Isis Pharmaceuticals - Pioneering antisense drug discovery - 500 Beiträge pro Seite

[McNay]

Isis Pharmaceuticals hat ein ähnliches Geschäftsmodell wie Morphosys und ist der Pionier schlechthin was antisense technology betrifft.
Die Firma ist bei uns, trotz Ihrer schon beachtlichen Größe recht unbekannt und hier im Board finden sich leider nur vereinzelte oder ältere Einträge zu dieser, meiner Meinung nach aussichtsreichen Aktie.
Als gute Übersicht habe ich mir mal erlaubt die website von Isis zu bedienen:
http://www.isispharm.com/

Can you provide a brief description of your Company?

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 22 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis has designed and executed a patent strategy that has provided the Company with strong and extensive protection for Isis drugs as well as all aspects of antisense drug discovery, development and manufacturing.

When was the Company founded and when did it go public?

Isis Pharmaceuticals, Inc. was founded in 1989. Isis conducted its initial public offering two years later in 1991.

What is Isis' stock symbol and on what exchange is it traded?

Isis is traded on the NASDAQ stock exchange under the symbol ISIS. Please note that prior to February 21, 2002 our symbol was ISIP.

How many shares are outstanding?

The number of shares of voting common stock outstanding as of November 1, 2010 was 99,231,375.

[McNay]

London (aktiencheck.de AG) - Jim Birchenough, Ryan Martins, und Charles J. Whitesell, Analysten von Barclays Capital, stufen die Aktie von ISIS Pharmaceuticals (ISIN US4643301090/ WKN 881866) weiterhin mit "overweight" ein. Das Kursziel werde nach wie vor bei 17 USD gesehen. (Analyse vom 05.11.2010) (08.11.2010/ac/a/u)

Rating-Update:

London (aktiencheck.de AG) - Jim Birchenough, Ryan Martins, und Charles J. Whitesell, Analysten von Barclays Capital, stufen die Aktie von ISIS Pharmaceuticals (ISIN US4643301090/ WKN 881866) weiterhin mit "overweight" ein. Das Kursziel werde nach wie vor bei 17 USD gesehen. (Analyse vom 05.11.2010) (08.11.2010/ac/a/u)

[McNay]

Interessant ist auch die Tocher von ISIS, Regulus Therapeutics, welche zusammen mit Alnylam Pharmaceuticals (Nasdaq: ALNY)2007 gegründet wurde und sich mit dem Thema microRNA beschäftigt.

Im Sommer wurde hier eine strategische Allianz mit Sanofi-Aventis S.A. vereinbart.

Paris - 22. Juni 2010 - Sanofi-aventis (EURONEXT: SAN und NYSE: SNY) und Regulus
Therapeutics Inc gaben heute die Vereinbarung einer weltweiten strategischen Allianz zur
Entdeckung, Entwicklung und Vermarktung von microRNA-Therapeutika bekannt. Die Partnerschaft
wird sich zunächst auf den Therapiebereich Fibrose fokussieren.
MicroRNA-basierte Wirkstoffe (dt. micro-Ribonukleinsäure) sind eine neue Klasse von kleinen nichtkodierenden
Ribonukleinsäuren, die die Genexpression regulieren indem sie in die RNA-Transkripte
der Zielregion eingreifen. Endogene microRNAs regulieren die Expression von über einem Drittel
aller menschlichen Gene. Der Zusammenhang von Funktionsstörungen der microRNA mit
bestimmten Krankheitsbildern hat zur Erforschung einer ganz neuen Klasse pharmazeutisch
relevanter Wirkstoffkandidaten geführt.
Sanofi-aventis und Regulus werden bei der Erforschung und der zielgerichteten präklinischen
Entwicklung von bis zu vier microRNA-Therapeutika zusammenarbeiten, was das erste Programm im
Bereich Fibrose mit microRNA-21 mit einschließt. Sanofi-aventis erhielt darüber hinaus eine weitere
Option die – sollte davon Gebrauch gemacht werden – dem Unternehmen den Zugang zu
Technologien verschafft, um weitere microRNA-basierte Wirkstoffe über die ersten vier Wirkstoffe
hinaus zu entwickeln.
„Regulus freut sich sehr über diese wichtige Partnerschaft mit sanofi-aventis, einem führenden
Gesundheitsunternehmen, das wichtige neue Therapieoptionen entwickelt, die von großem Nutzen
für Patienten weltweit sein können“, sagte Kleanthis G. Xanthopoulos, Ph.D., President and Chief
Executive Officer von Regulus. „Die Unterstützung von sanofi-aventis in dieser neuen Partnerschaft
wird uns in unserem Bestreben, das führende microRNA Unternehmen aufzubauen, bestärken. Wir
fühlen uns der herausragenden wissenschaftlichen Arbeit verpflichtet und möchten unsere Pipeline
von innovativen neuen Medikamenten beständig weiterentwickeln. Wir sind uns sicher, dass diese
neue Allianz unsere Möglichkeiten und Ressourcen signifikant erweitern wird und uns unterstützt auf
dem Weg, das führende Unternehmen in der Entdeckung und Entwicklung von microRNATherapeutika
zu werden.“
„Diese Partnerschaft bestätigt erneut das Engagement von sanofi-aventis in der Entwicklung
innovativer Therapien“, bekräftigte Marc Cluzel, M.D., Ph.D., Executive Vice President, Research &
Development, bei sanofi-aventis. „MicroRNA sind in der menschlichen Entwicklung und Physiologie
von großer Bedeutung. Zusammen mit Regulus werden wir Therapeutika entwickeln, diemöglicherweise einen Paradigmenwechsel in der Behandlung der wichtigsten Krankheiten eröffnen
und einen attraktiven neuen Behandlungsansatz für Patienten bieten können.“
Im Rahmen der Vereinbarung erhält Regulus eine Vorabzahlung in Höhe von 25 Mio. USD und eine
zukünftige Beteiligung in Höhe von 10 Mio. USD, die auf beiderseitiger Zustimmung nach
Unternehmensbewertung beruht. Die Allianz könnte auf einen Wert von über 750 Mio. USD erreichen
wenn man Vorabzahlungen, Beteiligungsinvestitionen, Forschungsausgaben und potenzielle
Meilensteinzahlungen für die präklinische und klinische Entwicklung und Vermarktung für
verschiedene Produkte einbezieht.
Regulus wurde 2007 gegründet und ist ein gemeinsames Tochterunternehmen von Alnylam
Pharmaceuticals (Nasdaq: ALNY) und Isis Pharmaceuticals (Nasdaq: ISIS).
Über microRNA
Die Entdeckung von microRNA beim Menschen ist einer der spannendsten wissenschaftlichen
Durchbrüche des letzten Jahrzehnts. MicroRNA sind kleine Moleküle, meist 20 bis 25 Nukleotide
lang, die keine Proteine kodieren, sondern stattdessen die Genexpression regulieren. Nahezu 700
micro-RNA wurden im menschlichen Genom identifiziert, und mehr als ein Drittel aller menschlichen
Gene sind nach heutigem Forschungsstand durch microRNA reguliert. Da eine einzige microRNA
ganze Netzwerke von Genen steuern kann, werden diese neuen Moleküle als die Hauptschaltstelle
bei der Regulierung des Genoms betrachtet. Darüber hinaus konnte nachgewiesen werden, dass
microRNA eine zentrale Rolle bei vielfältigen biologischen Prozessen, wie beispielsweise der
Immunantwort, der Kontrolle des Zellzyklus, des Stoffwechsels, der Virusreplikation, der
Stammzelldifferenzierung und der menschlichen Entwicklung spielen. Die meisten microRNA
kommen über viele Spezies hinweg vor, was für die evolutionäre Bedeutung dieser Moleküle als
Modulatoren essentieller biologischer Mechanismen spricht. Tatsächlich wurde nachgewiesen, dass
die microRNA-Expression oder –Funktion in vielen Krankheitsbildern deutlich verändert ist, z.B. bei
Krebs, Herzinfarkt oder Virusinfektionen. Die Möglichkeit, microRNA mit anti-miRs, Antisense-
Oligonukleotiden von microRNA, oder miR-Imitaten, d.h. doppelsträngigen Oligonukleotiden, die die
microRNA-Funktion ersetzen, anzugehen, eröffnet eine völlig neue Wirkstoffklasse und einen
einzigartigen Ansatz, Krankheiten durch die Modulation ganzer biologischer Prozesse zu behandeln.
Mehr Informationen zu microRNA erhalten Sie unter http://www.regulusrx.com/microrna/micrornaexplained.
php

Über Regulus Therapeutics Inc.
Regulus Therapeutics ist ein biopharmazeutisches Unternehmen, das im Bereich der Entdeckung
und Entwicklung innovativer, microRNA-basierter neuer Medikamente führend ist. Regulus entwickelt
microRNA als eine neue Klasse von Therapeutika in Zusammenarbeit mit einem großen Netzwerk
von akademischen Partnern und unterstützt die Erforschung und Entwicklung Oligonukleotidbasierter
Medikamente seiner Gründungsunternehmen Alnylam Pharmaceuticals (Nasdaq: ALNY)
und Isis Pharmaceuticals (Nasdaq: ISIS). Regulus bringt microRNA-Therapeutika in einigen
Bereichen in die klinische Forschung, wie z.B. bei Hepatitis C-Infektionen, Herz-
Kreislauferkrankungen, Fibrose, Onkologie, entzündlichen Autoimmunerkrankungen und
Stoffwechselkrankheiten. Regulus hält die Rechte an allen grundlegenden Patenten wie auch den
wichtigsten Patenten in diesem Bereich, was insgesamt mehr als 600 Patente und mehr als 300
ausstehende Patentanmeldungen umfasst. Vorrangig betrifft dies chemische Modifikationen von
Oligonukleotiden, die auf microRNA zu therapeutischen Zwecken abzielen.
Über sanofi-aventis
Sanofi-aventis ist ein führendes, globales Pharmaunternehmen, das therapeutische Lösungen
erforscht, entwickelt und vertreibt, um das Leben der Menschen zu verbessern. Sanofi-aventis ist an
den Börsen in Paris (EURONEXT: SAN) und New York (NYSE: SNY) gelistet.

[ipollit]

Antwort auf Beitrag Nr.: 40.694.656 von McNay am 11.12.10 17:46:52

habe zwar auch ISIS... so einfach ist das allerdings alles nicht. Z.B. scheint es bei den Pharmas inzwischen einige Skepsis bezüglich RNAi-Technologien zu geben:

http://www.faz.net/s/Rub7F74ED2FDF2B439794CC2D664921E7FF/Doc…

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

28. November 2010 Am Anfang existieren oft nur ein paar Labordaten und eine kühne Idee. Am Ende soll ein Patient im besten Fall eine Pille schlucken können oder eine Spritze erhalten, die seine Krankheit lindert oder gar heilt. Auf dem Weg dorthin entstehen Karrieren wie die von Roland Kreutzer - erst Forscher, dann Firmengründer, Beinahepleitier, Fusionspartner und Übernahme-Spielball. Nun steht er vor dem Aus.

Der Pharmakonzern Roche, dessen Kulmbacher Forschungszentrum Kreutzer zuletzt leitete, hat vergangene Woche Sparmaßnahmen und den Abbau von rund 4800 Arbeitsplätzen weltweit beschlossen. Der Vorstandsvorsitzende Severin Schwan gab für Deutschland zwar Entwarnung, und meist erwähnten Zeitungsberichte nur mit einem Satz das Ende der RNA-Technologie. Doch mit seinem Beschluss stellt Roche auch die Erforschung jenes neuartigen Therapiekonzepts ein, das 2006 mit dem Medizin-Nobelpreis gekürt wurde und das den Forscher Kreutzer zum Unternehmer werden ließ.

Es begann 1998 am Stehimbiss vor der Universität Bayreuth. Aufgeregt las Kreutzers Forscherkollege Stefan Limmer in der Mittagspause einen Nature-Artikel, in dem die späteren Nobelpreisträger Andrew Fire und Craig Mello die Entdeckung der sogenannten RNA-Interferenz schilderten. Sie hatten doppelsträngige Moleküle der Ribonukleinsäure (nach ihrer englischen Bezeichnung RNA abgekürzt) in die Zellen von Fadenwürmern geschleust und so die Umwandlung der Geninformation in ein Protein gestoppt: Die dafür zuständige Boten-RNA (mRNA) wurde abgefangen. "Wenn das beim Fadenwurm funktioniert, dann sollte das auch beim Menschen klappen", sagten sich die Molekulargenetiker in Bayreuth. Sie testeten die Technik an menschlichen Zellen und fanden früher als irgendjemand sonst einen Weg, mit kurzen doppelsträngigen RNA-Molekülen jedes beliebige menschliche Gen abzuschalten, also auch schädliche. Manche Krankheiten könnte man dementsprechend stilllegen - die Idee einer völlig neuen Behandlungsstrategie war geboren.

Mit Startkapital
Euphorisiert von ihrer Entdeckung, meldeten Limmer und Kreutzer 1999 das weltweit erste Patent auf RNA-Interferenz (RNAi) beim Menschen an und gründeten im Sommer 2000 ihre Biotechfirma Ribopharma in Kulmbach. Dann brach die Internet- und Biotech-Begeisterung an den Aktienmärkten ein: "2001 haben wir bestimmt bei 50 Risikokapital-Gesellschaften vorgesungen", erinnert sich Kreutzer. Aber keiner habe sich getraut, genug Geld in die Hand zu nehmen. Als Kreutzer schon mit dem Schlimmsten rechnete, entstand in Boston die RNAi-Firma Alnylam. Dort hatte man nicht nur wichtige Experten und ein international erfahrenes Management eingeworben, sondern auch 17 Millionen Dollar Startkapital. Die Kulmbacher suchten das Gespräch, und Ende 2002 war die Fusion von Ribopharma und Alnylam beschlossen - auf Augenhöhe, dachten Kreutzer und Limmer anfangs. Die Amerikaner hatten aber vor allem zwei Motive. Zum einen kamen sie so an die frühen Patente von Kreutzer und Limmer heran, und zum anderen hatte die Max-Planck-Gesellschaft (MPG) sie dazu gezwungen.

"Wenn es nach Alnylam gegangen wäre, hätte es die Fusion nie gegeben", sagt Peter Gruss. Der MPG-Präsident hatte es aber zur Bedingung gemacht, eine RNAi-Firma in Deutschland mindestens bis Ende 2007 zu unterhalten, wenn die Amerikaner die Patente exklusiv nutzen wollten, die der Biochemiker Thomas Tuschl 2002 am Göttinger Max-Planck-Institut unabhängig von Kreutzer und Limmer erarbeitet hatte. Alnylam schluckte die Kulmbacher Kröte. Und damit war die "in großen Teilen deutsche Entwicklung", das weiß Alnylam-Chef John Maraganore, in amerikanischer Hand.

Alnylam entwickelte sich bald zur ersten Adresse für RNA-Interferenz. Spätestens der Nobelpreis machte die großen Pharmaunternehmen auf das Forschungsfeld aufmerksam. Der Schweizer Konzern Novartis ließ sich eine Kooperation mit Alnylam 700 Millionen Dollar kosten, später flossen nochmals 500 Millionen. Auch sonst war das Interesse an der Methode groß. Der amerikanische Pharmariese Merck kaufte für 1,1 Milliarden Dollar die RNAi-Firma Sirna, und Unternehmen wie Pfizer, Astra-Zeneca und GlaxoSmithKline suchten sich jeweils für hohe dreistellige Millionensummen passende Biotech-Kooperationspartner.

Kurzsichtige Einschätzung
Im Sommer 2007 vereinbarte Roche eine milliardenschwere Kooperation mit Alnylam. Erst am Morgen nach der Feier zum fünfjährigen Firmenbestehen in Boston erfuhr Roland Kreutzer davon - und dass der Kulmbacher Standort an Roche übergeben werde. Ein Schock für den Gründer, der sich nur beruhigen konnte, als er hörte, dass Arbeitsplätze und Standort mindestens bis 2009 garantiert werden sollten. In Kulmbach entstand ein "Roche Center of Excellence" für die Entwicklung neuartiger Therapeutika auf Basis der RNA-Interferenz, und das Forschungsteam stürzte sich voller Elan in die Arbeit. Mit einem großen Konzern im Rücken hoffte Kreutzer, das Ziel einer RNAi-Therapie erreichen zu können.

Jetzt, drei Jahre später, stoppt der Schweizer Konzern überraschend jegliche RNAi-Forschung. Roche kappt nicht nur die Alnylam-Kooperation, sondern legt zugleich den Kulmbacher Standort still. Ressourcen müssten "gezielt in die chancenträchtigsten und für unser Portfolio entscheidende Bereiche" investiert werden, sagt dazu die Unternehmenssprecherin Claudia Schmitt.

Einen längeren Atem habe er sich schon erhofft, sagt ein hörbar enttäuschter Kreutzer am Telefon. "Das zeigt, wie kurzsichtig man bei Roche mit der Entwicklung neuer therapeutischer Programme umgeht", meint Thomas Tuschl, Mitgründer und Berater Alnylams, der heute an der Rockefeller University in New York arbeitet. Wissenschaftliche Gründe für einen Rückzug aus der RNAi-Forschung sieht Tuschl jedenfalls nicht.

Pharmariesen auf Rückzug
Das grundsätzliche Problem, wie doppelsträngige RNA in kranke Zellen geschleust werden soll, sei noch nicht zufriedenstellend gelöst, sagt hingegen Roche-Sprecherin Schmitt. Eine technische Hürde, die schon vor drei Jahren bestanden habe, "und seitdem hat man enorme Fortschritte gemacht", sagt Tuschl. Inzwischen könne man die Moleküle effektiv in Zellen transportieren, außerdem gebe es erste klinische Testreihen. Trotz einer vergleichsweise kurzen Entwicklungszeit werden RNAi-Therapien bereits an Patienten erprobt (Sonntagszeitung vom 28. 3. 2010).

Allerdings ist Roche nicht der einzige Pharmariese, der sich zurückzieht. Novartis hat im Herbst den Großteil seiner RNAi-Forschung mit Alnylam eingestellt. "Die Konzerne werden diese Entscheidungen noch bedauern", ist Tuschl überzeugt. Ein ähnliches Beispiel seien die monoklonalen Antikörper - heute wichtige Krebsmedikamente: "Big Pharma" habe sich sehr ignorant dem Fortschritt gegenüber verhalten, und der Biotechbranche die Arbeit überlassen.

Auch damals hätten Pharmafirmen früh investiert, um dann kalte Füße zu bekommen, auszusteigen und erst sehr spät wieder auf den Zug aufzuspringen, sagt Alnylam-Chef Maraganore. "Ich wäre nicht überrascht, wenn es sich mit RNA-Interferenz ähnlich verhalten würde." Aber ein großer Unterschied besteht: Heute fehlt Biotechfirmen oft das Risikokapital, um Entdeckungen von Forschern wie Roland Kreutzer aufzugreifen und für die Praxis umzusetzen.

Den Trend, dass sich die großen Pharmafirmen immer häufiger aus der Weiterentwicklung neuartiger Ansätze zurückziehen, sieht Jörn Erselius von der Technologie-Transfer-Gesellschaft Max-Planck-Innovation mit Sorge. "Wir müssen nach einem neuen Modell suchen, wie Forschung in Therapien übersetzt werden kann." Sonst entscheiden allein wirtschaftliche Interessen und Strukturen über Erfolg oder Misserfolg guter Ideen. Die Geschichte von Ribopharma ist beispielhaft dafür.

Text: F.A.S.

****

mfg ipollit

[McNay]

Antwort auf Beitrag Nr.: 40.695.071 von ipollit am 11.12.10 19:57:03

Hallo ipollit,

danke für deinen kritischen Beitrag. Den kannte ich noch nicht.
Das Risiko von Fehlschlägen bzgl. dieser Technologie ist sicherlich nicht zu unterschätzen, auch musste ISIS auch selbst ja schon den einen oder anderen Fehlschlag weg stecken, weswegen der Kurs durchaus auch etwas unter Druck geraten ist. Sonst würden wir jetzt nicht bei 9-10 $ stehen, sondern uns in ganz anderen Dimensionen befinden.

Bzgl. der gemeinsamen Tochter Regulus Therapeutics bleibt abzuwarten in wie weit sich damit ordentlich Geld verdienen lässt.

Ich selbst halte auch nur einen für mich verhältnismäßig kleinen Anteil von Aktien von ISIS, da ich auch gerne etwas streue. Neben ISIS habe ich schon lange eine MOR und eine Immunogen in meinen Depot, dass reicht mir dann auch

[Berliner_Landstreicher]

Die Entwicklung eines Antisense Wirkstoffes ist mit den gleichen Risiken verbunden, wie jedes andere Medikament. Ich selber bin auch sehr an dieser Entwicklung interessiert und investiert. In Solvay´s Tochterunternehmen Girindus, die sich mit der Synthese von Antisense befassen. Auch das Problem mit der zielgerichteten Anwendung ist mir bekannt. Tatsache ist allerdings auch, dass das Problem vor seiner Lösung steht. Das steht auch in dem gleichen Artikel. In den letzten Jahren haben es bereits Medikamente in die Phase 3 geschafft.

Bsp.

Prosensa (Kooperation mit Glaxo) mit PRO51
Antisense Pharma mit Trabedersen (Orphan Drug Status bei der FDA) oder
Isis mit Mipomersen
uvm

Und 2 sind bereits zugelassen.

[McNay]

Antwort auf Beitrag Nr.: 40.696.408 von Berliner_Landstreicher am 12.12.10 14:58:17

Hallo Berliner_Landstreicher,

willkommen im Thread. Ich bin über jeden sinnvollen Beitrag froh und vielleicht wird dadurch der eine oder andere Aufmerksam auf die Diskussion hier und bringt auch seine Sichtweise mit ein. Ich denke hier bei w:o werden wohl einige mehr ein paar Isis Aktien besitzen, als man so denkt.

Bzgl. Antisense sehe ich das genauso wie du, ohne gewisse Risiken (auch wirtschaftliche) gibt es keinen Fortschritt und vermutlich auch keine neuen großartigen Medikamenten Entwicklungen.
Ipollit ist ja selber beteiligt an ISIS, ich denke der Beitrag der FAZ ist auch mehr gesellschaftskritisch gemeint und hat das Vorgehen von Pharmariesen insbesondere hier Roche angeprangert.
An diesen Beitrag in der FAZ kann man auch schön sehen, wie wichtig der Aktienmarkt für innovative Unternehmen ist, sich Geld zu beschaffen. Denn auf Partner in Wirtschaft oder Banken ist größtenteils kein Verlass. Die kaufen lieber verbriefte Wertpapiere über Schrottimmobilien weltweit ... das ist eindeutig risikoloser ... auch Staatsanleihen sollen ja sehr sicher sein

[ipollit]

Antwort auf Beitrag Nr.: 40.696.022 von McNay am 12.12.10 12:38:54

der Kurs von ISIS hängt meiner Meinung recht stark vom Mipomersen ab. Insbesondere wegen der erhöhten Leberenzyme wurde das Mittel zuletzt sehr kritisch gesehen, da diese ein Hinweis auf Leberschäden sein können und ein Schädigung der Leber eine nicht akzeptable Nebenwirkung ist. Unklar ist auch, ob Mipomersen ein Nischenprodukt sein wird für die, die lebensbedrohlich hohe Cholesterinwerte im Blut haben oder ob es in der breiteren Masse mit erhöhten Cholesterinwerten z.B. bei unzureichender Wirksamkeit von Statinen Anwendung findet. Nur im letzteren Fall besteht die Chance, dass es einmal Mrd-Umsätze generiert.

Ist nicht neu, aber zu diese Thema:

http://www.bnet.com/blog/pharma/genzymes-mipomersen-liver-si…

Genzyme's Mipomersen: Liver Side Effects Could Limit a Promising Cholesterol Drug
By David Phillips | March 29, 2010

Genzyme’s mipomersen, a promising new cholesterol drug, could offer new hope for patients who don’t respond to existing lipid-lowering drugs such as statins. But there are also troubling questions about a potential long-term, adverse effect of mipomersen on the liver.

Mipomersen is an antisense inhibitor of apo-B protein synthesis, the first drug of its type. Genzyme (GENZ) intends to first seek approval in the U.S. and Europe for mipomersen in those patients with homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder affecting one in a million people, in the first half of 2011. HoFH patients have extremely high cholesterol levels (greater than 500 mg per deciliter) and exhibit early signs of cardiovascular disease in all major arterial beds (including the neck, heart, and legs), resultant from defective low-density lipoprotein (LDL-c) receptors in the liver that are unable to remove LDL-c from circulation.



In a pivotal late-stage clinical trial of patients with HoFH, mipomersen reduced plasma LDL-c levels by almost 25 percent compared to placebo when added to existing lipid-lowering drugs (although most patients failed to reach targeted LDL goals).

Study investigators, led by Frederick J Raal, concluded in their findings, which are found online in Lancet, that “mipomersen could be a valuable addition to the drugs used in the management of homozygous familial hypercholesterolemia and should prove useful in the management of other forms of severe refractory hypercholesterolemia.”

Results, however, also raised questions about mipomersen’s safety and tolerability, as 76 percent and 12 percent of patients in the mipomersen group had injection-site reactions and increased liver enzymes of three times or more the upper limit of normal (with MRI findings of increased intra-hepatic fat content too).

Most experts concur with study investigators that mipomersen appears to offer a viable option for patients with severe, refractory hypercholesterolemia. In an editorial accompanying the Lancet article, R. Dermot Neely and Margaret F. Bassendine (of the Royal Victoria Infirmary and Newcastle University, England), said: “This new treatment paradigm appears to offer patients who would otherwise be dependent on weekly LDL apheresis a less onerous alternative.” LDL apherisis is a blood-filtering procedure that removes the “bad” cholesterol in a method similar to dialysis, and can cost upwards of $100,000 per year.

However, Neely judiciously noted, too, that hepatic fat increases were only measured (MRI) in the four folks with abnormally high ALT readings. Consequently, he concluded that longer studies with greater numbers of participants will be needed to provide reassurance that more significant fat accumulation and progression to non-alcoholic, irreversible liver damage does not occur — especially if mipomersen treatment is extended to common lipid disorders with more heterogeneous underlying causes (such as co-morbid diseases like diabetes).

Pharmacology studies evaluating the enzyme activities of mipomersen provide evidence that supports the use of mipomersen in combination with oral lipid-lowering agents. For example, mipomersen exhibited no clinically relevant pharmacokinetic interactions with the disposition and clearance of Zocor (simvastatin), ezetimibe, or the combination of the two, marketed as Vytorin (simvastatin/ezetimibe). Moreover, mipomersen did not inhibit any of the major hepatic enzymes involved in metabolizing lipid-lowering, psychotropic or other classes of drugs requiring “first-pass” through the liver to be converted to their active compounds.

If not drug interference, what is the causation behind mipomersen-related liver issues? In email correspondence, Dermot Neely elucidated the mechanism by which hepatic fat is increased with mipomersen:

Fat in the liver can be burned, stored or exported to other parts of the body. The mode of action of mipomersen is to reduce production of the carrier protein (apolipoprotein B) required for the export of fat (and cholesterol) from liver cells. Therefore if the liver continues to produce fat (from sugars, etc.) or receive deliveries of fat (e.g. released from fat stores) and is unable to burn this off in the production of energy (fat oxidation), fat stored in the liver will increase, resulting in an increase in transaminases [liver enzymes].

In addition, Drs. Neely and Bassendine cautioned that injection-site reactions occurred in most of the mipomersen-treated patients (76 percent), to the extent that such side-effects could have confounded the blinding of treatment. Of greater concern, could these events be immune-mediated reactions? To date, (in all studies) no antibodies to mipomersen have been detected so far, but the doctors prudently suggest longer-term monitoring will be necessary to ensure patients do not develop treatment resistance or autoimmunity.

John J Kastelein, (Chairman of the Department of Vascular Medicine at the Academic Medical Centre Amsterdam), and who has clinically investigated the effect of apo-B synthesis inhibition on liver triglyceride contents in FH patients, told me that “it shouldn’t be entirely unexpected that treated patients showed a trend towards an increase in intra-hepatic fat content (due to mode of action).”

Moreover, liver fat is not to be confused with liver toxicity — nor elevations of liver enzymes. In fact, most obese individuals have more liver fat — and for decades — than any of the guys in our mipomersen studies.

