciferase activity dropped by more than half.

The team is now designing nanoparticles to target genes that promote tumor growth, and is also working on shutting off genes involved in other genetic diseases.

The research was funded by the National Institutes of Health, the Center for Cancer Nanotechnology Excellence, Alnylam Pharmaceuticals and the National Research Foundation of Korea.

http://web.mit.edu/newsoffice/2012/rna-interference-lightwei…

[aktianer]

die Selbstbedienung am gut gedeckten Tisch durch Beförderungen samt Gehaltserhöhungen geht weiter:

Business WirePress Release: Alnylam Pharmaceuticals – Wed, Jun 27, 2012 8:00 AM EDT
Alnylam Expands and Develops Management Team
– Appoints Oved Amitay to Vice President, Head of Commercial –
– Promotes Akshay Vaishnaw to Executive Vice President and Chief Medical Officer;
Jared Gollob to Vice President, Clinical Research; and,
Lubomir Nechev to Vice President, Process Sciences –

http://finance.yahoo.com/news/alnylam-expands-develops-manag…

[Fruehrentner]

Gab ja nen satten Kurssprung!

[Fruehrentner]

Alnylam Presents Complete Results from Phase IIb Trial with ALN-RSV01, an Inhaled RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus (RSV) Infection

04 Sep 2012

– ALN-RSV01 Reduces Bronchiolitis Obliterans Syndrome (BOS) in RSV-Infected Lung Transplant Patients –

– Alnylam to Discuss Results with U.S. and European Regulatory Authorities and Communicate Future Development Plans at Year End –

CAMBRIDGE, MA, USA I September 4, 2012 I Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today complete results from its Phase IIb trial with ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection in lung transplant patients. The data were presented at the European Respiratory Society’s (ERS) Annual Congress held in Vienna, September 1-5, 2012. As reported previously, the study narrowly missed the primary endpoint of reduced day 180 BOS in an “intent-to-treat” (ITTc) analysis of confirmed RSV infected patients, but achieved statistically significant reductions in prospectively defined analyses of ITTc patients with their “last observation carried forward” (LOCF), and of ITTc patients treated “per protocol” (PP). At the ERS meeting, new results were presented on secondary endpoints and certain post-hoc analyses that support the efficacy of ALN-RSV01 in this setting. Further, and as reported earlier, ALN-RSV01 was found to be generally safe and well tolerated in the study. Alnylam plans to discuss these complete results with U.S. and European regulatory authorities, and communicate future development plans for ALN-RSV01 at year’s end.

“Our Phase IIb study results demonstrate that inhaled ALN-RSV01 reduces the incidence of new or progressive BOS in RSV-infected lung transplant patients. The complete results presented at the ERS meeting continue to show that ALN-RSV01 is associated with a significant treatment effect, including results of a multivariate logistic regression analysis where treatment with ALN-RSV01 showed an over eight-fold reduced risk in developing day 180 BOS. Further, we showed a statistically significant effect on the secondary endpoint of day 90 BOS, and demonstrated a particularly strong effect of over 80% in patients receiving ALN-RSV01 within five days of symptom onset,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Alnylam. “Our plans are to discuss these results with U.S. and European regulatory authorities later this year and then communicate next steps, if any, for our ALN-RSV program. In the meanwhile, we continue to execute on our ‘Alnylam 5x15’ product strategy with a focus on our transthyretin-mediated amyloidosis and hemophilia programs.”

“Community acquired respiratory infections, including RSV, represent a significant risk for lung transplant patients, as infection may be associated with the development of new or progressive BOS. Indeed, BOS is the leading cause of death in patients beyond the first year of transplantation,” said Jens Gottlieb, M.D., principal investigator, Hannover Medical School. “Amongst other study findings, ALN-RSV01 treatment shows a clinically meaningful effect on the incidence of day 180 BOS, and these results appear to be quite robust even in the context of concomitant therapies such as ribavirin and steroids. There is clearly an unmet medical need for an effective RSV therapy for lung transplant patients, and ALN-RSV01 holds considerable potential as an innovative therapeutic for the prevention RSV-induced BOS.”

As reported previously, the Phase IIb trial was an international multi-center, randomized, double-blind, placebo-controlled study of ALN-RSV01 in RSV-infected lung transplant patients. RSV infection in lung transplant patients represents a significant unmet medical need as it can lead to the development of new or progressive BOS, an irreversible fibro-occlusive pathology of the airways that is the biggest cause of chronic allograft dysfunction and mortality in lung transplant patients, with an approximately 50% mortality within five years of onset. The primary endpoint of the Phase IIb trial was the incidence of new or progressive BOS at 180 days. The trial enrolled 87 patients who were randomized in a one-to-one, ALN-RSV01-to-placebo ratio; a total of 33 sites participated from six countries. Based on central laboratory confirmation of RSV infection, a total of 44 patients were randomized to receive ALN-RSV01 and 33 patients were randomized to receive placebo, defining the overall intent-to-treat study cohort (ITTc). Data from the study show that ALN-RSV01 missed the primary endpoint of new or progressive BOS at 180 days in the ITTc population (p=0.058). However, ALN-RSV01 treatment was associated with a statistically significant reduction in the incidence of day 180 BOS in the prospectively defined LOCF (p=0.028) and PP (p=0.025) analyses. In all analyses, treatment with ALN-RSV01, as compared with placebo, was associated with a clinically meaningful reduction in the incidence of day 180 BOS with a treatment effect of greater than 50%.

