Cortex Pharmaceuticals 3 - 500 Beiträge pro Seite

[Erbse1]

Hallo liebe Cortex Pharmaceuticals Freunde. Der alte Thread ist schon ziemlich lang geworden und ich möchte Euch bitten die Beiträge hier in diesem Thread zu posten.
Dieses Jahr stehen Für Cortex viele Entscheidungen an, die sich ganz gravierend auf den Kurs auswirken können. Es lohnt sich also ständig am Ball zu bleiben.

Zur Recherche zu dem letzten Thread folgender link
http://www.wallstreet-online.de/ws/community/board/threadpag…

Beiträge in Englisch aus dem Yahoo Board gibts unter folgendem link
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Informationen direkt von Cortex Pharmaceuticals unter folgendem link
http://www.cortexpharm.com/main.html

Ich freue mich über jeden sinnvollen Beitrag zu unserem Thema.

Also machts mal gut
Erbse1

[Erbse1]

Vor einigen Tagen hat sich ein Cortex Investor Forum gegründet. Leider geht das nur mit Anmeldung. Neue Mitglieder sind stets willkommen. Sehr interessant sind die informativen DIAS von Cortex. Leider kann ich sie nicht kopieren. Also einfach anmelden unter folgendem link.

http://finance.groups.yahoo.com/group/CortexInvestorsForum/

Schönen Tag noch
Erbse

[Erbse1]

Weitere Informationen zu Cortex und vielen anderen Firmen gibt es hier. Bei Bedarf werden die Beiträge aktuallisiert. Guter Neuro-Börsenbrief, der sein Geld wert ist.

http://www.neuroinvestment.com/commentsnew.html

Schönen Tag noch
Erbse

[Erbse1]

Damit ihr nicht so lange suchen braucht, die wichtigsten links

Der Brief des CEO Roger Stoll an die Aktionäre für die zukünftige Entwicklung:
http://www.cortexpharm.com/html/investor/04letter.html


Überblick des Mitstreiters gfp927z aus dem Yahoo Board von der letzten Konferenz:
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…


Eine Zusammenfassung und Empfehlung vom Börsenbrief Biotech monthly :
http://www.cortexpharm.com/pdfs/Cortex%20%20Anniversary%2020…


Wenn ich Fragen beantworten kann, stehe ich für weitere Informationen gerne zu Verfügung.

Machts mal gut
Erbse

[Erbse1]

Habe eben noch ein bischen in Sachen Cortex gestöbert. Dabei viel mir eine medizinische Abhandlung auf.

Glutamate as a therapeutic target in psychiatric disorders.

Javitt DC.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d…

Dies ist deswegen so interessant, da Cortex mit Organon mit ORG 24448 in der Endphase der zweiten Testphase ist.
ORG 24448 wäre somit als Combotherapie mit allen anderen Schizophreniemedikamenten denkbar.
Aus einem kleinen Versuch mit psychotisch erkrankten Menschen ist bei CX516 keine nennenswerte Verbesserung der Positivsymptomatik sichtbar.
Hoffen wir also auf eine Verbesserung der kognitiven Performance bei ORG 24448. Dies würde dann auch die Theorie des Nobelpreisträgers Arvid Carlsson bestätigen, bei der von einer Störung des Dopamin- und Glutamatstoffwechsels bei Schizophrenie ausgegangen wird.
Dies wäre für Cortex ein riesiger Erfolg, da ORG 24448 als zusätzliches Medikament zu allen anderen Medikamenten gegeben werden müßte.

Schönen Tag noch
Erbse

[Erbse1]

Gary Lynch und Mitarbeiter

Hinter der ganzen Arbeit mit den Ampakinen steht der Cortex Mitbegründer Gary Lynch.
Viele Leute spekulieren darauf, daß er auch für seine Arbeit den Nobelpreis erhalten wird, zumindestens hätte er ihn verdient.
Hier kurz einige Sätze aus einer Abhandlung von Lynch zu den Ampa Rezeptoren.
AMPA receptor modulators as cognitive enhancers.

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors mediate fast excitatory transmission throughout the central nervous system. Positive modulation of these receptors can potentially enhance cognition by, firstly, offsetting losses of glutamatergic synapses; secondly, promoting synaptic plasticity; and thirdly, increasing the production of trophic factors. The advent of small molecules that selectively enhance AMPA receptors in the brain made it possible to test these hypotheses. Preclinical experiments indicate that the compounds accelerate the encoding of memory and have positive effects on models of cognitive dysfunction. Initial results with human subjects are also positive. AMPA receptor modulators thus represent an entirely new approach to cognitive enhancement and the treatment of diverse brain disorders.

Publication Types:
Review
Review, Tutorial

PMID: 15018832 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d…

Für Leute die sich noch weiter mit Gary Lynch beschäftigen wollen folgend der Link zu der Homepage.
http://lynchlab.ucicom.uci.edu/index.htm

Schönen Tag noch
Erbse1

[Erbse1]

Für mich eine Überraschung von Cortex Partner Organon bei den Ampakinen. Bisher war die Testphase mit ORG 24448 bei Schizophrenie und eine Testsubstanz in der frühen Phase bei Depression bekannt .
Aus dem letzten Analystenpapier von Organon ist neben ORG 24448 von zwei zusätzlichen Komponenten die Rede.

Quelle:
http://www.google.de/search?num=30&hl=de&newwindow=1&q=ampa+…

Ich bekomme den Artikel nicht direkt verlinkt. Gemeint ist der folgende Bericht.
Organon Research & Development Maximizing Productivity

Meine Frage geht dahin. Was ist die zusätzliche Testsubstanz und für welches Anwendungsgebiet ist sie bestimmt?

Werde der Frage mal nachgehen.

Schönen Tag noch
Erbse

[BrauchGeld]

Hallo Erbse

Ich wollte gern wissen was Du von PhytoPharm hälst ,das u.a. auch in bereich Demenz-Erkrankungen tätig ist.
Vor allem interessiert mich ob sich hier ein einstieg lohnt.

http://www.phytopharm.co.uk

http://www.phytopharm.co.uk/prod_develop.html

http://www.phytopharm.co.uk/press_releases.html

Danke

Gruss
B.M.

[Erbse1]

Hallo BrauchGeld, die Frage kann ich dir leider nicht beantworten. Letzendlich hängt das davon ab, ob ein Produkt auch alle drei Testphasen erfolgreich durchläuft. Ich kenne Deine Aktie leider nicht und habe mich noch nicht mit ihr beschäftigt. Ich denke mal es gehört auch eine ganze Menge Glück dazu aufs richtige Pferd zu setzen. Nur leider kann ich dir keinen Tip geben. Eine gute Recherche kann allenfalls die Chancen erhöhen. Ob ein Produkt auch erfolgreich besteht ist was ganz anderes.
Ich möchte dir das mal am Beispiel Titan Pharma erklären. Die habe ich super recherchiert und das Medikament wurde schon als das Psychosemedikament gehandelt. Nur hatte sie den Nachteil mit der Verlängerung des QT Intervalls beim Herzen . Jahrelange Arbeit waren dahin. Die Folgen waren halt ein totaler Absturz und die beste Recherche hat nichts genutzt.
Tut mir leid, daß ich dir leider nicht helfen kann.

Schönes Wochenende noch.
Erbse

[Erbse1]

Hallo liebe Cortex Freunde. Hier einige Grundlagen für Leute die sich in das Thema einarbeiten wollen. Bei mir ist es so, daß ich leider auch nicht jede Einzelheit verstehe

Glutamate receptors and nerve cell communication
Role of glutamate and AMPA receptors in nerve cell communication for non-scientists
http://www.bris.ac.uk/synaptic/info/glutamate.html




Cortex beschäftigt sich mit den AMPA Rezeptoren

Schönen Tag noch
Erbse

[Erbse1]

Habe in meinem Archiv noch etwas in Deutsch gefunden.

Die Familie der ionotropen Glutamatrezeptoren
Text von Jörg Geiger, Institut für Physiologie I der Universität Freiburg
http://neuro.biologie.uni-freiburg.de/Skriptum/4-5-5.htm

[Erbse1]

Memory enhancement: the search for mechanism-based drugs
Gary Lynch


Figure 1:
Targets for the development of memory-enhancing drugs.

The production of memory-related synaptic changes occurs in three stages. Step 1: induction. Released transmitter binds to AMPA-type glutamate receptors, which then depolarize the postsynaptic region and unblock NMDA-type receptors. Step 2: expression. NMDA receptors admit calcium and thereby modify AMPA receptors so as to increase the size of subsequent excitatory currents. Step 3: consolidation. NMDA receptors also trigger changes that stabilize the modifications to the AMPA receptors. A rapidly developing aspect of this (3A) involves adhesion receptors, whereas a more delayed component requires genomic events (3B). Current strategies for drug development (red asterisks) target the AMPA receptor component of induction or the gene-signaling component of consolidation.

[Erbse1]

Hallo liebe Cortex Fans. Exclusiv der Ampakine-Aricept Vergleich. Dies ist ein Versuch mit Affen und die Ergebnisse müßen halt erst noch in den einzelnen Testphasen bestätigt werden. Sollten sich diese Ergebnisse aber bestätigen, so werden wir mit Cortex noch viel Freude haben.

Schönen Tag noch
Erbse


Bild von der letzten Cortex Präsentation

[Erbse1]

Hallo liebe Cortex Fans, jetzt wird die Sache bei CX717 und Schlafentzug langsam spannend. Die Phase 2 wird wohl innerhalb von wenigen Monaten über die Bühne gehen. Gleich folgen ein paar beindruckende Schaubilder zu den Versuchen mit CX717.

Interesse gerade an diesen Versuchen zeigt die DARPA, die an einer militärischen Nutzung brennend interessiert ist.
Folgend die kurze Einlassung der DARPA.

Preventing Sleep Deprivation
http://www.darpa.mil/dso/thrust/biosci/cap.htm

Der Versuchsaufbau zu den Tests bei Schlafentzug


Die Ergebnisse von CX717


Ein beeindruckendes EEG


Noch beeindruckender der Vergleich mit Aricept


Schönen Tag noch
Erbse

[Erbse1]

Hier noch ein Bild für Fachleute als Ergänzung zu den gestrigen Schaubildern.



Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans. Folgender link führt zu der kompletten DIA Serie mit vielen Informationen des CEO Stoll von der letzten Präsentation. Das Volumen von Cortex zieht in letzter Zeit mächtig an. Kann ganz gut sein, daß Ergebnisse von Fragile X, Schizophrenie oder auch eine neue Auslizensierung anliegen.

http://www.vm-elsig.de/achim/1.htm



Schönes Wochenende wünscht Euch
Erbse

[kalabrienfan]

Hallo Erbse,
gleich vorneweg, ich hab keine Cortex Aktien. Ich finde
Deine Arbeit hier aber so klasse, daß ich mich nächste
Woche, da hab ich Urlaub, mal intensiv mit Cortex beschäftigen werde. Ich habe beruflich mit Demenzpräparaten
zu tun, aber dem NMDA-Antagonist- Wirkansatz.
Im Prinzip klingt das alles sehr spannend, ich melde mich
wieder.
Kala

[Erbse1]

Hier gehts zur Cortex DIA Show

Wenn ihr das Bild noch mal sehen wollt einfach auf der linken Seite kleines Vorschaubild anklicken.

http://www.vm-elsig.de/achim/dia0/

Viel Spaß beim Anschauen
Erbse

[Erbse1]

The next DIA Show Cortex Pharmaceuticals

http://www.vm-elsig.de/achim/dia1/

[Erbse1]

Letzte Aktionärsversammlung mit Media Player mit Ton Cortex Pharmaceuticals
http://www.cortexpharm.com/html/Webcast.html

Längere Präsentation von der letzten Aktionärsversammlung in Englisch. Sehr informativ. Dauert wohl etwas länger. Windows Media Player erforderlich. Eine kurze Zusammenfassung gibts in den zwei DIA Shows in den zwei vorherigen links ohne Ton.

Schönen Tag noch
Erbse

[Erbse1]

Interessanter Artikel aus der Ärztezeitung, bei dem bei verringertem Tiefschlaf von Gedächtnisdefiziten ausgegangen wird. Genau hier setzt Cortex bei Schlafentzug mit CX717 und Organon bei Schizophrenie mit ORG24448 an.

Schönen Tag noch
Erbse


Ärzte Zeitung, 20.01.2005


Je mehr Tiefschlaf, desto besser das Gedächtnis
Möglicher Therapieansatz bei Schizophrenie-Patienten mit Gedächtnisstörungen / Studie an der Uniklinik in Kiel
KIEL (nke). Wenn der Tiefschlaf gestört ist, zum Beispiel aufgrund einer seelischen Erkrankung, schadet das dem Gedächtnis. Den Zusammenhang zwischen Schlafstörung und Lernleistung haben Kieler Schlafmediziner bei Patienten mit Schizophrenie nachgewiesen.

Wer nicht genug schläft, kann nicht gut lernen. Denn während des Schlafs wird Gelerntes im Gedächtnis gespeichert. Grundsätzlich unterscheiden Gedächtnisforscher zwischen Gedächtnis, daß durch bewußtes Lernen entsteht, etwa beim Lernen von Prüfungsstoff, sowie Gedächtnis, das weitgehend unbewußt entsteht, etwa beim Lernen von Bewegungsabläufen. Für das bewußte Gedächtnis ist vor allem der Tiefschlaf, für das unbewußte Gedächtnis eher der Traumschlaf nötig, berichtet Dr. Robert Göder aus Kiel.

Bei Patienten mit Schizophrenie ist oft das bewußte Gedächtnis gestört. Die Patienten haben oft auch Schlafstörungen. Ob es einen Zusammenhang zischen Schlaf- und Gedächtnisstörungen bei Schizophrenie gibt, haben der Leiter des Schlaflabors der Kieler Universitätsklinik und sein Team jetzt bei 17 Patienten und 17 Gesunden untersucht (J Psychiatr Res 38, 2004, 591).

Vor dem Zubettgehen und nach dem Aufwachen mußten die Studienteilnehmer spezifische Gedächtnistests ablegen. Damit sollte die Lernleistung über die Nacht festgestellt werden. Dazwischen wurde der Schlaf dokumentiert.

Patienten mit Schizophrenie benötigten mehr Zeit bis zum Einschlafen, schliefen schlechter und hatten insgesamt weniger Tiefschlaf im Vergleich mit gesunden Teilnehmern. Die Gedächtnisleistung war, wie erwartete, ebenfalls schlechter als bei Gesunden. "Je mehr Tiefschlaf die Patienten hatten, desto besser war die Gedächtnis-Leistung. Je weniger, desto schlechter die Leistung", so Dr. Dunja Hinze-Selch von der Uniklinik Kiel zur "Ärzte Zeitung".

Unklar ist noch, ob die Dauer des Tiefschlafs oder der Anteil des Tiefschlafs an der gesamten Schlafdauer entscheidend ist. "Im Moment sieht es so aus, daß es beim Tiefschlaf einen Schwellenwert gibt. 20 bis 25 Minuten Tiefschlaf könnte so ein Wert sein, der für die maximale Lernleistung nötig ist."

Aus diesen Befunden ergibt sich auch ein neuer Therapieansatz für die Betroffenen. So könnten durch gezielte Beeinflussung des Schlafes, etwa durch Medikamente, auch das Gedächtnis verbessert werden. Denn die eingeschränkte Gedächtnisleistung belastet die Schizophrenie-Patienten sehr und behindert deren soziale Integration. Medikamente, die gezielt den Tiefschlaf fördern, gibt es jedoch noch nicht, es wird aber daran geforscht.

Wäre eine solche Pille, mit der man den Tiefschlaf verlängert, nicht auch für Gesunde interessant? Göder ist skeptisch: "Ob man als Gesunder viel besser lernt, wenn man noch mehr Tiefschlaf hat, ist sehr fraglich. Von einem solchen Medikament könnten vermutlich vor allem die Menschen profitieren, die aufgrund einer Erkrankung keinen Tiefschlaf mehr haben. Sie könnten eventuell einen Teil der Gedächtnis-Defizite wieder ausgleichen."

http://www.aerztezeitung.de/docs/2005/01/20/009a1301.asp?cat…

[Erbse1]

Ein sehr umfangreicher guter Artikel in der GEO Zeitschrift
Lernen-Serie, Teil 4: Doping fürs Gehirn

Wissenschaftler arbeiten an Arzneien, die einem schwindenden Gedächtnis aufhelfen und das Denken schärfen sollen. Aber wie weit dürfen wir gehen bei der Manipulation unserer grauen Zellen?
http://www.geo.de/GEO/medizin_psychologie/psychologie/2005_0…

[Erbse1]

Radiosendung vom Deutschlandfunk über Ampakine
http://www.dradio.de/dlf/sendungen/forschak/333410/
Media Player erforderlich. Dauer ca: 4:30 Min

Biochemische Gedächtnisstütze US-Mediziner testen Neurowirkstoff Ampakin Wer schon einmal mit Kindern Memory gespielt hat, wird sich daran erinnern kein Bein auf die Erde bekommen zu haben. Kein Wund ...

Schönes Wochenende
Erbse

[Erbse1]

Organon’s compound, Org 24448, selected to test efficacy of cognitive dysfunction in schizophrenia

Cortex hat ORG24448 an Organon auslizensiert

The National Institute of Mental Health (NIMH) sponsored network called Treatment Units for Research on Neurocognition in Schizophrenia (TURNS) has selected Organon’s compound, Org 24448, to undergo testing as part of its effort to facilitate the development of medications to enhance cognition in patients with schizophrenia.

Kompletter Text unter folgendem link
http://www.news-medical.net/?id=7455

Schönen Tag noch
Erbse

[lisa46]

gestern kam ein Bericht zu dem Unternehmen auf SpiegelTV

recht interessant!

[Erbse1]

Nach der guten Nachricht von gestern, heute einige Informationen zu Fragile X. Die Ergebnisse mit CX516 dürften wohl in nächster Zeit veröffentlicht werden. Von den Daten wird allenfalls ein Hinweis auf die Wirksamkeit von CX516 erwartet. Es ist sehr schwach wirksam und muß also hoch dosiert werden. Aus den MCI Versuchen ist bekannt, daß viele Patienten über Magen-Darm Problemen klagten, da es sehr hoch dosiert werden mußte.
Außerdem ist bei CX516 über die sehr kurze Halbwertszeit zu klagen. Es baut sich also schon innerhalb weniger Minute im Körper ab.
Fragile X dürfte bei Cortex wohl eine der ersten "Orphan Anwendungen" sein. Ich denke mal, daß eine weitaus stärkere Substanz als CX516, das im Augenblick getestet wird, dafür gewählt wird.
Folgend noch einiges Wissenswertes über Fragile X und die Phase2 Versuche.



Elizabeth Berry-Kravis, MD, PhD
RUSH University, Chicago

Dr. Berry-Kravis ist Leiterin des jetzt laufendes Versuches mit CX 516

Clinical Trial of a New Medication in Adults with Fragile X
http://www.fraxa.org/ra_Berry-Kravis.aspx

Weitere Informationen im nächsten link in einem ausführlichen Interview.
Fragile X/Autism Help -- Full-Length Doctor`s Interview
http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=8…

Ergänzend zu dem Interview bietet sich eine DIA Show mit viel Informationen von einer Cortex Präsentation an. Alles Wissenswete mit einigen DIAS.
Hier gehts zur DIA Show über FRAGILE X
http://vm-elsig.de/achim/Fragile/


Wünsche allen noch einen schönen Tag
Erbse

[lisa46]

Kurze Frage!

Fragile - gehört das zu Cortex?!

[Erbse1]

Hallo Lisa,
Fragile X gehört nicht Cortex. Fragile X ist eine Erkrankung. Ein Wirkstoff von Cortex , CX 516, wird im Augenblick in einer Testphase 2 von FRAXA gegen einige Aspekte dieser Krankheit getestet. Es ist aber sehr wahrscheinlich, daß eine stärkere Substanz von Cortex letztendlich zur Marktreife gebracht werden soll.
Ich hoffe, ich habe Deine Frage richtig verstanden.
Liebe Grüße
Erbse

[lisa46]

ja danke!

Was ist denn von den Gerüchten zu halten, Cortex habe kein Geld mehr weiterzutesten!?

Und ist nicht Roche an Bord?!

[Erbse1]

Nein Lisa, Roche ist bisher nicht an Board. Roche hat sich bei einem Konkurrenten Memory Pharma engagiert.
Geld ist nach einigen Kapitalmaßnahmen für ca 3 Jahre vorhanden.
Es ist geplant einige Substanzen an größere Pharmaunternehmen auszulizensieren und so den weiteren Erhalt der Firma zu sichern.
Diese Informationen stehen aber alle unter dem link an den Brief an die Aktionäre vom CEO Stoll.
Liebe Grüße
Erbse

[Erbse1]

Hier ein Abstrakt, der die Möglichkeiten der Ampakine aufzeigt:

Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d…

Schönen Tag noch
Erbse

[lisa46]

Hallo!

Hat denn jemand von euch auch nähere Infos zu der finanziellen Situation von Cortex?

Wie hoch ist die Cash-Burn-Rate und wie schätzt man die Chancen auf zukünftige Vermarktungen ein, etc. ect. etc...?

Wie seht ihr die Aktienentwicklung!? War das heute der Tiefpunkt bei 2,45 $ in den USA!? Wie ist die Aktie bewertet? Wieviele Stück gibt es?
Wie gut ist das Management dieser Firma? Kann man von ihnen ein schönes Wachstum für die Zukunft erwarten. Gibt es BWL`ler in der Firma oder ist der Laden durchweg von Forschern / Wissenschaftlern durchzogen?!

Beste Grüße und weiterhin viel Erfolg,

Thomas

[Erbse1]

Hallo Thomas,
du solltest Dir auch etwas Mühe machen. Ich poste seit drei Jahren regelmäßig zu Cortex. Lies bitte die letzten zwei Threads zu Cortex und es werden Dir fast alle Fragen komplett beantwortet. Ich habe wirklich keine Lust Dir eine komplette Analyse zu Cortex zu schreiben, nur weil du keine Lust oder Zeit zu eigener Recherche hast. An Deinen Fragen merke ich , daß Du noch nicht einmal diesen Thread gelesen hast..
Ich habe keine Lust dir Deine Arbeit zu machen. Du brauchst nur die links anzuklicken und die Fragen werden Dir beantwortet. Gehe doch auch mal auf die Cortex Homepage. Lies diesen Thread durch und klicke auf die links.
Liebe Grüße
Erbse

[Erbse1]

Hallo liebe Cortex Fans,
folgend ein link zur aktuellen Patentsituation in Europa mit dem Eli Lilly Disput.
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Der nächste Bericht beschreibt die Planung für die nähere Zukunft und die finanzielle Situation von Cortex.
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Schönen Tag noch
Erbse

[Erbse1]

News von Heute
Cortex Pharmaceuticals Receives FDA Permission to Commence Phase II Alzheimer`s Disease Imaging Study with AMPAKINE CX717
http://biz.yahoo.com/bw/050131/315195_1.html

[Erbse1]

Hallo liebe Cortex Fans,
hab eine interessante Seite gefunden, die sich unter Anderem auch mit unserer Thematik beschäftigt. Den Artikel über Cortex kopier ich mal hier rein. Weitere Hintergrundartikel gibts unter dem link.

Schönen Tag noch
Erbse

http://www.ams.or.at/wien/biz/vision/archiv/rund107.htm

Beispiele für konkrete Anwendungen

Neuro-Pharmakologie
Eigentlich ist es ein ganz normaler Prozess: Im Alter lässt das Gedächtnis nach. Wenn es jedoch immer mehr alte Menschen gibt, die zugleich immer jünger sein wollen, wird dieser Vorgang zu einem Problem.Und damit zu einer echten Herausforderung für die Neuro-Pharmakologie, deren Forscher dazu beizutragen versuchen, degenerative Hirnerkrankungen künftig wenn nicht zu heilen, dann doch zumindest wirksam aufzuhalten.Und damit gleichzeitig die Bedürfnisse all jener zu befriedigen, die sich in der Wissensgesellschaft der Zukunft auch als Gesunde nach einem effektiven Mittel zur Steigerung von Konzentrationsfähigkeit und Gedächtnisleistung sehnen.

Anti-Aging und Pro-Braining:
"Die Generation der heute 40- bis 60-jährigen Amerikaner hat sich wie keine andere vor ihr dem ehrgeizigen Ziel verschrieben, den Alterungsprozess aufzuhalten." Mit dieser Analyse bringt der Gerontologe Dr. Ken Dytchwald (in: "American Demographics" 5/03) auf den Punkt, was die Märkte in den USA und anderen westlichen Regionen in den nächsten Jahren am meisten umtreiben wird: das Bedürfnis ihrer alternden Bewohner nach Jugendlichkeit und Selbstverbesserung. In einer Gesellschaft, die konsequent auf die körperliche und geistige Fitness des Individuums ausgerichtet ist, wird Enhancement zur Selbstverständlichkeit.

Eine Sorge, die zwar verfrüht (der größere Teil der Alzheimer-Patienten ist heute über 80 Jahre alt), aber nicht ganz unbegründet ist: Allein in Deutschland leben mittlerweile bereits fast eine Million Demenzkranke, von denen zwei Drittel von der Alzheimer-Krankheit betroffen sind. Die steigende Lebenserwartung bringt es mit sich, dass sich diese Zahl bis zum Jahr 2050 auf mehr als zwei Millionen verdoppeln wird – sofern kein Durchbruch in Prävention und Therapie gelingt. In Österreich stellt sich die Situation vergleichbar dar: Demnach könnte sich die Zahl der Demenz-Patienten bis zum Jahr 2050 auf knapp 250.000 erhöht haben, noch in den 50er Jahren waren es nur 35.000, so die Ergebnisse einer Berechnung an der Wiener Uni-Klinik für Psychiatrie.

Kein Wunder also, dass die Pharma-Forschung in diesem Segment mit Hochdruck vorangetrieben wird und neben den Branchenriesen auch allerhand junge und kleinere Firmen fieberhaft an der Entwicklung neuartiger Gedächtnis- und Lernpillen arbeiten. Denn auch das zeichnet sich ab: Sollte es gelingen, die schweren manifesten Hirnerkrankungen mittels Neuro-Pharmakologie in den Griff zu bekommen, könnten davon auch all jene profitieren, die an milden kognitiven Störungen (MCI,Mild Cognitive Impairment), sprich der Altersvergesslichkeit, leiden – was auf rund 60 Prozent der Älteren zutrifft und inzwischen zumindest in den USA von der Federal Drug Administration sogar als Krankheit anerkannt worden ist.

Und nicht zuletzt werden sich auch die (noch) ganz Gesunden für die Medizin interessieren, die ihnen helfen kann, die Anforderungen in ihrem Alltag mit höchster Konzentration und Gedächtniskraft zu bestehen. Schon heute wird die "pharmakologische Optimierung überall eingesetzt: zur Verbesserung der Stimmung, der Wahrnehmung und von vegetativen Funktionen wie Schlaf, Appetit und Sex", fasst Neuropsychologin Dr. Martha Farah die Entwicklung zusammen (in: "Technology Review" 10/03). So dient etwa Prozac in den USA nicht mehr nur der Behandlung von schweren Depressionen, sondern wird auch von Menschen eingenommen, die sich davon mehr Selbstvertrauen und Lebensfreude erhoffen.