Kastelein did concur, however, with Neely that it would be prudent to have more long-term studies on the observed effects of mipomersen on hepatic function, as the affect of prolonged and profound reductions in apo-B on intra-hepatic fat content is unknown.

This risk assessment ought not be taken lightly, in my opinion. In the future likely candidates for adjunctive mipomersen injections — if Genzyme has its way — would include the broader range of at-risk patients already on maximal doses of statin therapies, but with circulating LDL still above recommended Adult Treatment Panel guidelines (not due to FH). A cohort of such study candidates should include those dyslipidemic patients with co-morbid diseases like diabetes, obesity, and/or pro-thrombotic states like advanced vascular disease — patients whose livers are likely already “stressed-out” (as assessed by ALT levels). Consequently it is critical to collect as much observable data as possible to help assess the risk-reward benefit of adjunctive treatment in such patients.

So there’s the rub, the folks who need the drug the most are at greatest risk for increases in stores of hepatic fat and elevated liver enzymes.

Without lipid-lowering therapy, hoFH patients rarely live beyond age 30. That statistic in mind, Kastelein finds no reason to refute claims by study investigators, too, that the additional 25 percent mean reduction in circulating LDL-c brought about by mipomersen could offer major clinical benefits to patients with HoFH. “Mipomersen heralds a new age of DNA-based therapies that can truly change the course of disease in these unlucky folks with mutated alleles resulting in severely high cholesterol levels,” he said.

Genzyme has a significant head start on other anti-sense competitors, with few even beyond animal or “proof-of-concept” studies. A company spokeswoman said two ongoing Phase 3 trials evaluating mipomersen in high-risk, high cholesterol patients are both incorporating comprehensive MRI measurements of hepatic fat content. Initial results are expected this summer, and will hopefully provide additional data on liver safety issues.


**********

http://www.bnet.com/blog/pharma/isis-pharmaceuticals-new-cho…

Isis Pharmaceuticals' New Cholesterol Drug Might Be a Hit, But It Won't Be Soon
By David Phillips | March 26, 2010

Isis Pharmaceuticals has big hopes for its novel drug mipomersen, which it wants to use for treating high cholesterol in otherwise difficult-to-treat patients. But liver-related side effects and the fact that the drug requires injections — as opposed to rival cholesterol pills — could make it a tough sell, potentially limiting its market-share prospects.

Mipomersen, a first-in-class apo-B synthesis inhibitor, works by decreasing the production of apo-B, a protein critical to the synthesis and transport of LDL and VLDL cholesterol — the “bad” lipids involved in the buildup of plaque in the arteries and the development of heart disease — through the bloodstream.

Whether mipomersen rises to $1 billion-plus blockbuster status or remains a niche drug with $250 million peak sales will depend on how the FDA feels about approving the drug for use in a broad pool of high-risk patients with uncontrolled LDL, despite taking maximum doses of lipid-lowering drugs such as statins like Pfizer’s Lipitor. There are about a million patients refractory to statin-therapy in the U.S. and Europe who are likely candidates for this indication, according to Isis chief executive officer Stan Crooke.



In January 2008, Isis sold development and marketing rights of mipomersen to Genzyme, receiving an up-front payment of $300 million ($150 million for Isis stock at $30 per share and a $175 million license fee). Isis also has the opportunity to receive from Genzyme up to $825 million in development and regulatory milestone payments plus significant commercial payments — contingent on an agreed-on, stepwise plan that gets mipomersen to market(s) for treatment in a variety of at-risk population groups refractory to current therapies, such as the popular “statin” drugs (like Crestor and Lipitor).

Genzyme intends to first seek approval in the U.S. and Europe for mipomersen in those patients with homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder affecting one in a million people, in the first half of 2011. HoFH patients have extremely high cholesterol levels (greater than 500 mg per deciliter) and exhibit early signs of cardiovascular disease in all major arterial beds (including the neck, heart, and legs), resultant from defective LDL-c receptors in the liver that are unable to remove LDL-c from circulation. Ergo, a therapy aimed at reducing LDL production at its source could be an attractive option.

Assuming successful submissions, Genzyme plans a second submission in Europe for the more common heterozygous form of the disease (HeFH), which affects one in 500 people.

Stan Crooke told analysts on the fourth-quarter 2009 earnings call that (according to Genzyme) there are 25,000 to 30,000 patients with HoFH who could use mipomersen in the U.S. and Europe and an additional 25,000 HeFH-patients (in Europe) for therapy.

Late-stage studies assessing the efficacy of mipomersen (weekly injection of 200 mg dose), when added to existing lipid-lowering drugs, showed success in meeting primary endpoints: LDL-c reductions of 25 percent and 28 percent in cohorts of HoFH and HeFH- treated patients.

Isis and Genzyme may want to keep that celebratory champagne on ice for now, as new safety data from the HoFH study (published in Lancet) connected the drug to elevated liver enzymes and fat deposits in the liver: four patients (12 percent) of mipomersen-treated patients had increases in liver enzymes (ALT) of three times (or more) the upper limit of normal and showed increases in hepatic fat, too.

Responding to repeated queries on the safety of mipomersen, chief executive Cooke stressed to analysts on the earnings call that the collective body of data to date shows mipomersen to be a safe drug:

With mipomersen, we have no drug-drug interactions, we have no central nervous system toxicity that we’ve identified, no cardiovascular toxicity and no muscle toxicity. So in that sense, mipomersen is an ideal drug to be added to patients who are typically taking 10 to 15 drugs on top of mipomersen.

Going forward, Genzyme is also looking at how best to facilitate uptake by physicians and improve patient compliance — once the drug is commercialized for the high-risk, high cholesterol patients refractory to other lipid-lowering drugs. As an oral formulation hasn’t moved beyond proof-of-concept, the companies hope to eliminate unnecessary discomfort through the introduction of a needle-less injector.

Nonetheless, before the companies can get to the lucrative lipid-lowering markets, they must fix the potholes on the current road: addressing likely FDA and European concerns of liver safety issues in FH patients. Genzyme is enrolling patients in an alternate dosing study. Although formal guidance on trial endpoints haven’t been issued to analysts, investigators are probably focused on two salient outcomes: Would variable dosing — as opposed to labeled dosing of be 200 mg in once-weekly shot — reduce risk of ALT elevations and increases in hepatic fat? And, would temporarily lowering the dose be advisable (following a dramatic reduction in lipid markers, such as apo-B)? To date, late-stage studies have been blinded and protocols didn’t offer this flexibility of dosing.

With almost $575 million in the bank, and other promising compounds in its pipeline, Isis can weather a likely delay — and pushback — of Genzyme’s initial regulatory filing date for mipomersen (planned for mid-2011).

****

mfg ipollit

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 40.696.473 von McNay am 12.12.10 15:30:24

Bei Mipomersen ist doch glaub ich das Problem, dass es erhöhte Leberwerte gibt. Ansonsten wohl ein klarer Zulassungskandidat für schwer behandelbare Diabetes. Aber wenn das nicht signifikant ist, dann sehe ich keinen Grund, warum die FDA da nicht "ja" sagen sollte.

Das eine zugelassene Medikament ist Vitravene und das andere ist was gegen grünen o. grauen Star.

Deshalb gehe ich erst einmal den indirekten Weg und investiere nicht gleich in Unternehmen, sondern such mir Profiteure die von der Entwicklung in diesem Bereich profitieren, ohne der direkten Gefahr des Scheiterns ausgesetzt sind. Und beobachte natürlich was so passiert.

[Berliner_Landstreicher]

Ich bin mir fast sicher, das Isis den ersten Antisense Blockbuster auf den Markt bringen wird. An der Wirkung gibt es aber auch nix zu meckern. Auch glaube ich, dass die FDA Mipomersen durchwinken wird. Es wäre für die gesamte Antisense Forschung ein enormer Push. Und das will die FDA. Deshalb wird Mipomersen den Sprung auf den Markt schaffen.

Gruß!

[ipollit]

Antwort auf Beitrag Nr.: 40.729.827 von Berliner_Landstreicher am 17.12.10 17:24:44

"dass die FDA Mipomersen durchwinken wird." ... die FDA winkt keine Medikamenten durch. Im Zweifelsfall wird die FDA eher keine Zulassung geben.

"Und das will die FDA"... wie kommst du denn darauf? Die FDA möchte nichts auf den Markt bringen, was sie hinterher wieder vom Markt nehmen muss. Also am besten möglichst wenig und wenn schon, dann nichts komplett neues und damit unbekanntes auf den Markt bringen... ich denke, dass ist eher im Interesse der FDA.

Außerdem... ob Mipomersen ein kommerzieller Erfolg wird, hängt nicht (nur) von der Zulassung ab, sondern davon, ob es auch eine breitere Anwendung findet. Das ist genauso offen.

mfg ipollit

[McNay]

Isis Initiates Phase 1 Clinical Trial of ISIS-APOCIIIRx to Treat Hypertriglyceridemia

CARLSBAD, Calif., Dec. 21, 2010 /PRNewswire via COMTEX/ --

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced the initiation of a Phase 1 study of ISIS-APOCIIIRx, an antisense drug designed to lower triglycerides to treat a variety of diseases associated with elevated triglycerides. Hypertriglyceridemia, a condition characterized by elevated levels of triglycerides, is an independent risk factor for cardiovascular disease and is a component of numerous cardiovascular and metabolic diseases, including metabolic syndrome. ISIS-APOCIIIRx inhibits the production of apolipoprotein C-III (apoC-III), a traditionally "undruggable" target that plays a central role in the regulation of triglycerides.

"Humans who cannot produce apoC-III have lower triglycerides and LDL-C levels, increased HDL levels and a lower risk of cardiovascular disease, suggesting that apoC-III inhibition could provide an effective new tool for lipid management. Many of the current therapies designed to lower triglycerides are associated with undesirable side effects, such as flushing, the most common side effect of niacin," said Rosanne Crooke, Ph.D., Vice President, Cardiovascular Diseases Drug Discovery Research at Isis. "In preclinical studies, antisense inhibition of apoC-III reduced the target mRNA and protein, lowered triglyceride levels in plasma, mitigated symptoms of metabolic syndrome and decreased atherosclerosis."

"ApoC-III is an excellent antisense target to reduce triglyceride levels and is another example of the broad applicability of our technology to selectively inhibit targets that could have a profound impact on diseases. ApoC-III inhibits the clearance of triglycerides from the blood. It is produced in the liver, a tissue that antisense drugs work very effectively in, and it is a target that has been difficult to inhibit with traditional approaches," said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. "We plan to develop ISIS-APOCIIIRx in a staged program similar to mipomersen, in which we will first evaluate the drug in very sick patients who cannot adequately lower their triglyceride levels using available therapies and who, as a result, have few therapeutic options. In this regard, we can exploit the knowledge we have gained from our mipomersen and PCSK9 programs to inform our development plan for ISIS-APOCIIIRx."

ABOUT ISIS-APOCIIIRx

ISIS-APOCIIIRx targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides. Recent data suggest that loss-of-function mutations within the apoC-III gene lower triglyceride levels and appear to improve health and extend longevity. In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates. In addition, apoC-III mediates insulin resistance, leading to worsening of the metabolic syndrome.

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 22 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis has designed and executed a patent strategy that has provided the Company with strong and extensive protection for Isis' drugs as well as all aspects of antisense drug discovery, development and manufacturing. Additional information about Isis is available at www.isispharm.com.

[McNay]

Isis Initiates Broad Phase 2 Program of ISIS-EIF4ERx in Cancer
Initial Studies Target Patients with Non-small Cell Lung Cancer and Prostate Cancer

CARLSBAD, Calif., Jan. 4, 2011 /PRNewswire via COMTEX/ --

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced the initiation of two Phase 2 studies of ISIS-EIF4ERx in patients with non-small cell lung cancer and prostate cancer. These studies are part of Isis' broad Phase 2 development program designed to evaluate ISIS-EIF4ERx in multiple types of cancer. ISIS-EIF4ERx targets eukaryotic initiation factor-4E (eIF-4E), a traditionally "undruggable" target that is thought to promote tumor growth and metastasis in many cancers.

"eIF-4E may represent a novel and broadly applicable target for cancers because it promotes cancer cell growth in many types of cancer," said Brett P. Monia, Ph.D., Vice President, Drug Discovery & Corporate Development at Isis. "In the Phase 1 study, ISIS-EIF4ERx reduced eIF-4E in tumors and was well tolerated at doses up to 1200 mg per week in patients with a variety of cancers. Initially, our Phase 2 program will evaluate ISIS-EIF4ERx in combination with first-line treatments in prostate cancer and non-small cell lung cancer. We plan to expand our Phase 2 program over time to evaluate ISIS-EIF4ERx in other cancers that over-express eIF-4E."

The first Phase 2 study is evaluating the safety and efficacy of ISIS-EIF4ERx in combination with carboplatin and paclitaxel in patients with non-small cell lung cancer. The second Phase 2 study is evaluating the safety and efficacy of ISIS-EIF4ERx in combination with docetaxel and prednisone in patients with castrate-resistant prostate cancer. Each randomized, controlled study will enroll approximately 100 patients. The endpoints for both studies include progression-free survival, response rates, overall survival, time to progression and the reduction of a variety of biomarkers.

"We are very encouraged by results obtained by our partners with our antisense anti-cancer drugs. We and our partners have shown that antisense drugs have unique effects in cancer without exacerbating the toxicity of chemotherapeutic agents. Our technology allows us to approach the many 'undruggable' targets that are of interest to treat cancer," continued Dr. Monia. "Data from these initial Phase 2 ISIS-EIF4ERx studies will also help inform future development decisions for patients with other types of cancer."

ABOUT ISIS-EIF4ERx

ISIS-EIF4ERx targets the gene that is responsible for the production of a protein, eIF-4E, which is over-expressed in a variety of cancers, including prostate, lung, ovarian, liver, breast, head and neck, bladder, colon, thyroid and lymphoma. eIF-4E facilitates the synthesis of tumor angiogenic factors, which are factors that facilitate the growth of new blood vessels to support the development and progression of tumors, growth factors and survival factors by selectively enhancing their translation. In preclinical studies, Isis and collaborators demonstrated marked anti-cancer activity in a broad range of animal models of cancer and provided the first in vivo evidence that tumor growth may be more susceptible to eIF-4E inhibition than growth of normal tissue. Eli Lilly and Company has certain rights to license ISIS-EIF4ERx.

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 22 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis has designed and executed a patent strategy that has provided the Company with strong and extensive protection for Isis' drugs as well as all aspects of antisense drug discovery, development and manufacturing. Additional information about Isis is available at www.isispharm.com.

[McNay]

01.05.11
Regulus Therapeutics Promotes Garry E. Menzel, Ph.D., to Chief Operating Officer and Executive Vice President of Finance

La Jolla, Calif., January 5, 2011 – Regulus Therapeutics Inc., a leading microRNA therapeutics company, announced today that it has promoted Garry E. Menzel, Ph.D., to Chief Operating Officer and Executive Vice President of Finance. In this new expanded role Dr. Menzel will oversee the Company’s operations and finances, setting strategy to support the advancement of multiple microRNA therapeutic programs towards the clinic.

“Over the past two and a half years Garry has provided exemplary leadership at Regulus and has been instrumental in several transformative events for the Company. These include developing our long range strategic plan, transitioning Regulus to an independent C-Corporation, and securing investments and revenues from our pharmaceutical partners sanofi-aventis and GlaxoSmithKline that should provide Regulus with several years of cash going forward,” said Kleanthis G. Xanthopoulos, Ph.D., President and CEO of Regulus. “The future of Regulus is very bright and we expect to achieve milestones in 2011, including the development of clinical candidates in both our partnered and proprietary programs.”

“It is a very exciting time to be part of the leadership team at Regulus and participate in creating a high-value company discovering and developing medicines using a technology platform that targets microRNAs,” said Garry E. Menzel, Ph.D., newly promoted Chief Operating Officer and Executive Vice President of Finance of Regulus. “Regulus has quickly established itself as a leader in microRNA therapeutics and offers a rare and exciting opportunity to develop drugs for a brand new target space by leveraging a mature oligonucleotide drug platform.”

Before joining Regulus, Dr. Menzel had a long and distinguished career in the financial industry running the global biotechnology practices for Goldman Sachs and Credit Suisse. He joined Goldman Sachs in 1994, where he was a Managing Director and founding member of the Healthcare Group. In 2004, Dr. Menzel joined Credit Suisse as a Managing Director. He served a broad range of biotechnology and pharmaceutical clients around the world, raising capital and negotiating merger agreements for some of the industry’s most significant transactions. Previously, Dr. Menzel was a strategy consultant for Bain & Company, working on a variety of projects in Europe and Asia. Dr. Menzel earned a B.Sc. with Honors in Biochemistry from the Imperial College of Science & Technology in 1985, a Ph.D. in Molecular Biology from the University of Cambridge in 1988, and a M.B.A. from the Stanford Graduate School of Business in 1994. He is an Associate of the Royal College of Science. Dr. Menzel serves as a director on the board of the Institute for Systems Biology and is an executive board member of the Epilepsy Therapy Project, where he chairs the Business Advisory Committee.

[McNay]

Isis Pharmaceuticals Adds Two New Drugs to Development Pipeline

ISIS-FGFR4Rx to Treat Obesity
ISIS-STAT3Rx to Treat Cancer
Conference Call, January 6th, 12:00 p.m. EST at www.isispharm.com
Isis to Present Additional Details on Both Programs

CARLSBAD, Calif., Jan. 6, 2011 /PRNewswire via COMTEX/ --

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that it has added two new drugs to its development pipeline, ISIS-FGFR4Rx and ISIS-STAT3Rx.

ISIS-FGFR4Rx is designed to treat obesity by increasing metabolism, particularly by increasing lipid and fat burning. ISIS-FGFR4Rx specifically blocks the production of fibroblast growth factor receptor 4 (FGFR4) in the liver and fat tissue. In addition, ISIS-FGFR4Rx should not reduce FGFR4 expression in the central nervous system (CNS) or heart, thereby avoiding the CNS and cardiovascular side effects associated with many obesity drugs in development. In preclinical studies, inhibition of FGFR4 lowered body weight and enhanced weight loss when administered as a single agent, in combination with a caloric-restricted diet and in combination with an appetite-suppressing drug and a caloric-restricted diet. The reduction in body weight was accompanied by an improvement in insulin sensitivity. ISIS-FGFR4Rx was safe and well tolerated in multiple species. ISIS-FGFR4Rx is the first drug in Isis' metabolic franchise to treat obesity.

"Obesity has become an epidemic. It is a condition that increases the risk of diabetes, heart disease, stroke, arthritis and some cancers, and an area where most centrally acting drugs have failed due to side-effects. Consequently, our peripherally acting drugs such as ISIS-FGFR4Rx could have significant therapeutic benefit without the associated central nervous system toxicities that plague many other anti-obesity drugs. Our ability to selectively target FGFR4 in only the tissues where FGFR4 plays an important role in modulating body weight, makes it an ideal target for our antisense technology," said Sanjay Bhanot, M.D., Ph.D., Vice President, Metabolic Disorders and Head of Translational Medicine at Isis Pharmaceuticals. "In our preclinical studies, we observed reductions in body fat, reversal of existing obesity and improved insulin sensitivity with ISIS-FGFR4Rx, making this a promising drug with an exciting therapeutic profile."

ISIS-STAT3Rx is designed to treat cancer by inhibiting the production of a gene critical for tumor cell growth and survival. Signal transducer and activator of transcription 3 (STAT3) is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma and promotes tumor cell growth and prevents cell death. In preclinical studies, ISIS-STAT3Rx demonstrated antitumor activity in animal models of human cancer with an attractive safety profile. ISIS-STAT3Rx will be evaluated in a variety of cancers where STAT3 is believed to play a key role such as liver cancers and multiple myeloma.

"Cancer is a therapeutic area in which we believe antisense drugs could have a profound treatment impact. STAT3 is a target that is widely viewed as promising, but it is inaccessible to traditional drug approaches due to the nature of the protein and its function in the cell," said Brett P. Monia, Ph.D., Vice President, Drug Discovery and Corporate Development. "ISIS-STAT3Rx adds to our already broad and mature cancer franchise consisting of a Phase 3 drug and three Phase 2 drugs, each with promising clinical data. These drugs inhibit many of the processes that tumor cells use to grow, proliferate, and metastasize."

[McNay]

Noch eine ältere Empfehlung aus 12/2010:

Isis (ISIS): 'Deep Pipeline, Long-Term Value'
Posted Dec 17th 2010 1:00PM by Steven Halpern

"After releasing their 3Q financials. the stock price at Isis Pharmacueticals (ISIS) perked up as their large cash position and deep pipeline have attracted some new investors," notes biotech expert John McCamant.

The editor of The Medical Technology Stock Letter explains, "When investors investigate the ISIS story and all its parts, they come away with an appreciation for all the potential long-term value being created at the company.

"In Q3, the company reported a loss from operations of $8.9 million and $32.5 million for the three and nine months ended September 30, 2010, respectively, compared to $10.4 million and $15.9 million for the same periods in 2009.

"They expect to end the year with a very healthy cash position of $450 million. Meanwhile, on the conference call, the company focused on mipomersen and the upcoming filing for FDA approval as well as some of their more prominent pipeline programs.

"Starting with ISIS' most advanced drug development candidate, mipomersen, they stated that they have completed all the necessary studies to file for marketing approval in the first half of next year in both the US and Europe.

"The company and their partner, Genzyme, are targeting homozygous FH patients with severely high levels of LDL (bad cholesterol).

"Despite taking currently available treatments they still have extremely high cardio-vascular risk. At this point in time these patients have two options: they can either get apheresis or they can wait for their next cardio-vascular event.

"This leaves the door wide open for mipomersen and the commercial opportunity for this patient population is significant.

"In just the U.S., Europe and Japan, Genzyme estimates that there are about 35,000 patients, which represents a significant and clearly attainable commercial opportunity for mipomersen.

"Genzyme is actively formulating the commercial plans and given their track record of milking orphan drugs for all they can get, we are confident that their significant marketing efforts will maximize the opportunity.

"At current price levels, ISIS stock has very little of the potential for mipomersen factored in to the valuation.

"When discussing their pipeline, ISIS started by saying they have initiated a Phase II trial in cancer patients with their antisense drug EIF4E, which targets a protein with the same name (eIF-4E).

"This drug development candidate may work in multiple types of cancer, because eIF-4E regulates the expression of a number of proteins that are essential for cell survival.

"The company believes that inhabitation of eIF-4E in tumor cells should effect tumor survival, angiogenesis, proliferation and mitosis, as well as resistance to chemotherapy.

"ISIS also discussed their C-reactive protein (CRP) drug development candidate and said they are preparing to start a broad Phase II program to evaluate whether lowering CRP can provide benefit to patients.

"Inhibiting CRP is attractive for drug development because there are numerous diseases in which chronically elevated CRP is associated with poor outcomes

"We expect the Phase II programs in rheumatoid arthritis and multiple myeloma to provide important information about the potential therapeutic benefit of reducing CRP in diseases with both acute and chronically elevated CRP.

"Good Phase II data would allow the company to partner the drug candidate on very good terms as the potential markets for inhibiting CRP are very large and attractive for potential Big Pharma partners.

"We continue to believe that ISIS' full value is not currently reflected in their share price. ISIS is a buy under $12."

Steven Halpern's TheStockAdvisors.com offers a free daily review of the favorite stock ideas of the nation's top financial newsletter advisors.

[Berliner_Landstreicher]

Antwort auf Beitrag Nr.: 40.732.937 von ipollit am 18.12.10 15:20:44

Ick kenne ein Medikament, dass unter Verdacht steht für Herzinfarkte verantwortlich zu sein und mit Restriktionen auch zugelassen wurde.

Entereg von Adolor.

Nee, nee iM wird viel Hektik und Panik wegen dieser obesity drugs gemacht. Da kann ich die FDA schon verstehen, wenn sie bei Nebenwirkungen den Riegel vorschiebt. Die Fettsäcke sollten lieber 1h durch den Park loofen, als sich die Pillen in die verfressene Birne zu werfen. Und Mipomersen wirkt so überzeugend, dass der Nutzen die Risiken bei weitem übersteigt.

Also, Berlin sagt "zulassen". Und was wir sagen ist Gesetz, denn wir sind die Größten! Ihr Bauern!

[McNay]

Data from Two Mipomersen Phase 3 Trials Presented at ACC

Study in Patients with Severe Familial Hypercholesterolemia Meets Primary Endpoint with 36 Percent LDL-C Reduction

CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Genzyme Corp., a subsidiary of sanofi-aventis Group (EURONEXT: SAN and NYSE: SNY), and Isis Pharmaceuticals Inc. (NASDAQ: ISIS) announced today that data from two phase 3 studies of mipomersen in patients who had high cholesterol levels while on lipid-lowering therapy were presented at the American College of Cardiology’s 60th Annual Scientific Session.

In the study in patients with severe heterozygous familial hypercholesterolemia (heFH), mipomersen reduced LDL-C, the primary endpoint, by 36 percent compared with a 13 percent increase for placebo (p<0.001). This study, which was presented today by Jean-Claude Tardif, M.D., of the Montreal Heart Institute, Montreal, Canada, also met each of its secondary endpoints. Frequently observed adverse events were injection site reactions, flu-like symptoms and elevations in liver transaminases, as seen in previous studies.

"We are excited about the potential of mipomersen to help these patients, who are in great need of new treatment options,” said Paula Soteropoulos, vice president and general manager of Genzyme’s cardiovascular business. "We are committed to advancing our mipomersen development and commercialization plan to bring this uniquely targeted treatment to these patients, who are left behind by current treatments."

This double-blind, placebo-controlled trial included 58 patients with severe heFH, who were already taking maximally tolerated lipid-lowering medications. Severe heFH patients were defined as those who had LDL-C levels ≥ 300 mg/dL or those who had LDL-C levels ≥ 200 mg/dL with coronary heart disease (CHD) or other forms of clinical atherosclerotic disease. Patients were randomized 2:1 to receive a self-administered 200 mg subcutaneous injection of mipomersen or placebo weekly for 26 weeks. This study was conducted at 26 sites in North America, Europe and South Africa.

Patients treated with mipomersen had an average LDL-C at baseline of 276 mg/dL. At the end of the trial, these patients had an average LDL-C level of 175 mg/dL, representing an average LDL-C reduction of 101 mg/dL (36 percent). The reductions observed in the study were in addition to those achieved with the patients’ existing maximally tolerated lipid-lowering regimens.

Patients treated with mipomersen also experienced reductions in other atherogenic lipids, including: a 36 percent reduction in apolipoprotein B (apo-B) compared with an 11 percent increase for placebo; a 33 percent reduction in lipoprotein a (Lp(a)) compared with a 1 percent reduction for placebo; a 34 percent reduction in non-HDL-cholesterol compared with a 14 percent increase for placebo; and a 28 percent reduction in total cholesterol compared with an 11 percent increase for placebo (all p<0.001). Study results are based on an intent-to-treat analysis (full analysis set).

Of the 39 patients treated with mipomersen, 27 completed treatment; of the 19 patients treated with placebo, 18 completed treatment. Eight of the discontinuations in the mipomersen group were reported as being related to adverse events, the nature of which was generally similar to previous studies. The placebo discontinuation was reported as being related to an adverse event. The most common adverse events were injection site reactions (90 percent mipomersen; 32 percent placebo) and flu-like symptoms (46 percent mipomersen; 21 percent placebo.) There was one death in the study due to acute coronary syndrome in a patient treated with mipomersen.

Elevations in liver transaminases (ALTs) in patients treated with mipomersen were observed that were generally similar in character with those seen in other studies. In this study, 15 percent of mipomersen patients had persistent ALT elevations above 3X ULN (three times the upper limit of normal) during the treatment period. Persistent is defined as consecutive elevations at least one week apart. No patients had changes in laboratory tests indicative of clinically significant hepatic dysfunction, and there were no Hy’s Law cases. In general, increases in ALT levels appeared to be associated with rapid and larger drops in LDL-C.

“There remains a significant unmet medical need for new lipid-lowering therapies for patients such as those included in this study,” said Mary McGowan, M.D., of the Concord Hospital Cholesterol Treatment Center, Concord, N.H. “These are patients who are on maximally tolerated doses of currently available treatments, and still very far from appropriate target goals, leaving them at high risk of cardiovascular events. These patients have a need for additional lipid lowering, which mipomersen could potentially provide.”