New study findings presented at the ERS meeting included results from key secondary endpoints and certain post-hoc analyses of data. As it pertains to key secondary endpoints, ALN-RSV01 treatment resulted in a statistically significant reduction in day 90 BOS as compared with placebo as measured in the ITTc population (p=0.044) with an overall effect size of 52%. Further, ALN-RSV01 showed an enhanced treatment effect size of 88% toward day 180 BOS in patients treated within five days from symptom onset (p=0.0095). Other secondary endpoints including viral parameters and symptom score were not significantly different between ALN-RSV01 and placebo. A number of post-hoc analyses were also performed. In a logistic regression analysis adjusting for multiple variables, treatment with ALN-RSV01 was found to be associated with a significantly reduced risk of developing day 180 BOS, with an odds ratio of 8.5 (95% confidence intervals of 1.7 and 41.7). Further, the effects of ALN-RSV01 on day 180 BOS persisted when controlled for the concomitant administration of pulse-dose steroids. A direct comparison of patients receiving ALN-RSV01 in the absence of ribavirin versus placebo patients receiving inhaled ribavirin, the current standard of care at some centers, showed that ALN-RSV01 was associated with a statistically significant reduction in new or progressive BOS at day 180 (p=0.022). There was a similar incidence of reported adverse events in placebo (81%) and study drug (73.3%) treatment arms. Serious adverse events were also reported with similar incidence in patients receiving placebo (9.5%) and ALN-RSV01 (11%). In aggregate, the newly presented results support the conclusion that treatment of RSV-infected lung transplant patients with ALN-RSV01 is generally safe and well tolerated and associated with a decreased incidence of new or progressive BOS.

Alnylam’s RSV program is partnered with Cubist Pharmaceuticals in North America and the rest of the world outside of Asia, where the program is partnered with Kyowa Hakko Kirin Co., Ltd. These partners maintain certain opt-in rights for the development of ALN-RSV01.

About Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a highly contagious virus that is the most common identified cause of lower respiratory tract infections in children under one year of age. The clinical manifestations of RSV infection depend on the patient’s age and health status. Older children and adults often have a milder course, with cold-like symptoms, while infants and immune-compromised patients can have a more severe illness that results in bronchiolitis, pneumonia and in some instances death. In the pediatric and adult populations, RSV accounts for more than 300,000 hospitalizations per year in the U.S. RSV infection in lung transplant patients represents an important unmet medical need. Lung transplant patients infected with RSV are at risk for both acute rejection and a bronchiolitis obliterans syndrome (BOS). BOS is a progressive inflammatory and fibrotic lesion of the small airways resulting in an irreversible loss of function in the transplanted lung, and is associated with approximately 50% mortality within five years. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.

[Fruehrentner]

Was tut sich hier?

[sufenta]

Antwort auf Beitrag Nr.: 44.039.886 von Fruehrentner am 18.01.13 22:57:44

Die haben gerade richtig Kohle eingesammelt um Gas zu geben: schau die Nachrichten bei seeking a. Bin seit 21,50 drin.Hoffe kurzfristig bis 30.

[sufenta]

Ergänzung:

Eigentlich wollten sie initial gar nicht soviele shares offerieren, aber wegen der imensen Nachfrage wurde/mußte ! die Anzahl erhöht werden, so dass sie letztlich > 150MIO US-Dollar eingenommen haben!

Quelle: siehe aktuelle Nachrichten bei yahoo

Die 30 sehen wir denke ich bald!

Grüsse,s.

[sufenta]

Zitat von sufenta: Ergänzung:

Eigentlich wollten sie initial gar nicht soviele shares offerieren, aber wegen der imensen Nachfrage wurde/mußte ! die Anzahl erhöht werden, so dass sie letztlich > 150MIO US-Dollar eingenommen haben!

Quelle: siehe aktuelle Nachrichten bei yahoo

Die 30 sehen wir denke ich bald!

Grüsse,s.

-Lesezeichen-

30, bald sind wir da.