Stand der Forschung:
"Die großen Pharma-Unternehmen erforschen solche Substanzen nicht nur zur Behandlung von Demenzerkrankungen, sondern auch im Hinblick auf ganz normale Menschen – dort wartet der Profit. Die Behandlung der Demenzerkrankungen liefert ihnen die medizinische Rechtfertigung." meint Neurowissenschaftler Prof. James McGaugh in: "Technology Review" 10/03

• "Früher oder später wird es Medikamente geben, die zumindest Teile unseres Denkens verbessern", gibt sich Neurowissenschaftler Dr. Gary Lynch optimistisch und hat zum schnelleren Erreichen dieses Ziels das Unternehmen Cortex Pharmaceuticals gegründet. Der bislang größte Erfolg der Forscher dieser Firma: die Entwicklung so genannter Ampakine, einer Wirkstoffgruppe, die die Funktionen des Ionenkanals an der Nervenzelle verändern, so dass mehr Kalzium-Ionen hineinströmen können und damit das Signal zur Gedächtnisbildung verstärkt wird. Die ersten Tests mit Patienten verlaufen erfolgreich.

• Auch bei Memory Pharmaceuticals sind die ersten Tests mit Patienten angelaufen. Das Unternehmen arbeitet unter Federführung des Nobelpreisträgers Prof. Eric Kandel an der Entwicklung eines PDE-4-Hemmers. Der neue Wirkstoff soll den Abbau eines Signalmoleküls (cAMP) durch das Enzym Phosphodiesterase (PDE) blocken und so einen positiven Einfluss auf die degenerativen Hirnveränderungen ausüben. Mit beteiligt an der Entwicklung ist Großkonzern Roche.

• Zur Erreichung eines anderen Forschungsziels ist man bei der Firma Memory Pharmaceuticals eine Lizenzvereinbarung mit Bayer eingegangen, so dass das Leverkusener Unternehmen im Falle des Erfolgs die Vermarktungsrechte am Wirkstoff MEM 1003 besitzen wird. Auch dieser soll Veränderungen am Ionenkanal der Nervenzellen bewirken – die erste klinische Testphase ist inzwischen abgeschlossen. Schließlich arbeiten auch Forschergruppen bei den Pharma-Riesen GlaxoSmithKline, Johnson & Johnson und Merck sowie von zahlreichen jungen Pharma-Unternehmen wie Helicon, Axonyx oder NeuroLogic an der Erforschung neuer Neuro-Pillen.

Prognose des Zukunftsinstituts (Matthias Horx):
"Cognition Enhancer sind eine Zeitbombe" äußert der Alzheimer-Experte und Neuroforscher vom European Molecular Biology Laboratory in Heidelberg, Prof. Konrad Beyreuther. Schließlich rückt mit den neuartigen Hirnpillen auch die Essenz des Menschlichen in Griffweite: die pharmakologische Verstärkung und biochemische Lenkung der Hirnfunktionen. Doch was für die einen Anlass zu Besorgnis erregender Diskussion über die ethischen Aspekte eines solchen Brain-Tunings gibt, stellt für die anderen den größten Pharma-Markt der Zukunft dar. Die Möglichkeit, die eigene Kreativität und mentale Fitness zu verbessern, wird weltweit künftig noch mehr Menschen faszinieren. Und der wachsende Patientenstamm mit echten degenerativen Hirnerkrankungen pusht die Entwicklung zusätzlich.

(Der Zukunftsletter erscheint 12-14mal im Jahr, jeweils zum Preis von 15,24 Euro im Verlag für die Deutsche Wirtschaft AG, Theodor-Heuss-Str 2-4, D-53177 Bonn, Deutschland; http://www.zukunftsletter.de oder http://www.zukunftsinstitut.de; Oktober 2004)

[Erbse1]

Hallo liebe Cortex Freunde,
es tut sich langsam was bei den Fragile X Versuchen. Letzte Woche kam die Meldung, daß die Rekrutierung abgeschlossen ist.

Effects of CX516 on Functioning in Fragile X Syndrome and Autism
This study has been completed.

http://www.clinicaltrials.gov/ct/show/NCT00054730

Erfahrungsgemäß dauert es dann noch einige Zeit, bis die Ergebnisse ausgewertet sind.




Dazu die Meldung von FRAXA

<<<Since June 2002, a landmark clinical trial has been underway to evaluate this new potential treatment for Fragile X and autism. The compound being tested, Ampakine CX516, may help improve learning and memory in Fragile X by correcting a defect in the strength of brain cell communications. This is a two year clinical trial of the first specific treatment for learning and memory deficits in Fragile X. The trial should be completed by the end of 2004; it will then take some time to analyze and publish the results.>>>
http://www.fraxa.org/ra_Berry-Kravis.aspx

Hintergrundinformationen zu Fragile X gibt es einige Postings zurück. Zu erwarten ist, daß wohl eine potentere Substanz als CX516 zur Marktreife gebracht werden soll. Gespannt bin ich aber trotzdem auf die Ergebnisse mit CX516.

Hier noch mal der link zu der DIA Show von einer Cortex Präsentation zu Fragile X.

http://vm-elsig.de/achim/Fragile/

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,

heute möchte ich mal einige Gedanken zu dem Gebiet Schizophrenie und der letzten Meldung zu ORG-24448 äußern.

Wissenswertes und einige Grundlagen zu dieser Erkrankung gibts unter folgendem link.

Grundwissen Schizophrenie
Was sind Psychosen?
http://www.bayervital.de/pages/therapiegebiete/schizophrenie…

Weitere Informationen zu dem Themengebiet Schizophrenie gibts unter den folgenden links.

http://www.biospace.com/news_rxtarget.cfm?RxTargetID=188
http://www.hubin.org/news/archive/index_en.html
http://www.docguide.com/news/content.nsf/PatientResAllCateg/…

Der nächste Bericht beschreibt die aktuelle Entwicklung im Bereich der Psychosemedikamente. Dies dürfte auch kalabrienfan interessieren, da hier auch Memantine aufgeführt wird. Memantine sowie einige andere Kandidaten werden in Testphase 2 gegen die kognitive Symptomatik getestet. Von Aricept ist mir bisher kein Test gegen die kognitive Symptomatik bekannt. Die Daten vom Schaubild können dann allerdigs nur als grober Hinweis gedeutet werden.

New Schizophrenia Medications in the Pipeline

http://www.schizophrenia.com/newmeds2004.htm

Interessant wird die ganze Tatsache dadurch, daß Aricept im Tierversuch gegen CX717 getestet wurde. Gleich folgt ein Schaubild zu diesem Test. Dieser Test wurde allerdings bei Schlafentzugsversuchen durchgeführt.
Es besteht allerdings ein Zusammenhang von Schlafstörungen bei Schizophrenieerkrankten und kognitiver Leistungsminderung.

Möglicher Therapieansatz bei Schizophrenie-Patienten mit Gedächtnisstörungen
Je mehr Tiefschlaf, desto besser das Gedächtnis
http://www.aerztezeitung.de/docs/2005/01/20/009a1301.asp?cat…
ORG24448 gehört zur gleichen Wirkstoffgruppe wie CX717 , so daß wir von einem ähnlichen Wirkprofil wie bei CX717 ausgehen können.



Es wundert mich also nicht, daß ORG24448 als einer von bisher zwei Kanditaten von Turns augesucht wurde.



<<<Two compounds were selected to move forward for inclusion in TURNS conducted clinical trials. Org 24448, developed by Organon Inc., modulates the activity of AMPA-R receptors in the glutamate system. TC-1734, developed by Targacept Inc., is a partial agonist of the alpha-4-beta-2 nicotinic acetylcholine receptor. The TURNS network is planning to study these compounds in separate trials during the spring and summer of 2005. >>>

Dabei werden folgende Aspekte untersucht.

Overview of Impaired Cognition in Schizophrenia

Schizophrenia is associated with a range of impairments in neurocognitive domains that include memory, attention, executive functioning, and psychomotor performance. These impairments appear to be a core feature of schizophrenia because such deficits are found in attenuated form in first-degree relatives of patients and because they are independent of the psychotic symptoms of the illness. Cognitive impairments are common at the onset of schizophrenia and can frequently be identified in childhood, well before psychotic symptoms emerge. In contrast to psychotic symptoms which are typically episodic, impairments in cognition appear to be a stable feature of the illness. Most contemporary models for conceptualizing schizophrenia recognize that impairments in neurocognition should be included as a distinct feature of the disorder, in addition to negative symptoms, positive symptoms, and thought disorganization.

Given the wide range of cognitive deficits in schizophrenia, there is uncertainty about which domains are the most important to measure and to treat. One of the key goals of the NIMH Contract: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), is to identify the cognitive domains to be assessed in the NIMH consensus battery that will be used in TURNS, and in other clinical trials of pro-cognitive medications for schizophrenia. Based on a review of existing data sets, the MATRICS Neurocognition Committee concluded that there was empirical support for six separable cognitive domains: Verbal Learning and Memory, Speed of Processing, Working Memory, Reasoning and Problem Solving, Attention/ Vigilance, and Visual Learning and Memory. Based on responses from participants at the first MATRICS consensus meeting, held in April 2003, one additional domain was considered important to assess in the MATRICS battery: Social Cognition.

Cognitive impairments are important as a treatment target because they have a substantial impact on the outcome of schizophrenia. Literature reviews by Green and colleagues have demonstrated that there are consistent relationships between cognitive deficits measured in the laboratory and functional outcome in schizophrenia, including social outcome, vocational outcome, and success in rehabilitation programs. These relationships between neurocognitive deficits and functional outcome are found in both cross sectional and longitudinal studies. In contrast to cognitive deficits, clinical symptoms are only weakly related to functional outcome in schizophrenia. The magnitudes for the relationships between cognitive deficits and functional outcome are medium for individual cognitive constructs (such as those identified as separable factors by the MATRICS Neurocognition Committee) and the relationships can be large when summary scores (e.g., composites of several cognitive functions) are used. This literature on cognitive linkages to functional outcome provides a rather compelling rationale for intervention at the level of cognition.

Antipsychotic medications may lead to some improvement in cognition in schizophrenia, although the overall effects are relatively weak. A body of research suggests that second generation antipsychotic medications appear to have beneficial effects on cognition, at least when compared with first generation agents. However, patients with schizophrenia often perform two or three standard deviations below the mean of controls on neurocognitive tests and newer antipsychotic drugs only make up a fraction of that difference. This gap in the effectiveness of antipsychotic drugs for neurocognition has inspired a search for co-treatments that can be added to an antipsychotic to improve cognition.

Dies wars erstmal zu diesem Themengebiet

Schönen Tag noch
Erbse

[Erbse1]

Auch der Neuroinvestor hat sich gestern zu dem Themengebiet ORG24448 geäußert. Ich kopier den Artikel mal kurz hier rein.
Schönen Tag noch
Erbse

I think the schizophrenia story has moved beyond the `colossally speculative`. The decision by the NIMH sponsored TURNS group--whose task it is to find sz drug adjuncts that will improve cognition--was to choose two drugs for Phase II trials: They chose a nicotinic agonist from Targacept and Org24448.There were quite a number of candidates (who wouldnt want a Phase II run on NIMH`s dime--other than BPs?). This is--to me--the first independent indication that Org24448 has looked good in Phase II--the drug would not have been chosen without a look at that data. This may only be a proxy for having demonstrated efficacy, but it does say something beyond theoretical rationale. And it`s not like there aren`t a lot of companies looking to improve negative and cognitive sx in sz, I am preparing a review of sz right now, and it`s a hot area.

I believe schizophrenia could be the first major indication in which an Ampakine receives approval. It`s the only one in Phase IIb. I suspect Cortex`s royalties are tiered--I vaguely remember (my records are all in storage due to a relocation in progress) Vince Simmon making reference to the 8-10% range, but I believe Roger Stoll has reported `double digits`--perhaps it`s once sales reach a certain threshold. The problem with the Organon deal was not so much the royalty rates, as the paltry upfront and milestone payments--it was very backloaded, and Organon has been a sloth of a partner.

No one--even, so far as I can tell, Cortex--had gotten access to Organon`s Phase II sz data in detail until the TURNS committee did, and I personally am impressed that Org24448 was chosen. My understanding is that they would have been even happier to use CX717, but since Organon holds the schizophrenia license.....

COR management isn`t in a position to `trumpet` Org24448. And what biotech `experts` have seen the data? None--just the TURNS group. So their response does mean something to me, and it will mean something to BP companies assessing Ampakine partnership options. Will that in itself will add value to the stock price before the TURNS data comes out in 2006? Maybe not, but I am excited about it.

NeuroInvestment

Quelle:
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Coverage initiated on Cortex Pharm by Rodman & Renshaw

09:38 COR Cortex Pharm: started with Outperform and $8 price tgt at Rodman & Renshaw (2.70 +0.11)

Rodman & Renshaw initiates COR with an Outperform and $8 price tgt. Firm notes that memory and cognition disorders impact approximately 200 mln people worldwide, and the so-called AMPA receptor appears to be the most validated memory target. They believe COR is the pioneer in the development of AMPA-modulating compounds. Following a recent setback of a competitor, firm believes that within 6-12 months, Cortex could have the most advanced AMPA modulator and memory enhancer in mid-stage development. With successful clinical results and a partner on board, firm believes Cortex`s enterprise value could jump from its current $60 mln to the $250 mln level.

Schönen Tag noch
Erbse

[netStarHamburg]

Der ehemalige CEO von Questcor Pharmaceuticals / QSC / 899085 soll CEO von Cortex / COR werden.

QSC halte ich als Turnaround-Kandidaten für sehr interessant.

[Erbse1]

Wenn ich das richtig sehe, ist Cortex CEO Stoll gelegentlich mit an Board als Direktor von Questcor

<<<In addition to the Cortex board, Dr. Stoll currently serves as a member of the boards of directors of Agensys, Inc., Questcor Pharmaceuticals, Inc., and LifePoint, Inc. Dr. Stoll obtained a B.S. in Pharmacy from Ferris State University and a Ph.D. in Biopharmaceutics from the University of Connecticut.>>>>

http://www.cortexpharm.com/html/corp/index.html

Wenn Deine Meldung stimmen sollte bitte mit Quellenangabe. Ich halte es einfach nur für ein Gerücht

Liebe Grüße
Erbse

[netStarHamburg]

Sorry, meine Fehlinterpretation eines Beitrags auf dem QSC-Yahoo-Board.
Der ehemalige CEO von QSC, Charles J. Casamento ist BOD-Mitglied bei COR, nicht CEO.

COR & QSC scheinen Verbindungen untereinander zu haben.

Bin seit 2004 in QSC investiert.

Turnaroundwert, Insiderkäufe, Fonds und das bei einem (noch) Pennystock...schaun wir mal

[puhvogel]

Es gibt drei Firmen/Aktien, die ich regelrecht hasse. Und Questcor ist eine von Ihnen, die einzige Biotech übrigens.

Wenn der Casamento CEO von Cortex wird, dann verkaufe ich die sofort. Der hat schon Cypros mit seiner spannenden Pipeline zerstört. Ich weiß nicht, wie es der Casamento immer wieder schafft, Geld zu beschaffen und Leute zu beeindrucken, aber der muß hypnotische Fähigkeiten besitzen.

[Coluche]

Hallo puhvogel, kannst du deine Abneigung etwas präzisieren. Das sind für mich immer Hinweise, denen man mehr Beachtung schenken sollte als man dies hinlänglich tut.

Bin immer noch in Cortex investiert und möchte mich an dieser Stelle auch mal wieder bei Erbse für seine unermüdliche Arbeit bedanken (selbst bin ich bei HGRD nicht immer so fleißig ;-)).

Hatte mich dieser Tage mal mit einem Wissenschaftler aus der Neuropharmazie unterhalten, der Cortex als ein spannendes Investment sieht, ihnen aber nicht so viel zutraut, da er davon überzeugt ist, daß die Patente auf diese Ampakine auf Dauer nicht haltbar sind (seien wie ein Patent auf Wasser - aus wissenschaftlicher Sicht), und Ely-Lilli nur deshalb verloren hat, weil sie den Rechtsstreit mit Cortex unterschätzt hatten.

Er empfiehlt, sich mal mit Memory Pharma und Neurochem zu beschäftigen und diese als Diversifikation in ein Neuro-Pharma-Portfolio mit aufzunehmen. Werd ich mal recherchieren.

Gruß Coluche

[Erbse1]

Hallo Coluche,
schön mal wieder von dir zu hören. Zur Patentlage habe ich ein Schaubild von der letzten Cortex Präsentation. Es handelt sich dabei gar nicht um nur nur ein Patent, sondern um eine ganze Reihe. Streitig ist im Augenblick nur eins zur Erteilung in Europa.

Als zweites hänge ich noch ein Bild zur Aktienanzahl von Cortex vor der letzten Kapitalmaßnahme dran. Tatsächlich ist man jetzt bei einer Gesamtzahl von ca. 50 Millionen angelangt.

Schönen Tag noch
Erbse

[Erbse1]

Artikel zu Fragile X mit Ankündigung baldiger Veröffentlichung Der Phase 2 Versuche.

Grüße
Erbse

Research suggests brain drugs can ease a common mental defect

Scientists in the Phila. region used fruit flies to study the potential for fragile X treatments.

By Stacey Burling

Inquirer Staff Writer


New research lends support to the idea that medications aimed at fixing chemical abnormalities in the brain may one day help people with the most common form of inherited mental retardation: fragile X syndrome.

Scientists at the University of Pennsylvania, Drexel University and Albert Einstein medical schools found that treatment with several drugs improved learning in fruit flies that had the same genetic abnormality as people with fragile X. The drugs - lithium, a mood stabilizer often used to treat bipolar disorder, and several medications not approved by the FDA - are believed to improve connections between neurons in a chemical system important for learning and memory.

It`s difficult to know how the medications might affect humans, said Thomas A. Jongens, associate professor of genetics at Penn and senior author of the study published in today`s issue of Neuron. "The hope is that these drugs might actually ameliorate some of the symptoms of fragile X."

Other genetics experts cautioned that there are big differences between fruit flies and humans, but said the new study bolsters similar findings in mice.

Fragile X, caused by malfunctioning of the FMR1 gene, affects 1 in 4,000 males and 1 in 8,000 females. Characteristics include low IQ, short-term memory deficits, autistic behavior and attention problems.

In the experiment, Jongen said, normal male fruit flies were placed with females who had already mated. They were rejected in no uncertain terms. The males were traumatized by the rejection, Jongen said, and would not romance a virgin fly for at least three hours after the experience. Fruit fly experts consider this learning.

Under the same circumstances, flies with the fragile X-like mutation behaved as if they had never been rejected. But, after eating any of the five drugs, they acted like normal fruit flies, Jongen said.

Stephen Warren, a human geneticist at Emory University, said he and Mark Bear, a neuroscientist at the Massachusetts Institute of Technology, first theorized about two years ago that animals with the genetic malfunction have what are called overactive metabotropic glutamate receptors. These receptors, Warren said, tend to overproduce proteins which then disrupt connections between brain nerve cells.

Jongens` team tested four investigational drugs that block action at the receptors, and lithium, which disrupts the pathway farther down the line. The investigational drugs are unlikely to get FDA approval, he said, because of their side effects.

All the drugs seemed to be equally effective at improving memory in the flies who were missing the fly equivalent of the FMR1 gene.

Brenda Finucane, executive director of genetic services at Elwyn Inc., said short-term memory is a significant problem for people with fragile X. "It takes them many, many repetitions before they can get something into long-term memory," she said. Long-term memory functioning is quite good, she added.

Lithium is used in some people who have the disorder and bipolar symptoms. She said she had never heard of a dramatic change in thinking ability in people taking the medication. That doesn`t mean, she said, that "there couldn`t be subtle but important differences."

Jongens said clinical trials will now be done to evaluate the drug`s effect on cognition.

Cortex Pharmaceuticals, in Irvine, Calif., is testing another drug, called CX516, in people with fragile X syndrome. Results should be available "relatively soon," said Hank Mansback, the company`s chief medical officer.

[Erbse1]

Hallo liebe Cortex Fans,
Cortex präsentiert mal wieder. Es ist sehr gut möglich, daß hier die Ergebnisse von CX717 bei Schlafentzug präsentiert werden.
Außerdem stehen noch in nächster Zeit die Phase 2 Ergebnisse bei Fragile X mit CX516 an.

Schönen Tag noch
Erbse

NEW YORK--(BUSINESS WIRE)--March 7, 2005--Rodman & Renshaw is pleased to announce that its 2nd Annual Global Healthcare Conference will take place at the Intercontinental Hotel in Paris, from 4th May to 6th May 2005.

http://www.companynewsgroup.com/communique.asp?co_id=98975

[Erbse1]

Zu Fragile X gibt es eine Stellungnahme von Elizabeth Berry-Kravis. Dabei ist von CX717 als wirkungsvolleres Medikament die Rede. Gleichzeitig ist dies der Hauptkandidat zur Auslizensierung. Mal sehen wie Cortex dieses Problem löst.
Schönen Tag noch
Erbse

Folgendes posting ist eine Anfrage von dem user ombowstring aus dem Yahoo-Board.

I contacted Elizabeth Kravis-Berry, who is doing the CX516 study in Chicago for Fragile X. This was her response:

John - My hospital referral service for clinical trials forwarded your email to me. We just finished the CX516 study and are in the process of analyzing the data. The study was foremoest a safety study but we have some efficacy data. It will be written up for publication this Spring or Summer. I am in close contact with Roger Stoll at all times and we have discussed the possibility of a CX717 trial in fragile X as it is likely that compound will be more effective than CX516. Certainly if we can show an ampakine is helpful in fragile X, we would push for an Orphan Drug indication through the FDA. Thanks for your interest.

Liz Berry-Kravis

http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hab noch einen tollen Artikel zu Schizophrenie gefunden.
Dank an den User gfp927z. Auch der Neuroinvestor schreibt diesen Monat zu diesem Thema.
Schönen Tag noch
Erbse

Schizophrenia / cognition / Ampakines

Using an Ampakine in combination with the current atypical antipsychotic meds is emerging as one of the most promising indications for Ampakines, and is in fact our most advanced clinical program (partnered with Organon).

The recent selection of Org-24448 (CX-691) by NIMH/TURNS for their combo Schizo Phase 2b was a major validation for Cortex`s low impact family of compounds and for the Ampakine platform as a whole. NIMH/TURNS undoubtedly based their decision upon seeing Organon`s as yet unpublished Org-24448 Phase 2 Schizo data, so their decision is a strong signal that Org-24448 has been helping these Schizo patients considerably, and has had good safety characteristics. NIMH/TURNS selected Org-24448 ahead of the large number of other drugs submitted. As we know, Org-24448 is a sister compound of CX-717, both developed by Cortex and the lead compounds in our low impact family.

Preclinical studies have shown that the activity of even subthreshold doses of antipsychotics like Clozapine are greatly enhanced by Ampakines (see post 18702).
In the glutamate/dopamine hypothesis of Schizophrenia, the dopamine pathways are seen as being overactive (causing delusions / hallucinations), while the glutamte pathways are underactive (contributing to cognitive impairment). In fact, beyond mere cognitive impairment, glutamatergic hypofunction (particularly of the NMDA receptor) may also contribute to the other major psychotic symptoms. Current antipsychotic meds do nothing to correct the glutamate underactivity, and often exacerbate the patient`s cognitive impairment, along with causing a host of other serious side effects.

Using an Ampakine not helps to upregulate the underactive glutamate pathways, but also may allow lower dosing of the atypical antipsychotics meds, thereby lessening their various side effects (weight gain, sexual dysfunction, diabetes, agranulocytosis, cataracts, etc).

Low impact type Ampakines are particularly well suited for Schizophrenia, since significant neurotrophin upregulation isn`t a requirement, but very high safety is. Ampakines also upregulate NMDA activity indirectly (NMDA receptors being part of the underactive glutamatergic pathways), since NMDA receptors are downstream of AMPA receptor activity. In addition, Ampakines may prove to be safer than direct NMDA agonists, in part because Ampakines are allosteric and as such don`t create their own neuronal activity, but merely amplify/prolong the normal neuronal activity that is already present

http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Fans, habe zu der Fragile X Thematik eine Radiosendung gefunden. Es geht um den englischen Artikel mit den Fruchtfliegen.

Pille gegen Erbkrankheit

Gedächtnisstütze für kranke Fliegen
Von Volkart Wildermuth
Medizin. - Geistige Behinderung. Diese Diagnose ist immer ein Schock für die Eltern. Es gibt viele Hilfen für diese Kinder, aber keine Heilung. Mit dieser pessimistischen Prognose wollen sich viele Forscher nicht mehr zufrieden geben. Sie suchen nach Medikamenten, die dem Verstand auf die Beine helfen sollen. Noch wagen sie sich allerdings nicht an die Patienten heran. Sie versuchen zuerst einmal kranken Fliegen zu helfen, wie sie in der aktuellen Ausgabe der Zeitschrift "Neuron" berichten.>>>>

Den kompletten Artikel und die Radiosendung vom Deutschlandfunk gibts unter folgendem link.
http://www.dradio.de/dlf/sendungen/forschak/352924/

Schönen Tag noch
Erbse

[Erbse1]

Es liegt eine Stellungnahme zu den Fragile X Versuchen. Wie erwartet ist CX 516 nicht potent genug.

Ich denke mal dieses Ergebnis hat jeder erwartet.

Liebe Grüße
Erbse

Clinical Trial of a New Medication in Adults with Fragile X


Elizabeth Berry-Kravis, MD, PhD
RUSH University, Chicago

This two year study was originally funded in 2001 and renewed in 2002 for a total of $144,000.





In June 2002, a two year clinical trial was started to evaluate the first specific treatment for learning and memory deficits in Fragile X and autism.

Over the past decade, several pharmaceutical companies have been developing a new class of medications, Ampakines, which seem to enhance learning. Ampakines may help improve learning and memory in Fragile X by correcting a defect in the strength of brain cell communications. The compound used in this trial, Ampakine CX516, is the first of a series of compounds developed by Cortex Pharmaceuticals.

This two-year study has concluded as of March, 2005. A total of 49 adults with fragile X at RUSH University and 8 at the University of California at Davis (funded by the MIND Institute) have taken either the drug or placebo (sugar pills) for a 4 week period. Dr. Elizabeth Berry-Kravis and her team are currently analyzing the massive amount of data that was collected during the study. The study was "double blind" which means that neither the participants nor the doctors knew which people were on drug and which were not.

In early March 2005, Dr. Berry-Kravis and her team officially broke the blind and they now know which participants were taking CX516. Although the data analysis will continue for several months, it does not appear that the drug had a significant effect on thinking skills in fragile X participants. Behavioral information is still being analyzed.

Although the drug did not show therapeutic effects on participants with fragile X, the team has obtained valuable information regarding how to best test individuals with fragile X syndrome in a medication study. This new knowledge will help immensely in designing upcoming medication studies.

What does this mean for the future of ampakines as treatments for fragile X? The compound used in this trial, CX516, has been demonstrated to be very safe but not potent. Weak ampakines needed to be tested initially to make sure they were not dangerous to people. In fact, the dose of CX516 might have to be as much as four times higher to see good effects on cognitive skills.