Results of a phase 3 study of mipomersen in patients with high cholesterol at high risk for CHD were also presented in a poster at ACC. In this study, mipomersen reduced LDL-C, the primary endpoint, by 37 percent compared with a 5 percent reduction for placebo (p<0.001). The study, which was presented by William Cromwell, M.D., of the Presbyterian Cardiovascular Institute, Charlotte, N.C., also met each of its secondary endpoints.

This double-blind, placebo-controlled trial included 158 patients with hypercholesterolemia (LDL-C ≥ 100 mg/dL) and at high risk of developing CHD who were taking a maximally tolerated dose of a statin. Patients were randomized 2:1 to receive a self-administered 200 mg subcutaneous injection of mipomersen or placebo weekly for 26 weeks.

Patients treated with mipomersen had an average LDL-C at baseline of 123 mg/dL. At the end of the study, these patients had an average LDL-C level of 75 mg/dL, representing an average LDL-C reduction of 48 mg/dL (37 percent). Half of the mipomersen-treated patients achieved LDL-C levels of less than 70 mg/dL, a recognized treatment goal for high-risk patients. The reductions observed in the study were in addition to those achieved with the patients’ existing maximally tolerated statin regimens. Patients treated with mipomersen also experienced statistically significant reductions in apo-B, Lp(a), non-HDL-cholesterol and total cholesterol. Study results are based on an intent-to-treat analysis (full analysis set).

Of the 105 patients treated with mipomersen, 60 completed treatment; of the 53 patients treated with placebo, 44 completed treatment. Twenty-six of the discontinuations in the mipomersen group were reported as being related to adverse events, the nature of which was generally similar to previous studies. Two of the discontinuations in the placebo group were reported as being related to adverse events. The most common adverse events were injection site reactions and flu-like symptoms. There was one death during the on-treatment study period due to acute myocardial infarction in a patient treated with placebo. During the post-treatment follow-up period, one patient died due to liver failure, acetaminophen toxicity, pneumonia and myocardial infarction 149 days after receiving the last dose of mipomersen treatment.

Elevations in ALTs in patients treated with mipomersen were observed that were generally similar in character with those seen in other studies. In this study, 10 percent of patients had persistent ALT elevations above 3X ULN during the treatment period. Persistent is defined as consecutive elevations at least one week apart. As measured by MRI, mipomersen-treated patients had a moderate increase in liver fat from baseline compared with placebo-treated patients. In general, increases in liver transaminases and liver fat appeared to be associated with the greatest reductions of LDL-C, and in the six-month follow-up period after treatment was discontinued, returned toward baseline along with all lipids, including LDL-C, apo-B and Lp(a).

About Mipomersen

Mipomersen is a first-in-class apo-B synthesis inhibitor currently in late-stage development. It is intended to reduce LDL-C by preventing the formation of atherogenic lipids. It acts by decreasing the production of apo-B, which provides the structural core for all atherogenic lipids, including LDL-C, which carry cholesterol through the bloodstream.

Genzyme and Isis have completed the four phase 3 studies that are planned to be included in the initial U.S. and EU filings for marketing approval of mipomersen. As previously reported, the phase 3 study of mipomersen in homozygous (ho) FH patients met its primary endpoint with 25 percent LDL-C reduction, and the phase 3 study in heFH patients met its primary endpoint with a 28 percent LDL-C reduction.

Genzyme expects to file for EU marketing approval of mipomersen for the treatment of patients with hoFH and severe heFH in the first half of this year. Genzyme also expects to file for U.S. approval for the hoFH indication in the second half of this year.

For more information about FH and mipomersen, please visit:

http://www.multimedianewscenter.com/genzyme/mipomersen-data-…

[McNay]

WESTON, Mass. & CARLSBAD, Calif. --(BUSINESS WIRE)--Jan. 4, 2012-- Biogen Idec (NASDAQ: BIIB) and Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that they have entered into an exclusive, worldwide option and collaboration agreement under which the companies will develop and commercialize Isis' antisense investigational drug, ISIS-SMNRx, for the treatment of spinal muscular atrophy (SMA).

SMA is a genetic neuromuscular disease characterized by muscle atrophy and weakness, and it is the most common genetic cause of infant mortality. One child out of every 10,000 births worldwide is born with SMA. Children with SMA generally appear normal at birth, with symptoms developing as early as a few months after birth, and in the most severe form of the disease, children have a significantly shortened lifespan. Isis' ISIS-SMNRx is designed to compensate for the underlying genetic defect that causes SMA.

Under the terms of the agreement, Isis will receive an upfront payment of $29 million and is eligible to receive up to $45 million in milestone payments associated with the clinical development of ISIS-SMNRx prior to licensing. Biogen Idec has the option to license ISIS-SMNRx until completion of the first successful Phase 2/3 trial. Isis could receive up to another $225 million in a license fee and regulatory milestone payments. In addition, Isis will receive double-digit royalties on sales of ISIS-SMNRx. Isis will be responsible for global development of ISIS-SMNRx through the completion of Phase 2/3 registrational clinical trials, with Biogen Idec providing advice on the clinical trial design and regulatory strategy. If Biogen Idec exercises its option, it will assume global development, regulatory and commercialization responsibilities.

"SMA is a heartbreaking disease – it can kill children before their 2nd birthday and there are currently no therapies to treat the disease," said George A. Scangos, Ph.D., CEO of Biogen Idec. "It is exactly the kind of disease and program that we are focused on at Biogen Idec. The unmet need could not be any greater, the program fits with our mission to bring innovative therapies to patients with serious neurologic diseases, and Isis' antisense compound has the potential to be a highly effective, first-to-market therapy for this deadly disease. We have the utmost respect for Isis' scientific leadership and expertise in antisense technology, and we have crafted a collaboration that brings together our two companies' strengths toward a common goal."

"Biogen Idec's expertise in the global development and commercialization of innovative new therapies for neurologic diseases is a great strategic fit to advance ISIS-SMNRx," said Stanley T. Crooke, M.D., Ph.D., Chairman of the Board and Chief Executive Officer. "This alliance is consistent with our business strategy to develop antisense drugs to proof-of-concept with a knowledgeable partner that is committed to supporting the rapid development of the drug. Given the severity of the unmet need in SMA, our proof-of-concept studies should also serve as the registrational trials for ISIS-SMNRx. We believe that, together with Biogen Idec, we will be able to expeditiously develop this investigational drug in hopes of bringing to market an effective and desperately needed treatment to improve the lives of children with SMA."

About SMA

SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in the United States, Europe and Japan. One in 50 people, the equivalent of about 6 million people in the United States, are carriers of the SMA gene. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA. SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord responsible for neuromuscular growth and function. The severity of SMA correlates with the amount of SMN protein. Infants with Type 1 SMA, the most severe form of the disease, produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

About ISIS-SMNRx

ISIS-SMNRx is designed to treat all types of childhood SMA by altering the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. In December 2011, Isis initiated the first Phase 1 clinical study evaluating ISIS-SMNRx in children with SMA. The Phase 1 study is a single-dose, dose-escalation study designed to assess the safety, tolerability and the pharmacokinetic profile of the drug in children between the ages of 2 and 14 who are medically stable. In this study, ISIS-SMNRx will be administered intrathecally as a single injection directly into the spinal fluid. Isis plans to follow this study with a Phase 1 multiple-ascending dose study.

Isis acknowledges support from the following organizations for ISIS-SMNRx: Muscular Dystrophy Association, SMA Foundation, Families of SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

[cristrader]

Hallo!


Man stelle sich vor Ende der Achtziger Jahre hätte es ein Biotech gegeben mit einer ähnlich marktbeherrschenden Position im Bereich monoklonaler Antikörper wie Isis derzeit im Bereich Antisense. Was wäre dieses Biotech heute wert? 150-200 MRD $?

Small molecules und monoklonale Antikörper sind die zurzeit dominierenden Entwicklungsplattformen in der Medikamentenentwicklung. Diese beiden Technologien bekämpfen im Prinzip die Symptome von Krankheiten in der Regel auf Proteinebene.

Die Antisense Technologie packt das Übel hingegen direkt an der Wurzel an - und zwar direkt an der RNA!

Es gibt unterschiedliche Wirk-Mechanismen u.a. RNase H, RNAi, RNA splicing, microRNA und andere, wobei die einstmals gehypte RNAI-Technologie (Alnylam) in den letzten Jahren gravierende Rückschläge hinnehmen musste und immer mehr an Bedeutung verliert.

Nach mehr als zwanzig Jahren Forschung und zahlreichen Rückschlägen scheint Isis nun endlich den Durchbruch mit seiner Antisense Technologie geschafft zu haben und ist auf dem besten Weg Antisense als dritte Medikamentenentwicklungstechnologie zu etablieren.

Das Annual Meeting letzte Woche mit der Webcast Präsentation war einfach phänomenal! Ein absolutes MUSS für jeden Biotech Interessierten.

Webcast: http://www.media-server.com/m/acs/6e6c63cb736159923faaff4b4a…http://www.media-server.com/m/acs/6e6c63cb736159923faaff4b4a…

Transcript: http://seekingalpha.com/article/645641-isis-pharmaceuticals-…

Slides: http://www.isispharm.com/Site_Gfx/pdf/060712-Annual-Meeting-…

Detaillierte Infos zur Technologie/Patente/Medikamentenprogramme
http://www.isispharm.com/Pipeline/Current-Advances.htm


Grüße cristrader

[cristrader]

Wer in Isis investiert ist sollte das Isis Board von InvestorVillage verfolgen. http://www.investorvillage.com/smbd.asp?mb=1373&pt=m

Interview mit einem Direktor von Isis während des Annual Meetings durch ein sehr aktives Mitglied des IV-Boards: (Unbezahlbare Infos!!!)

I'm going to talk in random thoughts from my conversation with SB. I first ask him about the MTP inhibitor. He himself noted that he did not think it was a big risk or threat to Mipo's success. He noted that ISIS has an MTP inhibitor and CETP inhibitor in house in their portfolios. He noted that when ISIS was working with the drug they knew very quickly that it wasn't for them. He stated that he knows DR from UoP and he had gotten some of that MTP inhibitor from DR to study in the lab. They then treated a rat with the rat dose equivalent and then after an elapsed time(usual protocol) they then sent the specimen to Metabolemics(sp) a small company that ISIS subcontracts with in the LA area. He noted that shortly after Metabolemics(sp) received the specimen the lab company called up SB and ask him, "Where did you get that drug?" And the second thing that they said was "Don't develop it." I've never seen SB so negative toward a drug. He will usually give you both sides with other competitors and give credit where credit is due. He first told me about GLP1 inhibitors long before I even know about them. He gave them a very fair shake and nice evaluation. Not with this time, not with this MTP inhibitor drug. He also shared the same worries about malabsorption that I did. Noting the patients on this drug will have to be monitored much more closely than a Mipo patient will have to be monitored and for many more parameters. I ask him if he thought that monitoring would be similiar similiar to a cross between a baratric surgerical patient and a Mipo patient and he said yes. With his own experience in the lab with ISIS own MTP inhibitor he noted that the liver was covered with "milk" in how it looked,"what a mess" is how he termed it. He further noted that the liver fat between the two drugs were subject to different variables and causation of risk. The liver fat produced by the MTP inhibitor was formed more upstream and that liver fat was subject to oxidation via perioxisomes that the liver fat developed by Mipo was not thus creating a much greater risk for liver fat derived inflammation. So equipotent elevation levels really weren't equal. He noted that the risk for liver inflammation was much higher with the MTP inhibitor all other things being the same. In fact he noted that the Mipo patient would not ever be exposed to that same endogenous risk and he was sure of that. He also expressed a great deal of concern about the fatty infiltration of the small intestine with the MTP inhibitor. He went into great detail on this and it was pretty close to issues/concerns that we have discussed here. I also ask him if ISIS drug that was a DGAT2 inhibitor could eventually be used with Mipo patients to further quell fears of a fatty liver and if it could be used on those patients that seemed to get the biggest response from Mipo's use and also thus having the highest amounts of liver fat and he noted "that is a very big possibility." I ask him if this could be the reason that ISIS was being slow in regards to the 2.5 drug, he noted that was not the reason entirely.


This is a person that does work for ISIS yes, but I think he was being very objective in how he approached this evaluation, and in my past experience with him he is scientist first. I know this because I've been talking to him for eleven years now. He also noted that with use of Mipo for over one year a person would actually see less liver fat than they had at their baseline before using Mipo. He admitted that the drug will never be used as a liver fat reducer, but that Mipo at least showed again that the adaptability of the liver that was seen in animal studies did in fact show the exact same findings in humans. He further elaborated on the increased info that ISIS has gleaned in the last two years about the liver fat with Mipo's use and they feel even more comfortable in regards to the safety of Mipo with this issue. He also stated that he was extremely confident that once long term studies come out that Mipo will differeniate itself "clearly" in the fact that it lowers all putative particles, not just LDL, and maybe Lp(a) as compared to the MTP inhibitor. That this would further clarify the outcomes and superiority of Mipo over the MTP inhibitor. He further noted that as a researcher he would have a definite worry about the fatty infiltration of the small intestine on a chronic basis. Your chance of having a small intestinal tumor is about the same as winning the lotto. You hardly ever see anyone who has a small intestinal tumor. Any tumor that shows up at all in the small intestine with such small numbers of patients being studied would certainly put this compound in jeporady for recall. He also expressed disbelief in regards to AEGR's going after approval with such small numbers and a single arm trial. He disagrees with people on this board in regards to that issue. He thinks that if it does get approved that the numbers for use for it's use will be very small once everything is known about the drug. So in essence it's use would be forever limited and the reverse pyramid of expanded use would not be possible as the longer you study it the more worries you will have arise(I would rather rely on this kind of info straight from the people directly involved than to try and do some literature research on the subject and quoting info from as far back as who knows to help purport an argument.....maybe it's just me). He noted that when he talked to many nonaligned researchers they also shared his disbelief and doubts for the MTP compound for the future. I ask him if he felt better about Mipo's chances for success now or three years ago.....and he said without a doubt he felt better about Mipo now more than ever. I said to him, "don't the people at ISIS realize that if there were no such thing as ISR's, elevated liver enzymes, and if Mipo showed superior plaque reduction from anything that is presently out there that all of you at ISIS would be millionaires." He got a big smile on his face and said, "That's exactly what we're trying to do." He also noted that the ISR's are less now but that ISIS was doing what they could to make them even less bothersome. This was confirmed by SH and LP as well. I ask him if he thought that some of the data quoted about the those two issues were overblown and if the liver elevation problem wasn't really a non-problem for the most part, and the ISR's were in fact less when looked at later on in the further evaluation of the compound and he again said yes. Also, SB felt that most of the effect from the MTP LDL reduction comes from the diarrhea it causes at the upper doses(I guess if you used Mipo and OTC Xenical you could get the same effect).

I then ask him about the PCSK9 inhibitors. He noted noted to me that he thought they were about two years back with this latest FDA concern from where they were just four months ago. The concern deals with the fact that the FDA worries about the lowering of LDL via close to the same mechanism of statins and PCSK9 inhibitors. That too much with this combination(I wouldn't have ever thought of this myself, but it is a fact) could potentially have dilaterious effects. Specically the FDA is worried about the ruputure of cell membranes with an LDL lowered too low via this combo method, and the effect that these two mechanisms of lipid lowering used in conjunction will have on a person's immune system if used together. He went into great detail as to the reason.....I got caught in a little bit of a daydream. SH had previously pointed out to me as well, and also that this is the first time that an Mab has EVER had to do carc studies with the FDA for drug development. When you think about all of the Mab's developed in the last 25 years that says something, at least to me. I ask him couldn't both of these issues be addressed at the same time and he said yes, but it will still take "two years." SB believes also that the numbers won't hold for the PCSK9 inhibitors over the long run. He stated that he had seen in the lab on multiple occasions that at higher doses, dosed over longer periods of time that the numbers don't hold up in regards to lipid lowering like what has been reported. I ask if it was due to tachyphylaxis and he said "in part", but thought other variables were in place possibly as well. He couldn't explain it, but noted that it was repeated on multiple occasions by ISIS in the lab, and from what he had seen in other studies as well. He noted also that AMGN was doing a small study to see if their PCSK9 inhibitor would work in HoF....which as expected would most probably not work. He couldn't envision even taking any money to do this as it didn't make any sense to him at all.

People can say what they want, but when I left that meeting I thought how could anyone think that the MTP inhibitor is going to be anything like what Mr. Beer would like to have you believe. Just like when a Sandisc ringer came over to the ISIS board to raise trouble and hackles only to vanish, I believe that someone who represented AEGR was at that ISIS meeting and made sure that there was the release of that article that Orange posted. In other words, the timing of that release was no fluke/coincidence. I know that there is obvious prejudice on my part, and probably on SB's part, but when you tease things out with all of these lipid lowering agents....hearing from an expert who did have exposure to all of these different agents and variables involved, I just have to think the others are in for some demotion over time, and for Mipo...how could it be regarded any lower by the lay public? t


Addendum to above: SB when discussing the CETP inhibitors had noted that if these two remaining ones fail he doubts that this biomarker target will ever be used again as that would be asking big pharma to seek a fourth generation drug with all previous ones failing. Given the present landscape in regards to drug development with big pharma he just could see the chance being taken. He also noted that the more we learn about the HDL situation the more we know we need more information. As an aside, a group of cardiologists on heartwire.com have just come out pleading to the public to not give up on HDL as an approach for lowering CV risk, some could say the same for Mipo IMO, especially from what I've seen.


I brought up the DM drugs to him. He noted that ISIS will probably never try and develop a drug for DM type 1 as this population of diabetics makes up only 15% of all diabetics, and though ISIS wants drugs that can't be made easily by others, they also want a population with a certain size when making common drugs with unique actions. He noted that all drugs were coming along nicely and faster in their redevelopment, this was later confirmed by LP to Endspeed. When asked if ISIS would sell them as a package, he noted no unless something really unusual and big came up. This is in contrast to what we thought he said last year. I asked him if he still really believed in them and he noted most definitely. He noted that with all P-par gamma inhibitors going down hill in regards to safety issues and perceived risk by the public with their use that diabetic treatment really had no real safe insulin sensitizer drug out there. I mentioned that Symlin was and he said that drug was primarily in DM type 1 patients. I then ask him about the topic we had last year about ISIS going for the indication for patients on atypical antipyschotics who gained six pounds in three weeks, to use that drug for that population. He noted that ISIS was looking at that. Only problem would be that the FDA will demand that a study be done on each drug separately. I noted how just on the generic form of Zyprexa, and Risperdil and he noted that they had that conversation in one of their group meetings. He is still very interested in this population group as these unfortunate people have longevity of some 25 to 35 years less than the average population, worsened to a great deal by these antipychotics that cause all that extra weight gain. He also was extremely hopeful about their Fibroblast growth factor IV inhibitor. t

Part two:

I ask him about the RNAi drugs. He became very serious and noted that they may be done. Their delivery system is still lacking even the new one in the fact that the double stranded molecule still revs up the immune system way too much. I ask him about the newest newest delivery system...and he noted it was better but still big problems remain that won't be easily figured out. Time frame again noted at least another five years before you're going to see anything from them, if EVER. I then ask him about genetic splicing. He noted that the "stock" for genetic splicing has gone down compared to three years ago. He noted it was technically more difficult to develop drugs this way than anticipated, and that there were only three companies with a genetic splicing drug in studies that he was aware of. ISIS, AVII, and I forget the other one. He noted that in his opinion the ISIS drug had the biggest chance for success but that AVII's also stood a good chance of eventually making it and progressing the genetic splicing cause. In regards to the three drugs going for treatment for SMA(of which is a genetic splicing drug) he felt that ISIS drug was far and away the drug head and shoulders above the other two. I ask him about mRNA drugs and he noted again that their stock had gone down somewhat due to the complexity in the lab. According to him, several years yet before we see anything serious from that form of RNA medicine. I ask him about ssRNAi technology. He noted that so far their stock had gone down somewhat too in the fact that the drugs just weren't as potent as ANS drugs no matter what that were able to do as of yet. He did note that the ssRNAi technology may still be the salvation for RNAi companies and if that were to be the case ISIS owned about 95% of all patents for those types of drugs. ISIS was talking to several companies in this regard....not ALNY due to some contractual arrangements that slipped by me. In regards to the 2.5 generation drugs he noted that they had a lot of hope and looked good, but some things still had to be sorted out in the lab with them as well. I noted that when you looked at the big picture, ANS was chugging along and the others seemed to have hit road blocks and were falling farther behing at this time and he agreed with me. Again I'm speaking in random here, I ask him about succession in regards to someone taking over for Dr. Crooke and he noted that was inner corporate info but that a plan had been in place for over 5 years. t

Part III:

I discussed with SH several issues. I first ask him about competitors in regards to TTR. He noted that the "other" guys are still very far behind in regards to problems with their delivery system, and their data to move forward in the lab was also very far behind. When he talked to me last year he noted that they were little more than proof of concept. I ask him if they were in a better position than that this year and he said NO. Conservative length of being behind for them as perceived by SH, again about five years. I ask him about safety for any of ISIS products and he noted that he has more confidence than ever in regards to the safety aspect. He was the one that originally pointed out the Carc studies being needed to be done in regards to the Mab's before they never were required in any Mab medicine before. He again, as a second opinion within that we got through the day, the same company of course, he also expressed the same concern about the MTP inhibitor's cheezy data and the same disbelief that they could get this far with that amount of data. This from a person who makes his living looking at toxicity of drugs. Even he was amazed, he didn't buy the idea of all you need is a super small population for an orphan drug.....he didn't buy that argument at all. You could argue that he is being super conservative as that's his job, but I look at it another way but said the same way, "that's his job" and he does have that concern. t


In general it was a smaller attended meeting. The employees that were there seemed extremely happy, and confident for the future. This isn't rink-dink company. They certainly have vision, they have products, they have products that are unique and probably IMO first in class for whatever they are going for. I talked to LP and asked her about not many competitors in ANS. She noted that they felt lonely for awhile, but now they feel quite good about being close to the only ones in that space. t

Part IV:

I'm going to try and clean up my poor wording on previous posts. I apologize for that, if you know me you know that I'm low tech and a very poor typer. Just want to say that we were the first people to arrive at the meeting and the last to leave, Endspeed, Frank, Life, and myself. There are several intangibles that can not be fully expressed via these type of communications. I will say that SB was unbelieveable. I said I had him in a biological headlock for an hour, it was really about two hours. I ask him at least 150 questions. The program was supposed to end at 5 pm. We didn't finally let him out of that headlock until about 6:10 pm. He had his sleeves rolled up and was prepared to stay as long as I wanted. I just started to feel guilty and that it was unfair to ask that of him so I reluctantly relented and let him go, but what a tremendous person. Thus my forever thanks to him for his help and info. I also would like to explain my deamenor and the reason I've posted what I have and will post things as they come to me. I have in the past kept everything to myself with the exception of the few people who know and have the same committment to this investment that I believe in. That being that this is an investment of a lifetime, if it gets a chance to grow as visualized. In the past I would come out at times on this board with info when the direction on the board was extremely negative, or going in the wrong direction from what I've seen to be the truth and I knew that things were different and definitely not that bleak. I approached it differently this year for two reasons, Mipo may be much bigger than envisioned(at least from its zero status that it now "enjoys", and the time for ISIS full recoginition is close at hand. This isn't a jab at Marc or others, but just think if there is no one to give the other side this info would not be available. This is like following a multiple choice test in high school and if you get the first answer wrong then all of the others become wrong as well. In the situation about SNY wanting to junk Mipo is definitely not true. I have heard it from probably the third most powerful person at ISIS. This becomes more magnified and clear when you look at the situation and variables put forth in what the PCSK9 inhibitors find themselves in with this FDA new requirements problem/issue. And doesn't that make sense? Is there really a free lunch in biotech, big pharma, medicine, etc. And the info brought forward does in my mind explain why ISIS is right, and SNY is not trying to junk the ugly stepsister Mipo. SNY knew about the FDA thing for PCSK9 inhibitors at about the same time that Dr. Crooke did. You also look at the info in regards to the MTP inhibitors. Doesn't it make sense for ISIS to follow what they believe in from what they have seen in the past in the lab? That AEGR MTP lab work done by SB was before the 2007 AEGR company formation, but does it really make a person in the know with that kind experience make you want to migrate over that way? Would you have confidence in the that MTP inhibitor knowing what SB and ISIS did? If you are an investor in AEGR, would you have confidence that your patented dose adjustment schedule with numbers is going to hold in patent court? Especially from what we've seen in the real world with the likes of TEVA et al. And doesn't it make you at least think that the whole truth has not been given out in a simplified mysterious report from Alpha on the tremendous potential of the MTP inhibitor? One of the top ten things I heard at this meeting was the differentiation of the fatty infiltration of the liver between the two compounds as brought forth by SB. Two of the other top three was the answer to Frank's question and the fact that the TTR was going straight to phase III status.

The info that my friend who is a lipidologist had given me before rang through again in regards to Mipo in Lp(a). My friend had told me that the person in India who is regarded as the premier lipidologist in India had noted that the people in the world with the fastest development of CV disease were people in India who moved from India where they have a primarily vegetarian diet to a Westernized diet when they move from India to England and the reason thought to be the most important in that phenomenon is Lp(a). We look at cheezy data from the other side and people rationalize that this paper from them is excellent and further proof of the demise of Mipo. Doesn't some of what we've said here make you question that? The fact that it isn't just one person saying something but rather several reporting the same thoughts. This is as close to inside info that is legal that a person can get.

In looking at Mipo's potential use, all I'd even want would be the present populations they are going for, the CKD patient(the two lecturers I take my info from in this regard are George Bakruis(sp), and the Chief of Nephrology at a San Francisco hospital whose name alludes me, but I could pick it out in a multiple choice test), and those patients with elevated Lp(a). Contrary to what Orange had stated, SB had noted that any patient with extremely high levels of Lp(a) was at increased risk of CV disease no matter what their other lipid levels were, and according to him they plan on pursuing that. And he again pointed out this distinct Indian population as the source of their info and goals.

When I talked to SB I ask him if Mipo wouldn't be an excellent choice in the Stage V CKD patient and he stated yes, as did SH. SH was not aware of the SHARPE trial, but when I told him the info I had gleaned from it he said that it made sense to him and that he would look into it. He knows us from seeing us for over five years. I believe that next time I see him God willing he will have looked into it. Lifescifund had noted to him that we didn't realize how important he was when we all started attending these meetings many years ago, but that we sure appreciated him now. He's not going to give us inside info, but he will to the best of his ability give us info that the general public may not be aware of or think of asking. That is the intangible verba that we as ISIS investors can certainly use. He, like SB is also an invaluable resource.

I won't go into all of the issues brought up that I think were untruths/concerns noted on this board that IMO from the start and reconfirmed to be false, or misconstued thoughts corrected at this meeting. I do want to say that unless you attended the meeting you have no idea of the energy, the confidence, the quiet swagger, and the atmosphere in general. These people aren't there to absorb a paycheck, they are there to change the world. I do love the stock and the people....guilty as charged. But in my defense, I don't like any other stocks. What are we the little people to put are money in? Oil companies with limited resources, fast food places, airlines? Sorry Endspeed. This is the investment of a lifetime IMO. All of the other so-called competitors have fallen farther behing ISIS and ANS in the last two years in this regard and because of some of the reasons I recorded here put forth to me by what I consider world experts in this field. Every time Congress says they are going to fix the broken health care system it sets us/me back. I think some like Robo2 and others can relate to what I'm saying in this regard. More work, more malpractice risk, less pay, more red tape. I have a son with high functioning Autism, my brother the biggest producer in our corporation has prematurely retired. He is fed up with the "fixing" of the broken health care system by Congress and others in charge who don't really know what transpires in medicine in everyday life. So I'm going to try and back up what I say in my dream for the future for myself, my friends who have trusted me, and us little people on this board. I apologize in advance if someone gets in the way and I'm not a gentleman....but I will try and back up what I say with facts as the company sees them that I can get related to me. t

Part V:

I'm going to talk about Excalliard first. Most of the questions were asked by another person who I've seen at the annual meetings before but don't know him personally. He ask, "didn't Excalliard sell out to PFE too cheaply?" SB noted that they did get the price extremely cheap. He noted however that the company was made up of four individuals from the start and they were the employees. They all are doing very well now, "they are laughing at us" is how he termed it good naturelly. The leader a former ISIS employee that had to be let go when ISIS had that major downsizing after the Alicoforsen failure. He presented his idea to Dr. Crooke and even though Dr. Crooke didn't think he'd be successful Dr. Crooke relented because this individual had already arranged for most of the funds needed via venture capital. The drug exceeded everyone's expectations. SB noted however that while this was going on the leader of the company got sick(I didn't want to ask with what, not my place). So you had the dynamics of the company changing and with that event, the strong interest by PFE, and the venture capital people that were backing up the project at Excalliard seeing dollars and wanting the huge return that they saw with just this little offer from PFE which the Excalliard team thus took it.