[Fruehrentner]

Alnylam Scientists Present Pre-clinical Data with ALN-CC5, an RNAi Therapeutic Targeting Complement Component C5 for the Treatment of Complement-Mediated Diseases

Thursday, 20 June 2013 14:32 |


– New Research Presented at 6th International Conference on Complement Therapeutics Demonstrates Potent, Dose-Dependent, and Durable Silencing of Serum C5 and Inhibition of Complement Hemolytic Activity by Approximately 90%

– ALN-CC5 Advanced as New “Alnylam 5x15” Program Using Company’s GalNAc-Conjugate Delivery Technology Enabling Subcutaneous Dose Administration

– Company Expands Pipeline Guidance and Expects to Nominate Development Candidate by Late 2013 –

CAMBRIDGE, MA, USA I June 20, 2013 I Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data with ALN-CC5, an RNAi therapeutic targeting complement component C5. These data were presented at the 6th International Conference on Complement Therapeutics being held June 18 - 23, 2013 in Kos, Greece. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in serious, life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. C5 is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune defense against certain infections and intravenously administered anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. In a presentation titled “Development of an RNAi Therapeutic Silencing the C5 Component of Complement,” Alnylam scientists presented pre-clinical results showing potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90% with a subcutaneously administered RNAi therapeutic. Alnylam believes that ALN-CC5 – part of the company’s “Alnylam 5x15” product strategy – represents a novel approach for the treatment of complement-mediated diseases; the company expects to nominate a development candidate for clinical advancement in late 2013.

“C5 is a genetically and clinically validated target that exemplifies the potential of Alnylam’s ‘5x15’ product strategy for innovative new medicines. First, C5 is predominantly expressed in liver, where we have established clinical activity and tolerability for RNAi therapeutics. In addition, our clinical development plan for an RNAi therapeutic targeting C5 will be facilitated by serum biomarkers in Phase I trials and a relatively streamlined and focused path for advanced development,” said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development at Alnylam. “Indeed, we believe that a subcutaneously administered RNAi therapeutic targeting C5 could represent an important advance for the treatment of a broad range of complement-mediated diseases.”

New data presented at the scientific meeting showed that a GalNAc-siRNA conjugate targeting the C5 mRNA resulted in potent, dose-dependent, and durable silencing of C5 liver mRNA, knockdown of C5 serum protein levels, and inhibition of complement-mediated hemolysis activity. Specifically, a prototype GalNAc-siRNA conjugate targeting C5 showed a single dose ED50 for C5 knockdown of approximately 0.6 mg/kg in rodent models. In multi-dose experiments, subcutaneous administration of the GalNAc-siRNA conjugate resulted in approximately 90% knockdown of serum C5 levels at doses of ≥1.25 mg/kg. Additional multi-dose experiments showed that the current lead candidate siRNA could achieve an approximately 90% inhibition of complement-mediated hemolytic activity in the rat at subcutaneous doses of 5 mg/kg; these effects were rapid, dose-dependent, and durable for weeks after cessation of treatment. The company is performing additional optimization of the GalNAc-siRNA conjugate lead molecule and expects to nominate its ALN-CC5 development candidate in late 2013.

“The complement system plays a central role in immunity as part of host defense. However, dysregulation of this pathway can lead to life-threatening complications in a wide range of human diseases including PNH, aHUS, myasthenia gravis, neuromyelitis optica, amongst others,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Alnylam. “We are excited about these pre-clinical data showing potent, dose-dependent, and durable knockdown of serum C5 with about 90% inhibition of hemolysis activity using a subcutaneously administered RNAi therapeutic. We believe that if these results can extend in the clinical setting, they could represent a very promising therapeutic strategy and new treatment option for patients with complement-mediated diseases.”

[Fruehrentner]

neue Höchststände

[aktianer]

Antwort auf Beitrag Nr.: 45.006.189 von Fruehrentner am 08.07.13 23:17:33

wow, da kommt langsam Freude auf: heute ein 6 U$-Sprung auf 43 U$!

[Fruehrentner]

unglaublich!!

Und ich hab's nur auf der watch list

[aktianer]

das tut mir aber leid, denn Du hast ja den Threat am Leben gehalten. Schon aus diesem Grund hätte es Dir wirklich gegönnt an der Kursentwicklung teilhaben zu können.

Ich selbst hab hier nur das Glück gehabt, dass die Stücke schon lange im Depot lagen und ich sie vor allem wegen der Steuerfreiheit im Depot behalten habe. Es gab ja genügend Rückschläge und Maganore schien mir nicht der Fähigste zu sein, im Grunde hoffte ich vor allem noch auf die wissenschaftlichen Fähigkeiten von Rudi Tuschl.