Because the drug was safe and did not cause side effects like seizures, future trials can be considered using more potent ampakines more likely to provide cognitive benefit. Potent ampakines which last longer in the body are currently being tested in the mouse model of fragile X (see research project of Dr. Julie Lauterborn). The outcome of this and other studies will help determine whether stronger ampakines may be effective in treating fragile X; new trials will be planned if stonger ampakines seem likely to help.

We are grateful to all the wonderful families and adult Fragile X subjects who have made the considerable effort required to participate in this study. They are helping lay the groundwork for future treatment of cognition in Fragile X syndrome.

Kompletten Artikel unter folgendem link
http://www.fraxa.org/ra_Berry-Kravis.aspx

[Erbse1]

Hallo liebe Cortex Fans, habe einen interessanten Artikel zu Schizophrenie und kognitiven Defiziten gefunden.
Das Manko bei dieser Erkrankung ist nun, daß sehr wohl die Positivsymptomatik, also die Wahnideen behandelt werden. Bei den kognitiven Symptomen dagegen sieht es dann nicht mehr so gut aus.
Es wird also sehr lange dauern bis die Krankheit Schizophrenie als Ganzes gesehen wird, also mit Positivsymptomatik, Negativsymptomatik und den kognitiven Defiziten.
Dies betrifft auch Cortex mit ORG24448. Sollten die Ergebnisse positiv ausfallen, so liegt ein langer schwieriger Weg bei der Vermarktung vor Organon und Cortex.
Es wird sich sicher auch nicht jeder die Medikamente leisten können, wenn sie dann einmal auf dem Markt sein sollten.
In der Psychiatrie allerdings dauert alles sehr lange. Dies dürfte auch bei ORG24448 der Fall sein.
Folgend noch der link zu dem Artikel.

Schönen Tag noch
Erbse

Common Schizophrenia Symptoms Often Overlooked By Physicians
http://www.docguide.com/news/content.nsf/news/8525697700573E…

[Erbse1]

Der Neuroinvestor meldet sich auch noch mal in Sachen Cortex.

Cortex
(March 2005 issue comment)

The share price remained surprisingly stagnant with little volume--given the events cropping up over the next several months. Data for CX717 in April should be enough to elicit--within the ensuing three to six months-- the signing of a deal between Cortex and one of the numerous Big and midsize Pharma companies interested in partnering. We have been asked by several investors and observers why we maintain such a high target given Cortex`s laggard price performance--the best answer is to look at Neurogen January 2003-April 2004. During that period they partnered their VR-1 pain program with Merck, for $30 million upfront (half in equity), even though it had--and has--not yet reached the clinic. The market cap over the following 15 months went from $60 million to $350 million, and has remained strong even though the complement and CRF programs have both had serious setbacks.
The confluence of IP interests and territory was important to Merck and Neurogen, and we would not be surprised to see a similar meshing of development priorities with the Cortex deal--which means the companies who have either R&D history with the area (Lilly, GSK), or CNS management with AMPA experience and interests (Amgen), As is discussed in this issue, the Organon-run AMPA modulator program in schizophrenia was one of two (along with a Targacept drug) to be chosen for clinical trials by the NIMH-sponsored TURNS program. Organon is already on record as saying that they want to outlicense/partner late clinical stage programs--Org24448/CX691 is nearing a suitable point. Cortex plus Organon`s schizophrenia rights (throwing in depression as a sweetener) would look great in a Big Pharma`s Christmas stocking. Our target remains 12.

http://www.neuroinvestment.com/CORXcom.html

Einen weiteren Überblick zu den Ampakinen gibts von gfp927z.

http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Jetzt ist erst mal Warten auf die CX717 Ergebnisse bei Schlafentzug angesagt. Viele rechnen schon im April damit.

Schönen Tag noch
Erbse

[Erbse1]

Hab noch einen interessanten Artikel zu MEMY und COR gefunden.

Wettlauf gegen das Vergessen: Forscher entwickeln Pillen für ein besseres Langzeitgedächtnis

http://www.wissenschaft.de/wissen/hintergrund/250429.html

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans, jetzt wirds langsam ernst. Die Ergebnisse bei Schlafentzug Phase 2A stehen an.
Hier die Ankündidung vom letzten SEC Filing.

<<<The Company is currently underway in a Phase I/II pilot efficacy in sleep deprivation in the U.K. Cortex hopes to have results from this trial by the end of April 2005, which may provide it with a dose range for future efficacy studies. Cortex plans to conduct several small pilot efficacy trials with CX717 during the first nine months of calendar 2005.>>>

Das gesamte Filing gibts unter folgendem link. Jede Menge Recherchestoff für Neueinsteiger.
http://secfilings.nasdaq.com/filingFrameset.asp?FileName=000…

Morgen gibts übrigens eine Konferenz von Cortex
Cortex to Host Conference Call to Discuss Results for the Six-Months Ended December 31, 2004
http://biz.yahoo.com/bw/050321/215253_1.html

Schönen Tag noch wünscht euch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde, folgend eine Zusammenfassung von der gestrigen Konferenz. Es geht alles seinen normalen Gang. Hoffen wir mal auf gute Ergebnisse Ende April.

Schönen Tag noch.
Erbse

Dank an gfp927z für die ganze Arbeit

A brief summary of today`s Conf call -

1) Finances - Cortex had $28 mil at the end of 2004, and Dr. Stoll expects expenses for 2005 to be approx $14 mil, +/- $1 mil.

2) CX-516 Fragile-X trial - Based on what we now know about CX-516, to get efficacy in Fragile-X would have required approx 3 grams of CX-516 given 4 or 5 times per day (the trial only dosed at 900 mg 3xday). So there`s no way that there could have been much efficacy shown in that trial. When the Frag-X trial was originally designed, they knew that CX-516 was weak, but the data showing just how weak it was came well after the Frag-X trial was underway. Dr. Berry-Kravis is very interested in trying a potent Ampakine. A higher impact Cortex compound was found to elevate BDNF levels by 2-3 fold after only 5 days of dosing in rats, and there was a positive impact seen in rats engineered to have the Fragile-X gene deficiency.

3) CX-717 UK Sleep Dep trial - The trial is in its final (4th) phase, which will be finished at the end of next week. This trial is measuring 10 different efficacy parameters, involving memory, cognition, and attention. The trial was blinded, and used 3 different dosing levels against placebo. The trial proceeded well and enrollment was good. The principal investigator estimates that data lock can occur by mid April, and Dr. Stoll says we can expect to see top line results by the end of April/early May at the latest (Cortex will be at the May 4-6 R+R Conference).

4) AD Phase 2a trial - Is now under IRB review at the Univ of Michigan. The trial should get underway by late May/early June, with an interim analysis by the end of June/early July. The interim analysis will allow them to see how it`s going, and up the dose if needed (as we know, there`s plenty of leeway to raise the dose as needed).

5) ADHD Phase 2a trial - The protocol will soon be submitted to IRB. Study should be underway by June and will use multiple dosings.

6) DARPA/Sleep Deprivation - Based on the outcome of the UK study, Dr. Stoll anticipates that there will be an announcement relative to further studies in Sleep Dep with DARPA.

7) 3 month tox studies in 2 species (CX-717)- monkey dosing completed, all monkeys came through A-OK, waiting for histopathology analyses of organs/tissues. Rats are in 22nd day of dosing, proceeding uneventfully. Full analysis by the end of August, which will allow a Phase 2b human trial with 3 month dosing to start in the last quarter of 2005 in either ADHD or AD.


8) Question + Answer section -

a) Status of new compounds - Two of the low impact backup compounds to CX-717 being developed are CX-727 and CX-701 (at the SHM, Dr. Rogers showed a graph comparing CX-717, CX-727, CX-701, and Aricept in Dr. Deadwyler`s primate delayed match to sample tests). Both look very promising, and are going through metabolic/pre-tox workup prior to full tox studies. By early May they should be able to make a decision on which one of these compounds to move into full toxicolgy.
High impact - Cortex has a VERY significant ongoing program in the high impact area. As mentioned previously, a high impact compound was found to elevate BDNF by 2.5-3 fold after 5 days of dosing in rats. Longer term dosing studies with low impacts to see if they stimulate BDNF upregulation over time are also ongoing.

b) Compounds for in-house program - Cortex will try to resist outlicensing the 2nd compound. A program to produce additional low impact compound analogs is being kicked into gear also (most of Cortex`s available resources over the last several years were going into high impacts. Now we have the funds to do both simultaneously). A BP partner will probably have considerable interest in our high impacts as well as the low impacts.

c) BP partners - Dr. Stoll can`t say publicly how many interested BPs there are, only that interest is very strong. There are lots of contacts, consistent contacts from companies that have followed Cortex`s progress closely. Dr. Stoll wants a carve out for Cortex (in-house program/indication), and the BP deal must be of sufficient magnitude to provide Cortex with substantial funds to move strongly ahead with the in-house program after the BP deal. Sleep Dep data might be enough to get some BP offers, the question then is are these offers good enough for Cortex?

d) Patents - Many of the patents expire around 2017 (2016-2018). Dr. Stoll wants to have as much time on the market under patent protection as possible. Ideally he`d like to have 3 or 4 compounds in the clinic to give us numerous "shots on goal" to increase the chances for success.

e) IP situation in Europe (Lilly/Glaxo challenge) - could take several years to resolve. Univ of Calif is backing Cortex, and our eventual BP partner will also provide strong backing/resources.

f) Dr. Deadwyler`s Sleep Dep primate paper - Dr. Deadwyler had a disagreement with a journal reviewer and is submitting it to another prestigious journal for publication. The amount of data is very large.

g) Organon/Org-24448 - Phase 2b Schizo mono trial had enrolled approx 40 patients, and the NIMH/TURNS Phase 2b Schizo combo trial plans to enroll 100 patients. Both are substantial trials. Servier is in early Phase 2 with S-18986.

http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Fans. Der Kurs schlägt ja einige Kapriolen in den letzten Tagen. Zur Beruhigung habe ich mir noch mal die Meldung von CX516 aus dem Jahre 2003 durchgelesen. Für mich wäre es sehr überraschend, wenn die Ergebnisse bei CX717 schlechter ausfallen würden

Positive Effects of CX516 in Human Sleep Deprivation Study

Preliminary findings suggest CX516, compared to placebo improves performance in dose-related fashion in healthy subjects after 31 hours without sleep

http://www.cortexpharm.com/html/news/03/10-21-03.html

Von FRAXA wird gemeldet, daß nach den Mausversuchen nun auch mit einer neuen Testphase bei Fragile X begonnen werden soll. Bis jetzt ist aber immer noch nicht veröffentlicht worden, um welche Substanz es sich handelt. Gerüchterweise ist von CX717 die Rede. Falls ich was Genaues weiß, werde ich es hier im Board posten.

<<< The new class of drugs called Ampakines, is an example: FRAXA has funded a trial of Ampakines in fragile X mice and now will fund a trial of this medication in adults with fragile X >>>

http://www.fraxa.org/research_summaryfindings.aspx

Bin jetzt selber gespannt auf die Ergebnisse mit CX717 bei Schlafentzug. Es kann sich dabei nur noch um wenige Tage handeln.

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans.

Cortex präsentiert am Mittwoch nächster Woche auf einer Konferenz in Paris. Interessenten steht eine Live Übertragung zur Verfügung. Den link gibts in der Kopie der Meldung. Die Ergebnisse der Testphase 2a bei Schlafentzug sollen dort präsentiert werden.
Auf dem Yahoo Board geht eine Meldung um, daß kurz vorher eine Meldung von Cortex veröffentlicht wird.

Schönes Wochenende
Erbse

Press Release Source: Cortex Pharmaceuticals, Inc.


Cortex`s CEO to Speak at the Rodman & Renshaw 2nd Annual Global Healthcare Conference on May 4th, 2005 in Paris, France
Monday April 25, 9:00 am ET


IRVINE, Calif.--(BUSINESS WIRE)--April 25, 2005--Cortex Pharmaceuticals, Inc. (AMEX: COR - News) announced that Roger G. Stoll, Ph.D., Chairman, President and CEO will speak at the Rodman & Renshaw 2nd Annual Global Healthcare Conference in Paris on Wednesday, May 4th at 10:30 AM (local time) at the Intercontinental Hotel. Cortex is one of 180 invited companies to present at this conference to be held May 4-5, 2005.
Dr. Stoll will provide an update on Cortex`s AMPAKINE® clinical development program, with specific details related to CX717 and discuss upcoming clinical milestones. AMPAKINE compounds amplify the effects of glutamate, the primary excitatory neurotransmitter in the brain responsible for higher-order behaviors and cognitive activities, such as, thinking, smelling, touching and memory.

A live webcast of the presentation can be accessed by logging onto http://www.wsw.com/webcast/rrshq5/cor/ and a replay will be available for 45 days following the conference.

[Erbse1]

Cortex Reports Positive Effects of its AMPAKINE-R- CX717 in Human Sleep Deprivation Study
Monday May 2, 9:01 am ET
Preliminary analysis suggests CX717, when compared to placebo, increased wakefulness in a dose-related manner and improved performance of those subjects that were impaired
http://biz.yahoo.com/bw/050502/25417.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans.
Gleich noch mal die äußerst positive Meldung Von AP. Da kann man sich schon entspannter die weitere Entwicklung von Cortex anschauen. Weitere Einzelheiten gibt es Mittwoch Vormittag auf der R&R Konferenz in Paris. Den link zur Live Übertragung habe ich bereits gepostet. Die Übertragung beginnt am Mittwoch um 10.30
Hier noch mal der link. Da braucht ihr nicht so lange suchen.
http://www.wsw.com/webcast/rrshq5/cor/

Schönen Tag noch
Erbse

Cortex Says Drug Boosts Alertness in Study
Cortex Pharma Reports Ampakine-R-CX717 Wakefulness Drug Boosts Alertness in Clinical Study

IRVINE, Calif. (AP) -- Shares of Cortex Pharmaceuticals Inc. jumped Monday as the company said clinical data showed that its wakefulness drug candidate Ampakine-R-CX717 had a dose related effect in keeping sleep-deprived subjects alert.

The clinical study tested three doses -- 100 milligrams, 300 milligrams and 1,000 milligrams -- and found that low levels of performance were alleviated in subjects who were sleep deprived for 27 hours. In the study, 16 young healthy men were tested on memory, attention, vigilance, reaction time, and executive function.

At a 100 milligram dose, the study found that individuals had increased wakefulness overnight, but that the effect did not extend into recovery sleep the next morning. In the 300 milligram and 1000 milligram doses, the alerting effect of the treatment extended well into the recovery sleep the next day, the company said.

Cortex is focused on the development of Ampakine drugs, which are designed to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer`s disease, attention-deficit hyperactivity disorder, or ADHD, and sleep disorders.

The company said it planned to conduct pilot studies in a variety of brain disorders that might benefit from Ampakine.

The National Commission on Sleep Disorders estimates that 40 million Americans are either chronically or intermittently affected with various sleep disorders, Cortex said.

[Erbse1]

Hallo liebe Cortex Freunde.
Folgend eine Zusammenfassung aus dem Yahoo Board von der heutigen Konferenz. Nochmals herzlichen Dank an den User gfp927z für seinen unermüdlichen Cortex Einsatz. Es schaut bis jetzt alles sehr sehr gut aus. Wir haben ja auch lange genug darauf gewartet.

Liebe Grüße
Erbse

In addition to what others have said already, here`s a brief summary of the topics presented by Dr. Stoll -

1) UK Sleep Dep trial - They`ve only had the results for ~1 week, but Dr. Stoll said that we saw some very good results in EVERY ONE of the patients who showed performance decline after being sleep deprived. Cortex wanted to sleep deprive for 42 hours, but the clinicians running the trial opted for a shorter 27 hours to be on the safe side, in spite of CX-717`s extremely high safety and complete lack of excitotocxicity potential in the Phase 1 (the upcoming larger DARPA trial will likely push the envelope much further). A few of the patients didn`t experience much of any cognitive decline from the shortened 27 hour protocol, but those who did all saw good improvement from CX-717, and the level of improvement was directly dose related, with the 300 and 1000 mg doses showing the best activity. The "maintenance of wakefulness" test was discussed (a key test which had been run on Provigil during its testing). At the 300 and 1000 mg doses, CX-717 showed considerable wakefulness effect even at 11:00 AM the next day, which is pretty impressive from a single dose (only Amphetamines would have a similar duration effect from a single dose). It sounded like Dr. Stoll had a few slides at the conference presentation that weren`t shown on the Internet, so perhaps we`ll see these at the next presentation. All in all it sounded like CX-717 performed very well in the study. One of the parameters they tested for was attention related, and Dr. Stoll said that these good results support the idea that ADHD may be a very good target for CX-717.

2) CX-929, a high impact compound, was shown to upregulate BDNF levels by 2.5 fold in rats, in both cortical and hippocampal areas of the brain.

3) Dr. Lynch recently was able to demonstrate that high impact Ampakines can prevent the age related loss of synaptic plasticity (LTP) that normally occurs in middle aged whole animals. With the Ampakine, the LTP decline that normally occurs from aging no longer occurred, and LTP remained at the same level as it is in the younger animals (there`s hope for us baby boomers yet folks :o)

4) CX-727, one of the low impact back-up Ampakines in development, was shown to upregulate BDNF levels 10-20% in whole animals, and may be able to upregulate BDNF by approx 30-40% when given over extended periods. Dr. Stoll said they`ve seen this demonstrated several times now, and they are convinced that low impacts can significantly upregulate BDNF over time (albeit less dramatically than a high impact, but 30-40 % is huge when combined with a low impact`s extremely high degree of safety). So the neuro "holy grail" concept may still be alive and well even without the high impact approach.

5) CX-717 vrs Aricept - Not discussed due to time constraints, the bar graph on slide 16 shows how vastly superior CX-717 is compared to Aricept in Dr. Deadwyler`s primate studies. As an ACHase inhibitor, Aricept has a high level of GI related side effects which severely restricts its dosing (in addition to having CNS activity, acetylcholine is a key neurotransmitter controlling GI motility).

6) Alzheimer`s pet scan trial - could start enrolling this month (interim analysis by early July, as estimated at the March 23 Conf call).

7) Shift Work Sleep Disorder trial - this was completely new news. Now going through IRB, the trial should initiate in July, and will be a multidosing study. Aimed at the Provigil market, this additional data could help enhance the overall partnering package. Provigil`s success has demonstrated to BPs just how lucrative the Sleep related area is. As I understand it, recent developments relating to Cephalon`s Provigil patent may delay the onset of generic competition, which would enhance the Sleep area`s profit potential for BPs.

8) ADHD trial - Starting this Summer, with a 3 week dosing protocol. Results of the attention parameters tested for in the Sleep study apparently suggest that ADHD may be a good target.

These 3 studies should be completed by the Fall, with ADHD being the last to be completed. The 3 month tox studies in two species will be completed by the end of August (this being required prior to doing longer term Phase 2b type studies).

9) As was noted by previous posters, slide 28 listed as a milestone goal for late 2005 the initiation of a 3 month CX-717 double blind, placebo controlled study in mild to moderate AD patients stabilized on Aricept. Dr. Stoll didn`t discuss this directly, only saying that a Phase 2b trial in either AD or ADHD is planned for late 2005, depending of course on the status of our BP negotiations.

10) Also not mentioned - one would expect that we should be hearing fairly soon about DARPA`s plans for a larger Sleep Dep trial with CX-717. DARPA`s interest in CX-717 was already extremely high, and should now be even greater.

[Erbse1]

Hallo liebe Cortex Fans.

Es beschäftigen sich jetzt immer mehr Sender mit unserer Thematik. Hier ein Beitrag vom WDR5. Leider habe ich nur ein Manuskript in Schriftform vorliegen. Feiner Beitrag unter Anderem zu Cortex und zu unserem Thema. Aus rechtlichen Gründen kann ich leider nur verlinken und keine Ausschnitte kopieren

Schönen Tag noch
Erbse


http://www.wdr5.de/sendungen/leonardo/manuskript/ms050414ged…

[Erbse1]

Nochmal ein Artikel zu den Schlafentzugversuchen. Langsam werden die Medien auf Cortex aufmerksam.

New drug offers jitter-free mental boost

A new class of drug may increase alertness without any of the jitteriness of over-stimulation, suggest the results of a small clinical trial released this week.

A compound dubbed CX717, a member of the new class called ampakines, significantly improved performance on tests of memory, attention, alertness, reaction time and problem solving in healthy men deprived of sleep.

The study was carried out by Julia Boyle at the Sleep Research Centre at the University of Surrey, UK, and her colleagues on behalf of Cortex Pharmaceuticals Inc., based in Irvine, California, US.

During the trial, 16 healthy young males were randomly assigned to take either 100 milligrams, 300 mg or 1000 mg of the drug, or given a placebo. By the end of the experiment, each volunteer had been assigned to all of the experimental groups, thus producing his own control scores.

The volunteers were hooked up to EEGs to measure brain wave activity and were put through a battery of tests. The first round of each session was after a good night’s sleep. Thereafter, they were tested every few hours throughout a sleepless night and into the next morning, during a total of 27 hours without rest.

The researchers found that the drug significantly improved performance on tests. And taking more of the drug improved performance for longer.

Short half-life
Ampakines work by binding to particular receptors in the brain, called AMPA-type glutamate receptors. This boosts the activity of glutamate, a neurotransmitter, and makes it easier to encode memory and to learn. And because of their short half-life - hours in this case - ampakines have few side effects.

The drug, which will have to undergo further clinical trials before being approved, is being considered as a possible treatment for narcolepsy, jet lag, attention-deficit hyperactivity disorder (ADHD) and even Alzheimer’s disease.

But it clearly has effects in the healthy population as well. “It generates a state of cortical wakefulness without stimulation,” says Gary Lynch at the University of California at Irvine, who invented ampakines.

Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia, US, sees no particular problem with people using such a drug to combat age-related memory loss. “Stimulating your brain with a reminder on a handheld digital device doesn’t seem that different to me from stimulating your brain with a drug,” he says.

http://www.newscientist.com/article.ns?id=dn7342

[Erbse1]

Hallo liebe Cortex Fans
Hier nochmals eine kurze Zusammenfassung der letzten Konferenz zu der weiteren Planung von Cortex. Ich kopiere mal die sehr schönen DIA von der Präsentation hier rein. Hier wird in wenigen Sätzen der weitere Ablauf klar.

Liebe Grüße
Erbse

[Erbse1]

Hallo liebe Cortex Fans. Hier noch ein Beitrag von der BBC mit einem Interview von Gary Lynch



`Memory pill` for the forgetful
US scientists have invented a pill that can boost memory.
http://news.bbc.co.uk/1/hi/health/4539551.stm

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans. Ich melde mich noch mal mit einem Beitrag in deutscher Sprache.
Liebe Grüße
Erbse


Pille fürs Köpfchen
Ein neues Medikament verspricht ein besseres Gedächtnis und mehr geistige Frische.
http://focus.msn.de/hps/fol/newsausgabe/newsausgabe.htm?id=1…

[Erbse1]

Der Neuroinvestor meldet sich mit einem neuen Kommentar.

Cortex (2.26): We held publication long enough to receive the initial results of the 16 pt Phase IIa in sleep deprivation. All the ingredients--solid primate data, highly controlled variables, even CX516`s low-potency foray--pointed to the probability of success, but that did not equal certainty, particularly with such a small sample. But CX717 did show a dose-related effect upon cognition--in a variety of measures, in normal subjects sleep-deprived for 27 hours. This in itself was not expected to create a major valuation move, but the right major media story, and an eventual Big Pharma agreement, will. There are many companies looking, and this human proof of principle should seal the deal over the next six months. It most likely will end up engaging one of the companies who have either R&D history with the area (Lilly, GSK), or CNS management with AMPA experience and interests (Amgen), The interested parties want access to both the more established low impact (lower neurotrophic activity, better safety) and high impact (more neurotrophin production, more safety risk) platforms. While we never predict buyouts, since doing so has the same probability of success as neuroprotection trials, Cortex is a micro-company that could be an appealing `munch` for a larger firm. Our target remains 12, though that would be next year. A year-end price of 8 is within reach given the kind of deal that we expect, particularly with ADHD, narcolepsy, and Excessive Daytime Sleepiness (EDS) all now given support as viable indications for full Phase II study by this Phase IIa.

http://www.neuroinvestment.com/CORXcom.html

[Erbse1]

Hallo liebe Cortex Fans.
Es gibt eine neue DIA Präsentation von Cortex mit den CX717 Ergebnissen aus Paris. Die vollständige Auswertung der Ergebnisse dauert noch einige Zeit. Hier jetzt der link von der Paris Präsentation.

http://www.wsw.com/webcast/rrshq5/cor/

Stellvertretend für die vielen Meldungen hier zwei Artikel in Deutsch. Die Inhalte ähneln sich, da sie sich alle auf die selbe Quelle beziehen.

Gedächtnispille soll mentale Fähigkeiten verbessern
Ampakine auch für Behandlung von Alzheimer denkbar
http://www.pressetext.at/pte.mc?pte=050512044&source=rss_0.9…


Neuer Wirkstoff hält das Gehirn auf Trab
http://rhein-zeitung.de/on/05/05/12/news/t/rzo150321.html?a

[Erbse1]

Hoffen wir mal, daß sich die Veröffentlichungen auch mal signifikant im Kurs niederschlagen. Nochmals eine Veröffentlichung aus der Fachpresse.

Schönes Wochenende
Erbse


This pill will make you smarter

HAVING problems performing in the sack? Take Viagra. Got the jitters before that important presentation? Try beta blockers. Need to stay awake to finish that assignment? Pop a Provigil pill.

For those prepared to pay, the growing list of "lifestyle drugs" is shifting the boundaries of what bodies and minds are capable of. Now a small clinical trial of the class of experimental drugs known as ampakines suggests these brain-boosters are destined to blur that line still further by offering improved memory.

The success of the unrelated drug Provigil (also called modafinil) has proved there is a huge market for drugs that can improve mental performance. The US Food and Drug Administration has approved it for treating narcolepsy, sleep apnoea - disrupted breathing during sleep - and the sleepiness caused by shift work. But it is widely taken "off-label" by healthy people to stay awake and alert. Sales of the drug, produced by Cephalon of West Chester, Philadelphia, have more than doubled since 2002, and continue to skyrocket (see Graphic).

Some may feel uncomfortable with the increasing availability of such pharmaceutical pick-me-ups, but others see them as no different from performance aids such as palmtop organisers. "Stimulating your brain with a reminder on a Blackberry doesn`t seem that different to me from stimulating your brain with a drug," says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia.

Ampakines work by boosting the activity of glutamate, a key neurotransmitter that makes it easier to learn and encode memory. They change the rules about what it takes to create a memory, and how strong those memories can be, says Gary Lynch of the University of California at Irvine, who invented the drugs. "We all have the same computer," he says, "but we`re running with different voltage levels." Ampakines up that "voltage".

The effects can be dramatic, as Julia Boyle at the University of Surrey, UK, and her colleagues have now shown. They tested an ampakine called CX717 on 16 healthy males aged between 18 and 45. The men were given either 100 milligrams, 300 mg or 1000 mg of the drug, or else a placebo. In repeated trials the volunteers cycled through the treatments so that their performance with different amounts of CX717 could be compared directly.

In each test session, the volunteers started with a full night`s sleep and the following morning and evening were given a battery of tests. These assessed memory, attention, alertness, reaction time and problem solving. Then, at 11 pm, the volunteers swallowed their pills and stayed up through the night. At midnight, 1 am, 3 am, 5 am and 9 am, they were re-tested on some of the tasks. And at 4 am, cruelly, they were tucked into bed in a darkened room and told to stay awake. The researchers measured heart rate and brainwave activity to monitor how alert the subjects were and whether they fell asleep.