When talking about the drug itself SB noted that it is an amazing compound and he couldn't argue that it could possibly be grossing more than a billion per year. The drug is being studied as we know in patients intraoperatively. The surgeon makes a stripe of the med over the area of the two opposing edges before suturing. He noted that ISIS has rights to the internal use of this biomarker site. Tet noted that the company said that this will take five years to develop. SB questioned that knowing that your results are pretty easy to study, and the compound has low absorption and thus low risk for systemic side-effects. This could be a situation where ISIS has really smartened up and they are under promising and hoping to over produce. He also noted that the compound in studies in regards to Keloids has been amazing. I'm assuming that PFE will have to do more FDA studies for that indication if in fact it pans out. I ask him about the use in hypertrophic scarring and he said that he felt that it would be effective there too but why not try for the worse population first, and they were working on the severe type of scarring. I should of ask but I think the initial indication if they get it will require only one time treatment where in regards to Keloid treatment will probably require multiple injections. Endspeed had noted that the amount of money that goes ISIS way will be 5-6%. If that is the case and the profits do hit a billion that would be $50 million per year.

In regards to new drugs. I ask SB if they were still pursuing a drug for CHF and he noted that they were. I then ask him if it was going to be for the Galentin3 target and he said no. ISIS according to him has a target that hits CHF earlier in the progression of the disease. BNP measures myocyete stretch, and Galetin3 measures fibrous formation. The latter is the patients who are end-stage CHF. This target that ISIS is working on hopes to interecede earlier and thus make a bigger difference in patients' lives who do have CHF. I then ask him if ISIS was still pursuing a pain medication like they had noted, and he stated yes. "It will be a genetically verified pain target." On further questioning he noted that it was the same target that when people are born with the lack of those pain sensors/targets they are in great danger. For example, a child not able to feel pain at all, they could hold their hands over a fire and feel nothing. This is different from other illnesses like Autism or others where they have a different perception of pain. This people feel nothing at all.....worse than the boy in a bubble, try boy in a tank. In any case, he noted that it is hoped that this drug will be able to treat chronic pain non-narcotically by down-regulating notably up-regulated pain receptors. He said it looks very promising to treat people with chronic pain such as chronic fibromyalia, chronic pain syndrome. Patients with Type 2 and Type 3 chronic pain. To give you an idea of what that is, Type 1 chronic pain is patients who have chronic pain from a known source with a known expected resolution of the pain sensation. Type 2 is chronic pain with a known source but without known expected resolution of the pain, and Type 3 pain is unknown source for the pain, and unknown expected resolution of the pain.

I then went into asking questions about the Factor XI drug. He is extremely excited about it and has been named the head of the coagulopathy division. He noted it works equally well in arterial and venous clots and the interest in that compound is unbelieveable. I then think I hit a sugar low because I don't remember much more about it. I would say that I did have the impression that if there is ever a "free lunch" this is it. I then ask him about the CRP inhibitor. I ask him if didn't this drug face simple competition from like Vitamin E and like I had posted earlier HEPA filter. He noted that this was well engrained inflammation. We all have flucuations in our CRP's, but these people never go down below a certain level and that level is always high. I then ask him about the atrial fibrillation patients. He noted from what he had seen it was doing extremely well. I ask him if this wasn't competing against a procedure, ablation therapy. He noted definitely NOT as this compound was being used on ablation failure patients.....if you think about that, that is a tough population to tackle. If you fail you're first ablation therapy the chances of a second, or third try are notably diminished. I would not have believed myself before....but if their data suggests this will work, that alone IMO would make this a big drug. I expressed to SB my continued fear of this drug being an octopus looking for a use, he again noted that previously had doubts but from what he has seen in the lab it looks promising.

To put to rest the question of whether or not ISIS will be able to handle all of these drugs, sort things out, and use capital efficiently my good friend Endspeed ask that of LP. She noted that definitely not a problem. She noted that nothing goes through with new projects unless it goes by her and only then if she knows that everything else they are working on is going according to plan. Ms. Parshall is an amazing person. Very humble, and unassuming....but if you notice whenever Dr. Crooke is running into problems, think he is running into problems, or just doesn't want to deal directly with something he turns it over to her. She handles things with grace....but she wields a lot of power IMO and you'd never know it.


In summary, if you listened to that unbelieveable talk from Dr. Crooke at the annual meeting plus the supplemental info supplied by the people at the meeting, How can anyone really say that this company is worth only $10.46 even with the large increase in price that it has had recently. GLTAL's, if any else comes back to recall I'll post it. t

[cristrader]

Zwar noch einige Jahre hin, aber die Behandlung/Heilung genetischer Defekte wird wohl nur mit Isis Antisense möglich sein.

http://www.utsandiego.com/news/2012/jun/20/ucsd-f/
UCSD finds possible way to treat Huntington's disease

In a possibly significant advance, UC San Diego researchers have found a way to turn off the mutated gene that causes Huntington's disease, an inherited and degenerative brain disorder for which there is no cure. The progress was made in research on mice and non-human primates using a drug that showed signs of not only slowing Huntington's, but reversing the disease's progression to a certain degree.

UCSD's Ludwig Institute for Cancer Research reports the advance in the June 21 online edition of the journal Neuron.

"One could effectively treat the disease if you just shut off that bad gene, and that is what we have done," said Donald Cleveland, the project's lead researcher and chair of the UCSD Department of Cellular and Molecular Medicine.


An MRI brain scan shows atrophy caused by Huntington's disease. Wikipedia Commons

Cleveland and his collaborators made the advance by developing a drug therapy that contains a piece of the mutated gene that causes Huntington's. The drug -- which also involves researchers from Isis Pharmaceuticals in Carlsbad -- basically silences the ill effects of the bad gene.

"We anticipate that we can go into human clinical trials with this drug in about 18 months," said Cleveland.

Scientists have spent decades looking for effective ways to treat Huntington's, which currently afflicts about 30,000 Americans. The diseases symptoms range from from psychiatric problems to uncontrolled movements and dementia.


http://www.nctimes.com/blogsnew/business/scitech/science-hun…

SCIENCE: Huntington's disease reversed -- in animal models -- with Isis drug

Symptoms of Huntington's disease have been reversed in animal models of the fatal neurodegenerative illness, according to a study published online today in the scientific journal Neuron.

Rodents given a single injection of a drug made by Carlsbad's Isis Pharmaceuticals demonstrated long-lasting recovery of near-normal movement and also appeared less agitated. The Isis drug appears to block Huntington's disease at its source, allowing injured neurons to recover.

The study, led by scientists from UC San Diego and Carlsbad-based Isis Pharmaceuticals, points the way to eventual testing of the therapy in humans. The drug could enter human clinical trials in a few years, if further studies go well, said C. Frank Bennett of Isis, one of the paper's authors, in an interview Monday.

Don W. Cleveland of UCSD, the study's senior author, made the point even more emphatically in a press release from Cell Press, the publisher of Neuron.

"Our approach is feasible for development now into a therapy for Huntington's disease in man," Cleveland said.

There is now no effective treatment for Huntington's, a genetically caused disease that occurs in about 30,000 Americans. However, a drug developed with technology licensed from UCSD is in clinical trials by Raptor Pharmaceutical Corp. to determine whether it can slow the progression by protecting neurons.

For more information about living with Huntinton's disease and potential treatments, go to the website of the Huntington's Disease Society of America.

Cause and treatment

Huntington's disease is produced by a mutated form of a protein called huntingtin. The mutant huntingtin protein accumulates in certain brain cells, gradually damaging and destroying them.

Medications ease the symptoms to a degree. But they do not stop or slow the underlying neural degeneration. That degeneration progressively reduces the ability to move, along with causing depression and other mental problems, ending in death.

But in rodents at least, neural function improved after the drug was injected into the cerebrospinal fluid, whether it was targeted at the normal or mutant protein. Improvement was detected about a month after the drug was injected, Bennett said.

The drug works through Isis's gene-blocking antisense technology, Bennett said. Antisense drugs are made up of sequences of RNA. This is the molecule that carries information from DNA to other parts of the cell, where it serves as a template to make proteins. The antisense RNA links up with the target RNA, preventing it from doing its job. By neutralizing the template RNA, the drug stops the disease-causing protein at its source.

The effect of antisense drugs is temporary; eventually more RNA will be made from DNA. Unless an antisense drug is given again, the protein synthesis will resume. But in the case of Huntington's disease, the effect of one dose turned out to be surprisingly long-lasting, Bennett said.

Huntington's patients produce the neuron-destroying protein for decades before its effects show up, Bennett said. So just as the disease takes long to manifest, stopping production of the protein even temporarily appears to produce long-lasting relief. At least that's true in rodents.

Making a difference

Unlike many genetic diseases, Huntington's is dominant; inheriting just one copy of the defective gene (from either parent) causes the disease. It varies in severity and age of onset depending on the severity of the mutation.

Most who develop Huntington's disease don't get it until they've grown up. Those with a severe form known as juvenile Huntington's disease exhibit symptoms before they're 20. The rodent models were given a model of the fast-appearing juvenile form of the disease so the drug's effectiveness could be assessed more rapidly, Bennett said.

The study was a team effort of academic institutions and biotech companies. It was led by UCSD's Cleveland. The first author was Holly B. Kordasiewicz of Isis Pharmaceuticals, formerly of the Ludwig Institute for Cancer Research at UCSD.

Kordasiewicz said she joined Isis last year because she wanted to help move the research out of the academic setting and into clinical trials, a field called translational medicine. At Isis, she's able to complete the process.

"I was able to do a lot of this translational drug discovery research in my training at UCSD," Kordasiewicz said. "It was doing that, doing something that's actually going to make a difference and help somebody that I got hooked to, and I wanted to follow it through, and Frank gave me the opportunity to come here."

"We stole her away," Bennett quipped.

The other co-authors are Melissa M. McAlonis, Kimberly A. Pytel and Jonathan W. Artates, all of the Ludwig Institute for Cancer Research and UCSD Department of Cellular and Molecular Medicine; Lisa M. Stanek, Seng H. Cheng and Lamya S. Shihabuddin, of Genzyme Corp.; Edward V. Wancewicz, Curt Mazur, Gene Hung of Isis Pharmaceuticals; and Andreas Weiss of Novartis Institutes for BioMedical Research.
>>

[McNay]

Hallo Cristrader,

ich dachte schon ich muss den Alleinunterhalter bei ISIS spielen. Ich bin auch long und ISIS hat sich von den Jahrestiefs schon schön erholt

Mal sehen, wo die Reise hingeht, vom Potenzial bin ich absolut überzeugt, auch wenn meine Aufmerksamkeit aktuell mehr Richtung NSPH gilt.

Was mich wundert, in Deutschland scheinen sich nur wenige für solche US-Werte zu begeistern, zu Unrecht wie ich finde.

[Stoxtrayder]

noch jemand hier (investiert)?

typischerweise habe ich mir ein paar Isis-Aktien vor ein paar Wochen zu Höchstkursen ins Depot gelegt. ein der Gründe war, dass der Vorstand von BB Biotech in einem Interview hat verlauten lassen, dass er (dieses Jahr noch betreffend) bei Isis gute News erwartet.

hm, mittlerweile bin ich ca. 15% im Minus. werde mal meinen SL bei 12$ legen...

Meinungen?

thx!

[cristrader]

Hallo!

Isis Pharmac. hat in den letzten Wochen einen schönen Lauf hinter sich und das trotz dem Scheitern von Kynamro in der EU. Persönlich gehe ich auch von einem Scheitern von Kynamro Ende des Monats in den USA aus. Das sollte aber kaum Auswirkungen auf die Zukunft von ISIS haben.

Die Präsentation von Isis bei der JP Morgan Konferenz war einfach sensationell und machte deutlich das Isis bei weitem die umfangreichste und vielversprechendste Pipeline im ganzen Biotechsektor besitzt.

Einige Highlights der Präsentation:

5 Medikamentenzulassungen in den nächsten 5 Jahren zu erwarten
9 verschiedene Pipelinekandidaten mit Phase II oder III-Ergebnissen in den nächsten 12 Monaten.
3-4 dieser Kandidaten stehen an zur Verpartnerung in 2013 mit lt. CEO Crooke Konditionen (Upfrontzahlungen/Milestones und Revenues)die die Kynamro Konditionen (u.a. 300 Mio Upfront) noch toppen sollen.
3 Phase III-Starts in 2013/Anfang 2014
4 weitere Phase II-Starts in 2013

Die wichtigste Aussage von CEO Stan Crooke : Das Interesse von Pharma/Biotechunternehmen an ISIS Pipelinekandidaten und Technologie befindet sich auf All-Time-High!!!

Wer sich für ISIS interessiert sollte sich unbedingt die Präsentation anschauen:

http://jpmorgan.metameetings.com/webcasts/healthcare13/direc…


Auf seekingalpha.com ist das Transcript erhältlich:
http://seekingalpha.com/article/1103921-isis-pharmaceuticals…


Kurzfristig besteht die Gefahr einer Kurskorrektur, inbesonders ein Scheitern der Kynamro Phase III Ende des Monats in den USA droht. Die Frage ist wie wird der Markt reagieren? Viele erhofften sich einen kräftigen Kursrücksetzer durch das Scheitern von Kynamro in Europa aber der Kurs reagierte seitdem mit einem fast 50% Kursanstieg.

Auf Sicht der nächsten Jahre spielt Kynamro wohl keine Rolle mehr zumindest kann es nur noch positiv überraschen. Der Focus richtet sich jetzt auf die gesamte Pipeline und Technologie.

Selbst wenn Kynamro keine Marktzulassung erhält war die Entwicklung doch kein totaler Flop denn die gebrachten Erkenntnisse sind unheimlich wichtig für die weitere Entwicklung von Isis und der Antisense-Technologie.

Kynamro:
-erstmals Beweis das die Antisense Technologie effektiv wirkt, mögliches Scheitern nur wegen Nebenwirkungen (aktuelle Medikamentenkandidaten haben weitaus geringeres Nebenwirkungsprofil)


Ich verfolge ISIS schon seit mehr als 5 Jahren und bin bisher mit meinem Investment mehr oder weniger auf die Nase gefallen. Ich bin aber zuversichtlich das der Wendepunkt in ISIS Performance nahe ist.


cristrader

[cristrader]

Antwort auf Beitrag Nr.: 44.009.513 von cristrader am 11.01.13 11:14:36

In a report published Monday, BMO Capital Markets reiterated its Outperform rating on Isis Pharmaceuticals (NASDAQ: ISIS) and raised its price target from $12.00 to $17.00.

BMO Capital Markets noted, “We are reiterating our Outperform rating on shares of ISIS and increasing our price target to $17 following our meeting with management. With the near-term focus on the KYNAMRO PDUFA, we are increasingly confident in approval and believe that upside potential extends beyond the initial commercial opportunity and to validation of an emerging late-stage pipeline. Relative to the value of KYNAMRO in HoFH, estimated at an NPV of $3/share, we believe that pipeline value is considerably greater, with an estimated NPV of $14/share, primarily driven by only 1 of 25 programs in the ASO for ApoCIII for triglycerides.”

[cristrader]

Antwort auf Beitrag Nr.: 44.020.007 von cristrader am 14.01.13 18:00:53

Die Analysten von BMO Capital geben der Pipeline ohne Kynamro einen Wert von 14$, wobei in die Bewertung fast ausschließlich der Kandidat APOCIII eingeht, was durchaus überrascht, weil andere Analysten eher dem Kandidat SMA einen höheren Wert zusprechen.

Interessant war die Äußerung von Stan Crooke nachdem er die mehr als vielversprechenden Kandidaten TTR und SMA vorstellte die beide für sich gesehen schon Blockbusterpotential haben bezüglich APOCIII:

"The final drug that I’ll talk about in this segment is APOC3, and of course we all want to do something for these kids with SMA, and these people with TTR. But from a company perspective, I think APOC3 is by far the most exciting.

APOC3 is a protein that’s made in the liver. It works in blood, and inhibits the enzyme that degrades triglycerides. Triglycerides are degraded in blood, is the way you clear them. So APOC3 is itself a cardiovascular risk factor. Triglycerides are a risk factor, and it’s very obvious that the next key thing in lipids is to fix triglycerides with better drugs.

We think we have it. We’ve already demonstrated that this drug works, in every animal model and in humans. In our first in human trial, we showed dose-dependent reductions of APOC3 and fasting and post-prandial triglycerides in human beings, with essentially no side effects, no [AOT] increases or anything else.

We have two trials that will unblind this year. They’re both tremendously important to us, and I encourage you to watch these carefully. The first is a study in patients who have severely elevated triglycerides.

This is a rare disease-like opportunity. There are about 200,000 patients with severe elevated triglycerides in Europe and the U.S. These people, in addition to their cardiovascular risk, have a much higher incidence of recurrent pancreatitis. That, of course, is a medical and surgical emergency, and it eventually leads to pancreas death and brittle diabetes.

So it’s an opportunity that we think can be very quickly developed. We have a study in 100 patients at three different doses, plus placebo, that will unblind in the middle of this year. What we hope to see is dramatic reductions of APOC3 and triglycerides, improvements in HDL, as well as LDL. So this is a really important study, and sets the stage, then, for our Phase III program.

We’re also looking at this drug in diabetics who have moderately elevated triglycerides. Of course, we expect to see APOC3 and triglycerides reduction, and we hope to see improvements in insulin sensitivity. So those two studies this year, then, allow us to move to Phase III at the end of this year in these patients with this severe hypertriglyceridemia. This is a program that we own entirely ourselves."


Ich finde es ist Wert sich APOCIII mal genauer anzusehen und welches Potential überhaupt in diesem Medikament steckt.

Interessant hierzu ist die Präsentation beim Phase II-Start von APOCIII Transcript
http://seekingalpha.com/article/561721-isis-pharmaceuticals-…

Hier ein paar Auszüge:
Dr. Witztum is a Professor of Medicine in the Department of Medicine and he is the Director of the Specialized Center for Research on Arteriosclerosis at the University of California, San Diego. He is Manager of the Journal of Lipid Research and world-recognized lipidologist

Dr. Joe Witztum:
"Isis has a very unique approach that is different than others and has developed a novel platform that directly and specifically can inhibit production of any given protein and I thought that was a very unique and valuable approach.

Among the areas where new agents are really needed is in the area of elevated triglyceride levels. So there really is, sort of, three types of problems. One diverse problem is illustrated on this slide and it represents patients that have extremely high triglycerides that is above a 1,000. These patients who have plasma that looks this end up in the medical emergency rooms and in hospitalizations because triglycerides that are very high like this leads to pancreatitis which is a severe pain in the abdomen and this can even end up resulting life threatening pancreatitis, which requires even surgery.

This is actually one of the common consoles I get as a lipidologist for patients in the hospital, and you can see on the slide; on the left side is a plasma in such a person. And actually you will probably thank yourself well it looks like milk, and the fact that it (Inaudible) what milk is, milk is the collection of very large triglyceride-rich lipoproteins that come from the intestine and from the liver and when they become very, very high, that’s what it looks like and you can imagine that’s not very helpful.

The problem is there really is no effective drug therapy for patients with such very high triglyceride levels, treatments that one uses for people with lower triglycerides such as niacin or fibrates for example or fish oils, really don’t work in this clinical setting. And the only real therapy is to remove fat in the diet and on occasions because that takes a while to be effective. One even has to do plasmapheresis where a very invasive procedure where triglycerides are literally physically removed.

Now the second sort of use that we see, needs that we have or patients who have triglycerides that are much lower than that, say, between 500 and 1000, this is a very common problem. The example I showed you earlier is very small example but this is very common and patients with a triglyceride levels are associated with obesity and insulin sensitivity and that make Type 2 diabetes much worse. Such patients have elevated APOCIII which inhibits the removal of triglycerides and third point is that both high triglycerides and high APOCIII are validated and independent risk factors for coronary vascular disease.

There are no current therapies in my opinion that effectively lower the very high triglycerides associated with pancreatitis and even the therapies we use for patients with moderate hypertriglyceridemia are not very effective and have many side effects. These include, for example, niacin, fibrates and even fish oils.

Now ISIS-APOCIIIRx directly inhibits the synthesis of apoC-III and in the studies conducted today have shown dramatic decreases in both apoC-III and in triglyceride levels and a very favorable safety profile and tolerability has been observed. So I am very excited about the approach that ISIS has taken which is to concentrate first on those with the highest triglyceride levels and which will provide a critically important questions also APOCIII and triglyceride.

Again because the ISIS-APOCIIIRx is specific to apoC-III, these studies will answer important questions about the overall importance of apoC-III to triglyceride levels at the clinical level. I actually am very happy to be a part of a growing franchise that ISIS has created and expect many new advances in therapy will be forthcoming that will be a great benefit to reducing cardiovascular disease."

Zum Marktpotential:
Richard Geary:
"we estimate there are approximately 3 million people in the United States and Europe today with triglycerides greater than 500 milligram per deciliter. These are patients who despite currently available therapies are still significantly over the normal upper limit of triglycerides. Many of them have other related disorders such as high LDL-C, elevated Lp(a) high VLDL or low HDL.

Frequently, these patients have insulin sensitivity issues putting them in the growing ranks of patients with metabolic syndrome and Type 2 diabetes. Within this group, there is a smaller subset of patients with triglycerides greater than 1000 milligrams per deciliter. We expect this subset of patients which we believe is more than 200,000 in the United States and Europe to be our initial patient population for commercialization. We believe our accelerated development plan could support submission for registration in this population as earliest 2016.

As with LDL-C, there are acceptable levels of triglycerides of course. Triglyceride levels of less than 150 milligram per deciliter is considered normal and acceptable, however, the American Heart Association recommends that triglyceride level of 100 milligram per deciliter or lower is optimal for heart health.

Triglyceride levels greater than 200 milligram per deciliter is considered high and triglyceride levels greater than 500 milligram per deciliter are considered very high. A simple blood panel can provide key information on triglyceride levels and patients with severely elevated triglycerides are often referred to the lipidologists."

===> 3 Mio Patienten >500 mg/deciliter triglyceride
===> 200.000 Patienten >1000 mg/deciliter triglyceride

Das Marktpotential ist unglaublich hoch. Alleine die 200.000 Hochrisikopatienten mit Trigyzerinwerten über 1000 mg/deziliter verursachen durch Operationen und sehr häufige Krankenhausaufhalte enorme Kosten.


Die Phase II-Ergebnisse sind wohl Mitte des Jahres zu erwarten. Werden die Phase I-Ergebnisse bezüglich Effektivität und Nebenwirkungsprofil bestätigt dann ....

Das Marktpotential kann man durchaus mit dem von Regenerons/Sanofis PCSK9-Medikament (SAR236553/REGN727 ) vergleichen. Regeneron hat nach Bekanntgabe der Phase II-Daten im letzten Jahr seine Marktkapitalisierung um 10 Mrd $ erhöht, was es überwiegend diesem einen Medikamentenkandidaten zu verdanken hat. Bei ISIS APOCIII bin ich aber schon mit weitaus weniger zufrieden

Klickt mal obigen Link an und lest schaut euch das komplette Transcript an es lohnt sich.

cristrader

[cristrader]

Pipeline update:

http://www.isispharm.com/Pipeline/index.htm

[cristrader]

Hallo,

Kynamro durch FDA zugelassen!!!


Genzyme and Isis Announce FDA Approval of KYNAMRO™ (mipomersen sodium) Injection for the Treatment of Homozygous Familial Hypercholesterolemia




CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)-- Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), and Isis Pharmaceuticals Inc. (ISIS), today announced that the U.S. Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for KYNAMROTM (mipomersen sodium) injection. KYNAMRO, given as a 200 mg weekly subcutaneous injection, has been approved as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

"Today's FDA approval of KYNAMRO is great news for patients with HoFH who are in need of additional treatment options for this rare, and often under-diagnosed disease," said Genzyme President and CEO, David Meeker, M.D. "As the leader in treatments for rare diseases, we are pleased to bring our expertise to HoFH patients living with this serious condition to better help them manage their disease."

HoFH is a rare inherited condition that makes the body unable to remove LDL cholesterol, often called the "bad" cholesterol, from the blood, causing abnormally high levels of circulating LDL cholesterol. In the United States, HoFH, an orphan indication, occurs in approximately one in one million individuals. For those with HoFH, heart attacks and death often occur before age 30.

"People living with Homozygous FH may not appear to be sick, but they live with the burden of this rare disease every day," said Katherine Wilemon, President and Founder the FH Foundation "The approval of KYNAMRO gives the HoFH community hope that HoFH can be effectively managed."

The FDA approval triggers a $25 million milestone payment to Isis from Genzyme.

"KYNAMRO is the first systemic antisense drug to reach the market and is the culmination of two decades of work to create a new, more efficient drug technology platform. As evidenced by our robust pipeline, our antisense drug discovery technology is applicable to many different diseases, including the treatment of a chronic and rare disease, like HoFH," said Stanley T. Crooke, M.D., Ph.D., Chairman of the Board and CEO of Isis. "We look forward to continuing to work with Genzyme toward a successful commercial launch of KYNAMRO and global expansion into other markets."

The FDA approval for KYNAMRO is supported by the largest clinical trial conducted to-date in the HoFH patient population. The randomized, double-blind, placebo-controlled, multi-center trial enrolled 51 patients age 12 to 53 years, including 7 patients age 12 to 16 years, who were maintaining a regimen of maximally-tolerated lipid lowering medications. Treatment with KYNAMRO further reduced LDL-C levels by an average of 113 mg/dL, or 25%, from a treated baseline of 439 mg/dL, and further reduced all measured endpoints for atherogenic particles. In March 2010, these data were published in The Lancet by Professor Raal, University of the Witwatersrand in South Africa.

Safety data for KYNAMRO are based on pooled results from four Phase 3, randomized, double-blind, placebo-controlled trials with a total of 390 patients of which 261 patients received weekly subcutaneous injections of 200 mg of KYNAMRO and 129 patients received placebo for a median treatment duration of 25 weeks. Eighteen percent of patients on KYNAMRO and 2% of patients on placebo discontinued treatment due to adverse reactions. The most common adverse reactions in patients treated with KYNAMRO that led to treatment discontinuation and occurred at a rate greater than placebo were: injection site reactions (5.0%), alanine aminotransferase (ALT) increased (3.4%), flu-like symptoms (2.7%), aspartate aminotransferase (AST) increased (2.3%), and liver function test abnormal (1.5%).

KYNAMRO is an antisense drug and is metabolized without affecting the CYP450 pathways used in commonly prescribed drugs, and thus has potential for no drug-drug interactions. No clinically relevant pharmacokinetic interactions were reported between KYNAMRO and warfarin, or between KYNAMRO and simvastatin or ezetimibe.

KYNAMRO contains a Boxed Warning citing the risk of hepatic toxicity. Patients taking KYNAMRO should have liver enzyme testing before starting the drug and periodically thereafter. See below for Important Safety Information about KYNAMRO.

The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.

Because of the risk of hepatotoxicity, KYNAMRO is available only through a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. The goals of the KYNAMRO REMS are:
•To educate prescribers about the risk of hepatotoxicity associated with the use of KYNAMRO, and the need to monitor patients during treatment with KYNAMRO as per product labeling.
•To restrict access to therapy with KYNAMRO to patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia (HoFH).

As part of its commitment to HoFH patients, Genzyme has developed KYNAMRO CornerstoneSM, an HoFH and KYNAMRO support program for healthcare providers, patients, and their families. KYNAMRO Cornerstone services include:
•Dedicated KYNAMRO Cornerstone Case Managers.
•Product & disease education for providers, patients, and families.
•In-person injection training, if requested.
•Reimbursement support, including out-of-pocket financial support, for patients who qualify.
•Coordination of KYNAMRO shipment and delivery.

KYNAMRO Cornerstone Case Managers are available live Monday-Friday from 9 am to 6 pm Eastern time. For more information about KYNAMRO Cornerstone, or about these support services call 1-877-KYNAMRO (877-596-2676). For additional information, please visit www.KYNAMRO.com.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF HEPATOTOXICITY

KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).

KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis.

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3 x ULN. Discontinue KYNAMRO for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.

OTHER WARNINGS AND PRECAUTIONS

Patients are advised to read the KYNAMRO medication guide before starting treatment with KYNAMRO, and each time they receive a refill. There may be new information. This information does not take the place of talking to a doctor about a medical condition or treatment.

KYNAMRO may cause serious side effects, including liver problems. A doctor should be informed of any liver problems, including liver problems while taking other medicines, or if a patient has any of these symptoms of liver problems while taking KYNAMRO: nausea, vomiting, fever, loss of appetite, being (or feeling) more tired than usual, yellowing of eyes or skin, dark urine, itching, or stomach pain.

Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.

Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity.

KYNAMRO should be used during pregnancy only if clearly needed. Females who become pregnant during KYNAMRO therapy should notify their healthcare provider.

Safety and effectiveness have not been established in pediatric patients.

KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis.

The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis have not been established; therefore, the use of KYNAMRO as an adjunct to LDL apheresis is not recommended.

CONTRAINDICATIONS

KYNAMRO is contraindicated in the following conditions:
•Moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease, including unexplained persistent elevations of serum transaminases.
•Patients with a known hypersensitivity to any component of this product.

COMMON SIDE EFFECTS

In clinical trials the most commonly-reported adverse reactions were injection site reactions occurring in 84% of patients receiving KYNAMRO versus 33% of placebo treated patients. The most common injection site reactions were erythema (59%), pain (56%), hematoma (32%), pruritus (29%), swelling (18%) and discoloration (17%). Injection site reactions did not occur with every injection but resulted in discontinuation of therapy in 5% of patients in pooled phase 3 trials.

Flu-like symptoms, defined as any one of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue and occurring within 2 days of injection, have been reported more frequently in patients receiving KYNAMRO (30%) versus placebo (16%) in the pooled Phase 3 trials. Flu-like symptoms did not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled phase 3 trials.

See full prescribing information for more details about Warnings & Precautions, complete list of Adverse Reactions and Boxed Warning.

About KYNAMRO (mipomersen sodium) injection

KYNAMRO is indicated as a first-in-class, oligonucleotide inhibitor, of apolipoprotein B-100 synthesis. KYNAMRO is an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). KYNAMRO reduces LDL-C by preventing the formation of atherogenic lipoproteins, the particles that carry cholesterol through the bloodstream. KYNAMRO acts by blocking the production of apo B, the protein that provides the structural core for these atherogenic particles, including LDL.

About Homozygous Familial Hypercholesterolemia (HoFH)

HoFH is a rare genetic disease characterized by extreme cholesterol levels. People with HoFH have inherited mutations that limit the body's ability to clear cholesterol. HoFH is extremely rare: it is believed to occur in only one out of every one million persons. As with other rare diseases, the true prevalence of HoFH may be underestimated because of inadequate data and under-diagnosis. Today, it is estimated that HoFH affects about 6,000 people globally. Medical literature includes different criteria for marking an HoFH diagnosis. HoFH may be diagnosed by clinical or genetic parameters, and may be considered in cases of unusually high LDL-C, such as greater than 500 mg/dL without treatment, or 300 mg/dL after taking cholesterol-lowering medication. Because HoFH is genetic, it is important that all family members of people with HoFH know their cholesterol levels, regardless of their age.

About Genzyme, a Sanofi Company

Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years. We accomplish our goals through world-class research and with the compassion and commitment of our employees. With a focus on rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the patients and families we serve. That goal guides and inspires us every day. Genzyme's portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking and life-saving advances in medicine. As a Sanofi company, Genzyme benefits from the reach and resources of one of the world's largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more at www.genzyme.com.

[Stoxtrayder]

Hi cristrader!

Da das sind doch mal News!

...und ich dachte schon, ich wäre der Einzigste hier bei W:O, der den Wert im Depot hat! Seit heute auch wieder mit '+/- Null'!

In Stuttgart schon 10,80 EURO, was umgerechnet ca. 14,50$ enstpricht! Ich denke die 15$-Marke wird die Woche noch erreicht...

PS: Was hälst du von Morphosys! Zwar ganz anderer Ansatz, aber auch recht 'viele Pfeiler im Köcher'! War beim upmove von 24 bis 30 mit dabei. Habe dann erstmal Gewinne mitgenommen. Warte nun auf eine Korrektur, um wieder mit einer 1.Posi einzusteigen.

[cristrader]

Antwort auf Beitrag Nr.: 44.081.924 von Stoxtrayder am 30.01.13 13:28:34

Hallo Stoxtrayder,

Sorry war schon einige Wochen nicht mehr auf W-O!

Verfolge Morphosys nicht mehr so genau. War vor paar Jahren sehr interessiert, aber Kurs war mir aber davongelaufen. Grundsätzlich gesehen halte ich Morphosys für den besten deutschen Biotech-Wert und auch den einzigen Wert der sich wirklich international etablieren kann. Allgemein gesehen ist die Entwicklung der deutschen Biotech-Szene ziemlich enttäuschend.

Bin sowieso sehr vorsichtig geworden was Biotech Investments angeht. Die einzige Ausnahme ist da ISIS Pharmaceuticals! Für mich die Biotech Aktie mit der umfangreichsten und vielversprechenden Pipelines im ganzen Sektor. Im Vergleich zu ALNY und SRPT ist ISIS absurd niedrig bewertet, aber das wird sich bald ändern! Nachdem die Hürde Kynamro-Zulassung erfolgreich genommen wurde, werden künftige Pipeline-Erfolge eine ganz andere Beachtung finden. Die nächsten wichtigen Meilensteine werden die SMA-Phase I Präsentation ca. 20.März auf med. Kongress mit anschl. ISIS Webcast am 21.03.13 und vor allen Dingen die APOIII Phase II-Daten Mitte 2013. Bestätigen sich die bisherigen APOIII-Daten ist "only the Sky the limit". ISIS hat zwar u.a. mit Factor XL und CRP weitere Multi-Blockbuster Kandidaten mit Proof of Concept-Ergebnissen in 2013, an das Potential von APOIII kommen diese jedoch nicht heran.

Wenn man sich die ISIS Pipeline anschaut und ein positive Entwicklung in den nächsten 5-10 Jahren voraussetzt, ist der Weg zu einer neuen Amgen, Celgene oder Gilead vorausgezeichnet, bei durchaus moderaten Risiko.

Wenn ich nur noch in eine einzige Aktie investieren dürfte, würde meine Wahl definitiv auf ISIS fallen!


Gestern gabs die Quartalszahlen:


Isis Reports Financial Results and Highlights for 2012
CARLSBAD, Calif., Feb. 28, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (ISIS) today announced its 2012 financial results and reviewed the highlights of the year. Isis ended the year in a strong financial position significantly outperforming both its pro forma net operating loss (NOL) guidance and its cash guidance for the year. For the year ended December 31, 2012, Isis had an NOL of $60.4 million compared to $61.3 million for 2011. Isis added a substantial amount of cash to its balance sheet throughout 2012, ending the year with nearly $375 million. On a GAAP basis, Isis reported a loss from operations of $26.1 million and $68.9 million for the three and twelve months ended December 31, 2012, respectively, compared to $18.6 million and $71.1 million for the same periods in 2011.

"Last month the FDA approved KYNAMRO™. KYNAMRO is the first systemic antisense drug to be sold commercially. This is an important event for patients with homozygous familial hypercholesterolemia, for Isis, and for our antisense technology. KYNAMRO's approval for chronic use in patients who have a severe and fatal disease highlights the potential of our technology to create drugs that could provide benefit for patients," said B. Lynne Parshall, chief operating officer of Isis. "In addition to KYNAMRO, we have a number of promising new drugs that will report later-stage clinical data this year, setting us up for an exciting year of pipeline activity."

"2012 was a strong year for Isis. We begin 2013 in a significantly improved financial position with nearly $375 million in cash. Since the beginning of 2013, we have already received a $25 million milestone payment from Genzyme and a $7.5 million milestone payment from GSK. With the commercial launch of KYNAMRO and a maturing pipeline of drugs, we have many opportunities for significant near-term revenue from partnerships while we are also setting the stage for significant future revenue growth," said Elizabeth L. Hougen, chief financial officer of Isis.

"In 2013, we are predicting another year of strong financial performance while continuing to advance our pipeline. Although we are planning to have more than a dozen drugs in later-stage clinical studies throughout the year, we are projecting only a slight increase in our 2013 spending compared to 2012. As such, we expect to end 2013 with a pro forma NOL in the mid $60 million range. We are also projecting to end the year with more than $325 million in cash. Our guidance is supported by our partnering successes in 2012. Because most drugs are not profitable in their first year of commercialization, and because it is too early in the year to predict the revenue trajectory of KYNAMRO, we are being conservative in our projections by not including KYNAMRO profit share revenue this year. We are pleased with the significant investment Genzyme is making to ensure a successful KYNAMRO launch. This investment should support strong revenue growth in the future. We are fortunate to have Genzyme with its expertise in selling and marketing orphan drugs commercializing KYNAMRO and we look forward to providing updates throughout the year on KYNAMRO's commercial success," concluded Ms. Hougen.

Upcoming Key Milestones

Receive KYNAMRO marketing opinion from the European regulatory agency
Initiate a Phase 2/3 program of ISIS-SMNRx in infants with spinal muscular atrophy
Report clinical data on ISIS-SMNRx at the American Academy of Neurology meeting in March
Report clinical data on ISIS-CRPRx in patients with rheumatoid arthritis
Report clinical data on ISIS-APOCIIIRx in patients with high triglycerides
Financial Results
All pro forma amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of pro forma and GAAP measures, which is provided later in this release.

Revenue
Revenue for the three and twelve months ended December 31, 2012 was $19.9 million and $102.0 million, respectively, compared to $32.4 million and $99.1 million for the same periods in 2011. Isis' revenue fluctuates based on the nature and timing of payments under agreements with Isis' partners, including license fees, milestone-related payments and other payments. For example, in 2012, Isis recognized revenue from new sources in connection with the license for ISIS-STAT3Rx which Isis granted to AstraZeneca under its recently announced strategic alliance on RNA therapeutics for cancer, its three new collaborations with Biogen Idec and the KYNAMRO FDA acceptance milestone from Genzyme. At the same time, in 2012, Isis' revenue from amortization of the upfront payments associated with the Genzyme collaboration ended as planned midyear.

Isis earned a $25 million milestone payment from Genzyme in January 2013 for FDA approval of KYNAMRO and a $7.5 million milestone payment from GSK in February 2013 for the initiation of the Phase 2/3 study of ISIS-TTRRx. Isis will reflect both of these milestone payments in its first quarter 2013 financial results.

Operating Expenses
On a pro forma basis, operating expenses for the three and twelve months ended December 31, 2012 were $44.2 million and $162.4 million, respectively, compared to $48.8 million and $160.3 million for the same periods in 2011. In 2012, Isis was able to advance and expand its pipeline while maintaining its operating expenses essentially flat to 2011.

On a GAAP basis, Isis' operating expenses for the three and twelve months ended December 31, 2012 were $46.0 million and $171.0 million, respectively, compared to $51.0 million and $170.2 million for the same periods in 2011.

Early Retirement of Debt
In August 2012, Isis issued $201.3 million of 2 ¾% convertible senior notes due 2019 (2 ¾% Notes). In September 2012, Isis used a substantial portion of the net proceeds from the issuance of these notes to redeem the entire $162.5 million of the Company's 2 ⅝% convertible subordinated notes (2 ⅝% Notes). As a result of the early redemption of the 2 ⅝% Notes, Isis recognized a $4.8 million loss primarily related to a non-cash write-off of the unamortized portion of the debt discount and debt issuance costs.

Gain on Investment in Regulus Therapeutics Inc.
In October 2012, Regulus Therapeutics, Inc., a company Isis co-founded, completed an initial public offering. In the fourth quarter, as a result of the IPO, Isis recorded an $18.4 million gain to reflect the Company's change in its ownership percentage in Regulus. Also in the fourth quarter, Isis stopped using the equity method to account for its investment in Regulus and instead began accounting for it at fair value. Isis now owns approximately seven million shares, or 17%, of Regulus' common stock on a fully diluted basis.

Net Loss
Isis reported a net loss of $2.6 million and $65.5 million for the three and twelve months ended December 31, 2012, respectively, compared to $20.0 million and $84.8 million for the same periods in 2011. Basic and diluted net loss per share for the three and twelve months ended December 31, 2012 was $0.03 per share and $0.65 per share, compared to $0.20 per share and $0.85 per share for the same periods in 2011. In 2012, Isis' net loss was significantly lower than 2011 primarily due to the $18.4 million gain from its investment in Regulus and the related $9.1 million tax benefit offset, in part, by an increase in Isis' net operating loss, the $4.8 million loss on Isis' early retirement of its 2 ⅝% Notes, and an increase in interest expense. Isis' interest expense was higher than in 2011 due to additional non-cash interest expense Isis recorded for the long-term liability associated with its primary research and development facility and slightly higher interest expense related to Isis' 2 ¾% Notes.

Balance Sheet
As of December 31, 2012, Isis had cash, cash equivalents and short-term investments of $374.4 million compared to $343.7 million at December 31, 2011 and had working capital of $349.1 million at December 31, 2012 compared to $284.0 million at December 31, 2011. During 2012, Isis received a substantial amount of cash, including $96 million in upfront payments from Biogen Idec and AstraZeneca, a $25 million milestone payment from Genzyme for FDA acceptance of the KYNAMRO NDA and approximately $30 million in net proceeds from Isis' issuance of its 2 ¾% Notes. Isis' working capital increased significantly in 2012 primarily due to the cash Isis received in 2012 and an increase in current assets resulting from Isis' investment in Regulus because Isis is now recording its investment at fair value. At December 31, 2012, the carrying value of Isis' investment in Regulus was $33.6 million.

2013 Goals
"We expect 2013 to be a year of substantial growth and maturation for Isis. We believe that the initial commercial launch of KYNAMRO will be successful and we support Genzyme's ongoing development efforts for KYNAMRO with the FOCUS FH study, which Genzyme is conducting under a special protocol assessment with the FDA," continued Ms. Parshall. "Beyond KYNAMRO, we have a number of drugs in our pipeline that will complete later-stage clinical studies, which are designed to provide clear evidence that these drugs have the potential to work in patients in numerous different diseases. In addition, we plan to advance many other drugs in our pipeline, creating additional opportunities for significant long-term revenue. And finally, we expect to explore partnering opportunities that are the right fit for Isis and designed to provide the most benefit to our programs and drugs, the best balance of risk and commercial participation, while allowing us to continue to do what we do best, drug discovery and early drug development."

In 2013, Isis plans to achieve the following goals itself and with its partners:

Together with Genzyme, Isis will continue to support KYNAMRO development, marketing and commercialization activities.
Support commercial launch in the United States for patients with HoFH.
Continue enrollment in FOCUS FH.
Pursue marketing approval in Europe for HoFH in the first half of 2013.
Mature its pipeline:
Complete and report late-stage clinical data from Phase 2 or Phase 3 studies from up to nine drugs in its pipeline.
Initiate Phase 2/3 or Phase 3 studies on two or three drugs for severe and rare diseases.
Initiate Phase 2 studies on up to five drugs in its pipeline.
Broaden its pipeline by adding up to five new drugs.
Continue to successfully execute its business strategy to generate revenue and cash.
Business Highlights
"2012 was a year of significant achievements for Isis. Together with Genzyme we successfully completed the final steps to bring KYNAMRO to the market in the US for patients with HoFH. We continued to mature and expand our severe and rare disease franchise, receiving orphan drug designation for two of the drugs in this franchise. We reported clinical data on seven drugs in our pipeline and advanced three drugs into Phase 2 clinical studies that we plan to report data from this year, which could support significant licensing opportunities for us," continued Ms. Parshall.

"And finally, we have been successful in implementing our business strategy and establishing strategic partnerships that provide us with significant value. We established three collaborations with Biogen Idec focused on neurologic severe and rare diseases. Biogen Idec's extensive expertise and experience in neurological diseases makes Biogen Idec an ideal partner to work with us to build a neurologic disease franchise. In addition, we established a collaboration with AstraZeneca that allows us to broaden and expand our antisense drug discovery and development efforts and apply our antisense technology to novel oncology targets with a global leader in cancer drug development and commercialization," concluded Ms. Parshall.

Drug Development Highlights for 2012/ Early 2013

Isis and Genzyme were successful in bringing KYNAMRO to the market for patients with HoFH. These patients are at high cardiovascular risk and may not be able to reduce their LDL-C sufficiently with currently available lipid-lowering therapies.
KYNAMRO was approved for marketing in the United States by the US FDA for the treatment of patients with HoFH.
Isis received a total of $50 million in milestone payments from Genzyme related to the NDA acceptance in 2012 and marketing approval of KYNAMRO by the FDA in 2013.
Genzyme continues to enroll the FOCUS FH study, which is designed to provide 60-week safety and efficacy data in FH patients to support an additional regulatory filing. Genzyme reached an agreement with the FDA on the design of the FOCUS FH study via a Special Protocol Assessment, or SPA.
Genzyme submitted a request for re-examination of the EMA's negative opinion on the marketing authorization application for KYNAMRO and expects to report the outcome of the re-examination in the first half of 2013.
Isis received European GMP certification of its manufacturing facility for production of drug substance to support KYNAMRO commercial launch.
Clinical investigators presented KYNAMRO data at important cardiovascular medical meetings throughout the year.
Dr. Raul Santos presented data from the long-term extension study of KYNAMRO at the International Symposium on Atherosclerosis. These data highlighted the long-term safety and efficacy of KYNAMRO in patients who have been treated with KYNAMRO.
Dr. Klaus Parhofer presented an analysis of data from the KYNAMRO Phase 3 study in patients with severe heterozygous FH at the European Society of Cardiology. These data highlighted the potential of KYNAMRO to reduce the need for apheresis by lowering LDL-C values below the thresholds for apheresis eligibility in patients with severe heterozygous FH.
Dr. Sotirios Tsimikas presented an analysis of Lp(a) data from the KYNAMRO Phase 3 program at the European Atherosclerosis Society. These data demonstrated sustained reductions of Lp(a), an independent risk factor for cardiovascular disease.
Isis and its partners reported positive clinical data on seven drugs and Isis added four drugs to its pipeline.
Isis and its partners initiated Phase 2 or Phase 3 clinical studies on eight drugs.
Isis received Orphan Drug Designation and Fast Track Status in the US for ISIS-SMNRx and ISIS-TTRRx. Isis received Orphan Drug Designation in the EU for ISIS-SMNRx.
Corporate Highlights for 2012/ Early 2013

Isis formed three new strategic alliances with Biogen Idec to develop and commercialize antisense drugs for severe and rare and neurologic diseases. In total all three alliances are valued at up to $1.2 billion.
Isis entered into an alliance with Biogen Idec to develop and commercialize its drug, ISIS-SMNRx, to treat SMA. Isis received a $29 million upfront payment and is eligible to receive up to an additional $270 million in a license fee and milestone payments, and double-digit royalties on sales of ISIS-SMNRx.
Isis entered into an alliance with Biogen Idec to develop and commercialize a drug to treat myotonic dystrophy. Isis received a $12 million upfront payment and is eligible to receive up to an additional $259 million in a licensing fee and milestone payments. Isis is also eligible to receive double-digit royalties on product sales.
Isis entered into an alliance with Biogen Idec to discover and develop antisense drugs against three targets to treat neurological or neuromuscular disorders. Isis received a $30 million upfront payment and is eligible to receive up to another $200 million in a license fee and regulatory milestone payments per program. Isis is also eligible to receive double-digit royalties on product sales for each drug.
Isis formed a new strategic alliance with AstraZeneca to discover and develop antisense drugs against five cancer targets, which included a license to develop and commercialize ISIS-STAT3Rx.
The agreement comprises $31 million in upfront and near-term payments, including a $25 million payment Isis has received followed by a $6 million payment Isis is eligible to receive in the second quarter of 2013 assuming the research program is continuing. Isis is also eligible to receive milestone payments, license fees and royalties.
Isis added the first drug from its research collaboration, ISIS-AZ1Rx, to the pipeline.
Isis and GlaxoSmithKline amended the clinical development plan and financial terms relating to ISIS-TTRRx to support an accelerated development plan for the drug. As a result of the revised agreement, Isis received a $2.5 million upfront payment.
Isis received a $7.5 million milestone payment upon initiation of the Phase 2/3 study for ISIS-TTRRx.
Isis is also eligible to earn an additional $50 million in pre-licensing milestone payments to support the ISIS-TTRRx Phase 2/3 study.
Isis benefited as its partners advanced RNA-based technologies and products incorporating its technology.
Isis received $2.7 million from Alnylam as a result of Alnylam's licenses that included Isis' patents.
Isis received $1.3 million from Pfizer triggered by Pfizer's decision to advance EXC 001 into a Phase 2 study.
Regulus Therapeutics completed an initial public offering and is now traded on The NASDAQ Global Market under the ticker RGLS. Isis purchased $3 million of Regulus' common stock at the offering price and remains a significant shareholder with approximately 17% ownership on a fully diluted basis, which is valued at approximately $36 million.
Isis completed a successful $201.3 million convertible debt financing. Isis used the majority of the proceeds of this financing to redeem its outstanding $162.5 million 2 ⅝% subordinated convertible debt.
The securities class action lawsuit was voluntarily withdrawn and there are no pending lawsuits related to any violation of securities laws.
Isis and its collaborators published papers in leading scientific journals demonstrating the broad applicability of its technologies.
A paper in Nature demonstrating that an antisense compound selectively and rapidly reduced target RNA in skeletal muscle and alleviated disease in animal models of myotonic dystrophy.
A paper in Neuron demonstrating that an antisense compound reversed disease in animal models of Huntington's disease.
Two papers in the journal Cell demonstrating that single-stranded RNA-like antisense technology can activate the RNAi pathway and inhibit the expression of targeted genes.
Conference Call
At 12:00 p.m. Eastern Time today, February 28, 2013, Isis will conduct a live webcast conference call to discuss this earnings release and related activities. Interested parties may listen to the call by dialing 866-323-2841 and provide the conference identification number "90809537", or access the webcast at www.isispharm.com. A webcast replay will be available for a limited time at the same address.



Earnings Call transcript:
http://seekingalpha.com/article/1235741-isis-pharmaceuticals…

Chad Messer - Needham & Company
Yes, thanks. Thanks for taking my question. So, if you look at a lot of the great partnerships you have, Biogen, Genzyme, a lot of these for rare diseases, genetic diseases more orphan type things. But in the list of some of the upcoming potential new partnerships that you could start pursuing in the next year or two, there is a lot of very large and broad indication.

So inflammation, cancer, thrombosis, how does that affect? What you are looking for both in a partner and in partnership terms? And then if I may out of sort of the near-term partnership opportunities, which one do you think represents the greatest to value to Isis’ shareholders?

Stanley T. Crooke - Chairman and Chief Executive Officer
Thanks for the question, Chad. One thing to – I just feel I need to remind people is when you look at deals that we have today, you’re looking at a cross section and you have to look back to when we did the deals and what our circumstances were when we did those deals.

Our goal in 2012 was to partner our neuro program and to partner our cancer programs. The reason that those were our major goals are, first, our neuro program while exciting was very new and was associated with meaningful risk that we couldn’t judge that begin and end with the fact that we’re giving these drugs directly into the spinal fluid. And there are also other risks that are associated with just challenges of doing work in the central nervous system.

And what we wanted for that constellation of activities is a partner who was really excited about the technology and knew this space that would work cooperatively with us. We think what we achieved there is really remarkable and we think the three transactions we’ve had with Biogen and the progress made is just wonderful performance.

The second space was cancer. And again, the thinking there was that we needed to invest very broadly in Phase 2 trials for STAT3 which to do it well would be maybe $40 million or more dollars. And we needed a partner that was committed to doing that with us to support that and to share some of the risk. We got that done.

Now that we have all that behind us and we’re financially secure and we’re expecting to see revenues from KYNAMRO, our approach is to retain many of our drugs longer and the goal of course is to be able to do transactions that give us a bigger piece of the commercial revenue while still getting larger front fees and milestones. I think we’ve been very successful with that for the last 23 years. And it’s easier today as it’s ever been because the interest is so high, and the prices are going up.
So if you look at our portfolio of drugs and ask which ones would we likely keep longer and which ones might we even do some Phase 3 work ourselves, they would be the drugs where we have a very clear, unequivocal demonstration of efficacy in Phase 2 and a straight forward process and cost effective process in Phase 3.

So if you look at the drugs in the portfolio that don’t need that clearly, CRP, the cancer drugs, the metabolic drugs, all are candidates for licensure. Factor XI is a critical opportunity for partnering. ApoCIII is a mix because we do think we have a straight forward path to a commercial opportunity with ApoCIII, but its potential of course is very broad and so we may partner that as well. But our circumstances there would dictate that we would do very differently.

I don’t know if I answered your question. I guess the last question you asked is one of the things I’m most excited about as potential partnering? ApoCIII, even though we may not partner it, we won’t partner until we get the price that we want. CRP, Factor XI and a couple of the diabetes drugs are the things I’m most excited about.

Stanley T Crooke

I’ll just add one final comment. I think we’re now in the financial position that we don’t need to partner and we are in the financial position that we can retain our drugs until we are confident that they’re at a significant value infection point. And the level of interest that we have in the technology of the drugs is extremely high. And so we are going to be very selective about when we do deals, what deals we do and who we’re dealing with.

Stanley T Crooke

"We think 2013 is going to be a great year for us and for our investors and we think we’re just at the tip of the ice berg of value that antisense technology is going to create."


cristrader

[cristrader]

Vergleich ISIS vs ALNY
http://seekingalpha.com/article/1220311-biotech-bubble-alnyl…

A comparison between Alnylam and Isis Pharmaceuticals (ISIS) illustrates this point clearly. Both of these companies compete directly within the RNAi space, yet Isis has a far broader product portfolio which is in later stages of development.

ISIS
ALNY

Phase III products or above
ISIS: 4
ALNY: Zero

Phase II products
ISIS: 14
ALNY: 1 ongoing

2012 Revenue
ISIS: $99 million
ALNY: $67 million


Market cap
ISIS: $1.5 billion
ALNY: $1.5 billion

Price change
ISIS: 102%
ALNY: 190%


* Stock price change since Jan 1, 2012

As can be seen, Alnylam has significantly outperformed Isis even though Alnylam has no Phase III products and only one Phase II product still active. In comparison to Isis, Alnylam has virtually no pipeline. Yet the two companies now have identical market caps and Alnylam's price performance has been near double that of Isis since January 2012.

The value of a successful Phase II for ALN-TTR02

ALN-TTR02 and ALN-TTRsc are intended to be orphan drugs to treat ultra-rare indications (FAP and FAC) affecting just 50,000 individuals worldwide.

There are already multiple competing products being brought by competitors which are further along than Alnylam. Pfizer (PFE) has Vyndaqel which is in Phase III in the US and is already approved in Europe. Isis, along with partner Glaxo (GSK), has ISIS-TRRx which is proceeding with a Phase II/III study.

Despite the fact that it is farthest behind with a drug that may end up losing in a winner-take-all race for orphan status, the market is awarding a $800 million valuation to this single drug, which has yet to even complete Phase II.

By comparison, the entire value of Isis is only $1.5 billion, which includes its own similar (and more advanced drug) along with a pipeline of more than a dozen other advanced products.


Der Seeking Alpha Artikel ist von einem Short (ALNY) geschrieben. Der Vergleich mit ISIS ist aber absolut plausibel und korrekt. ALNY hat mit seiner Technologie auf längere Sicht sicher hervorragende Chancen, nur die aktuelle Bewertung im Vergleich zu ISIS ist ein Witz und ist eigentlich nur mit einer geplanten Übernahme zu erklären.

cristrader

[cristrader]

Neues Dreijahreshoch!!!

Der Chart wird zunehmend interessanter! Jetzt müssen nur noch die Hochs von 2009/2010 geknackt werden, dann wird es spannend!

[cristrader]

Isis Ready To Break Out Ahead Of Conference, Myriad Catalysts This Year


http://seekingalpha.com/article/1247061-isis-ready-to-break-…

By Rajesh Patel, Ph.D.