Trotzdem, so schön die Kursentwicklung der letzten Zeit ist, im Vergleich zur ehemaligen Joint-Venture-Tochter Regulus (war ein Joint-Venture mit Isis) ist die Kursenticklung von Alny immer noch bescheiden, denn Regulus kam erst im Oktober 2012 am die Börse und hat sich beinahe verdreifacht. Auch Isis ist wesentlich besser gelaufen als Alny. Bin jetzt gespannt, ob man das Niveau halten kann oder ob dies einfach ein Übertreibung ist. Vor kurzem wurden Kursziele von 36 bis 42 U$ ausgegeben, die sind ja nun erreicht.

Das alleine könnte könnte schon in den nächsten Tagen zu beträchtlichen Gewinnmitnahmen mit entsprechenden Kursrückgängen führen; zudem dürfte auch Maganore mal wieder Stücke verkaufen mit entsprechenden Reaktionen. Da ergeben sich vielleicht doch noch Einstiegschancen.

Grundsätzlich glaube ich, dass nach vermeintlichen Jahres des Stillstands und der Rückschläge die Silence-Technologie inzwischen ein gutes Stück vorwärts gekommen ist.

[Fruehrentner]

danke aktianer.

Die anderen von Dir erwähnten, gut gelaufenen Aktien sind mir leider unbekannt. Muss ich mir mal ansehen.

Sagt die SILENCE THERAPEUTICS etwas?

[aktianer]

Antwort auf Beitrag Nr.: 45.029.551 von Fruehrentner am 11.07.13 21:38:17

hab mir jetzt Silence Therapeutics mal angeschaut. Scheint eine interessantes Unternehmen zu sein, vor allem weil man sich als eines der ersten Unternehmen auch in Richtung Krebsbekämpfung entwickelt hat. Hier ist man allerdings noch ziemlich am Anfang. Bis Mitte 2014 will man offenbar die Rekrutierung der Patienten für die klinische Phase IIa abgeschlossen haben, Ergebnisse der Studie sollen ein Jahr später vorliegen, also Mitte 2015. Das ist ein relativ langer Zeitraum ohne grosse Nachrichten aus diesem Sektor.

Deshalb finde ich auch die anderen Pipeline-Entwicklungen für die Kursentwicklung wichtiger, hier ist man ja z.T. bereits in Phase IIb. Man hat dort auch zweifellos namhafte Partner, unklar ist aber, ob man hier tatsächlich grössere Lizengebühren im Erfolgsfall einheimsen kannn.

Beachten muss aber man auch, dass sich der Kurs binnen einem Jahr schon vervierfacht hat. Zudem haben die Grossaktionäre dieses Unternehmen (firmierte zuvor als ATUGen) aus heutiger Sicht zu einem Spottpreis übernommen. Da könnten beträchtliche Gewinnrealisierungen drohen und noch gefährlicher: die Grossaktionäre sind Insider und werden rechtzeitig (falls sich negative Ergebnisse abzeichnen) ihre Bestände reduzieren. Also mir wäre das im Moment bei diesem Kurs zu heiss.

[Fruehrentner]

aktianer,

danke für deine Einschätzung zu Silence Therapeutics.

Hier noch ein Tip: PRANA BIOTECHNOLOGY (s. thread hier auf W O)

[Fruehrentner]

Allzeithoch

[aktianer]

Antwort auf Beitrag Nr.: 45.371.507 von Fruehrentner am 02.09.13 21:23:41

läuft unerwartet stark nach einer kleinen Konsolidierung (auf ca. 43) weiter; eigentlich hatte ich ja einen stärkeren Rückgang erwartet; der CEO Maganore übte im Juli und August Optionen über je 60000 Stück (Kaufpreis 0,95 U$) aus und verkaufte die bezogenen Aktien zu 37 U$ bzw. die zweite Tranche zu ca. 48,90 U$ im Schnitt. Auch andere Führungspersonen haben Kasse gemacht.
Dass es hier nicht zu dem "üblichen" Rückgang kam ist insbesondere nach dem kräftigen Kursanstieg erstaunlich. Vielleicht deutet sich hier eine Übernahme ab?
Die anderen beiden von mir genannten Werte aus diesem Bereich, ISIS und Regulus haben auf jeden Fall nach den starken Kurssteigerungen eine heftige Konsolidierung erlebt!
Regulus ist immer noch 25% unter dem Höchstkurs.
Übrigens hat die von Dir empfohlenen Silence Therapeutics heute einen schönen Sprung von 9% hingelegt. Es scheint so, als wäre ich hier doch zu skeptisch gewesen! Andererseits hätte man beim auch Kauf einer ISIS in der Konsolierung auch einen schönen Zugewinn erzielen können, vielleicht bei geringerem Risiko. Aber ich muss zugeben, dass ich die Kursrückgänge bei Regulus und ISIS mit der anschliessenden Erholung erst jetzt registriert habe. Schade!

[Fruehrentner]

ALNYLAM heute eine Rakete!!

[fmhbolero]

Alnylam Keeps Making New Strides In RNAi Research

Der Artikel auf biotechpicklist klingt nicht schlecht.