“Even the lowest dose of CX717 improved the wakefulness and cognitive performance of sleep-deprived people”Even the lowest dose of CX717 significantly improved the sleep-deprived volunteers` wakefulness and cognitive performance. And the more ampakine they took, the more they improved and the longer the effect lasted. Roger Stoll, CEO of Cortex, the Irvine-based company in California that owns the drug, announced the trial results at an investors` conference on 4 May. While specifics were scant, he mentioned that in the dark room, for instance, most volunteers taking placebo dozed off within about 3 minutes, while some ampakine users stayed awake for the entire 15-minute test. And on a test of sustained attention, effects kicked in within an hour of consuming the drug, he revealed. Crucially, the subjects suffered none of the jitteriness that comes with caffeine or amphetamines. "It generates a state of cortical wakefulness without stimulation," says Lynch.

CX717 will have to undergo further clinical trials before gaining approval as a drug. Cortex is considering it as a possible treatment for narcolepsy, jet lag, attention deficit hyperactivity disorder, and Alzheimer`s disease.

Meanwhile animal studies hint at even more impressive effects. Research on rhesus macaques, carried out for the US military by Sam Deadwyler at Wake Forest University School of Medicine in Winston-Salem, North Carolina, found that sleep-deprived monkeys on CX717 actually performed better on reaction time and accuracy tests than when they were well rested. And non-sleep-deprived monkeys given the drug did better still.

From issue 2499 of New Scientist magazine, 14 May 2005, page 6
http://www.newscientist.com/channel/being-human/mg18624994.7…

[Erbse1]

Hallo liebe Cortex Fans,

ich habe die Paris Präsentation mal auf einen anderen Server gelegt und eine neue DIA Präsentation gemacht. So bleiben die Bilder auch länger erhalten, da der link von R&R bald nicht mehr funktioniert.
Für das nächste Bild einfach nur auf das kleine Vorschaubild klicken.
Am Schluß dieses Beitrages gibts den Kommentar des users gfp927z zu einigen Bildern.



Der folgende link zeigt die DIA Show der Paris Präsentation mit CX717 Ergebnissen
http://www.vm-elsig.de/achim/dia3/

Der nächste link ist der Tonbeitrag des CEO Stoll von der Paris Präsentation Dauer ca. 23 Min.
http://www.vm-elsig.de/achim/dia3/mm1.html

Es folgt der Kommentar von gfp zu einigen Bildern

The new slides have graphs/charts showing what Dr. Stoll discussed in the Paris presentation -
1) CX-614 and CX-929`s effects on raising BDNF levels in rats (slide 10). Nice big increases shown.

2) CX-929`s effects on reversing age related losses in synaptic plasticity (LTP) in whole animals (slide 11). This was recently demonstrated by Dr. Lynch. Very impressive.

3) CX-727`s effects on raising BDNF expression in rats (slide 12). This is a very good sign - that even low impacts can upregulate BDNF over extended dosing periods.

4) Human plasma concentrations for the various oral doses of CX-717 - 100, 300, 1000 mg (slide 16).

5) Diagram showing the design of the UK Sleep trial (slide 17).

6) Chart showing the alerting effect results (wakefulness) (slide 18). This shows a very clear dose related response.

7) Chart showing the persistent alerting effect at higher doses of CX-717 11-17 hours post dosing, measured by the polysomogram (slide 19).

8) Chart showing improvement in attention in subjects with impaired performance (slide 21). This slide is a little confusing, but a really surprising thing here was the tremendous improvement seen between the CX-717 group vrs placebo after the patients had their recovery sleep (17.5 hours post dosing). After sleeping, the subjects who received CX-717 showed big dose related attention improvements compared to the placebo group (ie - the placebo group remained very "groggy" even after recovery sleep, compared to the CX-717 group). What these folks really need is a cup of my Java (to quote Steve Martin :o)

Anyway, the data looks good. Will be getting even more detailed data soon according to today`s press release.

http://messages.yahoo.com/bbs?.mm=FN&action=m&board=16042432…

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde. Nächsten Montag ist eine Konferenz geplant.

Cortex to Host Conference Call to Discuss the Progress of AMPAKINE CX717 from the Most Recent Phase IIa Study
Call Scheduled for Monday, June 13, 2005 at 1:00 P.M. -EDT-
http://biz.yahoo.com/bw/050607/75504.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde. Neuer Artikel in der Financial Times Deutschland



Doping fürs Gehirn

von Constanze Böttcher
Ein neuer Wirkstoff kann die Hirnleistung steigern und auch bei Gedächtnisverlust helfen. Bei Tests brachte das Medikament CX717 die Hirnleistung von Probanden auf Hochtouren.

http://www.ftd.de/rd/9503.html

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
folgend die Präsentation vom 13.06. mit den CX717 Ergebnissen.
Angefügt innerhalb der DIA Show ist die Diskussion im Anschluß an die Präsentation.



http://www.vm-elsig.de/achim/dia04/

Liebe Grüße
Erbse

[Erbse1]

Super, die DARPA finanziert die nächste Runde

DARPA to Sponsor Evaluation of the AMPAKINE CX717 in a New Study in Shift Work

http://biz.yahoo.com/bw/050621/215583.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Auszeichnung für den CEO von Cortex Roger. G. Stoll


Stoll Receives the Albert Einstein Award for Outstanding Achievement in Life Sciences

http://biz.yahoo.com/bw/050707/75409.html?.v=1

[Erbse1]

Hallo liebe Cortex Fans,
folgend ein kleiner Beitrag des Neuroinvestor aus der Juli Ausgabe.

Schönen Tag noch
Erbse

From the July 2005 issue:

We never expected that the price would be so constrained after successful Phase IIa data was released. One must wonder why, and the conclusion we have come to is that Cortex `cried wolf` for so long with CX516 that the novelty is gone, and the Market is habituated to the sound of Cortex making its case. But there are many companies looking, perhaps as many as twelve have interest, some of them quite ardent. We still expect the partnership deal to involve one of the companies who have either R&D history with the area (Lilly, GSK), or CNS management with AMPA experience and interests (Amgen), The interested parties want access to both the more established low impact (lower neurotrophic activity, better safety) and high impact (more neurotrophin production, more safety risk) platforms. The unknown is whether Cortex will get the upfront money they want before their Alzheimer`s, shiftwork, and ADHD trials wind up during 2H:05. While we never predict buyouts, Cortex is a micro-company that could be an appealing, and inexpensive, `munch` for a larger firm. Our target remains 12, though that would be next year. A year-end price of 8 is perhaps still within reach given the kind of deal that we expect, particularly with ADHD, narcolepsy, and Excessive Daytime Sleepiness (EDS) all now given support as viable indications for full Phase II trials by this Phase IIa. But it will require a groundswell of institutional interest fueled by media coverage to get there.

Quelle:
http://www.neuroinvestment.com/CORXcom.html

[Erbse1]

Cortex Commences Enrollment in Two Additional Phase IIa Studies with AMPAKINE CX717

ADHD and Alzheimer`s Disease Studies Are Underway

http://biz.yahoo.com/bw/050728/285204.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
leider ist der Kursverlauf in den letzten drei Monaten nicht nach meinem Geschmack und auf dem Yahoo Board wird viel über Hedge Fonds und über eine neue Kapitalmaßnahme im nächsten Jahr spekuliert.

Seitens des Militärs besteht ein großes Interesse an den Ampakinen.


Unter folgendem Link gibts einen kleinen Bericht zu der Schlafentzugsproblematik und der Rolle der Ampakine.

http://www.darpa.mil/dso/thrust/biosci/cap.htm
Preventing Sleep Deprivation


Anfang nächsten Monat gibts eine neue Konferenz von Cortex. Es ist sehr gut möglich, daß hier die Alzheimer Pet Scans präsentiert werden.

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
hier aus dem Yahoo-Board ein kleiner Überblick zu den einzelnen Testphasen und eine Beurteilung des sehr gut informierten user gfp927z.
Machts mal gut
Erbse

1) If all the remaining Phase 2a studies are clearly positive, then a BP deal will happen.

2) If they`re all mediocre (very unlikely) then we have a problem, but the odds of this scenario are about zilch IMO. Looking at each trial -

a) AD - I`m fairly certain that CX-717 has already shown increased glucose metabolism in preclinical animal studies (I had a link to a paper on this but the link expired so I haven`t been able to review that paper), so the PET scan study should have a very good chance of success. Getting a decent, measurable improvement in cognitive functioning after only a single dose of CX-717 is a tougher hurdle, but certainly very possible. The PET scan results are the chief "endpoint" of the trial though, with any measurable cognitive improvement a nice bonus.

b) Shift Work - is very similar to Sleep Dep (and they will in fact be limiting the Shift Work patients to only 4 hours of recovery sleep per day), so that indication has a very good liklihood of success IMO. Plus we`ll be dosing once/day for 4 days, and the high dose is 1000 mg which should be enough to show good results (remember, the Sleep Dep study showed good results after only a single dose, in the patients who showed impairment. Just about everybody in this study should show some impairment).

c) ADHD - this is probably the riskiest of the 3 trials, but if there`s an effect to be seen, 800 mg BID should do it, since that`s a very high dose, and we`ll be dosing for 3 weeks. My concern about such a high dose causing side effects and dropouts is still there, and I would still prefer to include an intermediate dose (say 400-500 mg BID) just in case. But hopefully Dr. Mansbach and Quintiles knew what they were doing when they designed this trial. He has access to all the Phase 1 data, and has undoubtedly based the trial design on all the info available to him.

3) If it`s a split decision, with AD fair, Shift Work good/very good, but ADHD inconclusive or outright bad, then it`s a tough call and we might have to do an in-house Phase 2b to attract a sufficiently good BP deal. On the other hand, if only ADHD is questionable, and a particular BP doesn`t care much about ADHD anyway, then could still get a deal.

Summarizing - IMO, we`ll see good results in AD and Shift Work. ADHD will probably also be good, but is somewhat higher risk. In addition, I expect a PIPE before we get all the Phase 2a results, though I don`t think the PIPE will be greeted all that negatively (since it increases our negotiating position with BPs, hedges our clinical risk, and provides funds for an in-house Phase 2b if we need to do one). I also think the trials will take somewhat longer than expected, but this is something we`re already used to seeing. So, my scenario is for PIPE (Dec/Jan period), good (but slightly delayed) trial results (Jan/Feb), with the BP deal shortly thereafter (Spring). Anyway, that`s my (semi) educated guess.

Quelle:http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Fans,
falls es hier in Deutschland überhaupt noch welche gibt.
Es gibt einen weiteren guten Artikel über die Ampakine in der Zeitschrift Popular Science. Die Ausführungen über Lynch und Cortex befinden sich auf Seite 2.
Nächsten Mittwoch gibts eine Konferenz von Cortex.

Liebe Grüße
Erbse


Will Drugs Make Us Smarter and Happier?
A new understanding of brain chemistry could usher in an age of biologically enhanced humans
http://www.popsci.com/popsci/futurebody/article/0,20967,1088…
Hier der link auf Seite 2
http://www.popsci.com/popsci/futurebody/article/0,20967,1088…

[puhvogel]

Hallo Erbse, es gibt sie noch......

[Coluche]

... freilich gibt es die noch

Und bei dieser Gelegenheit mal wieder ein herzliches Dankeschön an Dich, liebe Erbse für deine Unermüdliche Arbeit.

Habe mir aktuell mal GPC auf die Watchlist gesetzt. Falls die mit Ihrem Prostataprojekt durchkommen ist die Liqui gesichert, und mit Axxima habe sie spottbillig einen kleinen Konkurrenten von Vertex bekommen, was noch keiner richtig bemerkt hat. Axxima war sehr gut unterwegs in der Kinase- und Protease-Inhibitorenforschung, ihnen ist leider die Liqui ausgegangen bzw. die Anteilseigner wollten nicht mehr nachlegen. ... nur so als Tip für die Watchlist.

Ansonsten denke ich, wird es bei Cortex in einigen Monaten richtig spannend.

Gruß Coluche

[Erbse1]

Hallo liebe Cortex Fans,
ganz besonders an Puhvogel und Coluche. Die Quartalsmeldung von Cortex ist raus. Im finanziellen Bereich läuft es wie geplant. Die einzelnen Testphasen fressen ganz schön Geld, liegen aber im erwarteten Rahmen.

Leider kann ich an der Konferenz nicht teilnehmen, doch ich erwarte Mittwoch nichts aufregendes. Wie Coluche erwähnt hat, werden die aufregenden Sachen wohl gegen Ende des Jahres anstehen.
Zum Stand der einzelnen Testphasen kopiere ich mal einen Ausschnitt aus der letzten Meldung.
Liebe Grüße
Erbse

As recently reported, Cortex has begun enrollment in its second and third Phase IIa studies with CX717: one in Attention Deficit Hyperactivity Disorder and the other in mild to moderate Alzheimer`s disease. These studies follow results from the first Phase IIa trial with CX717 that suggest that when compared to placebo, the compound increased wakefulness in a dose-related manner and improved cognitive performance in healthy male subjects that were deprived of sleep. A fourth Phase IIa study in simulated night shift work is scheduled to start enrollment at the end of August. Cortex anticipates that information relative to the outcome of these studies will be available toward the end of 2005 or sooner, depending on patient enrollment.
Cortex Reports Second Quarter Results
http://biz.yahoo.com/bw/050815/155783.html?.v=1

[Erbse1]

Hallo liebe Cortex Freunde,

ich konnte gestern an der Konferenz nicht teilnehmen. Ist nicht so schlimm, da gfp927z die wichtigsten Punkte für uns gepostet hat.
An dem Kursrückgang in den letzten Wochen ist wohl ein kanadischer Fond zuständig, der wohl weit über eine Millionen Aktien über die Börse abwickelt.

Folgend die Zusammenfassung von der Konferenz gestern.

1) At the end of July, Cortex had over $22 mil in cash, and should have approx $14 mil at year end.

2) ADHD study is enrolling very well. (This is good, since this is the study expected to take the longest - 60 patients, 2 period crossover study, with dosing / washout / dosing period of approx 7-8 weeks for each patient).

3) AD study is enrolling a little bit slower, but we`re trying to speed up enrollment (they only need a total of 12 AD patients for the study though, plus some age matched normal controls).

4) Shift Work study should get its final approval next week and should start enrolling in early September. This is slightly later than planned, but a military research organization is running this trial (DARPA funded). This shouldn`t be a problem though, since the trial only runs for 4 days (4 nights of shift work) on 48 subjects.

5) Recent PR activities include monthly meetings with analysts and fund managers (20 meetings in the past month). Also there`s a recent article on Cortex/Dr. Lynch in Popular Science magazine (on the newstands this week). Also - in NY, Cortex participated in a call-in meeting with anchors/commentators from 8 different television networks (PR was issued) and discussed memory/AD topics and Ampakines.

6) Dr. Deadwyler`s article on the effects of CX-717 and other Ampakines in primates is coming out in the next week or so. In addition, Dr. Lynch is about to publish a significant article on high impact compounds.

7) Over the past several weeks, there was a fund in Canada who recently had to liquidate several of their stock positions to raise cash. Cortex tried to put them in touch with other funds interested in increasing their position in Cortex, but they couldn`t come to an agreement on the price, so the Canadian fund had to liquidate its position on the open market (over 1 mil shares), and this has put some pressure on the stock in the last several weeks. The vast majority of these shares have already been sold into the market, and we should be through this situation very shortly. I`d like to personally thank the Canadian fund for giving me the opportunity to reload at attractive prices :o)

8) BP deal - we continue talking to a large number of large and medium size companies. Improving our chances for a good BP deal will be the Phase 2a data expected around year end, the completion of the 3 month tox study, and the availability soon of tablet dosing for CX-717 (tablets provide more consistent release dosing, and are more convenient than capsules. This is a plus for larger/longer studies). CX-717 is extremely stable, and there have been no shelflife concerns at all.

Q+A -

1) Dr. Deadwyler`s primate paper will be published in the Public Library of Science, Biology section, coming out in the next few weeks. This should be an interesting paper - there should be comparative data on not only CX-717 but also numerous other Ampakines compounds (we know he`s tested at least CX-717, CX-727, CX-1036, CX-701, Aricept, and probably some high impacts). Beyond the delayed match to sample tests, Dr. Deadwyler has also reportedly done PET scans, EEGs, spectral density tests, and direct intra-brain measurements in his primates.

2) Dr. Stoll doesn`t see any need for a financing in 2005. Next year we`ll need more money, but the goal is to obtain this cash from the BP deal.

3) High impact program - should have a viable lead compound by year end. The challenge is to get significant neurotrophin upregulation combined with an adequate safety margin, and we`re starting to see progress in achieving this.

4) We have a low impact backup compound progressing toward scale up. Then we can go into tox and then into a human Phase 1 next year. (I`m assuming this is CX-727, but he hasn`t publicly specified which compound it is yet).

5) ADHD trial timetable - so far the enrollment has proceeded very nicely and we`re extremely happy with how the enrollment is moving (Quintiles is the CRO). The protocol for this study has already been used successfully with Adderall, Concerta, and Strattera.

6) Dr. Tracy confirmed hearing that an NIMH funded trial for Depression is enrolling using Org-24448.

7) PET scan discussion - its value in showing changes in brain activity/cellular metabolism in regional areas of the brain. (The CX-717 AD trial is using the PET scan. The Org-24448 Depression trial will also reportedly be doing PET scans in some of their patients).

[Erbse1]

Hallo liebe Cortex Fans,
ich melde mich nochmal mit einem Abstrakt zu CX717 bei Schlafentzug.
Liebe Grüße
Erbse

Facilitation of Task Performance and Removal of the Effects of Sleep Deprivation by an Ampakine (CX717) in Nonhuman Primates.

Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America.

The deleterious effects of prolonged sleep deprivation on behavior and cognition are a concern in modern society. Persons at risk for impaired performance and health-related issues resulting from prolonged sleep loss would benefit from agents capable of reducing these detrimental effects at the time they are sleep deprived. Agents capable of improving cognition by enhancing brain activity under normal circumstances may also have the potential to reduce the harmful or unwanted effects of sleep deprivation. The significant prevalence of excitatory alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamatergic receptors in the brain provides a basis for implementing a class of drugs that could act to alter or remove the effects of sleep deprivation. The ampakine CX717 (Cortex Pharmaceuticals), a positive allosteric modulator of AMPA receptors, was tested for its ability to enhance performance of a cognitive, delayed match-to-sample task under normal circumstances in well-trained monkeys, as well as alleviate the detrimental effects of 30-36 h of sleep deprivation.

CX717 produced a dose-dependent enhancement of task performance under normal alert testing conditions. Concomitant measures of regional cerebral metabolic rates for glucose (CMR(glc)) during the task, utilizing positron emission tomography, revealed increased activity in prefrontal cortex, dorsal striatum, and medial temporal lobe (including hippocampus) that was significantly enhanced over normal alert conditions following administration of CX717.

A single night of sleep deprivation produced severe impairments in performance in the same monkeys, accompanied by significant alterations in task-related CMR(glc) in these same brain regions. However, CX717 administered to sleep-deprived monkeys produced a striking removal of the behavioral impairment and returned performance to above-normal levels even though animals were sleep deprived. Consistent with this recovery, CMR(glc) in all but one brain region affected by sleep deprivation was also returned to the normal alert pattern by the drug. The ampakine CX717, in addition to enhancing cognitive performance under normal alert conditions, also proved effective in alleviating impairment of performance due to sleep deprivation. Therefore, the ability to activate specific brain regions under normal alert conditions and alter the deleterious effects of sleep deprivation on activity in those same regions indicate a potential role for ampakines in sustaining performance under these types of adverse conditions.

[Erbse1]

Hallo liebe Cortex Fans. Der komplette Artikel zu den CX717 Versuchen wurde veröffentlicht. Also jede Menge lesenswertes zu den Ampakinen.


Facilitation of Task Performance and Removal of the Effects of Sleep Deprivation by an Ampakine (CX717) in Nonhuman Primates.

http://biology.plosjournals.org/perlserv/?request=get-docume…

Schönen Tag noch
Erbse

[Erbse1]

Stellvertretend für die Menge an Meldungen hier nur ein Artikel von der BBC


Drug `reverses sleep lack effect`
A drug could reverse the effects of sleep deprivation in the brain, a US study of monkeys has suggested.

http://news.bbc.co.uk/1/hi/health/4173078.stm

Zusätzlich noch die Meldung von Cortex zu der Veröffentlichung
Publication in the Journal PLoS Biology Supports Cortex Pharmaceutical`s CX717 AMPAKINE Compound as a Potential New Treatment for Cognitive Impairments

http://biz.yahoo.com/bw/050823/235178.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,

das Interesse im Augenblick ist riesengroß. Für Interessenten deshalb noch mal den Stand zu den einzelnen Testphasen. Der Artikel stammt von dem user gfp927z. Es lohnt sich also die letzten Beiträge mal zu lesen.
Liebe Grüße

Here`s a brief summary of the current clinical human trials for Cortex developed compounds -

CX-717 -

1) Sleep Deprivation - Phase 2a, 16 subjects (completed).

2) AD PET scan study - Phase 2a, 12 patients, completion approx September.

3) ADHD - Phase 2a, 60 adult patients, completion approx year end.

4) Shift Work - Phase 2a, 48 subjects, funded by DARPA, completion approx year end.


Org-24448 (CX-691) -

1) Schizophrenia - mono therapy, Phase 2b, (partner Organon).

2) Schizophrenia - combo therapy, Phase 2b, 100 patients, NIMH/TURNS, (partner Organon).

3) Depression - Phase 2b, 90/70 patients, NIMH, (partner Organon).


Other human trials of non-Cortex developed compounds -

1) S-18986 - Phase 2a study, likely in AD.
(partner Servier). S-18986 is a Benzothiadiazide.

2) Lilly - though Lilly has a ton of compounds (Biarylpropylsulfonamides), and have done a lot of preclinical work in the AMPA upmodulation area (AD, Parkinson`s, Schizo/Depression, etc), they currently have no human trials that I`m aware of. Lilly`s Alzheimer`s Phase 2 with LY-451395 was halted last year apparently due to excitotoxicity related side effects (a characteristic of their Biarylpropylsulfonamides).

3) Glaxo/NeuroSearch - no human trials yet that I`m aware of. NeuroSearch`s compounds appear to be similar to Servier`s (Benzothiadiazide and related families), though they may also have some Benzoxazine derivatives.

4) Boehringer Ingelheim - no human trials that I`m aware of. They appear to be working with Napthothiazines.


So Cortex`s super-safe low impact compounds are way ahead clinically, and of course Organon/Servier are both already partnered with Cortex. Both Lilly and Glaxo could benefit tremendously by gaining access to Cortex`s technology, compounds, and patents (via partnering or acquisition). In addition to Cortex`s low impact technology, they could get access to Cortex`s new high impacts. Amgen is another possibility, since they are seeking a presence in the neuro area, and their head of neuroscience came from Lilly (Dr. Fibiger, formerly Lilly`s VP of Neuroscience). Other interesting personnel interconnections among these companies include -

Dr. Mansbach - Cortex`s head of clinical development since Sept 2004, came from Glaxo (he was Glaxo`s Senior Director of Clinical Development, Neurosciences), and

Dr. Tollefson - he joined Cortex`s board in March 2004, and was a heavy hitter at Lilly.

Quelle:http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Freunde.

Ich melde mich noch mal zu den Meldungen der Schlafentzugversuchen. Die Artikel sind in Deutsch.


Medikament kehrt Folgen des Schlafentzugs um
Eine Arznei aus der Stoffgruppe der Ampakine soll helfen Schlafmangel zu überbrücken und dabei dennoch fit zu bleiben. Wer profitiert? Beispielsweise Schichtarbeiter und natürlich Ärzte, hoffen die Forscher.

http://www.aerztlichepraxis.de/artikel?number=1124793500


Kampferprobt kommen die Meldungen aus Österreich.



Muntermacher für den Krieg
US-Forscher finden ein Aufputschmittel ohne Nebenwirkung.

http://www.diepresse.com/Artikel.aspx?channel=h&ressort=ws&i…


Wie bereits von mir angekündigt findet am 8. September eine Konferenz von Cortex statt. Es ist sehr gut möglich, daß hier die Alzheimer PET Scans präsentiert werden.

Cortex`s CEO to Speak at the Roth Capital Partners New York Conference on September 8th, 2005

http://biz.yahoo.com/bw/050824/245166.html?.v=1

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Fans, hier eine kurze Zusammenfassung der heutigen Konferenz von dem user gfp927z.
Die komplette Konferenz in Ton gibts im vorherigen Hinweis zur Konferenz.

Liebe Grüße
Erbse

Some highlights from today`s Roth Conf presentation -

Servier is looking for approx 3 high impact compounds from the ongoing collaboration with Cortex. CX-929 is apparently one of the high impact compounds that has come out this Cortex/Servier collaboration. Dr. Lynch has used CX-929 to demonstrate tremendous upregulation of BDNF in rats.

Dr. Stoll discussed Lilly`s previously published Parkinson`s preclinical studies using their high impact AMPA upregulators (LY-404187, LY-503430) which showed the reversal to normal of Parkinson`s symptoms, and the regrowth of lost brain tissue. This suggests that high impact compounds can reverse the effects of Parkinson`s disease.

CX-727 showed an elevation of BDNF of approx 10-20% after 2 months of dosing in animals, indicating that low impacts can also modestly upregulate BDNF.

A comprehensive review of the recently published Deadwyler primate data was given. These studies showed that CX-717 totally reversed the cognitive deficits of sleep deprivation. PET scans of these primates showed tremendous upregulation of glucose metabolism in certain areas of the brain (hippocampus, cerebral cortex, visual cortex), indicating that CX-717 was causing increased activity in the desired areas of the brain (the current AD PET scan trial will confirm that these same changes also occur in humans).

Review of the UK Sleep Deprivation trial results was given. Dr. Stoll also mentioned that the UK investigator had noted that CX-717 was the only drug they had ever tested which caused cerebral arousal without producing any systemic arousal/side effects (changes in blood pressure, heart rate, body temperature, etc).

Review of Phase 1 - CX-717 has a 9-10 hour halflife, excellent safety, linear kinetics.

AD trial - should have an interim analysis in a month.

ADHD - Enrollment is going very well, with half the patients already enrolled.

Shift Work - DARPA is paying all the trial costs. This trial is run by a military research organization, and got started slightly late, so the results might be just after the end of the year.

The CX-717 3 month tox study in 2 species is completed.

There are lots of licensing discussions underway, and a partnership should be coming to fruition.

Quelle:http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Fans,
der Neuroinvestor meldet sich auch mit einem weiteren Beitrag
Schönes Wochenende
Erbse

the September 2005 issue:

While there have been rumors of a term sheet in place, that is not true, about a dozen companies are still actively interested in the partnership. `Partnership` can mean something very different depending on the company involved: different firms have varying areas of interest, and a company pursuing Alzheimer`s may have no interest in ADHD, and vice versa, Indeed, it may be a rare animal that is interested in all of the major Ampakine indication possibilities.