Shares of ISIS Pharmaceuticals (ISIS) were up over 8% at the close of trading on Monday, just days ahead of the American Association of Neurology (AAN) conference which begins March 16th. In our last article about ISIS we suggested that the AAN conference would be the next catalyst for ISIS, as the company would be presenting data from their Phase 1 trial of ISIS-SMNRx, an investigational drug candidate to treat spinal muscular neuropathy in children and infants (You can read the abstract of the presentation here). At the end of January, we anticipated that the stock would climb on the back of the Kynamro approval, in anticipation of this early-stage presentation, and in advance of numerous data releases in the first half of the year; shares are up 13% since.

Monday's gains appear to be the beginning of the move we predicted earlier, with the stock moving higher than its previous highs before the Kynamro Advisory Committee meeting late last year. The close above the $16 level, followed by further upward movement on Tuesday, would be a strong signal that the stock is ready to break out from the round-bottom pattern evident on the 2-year chart.

At a $1.65B market capitalization, we see ISIS as significantly undervalued given the number of pipeline candidates (and noteworthy partnerships) the company has. With up to 8 Phase II and one Phase III trial reading out this year, ISIS has numerous potential value drivers throughout the year. And in the eyes of many, the Kynamro approval in January offered clear validation of Isis' antisense technology, a platform that had been met with trepidation for years. Following the AAN conference, the next catalysts for ISIS are the top-line results from Phase 2 trials of ISIS-APOCIIIRx and ISIS-CRPRx -- for the treatment of very high triglyceride levels (>500 mg/dL) and rheumatoid arthritis respectively -- before the end of Q2. With numerous catalysts and relatively defined time frames around which to trade, Isis should continue to gain visibility and pique interest within the biotech segment.

[cristrader]

Zwar von Anfang Januar und bevor der Kynamro-Zulassung aber trotzdem eine fantastische Präsentation!

http://www.buenavistainv.com/dbimages/JP%20Morgan%20Healthca…

[cristrader]

Isis scheint auf hohem Niveau zu konsolidieren. Kann die Präsentation der SMA-Ergebnisse auf der AAN-Konferenz (American Association of Neurology )am
20.März kaum erwarten.

ISIS-SMNRx ist vom Potential und Krankheitssymptomen (Muskelschwund)vergleichbar mit Sareptas Duchenne muscular dystrophy-Kandidat. SMA ist die am häufigsten vorkommende genetisch bedingte Todesursache bei Kleinkindern. In den USA, Europa und Japan gibt es etwa 30000-35000 Betroffene. Bisher gibt es noch keine zugelassene Therapie.

Durch ein fehlerhaftes Gen wird die Produktion des SMN-Proteins verhindert. ISIS greift auf RNA-Ebene in den Prozess ein so das ein funktionales SMN-Protein entsteht.

ISIS-SMNRx
Phase 1 Single-Dose Study in SMA Patients (Dosing Completed)
Open-label, single-dose study to evaluate the safety and tolerability of ISIS-SMNRx
in SMA patients 2-14 years of age
Intrathecal dosing was well tolerated
Feasibility of infrequent dosing demonstrated
Improvements in muscle function observed in a number of children
Abstract accepted for a special presentation at the American Academy of
Neurology meeting in March 2013

Die Studie umfasste insgesamt 28 Patienten mit unterschiedlichen Dosierungen. Die genauen Ergebnisse werden am 20.März auf der AAN präsentiert und am 21.März veranstaltet ISIS nochmal eine spezielle Pressekonferenz.

[Stockfinder]

habe heute eine erste Position zu 18 $ aufgebaut, die Pipeline klingt vielversprechend. Durch die Zulassung von Kynamro hat die Firma zudem bewiesen, dass sie Studien trotz einiger Hürden durchbringt und Medikamente zur Zulassung bringen kann. Zudem ist für 2013 scheinbar mit jeder Menge Nachrichten zu rechnen.

[cristrader]

Antwort auf Beitrag Nr.: 44.247.446 von Stockfinder am 13.03.13 16:47:00

Hallo Stockfinder!

Schön das du dabei bist! Leider wurde die wichtige Charthürde bei 18,05$ gestern nicht durchbrochen. Selbst bin ich mit 20$ Januar´14 Optionen stark investiert.

Gestern gab es wieder eine Präsentation:

ISIS Pharmaceuticals' Management Presents at 2013 Barclays Global Healthcare Conference (Transcript)


http://seekingalpha.com/article/1271791-isis-pharmaceuticals…

Für mich gab es nicht viel Neues, war aber doch wie immer beeindruckend. Habe mir in den letzten Jahren jedes Webcast angehört. Gestern wurden u.a. nochmal die Phase I-Ergebnisse vom Krebsmedikament ISIS-STAT3 hervorgehoben.

"So as I mentioned before STAT3 is our first drug using the 2.5-technology. 2.5 as compared to 2.0 is approximately 10 times more potent. Patients have good tolerability. This is an example of a patient treated in MD Anderson Hospital in a Phase 1 study. This patient had diffused large B-cell lymphoma, had been refractory to 12 prior therapies, had not obtained a partial response.

We had enrolled three patients with diffused large B-cell lymphoma into this trial. Two of the three have had sustained partial responses. This woman is a 63-year-old woman who failed 12 prior therapies, has remained stable for 11 months now receiving monotherapy, IV administered weekly STAT3 therapy at MD Anderson Hospital."

Bei einer Studie an nur drei Patienten sind die bisherigen Egebnisse sensationell. Mit Partner AstraZeneca wird ein breit gefächertes Phase II-Programm gestartet. Erste Phase II-Ergebnisse werden bereits Ende 2013/Anfang 2014 erwartet. Dieses Medikament ist eines von zahlreichen Programmen das noch in keinerlei Analystenberechnungen einfließt. Bisher werden eigentlich nur Kynamro, APOCIII und SMN in die Bewertungen mit aufgenommen. Bei den zahlreichen Phase II/III-Ergebnissen die in den nächsten zwei Jahren anstehen, besteht daher erhebliches Kurspotential.

Nächsten Mittwoch die AAN-Konferenz mit den SMA-Ergebnissen wird hoffentlich den nächsten Kurssprung einläuten, bevor Mitte des Jahres die APOCIII-Phase II-Ergebnisse verkündet werden und die Party richtig losgeht. Die Phase II-Studie müsste meinen Berechnungen zufolge Ende Januar bzw. spätestens Anfang Februar beendet worden sein. Jetzt müssen natürlich die ganzen Daten ausgewertet werden was einige Monate in Anspruch nimmt.

cristrader

[Stoxtrayder]

@cristrader: Danke an der Stelle nochmals für diese ganzen hochinformativen News inkl. persönlicher Meinung. Wenn ich all das hier so lese, werde ich meine Anteile vorerst doch behalten. Hatte die Tage über daran gedacht, zu verkaufen (Misch-EK beträgt 11 EURO), da mir der Chart doch recht überhitzt aussieht, aber da die nächsten Wochen die News ja augenscheinlich nicht weniger werden bzg. Pipeline bleibe ich da auf jeden Fall mit an Bord... und falls doch ein Rücksetze kommen sollte, werde ich weiterhin aufstocken.

by the way: mit stockfinder sind wir hier schon zu dritt...
vielleicht finden sich (bei der Kursentwicklung/Aussichten) noch mehrere ISIS-Investierte/Interessierte.

[cristrader]

Antwort auf Beitrag Nr.: 44.255.079 von Stoxtrayder am 15.03.13 00:42:21

Hallo Stoxtrayder,

ist leider sehr ruhig auf Wallstreet-Online geworden. User scheinen sich im Biotech-Board wohl nur für Penny-Aktien mit mehr als zweifelhaften Erfolgsaussichten zu interessieren.


Zehn Jahre nach Entschlüsselung des menschlichen Genoms befindet sich die genetische Revolution noch immer in der Anfangphase der Entwicklung. Mit der fortschreitenden, technischen Entwicklung und den daraus folgenden Erkenntnissen, welche Faktoren oder auch Gene bestimmte Krankheiten verursachen, ergibt sich auch eine Vielzahl neuer Ansatzpunkte (Targets) zur Entwicklung neuer Therapien. Viele dieser Targets lassen sich durch traditionelle Methoden(Small Molecules und Antikörper) gar nicht angreifen, da diese erst ab Proteinebene eingreifen. ISIS mit seiner Antisensetechnologie sowie die wenigen anderen RNA/RNAI-Biotechs wie z.B. ALNY,SPRT oder RGLS greifen bereits auf RNA-Ebene in den Krankheitsprozess ein, das heißt das krankheitsverursachende Protein wird gar nicht erst produziert bzw. wird wie im Fall von ISIS-SMN erst korrekt produziert. Antisense/RNAi, als dritte Medikamentenklasse, befindet sich, mit Kynamro als erstem Vertreter, noch gar nicht im Bewußtsein der meisten Biotech-Investoren. Das wird sich in den nächsten Jahren ändern!!! Was ich mir wünsche wäre eine Übernahme eines Biotechs im RNA-Bereich (aber ganz gewiss nicht eine von ISIS ).

Kleiner Tip: Als ISIS Investor tägliche Pflichtlektüre!
http://www.investorvillage.com/smbd.asp?mb=1373&pt=m

[Steel21x]

Hallo,

ein sehr interessanter Wert bin aber noch nicht investiert.Gibt es denn Umsatzprognosen für Kynamro, weiss das einer von euch beiden?

Grüße

[cristrader]

Antwort auf Beitrag Nr.: 44.261.863 von Steel21x am 16.03.13 21:26:40

Hallo Steel21x!

Von Kynamro sind kurzfristig noch keine großen Umsätze zu erwarten. In der Indikation HoFH sind Peak Sales von 300-400 Mio US$ zu erwarten. Kynamro konkurriert mit Aegerion Pharmaceuticals Medikament Juxtapid, das einen Monat früher, für die gleiche Indikation, zugelassen wurde. Juxtapid werden nach Wallstreet´s Meinung etwas bessere Marktchancen eingeräumt.
Juxtapid ist im Gegensatz zu Kynamro oral verabreichbar und hat etwas bessere klinische Ergebnisse. Nebenwirkungen sind etwa vergleichbar mit der von Kynamro. Wer Juxtapid einnimmt muss allerdings eine ultrastrenge Diät einhalten zudem kostet die Behandlung etwa 270.000$(Kynamro 170.000). ISIS Partner Sanofi/Genzyme hat auch sicherlich die erheblich bessere Vertriebsstrucktur von daher muss man abwarten wer das Rennen gewinnt.


Kynamro wird meiner Meinung finanziell gesehen langfristig keine wichtige Rolle spielen. Kynamros Wert liegt vor allem in der Validierung der Antisensetechnologie und der riesigen Pipeline von ISIS.

[Stockfinder]

sehr starkes Volumen zu Beginn und up, +6,5 %.....

[Stockfinder]

Isis wird in Kürze schon Sarepta bei der Performance ablösen. Im 2. Halbjahr dürfte die Firma meiner Meinung nach zu den Highflyern gehören. Der Kurs steigt stetig, die 20 $ sind greifbar...

[cristrader]

Hallo!

Haben ereignisreiche Wochen hinter uns und es wird mal wieder Zeit für ein Update

Die SMA-Präsentation auf der AAN Konferenz am 20.03.13 waren sehr vielversprechend.

Data From ISIS-SMN Rx Phase 1 Study in Children With Spinal Muscular Atrophy Presented at the American Academy of Neurology Meeting

CARLSBAD, Calif., March 20, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (ISIS) announced that data from the Phase 1 study of ISIS-SMNRx in children with spinal muscular atrophy (SMA) were presented today at the 65th American Academy of Neurology (AAN) Annual Meeting by Dr. Claudia Chiriboga, from Columbia University Medical Center. In the presentation, Dr. Chiriboga reported that, in this single-dose, open-label study, ISIS-SMNRx was well tolerated in children with SMA at all dose levels tested and that improvements were observed in Hammersmith scores, a measure of muscle function, in a number of the children. SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness and is the most common genetic cause of infant mortality. ISIS-SMNRx is an antisense drug designed to treat all types of SMA.

"SMA is a devastating disease that results in severe muscle weakness and respiratory failure in infants and children. Current treatments are supportive and do not address the underlying genetic cause of SMA, the loss of SMN protein, which is critical to the health and survival of nerve cells responsible for neuromuscular growth and function. ISIS-SMNRx is designed to address the underlying genetic problem for patients with SMA by increasing the production of functional SMN protein," said Claudia Chiriboga, M.D., associate professor of clinical neurology and pediatrics at Columbia University Medical Center. "I am pleased to report that ISIS-SMNRx administration was very well tolerated in these young children with a safety profile that supports additional development of the drug. The improvements in muscle function observed in this study following a single dose of the drug were encouraging. For these reasons, I am very excited about the potential benefit of ISIS-SMNRx for children with this terrible disease."

In the presentation titled, 'Results of an Open-Label, Escalating Dose Study To Assess the Safety, Tolerability, and Dose Range Finding of a Single Intrathecal Dose of ISIS-SMNRx in Patients with Spinal Muscular Atrophy', Dr Chiriboga reported that ISIS-SMNRx was well tolerated when administered intrathecally as a single dose directly into the spinal fluid and that no safety concerns related to the drug were identified. In addition, the intrathecal injection procedure was well tolerated in children with SMA. Concentrations of ISIS-SMNRx measured in cerebral spinal fluid were consistent with levels predicted from preclinical studies, indicating that the drug half-life in nervous system tissues is very long and that dosing once every six to nine months is feasible. Although the study was not designed to provide evidence of functional activity, clinically significant, dose-dependent improvements in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a measure of muscle function, were observed in these children. The mean increase in the HFMSE scores observed in the highest dose cohort (9 mg) at 3 months was 3.1 points or a 17.6% increase from baseline, with six of ten patients experiencing an increase of 4 to 7 points. Observed improvements in HFMSE scores equal to or greater than a 4 point increase were distributed by age with half (3) in children under the age of five and half in children five and older. Children who participated in this study are allowed to either enter the ongoing multiple-dose Phase 1b/2a study or a separate re-dosing study. Please click here to access Dr. Chiriboga's AAN slide presentation.

"SMA is a heartbreaking disease. Children with SMA are bright and engaging, but often never achieve the simplest motor milestones like walking, crawling, or sitting up. In its most severe form, children do not live beyond 2 years of age. Even in milder cases, SMA patients inexorably grow weaker and experience the loss of the few abilities they did acquire. In addition to motor losses, SMA patients young and old are at constant risk of tragic consequences from simple respiratory infections that you and I take in stride," said Karen S. Chen, Ph.D., chief scientific officer at the SMA Foundation. "The landmark science behind ISIS-SMNRx is compelling and it has a chance to fill the therapeutic void for SMA and transform the hopes and futures of thousands of patients and families."

The Phase 1 study of ISIS-SMNRx was an open-label, single-dose, dose-escalation study designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMNRx in medically stable children from age 2-14. In this study, 28 children, including 15 with Type II SMA and 13 with Type III SMA, received ISIS-SMNRx as a single dose of 1, 3, 6, or 9 mg administered intrathecally. ISIS-SMNRx concentrations in plasma and cerebral spinal fluid were measured to provide information on the dose concentration and frequency for future studies. In addition, exploratory analyses of changes in motor function were conducted. Gross motor movements were measured in all children throughout the study using the Hammersmith Motor Function Scale-Expanded (HFMSE), a modified version of the Hammersmith Functional Motor Scale. The HFMSE is used to assess responses on 33 motor function tasks, each scored on a scale from 0 to 2 and allows for assessment of any SMA patient aged 2 or older. HFMSE has demonstrated good test-retest reliability in other studies.

"ISIS-SMNRx is our first drug to modify the splicing of RNA to increase the production of a functional SMN protein. This Phase 1 study is the first time that we have administered an antisense drug to patients as young as 2 years of age. We are very encouraged that the drug was safe and that intrathecal dosing was tolerated well by these children even at the highest dose level," said C. Frank Bennett, Ph.D., senior vice president of research at Isis.

"Early evidence of activity in these children is encouraging, but it is important to note that this was an open-label study without a control arm," said Stanley T. Crooke, M.D., Ph.D., chairman of the board and chief executive officer at Isis. "We are cautiously optimistic with the observed improvements in muscle function in the higher dose cohort, however, we will need further clinical data from a controlled study to assess the safety and activity of this drug in patients with SMA. We plan to have additional clinical data from our ongoing multiple-dose study in children with SMA by late 2013 or early 2014. We also plan to initiate a Phase 2/3 program in infants this year and a Phase 2/3 study in children in the first half of 2014."

ABOUT ISIS-SMNRx
ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. Isis is currently in collaboration with Biogen Idec to develop and potentially commercialize the investigational compound, ISIS-SMNRx, to treat all types of SMA. Under the terms of the January 2012 agreement, Isis is responsible for global development and Biogen Idec has the option to license the compound until completion of the first successful Phase 2/3 study. ISIS-SMNRx is currently being evaluated in a Phase 1b/2a multiple-dose, dose-escalation study in children with SMA. In this study, children will either receive two or three doses of ISIS-SMNRx over the course of the study.

ABOUT SMA
SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in the United States, Europe and Japan. SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord responsible for neuromuscular growth and function. One in 50 people, the equivalent of about 6 million people in the United States, are carriers of a defective SMN1 gene, which is unable to produce fully functional SMN protein. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA. The severity of SMA correlates with the amount of SMN protein. Infants with Type I SMA, the most severe form of the disease, produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

Isis acknowledges support from the following organizations for ISIS-SMNRx: Muscular Dystrophy Association, SMA Foundation, Families of SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School

http://www.isispharm.com/pdfs/AAN_Chiriboga_Presentation.pdf
http://www.isispharm.com/pdfs/AAN_Isis_Investor-Event.pdf

Transcript von der Pressekonferenz:
http://us.rd.yahoo.com/finance/external/xtrsa/SIG=14t2n0h51/…

Anfänglicher Kurssprung bis 19.52$ wurde jäh gestoppt da ausgerechnet am gleichen Tag die EU Kynamro erneut die Zulassung verweigerte, was aber erst am 22.03. publik wurde. Abverkauf bis zum Tiefstand von 15.92$ folgte.
Es folgten die Bekanntgabe der Veröffentlichung von vielversprechenden APOCIII-Phase I-Daten in einem Magazin "Circulation Research", den Phase I-Start eines weiteren Medikamentes (ISIS-APOARx)und schließlich die Partnerschaft mit Roche zur Entwicklung von Medikamenten gegen Huntington´s Disease u.a. mit 30 Mio Upfront-Zahlung, was eine weitere Validierung der Antisense-Technologie darstellt. Gestern hatten wir ein 11-Jahreshoch 19,68$ erklommen.



Roche and Isis Pharmaceuticals Form Alliance for Huntington's Disease

BASEL, Switzerland, and CARLSBAD, Calif., April 8, 2013 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) and Isis Pharmaceuticals, Inc (NASDAQ: ISIS) today announced that they have formed an alliance to develop treatments for Huntington's disease (HD) based on Isis' antisense oligonucleotide (ASO) technology. This alliance combines Isis' antisense expertise with Roche's scientific expertise in developing neurodegenerative therapeutics. In addition, Isis and Roche will be collaborating to combine Isis' ASOs and Roche's proprietary "brain shuttle" program with the objective of increasing the brain penetration of ASOs with systemic administration.

Huntington's disease is an inherited genetic brain disorder that results in the progressive loss of both mental faculties and physical control. Symptoms usually appear between the ages of 30 to 50, and worsen over a 10 to 25 year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective treatment or cure for the disease, and current treatments focus on reducing the severity of some disease symptoms.

Initially, research will focus on Isis' lead drug candidate that blocks production of all forms of the huntingtin (HTT) protein, the protein responsible for HD and thus has the potential to treat all HD patients. Isis is also conducting research into treatments that specifically block production of the disease-causing forms of the HTT protein which has the potential to treat subsets of HD patients. In parallel, Roche will combine its proprietary brain shuttle technology with Isis ASO technology that, if successful, will also allow systemic administration of antisense drugs to treat asymptomatic patients.

Under the terms of the agreement, Roche will make an upfront payment of $30 million to Isis, with total payments related to license fee and pre- and post-licensing milestone payments reaching potentially $362 million, including up to $80 million in potential commercial milestone payments. In addition, Isis will receive tiered royalties on sales of the drugs. Roche has the option to license the drugs from Isis through the completion of the first Phase 1 trial. Prior to option exercise, Isis is responsible for the discovery and development of an antisense drug targeting HTT protein. Roche and Isis will work collaboratively on the discovery of an antisense drug utilizing Roche's "brain shuttle" program. If Roche exercises its option, it will be responsible for global development, regulatory and commercialization activities for all drugs arising out of the collaboration.

Commenting on the deal, Luca Santarelli, Head of Neuroscience and Small Molecules Research at Roche, said: "Huntington's is a severely debilitating neurodegenerative disease and a large unmet medical need. Patients experience gradually worsening motor function and psychological disturbances, with a significant shortening of life expectancy after the disease is diagnosed. Treatments are urgently needed, and we believe that the Isis approach in combination with Roche's brain shuttle represent one of the most advanced programs targeting the cause of HD with the aim of slowing down or halting the progression of this disease."

Shafique Virani, Global Head Neuroscience, Cardiovascular & Metabolism at Roche Partnering, added: "Central to the partnership is Roche's brain shuttle program, which we see as highly complementary to Isis' drug development work. This dual track development program ensures whichever candidate compound proves to be most promising -- Isis' lead target or Roche's brain shuttle version -- can be taken forward to pivotal clinical trials."

"We are pleased to be working with Roche, a global leader in drug development with significant experience in developing and commercializing drugs to treat neurological diseases. We believe that Roche's expertise in developing CNS drugs, along with their clinical development experience, will greatly enhance our development efforts for this program and allow us to move forward more rapidly. In addition, by utilizing Roche's brain shuttle technology with our antisense drug discovery capabilities, we have the potential to significantly improve the therapeutic potential for this program," said B. Lynne Parshall, Chief Operating Officer of Isis. "By partnering our more complex and nuanced research and development programs earlier in development, like our Huntington's disease CNS program, we add value and resources with partners that bring unique benefits."

"We are excited to be working with Roche," said Frank Bennett, Senior Vice President of Research at Isis. "We believe our mature antisense drug discovery platform is a perfect fit for Roche's neuroscience franchise, and we anticipate a fruitful collaboration to advance our pre-clinical compounds."

CHDI Foundation, a non-profit foundation exclusively dedicated to the development of therapies that slow the progression of HD, provided financial and scientific support to Isis' HD drug discovery program through a development collaboration with Isis. CHDI's support has enabled Isis to make significant progress in discovering a drug to treat HD. Together Isis and CHDI demonstrated that antisense compounds can be used to inhibit the production of HTT protein in both brain and peripheral tissues, and that the inhibition of normal HTT protein was well tolerated. Over time, CHDI will be reimbursed for its support of Isis' program out of the milestone payments received by Isis. CHDI will receive $1.5 million associated with the signing of the Roche agreement. CHDI will continue to provide advice to Isis and Roche on the development of antisense drugs to treat patients with HD.

Isis also recognizes the tremendous benefit provided to its HD program by its academic collaborators, Drs. Don Cleveland at the Ludwig Institute, University of California San Diego and David Corey at University of Texas Southwestern. These collaborators have been instrumental in Isis' early preclinical work demonstrating that antisense drugs can inhibit the HTT protein and produce activity in animal models of disease.



"Totgesagte leben länger" heißt es so schön. Nach dem jahrelangen Abgesang der RNA-Technologien wie Antisense und RNAI scheint der ganze Sektor vor einer neuen Boomphase. Einige Pharmaunternehmen wie AstraZeneca, Biogen Idec, GSK und Roche sind sich bereits am positionieren, die Anzahl der Deals im RNA-Bereich ist schon beachtlich.

Die Kursentwicklung bei ISIS ist durch die vielen kleineren Deals (aber durchaus mit Blockbusterpotential ) und News sehr erfreulich dabei kommen die wirklichen Big-News erst in den nächsten Monaten.

Als nächstes sind die Phase II-Ergebnisse von ISIS-CRPrx in der Indikation RA "rheumatoid arthritis " zu erwarten. Das C-reactive protein (CRP) ist ein Biomarker. Das CRP wird als unspezifischer Entzündungsparameter unter anderem zur Beurteilung des Schweregrades entzündlicher Erkrankungen herangezogen und tritt u.a. bei Herzkrankheiten und allen möglichen Autoimmunkrankheiten in erhöhter Konzentration auf. In Phase I an gesunden Patienten wurde die CRP-Konzentration dosisabhängig wie erwünscht herabgesetzt. Ich denke die Herabsetzung der CRP-Konzentration wird auch in den ersten beiden Studien RA und Atrial Fibrillation erfolgen. Die Frage wird sein, ob die reine Herabsetzung des CRP-Wertes auch einhergeht mit einer Verbesserung der klinischen Symptome. Sollte die Frage bejaht werden wartet ein 20 MRD $ Markt in den zahlreichen Indikationen. Die Pharmaindustrie wird Schlange stehen!

Als nächstes folgen Mitte des Jahres die Phase II-Daten von ISIS-APOCIII. Die Auswertung der Daten müsste bereits seit Anfang Februar am Laufen sein. Wie bereits in früheren Kommentaren erwähnt sehe ich APOCIII als Kandidat mit dem größten Marktpotential.

Die Phase II-Daten vom Thrombosemedikament ISIS-Faktor XI gegen Ende des Jahres bergen auch das Potential die aktuelle Marktkapitalisation zu verdoppeln.

Die zahlreichen sonstigen zu erwartenden News sind da schon fast zu vernachlässigen!



cristrader

[Stoxtrayder]

hm, bei DEN Aussichten wundert es mich immer wieder, dass sich Big Pharma noch nicht eingekauft hat bzw. den Laden nicht komplett übernommen hat?! Wie steht es dieszbezüglich bei ISIS mit der Aktionärsstruktur aus? Gibt es da Hinweise im Netz?

hoffentlich gibt es keine Übernahme, meine Aktien werde ich unter 50$ nicht hergeben...

[cristrader]

Hallo,

also in ca. 2 Jahren mit ca. 9-10 Phase III/15 Phase II-Medikamenten und nach Verpartnerung von APOCIII, Factor XL, CRP und den drei Diabetes-Medikamenten also ab Kursen im dreistelligen Bereich ist eine feindliche Übernahmeschlacht durchaus erwünscht! .

Zur Investorenstruktur: Sanofi/Genzyme hält seit dem Kynamro-Deal 5% der Aktien. Der größte Investor ist die größte Fondgesellschaft der Welt (Fidelity) mit ca. 15% . Eine einvernehmliche Übernahme wird es m.M. nicht so schnell geben. ISIS ist nicht an einer Übernahme interessiert und hat bewusst seine Partnerschaften breit gestreut. Mit Sanofi, GSK, BiogenIdec, AstraZeneca und Roche gibt es zumindest genug Involvierte die der Konkurrenz ISIS nicht zu einem Schnäppchenpreis überlassen werden.

[cristrader]

Wow! Vertex steigert AH seine Marktkapitlisierung um mehr als 5 Mrd. $ und das nur wegen eines Medikamentes mit positiven Phase II-Daten.

ISIS hat bis Ende 2013/Anfang 2014 Phase II und Phase III-Daten von 9 verschieden Medikamenten angekündigt.

[cristrader]

Antwort auf Beitrag Nr.: 44.465.209 von cristrader am 18.04.13 23:17:41

BMO Capital Maintains Outperform on Isis Pharmaceuticals, Inc., Raises PT to $31.00

Juan Lopez, Benzinga Staff Writer
April 19, 2013 7:47 AM

[cristrader]

Antwort auf Beitrag Nr.: 44.469.893 von cristrader am 19.04.13 14:34:52

Neues Jahreshoch!

UPDATE: BMO Capital Markets Raises PT on Isis Pharmaceuticals Following Development Head Meeting
11:00a ET April 19, 2013 (Benzinga)

In a report published Friday, BMO Capital Markets analyst Jim Birchenough reiterated an Outperform rating on Isis Pharmaceuticals (NASDAQ: ISIS), and raised the price target from $22.00 to $31.00.