The other issue has to do with how much data different companies want before being willing to set a term sheet in writing. Our hunch is that the PET scan data from Alzheimer`s patients, due this month, may be the key ingredient for the companies whose interests are indeed focused upon Alzheimer`s. On the other hand, we are quite sure that there are psychiatrically oriented partner candidates who are largely interested in schizophrenia, depression, and perhaps ADHD. If one of those companies steps up, the complicating factor will of course be Organon--both Cortex and Organon have to agree to sublicenses. Given that schizophrenia is the most clinically advanced program, we believe that this particular indication area would be the most valuable in a licensing deal. One other variable in play is the availability of CX717 for Cortex`s inhouse orphan indication program, Fragile X at the forefront of possibilities. The biggest `name` partners, those whose embrace would mean instant credibility, are less likely to cede any access to CX717 (and its backup CX727), they will want full control. Companies which are a tier or two down in size, albeit still enormous compared to Cortex, might be more flexible, which would allow instant entrance into clinical development for the orphans on Cortex`s part.

Would the credibility be worth the 18 month delay that giving up CX717 would require? That depends on the numbers. Cortex still believes a deal could be done by year-end, we think that is a 50/50 proposition at best. Both shiftwork and ADHD are likely to have their Phase IIa data late 2005, and the more conservative read of the situation is that the deal that Cortex really wants will not be there for the taking without Phase IIa corroboration. As we have noted before, Cortex is a micro-company that could be an appealing `munch` for a larger firm. We have been citing a target of 12, but because we believe profit-taking would be wise if the share were to get anywhere near 8, we are going to reset the target to 8, so that there is no confusion therein. And given that a Canadian fund sold off a large position, thus keeping the price near its lows, it would be an extreme optimist who would not start taking some profits at 5 and above.

Quelle:http://www.neuroinvestment.com/CORXcom.html

[Erbse1]

Hier eine Meldung aus Russland. Ist nichts Neues dabei,aber ich kann mir einfach nicht verkneifen die Meldung in diesem Thread zu posten.

Viele Grüße
Erbse



Wonder drug beats effects of sleep deprivation
http://newsfromrussia.com/science/2005/08/23/61600.html

[Erbse1]

Hallo liebe Cortex Fans,
ich melde mich noch mal mit einigen weiteren Erläuterungen zu den Versuchen mit ORG 24448. Organon hat diese Substanz von Cortex einlizensiert. Auf einer Schizophrenie Konferenz wurden noch einige Einzelheiten bekannt.

Liebe Grüße
Erbse



Cognition in Schizophrenia: The MATRICS Initiative

In the symposium, "Enhancing Neurocognition in Schizophrenia," Wayne S. Fenton, MD, of the National Institute of Mental Health (NIMH), introduced the Measurement and Treatment Research to Improve Cognition in Schizophrenia, known as the MATRICS Initiative.[11] He described it as, "a collaboration between NIMH, the University of California, Los Angeles, and the United States Food and Drug Administration to combine what we`ve learned on the basic science of cognition in schizophrenia and push translation toward treatment."

Keith Nuechterlein, PhD, of the University of California, Los Angeles (UCLA), said that this field has matured slowly because of methodologic uncertainties such as defining targets for intervention, measuring outcomes, and designing appropriate and meaningful studies.[12] He discussed the recent effort to create a standardized cognitive test battery by the MATRICS Initiative neurocognition committee. The committee targeted 7 cognitive domains most affected by schizophrenia[13]:

Speed of processing
Verbal learning and memory
Visual learning and memory
Reasoning and problem solving (executive functioning)
Attention and vigilance
Working memory
Social cognition


After considering more than 90 tests, the committee selected 20 for further study in the Psychometric and Standardization Study, which involved 176 patients with schizophrenia tested at 5 sites. The tests were evaluated on criteria like test-retest reliability; and relationship to functional outcome, such as community functioning. The proposed final battery of 10 tests, which takes about 1 hour to administer, is available online at a Web site set up by UCLA.[14] The federal agencies have received the final recommendations from the MATRICS committee and will require that clinical trials of cognitive enhancers for schizophrenia use this battery of tests to measure outcomes.

TURNS Institutions and Pharmacologic Agents
Robert Buchanan, MD, said that his institution, the Maryland Psychiatric Research Center, University of Maryland in Baltimore, is one of 7 research sites in the Treatment Units for Research on Neurocognition in Schizophrenia (TURNS).[15] These institutions will conduct studies of promising cognitive enhancers for schizophrenia as identified by the MATRICS neuropharmacology committee.[16] Criteria considered in selection of potential agents include efficacy, pharmacokinetics, safety, tolerability, and innovation. Of 50 agents identified, he called the 2 "front runners" ispronicline and Organon`s compound ORG 24448.

Ispronicline (Targacept, Inc., Winston-Salem, North Carolina) is an alpha-4-beta-2 nicotinic receptor partial agonist, more potent than nicotine at this receptor. It allows once-daily dosing and induces cytochrome P450 1A2. In animal studies, it shows no evidence of tolerance. Studies in normal humans as well as those with age-associated memory impairment and mild cognitive impairment have taken place. "The TURNS study will be the first evaluation of its use in schizophrenia," Dr. Buchanan said.

ORG 24448 is an allosteric modulator of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor and has been tested in animal models of cognition with no evidence of tolerance or proconvulsant activity. Human studies to assess maximum tolerated dose are underway.

According to Dr. Buchanan, subjects who participate in TURNS studies will need to have a DSM-IV diagnosis of schizophrenia and be stable on a second-generation antipsychotic other than clozapine or, in the case of ispronicline, olanzapine because of its anticholinergic effect. The studies will include men and women aged 18 to 55 years who have a MATRICS cognitive-test-battery score below a specific cut-off at baseline. The double-blind design includes 3 parallel arms -- 2 medication dosages, 1 placebo -- with outcomes measured by the MATRICS consensus cognitive battery, standardized scales for other symptoms of schizophrenia, and standardized measures of community functioning. Investigators will also follow biological markers such as functional magnetic resonance imaging, evoked response potentials, magnetic resonance spectroscopy, and prepulse inhibition to startle.

Quelle:http://www.medscape.com/viewarticle/504415_3

[Erbse1]

Eine weitere Empfehlung Cortex zu kaufen. Ich denke mal, daß die positiven Kommentare anhalten werden.

Schönen Tag noch
Erbse



Invest in the next miracle drugs

<<Cortex Pharmaceuticals (COR, news, msgs) is developing a drug that may improve alertness and memory by changing how nerve cells in the brain communicate. It could be used to treat problems like Alzheimer’s, sleep deprivation, autism and attention deficit disorder. Garren says that the drug`s animal-testing studies look promising, and that by end of year "we may know more about its efficacy in humans.">>>

Quelle:http://moneycentral.msn.com/content/P127491.asp

[pwoell]

Hallo Erbse1

Du bist mir schon vor einigen Jahren im Yahoo Forum aufgefallen mit guten Kommentaren zu Coretx - vielen Dank. Leider habe ich nicht die Zeit alle Entwicklungen rund um Cortex mitzuverfolgen und beteilige mich daher auch nicht an den Diskussionen, welche ich aber als Informationsquelle sehr schätze.

Ich bin bereits seit bald 6 Jahren Aktionär von Cortex. Leider haben sich meine Hoffnungen in diesen Titel bis jetzt nicht bestätigt und ich bin immer noch unter Einstand. Und trotzdem glaube ich, dass dieser Titel eines Tages nach oben abziehen könnte, wenn die Produktentwicklung in Gang kommt. Dies ist auch der einzige Grund, weshlab ich diesen Titel (als einzigen) sol lange halte und mir gerade überlege ob ich noch zukaufen soll. Auf der anderen Seite wurde ich aber schon einge Male entäuscht. Immer wenn ich das Gefühl hatte jezt gehts nach Norden, kam der Hammerschlag und der Titel hat seine Gewinne wieder abgegeben.

Da ich Dir aufgrund Deiner gescheiten Postings einige Kompetenzen zutraue und ich weiss, dass Du diesen Titel seit Jahren beobachtest würde es mich interessieren wie Du die Lage einschätzt. Ich würde mich daher freuen etwas von Dir zu hören.

Beste Grüsse aus der Schweiz
pwoell

[Erbse1]

Hallo pwoell,
freut mich Dein Interesse an Cortex. Es ist schwer für mich die Lage bei Cortex einzuschätzen. Ich bin wissentschaflich gesehen ein Laie und ein miserabler Börsianer. Es bleibt mir also nur die Beobachterrolle bei Cortex.
Doch einige Gedanken sollten uns doch weiterhelfen.
Der damalige CEO Vincent Simmon hat es verpasst parallel zu CX 516 weitere Substanzen voranzutreiben. Nach dem Scheitern von CX 516 hatte Cortex große Mühe den Konkurs zu vermeiden.
Mit CX 717 und Roger Stoll ging es wieder bergauf und es wurden erfolgreich zur Liquiditätssicherung einige Kapitalmaßnahmen durchgeführt. Die Ergebnisse zu CX 717 kann man hier der aktuellen Presse entnehmen.

Zu den Zukunftsaussichten. Cortex ist im Augenblick mit ca 80 Mill. $ bewertet. Provigil wird auch bei ähnlichen Anwendungsgebieten in Verbindung gebracht wie CX 717 und macht dieses Jahr einen Umsatz von ca. 600 Mill. $. Sicher wird Cortex eine Vereinbarung mit DARPA haben, doch die Hälfte des Gewinns dürfte wohl bei Cortex verbleiben.
Rechnet man ca. das Achtfache des Umsatzes oder ca. das Zwanzigfache des Gewinnes so hat man einen Richtwert, mit dem Cortex bei erfolgreicher Zulassung bewertet werden düfte. In ferner Zukunft (4-8Jahre)rechne ich mit einer Bewertung die zwischen 2Milliarden und 10 Milliarden $ liegen dürfte. Dies ist davon abhängig in wie vielen Gebieten die Substanzen auch erfolgreich zugelassen werden. Allerdings besteht auch die Gefahr, daß Cortex von einem großen Pharmapartner aufgekauft wird.
Ich selber bin optimistisch eingestellt und hoffe, daß keine überraschenden Nebenwirkungen bei den weiteren Testphasen eintreten.

Jetzt noch einige Anmerkungen in eigener Sache. Einige Kollegen haben ein Board zu Cortex gebastelt, da wir uns unabhängig von den hiesigen Boardbetreibern machen wollen und das Yahoo Board wochenlang down ist. Wir befinden uns noch in der Testphase, aber es kann schon gepostet werden und man kann sich schon anmelden. Wir würden uns freuen, wenn ihr mal reinschaut.

Achtung Neues Cortex Board---New Cortex Board

http://www.erbse.vm-elsig.de/form/base/YaBB.pl

Mit diesem link kommt ihr zu dem neuen Cortex Pharma Board.

Schönes Wochenende
Erbse1

[Erbse1]

Hallo Liebe Cortex Freunde, hab noch einen schönen Artikel zu der Thematik Schlafentzug gefunden.

Clocking in Pillow Time without the Pillow

<<<If you snooze, you lose those uncomely grayish-brown crescents below your eyes. If you don`t snooze, you lose a lot more. The body can`t fight off infection, the muscles can`t regenerate as quickly, the mind can`t learn new words, and the eyes can`t focus on the road. You also gain things: a bad mood and increased risk for diabetes, high blood pressure, and heart problems. Indeed, the effects of sleep deprivation can be so serious that some sleep scientists liken lifetime sleep debt to a heavy backpack: every sleep hour missed adds an extra pound to your pack until it weighs you down.

For people without time for a daily eight hours in the sack, drugs that counteract the effects of sleep deprivation could serve as substitutes. In a new study, Sam Deadwyler and colleagues have explored this possibility by giving dog-tired rhesus monkeys a drug shown to improve the functioning of alert brains. They found that sleepy monkeys taking the drug performed tasks better and had increased metabolic activity in several regions of their brains. This suggests that the cognitive effects of sleep deprivation can be reduced chemically.>>>

Gesamter Artikelhttp://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112705265…

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,

Cortex will sich 25.000.000 neue Aktien genehmigen lassen. Kann gut sein, daß diese Aktien für eine ausstehende Partnerschaft mit einer größeren Pharmafirma benötigt werden. Die Zukunft wird zeigen, wofür die zusätzlichen Aktien letztendlich benötigt werden.

The Board of Directors unanimously recommends that you vote FOR the proposal to amend the Restated Certificate of Incorporation to increase the authorized number of shares of Common Stock from 50,000,000 to 75,000,000

Quelle:http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112840036…

Weiterhin gibts Neuigkeiten vom neuen Cortex Board zu vermelden. Wir haben zusätzlich einen Chat eingebaut, der natürlich auch von allen anderen genutzt werden kann.
Hier also nochmals der link zu dem neuen Cortex Pharma Board mit sehr vielen Artikeln.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde, der neue Brief des CEO Stoll an die Aktionäre ist da.

ROGER STOLL: TO OUR SHAREHOLDERS AND FRIENDS: 2005

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=113024743…

Steht vieles zur aktuellen Lage drin. Sehr lesenswert für alle Cortex Interessierte.

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
unter folgendem link eine Veröffentlichung zu dem Thema Ampakine und Schizophrenie bzw. Psychose.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=113041291…

Die nächsten drei vier Monate werden jetzt wohl extrem wichtig für Cortex. Ich poste jetzt nicht mehr regelmäßig hier im Wallstreet Board. Interessenten finden die neuesten Nachrichten im neuen Cortex Board oder auf dem Yahoo Board.Also einfach mal vorbei schauen.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl
oder
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
es gibt einen aktuellen Überblick vom user gfp927z. Nochmals herzlichen Dank an gfp927z für all seine Mühe sein Wissen mit uns zu teilen.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112736027…

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
vor kuzem war Jahreshauptversammlung bei Cortex. Es geht alles seinen normalen Gang. Bemerkenswert ist, daß der CEO Stoll eine neue Strategie andenkt. Es soll eine weitere Substanz einlizensiert werden. So könnten dann die Ampakine als ganzes Paket auslizensiert werden. Dies ist nur eine zusätzliche Option zu der bisherigen Planung. Dabei wollte Cortex die großen Anwendungsgebiete auslizensieren und kleinere Anwendungsgebiete in Eigenregie zur Marktreife bringen. Bin selber gespannt welche Strategie dann letztendlich dann zum Tragen kommt.

Interessenten können sich die Jahreshauptversammlung unter folgenedem link aufrufen. Die Dauer beträgt ca. 1Std.25Min.

http://www.cortexpharm.com/html/news/index.html

Die Ergebnisse aus den einzelnen Versuchsreihen werden jetzt im ersten Quartal nächsten Jahres erwartet. Einzelheiten könnt Ihr ja aus der Jahreshauptversammlung entnehmen.

Machts mal gut
Erbse1

[Erbse1]

Hallo Cortex Freunde,

unter dem folgendem link gibts eine Zusammenfassung von der Jahreshauptversammlung von dem unermüdlichen user gfp927z.
http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=113353267…

Weiterhin gibts eine rege Diskussion auf dem Yahoo Board.
http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

Schönen Tag noch
Erbse

[Erbse1]

Cortex Pressemeldung von Heute. Für Insider nichts Neues, trotzdem lesenswert.

Liebe Grüße
Erbse


Help for the Sleep-Deprived Brain

Monday December 5, 5:08 am ET

IRVINE, Calif., Dec. 5 /PRNewswire/ -- Sleep deprivation can take its toll on body and mind, leading to dull thinking and slower reaction times. That can be dangerous while driving and also at work. A regular pattern of restful sleep may be the solution. But for some shift workers, health care professionals, and military personnel, that`s not always possible.

Shift workers and military personnel disrupt their sleep-wake cycles on a regular basis, often remaining awake for 24 hours at a stretch or even longer. This leads to reduced hand-to-eye coordination that is astonishing similar to a blood alcohol content of 0.1.

"Since sleep disorders are a tremendous drain on the productivity and safety of our country, there is an urgent need for a solution that can help the sleep deprived regain cognitive and psychomotor functions," says Dr. Roger Stoll, CEO of Cortex Pharmaceuticals, a neuroscience company focused on innovative drug therapy including their leading ampakine compound, CX717 which targets various neurological and psychiatric disorders.

"CX717 is a type of drug called an ampakine. Ampakine drugs act to increase the strength of signals at key connections between brain cells," says Dr. Stoll. "Ampakine drugs are designed to up-regulate to the principle neurotransmitters in the brain. CX717 amplifies signals, and may also increase the amount of growth factors in the brain."

The U.S. Department of Defense Advanced Research Projects Agency (DARPA) recently tested CX717 in a sleep deprivation study in primates led by Sam Deadwyler, Ph.D, a senior researcher at the physiology and pharmacology department of Wake Forest University. The study, recently published in the Public Library of Science, Biology, found that CX717 administered to sleep- deprived monkeys improved cognitive performance and also reversed the delirious effects of sleep deprivation.

Through the first Phase IIa clinical trial conducted in the United Kingdom, the company gained evidence that CX717 promotes wakefulness may improve memory and attention, and was safe and tolerable. "We were particularly impressed in both the increased attention and vigilance scores and the cerebral arousal this first study identified in human subjects who had been sleep deprived," said Dr. Stoll.

America is arguably the most sleep-deprived nation in the world. The National Commission on Sleep Disorders estimates that 40 million Americans are either chronically or intermittently affected with various sleep disorders.

For more information about CX717, log on to http://www.cortexpharm.com

[Erbse1]

Hallo liebe Cortex Freunde,
noch eine Meldung von letzter Woche. Ist eigentlich nicht so interessant, aber der Vollständigkeit halber poste ich sie mal trotzdem. Cortex hat sich eine Erhöhung von 50 auf 75 Millionen Aktien absegnen lassen.

Schönes Wochenende noch
Erbse

Industry Expert Assesses Cortex`s
Orphan Drug Strategy

Webcast Of Presentation Available On-Line Until January 2

IRVINE, CA (December 13, 2005) — At the annual shareholder meeting for Cortex Pharmaceuticals, Inc. (AMEX: COR), the Company’s orphan drug strategy for the Ampakine® technology was discussed by the CEO, Roger G. Stoll, Ph.D. and a guest speaker, Curt Friehs, founder and president of Kronos Associates.

A webcast of the meeting is available now through January 2, 2006 via the following link http://www.investorcalendar.com/IC/CEPage.asp?ID=98161.

Mr. Friehs, who is a consultant to Cortex, is an industry renowned marketing expert with broad experience, most notably at Upjohn (now wholly owned by Pfizer), and at Wallace Laboratories. At the shareholder meeting, Mr. Friehs explained that orphan drugs offer Cortex an attractive commercial opportunity by addressing a distinct group of underserved patients, including those with Fragile X, excessive daytime sleepiness due to narcolepsy, loss of memory due to electroconvulsive therapy, as well as other possible orphan drug indications and further expansion into autism and post seizure therapy. Furthermore, Cortex’s strategy could facilitate the Company’s eventual transition to a larger organization that would be capable of marketing drugs for much larger patient populations.

Dr. Stoll, who hosted the meeting, stressed that the orphan drug approach may allow a small company like Cortex to get products to market faster, at less cost than the major indications often discussed for the Ampakine drugs. He also pointed out in detail the profound unmet medical needs for such orphan indications within central nervous system disorders and how they could be addressed by Cortex’s Ampakine technology platform, including the Company’s Ampakine compound, CX717. Dr. Stoll also reported on Cortex’s clinical development programs and anticipated licensing endeavors.

At this meeting the substantial majority of shareholders approved the proposed increase in the Company’s authorized shares from 50,000,000 common shares to 75,000,000 common shares and approved both the recommended board of directors and the Company’s external auditors.

[Erbse1]

Neue Studie von ORG24448 gegen Depression in der Planung.

Randomized, Placebo-Controlled Trial of an AMPAkine in Major Depressive Disorder

Further Study Details:
Primary Outcomes: Reduction of depressive symptoms as measured by the several depression rating scales at 8 weeks
Secondary Outcomes: Effect on neuropsychological functioning measured at 7 weeks

Study start: January 2006; Expected completion: January 2009

Major depressive disorder (MDD) is a common, severe, chronic and often life-threatening illness. Major depression contributes to significant morbidity and mortality. Available pharmacotherapies for major depression are suboptimal in terms of speed of onset, efficacy, and tolerability. Current medications for severe, chronic mood disorders are not based on pathophysiological models of illness, but rather are variation of monoaminergic-based therapies. Org 24448 represents a new treatment approach for depression, by potentiating the AMPA receptor subfamily of ionotropic glutamate receptors. This drug has been shown to have antidepressant features in preclinical models, as well as cognitive-enhancing qualities.

Source:http://www.clinicaltrials.gov/ct/show/NCT00262665?order=2" target="_blank" rel="nofollow ugc noopener">
http://www.clinicaltrials.gov/ct/show/NCT00262665?order=2

Bis demnächst
Erbse

[Erbse1]

Hab gleich noch eine weitere Studie mit S18986 entdeckt. Servier hat von Cortex die Ampakine einlizensiert.
Schönen Tag noch
Erbse

Efficacy and Safety of S18986 in the Treatment of Mild Cognitive Impairment Patients

Quelle:http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112702074…

[Erbse1]

Neuer Abstrakt von Gary Lynch. Klingt alles sehr kurz gehalten und optimistisch.

Grüße
Erbse


Glutamate-based therapeutic approaches: ampakines.

Lynch G.

University of California, Department of Psychiatry and Human Behavior, Irvine, California 92617, USA.

Ampakines are a structurally diverse family of small molecules that positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, and thereby enhance fast, excitatory transmission throughout the brain. Surprisingly, ampakines have discrete effects on brain activity and behavior. Because their excitatory synaptic targets mediate communication between cortical regions, serve as sites of memory encoding, and regulate the production of growth factors, ampakines have a broad range of potential therapeutic applications. Several of these possibilities have been tested with positive results in preclinical models; preliminary clinical work has also been encouraging.

[Erbse1]

Hallo liebe Cortex Freunde,
der Neuroinvestor meldet sich mit einem kurzem Kommentar ins neue Jahr. Zu den Ergebnissen sinds jetzt nur noch wenige Wochen.
Liebe Grüße
Erbse

From the January 2006 issue:

Cortex is at various stages of discussion with sixteen suitors for the Ampakine platform. The 60pt ADHD Phase II that is completely enrolled stands to be the critical human trial. Enough of the interested companies have or want an ADHD franchise that we expect positive data to drive the final deal, if Cortex and a more impulsive BP company have not concluded a deal before that. Cortex is still committed to keeping CX717 for an orphan indication, and is also looking to inlicense a PhIII compound from a partner or other BP source. The DARPA funded sleep deprivation trial has begun enrolling strongly, and could report in late-February. But the AD PET scan study has gone almost nowhere (three patients enrolled) due to its exclusion of memantine patients. This is the best molecular platform and related IP currently for sale in the CNS industry.

[Coluche]

Hallo Erbse,

zunächst einmal ein herzliches Dankeschön für deine unermüdliche Arbeit hier im Board im vergangenen jahr. Wünsche dir ein erfolgreiches und gutes Jahr 2006.

Habe über den Jahreswechsel dies meisten meiner HGRD`s in Cortex umgewandelt, hoffe es war kein Fehler.

Aber ich denke, der aktuelle Kurs bei steigenden umsätzen lästt auf positives hoffen.

In den nächsten Wochen wird sich bei Cortex hinsichtlich Meldungen und Ergebnisse einiges tun. Hoffe nur, daß sie das genehmigte Kapital für eine vernünftige Maßnahme im Sinne von uns Kleinaktionären einsetzen.

Gruß Coluche

[Erbse1]

Hallo liebe Cortex Fans, ich melde mich noch mal mit einem Artikel aus dem TIME Magazin.



Can You Find Concentration in a Bottle?

A guide to today`s brain-boosting pills and supplements and what`s in the pipeline

Quelle:http://www.time.com/time/magazine/article/0,9171,1147202-1,0…

Schönen Tag noch
Erbse

[Coluche]

Ein Mark Varney von Sepracor ist zu Cortex als COO gekommen. Er hat gleich 700.000 Share-Options zum Einstandspreis vom 30.01. (ca. 2,95 $) bekommen.

Er soll wohl eine Coryphäe in der Entwicklung bei Sepracor gewesen sein, Vic-President. Wenn das dort die zweite Ebene ist, ist das o.k., wenns wie bei den Amibanken ist (zwischen Vice-President und COO noch ein Senior-Vice-President und ein Executive-Vice-President, also Ebene 4), wäre nicht so gut.

Aber nachdem der Kurs auf diese Meldung bei hohem Umsatz ansteigt, ist es eher postitiv zu werten.

Im übrigen muß er wohl bei Sepracor tatsächlich was zu sagen gehabt haben. Neuroinvestor berichtet, daß man dort große Stücke auf ihn gehalten hat/noch hält; war dann doch eher 2. Ebene. Die Logik scheint auch zu sein, daß wenn er von einer sicheren und gut dotierten Stelle eines mit ca. 5,5 Mrd. $ bewerteten Unternehmens zu Cortex wechselt, er dort deutlich höhere Chancen und Potenzial sieht.

3,14 $ ist immerhin ein guter Anstieg.

Gruß Coluche

[Coluche]

...ach ja, Erbse, Dein Artikel aus der Times wird gerade im Yahoo-Board gesucht.

[Erbse1]

Hallo liebe Cortex Freunde,
ich denke mal jetzt stehen die Ergebnisse an. Es kann sich jetzt nur noch um Tage handeln. Es gibt bei Schlafentzug weitere Veröffentlichungen. Im New Scientist und Scotsman.

Liebe Grüße
Erbse



Lifestyle pills that promise to end the need for sleep

IAN JOHNSTON
SCIENCE CORRESPONDENT
A NEW class of drugs that promise to "cure" the need for sleep are being developed to help people cope with the 24/7 society.

It is claimed that the range of lifestyle pills will abolish the need for sleep for days at a time by creating a form of sleep that offers the benefits of a good night`s rest in a fraction of the time.


The research, reported in the New Scientist magazine today, is partly being driven by the United States military`s quest for a "metabolically dominant soldier" who can fight on when the enemy falls asleep, and partly to help nightshift workers and others who are struggling with over-tiredness.

Researchers are hoping to build on the success of the drug Modafinil, a stimulant launched seven years ago that allows people to wake up refreshed after just four hours of sleep.

Unlike caffeine or amphetamines it appears not to leave people with the jitters, euphoria and eventual "crash", and does not require a "sleep debt" to be repaid. Sales have climbed from £14.2 million in 1999 to £330 million in 2005. A new drug, called CX717, is being tested by Cortex Pharmaceuticals in California. the drug appears to help people maintain normal alertness, despite extended sleep deprivation.

Tests on 11 rhesus monkeys showed that they were performing better after 36 hours of continual wakefulness than monkeys that had not been drugged were after normal sleep.

Professor Russell Foster, a molecular neuroscientist and sleep expert at Imperial College London, said: "What is exciting is we are beginning really now to understand the basic mechanisms under-lying sleep. It is very complicated - there are lots of different parts of the brain involved.

"But if we genuinely understand the mechanisms of sleep, we could attempt to mimic that with a drug. I have no doubt, at some level, we`ll be able to mimic sleep, but we are a long way off."

However, he cautioned that sleep was vital for the brain to function properly. "In a society increasingly dependant on creativity, we know sleep is crucial. We know that the ability to see new pathways and generate new ideas is critically dependant on a good night`s sleep," Prof Foster said.

He said that Modafinil had originally been developed as a treatment for narcolepsy, but was now being used as a stimulant. "It`s probably mimicking part of the arousal system of the brain," he said. "I`d be very careful about long-term use. It is now being pushed as a cure for sleep and it really isn`t. It is one way to override the need for sleep, short-term. You can become dependant on these drugs for normal cognitive function."

But Prof Foster said he doubted such concerns would stand in the way of new drugs coming on to the market.

"I`m a pragmatist. I don`t think we are going to be able to change the 24/7 society," he said. "The more we understand about the body`s 24-hour clock, the more we will be able to override it.

"In ten to 20 years, we`ll be able to pharmacologically turn sleep off. Mimicking sleep will take longer, but I can see it happening."

He said it was easy to tell if someone was getting enough sleep. "If you are woken up in the morning by an alarm clock, the answer is no. You should wake up normally," he said.

CX717 will be tested later this year by the US Defence Advanced Research Projects Agency based in Arlington, Virginia, which will push 48 volunteers to their limit on the drug.

But the prospect of a world where people are awake almost every hour of every day is alarming experts.

Neil Stanley, head of sleep research at the Human Psychopharmacology Research Unit at the University of Surrey, said: "I think that would be the most hideous thing to happen to society."

Quelle:http://news.scotsman.com/health.cfm?id=241212006

Weiter noch die Vorschau von New Scientist:



Article Preview
Get ready for 24-hour living
18 February 2006
Graham Lawton
Magazine issue 2539
A new wave of drugs will make it a breeze to go days without sleep, and give you a good night`s shut-eye in two hours - are you ready for 24-hour living?
SO MUCH to do, so little time. Between a hectic work schedule and a thriving social life, Yves (not his real name), a 31- year-old software developer from Seattle, often doesn`t have time for a full night`s sleep. So he swallows something to make sure he doesn`t need one. "If I take a dose just before I go to bed, I can wake up after 4 or 5 hours and feel refreshed," he says. "The alarm goes off and I`m like, let`s go!"

Yves is talking about modafinil, a stimulant that since its launch seven years ago has acquired a near-mythical reputation for wiring you awake without the jitters, euphoria and eventual crash that come after caffeine or amphetamines. Yves has been popping modafinil on and off for the past three years and says it is "tremendously useful". "I find I can be very productive at work," he says. "I`m ...

The complete article is 3505 words long.

Quelle:http://www.newscientist.com/channel/health/mg18925391.300

[Erbse1]

Cortex`s CEO Roger Stoll to Speak at the Roth Capital Partners 18th Annual Orange County Conference

IRVINE, Calif.--(BUSINESS WIRE)--Feb. 16, 2006--Cortex Pharmaceuticals, Inc. (AMEX: COR) Chairman, President and CEO, Roger G. Stoll, Ph.D., will speak at the Roth Capital Partners 18th Annual Orange County Conference at the St. Regis Monarch Beach Resort & Spa in Dana Point, CA. Cortex`s presentation is scheduled for 8:00 am PST (11:00 am EST) on Wednesday, February 22nd 2006. The conference will feature over 250 small-cap companies across a broad spectrum of sectors, including technology, healthcare, financial services and consumer products.

Dr. Stoll will discuss the status of the three Phase IIa studies with its lead AMPAKINE(R), CX717 in ADHD, Excessive Daytime Sleepiness (EDS) associated with simulated Shift Work and the PET Scan Study in mild-moderate Alzheimer`s disease. Dr. Stoll will also discuss the recent hiring of Dr. Mark Varney as COO & CSO, an update on corporate partnering efforts and the potential in-licensing strategy of a late stage non-AMPAKINE product candidate(s) for "Orphan Drug" indication(s), in which the Company`s AMPAKINE technology platform could be additive. Ampakine(R) compounds safely amplify the effects of glutamate. Glutamate is the primary excitatory neurotransmitter in the brain and is responsible for higher-order behaviors and cognitive activities such as, thinking, smelling, touching and memory.

A live webcast of the presentation can be accessed by logging onto http://www.wsw.com/webcast/roth7/cor/ and a replay will be available for 45 days following the conference

Bin mal gespannt auf die neue Einlizensierungsstrategie und was sich dahinter verbirgt. Ansonsten warte ich sehnsüchtig auf die Ergebnisse.

Schönen Tag noch
Erbse1

[Erbse1]

Hallo liebe Cortex Freunde,

folgend eine Abschrift der Roth Konferenz angefertigt von ryanfearfrost . Weiterhin eine kurze Zusammenfassung des users gfp927z. Im Anschluß daran noch ein kurzer Kommentar des Cortex CEO Stoll.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=114076848…

Die wichtigsten Daten aber hier in wenigen Sätzen.

-ADHD Ergebnisse in ca. 10 Tagen.
-Schlafentzug Ergebnisse in ca 2-3 Wochen. Die Veröffentlichung der Daten kann noch etwas dauern, da die DARPA die Veröffentlichung absegnen muß.
- PET Scan Studien dauern noch etwas länger. Einzelheiten bitte aus dem obigen link entnehmen.

Schönen Tag noch
Erbse1

[Erbse1]

Hallo liebe Cortex Freunde,
habe den Newscientist Artikel auftreiben können. Es geht hier unter anderem um die DARPA, Cortex CEO Stoll und CX717

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=114006495…

Es tut sich auch Neues bei Organon. Es sollen bald Ergebnisse mit Org 24448 und Schizophrenie vorliegen. Nach Informationen des NeuroInvestor wird Ende März genannt.

Der Kursverlauf in den letzten Tagen ist zwar unerfreulich. Ob ein Zusammenhang mit den ADHD Ergebnissen besteht werden wir ja warscheinlich kommende Woche erfahren.

Machts mal gut
Erbse

[Erbse1]

Cortex Reports Positive Results with CX717 on the Primary Outcome Measure in Adult ADHD Study

IRVINE, Calif.--(BUSINESS WIRE)--March 6, 2006--Cortex Pharmaceuticals, Inc.`s (AMEX: COR - News), lead AMPAKINE® drug, CX717, showed positive results for the treatment of adults with Attention Deficit Hyperactivity Disorder (ADHD). Forty-nine patients with ADHD completed the randomized, double-blind, placebo-controlled, two-way crossover design performed at seven US sites. Cortex undertook this Phase IIa clinical trial to assess both the dose of drug required and the effectiveness of CX717 in an adult ADHD population. The primary outcome measure was the ADHD Rating Scale (ADHD-RS) which evaluates both the inattentiveness and hyperactivity symptoms. The overall ADHD-RS score showed a positive trend in the 800mg twice daily (bid) dose group (n = 22) with a statistically significant effect on the hyperactivity subscale (p=0.050) compared to placebo. The 200mg bid dose (n = 27) did not show a significant effect. CX717 was well tolerated, and there were no serious adverse events or other significant safety concerns with either dose. Further, no increases in blood pressure or heart rate were observed on either dose of CX717.
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"The results from this Phase IIa study in adults with ADHD show that CX717 provided a clinically relevant response on the ADHD Rating Scale though the results will need to be verified in a larger study," said Lenard Adler, MD, the lead investigator of the study, Director for the Adult ADHD Program, and Associate Professor of Psychiatry and Neurology at New York University School of Medicine. "I am encouraged by the performance of CX717 which could lead to the development of a new pharmacotherapy for the treatment of ADHD."

"We are delighted that we achieved a response with the 22 completers in the 800mg bid dose group," said Dr. Roger Stoll, Chairman & CEO of Cortex. "It goes without saying that further studies with CX717 will be conducted in larger patient populations to further define the therapeutic dose and frequency of dosing. We believe that the market may be very interested in a non-stimulant ADHD drug with reduced cardiovascular concerns, which CX717 might offer. Where previous results reported for CX717 were in sleep deprived, normal subjects, this is the first study we have completed in a patient population with CX717 and represents real progress for Cortex ."

ABOUT THE STUDY

The study was a randomized, double-blind, placebo-controlled, multi-center, 2-period crossover. Each subject received placebo during one treatment and either CX717 200 mg bid or CX717 800 mg bid in the other treatment period. Each treatment period was 3 weeks with a 2 week washout in between. Sixty-eight subjects were randomized of whom 65 took either CX717 or placebo. Of those 65, 49 completed all assessments in both treatment periods. Most subjects who withdrew did so for non-treatment related reasons. The results presented here are for the primary outcome measure (the ADHD-RS). Analyses of other parameters are ongoing.

ABOUT ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric disorder characterized by inattentiveness, poor impulse control and hyperactivity. The disorder was historically thought of as a childhood illness. Longitudinal studies however have documented the persistence of symptoms into adulthood in a large percentage of childhood sufferers. The prevalence of ADHD is estimated at 2 - 4% of adults. ADHD exacts a significant toll on social relationships, education, and vocational attainment. Relative to those without the disorder, adults with ADHD tend to have higher rates of divorce, lower grade point averages in school, lower graduation rates, lower socioeconomic status, and more frequent problems with unemployment

Conference Call

Cortex will host a conference call and webcast on Wednesday, March 8th, at 10a.m. EST, to discuss today`s announcement. Following the conference call, the company will open the phone lines to answer questions from investors and members of the media. Those who wish to participate may do so using the following dial-in information: In the United States, call [phone]. Internationally, call [phone]. An audio replay of the conference call will be available through Friday, March 24, 2006 by dialing [phone] for U.S. participants and [phone] for international participants. When prompted, participants should enter pass code 286 and conference ID number 195248. For the webcast please use the following link: http://www.vcall.com/IC/CEPage.asp?ID=102220. A replay of the webcast will be available through March 24, 2006.

Schönen Tag noch
Erbse

[puhvogel]

Es fehlen eine Menge Daten, speziell das Ergebnis beim ADHD-RS Score, und der Stoll betreibt ein wenig Data-Mining, aber soo schlecht sieht das nur auch nicht aus, dass man nun als Insider im Vorfeld verkaufe müsste.
Der Kursverfall der letzten Tage hatte also wohl andere Gründe. Momentan in der Frühbörse ein fettes Plus von 30 %.

[Erbse1]

Schneller Kommentar des NeuroInvestor.

The ADHD Phase IIa results came out better than we had dared expect. The dosing had tested the extremes, with extremely small sample sizes. The 200mg BID dose was a washout, but the 800mg BID dosing showed a "positive trend" on the overall ADHD scale score used as the primary endpoint-- will be of interest to see what `positive trend` means, although with n=22, that indicates a good magnitude of effect, reinforced by the crossover design. It won`t matter to a BP if it is 92% likely due to the drug, or 88%, here p=.05 would not be expected. It also was not expected on the hyperactivity subscale: p=.05 there is remarkable. Our conjecture had been that CX717 might end up primarily used with inattentive type ADHD, since the putative mechanism of this type of Ampakine would seem intuitively to be best suited for attentional symptoms. But these data suggest that it may be applicable across the board for both attentional and hyperactivity symptoms.
Not that it would be the first nonstimulant to do so, Provigil also showed efficacy in both subscales---albeit in studies involving 600+ patients, a far larger sample. It will be a while, and larger trials, before any reasonable comment can be made about their comparative magnitudes of effect. There had been some concern about the number of noncompleters, though the crossover design is harder for ADHD patients to adhere to, since they have to tolerate a washout, then return for a second treatment condition. Cortex has stated that "most" of the noncompleters were not due to drug, but it will be of interest whether those who were ended up skewed into the 800mg cohort. This is probably near the upper dosing limit, their partner will pay for Phase II trials looking at midrange doses.

In January we had reiterated that "this is the best molecular platform and related IP currently for sale in the CNS industry. These results validate that expectation. There are a number of Big Pharma companies which had been careful about the valuation of the Ampakine platform for attentional disorders. Now, those with interests in both attention/sleep deprivation, in the style of Cephalon`s Provigil, and in neurodegeneration, are going to be bidding up the value of a partnership that gives ample weight to both categories. With DARPA sleep deprivation data in three weeks, and the past Phase IIa data augurs well for those results; possible Organon information regarding their schizophrenia Phase IIb later this month, and a Big Pharma deal by the end of 2Q, the next few months will see Cortex finally live up to all of its predicted potential.

Machts mal gut
Erbse1

[Coluche]

Hallo Erbse,

nach den Entwicklungen der vergangenen Tage gibt es für mich zwei Dinge festzuhalen:


1. An Dich ganz explizit ein ganz herzliches Danke !!! für alle Deine unermüdliche Arbeit hier im Board.



2. Wir sind mit Cortex auf einem guten Weg


Gruß Coluche

[Erbse1]

Hallo coluche, liebe Cortex Freunde,

danke erstmal für die Blumen.
Zur Meldung vom Montag einen Presseartikel von der LA.Times. Sieht prima aus die Lage bei Cortex. Es kann jetzt ganz schnell sehr hoch gehen. Ich denke heute legen wir erst mal eine kleine Pause ein.

Liebe Grüße
Erbse




Promising Results for Attention Drug

A medication from Cortex Pharmaceuticals significantly reduced symptoms in initial trials. Shares jump 32%.
By Terry McDermott, Times Staff Writer
March 7, 2006


Irvine-based Cortex Pharmaceuticals Inc. announced positive results Monday from initial clinical trials for a drug to treat attention deficit hyperactivity disorder.

The test, conducted on 65 people across the U.S., showed that the drug significantly reduced key ADHD symptoms, said Lenard Adler of the New York University School of Medicine, who ran one of the trials.

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Cortex immediately announced it would take the drug, one of a family of drugs called ampakines, into larger trials.

Shares in the tiny company jumped more than 32% to $3.04 after news of the trial was released, nearing a 52-week high.

Cortex has been working to develop ampakines almost since they were invented 15 years ago in the lab of Gary Lynch at UC Irvine, and the results by far made for the best day in the beleaguered company`s history.

Since it was founded in 1987, Cortex has had a new chief executive about every other year. The company has struggled financially and nearly went out of business more than once.

Current CEO Roger Stoll said the company had been in negotiations with pharmaceutical companies to license the compound, called CX717, even before the trial results were announced. He said eight or nine companies had expressed interest, with about half of those expressing new interest Monday.

Stoll said such a deal could eventually be worth several hundred million dollars to Cortex. The money would allow the company to develop ampakines for other disorders, which include Alzheimer`s disease, schizophrenia, Huntington`s and some forms of mental retardation.

Treatment of ADHD is a multibillion-dollar-a-year business. It affects an estimated 4% of the children in the United States. ADHD is thought to be caused by too much or too little production of certain chemicals, called neurotransmitters, in the brain. The main treatment to date has been the prescription of stimulants such as Ritalin and Adderall, which increase or inhibit production of one or more of the neurotransmitters.

More than 31 million prescriptions were written for the disorder last year, according to IMS Health Inc., a company that compiles pharmaceutical industry data. However, a federal Food and Drug Administration expert panel warned last month that the stimulants posed a risk for strokes and heart attacks and recommended that a strong warning accompany sale of the drugs. The FDA has not acted on that recommendation.

The Cortex drug is not a stimulant and theoretically would have no such risk. In fact, no significant side effects were uncovered in the trial.

Arvid Carlsson, a scientific advisor to Cortex who won a Nobel Prize for his studies of dopamine, one of the neurotransmitters involved in ADHD, said ampakines could be safer because they interact with different portions of the brain circuits that regulate behavior.

"It makes sense that if you have a very different target, some of the problems that are caused by these other drugs can be avoided," he said. "It`s an exciting — though preliminary — finding."

Quelle:http://www.latimes.com/business/la-fi-adhd7mar07,1,5402637.s…

[Erbse1]

Hallo liebe Cortex Freunde,

folgend ein Upgrade von Rodman&Renshaw. Ich denke mal, daß bald auch andere Analysten auf Cortex aufmerksam werden. Die Entwicklung der letzten Tage war einfach super. Wichtige Punkte, die in nächster Zeit anstehen.

-Ergebnisse Schlafentzugstudie in Zusammenarbeit mit DARPA
-Ergebnisse Schizophrenie Studie 2b in Zusammenarbeit mit Organon.
-PET Scan Studie Ergebnisse bei Alzheimer wird wohl erst im Sommer/Herbst vorliegen.
-Auslizensierung von CX717 an einen großen Partner.

Es lohnt sich also Cortex in nächster Zeit zu beobachten.
Schönen Tag noch
Erbse

R&R Cortex comment and upgrade

<<TRANSFORMATION IN THE MAKING Last Friday, we hosted a lunch with Cortex management. It is becoming clear that the company is about to undergo a significant transformation. In 12 months, lead compound, CX717 may be in advanced trials for multiple indications, presumably with a corporate partner. Cortex plan to retain rights and to further develop orphan indications with either CX717 or with follow on compounds. The company also anticipates to license in a Phase II/III drug candidate, which maybe synergistic with AMPAKINEs. A successfully executed strategy could elevate Cortex in line with peers that are currently valued in the $375MM range (see page 3-4). Therefore, we are increasing our 12-month price target from $8 to $12 per share and maintain our Market Outperform / Speculative Risk rating.



EXPANDING MARKET POTENTIAL & INTEREST We have come to realize that CX717 may indeed have blockbuster potential in multiple indications. Following the disclosure of the initial ADHD data, management received “significant” interest from potential licensing partners. We are not surprised.



VS. AMPHETAMINES & MODAFINIL It is likely, that amphetamine drugs may get a black box warning for potential cardiovascular issues. CX717 did not impact blood pressure and heart rate so far. Cephalon’s (CEPH, Outperform) non-amphetamine modafinil have failed in adult ADHD. Yet, in narcolepsy and excessive daytime sleepiness (EDSS), modafinil recorded sales of over $500MM last year. The drug is a scheduled substance. While so far CX717 does not appear to have reinforcing properties in animals or in humans, formal testing is required to prove this point.



VS. STRATTERA Efficacy seen with CX717 may be at par (if not better) with Eli Lilly’s (LLY, Not Rated) non-stimulant, Strattera. Strattera sales declined by 17% to $552MM in 2005, presumably because of the black box label warning on associated suicidal thoughts and associated liver toxicity. Should the upcoming CX717 shift-work study (within a month) be positive, we could begin to think of CX717 having the combined efficacy of modafinil and Strattera with a potentially benign side-effect profile. Nearly 40% of CX717-treated patients (BID) complained about insomnia. This bodes well for the shift-work study, where among others, wakefulness promoting property is being tested.



COMPRESSING TIMELINES From our conversations with management, we conclude that they might be leaning toward developing CX717 for ADHD and sleep disorders first, because of the inherently faster time to market. The observation period in a typical ADHD study is 8 weeks vs. 12-24 months in Alzheimer’s disease. >>

This is from Annie Li, biotech analyst at Rodman & Renshaw

Quelle:http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112697844…

[Erbse1]

Hallo liebe Cortex Freunde,
nun ist auch der Aktionär auf diesen Wert aufmerksam geworden und hat ihn ins Musterdepot aufgenommen.
Ich denke mal, es wird nicht die letzte Empfehlung sein.

Schönen Tag noch
Erbse


Schnelle 60 Prozent

Mit einer Stop-buy-Order am Ausbruchsniveau soll dieser neue Musterdepotwert danach bis zum nächsten starken Widerstand durchmarschieren und dem Portfolio einen satten Gewinn einbringen.

Die Verantwortlichen für das Musterdepot von Der Darvas Investor wollen 1500 Aktien von Cortex Pharmaceuticals (WKN 879005) mit einem Stop-buy von 5,01 US-Dollar aufnehmen. Der Stop-Loss wird bei 4,64 Dollar gesetzt. Der nächste bedeutende Widerstand liegt bei gut acht Dollar und stammt aus dem Jahr 2000. Cortex entwickelt Pharmazeutika zur Behandlung von neurologischen und psychiatrischen Störungen, wie etwa Alzheimer, Schizophrenie, Depressionen oder Parkinson. Erfolgreich verlaufene Phase-II-Tests für das Mittel "CX717" gegen das Aufmerksamkeits-Defizit-Syndrom haben den Aktienkurs jüngst nach oben getrieben. Die Analysten von Rodman+Renshaw würden "CX717" Blockbusterpotenzial zutrauen und demnächst einen Kooperationsvertrag mit einem großen Pharmaunternehmen erwarten. Sollte sich "CX717" auch gegen Schizophrenie und Gedächtnisverlust als wirksam erweisen, sind noch höhere Kurse möglich. Doch schon jetzt hat Rodman+Renshaw das Kursziel von acht auf 12 Dollar erhöht und die Papiere mit "outperform-speculative-risk" eingestuft.

[Erbse1]

Noch ein Hinweis auf die Org 24448 Ergebnisse. Lassen wir uns überraschen, was die Ergebnisse bringen.

Schönen Tag noch
Erbse

Rodman & Renshaw
CORTEX PHARMACEUTICALS (COR)
BIOTECHNOLOGY
MARKET OUTPERFORM / SPECULATIVE RISK
COMPANY UPDATE
MARCH 21, 2006

COR: CORTEX COMPOUND MAY BE SHOWCASED BY ORGANON

CX691 (ORG24448) MAY SEE SPOTLIGHT Next Monday,
Organon will host an analyst day to discuss its clinical pipeline.
We believe that this may be an occasion to present progress
made with Org24448 (previously known as CX691), in Phase II
development for treatment of schizophrenia. If Org24448
proves effective in schizophrenia patients, this will bolster the
validity of the AMPAKINE platform. We expect Cortex to ink a
partnership agreement shortly on its lead molecule, CX717, and
reiterate our Market Outperform / Speculative Risk rating.
FURTHER VALIDATION Since Org24448 is a follow-on
compound to CX516, the original lead molecule from Cortex’s
AMPAKINE platform, positive results are likely to underscore
the therapeutic potential of the AMPAKINE molecules.
However, Org24448 is less potent, less stable and has a
shorter half-life than CX717, and therefore, if clinical efficacy is
seen with Org24448, this should only make expectations that
much higher for CX717 (see Table 1, Page 2). Even if
Org24448 does not prove effective, this should not dampen
expectations for CX717. We currently do not factor royalties
(single-digit?) on Org24448 into our valuation of Cortex.
AMPA MODULATION IN SCHIZOPHRENIA Schizophrenia is
a chronic, severe and disabling brain disease. Over 2MM
Americans suffer from the disease in a given year. Although
current medications are effective in treating positive disease
symptoms, such as hallucinations and delusions, the cognitive
impairments in schizophrenic patients are responsible for much
of the disease-associated disability and represent an unmet
medical need. A reduced level of glutamate-mediated
excitatory stimulation has been implicated in schizophrenia.
Org24448 was shown to markedly alleviate cognitive
dysfunction in earlier studies and restores excitatory stimulation
via its AMPA receptor-modulating activity.
CX717 PICKING UP SPEED We await further indications of
CX717’s efficacy in the DARPA-sponsored shift-work study,
and believe this compound to be the pre-eminent low-impact
AMPAKINE, combining efficacy and safety. From our
conversations with management, we conclude that they are
leaning toward developing CX717 for ADHD and sleep
disorders first, because of the shorter trial time. The
observation period in an ADHD study is 8 weeks vs. 12-24
months in Alzheimer’s disease.
KEY RISK Our recommendation for Cortex takes into account
that memory/cognition-related disorders represent one of the
most difficult-to-treat, and thus highest risk, therapeutic
categories. Cortex will need to partner its drugs to continue
their development in the absence of additional financing.

[Erbse1]

Hallo liebe Cortex Freunde,
am Montag steht die Konferenz bei Organon an. Es ist sehr gut möglich, daß hier Ergebnisse zu ORG 24448 veröffentlicht werden. Hierbei handelt es sich sehr warscheinlich um die Ergebnisse der Mono Therapie. Org 24448 wird auch als Kombi Therapie mit atypischen Neuroleptika getestet. Diese Versuche wurden meines Wissens später gestartet und dürften noch etwas dauern. Sollten die Versuche mit der Mono Therapie eine positive Wirkung bei Schizophrenie zeigen, dürfte dies am Montag eine große Auswirkung auf den Kurs von Cortex haben. Für Interessierte hier der link zur ORGANON Konferenz.
http://media.corporate-ir.net/media_files/nsd/akzoy/AKZONobe…

Zum weiteren Verständnis der Dopamin Glutamat Theorie gibt es zwei kleinere Beiträge von gfp927z und dem Neuroinvestor. Es lohnt sich hier mal reinzuschauen. Die Beiträge sind leider in Englisch.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112756146…

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=112736027…

Schönes Wochenende noch
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 20.945.520 von Erbse1 am 25.03.06 05:19:18

Hallo liebe Cortex Fans,

bei der Organon Konferenz gabs nichts Neues. Einige Schaubilder, die die Wirkung der Ampakine zeigen. Ansonsten der Hinweis, daß alles normal weiter geht. Ein Schaubild deutet darauf hin, daß Org 24448 die kognitiven Defizite bei Schizophrenie zumindestens teilweise vermindert. Kein Hinweis darauf, daß Org 24448 auch gegen die Positivsymptomatik wirkt.
Interessenten können sich diese DIAS ja mal anschauen. Es handelt sich hierbei um die DIAS 30 - 36. Leider kann ich diese Bilder nicht kopieren.

http://www.akzonobel.com/NR/rdonlyres/9BED5F59-224C-4FA7-B68…

Ich denke mal, daß wir bei Organon noch viel Geduld brauchen.

In allernächster Zeit stehen aber noch die Schlafentzugergenisse von der DARPA an.

Weiterhin dann noch die Auslizensierung von CX717.

Schönen Tag wünscht euch
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 20.958.316 von Erbse1 am 27.03.06 13:30:16

Meldung von Heute.
Cortex will die Zusammenarbeit mit Servier beenden. Kann gut sein, daß dies schon die Vorbereitungen auf einen Vertrag mit einem größeren Partner sind. Es stehen aufregende Zeiten ins Haus.

Liebe Grüße
Erbse

Termination of a Material Definitive Agreement

Item 1.02. Termination of Material Definitive Agreement.
On March 21, 2006, Cortex Pharmaceuticals, Inc. (the "Company" delivered notice to the Institut de Recherches Internationales Servier and Les Laboratoires Servier (collectively, "Servier" that, pursuant to the terms of Section 3.1 of the Research Collaboration Agreement between the Company and Servier dated October 13, 2000, as amended (the "Agreement", the Company has elected to terminate the research phase of the collaboration (the "Research Phase" and the Agreement effective December 7, 2006. The Company is currently having further discussions with Servier regarding the possibility of terminating the Research Phase and Agreement at an earlier date.

Under the terms of the Agreement, the Company and Servier collaborated to identify, evaluate and develop AMPAKINE compounds for use in the treatment of memory impairment associated with aging and neurodegenerative diseases. Under the Agreement, the Company currently receives approximately $2,298,000 per year (subject to the Company providing agreed-upon levels of research) and Servier is obligated to continue this level of support until early December 2006, or an earlier termination date, if agreed upon by Servier.

The Research Phase and the Agreement shall continue in full force until the termination becomes effective (in any event, no later than December 7, 2006) and the Company will not incur any early termination penalties as result of this termination. The Company shall make every effort to wind down the Agreement in a constructive manner, reflecting the good relationship that the Company has had with Servier. The Licensing Agreement, dated October 13, 2000, as amended to date, will continue in accordance with its terms.