In the report, Birchenough noted, “The BMO Capital Markets US biotechnology team hosted a meeting this week with Isis Pharmaceuticals SVP of Clinical Development Dr. Richard Geary. Focus of the meeting was on a burgeoning pipeline of antisense oligonucleotide (ASO) therapeutics following recent approval of its first ASO therapeutic KYNAMRO. With 28 different ASO therapeutics in development, primary focus was on key late stage programs including wholly owned ISISApoC3-Rx for severe triglyceride elevation as well as partnered programs for ISIS-SMN-Rx for spinal muscular atrophy (SMA) and TTR associated familial amyloid polyneuropathy (FAP).”

Isis Pharmaceuticals closed on Thursday at $19.41.

[Stoxtrayder]

Schei...benkleister. einerseits finde ich es natürlich echt fein, dass meine Anteile stetig steigen, andererseits wollte ich nochmals nachlegen.

das mit Vertex ist ja echt ein Ding.

[cristrader]

Antwort auf Beitrag Nr.: 44.472.785 von Stoxtrayder am 19.04.13 19:48:38

Persönlich glaube ich das der richtige Kursschub jetzt erst bevorsteht, obwohl charttechnisch ein Kursrücksetzer durchaus wahrscheinlich ist. ISIS mit seiner jetzigen Marktkap. von 2 Mrd. und einem Kurs über 20 $ hat jetzt eine kritische Masse erreicht die zahlreiche neue Institutionelle anlockt. Bei Biotechs mit einer Marktkap. zwischen 1-10 Mrd. hat ISIS mit seinen 28 Medikamentenprogrammen sowieso die vielversprechenste Pipeline (oder kennt jemand eine ähnliche Pipeline?). Mein Kursziel ist dreistellig innerhalb der nächsten 2 Jahre Aber ich bin gewiß nicht objektiv, daher muss sich jeder selbst informieren und seine eigene Schlüsse ziehen!

[cristrader]

ISIS Pipeline

[cristrader]

Sorry Pipeline ist nicht ganz auf den neuesten Stand. FXI z.B. befindet sich in Phase II und wird noch dieses Jahr die Daten liefern. Aber als grober Überblick reichts wohl

[Stockfinder]

wenn ich sehe wo Vertex steht bzw. heute explodiert ist und auch wenn es kaum möglich ist beide Firmen miteinander zu vergleichen, dann müsste ISIS bei 14 Mrd. stehen und nicht Vertex. Jedoch ist es jedem Vertex-Aktionär natürlich gegönnt!

[Stoxtrayder]

naja, Morphosys hat auch einiges in der Pipeline. (s.Thread) dürften auch so an die 30 sein...?!

da warte ich ab, bis das Teil nochmals unter 30 zu haben ist, dann lege ich mir da auch (wieder) welche zu. vielleicht wenn der Gesamtmarkt noch etas schwächelt...btw. Mologen halte ich auch für sehr erfolgversprechen. Phase 3, da steht evtl. diese Jahr noch ein Auslizenzierung bevor!?

aber wir sind ja hier im Isis-Thread...

[cristrader]

Die Phase II-Daten von ISIS-CRPrx stehen in den nächsten 12 Wochen an. Hier mal ein paar interessante Statements zum Potential.

The next is CRP
And we know that we have the only selective CRP inhibitor to ever work in man. We showed a 70% reduction of CRP in normal volunteers. And we have two studies that will unblind this year, both tremendously important to us.


CRP is a well-known cause of inflammation and has been associated with cardiovascular and numerous other inflammatory
diseases and conditions. It is also a very controversial target like cholesterol was in the 1960s.
So two appropriate questions come to mind. First, why are we willing to risk R&D spending on such a controversial target? And
second, how will we develop the drug to mitigate the risks associated with a non-validated target?
We think we have great answers to both questions. First, we believe the risk is justified by the large opportunity. Inhibiting CRP
may result in significant benefits in many diseases, giving this drug a very large commercial potential. Second, we can mitigate
the risk of a non-validated target by identifying low-risk clinical opportunities in Phase 2 to prove the therapeutic value of CRP
inhibition. Because CRP is a complex glycoprotein, it is difficult to develop a small molecule drug to inhibit it. Therefore, if we
prove the opportunity, it is unlikely that there will be any meaningful competition.

In fact, we believe that the list of potential diseases that could be treated by reducing CRP levels is enormous, and our initial
clinical focus will not be in cardiovascular disease. In Phase 2 we will initially evaluate whether lowering CRP provides benefit
to patients in whom elevated CRP levels are associated with worse outcomes where we can show early and definitive proof of
concept, for example, in multiple myeloma or rheumatoid arthritis, late stage renal disease, organ transplants and atrial fibrillation.
From these studies we believe we can answer the question, can reducing CRP produce therapeutic benefit?
After we have a great deal of experience in patients in these other diseases, only then will we examine the role of reducing CRP
in chronic cardiovascular disease. Therefore, in Phase 2 we plan to explore several potential indications that are the most likely
to provide early evidence of clinical benefit.

Now what happens after Phase 2?
Remember that our strategy is to license our drugs after Phase 2 proof of concept.
Nevertheless,
before embarking on a program, we think carefully about Phase 3 and beyond. We believe that our Phase 2 program on CRP
should identify some disease, perhaps like
multiple myeloma
or end stage renal disease
or rheumatoid arthritis
that will be
amendable to relatively straightforward Phase 3 programs.
Others like some of the
cardiovascular indications
could require
outcome studies.
So we expect years of growth and valuable for our CRP inhibitor during which we will add new indications as
we and our partners complete the phased or staged development of our drug.
This will continue long after initial market launch.
We believe that we could find an ever increasing number of diseases to treat,
resulting in a remarkable commercial opportunity.

[cristrader]

Hallo,

nach der kräftigen Korrektur diese Woche geht es nächste Woche hoffentlich wieder bergauf.

Die Quartalzahlen waren prima mit einem Verlust von nur 1,7 Mio $ und aktuellen Barmitteln von 371 Mio.$. Gleichzeitig kam die völlig überraschende Nachricht einer Kapitalerhöhung um ca. 186 Mio $ (10,35 Mio Aktien zu 19$ (effektiv ca. 18$ nach Kosten))also eine Verwässerung um ca. 10%. Die KE wird von einem Konsortium aus Banken und Investmenthäusern unter der Leitung von Goldman Sachs und JP Morgan durchgeführt und wird wahrscheinlich am 15 Mai abgeschlossen sein. Mit Goldman Sachs und JPM haben wir uns wohl Coverage der beiden wichtigsten Investmenthäuser teuer erkauft! Die KE wurde mit einem Strategiewechsel begründet. ISIS will künftig geeignete Pipelinekandidaten länger in Eigenregie entwickeln und z. B. APOCIII alleine bis zur Zulassung zu führen, um mehr an künftigen Einnahmen zu partizipieren. Mittel- und langfristig gesehen absolut der richtige Schritt!

Was mich maßlos ärgert ist, das Stan Crooke in den letzten beiden Jahren immer und immer wieder ausdrücklich betonte, das ISIS keine KE mehr durchführen wird und uns Shareholder schlichtweg angelogen hat. Das das komplette Management in den letzten 14 Tagen massive Insiderverkäufe im Wissen der KE zu Kursen über 22$ tätigte macht das Ganze noch schlimmer.

Die Pressekonferenz fand ich auch nicht sonderlich positiv. Fragen zur KE wurden abgeblockt und da fast alle Analystenhäuser auch an der KE teilnahmen wurden auch aus rechtlichen Gründen kaum Fragen gestellt.

Der Kursrutsch kam meiner Ansicht nicht wegen der Dilution sondern wegen der Fragen und Zweifel die die KE und die Pressekonferenz hervorrufte.
- ISIS Management glaubt wohl selbst nicht mehr an einen kommerziellen Erfolg von Kynamro

- Die Statements im Bezug auf ISIS-CRPrx (Phase II- Daten in RA kommen in Kürze) sind weit weniger enthusiastisch als noch vor einigen Monaten. Da intern die Ergebnisse sicher bekannt sind und jetzt versucht wird die Erwartungen zu dämpfen, indem sie lediglich "hoffen" zumindest einen leichten Trend zur Besserung in den Indikationen zu erreichen, schürt zumindest Zweifel. Die Statements bezüglich APOCIII dessen Phase II-Ergebnisse intern ebenfalls schon bekannt sein müssen sind dagegen weitaus euphorischer. (irgendetwas stimmt mit W-O heute nicht, kann gar keine Links oder Textpassagen reinkopieren)


Nun mittel- und langfristig ändert aber nicht an der Story. ISIS ist eines der am besten kapitalisierten Biotechs mit der umfangreichsten Pipeline und der wohl effektivsten Medikamentenplattform. Bin gespannt auf die Analystenempfehlungen von Goldman Sachs und JPM und natürlich den kommenden Phase II-Daten.

cristrader

[cristrader]

Transcript:

http://seekingalpha.com/article/1412641-isis-pharmaceuticals…

Statement ISIS-CRPrx



Nicholas Bishop - Cowen and Company
Okay, great. Next we are then on the CRP program, I understand you could explain a little bit about the outcomes you are looking at with that you believe would, which proof of concept in an indication like RA by assuming don’t expect a significant ACR20 responses. So, just what the outcomes you are looking out there?

Stan Crooke - Chairman & CEO
The primary endpoint in all the Phase 2 trials is CRP reduction of course. But rheumatoid arthritis study we are looking at slightest symptoms of rheumatoid arthritis including all components that make up ACR20 to ACR50s joint count of physician assessment, patient assessment. And what we hope to see is at least trend in a favor of the drug with a correlation between the reduction in CRP and suggestions of improvement and disease. Obviously, as their study progresses and complete we will be able to analyze data and present it.

We are looking at several doses with top dose 300 to 400 milligrams a week. So another thing that we will be looking at is tolerability. Remember that this CRP drug is exemplary of this new crop of generation 2 drugs. Same chemistry as KYNAMRO and earlier generation 2 drugs for the better screening, advances and screening have allowed us to generate drugs that appear to be at least twice as potent as KYNAMRO and significantly better tolerating. So another thing that (I’m crazy) to pay attention to is, how we feel about the side effect profile of the drug?

Now, the atrial fibrillation study which is in progress and will be reported this year, but sometime next year, is similar and they will be looking at the ability to reduce CRP in patients who have elevated CRP and we will be monitoring these patients with – (inaudible) patients who have such severe recurrent atrail fibrillation that they have pacemakers. And so we are monitoring the incidence of requirements for pacing prior to drug during drug treatment and then after drug is discontinued in that study. And again, we hope for, as these are notably small Phase 2 trial, at least trends that support the drug maybe active in the treatment of that problem.

Statement KE:
B. Lynne Parshall - Director and COO
"With the successful performance for our technology in pipeline, strong collaborations in place and numerous reason in near-term clinical milestones we think now is the right time to take the next step in evolving our business strategy. We plan to do this by keeping some of our drugs into late stage development including into or even through Phase 3 clinical studies thereby creating a more valuable data package and derisking remaining activities to move the drug on the market in turn allowing us to obtain an even greater portion of the commercial revenue when we eventually partner them.

We have number of drugs in our pipeline that we’re considering keeping longer and these were generally fits in common criteria. We started to focus on smaller orphan or orphan like diseases in which we think antisense technology has the opportunity to offer unique benefit but we focus when indications were smaller less expensive and a faster clinical trials can be conducted. Preferability drugs will focus on indications in which Phase 1 and Phase 2 data may predict the results of Phase 3 result. That’s allowing the program to be derisked early in development.

In other words, features will be evaluated in clinical trials we can manage well and in which we expect to obtain the most information possible early to guide later stage development.

In addition to this clinical focus and areas in which we developed significant internal expertise to help ensure success of the clinical programs. For example, we consider drugs for therapeutic areas for which we not only understand the disease, but also notably in physicians who can work with us in conducting the trials. A good example of the drug meeting these criteria is ISIS-APOCIIIRx. This is antisense drug designed to patients with severely alleviate triglyceride. With KYNAMRO we gained valuable experience in designing and conducting clinical trials and with the disorders. And the same list of specialists that we work with to develop KYNAMRO will also be working on to develop ISIS-APOCIIIRx. In Phase 1 clinical trial, we showed that ISIS-APOCIIIRx significantly lower both APOCIII and triglycerides. We hope to replicate this data and patients with severely elevated triglycerides in our two ongoing Phase 2 study. It’s under the theory of the disease and the last of the triglycerides lowering agents for the patient population, we believe we will be able to move ISIS-APOCIIIRx rapidly through Phase 3 clinical study on our own because the patient population is at severe risk for both cardiovascular events and pancreatis, we also believe that a rapid less expensive registration pathway is possible."

[Stoxtrayder]

@cristrader:

Wie bewertest du das angekündigte Puplic Offering? Isis hat doch mit mehr als 300Mio.$ eigentlich genügend Cash in der Kasse...?! Kann man das mit einer Art Kapitalerhöhung vergleichen bzw. hat man als Aktionär hier in Deutschland Chance, an die Stücke ranzukommen?

Schade, wollte letzte Woche eigentlich bei knapp 19$ nochmals nachkaufen, sind ja schon wieder über der 20$-Marke.

[cristrader]

Antwort auf Beitrag Nr.: 44.656.893 von Stoxtrayder am 16.05.13 22:12:22

Hallo Stoxtrayder,

in meinem vorletzten Posting habe ich meine Verärgerung bereits deutlich gemacht. Insbesondere die ständige Lügerei von Stan Crooke nie wieder eine Kapitalerhöhung vornehmen zu müssen ärgert mich maßlos.

Den Strategiewechsel, indem ISIS künftig ausgesuchte Kandidaten länger in Eigenregie durch die klinische Entwicklung bis zur Marktzulassung führt, wird sich mittel- bis langfristig massiv positiv auswirken. Isis will einen höheren Anteil an künftigen Erlösen dazu muss auch etwas Risiko eingegangen werden. Auf der Webseite gibt es eine neue Webcast Präsentation bezüglich des Public Offering und des Strategiewechsels. Crooke erwähnt dabei wieder das das Interesse von Pharmaseite an Partnerschaften auf Alltimehigh sei.

Hier die Links zu den Slides und zum Webcast:

http://media.corporate-ir.net/media_files/IROL/22/222170/Inv…

http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-EventD…


Die Teilnahme an KE ist den beteiligten Investmenthäusern vorbehalten. Letzte Woche gab es aber die Gelegenheit günstiger als Instis Aktien zu erwerben.

[cristrader]

APOCIII News!

Phase II Daten der Studie die eigentlich erst Ende des Jahres fällig waren sind raus! Meine Juli Optionen freuen sich!

Isis Reports Phase 2 Data on ISIS-APOCIII Rx Showing Significant Reductions in Triglycerides and APOC-III in Patients with High Triglycerides and Type 2 Diabetes

Improvements in glucose control and insulin sensitivity also observed
Conference call webcast and slide presentation Monday, June 24, 8:30 a.m. ET at www.isispharm.com


CARLSBAD, Calif., June 23, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (ISIS) announced that data from the Phase 2 study of ISIS-APOCIIIRx in patients with high triglycerides and type 2 diabetes were presented today at the American Diabetes Association Scientific Sessions in Chicago. In this study, patients treated with ISIS-APOCIIIRx experienced an 88 percent reduction in apolipoprotein C-III (apoC-III), a 72 percent reduction in triglyceride levels, a 40 percent increase in high-density lipoprotein cholesterol (HDL-C), the 'good' cholesterol, and improvements in other atherogenic lipid parameters. In addition, patients dosed with ISIS-APOCIIIRx showed consistent trends toward enhanced insulin sensitivity with improvements in multiple measures of glucose control. Isis is also evaluating ISIS-APOCIIIRx in a separate Phase 2 study in patients with moderate to severe high triglycerides and plans to report data from this study this summer.

"Patients with high levels of triglycerides are at a significant risk for cardiovascular disease and stroke. Because high triglyceride levels are also associated with obesity and insulin insensitivity, reducing apoC-III and triglycerides in high-risk patients, like type 2 diabetic patients, may lead to improved insulin sensitivity and improvement of metabolic syndrome," said Joseph L. Witztum, M.D., professor of medicine, University of California, San Diego. "The data presented today on ISIS-APOCIIIRx are very encouraging and unique in that there is a significant and substantial reduction in both apoC-III and triglyceride levels with a significant increase in HDL and improvements across the board in the overall lipid parameters, including non-HDL-C. In addition, unlike many available triglyceride-lowering therapies, including diet, ISIS-APOCIIIRx did not raise LDL-C in these patients. There is no other drug in development that demonstrates the potential for such a broad therapeutic profile. The dramatic effect of ISIS-APOCIIIRx on all of these parameters could translate into significant benefit to many patients, including patients with high triglycerides and type 2 diabetes."

The Phase 2 study of ISIS-APOCIII­Rx was a blinded, randomized, placebo-controlled 13-week study designed to assess the safety and activity of ISIS-APOCIIIRx in patients with high triglycerides levels (between 200 and 500 mg/dL) and type 2 diabetes. After only 13 weeks of dosing, robust and prolonged, statistically significant mean reductions of 88 percent from baseline in apoC-III levels (pRx demonstrated a rapid, prolonged and statistically significant mean increase in HDL-C of 40 percent from baseline (p

In addition, consistent improvements in HbA1c and other measures of glucose control, including serum fructosamine and glycated albumin, were observed in patients dosed with ISIS-APOCIIIRx. The effects of ISIS-APOCIIIRx observed on measures of glucose control were in addition to those achieved with each patient's existing therapeutic regimen of metformin. Improvements in indicators of insulin sensitivity were also observed in patients suggesting that inhibition of apoC-III could improve insulin sensitivity in patients with high triglycerides and type 2 diabetes. ISIS-APOCIIIRx demonstrated a good safety profile in the study and was well tolerated in all subjects with no discontinuations, no clinically meaningful elevations in liver enzymes, no flu-like symptoms, no significant adverse events, and a low incidence of mild injection site reactions which were infrequent and typically resolved within a day or two.

"Our focus is to bring ISIS-APOCIIIRx to the market for patients with severe hypertriglyceridemia. These are patients who cannot reduce their triglycerides to safe levels with currently available medicines. We plan to report data from our ongoing Phase 2 program in very high triglyceride patients later this summer evaluating ISIS-APOCIIIRx in combination with fibrates and as a monotherapy," said Richard Geary, Ph.D., senior vice president of clinical development at Isis. "In the study we are reporting today, we observed rapid and prolonged reductions of apoC-III, triglycerides and other lipid parameters, as well as improvements in glucose control and insulin sensitivity. These data suggest that ISIS-APOCIIIRx could provide therapeutic benefit to patients with high triglycerides who are insulin insensitive, including patients who are obese or have type 2 diabetes. In addition, the positive effect of ISIS-APOCIIIRx on all atherogenic lipid parameters measured and the observed increase in HDL, significantly enhances the potential profile of the drug."

In this study, 11 patients were randomized 2:1 to receive a 300 mg dose of ISIS-APOCIIIRx or placebo via weekly subcutaneous injections for 13 weeks. Patients entering the study had a mean apoC-III level of 14.3 mg/dL, a mean triglyceride level of 259 mg/dL and a mean HDL level of 43.4 mg/dL.

ISIS-APOCIIIRx is an antisense drug that targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates. Humans with elevated levels of ApoC-III have increased dyslipidemia associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.

Conference Call
At 8:30 a.m. Eastern Time tomorrow, June 24, 2013, Isis will conduct a live webcast and slide presentation conference call to discuss the positive Phase 2 data presented today at the American Diabetes Association. Interested parties may listen to the call by dialing 866-652-5200, or access the webcast with or without audio at www.isispharm.com. A webcast replay will be available for a limited time at the same address.


cristrader

[cristrader]

"Patients with high levels of triglycerides are at a significant risk for cardiovascular disease and stroke. Because high triglyceride levels are also associated with obesity and insulin insensitivity, reducing apoC-III and triglycerides in high-risk patients, like type 2 diabetic patients, may lead to improved insulin sensitivity and improvement of metabolic syndrome," said Joseph L. Witztum, M.D., professor of medicine, University of California, San Diego. "The data presented today on ISIS-APOCIIIRx are very encouraging and unique in that there is a significant and substantial reduction in both apoC-III and triglyceride levels with a significant increase in HDL and improvements across the board in the overall lipid parameters, including non-HDL-C. In addition, unlike many available triglyceride-lowering therapies, including diet, ISIS-APOCIIIRx did not raise LDL-C in these patients. There is no other drug in development that demonstrates the potential for such a broad therapeutic profile. The dramatic effect of ISIS-APOCIIIRx on all of these parameters could translate into significant benefit to many patients, including patients with high triglycerides and type 2 diabetes."


Sind erst Zwischenergebnisse von nur 11 Patienten, aber wenn die bestätigt werden ...
. There is no other drug in development that demonstrates the potential for such a broad therapeutic profile.

Wie viele Diabetes Patienten gibt es weltweit

[Stockfinder]

habe letzte Woche noch von Sarepta in ISIS zusätzlich umgeschichtet - hat sich als richtig erwiesen. ISIS wird die nächste Biotech-Pharma-company mit Multi-Milliarden-Potenzial und Umsatz! Kursziel 100 $

[cristrader]

Präsentation war riesig. Die Ergebnisse sind geradezu sensationell. Wenn diese Werte bestätigt werden haben wir ein universell wirkendes Medikament im Bereich Herz-Kreislauf und Diabetes. Diese Studie war an Diabetes-Patienten mit Trigyzerinwerten von 200-500mg/dl. Diese Patientenzahl geht in die zig-Millionen. In den nächsten Wochen sehen wir noch zwei Phase-II Studien von Hochrisikopatienten mit bis zu 2000mg/dl, eine Gruppe mit Kombinationstherapie mit Fibraten und eine nur mit APOC3Rx. Die Patientenzahl dieser Studien ist deutlich höher.


BMO Capitaltoday maintained an Outperform rating on ISIS Pharmaceuticals (NASDAQ: ISIS) with a price target of $31.00. Analyst Jim Birchenough called recent Phase 2 data on ISIS- APOCIII in Type 2 diabetes "stunning." The findings are well beyond expectations and suggest unprecedented treatment benefits, he said.





Needham & Company analyst Chad Messer reiterated a Buy rating and raised his price target on ISIS Pharmaceuticals (NASDAQ: ISIS) from $26 to $29 following "impressive" ISIS-APOCIIIRx data which de-risks the key program.

Messer comments, "Over the weekend, ISIS presented data from the first of 3 Phase II studies of ISIS-APOCIIIRx. As previously observed in healthy volunteers, ISIS-APOCIIIRx treatment resulted in impressive reductions in APOCIII and triglycerides as well as other beneficial lipid changes. Importantly, in the current study ISIS-APOCIIIRx improved measures of glucose control and insulin sensitivity in a diabetic population. ISIS will initiate a pivotal study next year in patients with very elevated triglycerides and intends to complete the study before seeking a partner."

The analyst believes ISIS-APOCIIIRx is potentially one of the largest of many drivers for ISIS shares.


Freue mich schon morgen auf die Präsentation bei der Jahreshauptversammlung.

[Stoxtrayder]

Strike!!!

seeeeeehr schön! mit meinem Durschnitts-EK von 11 EURO mittlerweile 100% im Plus. das wird bein erster Tenbagger...unter 110 EURO gebe ich keine Aktie her! Eigentlich müsste man sogar (morgen/die Tage über nachkaufen, was das Zeug hält). ich tippe, dass wir diese Woche die 40$-Marke sehen werden! wer tippt dagegen?

[cristrader]

Isis explains reason behind stock offering

By Bradley J. Fikes5:51 p.m.June 27, 2013



CARLSBAD — Isis Pharmaceuticals held an unorthodox secondary stock offering in May. It brought Isis $174 million. But the biotech company didn’t need the money; it had $372 million in cash as of March 31. Moreover, offerings dilute shareholder value.

This week, the biotech company revealed the story behind it.

Isis now has the money to develop a promising cardiovascular drug to a more advanced stage before bringing in a partner to sell the drug, CEO Stanley T. Crooke said. Delaying a deal allows Isis to demonstrate more of the drug’s potential, and in the long run, make more money.

“It’s the most important asset in the company,” Crooke said.
Called APOCIIIRx, the drug is being tested in patients with very high levels of triglycerides, a risk factor for heart disease. Mid-stage results were released Sunday at the American Diabetes Association meeting in Chicago. Patients experienced dramatic drops in triglycerides, and improvement in cholesterol levels.

Impressed investors sent Isis shares soaring 29 percent Monday. The next day, Isis held its annual shareholders’ meeting.

There’s a great need for more effective cardiovascular drugs. Heart disease is the leading cause of death in the United States, killing nearly 600,000 in 2010, according to the U.S. Centers for Disease Control and Prevention. Coronary artery disease, the most common kind, costs the U.S. nearly $109 billion annually.

While the drug is being tested on patients with very high triglycerides, the potential market could be much wider, Crooke said in an interview after the meeting.

“This is a drug that clearly could bring benefit to a much broader group of patients than that,” Crooke said. “We have an exciting follow-on (study) we think will be even better.”
That study will be released later this summer.In 11 patients with severe hypertriglyceridemia, APOCIIIRx lowered by 88 percent the level of apolipoprotein C-III, a component of the “bad” LDL cholesterol. They also experienced a 72 percent reduction in triglycerides, and a 40 percent increase in the “good” HDL cholesterol.

Moreover, the drug increased sensitivity to insulin. This indicated a potential use for Type 2 diabetes, another blockbuster market.
Results were “well beyond expectations and suggest an unprecedented treatment benefit in type 2 diabetics with (high cholesterol levels),” said Jim Birchenough, a BMO Capital Markets analyst quoted by Reuters.

The drug showed no sign of causing liver damage, Isis said. That worry reduced the market potential for Kynamro, another Isis cardiovascular drug. Kynamro is being sold by Isis marketing partner Genzyme for patients with a rare genetic form of severely high cholesterol levels.

Crooke said some risk was always inherent in Kynamro’s mechanism of action. The drug acts on a genetic target called APO B100 to block production of a protein in the liver that carries cholesterol and other blood fats. Inhibiting that protein, part of LDL cholesterol, causes fat to build up in the liver.

“With APOCIII, all the data say the target is ideal,” Crooke said. “You can live without it, people do, there doesn’t appear to be any deleterious effects from reducing it. And you haven’t seen (all) the data yet. We’ll give you some more data this summer.”

[Stoxtrayder]

na da war ich mit meinen 40$ doch etwas zu euphorisch...

hätte gedacht, dass diese genialen Ergebnise nach ca. 30% Kursplus (doch) noch höhere Wellen schlagen. wird schon noch kommen...

@christrader: Crooke hat dieses Woche ja doch ein paar Aktien versilbert. Kann man ihm ja eigentlich nicht übel nehmen, oder!? Was ist deine Meinung dazu?
Hast du dich schon in der Präsenation (der HV) einlesen können? Oder gibt evtl. es einen Bericht im Netz?

btw, habe bei Morphosys doch wieder letzte Woche eine kleine Posi. aufgebaut. am Tag der Celgene-News...da gehe ich (auch) von 3-stelligen Kursen (wie bei ISIS) in den nächsten 1-2 Jahren aus! Deine Meinung?

Danke und noch einen schönen Sonntag!

[cristrader]

Hallo Stoxtrayder!

Habe mir die Präsentation angehört . Transcript http://seekingalpha.com/article/1521302-isis-pharmaceuticals…

Alles in allem eine gute Präsentation, aber für mich nichts wirklich Neues dabei. Leider haben die Insiderverkäufe das Momentum etwas zerstört. Das mit den Insiderverkäufen hat leider Tradition bei ISIS. Das ISIS Management hat seine Aktienoptionen eigentlich schon immer sofort versilbert, selbst zu Kursen von 6-7 $ gab es in den letzten Jahren immer wieder massive Insiderverkäufe (schön blöd).

Die APOCIIIrx Daten sind einfach nur phänomenal. Wenn diese Daten nur annähernd in weiteren Studien bestätigt werden hat APOCIII das Potential das umsatzstärkste Medikament überhaupt zu werden. In den nächsten Wochen werden noch zwei Phase II-Ergebnisse mit deutlich grösseren Patientengruppen veröffentlicht und persönlich erwarte ich mind. eine Kursverdopplung nach deren Verkündung. Das im Laufe des restlichen Jahres noch etwa 10 Phase II-Daten anderer Pipelinekandidaten fällig werden ist schon fast vernachlässigungswert. Das schöne am Target APOCIII ist das der Mensch es nicht braucht und somit das Fehlen keine neg. Auswirkungen hat. In der Tat gibt es Bevölkerungsgruppen die genetisch bedingt nur ein einen geringen Bruchteil von APOCIII in sich tragen und statistisch gesehen ein erheblich geringeres Vorkommen an Herzkrankheiten u.ä. aufweisen.