[Erbse1]

Antwort auf Beitrag Nr.: 20.958.883 von Erbse1 am 27.03.06 14:13:54

Klingt erst mal nicht gut. Ich warte erst mal weitere Nachrichten ab.
Erbse

FDA halts Cortex's experimental sleep drug trial
Mon Apr 3, 2006 8:47 AM ET
April 3 (Reuters) - Cortex Pharmaceuticals Inc. (COR.A: Quote, Profile, Research) on Monday said the U.S. Food and Drug Administration has placed the clinical trial of its sleep disorder drug, CX717, on hold due to concerns over some preclinical animal data.

The company said it was contacted by regulators on March 31 but has yet to receive a formal notification about the halt. The company expects to receive a written notification within seven to 10 days.

TEXT-Cortex Pharmaceuticals
The action is not related to results from any human clinical trials, the company said in a news release.

[Erbse1]

Antwort auf Beitrag Nr.: 21.053.446 von Erbse1 am 03.04.06 15:04:05

Kommentar des NeuroInvestor zur jetzigen Lage.

Preclinical data is important--not more important, but important--because it is a proxy for the human experience. What would happen if you give someone x10 the therapeutic dose? Useful to know from a side effect viewpoint, and in case of future intentional or unintentional overdose. But since we can't try that with humans, it is done preclinically. More importantly, the high-dose, extended use tox paradigm is to some degree an accelerated course--not that the kinetics are the same, but if 1 dog out of 20 shows liver changes after three months at a very high dose, might there be some cumulative effect that would show up after two years in humans at the regular therapeutic dose? You feel better about the latter if you don't have the former.

Again--there could not have been a blatant, 'smoking gun' issue that came out of the CX717 tox studies--but there could be some anomaly that is viewed differently if you are an FDA reviewer who has been ordered to make damn sure that no 'FDA allowed dangerous drug to be given to humans in spite of animal warnings' headline will ever come up on their watch.

Because there was no blatant smoking gun, I believe that the odds are that this will be solvable, and that clinical trials will resume, and shareholders will be able to breathe again. What lab or preclinical work will be required to do so, and how long it will take, is impossible to say until we know what the problem is. I am guessing at least another three month animal study. I think we will know more by the end of this week. If not, I will be away all of next week, and will have little, if any opportunity to check in.

NeuroInvestment

[Erbse1]

Frisch von der NeuroInvestor Homepage
Cortex
4/3/06 The CX717 Clinical Hold

Cortex has to find out in detail what aspect of the preclinical data raised the red flag for the FDA--and then negotiates with the FDA as to what additional animal data they need to allay those concerns. I'm not assuming the best-case scenario, that they simply have to answer questions. It would be prudent to assume they have to run a confirmatory animal tox study at the very least.

I have seen clinical holds for other drugs based on: 1) a few mice died, they didn't know why, the drug is now in PhIII 2)Pfizer’s Lyrica issue, where animals developed tumors, humans didn't/don't--it is now marketed in the US and EU; 3) a drug which caused liver problems in dogs, and the company decided to go to another molecule.

Unless you believe Stoll was deceptive about the BP negotiations--and I do not believe that at all--BPs were pursuing a partnership, and all of them have all the data the FDA has, via Cortex---as well as data no one else has, that they obtain from their own inhouse vetting of the compound. If there was a smoking gun, BPs would have been backpedaling in a hurry. Now--they will want to know what the FDA wants, and the timeframe and difficulty of that will determine to what degree offers stay on the table; are rewritten; or are pulled entirely. The FDA would not have data on CX717 that Cortex does not have. But their interpretation of CX717 safety data could be influenced by data from other companies on other AMPA-modulator compounds that Cortex has not seen. To illustrate: using the dog liver enzyme hypothesis just as a model--let's say out of 20 dogs, 1 showed significantly elevated liver enzymes after three months of treatment. Cortex and its BP partner candidates could deem this a statistical fluke, a dog with a bad liver to begin with, and not anything that would show up in humans at human-level doses. If the FDA had (for example) information from Lilly or Organon regarding other AMPA-modulators that triggered a nonfluky, correlated association with liver changes, they might not buy the interpretation offered by Cortex. Even based on a different molecule, they could insist that Cortex do a bigger dog study (the study, not the dogs) to more carefully assess the CX717 association, or lack thereof, with liver issues.

But that is the extent of info to which Cortex would not be privy, but the FDA would be. Anything on CX717, they know about it, unless it was work done inhouse by a potential partner, which the FDA would not have access to. Again--there could not have been a blatant, 'smoking gun' issue that came out of the CX717 tox studies--but there could be some anomaly that is viewed differently if you are an FDA reviewer who has been ordered to make damn sure that no 'FDA allowed dangerous drug to be given to humans in spite of animal warnings' headline will ever come up on their watch.

Because there was no apparent, overt, ‘smoking gun’, I believe that the odds are that this will be solvable, and that clinical trials will resume, and shareholders will be able to breathe again. What lab or preclinical work will be required to do so, and how long it will take, is impossible to say until we know what the problem is. I am guessing at least another three month animal study. I think we will know more by the end of this week.

One thing this guarantees--this is an example of what Stoll worried about when contemplating keeping CX717 inhouse and taking it all the way for sleep dep/or ADHD. The risk of something unforeseen happening. And the bar for safety is set all the higher for a drug aimed at ADHD/sleep dep: the FDA is extremely vigilant about giving a drug to people who are otherwise healthy.

Quelle:http://www.neuroinvestment.com/CORXcom.html

[Erbse1]

Antwort auf Beitrag Nr.: 21.062.607 von Erbse1 am 04.04.06 06:19:24

Hallo liebe Cortex Freunde,
Meldung von heute wird dankbar vom Markt aufgenommen. Interessenten bitte zum Yahoo Board wechseln. Hier wird heftig diskutiert.

Liebe Grüße
Erbse

Cortex Updates Progress on Clinical Hold of AMPAKINE CX717


IRVINE, Calif.--(BUSINESS WIRE)--Apr 13, 2006 - Cortex Pharmaceuticals, Inc. (AMEX: COR) indicated on April 3rd that the Company received a phone call from the U.S. Food and Drug Administration (FDA) that a clinical hold was being placed on AMPAKINE CX717 and further clarification would be outlined in a formal letter by the agency. The Company has now received this letter that reviews the rationale for the agency's action, which is based on preclinical animal data, and outlines the work required for the clinical hold to be removed. Based on the terms in the letter, the Company has begun the process to arrange for discussions with the appropriate experts within the agency to translate the request into specific acute preclinical studies related to the issues and recommendations provided by the agency.

Cortex is going to cooperate fully with the FDA and work diligently to address its concerns. After the FDA and Cortex have agreed upon a plan of work, the Company will inform shareholders of both the scope of the work involved and the anticipated timeframes for completing such studies. The Company's objective will be to have the FDA remove the clinical hold and allow Cortex to proceed with the clinical studies currently on hold as soon as possible.

[Erbse1]

Antwort auf Beitrag Nr.: 21.194.720 von Erbse1 am 13.04.06 16:47:37

Hier direkt die Antwort von RODMAN & RENSHAW auf die Meldung von Heute.


Cortex Pharmaceuticals
COR, Price: $2.77 (04/12/06), Market Cap: $92 MM (04/12/06)
Rating: Market Outperform; Target Price: $12.00
Elemer Piros, PhD – Senior Biotechnology Analyst (212.356.0525)
Clinical Hold
Cortex Pharmaceuticals indicated on April 3rd that the firm received a phone call from the FDA that a clinical hold was
being placed on the lead AMPAKINE molecule, CX717, and further clarification would be outlined in a formal letter by
the agency. The firm has now received this letter that revi ews the rationale for the agency's action, which is based on
preclinical animal data, and outlines the work required for the clinical hold to be removed. Based on the terms in the
letter, Cortex will translate the request into specific acute preclinical studies related to the issues and recommendations
provided by the agency, following discussions with the appropriate FDA experts.
Our First Take
· The FDA’s recommendations relate to acute, not long-term, preclinical studies. The additional experiments
that would be necessary are therefore likely to take days or weeks, not months, to complete.
· The action taken by the FDA is related to concerns over some preclinical animal data and not to results from
any human clinical trials.
· Encouragingly, Cortex is willing to provide information regarding the status of its discussions with the FDA and
the timeline required to perform the experiments necessary to enable removal of the clinical hold on CX717.
· Cortex will discuss directly with the FDA to clarify what is required to resume clinical testing.
· We believe that, given the acute nature of the preclinical studies that would be required and the proactive
response of Cortex to the FDA’s action, the clinical hold on CX717 could be removed within a few months.
· We retain our Market Outperform rating with a target price of $12 per share

[Erbse1]

Vielleicht ist bei Cortex das Problem doch etwas schwerwiegender.
Langsam müßten auch zu Org24448 Ergebnisse vorliegen, so daß man vielleicht von dieser Seite her einige Hinweise auf dieses Problem erhält. Leider kann ich an dieser Stelle nicht hilfreich sein. Ich muß einfach abwarten, was sich aus diesem Problem ergibt

Liebe Grüße
Erbse

Dr. Garren issued an alert tonight on COR that was quite negative. He said the "acute" phraseology means that the new studies could be done quite quickly, but his fear is that if the issue is a liver toxicity issue, then it could be a very serious issue, because liver toxicity in animals is a good predictor of liver toxicity in humans. He predicted there would be no BP deal until all the issues with the FDA are resolved. He feels the recent run-up is completely unjustified.

Since he had urged subscribers to sell at $2.90 when the hold was first placed on the clinical trials by the FDA, I don't think his alert tonight will have any impact on the stock price.
Quelle:http://finance.messages.yahoo.com/bbs?.mm=FN&action=m&board=…

[Erbse1]

Hallo liebe Cortex Freunde,
es gibt Neues zu vermelden von den Ampakinen und den angeordneten Halt von der FDA. Es werden zusätzliche Studien mit einer stärkeren Dosierung im Tierversuch eingefordert. Nach dem Kurs zu urteilen scheint Cortex die Problematik im Griff zu haben. Folgend noch der Kommentar des NeuroInvestor zur gestrigen Jahreshauptversammlung und anschließend noch ein link zu der Veranstaltung mit aktuellen DIAS zu den ADHD Versuchen.

Die Cortex kostet schon ganz schön Nerven. Ich glaube, ich werde langsam zu alt für die Börse.

Machts mal gut
Erbse

) Let me start with something that would be hard to be sure of from a conference call: the mood, There was no mistaking the upbeat confidence conveyed by Roger Stoll and Gary Lynch. Stoll made the necessary (and very true) statements that nothing is assured until they have corrective data in August, and the FDA responds in September. But had there been pessimism, the atmosphere would have been very different. He was also far more specific about timelines than I expected.
2) They have brought in three consultants who have worked at the FDA--including the woman who was in charge of tox studies under CNS Division Head Rusty Katz. They really could not do a better job in terms of getting 'into the culture' so as to not make any errors in their responses.
3) I wish that they would have been more specific about the histopathological 'fly in the ointment' . But Roger did concede that there were 12 monkeys in the high-dose group, which tells me that it was the high-dose group from which the (I think) single anomalous sample came. That's better than if it were one out of three, for example. The dosing does appear to be an issue (though not, so far as I can tell, Gfp, in relation to sleep deprivation)--and it is interesting that my joke about overdosing rats turns out to be true: the FDA really does want more data about just how much CX717 one can give a rat before they crumble. And it turns out that they tend to regurgitate before they ever reach that point, which makes it tougher to answer the FDA's question.
4) The notion of disease-modification via neurotrophin release was not as new as Gary Lynch made it sound--it's been discussed for years on this thread. But what was new was that they could return rats to 'normal' memory baseline with multiple exposures to a high-impact with a very short half-life--fifteen minutes or so. The only clear negative from the meeting was that the IND timeline for a high-impact is 2-3 years. Something has not gone as planned.
5) The ADHD data is better than previously thought, and DARPA is even slower.


Overall--I am not going to use the 'speed bump' term any more than I was willing to say 'slam dunk.' Any 'speed bump' that has a 5% chance of ripping the undercarriage from my car is more than just a bump. But a histopathological change in a single monkey organ from a high-dose group is a lot less worrisome than a trend towards liver enzyme elevations, for example. They had no idea there was a problem brewing--Gary Lynch told me that he'd been expecting that this SHM would be a celebration, with champagne. But from everything I can see, they are handling it well. While nothing can be promised, they made it clear they expect that this will be solved, and the clinical hold lifted.

NeuroInvestment

Folgender link führt zur Präsentation der Jahreshauptversammlung.

http://www.cortexpharm.com/main.html

[Erbse1]

Kommentar des NeuroInvestor.

Machts mal gut
Erbse


The CX717 Clinical Hold

The reason for the sudden clinical hold--and the FDA's own regulations require that it try to discuss the situation, first which they did not do--was some type of histopathological finding from an old high-dose primate study. Cortex has to look at tissue samples from that primate study, and do another one, literally giving monkeys CX717 until they vomit. The secondary issue, though this would not have in itself been reason for a hold, is that the Agency still doesn't think Cortex has done enough to find the absolute maximum tolerated dose of the drug. It's too safe. This is certainly a better scenario than the liver enzyme issue that we had speculated about. We were correct that there is no 'smoking gun' de facto doom for CX717.

In a review of clinical holds that have been made public, NI has found that at least 75% are resolved positively. Adding in the many issued to Big Pharma companies that are kept quiet, the rate is higher. The histopathological review of old samples will be the first thing to be completed, the additional primate and rat tox studies will be completed by early August, at which point Cortex will submit a report to the FDA, and in theory, the FDA has 30 days to respond.

The risk of course, small though we believe it is, is that another animal will show the same change, and this will no longer be a fluke. If that were to eventuate, that could be fatal for CX717. We are 95% confident that this will not occur. Our projection is that the clinical hold will be lifted by the end of September. Big Pharma discussions could begin earlier that month if the data is clean, and the path forward clear, even if not yet formally confirmed.

[Erbse1]

Cortex Announces Update on CX717 Clinical Hold


IRVINE, Calif.--(BUSINESS WIRE)--June 8, 2006--Cortex Pharmaceuticals, Inc. (AMEX: COR - News) announced that it has provided to the U.S. Food and Drug Administration the preclinical research plan for removal of the current clinical hold on AMPAKINE® CX717. The FDA recently provided a written response finding the proposed research plan to be acceptable. Both parties felt that the clarity of the proposed actions was sufficient such that a scheduled conference call for June 9, 2006 was no longer necessary.

"Cortex worked hard to address the concerns of the FDA and we are pleased that our proposals were on target in responding to the questions which the agency raised regarding CX717. We currently are on schedule with the timelines proposed for conducting the additional preclinical studies. In fact, Cortex has already completed the review of the relevant histological materials from a previously completed preclinical toxicology study, which was part of the FDA request to Cortex. As stated at our annual shareholder meeting, we plan to submit all the data to the FDA in September 2006. If the data obtained from the acute high dose toxicology studies are assessed positively by the FDA, we believe the FDA will remove CX717 from the current clinical hold," said Dr. Roger G. Stoll, President, CEO and Chairman of Cortex

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde. Es gibt einen guten Artikel in The Sunday Times:



Focus: What price a good night's sleep?

Gesamter Artikel unter folgendem link
http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=115000162…
>>
Scientists are on a quest to develop a pill that replaces the natural kip. John Arlidge reports on how shuteye has become a multi-billion-pound lifestyle product

Dr Roger Stoll is an explorer. He is boldly searching for a mythical land where the living is easy. At his suite of laboratories, he proudly introduces his expeditionary team — a bunch of plucky human guinea pigs from Guildford and some rhesus monkeys. His map consists of a series of squiggly graphs.
The land Stoll is searching for is Nod. In this pleasant place, the days and nights are long and full because people need only an hour or two of sleep.
Many people believe they need eight hours’ sleep a night to allow their brains to recover from the rigours of the day. But, it seems, there is not the time. Modern life is too demanding — and exciting — to turn out the light for eight hours, or even six, in every 24.
Wouldn’t it be wonderful if there were a pill that could replace sleep? There are illegal drugs that do so temporarily, but they leave you shattered later on. Stoll is trying to find the Viagra of sleep: a genuine shut-eye simulator that will make him a billionaire.

Stoll is the head of Cortex Pharmaceuticals, a US-based firm that is working with researchers at the University of Surrey to come up with the holy grail of behavioural medicine — a drug that mimics the effects and benefits of sleep.
He says brain scans on his monkeys and human guinea pigs suggest that the firm’s new drug, CX717, does just that — helping brains and bodies to recover without sleep.
“The potential is to help people to stay awake longer and sleep less,” he said.
Stoll is at the forefront of a growing army of medical researchers and entrepreneurs who are striving to make sleep a “new and improved” lifestyle product.
Pharmaceutical firms, which supply 3m prescription sleeping pills in Britain a year, are spending billions on research to win the race to develop the new simulated-sleep pill.

Drugs firms trumpet their success in creating pills that cure the need to sleep. Eli Lilly and Glaxo have joined the race with America’s Cortex.
There is more to this than just the hunt for a miracle pill. While we wait to be cured of the need for sleep, we have become obsessed with getting the best quality sleep that money can buy.
As a result, shut-eye — a subject that only insomniacs and sleepwalkers used to worry about — has become the fastest-growing sector of the £300 billion global pharmaceutical, leisure and wellbeing market.

In laboratories and boardrooms around the world sleep is being studied, graded, commodified, copied and packaged — and then sold as if it were a low-fat snack bar or a vitamin-enriched mineral water.
Mintel, the market research analyst, estimates that the sleep market has grown from £1.6 billion 10 years ago, when the height of slumber sophistication was a posturepedic bed, to more than £4 billion today, when even motels have their own pillow menu offering dozens of types of cover and filling. >>>

Allerdings möchte ich darauf hinweisen, daß im Augenblick Vorsicht angesagt ist bis die Differenzen mit der FDA ausgeräumt sind. Es ist ratsam die aktuelle Situation genauestens zu beobachten.

Schönen Tag noch
Erbse

[Erbse1]

Schlafentzugergebnisse werden am Dienstag präsentiert
Schönes Wochenende
Erbse

Quelle:http://messages.yahoo.com/bbs?.mm=FN&action=m&board=16042432…
RODMAN & RENSHAW

CORTEX PHARMACEUTICALS (COR)
BIOTECHNOLOGY
MARKET OUTPERFORM / SPECULATIVE RISK
COMPANY UPDATE
JUNE 16, 2006

COR: PRESENTATIONS AT SLEEP CONFERENCE

DATA ON CX717 TO BE PRESENTED Next Tuesday, June 20th,
Cortex representatives will present data on the activi ty of CX717,
Cortex’s lead AMPAKINE compound, in sleep deprivation studies at
the 20th Anniversary Meeting of the Associated Professional Sleep
Societies. The meeting is taking place in Salt Lake City, Utah.
CX717 is currently under clinical hold; Cortex aims to have the
entire data package addressing the FDA’s concerns submitted to
the FDA by the end of August. We reiterate our Market Outperform
/ Speculative Risk rating and $12 price target.
CX717 CONTINUES TO SHOW PROMISE Top-line results were
presented last year in a press release from a sleep deprivation
study involving 16 patients. The sleep deprivation data to be
presented at the conference includes further results from a study of
healthy volunteers who were deprived of sleep for 27 hours. CX717
showed activity at the highest dose tested (1000mg), enhancing
alertness, attention, information processing and sleep latency. (See
abstract on Page 3.) These results appear promising and confirm
the activity that was seen in studies of CX717 in sleep-deprived
monkeys. Coincidentally, according to previous guidance by
management, results from the 48-patient shift-work study conducted
by DARPA may be released near-term.
CLINICAL HOLD COULD BE REMOVED IN SEPTEMBER In
response to the FDA’s request for additional acute preclinical work
on CX717, Cortex has hired regulatory consultants, initiated
Maximum Tolerated Dose (MTD) studies in primates; begun
assessment of tissue from the previous primate study; and will begin
work on the rat MTD study in mid-May. A data package will be
completed by August and the FDA has indicated that it would
respond within 30 days. The clinical hold on CX717 could thus be
lifted in September.
EFFICACY ENCOURAGING CX717 showed encouraging results
in the Phase II study in patients with attention deficit hyperactivity
disorder (ADHD). Results were comparable to those obtained with
the Eli Lilly (LLY, Not Rated) drug Strattera in a pivotal trial. A
repeated measures statistical test showed that CX717 provoked a
statistically significant response on the overall ADHD Rating Scale
as well as both the hyperactivity and attentiveness subscales. No
safety issues were seen. Cortex should receive the data on CX717
performance in the DARPA-sponsored shift-work study shortly.
KEY RISK Our recommendation for Cortex takes into account that
memory/cognition-related disorders represent one of the most
difficult-to-treat, and thus highest risk, therapeutic categories.
Cortex will need to partner its drugs to continue their development in
the absence of additional financing.

[Erbse1]

Die Ergebisse scheinen auf den ersten Blick gegenüber Placebo nicht überlegen zu sein. Da hat auch keiner mit gerechnet.

Top-Line Findings on CX717 from the Darpa-Sponsored Shift Work Simulation Study Will Be Presented at Sleep 2006 Meeting
Wednesday June 21, 8:30 am ET
Additional CX717 Data from the UK Sleep Deprivation Study to Be Presented at the Same Meeting


IRVINE, Calif.--(BUSINESS WIRE)--June 21, 2006--Cortex Pharmaceuticals, Inc. (AMEX: COR - News), announced that results from two studies with its lead AMPAKINE® drug, CX717, will be presented at the Sleep 2006 meeting in Salt Lake City, UT. Dr. Thomas Balkin, Chief, Department of Behavioral Biology, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, will briefly present the top-line findings from the simulated night shift work study conducted at WRAIR and funded by the Defense Advanced Research Projects Agency (DARPA). That study assessed the effect of CX717 on cognitive performance and alertness across 4 nights of simulated night shift work and restricted daytime sleep. The primary finding from the study was that CX717 did not enhance cognitive performance relative to treatment with placebo. However, similar to the observations in the previously reported UK sleep deprivation study, CX717 did alter the recovery sleep architecture as measured by EEG polysomnography in a dose-related manner. The 1000 mg dose of CX717 statistically (p less than 0.05) reduced the amount of slow wave sleep during each of the 4 recovery sleep periods and increased (p less than 0.05) the minutes of wake time after sleep onset during 2 of the 4 recovery sleep periods. CX717 was well tolerated, and no serious adverse events or other significant safety concerns were observed.

Additionally, two presentations will be made detailing the positive findings from the UK sleep deprivation study performed at the University of Surrey in the United Kingdom. Dr. Julia Boyle, Acting Head, Human Psychopharmacology Research Unit, University of Surrey, Guildford, UK will present the primary results from the study. Dr. Nicola Wright, Centre for Human Sciences, QinetiQ, Farnborough, UK will present new data using spectral EEG polysomnography to evaluate the effect of CX717 on the recovery sleep period during the study. In support of the key study findings, the spectral EEG analysis indicated that CX717 increased the level of arousal during recovery sleep.

Differences in study design and the implementation of certain study procedures may have contributed to some of the divergent results between the shift work simulation study and the UK study. While Cortex has received a study report from WRAIR, we look forward to receiving the full data set in order to compare the exact differences in drug performance between the two sleep studies.

From a business perspective, the Company's licensing discussions have focused on ADHD, Alzheimer's disease, and other neurodegenerative disorders. The top-line findings from the DARPA-sponsored study do not have a direct impact on the potential of CX717 in those disorders. Cortex's strategy has always been to retain the sleep deprivation uses as well as Orphan Drug uses of the low impact AMPAKINE® drugs for its internal development program. Cortex does not anticipate that future partnering discussions would include sleep disorder indications such discussions are unlikely to be affected by the shift work study findings.

"Our Phase II pilot program which included studies in sleep deprivation, ADHD, and Alzheimer's disease was designed to help us determine the most promising development pathway for CX717," said Dr. Roger Stoll, Chairman & CEO of Cortex. "While we are pleased to see some of the findings from the UK study confirmed in the DARPA-sponsored study, given the strong signal from our study in adults with ADHD our current plan is to prioritize ADHD in our future studies with CX717. We also remain committed to the program in Alzheimer's disease as we await the results from our Phase II study in that disorder. Moreover, we anticipate having the opportunity to conduct additional studies on sleep disorders with either CX717 or with CX701, a back-up compound that should enter clinical trials early next year."

Cortex will host a conference call and webcast later today, at 2:00 p.m. ET, to further elaborate on this information. Following the conference call, the company will open the phone lines to answer questions from investors and members of the media. Those who wish to participate may do so using the following dial-in information: In the United States, call [phone]. Internationally, call [phone]. An audio replay of the conference call will be available through Wednesday, June 28, 2006 by dialing [phone] for U.S. participants and [phone] for international participants. When prompted, participants should enter account number 286 and conference ID number 206297. For the webcast please use the following link: http://www.vcall.com/IC/CEPage.asp?ID=106039. A replay of the webcast will be available through June 28, 2006.

About the shift work simulation study

The shift work study was a randomized, double-blind, placebo-controlled, parallel group study in healthy young adult male volunteers. Fifty (50) subjects were assigned to one of three CX717 dose groups or placebo. Study medication was taken once per evening for four days. Each night subjects were assessed on a variety of cognitive parameters and tests of alertness in a protocol designed to simulate night shift work. The subjects' daytime sleep was restricted to 4 hours per day to mimic operational conditions involving chronic, restricted sleep

Schönen Tag noch
Erbse

[Erbse1]

Cortex's CX717 Clinical Hold Update

IRVINE, Calif.--(BUSINESS WIRE)--July 18, 2006--Cortex Pharmaceuticals, Inc. (AMEX: COR - News) has completed the in-life phase of both the one week acute primate study and the two week acute rat toxicology studies with its AMPAKINE® compound CX717. The tissue samples are now being prepared for histopathology assessments. These studies were part of the toxicology assessments requested by the FDA and are essential for a decision to lift the clinical hold.


Furthermore, the original tissue slides from the 13 week primate study have been assessed by an expert pathology working group of five histopathologists and a written consensus report has been prepared. In addition to these examinations, Cortex has completed the extended assessment of additional tissue samples from that same set of primates.

The timelines defined by Cortex at its annual shareholder meeting this past May for conducting the extra toxicology testing requested by the Food and Drug Administration are being met by Cortex and its contract research organizations. At present Cortex is on schedule for meeting its target date for submission of its complete response to the FDA by the beginning of September, 2006. The agency has committed to a 30 day review of this data upon such a submission.

Schönen Tag noch
Erbse

[Erbse1]

Kommentar des NeuroInvestor zur aktuellen Lage

7/17/06 The CX717 Clinical Hold

Cortex was having a landmark 2006 when the FDA's clinical hold stopped them dead in their tracks in early April. We continue to believe that the CX717 safety questions raised by the FDA are resolvable, and that the clinical hold will be lifted by early fall. There is of course always the small--but not nonexistent--possibility that another cellular anomaly could be found, in which case they will be starting over with another compound. The ADHD data was considerably better than anyone had reason to expect given its small sample size, and is the single biggest draw for a partnership. The negative top-line DARPA results diverged from the path laid out by the pilot sleep deprivation study, and with DARPA being as forthcoming with details (even to Cortex) as the North Korean government is regarding missile preparations, it is currently impossible to assess whether there is a fatal flaw in the sleep deprivation scenario or not. Cortex is still committed to keeping CX717 for an orphan indication, (and now has a much better chance at keeping narcolepsy) and is also looking to inlicense a PhIII compound from a partner or other BP source. Once the hold is lifted, a BP Pharma partnership will be signed, perhaps before year-end.