Morphosys ist das mit Abstand beste deutsche Biotech und wird seinen Weg machen.

Grüsse cristrader (ohne H, cris kommt von einem meiner ersten Biotechinvestments Curis )

Crooke said. “We have an exciting follow-on (study) we think will be even better.”

[cristrader]

Positive Phase II APOCIII !!!
http://finance.yahoo.com/news/isis-reports-phase-2-data-1100…
Isis Reports Phase 2 Data on ISIS-APOCIII Rx Showing Significant Reductions of ApoC-III and Triglycerides in Patients With High Triglycerides Taking Fibrates

Reductions of up to 64 percent in Triglycerides Achieved
Majority of Patients Reached Triglyceride Levels Below 150 mg/dL
Conference call webcast and slide presentation Monday, July 22, 8:30 a.m. ET at www.isispharm.com

PR NewswirePress Release: Isis Pharmaceuticals, Inc. – 33 minutes ago...

CARLSBAD, Calif., July 22, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (ISIS) announced data from a Phase 2 study of ISIS-APOCIIIRx in patients with high to severely high triglycerides on stable doses of fibrates. In this study, patients treated with ISIS-APOCIIIRx experienced reductions of up to 70 percent in apolipoprotein C-III (apoC-III) and up to 64 percent in triglycerides. In addition, patients treated with ISIS-APOCIIIRx experienced an up to 52 percent increase in high-density lipoprotein cholesterol (HDL-C), the 'good' cholesterol, and an up to 77 percent reduction in apoC-III-associated very low-density lipoprotein (VLDL) particles. Isis is also evaluating ISIS-APOCIIIRx in this Phase 2 study as a monotherapy in patients with severely high triglycerides and plans to report these data at the European Society of Cardiology on August 31 in Amsterdam.

The Phase 2 study of ISIS-APOCIII­Rx was a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of ISIS-APOCIIIRx. The portion of the study reported today was conducted in patients with high to severely elevated triglyceride levels (between 225 and 2,000 mg/dL) on stable doses of fibrates.

Table 1: ISIS-APOCIIIRx Produced Statistically Significant Reductions of Triglycerides, ApoC-III and ApoC-III Associated VLDL in a Phase 2 Study in Patients With High Triglyceride Levels Treated With Stable Doses of Fibrates. Mean % Changes From Baseline at Primary Endpoint.




Placebo + Fibrate

(n=8)

ISIS-APOCIIIRx 200 mg + Fibrate

(n=8)

ISIS-APOCIIIRx 300 mg + Fibrate

(n=10)


ApoC-III

-2.2%

-59.4% (p

-70% (p


Triglycerides

[# patients achieving

triglyceride level

mg/dL]

-7.7%



[0/8]

-49.7% (p=0.03)



[5/8]

-63.9% (p=0.003)



[7/10]


ApoC-III VLDL

+8.4%

-65.9% (p=0.0006)

-77.4% (p=0.0003)


HDL-C

+5.9%

+47.4% (p=0.02)

+51.8% (p=0.008)


P value = vs. placebo + fibrate.

After 13 weeks of dosing, robust and prolonged, statistically significant mean percent reductions from baseline in apoC-III, triglycerides and VLDL-associated apoC-III particles were observed in both dose cohorts. Furthermore, patients treated with ISIS-APOCIIIRx demonstrated a rapid, prolonged and statistically significant mean percent increase from baseline in HDL-C in both dose cohorts with no statistically significant increase in low-density lipoprotein cholesterol (LDL-C) or non-HDL-C. The effects of ISIS-APOCIIIRx observed on these lipid parameters were in addition to those achieved with each patient's existing therapeutic regimen of fibrates.

"Patients with very high levels of triglycerides are at significant risk for cardiovascular disease, diabetes, pancreatitis and other complications. For these patients, there are very limited treatment options. Fibrates have been shown to reduce triglycerides; however fibrate therapy is not always effective nor widely used by these patients," said Daniel Gaudet, M.D., Ph.D., from the department of medicine, University of Montreal and scientific director, Genome Quebec Biobank Technology Center. "The data presented today on ISIS-APOCIIIRx are very encouraging because they show that ISIS-APOCIIIRx is additive to fibrates and are consistent with Isis' previous Phase 2 data in patients with moderately elevated triglycerides and type 2 diabetes. In both studies, rapid, robust reductions in apoC-III and triglycerides were observed. The positive effect of ISIS-APOCIIIRx on other key lipid parameters demonstrates the potential for ISIS-APOCIIIRx to provide therapeutic benefit to patients with very high triglycerides."

In this study, 26 patients received either 200 mg or 300 mg dose of ISIS-APOCIIIRx, or placebo via weekly subcutaneous injections. All patients were on stable doses of fibrates with average baseline levels of fasting triglycerides between 282 mg/dL and 457 mg/dL. The three groups of patients were reasonably well balanced in baseline characteristic.

In this study ISIS-APOCIIIRx was found to be generally safe and well tolerated. The most common adverse event (AE) was injection site reactions, which were infrequent and consisted of mild erythema that typically resolved within one to two days. There were no flu-like symptoms, no elevations of liver enzymes greater than three times upper limit of normal, no abnormalities in renal function and no clinically meaningful changes in other laboratory values. There was one patient who, four days after treatment, experienced a transient episode of a rash, low-grade fever, chills and headache, which resolved completely. This event was reported by the investigator as related to treatment, and classified as a serum sickness-like reaction (a serious AE). Subsequent detailed investigations demonstrated that it was not serum sickness.

"We are very encouraged by the two sets of positive data we have reported this summer demonstrating that treatment with ISIS-APOCIIIRx produced highly statistically significant and clinically meaningful reductions in apoC-III and triglycerides, and increases in HDL-C in patients with high triglycerides. In addition, the positive effect of ISIS-APOCIIIRx treatment on lipid parameters, improvements in glucose control and trends toward improvements in insulin sensitivity, suggest that ISIS-APOCIIIRx could have a broad therapeutic profile in addition to triglyceride lowering for patients with severely high triglycerides. We are also pleased with the data reported today. They demonstrate that ISIS-APOCIIIRx is additive to fibrates with robust reductions of apoC-III and triglycerides," said Richard Geary, Ph.D., senior vice president of development at Isis. "We look forward to sharing the results from our ongoing Phase 2 study evaluating ISIS-APOCIIIRx as a monotherapy in patients with severely high triglycerides. In this study, we hope to show that treatment with ISIS-APOCIIIRx in patients with severely high triglycerides also produces significant effects on apoC-III, triglycerides and HDL-C. Following completion of the Phase 2 program, we plan to discuss our Phase 3 plans with regulators and move rapidly into a Phase 3 program next year in patients with severely high triglycerides (greater than 880 mg/dL)."

ISIS-APOCIIIRx is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents. ISIS-APOCIIIRx targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates. Humans with elevated levels of apoC-III have increased dyslipidemia associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.

[Stoxtrayder]

hm, verhaltene (Kurs-)Reaktion auf diese tolle News...was ist Deine Meinung dazu, cristrader?

sell on good news oder nur eine kleine Konsolidierung? Crooke hat ja nochmals die letzten Wochen Anteile verkauft.

btw: was hälst du von Mologen?

[cristrader]

Antwort auf Beitrag Nr.: 45.109.525 von Stoxtrayder am 24.07.13 22:43:46

Hallo Stoxtrayder,

jede Aktie hat mal Phasen der Korrektur und ISIS hat keine Analysten die auch mal den Kurs stützen vielmehr haben die meisten Analysten ISIS Entwicklung total verschlafen. Die Anals von Piper Jaffray z.B. die zum Großteil für das Ausmaß der jetzigen Korrektur verantwortlich sind haben ihr Kursziel von 12$ auf 20 $ angehoben und gleichzeitig von neutral auf underweight geratet und CNBC hat sich voll auf dieses Rating gestürzt und die Abwärtstendenz verstärkt. Das Needham das Kursziel auf 36$ erhöht hat wurde dabei mal kurz unter den Tisch fallen gelassen. Aber die wirklich wichtigen Daten kommen erst am 31.August, nämlich die Patientengruppe bei der auch die Phase III durchgeführt wird.

[Stoxtrayder]

hm, die heutigen News lesen sich ja nicht so gut...hätte gedacht, das kommt kurstechnisch nicht so gut an, hat sich ja dafür ganz gut gehalten.7

nach ca. 20%iger Kurskorrektur müsste man doch wieder ein paar Anteile (nach-)kaufen?!

was meinst Du cristrader?

[Stockfinder]

Weiterer Zukauf auf der 27,60 $ - würde ab 25 $ eine nächste Position kaufen.

Zum Jahresende hin wird es richtig spannend, der 31. August wird ein weiterer Vorgeschmack.

[Stoxtrayder]

gestern nochmals ein paar Stücke dazugekauft. 20%-Korrektur von der Spitze aus gesehen. das sollte es doch gewesen sein!? meine neuer Misch-EK beträgt nun 13 EURO. Langfristig (2-3 Jahre) mein erster Tenbagger? Schön wärs

Vor Morphosys und Mologen anteilsmäßig nun größter Posten im Depot.
Mologen werde ich die nächsten Wochen auch nochmals aufstocken.

[Stockfinder]

habe nun zu 25,20 meine Positionsgröße ausgebaut und vollendet. Zur Zeit sieht es nach einer Bodenbildung um 25 $ aus. Die Pipeline ist und bleibt die wertvollste im Biotech-Sektor überhaupt, der Einstiegszeitpunkt scheint günstig.

[cristrader]

Hallo!

Die Phase2- Ergebnisse der APOCIII Monotherapie in Patienten mit extrem hohen Triglycerinwerten sind raus. Daten können im Prinzip kaum besser sein bin aber nicht sicher ob der Kurs davon profitieren wird. Die Kursentwicklung ist ziemlich irrational und völlig unter Kontrolle einiger Hedgefonds. Es ist für mich nicht nachvollziehbar wie ein Biotech wie Alnylam mit im Prinzip nichts in der Pipeline (einziges fortgeschrittenes Medikament in der Pipeline in der Indikation TTR ist mindestens ein Jahr zurück in der Entwicklung im Vergleich zum ISIS TTR Medikament) eine um eine halbe Mrd höhere Marktkap. haben kann.

Hier die News:

Isis Reports Interim Phase 2 Data on ISIS-APOCIII Rx as a Single Agent in Patients With Very High to Severely High Triglycerides

Statistically Significant Reductions of up to 75 percent in Triglycerides and up to 79 percent in ApoC-III

Conference call webcast and slide presentation Tuesday, Sept. 3, 11:30 a.m. ET at www.isispharm.com
CARLSBAD, Calif., Aug. 31, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced interim data from an ongoing Phase 2 study of ISIS-APOCIII(Rx) as a monotherapy in patients with very high to severely high triglycerides. These data were presented today by Dr. Daniel Gaudet at a PACE session occurring concurrently with the European Society of Cardiology in Amsterdam. In this study, patients treated with ISIS-APOCIII(Rx) achieved statistically significant mean reductions of up to 79 percent in apolipoprotein C-III (apoC-III) and up to 75 percent in triglycerides. In addition, patients treated with ISIS-APOCIII(Rx) achieved statistically significant mean increases of up to 57 percent in high-density lipoprotein cholesterol (HDL-C), the 'good' cholesterol. Patients also achieved up to 89 percent mean reduction in apoC-III-associated very low-density lipoprotein (VLDL) particles.

(Logo: http://photos.prnewswire.com/prnh/20130807/LA60006LOGO)

"Patients with very high levels of triglycerides experience a significant number of health problems, including type 2 diabetes, obesity, cardiovascular disease and, for patients with severely elevated triglycerides, pancreatitis. For these patients, there are very limited treatment options and what is needed is a much more effective drug that can be used as a single agent or in combination with other triglyceride-lowering agents," said Daniel Gaudet, M.D., Ph.D., from the department of medicine, University of Montreal and scientific director, Genome Quebec Biobank Technology Center. "The comprehensive Phase 2 data reported this summer demonstrate that ISIS-APOCIII(Rx) has the potential to fill this need."

The monotherapy portion of the ongoing Phase 2 study of ISIS-APOCIII(Rx) is a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of ISIS-APOCIII(Rx) in patients with very high to severely high triglyceride levels (between 440 and 2,000 mg/dL). The data reported today is an interim analysis of 28 patients who completed 13 weeks of treatment with ISIS-APOCIII(Rx) or placebo. In this study, patients treated with ISIS-APOCIII(Rx) experienced dose-dependent, robust and prolonged, mean percent reductions from baseline in apoC-III, triglycerides and apoC-III-associated VLDL particles. Furthermore, these patients demonstrated a rapid, prolonged and statistically significant mean percent increase from baseline in HDL-C.

Table 1: ISIS-APOCIII(Rx) Produced Statistically Significant Reductions of Triglycerides, ApoC-III and ApoC-III-associated VLDL as a Single Agent in a Phase 2 Study in Patients with Very High to Severely High Triglyceride Levels. Mean % Changes From Baseline at Primary Endpoint.*


Placebo ISIS-APOCIII(Rx) ISIS-APOCIII(Rx) ISIS-APOCIII(Rx)
(n=9) 100 mg (n=9) 200 mg (n=5) 300 mg (n=5)
------------- -------- ---------------- ---------------- ----------------
ApoC-III +5% -43% -72% -79%
(p=0.04) (p=0.004) (p=0.003)
------------- -------- ---------------- ---------------- ----------------
Triglycerides +26% -31% -65% -75%
(p=0.08) (p=0.02) (p=0.004)
------------- -------- ---------------- ---------------- ----------------
ApoC-III VLDL +19% -27% -73% -89%
(p=0.17) (p=0.003) (p=0.004)
------------- -------- ---------------- ---------------- ----------------
HDL-C +3% +30% +51% +57%
(p=0.08) (p=0.002) (p=0.001)
------------- -------- ---------------- ---------------- ----------------
non-HDL +17% -8% -5% -39%
(p=0.16) (p=0.36) (p=0.007)
------------- -------- ---------------- ---------------- ----------------
P value = vs. placebo *Interim analysis
-----------------------------------------------------------------------------
In the ongoing study, patients received 100 mg, 200 mg or 300 mg dose of ISIS-APOCIII(Rx,) or placebo via weekly subcutaneous injections. In this interim analysis, patients had an average fasting triglyceride level of 602 mg/dL with incoming triglyceride levels up to 1,822 mg/dL. In this study ISIS-APOCIII(Rx) was found to be generally safe and well tolerated. The most common adverse event (AE) was injection site reactions, which were infrequent, predominantly mild and typically resolved rapidly. There were no flu-like symptoms, no treatment-related elevations of liver enzymes greater than three times upper limit of normal, no abnormalities in renal function and no clinically meaningful changes in other laboratory values.

"We are pleased with the performance of ISIS-APOCIII(Rx) to date. We have now demonstrated that ISIS-APOCIII(Rx) is equally effective in patients with high to severely high triglycerides as well as in patients with high triglycerides and type 2 diabetes. We have demonstrated that ISIS-APOCIII(Rx) can work equally well as a single agent and in combination with fibrates to produce significant reductions in apoC-III and triglycerides, and increases in HDL-C. In addition, the positive effect of ISIS-APOCIII(Rx) treatment on lipid parameters, improvements in glucose control and trends toward improvements in insulin sensitivity, suggest that ISIS-APOCIII(Rx) could have a very attractive therapeutic profile for patients with severely high triglycerides, who often also have diabetes or metabolic syndrome," said Richard Geary, Ph.D., senior vice president of development at Isis. "We look forward to discussing our Phase 3 plans with regulators and moving rapidly into a Phase 3 program next year in patients with severely high triglycerides."

ISIS-APOCIII(Rx) is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents. ISIS-APOCIII(Rx) targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates. Humans with elevated levels of apoC-III have increased dyslipidemia associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.

Conference Call

At 11:30 a.m. Eastern Time Tuesday, Sept. 3, 2013, Isis will conduct a live webcast and slide presentation conference call to discuss the positive Phase 2 data presented today. Interested parties may listen to the call by dialing 866-652-5200, or access the webcast with or without audio at www.isispharm.com. A webcast replay will be available for a limited time at the same address.


Präsentation slides:
http://isispharm.com/pdfs/2013.08.31_ESC_presentation.pdf


Habe hier mal einen aktuellen Analystenreport von Canaccord Genuity Kursziel 23$ in dem APOCIII mit lächerlichen 0,14 $ per Aktie bewertet wird!
https://research.canaccordgenuity.com/_layouts/researchnotev…

Montag ist in USA Börsenfeiertag, bin gespannt auf die Kursentwicklung am Dienstag. Diese überragenden Phase II-Daten waren nach den beiden vorangegangenen Studien allerdings zu erwarten und möglicherweise sehen wir auch eine "Sell on the News"-Reaktion.

Grüße cristrader

[cristrader]

Biogen bets more on Isis technology for neurological drugs

(Reuters) - Biogen Idec has agreed to pay another $100 million upfront to Isis Pharmaceuticals Inc as part of a broad collaboration to develop new medicines for neurological disorders, the companies said on Monday.

The news sent Isis's shares up 9 percent in premarket trade.

The deal is the fourth between the companies in the last two years, and aims to use the "antisense" technology invented by Isis to accelerate discovery of drug targets for neurodegenerative diseases.

Biogen has the option of using the research to develop either antisense drugs, traditional small molecule drugs or antibody-based compounds.

Antisense drugs aim to interfere at the genetic level to prevent the formation of disease-causing proteins.

"This is a more expansive collaboration in which we will work together over the next several years to use the Isis technology to probe the biology of a disease, develop drug targets and then potentially take those molecules forward," Biogen Chief Executive Officer George Scangos said in a telephone interview.
Biogen is a leader in the market for drugs to treat multiple sclerosis, a progressive neurological disease that can lead to paralysis.

Biogen and Isis are already working to develop an experimental treatment for spinal muscular atrophy which is set to enter late-stage testing in humans. Earlier collaboration has also resulted in an experimental drug for myotonic dystrophy that will soon begin development.

By next year the companies expect to have drug candidates for three other targets, said Isis CEO Stanley Crooke.

"With the efficiency of antisense we believe we should have a drug moving forward pretty much every year," he said.

Crooke said the first focus of the new collaboration with Biogen will likely be neurodegenerative disorders, particularly those involved with motor dysfunction.

He put the potential value of the deal for Isis at "several billion dollars," noting that royalty payments for any eventual antisense drugs would be in the double digit percentages, with smaller payments for non-antisense compounds.

Isis shares were up at $30.35 in trading before the bell. They had closed at $27.92 on Friday on the Nasdaq.

Biogen shares were up slightly at $226 premarket. They had closed at $225.18.

[cristrader]

Großartiger Call!

Bis zu 4 Mrd $ an Milestones + zweistellige Royalties!!!

Mehrere solcher strategischer Partnerschaften geplant!!!

Hoffe auf ne Trendwende, zumindest charttechnisch ist der kurzfristige Abwärtstrend gebrochen.

cristrader

[Stoxtrayder]

dazu sag ich nur...

[cristrader]

Neues Allzeithoch!!!

Isis Reports Follow-Up Data From ISIS-SMN Rx Phase 1 Study In Children With Spinal Muscular Atrophy

Improvements in muscle function continue to be observed up to fourteen months after a single dose

CARLSBAD, Calif., Sept. 19, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that follow-up preliminary data from a single dose, open-label Phase 1 study of ISIS-SMNRx in children with spinal muscular atrophy (SMA), show that most SMA children receiving the two highest doses of the drug (6 mg and 9 mg) continued to show improvements in muscle function tests up to 14 months after a single injection of the drug. The Phase 1 data, including these preliminary follow-on data, will be presented at the International Congress of the World Muscle Society by Dr. Kathy Swoboda on Oct. 3, 2013. SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness and is the most common genetic cause of infant mortality. ISIS-SMNRx is an antisense drug designed to treat all types of SMA.

The preliminary data reported today is from a follow-up analysis of 24 children with SMA who participated in a Phase 1 single-dose, open-label study of ISIS-SMNRx. Analysis of motor function was performed in these children nine to 14 months following a single dose of ISIS-SMNRx using the Hammersmith Functional Motor Scale-Expanded (HFMSE). The improvements in HFSME scores were dose dependent with the largest improvements observed in children in the highest dose cohort (9 mg, mean = 5.75). Most children in the 9 mg dose cohort showed continuing improvements during follow up, with no children declining.

"SMA is a devastating disease that results in severe muscle weakness and respiratory compromise in the majority of affected patients. Treating children early in the course of the disease provides the greatest opportunity to reap substantial improvements in muscle strength and function, potentially resulting in a lifetime of benefit. ISIS-SMNRx targets the underlying primary cause of SMA, taking advantage of the backup gene, SMN2, present in all SMA patients," said Kathryn J. Swoboda, M.D., professor, department of neurology and director of pediatric motor disorders research program at the University of Utah, School of Medicine. "Preliminary results from Phase 1 clinical trials reveal a favorable safety profile, and appear to indicate that a single dose of the medication at the higher doses tested to date may result in sustained benefit over many months in some children. Thus, while early, we are excited to continue to work closely with Isis in further studies of ISIS-SMNRx in SMA."

"We are pleased with the progress we are making on ISIS-SMNRx. Although there was no placebo group, the continuing improvement for up to a year after a single dose observed in this study is encouraging, particularly when considered within the context of the dose response," said B. Lynne Parshall, chief operating officer at Isis. "Our ongoing Phase 2 program is proceeding well. The 6 mg dose group in our Phase 2 study in infants with Type I SMA has completed dosing. Based on the safety, pharmacokinetic and pharmacodynamic profile of ISIS-SMNRx we have observed to date, we have amended the infant study to increase the dose from 9 mg to 12 mg dose. We plan to start dosing this cohort soon. In our Phase 1b/2a multiple-dose study in children with Type II and Type III SMA, we have completed dosing in all three dose cohorts (3 mg, 6 mg and 9 mg), and we are considering adding a 12 mg dose cohort to this study. The FDA has expressed reservations about increasing the exposure in children with Type II and Type III SMA, and we are in ongoing discussions with them. We plan to report data from both of these ongoing studies late this year or early next year. We also plan to begin our Phase 3 clinical program early next year."

The Phase 1 study was an open-label, single-dose, dose-escalation study designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMNRx in medically stable children from age 2-14. In this study, children with Type II or Type III SMA received ISIS-SMNRx as a single dose of 1, 3, 6, or 9 mg administered intrathecally. In addition to measurements of drug concentration in plasma and cerebral spinal fluid, exploratory analyses of changes in motor function were conducted. Gross motor movements were measured using the HFMSE, a modified version of the Hammersmith Functional Motor Scale. The HFMSE is used to assess responses on 33 motor function tasks, each scored on a scale from 0 to 2 and allows for assessment of any SMA patient aged 2 or older. HFMSE has demonstrated good test-retest reliability in other studies.

Data from this study was reported at the American Academy of Neurology in March 2013, showing that a single-dose of ISIS-SMNRx was well tolerated in children with SMA at all dose levels tested and that improvements were observed in HFMSE scores in a number of children, with a mean increase in HFSME scores for the 9 mg cohort at three months was 3.1 points. The data to be reported at the World Muscle Congress in October is a follow on analysis of HFMSE in 24 children who had completed the Phase 1 study.

ABOUT ISIS-SMNRx
ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. Isis is currently in collaboration with Biogen Idec to develop and potentially commercialize the investigational compound, ISIS-SMNRx, to treat all types of SMA. Under the terms of the January 2012 agreement, Isis is responsible for global development and Biogen Idec has the option to license the compound until completion of the first successful Phase 2/3 study. ISIS-SMNRx is currently being evaluated in two Phase 1b/2a multiple-dose, dose-escalation studies. The first is in children with Type II or Type III SMA. The second is in infants with Type I SMA.

ABOUT SMA
SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in the United States, Europe and Japan. SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord responsible for neuromuscular growth and function. One in 50 people, the equivalent of about 6 million people in the United States, are carriers of a defective SMN1 gene, which is unable to produce fully functional SMN protein. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA. The severity of SMA correlates with the amount of SMN protein. Infants with Type I SMA, the most severe form of the disease, produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

Isis acknowledges support from the following organizations for ISIS-SMNRx: Muscular Dystrophy Association, SMA Foundation, Families of SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

[cristrader]

Weitere positive APOCIII-Phase 2 Daten in ultra orphan Population(3-5000 weltweit)familial chylomicronemia syndrome oder FCS

http://www.myfoxboston.com/story/23492533/isis-reports-phase…

[cristrader]

Präsentations-Slides von morgigem Webcast. Beeindruckend!

http://isispharm.com/pdfs/2013_09_23_APOCIII_FCS_data_webcas…

[Stoxtrayder]

Hallo miteinand

die heutige News zu ISIS-SMNRx wird ja wieder sehr gut vom Markt aufgenommen.

@cristrader: gibt es diese Jahr noch Termine bei Isis, die von (wichtiger) Relevanz sein könnten? z.B. PII oder PIII-Ergebnisse? unter 'Upcoming Events' auf der Homepage von Isis steht nicht so viel.

Danke!

PS: welche Kurse siehst du bis Ende 2014?

[cristrader]

Hallo Stoxtrayder!

Um den 20. Nov. findet die Jahreskonferenz der AHA (American Heart Association) statt, wo ISIS detaillierte APOCIII-Daten vorlegen wird.

Es ist schwierig zu sagen welche Daten noch in diesem Jahr oder erst zu Jahresbeginn bekanntgegeben werden.

So um den 5. Nov. kommen die Quartalzahlen zusammen mit einer neuen Guidance, worin die bisher unberücksichtigten Zahlungen (100 Mio Biogen Deal, 17 Mio an Milensteinen u.a) berücksichtigt werden. Gehe stark davon aus das ein positives Jahresergebnis dabei herauskommt.

Die Phase II-Daten von SMN und Factor XI erwarte ich erst Anfang nächsten Jahres. Phase II-Daten von STAT3 kommen vielleicht noch dieses Jahr.

Es kann jederzeit ein Biogen-ähnlicher Deal bekannt gegeben werden. Crooke deutete bereits an das mehrerer solcher Deals geplant sind.

Phase II vom Krebsmedikament ISIS-EIF4e sollten bald herauskommen.

Was gerne vergessen wird sind die optionsähnlichen Deals von ISIS. Bei SMN und bei STAT3 steht vor den Phase III-Starts Anfang/Mitte 2014 die Optionsausübung an mit fetten Meilensteinzahlungen, wobei sicherlich ein dreistelliger Miobetrag zusammenkommt.

Dreistellig ist übrigens auch mein Kursziel bis Ende 2014, Voraussetzung dafür sind aber positive Factor XI-Ergebnisse inclusive Partnerdeal. Ich denke 2014 wird auch die Diabetes-Pipeline wieder in den Focus rücken.

War jetzt nur ein schneller Überblick. Bei genauerer Betrachtung gibt es natürlich noch zahllose andere mögliche News aber die obengenannten reichen auch für ein Midcap Biotechunternehmen!

Grüße cristrader

[Stockfinder]

Sie steigt und steigt. 100 Dollar, wir kommen...

[Stoxtrayder]

Hm. Von knapp 60$ auf 30$ gefallen/korrigiert. Bei 35$ zu leider (zu früh) nachgekauft...wobei ich ehrlich sagen muss, dass ich nicht gedacht hätte, dass es soweit runter geht.

Wie sind die heute, veröffentlichen Daten zu bewerten?

thx!

[expertus]

Bin auch Mal eingestiegen. Sehr starke Pipeline. Könnte auch irgendwann ein Kandidat für eine Übernahme sein für eine grosse Pharmafirma, wo ja die Patente auslaufen und die Pipeline füllen müssen

[Stockfinder]

Nach der deutlichen Korrektur (ohne fundamentale Gründe) ist es wider Zeit einzusteigen. 90 % der Papiere liegen bei institutionellen Investoren. Isis verfügt über die umfangreicheste und beste Pipeline in der Branche. Bin schon einige Zeit investiert und habe unter 30 $ weiter zugekauft und werde es weiterhin zu handhaben.

Hier sind 100 $ und mehr in 1-2 Jahren drin, falls diese Perle nicht vorher vom Markt genommen wird...