Schönen Tag noch
Erbse

[Erbse1]

Das ist mal eine tolle Veröffentlichung, wenns dann mal in der Praxis klappen sollte. Erst muß allerdings der aktuelle Disput mit der FDA geklärt werden.

Schönen Tag noch
Erbse

Drug Triggers Body's Mechanism To Reverse Aging Effect on Memory Process Age

A drug made to enhance memory appears to trigger a natural mechanism in the brain that fully reverses age-related memory loss, even after the drug itself has left the body, according to researchers at UC Irvine.

Professors Christine Gall and Gary Lynch, along with Associate Researcher Julie Lauterborn, were among a group of scientists who conducted studies on rats with a class of drugs known as ampakines. Ampakines were developed in the early 1990s by UC researchers, including Lynch, to treat age-related memory impairment and may be useful for treating a number of central nervous system disorders, such as Alzheimer's disease and schizophrenia. In this study, the researchers showed that ampakine drugs continue to reverse the effects of aging on a brain mechanism thought to underlie learning and memory even after they are no longer in the body. They do so by boosting the production of a naturally occurring protein in the brain necessary for long-term memory formation.

The study appears in the August issue of the Journal of Neurophysiology.

"This is a significant discovery," said Gall, professor of anatomy and neurobiology. "Our results indicate the exciting possibility that ampakines could be used to treat learning and memory loss associated with normal aging."

The researchers treated two groups of middle-aged rats twice a day for four days with either a solution that contained ampakines or one that did not. They then studied the hippocampus region of the rats' brains, an area critical for memory and learning. They found that in the ampakine-treated rats, there was a significant increase in the production of brain-derived neurotrophic factor (BDNF), a protein known to play a key role in memory formation. They also found an increase in long-term potentiation (LTP), the process by which the connection between the brain cells is enhanced and memory is encoded. This enhancement is responsible for long-term cognitive function, higher learning and the ability to reason. With age, deficits in LTP emerge, and learning and memory loss occurs.

Significantly, restoration of LTP was found in the middle-aged rats' brains even after the ampakines had been cleared from the animals' bodies. The drug used in the injections has a half-life of only 15 minutes; the increase in LTP was seen in the rats' brains more than 18 hours later. According to the researchers, this study suggests that pharmaceutical products based on ampakines can be developed that do not need to be in the system at all times in order to be effective. Most drugs used to deal with central nervous system disorders, such as Parkinson's disease, are only effective when they are in the body. Further studies will be needed to determine exactly how long the effect on LTP will be maintained after the ampakines leave the system.

The lingering presence of LTP also appears to contribute to BDNF remaining in the body, researchers said. "Ampakines work in two important ways to improve learning and memory," Lauterborn said. "They directly stimulate the connection between nerve cells, which has an immediate effect of boosting LTP. But they also increase the presence of this important protein, BDNF, that can stay in the body and keep boosting memory after the drug has worn off."

Collaborators on the study were Christopher Rex, Ching-Yi Lin, Eniko A. Kramar and Gary Rogers of Cortex Pharmaceuticals.

The study was funded by grants from the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, and from National Institute of Mental Health. The ampakine drug was provided by Cortex

Quelle:http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=115405918…

[Erbse1]

Cortex präsentiert auf der Bear Stearns 19th Annual Healthcare Conference. Es stehen auch wichtige Entscheidungen an. Gespannt bin ich auf die Einlizensierung der nicht Ampakine Substanz.
Die Entscheidung der FDA zum weiteren Verlauf von CX717 steht an.
Lassen wir uns mal überraschen.
Liebe Grüße
Erbse

Cortex's CEO Roger Stoll to Present at the Bear Stearns 19th Annual Healthcare Conference


Chairman, President and CEO, Roger G. Stoll, Ph.D., will speak at the Bear Stearns 19th Annual Healthcare Conference to be held at The Grand Hyatt New York in New York City, NY. Dr. Stoll's presentation is scheduled for Monday, September 11, 2006 at 4:00p.m. EDT (1:00p.m. PDT) in Ballroom C (the Park Avenue Room). The conference will feature companies spanning all sectors of healthcare.

Dr. Stoll will provide an overview of Cortex's AMPAKINE® research program, including the progress related to the clinical hold status of its lead AMPAKINE®, CX717. He will provide an update on corporate partnering prospects and discuss the status of the Company's strategy to in-license late stage non-AMPAKINE central nervous system product candidate(s) for potential use in "Orphan Drug" indication(s). Such products would complement the activities underway with Cortex's AMPAKINE technology and strengthen the development pipeline for the company.

A live webcast of the presentation can be accessed by logging onto http://cc.talkpoint.com/BEAR002/091106a_cy/?entity=cortex and a replay will be available for 45 days following the conference.

[Erbse1]

Hallo liebe Cortex Freunde,
Cortex präsentiert bei dem Neuroscience Meeting 2006.



Es ist mit über 30000 Wissenschafler eines der größten Treffen überhaupt.
Die Ampakine und Cortex Pharmaceuticals sind mit ca. 10 Beiträgen vertreten. Einzelheiten könnt ihr den folgenden Abstrakten entnehmen. Hier gibt es jede Menge Neues. Die Beiträge sind leider alle in Englisch.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=115726056…

Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde. Diesmal ganz besonders an die älteren Semester unter uns. Folgender Abstrakt macht wieder Lebensmut.

The Effects of AMPA-Type Glutamate Receptor Modulators on Sexual Behavior of Aged Male Rats

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=115730749…

Na dann schlaft mal gut
Erbse

[Erbse1]

Hallo liebe Cortex Fans, die Entscheidung der FDA rückt langsam näher. Die Daten sind von Cortex übermittelt worden.

Cortex Submits Complete Response to FDA to Address Clinical Hold on CX717

IRVINE, Calif.--(BUSINESS WIRE)--Sept. 11, 2006--Cortex Pharmaceuticals, Inc. has submitted to the Food and Drug Administration (FDA) the Company's complete response to each of the points raised by the FDA regarding certain toxicology issues on its lead AMPAKINE® compound, CX717. By its regulations, the FDA is required to respond within 30 days as to whether it will remove or maintain the clinical hold. Cortex has every confidence the FDA will meet the required timeframe.

"Cortex has worked diligently over the past few months to address the concerns of the FDA," said Dr. Roger G. Stoll, President, CEO and Chairman of Cortex. "While we believe the submitted data is sufficient to release the hold and resume our clinical trials program on CX717, that decision is ultimately one that will be made by the FDA."

The Company has met the timeline it defined at its annual shareholder meeting in May 2006 for conducting additional toxicology studies required by the FDA and its submission of the complete response to the agency by early September. Cortex will inform shareholders once it has received notification of the FDA's decision. Prior to the clinical hold being placed on CX717, the Company had reported positive results of a Phase IIa study for the treatment of adults with Attention Deficit Hyperactivity Disorder (ADHD).

Schönen Tag noch
Erbse

[Erbse1]

Kommentar von Rodman & Renshaw

RODMAN & RENSHAW

Cortex Pharmaceuticals
COR, Price: $3.42 (9/8/06); Market Cap: $119MM (9/8/06)
Market Outperform, Target Price: $12

Complete Response Submitted on CX717 Clinical Hold
· This morning, Cortex Pharmaceuticals announced that the company has submitted to
the FDA the complete response to each of the points raised by the FDA regarding
certain toxicology issues on its lead AMPAKINE® compound, CX717. The FDA
originally placed CX717 on clinical hold in April of this year.
· By its regulations, the FDA is required to respond within 30 days as to whether it will
remove or maintain the clinical hold on the compound in light of the new data.
· We continue to believe that the FDA is likely to remove the clinical hold on the
compound in October.
· Once the clinical hold is lifted, we expect Cortex to resume discussions with potential
licensing partners for CX717.
· Prior to the FDA’s placing CX717 on clinical hold, Cortex reported results of a Phase IIa
study of CX717 in adults with ADHD. This trial showed significant efficacy of CX717 at
a dose of 800mg twice a day with no safety concerns.
· The compound was significantly more effective than placebo on the total ADHD Rating
Scale (p=0.0024) and on both the hyperactivity (p=0.0168) and inattentiveness
(p=0.0273) subscales.
· Results from this Phase IIa trial will be presented at the annual meeting of the American
Academy of Child and Adolescent Psychiatry in San Diego on October 27, 2006.
· We are encouraged by the timely submission of data to the FDA on CX717 and remain
confident that this information will prompt the FDA to remove the clinical hold from the
compound. We reiterate our Market Outperform rating and price target of $12 on
Cortex shares.

Weiterhin kurz eine Bemerkung des NeuroInvestor

That PR statement is all the more remarkable given Stoll's historical tendency to be rather understated in his commentary. It does indeed suggest that Cortex believes they are on the same page as the FDA, and probably are: and it is as far as Roger Stoll could go without tempting fate--or agency ire. It would not surprise me if it does not take the full 30 days to receive official word from the FDA--and I would now be profoundly shocked if the clinical hold is not lifted.

NeuroInvestment

[Erbse1]

Cortex' CX717 Released from Clinical Hold by FDA

IRVINE, Calif., Oct 09, 2006 (BUSINESS WIRE) -- Cortex Pharmaceuticals, Inc. (COR) received notification from the U.S. Food and Drug Administration (FDA) on the afternoon of Friday, October 6, 2006 that the clinical hold placed on its AMPAKINE(R) CX717 on March 31, 2006 was lifted. The Company may now resume the clinical trials that were underway at the time the clinical hold was put into effect. A detailed formal letter from the FDA is expected to follow within 10 days.

In agreeing to the lifting of the hold, Cortex committed to an FDA specified dose range for CX717. The Company expects to have further toxicological information available toward the end of this year, after completion of three-month toxicology trials in both monkeys and rats. The Company will then share those results with the FDA and mutually determine if the new information supports clinical investigations at higher dosage levels for CX717.

Roger Stoll, Ph.D., Chief Executive Officer of Cortex, commented, "The release from clinical hold is an important step for Cortex and the CX717 clinical program. It is fortunate that the Company had the foresight to initiate the three-month toxicology trials early this summer, so that we can have further information from these studies available before year end 2006."

After receiving the formal letter from the FDA regarding the lifting of the clinical hold, the Company will hold a conference call to update shareholders on the next steps with the CX717 program

Schönen Tag dann noch
Erbse

[Erbse1]

Schnell zu der heutigen Meldung der Kommentar des NeuroInvestor.

10/9/06 The CX717 Clinical Hold

As we had expected and predicted, the FDA lifted the clinical hold on Cortex's Ampakines today. Cortex had anticipated the request to conduct 3 month toxicity testing for a higher dose, and had already begun that testing, which means it will be done before year-end. We do not see that as a problem, if the FDA had seen anything of further concern in the testing done since the hold was put in place, the hold would not have been removed. It is the earmark of the current FDA emphasis on CYA that they wanted the additional three month tox testing done now. The lifting of the clinical hold allows the Big Pharma due diligence efforts to resume full-speed, although with the delay that has occurred, it is unlikely that the BP partnership will be consummated until 1Q:07.

Quelle:http://www.neuroinvestment.com/CORXcom.html

[Erbse1]

Cortex to Hold Conference Call on October 26 Following Release of CX717 from FDA Clinical Hold

Tuesday October 24, 10:10 am ET


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX:COR - News) received the formal letter from the U.S. Food and Drug Administration on Monday, October 23, 2006 regarding the lifting of the clinical hold on Cortex's lead product candidate, AMPAKINE® CX717. The Company will host a conference call at 4:00 p.m. ET (1:00 p.m. PT) on Thursday, October 26th to review the steps it is taking to advance the development of CX717.
Quelle:http://biz.yahoo.com/bw/061024/20061024005770.html?.v=1

Hoffen wir mal auf einen positiven Ausgang.
Schönen Tag noch
Erbse

[Erbse1]

Hallo liebe Cortex Freunde,
es schaut erst mal nicht so gut aus. Im Augenblick scheint die Weiterentwicklung von CX 717 bei ADHD nicht möglich. Eine Zusammenfassung der Konferenz und den Kommentar des NeuroInvestor gibt es unter dem folgeneden link.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=116170383…

Bin selber gespannt, wie weit es heute wieder runter geht.
Ich selber bin jetzt fast sechs Jahre in Cortex investiert und wie es scheint brauchen wir noch eine Menge an Geduld und Durchhaltevermögen.
Liebe Grüße
Erbse

[Erbse1]

Weiterer Kommentar des NeuroInvestor. Leider gehts an der Börse selten logisch zu. Dennoch stimme ich im großen und ganzen den Ausführungen zu.
Trotz allem noch einen schönen Tag
Erbse

10/27/06 Additional Comment on the Status and Valuation CX717
Watching the Cortex price drop below 2.00 this morning led us to review what happened after the FDA clinical hold was announced in April. The lowest it dropped at any time was 2.43, giving a fully diluted market cap of about US$120 million. That was at a time when the clinical hold prohibited any use of CX717 in humans. It was not known how long it would be until the hold would be lifted, if ever; whether this was a toxicity issue that might apply to other Ampa-modulators. In other words, the entire platform was in question, for all indications, for an indefinite amount of time.

Fast forward to today. At about 2.00 per share, the fully diluted market cap is $100 million. The FDA has basically said that use in humans is OK at low doses, pertinent to Alzheimer's--but that they have yet to be convinced that higher doses are OK. There is a timeline for answering those questions. We also now know that there was a company which had been prepared to offer a possibly attractive partnership deal for Alzheimer's last spring. We have also been told that the Cortex backups, and Organon's Org24448 (also known as Cortex's CX691) do not show evidence of this problem-i.e. it is not a class effect.

And now Cortex is worth about 20% less than in April? That makes no sense. At some point, the disconnect will be recognized, and the share price will recover--at least to a point higher than the nadirs of mid-April.

[Erbse1]

Folgender Artikel beschreibt sehr treffend die aktuelle Situation bei Cortex,

Schönes Wochenende
Erbse

Cortex Dives After Agreeing To FDA Dosing Restrictions
By Aaron Lorenzo

FDA-imposed dosing limits are preventing Cortex Pharmaceuticals Inc. from more broadly studying CX717 in humans for now, causing the company's stock to lose more than a third of its value Friday, although the agency lifted a seven-month clinical hold on the drug in the process.
The shares (AMEX:COR) fell $1.20 to close at $1.85, a 39 percent plunge, after CEO Roger Stoll detailed the investigational compound's "conservative" dosing curbs.
Without divulging a specific ceiling, he told investors on a conference call that the limits would allow Cortex to test it only in Alzheimer's patients, for which lower amounts are acceptable to see a treatment benefit. But that also means that the company, of Irvine, Calif., would not be able to continue clinical testing of CX717 in attention deficit hyperactivity disorder (ADHD) for the near term, because those patients necessitate higher doses that exceed the FDA boundaries.

"We had to accept their dose limitations," he said, in order to get the agency to remove a clinical hold on the product that's been in place since March. So Cortex received "half a loaf instead of a full loaf," Stoll added.

He said Alzheimer's studies require doses between 1 mg/kg and 3 mg/kg, while ADHD trials necessitate a dose range of 10 mg/kg to 20 mg/kg.

Going forward, Stoll said the company plans to ask the agency to "liberalize" its dose restrictions after completing additional animal toxicology studies that already are under way. More specifically, Cortex expects three-month tox trials in both monkeys and rats to generate complete reports for the FDA by the end of next quarter in order to expand to higher dosage levels and begin ADHD testing again.

Prior to the clinical hold, which resulted from animal toxicology findings rather than clinical testing problems, the company had reported positive Phase IIa results in adults with ADHD, an indication to which potential partners had been attracted, Stoll said. He noted "tremendous interest" in CX717 for both Alzheimer's and ADHD, but conceded that "it doesn't make much sense" to form a collaboration at the moment.

Stoll also indicated that Cortex likely would seek some form of financing next quarter, since no partnership funding is expected anytime soon. The company had about $15.5 million in cash reserves through June 30. To date, Cortex has spent about $2.5 million in "additional unplanned funds" related to CX717's clinical hold, he said.

Preliminary toxicology findings from animal studies should start coming in near the end of this year, though such data would be used to inform the company and not get submitted to the FDA.

CX717 is an ampakine compound, a class of drugs that enhance memory and cognition by acting on chemical pathways that impact at least 85 percent of all the neurotransmission occurring in the brain.

Stoll noted that because the technology relates to "a new science," there would be bumps in the road. In addition, he noted that if the FDA again rejects Cortex's plans for testing higher CX717 doses in ADHD patients, the company would have "a roadmap" for backup compounds already in development.

[Coluche]

Antwort auf Beitrag Nr.: 24.906.255 von Erbse1 am 28.10.06 08:00:24

Hallo Erbse,

melde mich mal wieder, da ich auch noch investiert bin.

Schade, daß es gestern solch einen Rückschlag gegeben hat, den ich in der Sache in diesem Ausmaß nicht für gerechtfertigt halte. Denke, da hat wohl auch das Downgrading mit dazu beigetragen.

Sicherlich ist nun mit einer Kapitalerhöhung zu rechnen, doch sehe ich nach wie vor goße Chancen für einen deutlichen Kursanstieg in den nächsten 12 Monaten.

Man muß nur bedenken, daß alle Vorstände jweils hunderttausende von Aktieboptionen halten, deren Optionspreis bei $ 3 liegt. Und darüber wird der Kurs auf jeden Fall wieder gehen.

Stoll hat im Interview ggf. auch einen Verkauf nicht ausgeschlossen bei dem richtigen Preis. Denke der dürfte nuf jeden Fall nicht unter $ 6 liegen.

Gruß coluche

[Erbse1]

Antwort auf Beitrag Nr.: 24.910.634 von Coluche am 28.10.06 11:34:55

Hallo coluche, freut mich von dir zu hören. Ich rechne auch mit einer weiteren Kapitalerhöhung. Eine Auslizensierung von CX 717 bei Alzheimer wäre auch denkbar, aber überraschend.
Stoll lässt Cortex nicht mehr trocken laufen.

Es tauchen aber von ORGANON positive Abstrakte zu Ampa Rezeptoren auf. Ich rechne von hier bald mit positive Meldung.

Recent advances in positive allosteric modulators of the AMPA receptor.

Morrow JA, Maclean JK, Jamieson C.
Department of Molecular Pharmacology Organon Laboratories Ltd., Newhouse, Lanarkshire, UK. [e-mail]

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propioic acid (AMPA) subtype of glutamate receptors mediate fast excitatory neurotransmission throughout the mammalian nervous system and participate in the forms of synaptic plasticity that are considered to underlie learning and memory. Positive allosteric modulators of these receptors are the subject of much investigation because of their emerging therapeutic potential for a range of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease. This review focuses on the most recent developments in preclinical and clinical research on novel classes of AMPA receptor positive modulators and highlights how the application of biostructural studies has increased our understanding of the biophysical effects produced by these drugs.

Schönes Wochenende noch und bis demnächst
Erbse

[lisa46]

na wie siehts hier aus?! geht noch was oder bald das licht aus?!

wie sieht's mit der finanzierung aus?

[Erbse1]

Hallo lisa,
hier der aktuelle Kommentar des NeuroInvestor. Mal sehen was draus wird. So genau weiß das jetzt keiner.

Grüße
Erbse

From the November issue of NeuroInvestment added 11/2/06

The CX717 histopathology was not as pristine as it first seemed--some high-dose rats showed the same cellular anomalies as that one single primate in the earlier studies. Yet loading up monkeys with equally massive doses did nothing, and neither species showed any behavioral or functional changes when given 1.5 grams per kilogram (!). But the FDA will not let them run the higher dose ADHD PhII until soon-to-be-completed 3 month tox studies are finished. Right now, they can only do Alzheimer's patients. 40%+ was carved off the share price due to the regulatory uncertainties and expectation of a PIPE--even though no PIPE is imminent (contrary to rumor). The good news isL the clinical hold per se is off, which means all negotiations with the FDA are less charged, less binary.

By sometime in January, Cortex will know whether the 'target organ' showed any changes with three month exposure, and at what doses. The hope is that a dose high enough to permit the 10mg/kg dosing needed for ADHD will be clean. Given that the monkeys given far higher doses for two weeks had no evidence of that mysterious 'signal', they have a chance of achieving that goal. But until the FDA actually gives a go-ahead, a cloud hangs over the ADHD indication. Cortex noted that they had been very close to an Alzheimer's deal before the hold was lifted--and it is possible that an AD company could offer a deal at this point, though the times will be less optimal than they would have been last spring.

Within the next two months, Cortex will need money (from a PIPE or a deal) to supplement the $9 million they will have at year-end. The timing is not good for an inlicensing, we would prefer to see that delayed, though Cortex is still leaning that way. Cortex may have other strategic options open to them--we believe--and have communicated--that they need to thoroughly assess these. Lilly could cement an AMPA franchise if they would only shift out of anachronistic insular thinking--so could Organon, and their need to enhance their IPO credentials is accentuated by asenapine's problems. If either of those companies were to develop a frontal lobe, they would see this as an ideal opportunity. Cortex will probably be stuck in the $2 range until January's information from the three month tox work is released--or if one of these two companies gets a clue.

[Erbse1]

Hallo Cortex Freunde,
Cortex hat schnell reagiert bevor das Geld knapp wird.
35 Millionen shelf offering. Das dürfte dann mit dem vorhandenen Geld gut 2 Jahre reichen.

http://www.sec.gov/Archives/edgar/data/849636/00011931250623…

Wir müßen jetzt erst mal die Ergebnisse der zusätzlichen Tierversuche zu CX717 abwarten. Hoffen wir mal, das es gut geht. Eine neue Substanz dauert wieder ca. 2-3 Jahre bis sie den heutigen Stand erreicht hat.Das wäre wieder eine lange Wartezeit.

Weiterhin sind auch die Ergebnisse von Organon zu Org 24448 bei Schizophrenie zu erwarten.
Einige Leute hoffen, daß bei Organon die Ampakine beschleunigt werden, da bei Asenapine nicht die erhofften Ergebnisse erreicht wurden. Organon spricht von "mixed results". Asenapine war der Hoffnungsträger von Organon bei Schizophrenie.

Org 24448 wird bei kognitiven Defiziten bei Schizophrenie getestet. Außerdem soll ein synergistischer Effekt mit anderen Psychosemedikamenten eintreten. Diese Aspekte werden zur Zeit untersucht.

Schönen Tag noch
Erbse

[Erbse1]

Wichtiger Abstrakt von Organon Zu Org 24448 (Farampator)

Acute Effects of the Ampakine Farampator on Memory and Information Processing in Healthy Elderly Volunteers.

Wezenberg E, Jan Verkes R, Ruigt GS, Hulstijn W, Sabbe BG.
1Department of Psychiatry (966), Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo.

Testing took place 1 h after drug intake, which was around T(max) for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT.

Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia. Neuropsychopharmacology advance online publication, 22 November 2006; doi:10.1038/sj.npp.1301257.

Quelle:http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=116429792…

[CharlesRichmond]

Antwort auf Beitrag Nr.: 25.626.379 von Erbse1 am 23.11.06 17:51:26

Erbse1,

ist das Ergebnis dieser Studie für Dich so überzeugend, dass Du Cortex für ein gutes Investment hälst?

Gruß

CR

[Erbse1]

Hallo CharlesRichmond, hallo Cortex Freunde,

Cortex ist im Augenblick sehr risikoreich, aber auch nur noch mit ca. 50 Millionen bewertet.
COR selber hatte sehr viel Pech mit der Entwicklung einer eigenen Substanz.

CX516 gescheitert wegen zu geringer Wirkung.

CX717 Probleme mit der FDA wegen toxigologischer Probleme.

Viel hängt davon ab, ob die neuen toxigologischen Cortex Studien ein positives Ergebniss liefern und CX 717 bei ADHD weiter entwickelt werden kann. Das würde dann Einnahmen in mittelfristiger Sicht, also in ca 3-4 Jahren bedeuten. Die Entscheidung der FDA hierzu steht wohl im 1.Quartal nächsten Jahres an. Eine Weiterntwicklung bei Alzheimer steht wohl nichts im Wege, ist aber an Servier auslizensiert. Im Tierversuch wird ein positiver Effekt mit Aricept beschrieben, muß dann noch am Menschen bestätigt werden.



CX691, Org 24448 oder auch Farampator genannt wurde von Cortex an Organon auslizensiert. Ersmals wurde in Studien positive Ergebnisse am Menschen erzielt, die eine Anwendung bei Schizophrenie und Alzheimer in Betracht ziehen. Bei Schizophrenie tauchen im allgemeinen drei Merkmale auf, die behandelt werden sollten.

1. Positivsymptomatik
2. Negativsymptomatik
3. kognitive Defizite

Farampator wird von Organon weiter als Monotherapie bei Schizophrenie getestet. Diese Versuche scheinen abgeschloßen und wir warten auf die Veröffentlichung der Ergebnisse. Weiterhin wird Farampator in Kombination mit Risperdal, also mit einem Psychosemittel erprobt. Sollte sich hier ein synergistischer Effekt mit anderen Psychosemitteln ergeben, wäre dies allerdings ein super Erfolg. Der Markt bei Psychosemedikamente beträgt zur Zeit ca. 12 Milliarden $. Es wäre schon was, wenn Farampator zusätzlich zu allen anderen Psychosemedikamente gegeben werden könnte. Einige Studien sprechen sogar von einer Verringerung der Dosierung. Dies wäre eine enorme Kosteneinsparung. Weiterhin tauchen die meisten Nebenwirkungen bei hohen Dosierungen auf. Es bleibt abzuwarten wie die Ergebnisse ausfallen. An Organon ist negativ zu bemerken, daß sie sich sehr viel Zeit für ihre Versuche nehmen und so wertvolle Patentrestlaufzeit verstreicht.
Weierhin wird Farampator noch vom NIMH bei Depression und von MATRICS zu kognitiven Defiziten bei Schizophrenie getestet.

S 26576 ist an Servier auslizensiert und wird zur Zeit in einer großen Studie bei MCI getestet. Die Veröffentlichungen hierzu sind sehr rar und wir müßen auch hier die Ergebnisse abwarten. Einige Fachleute befürchten auch hier toxikologische Probleme. Bis jetzt wurden aber hierzu keine negativen Meldungen veröffentlicht.

Es gibt noch einen Patentrechtsstreit in Europa mit Eli Lilly und Glaxo hat sich auch noch angehängt. In erster Instanz wurde das Cortex Patent bestätigt. Auch hier müßen wir das Ergebnis abwarten.

Es gibt viele Anwendungsgebiete, bei denen Ampakine in Betracht kommen. Ich halte Cortex aber im Moment für hochspekulativ. Bei Erfolg aber auch sehr ertragreich. Leider kann auch ich keine Ergebnisse vorhersagen und muß die Ereignisse, die da kommen werden auch abwarten.
Für weitere Recherchen zu COR bietet sich mein kleines Board an.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl

Ich hoffe ein wenig geholfen zu haben.

Grüße
Erbse

[Erbse1]

Gestern gabs eine Konferenz. Weitere Einzelheiten unter folgendem link und der Stellungnahme des NeuroInvestor.

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=116464889…

NeuroInvestor
Bank of Montreal presentation:

There were two elements today regarding high-impacts and neurodegeneration, one of which was understated, but huge:

Cortex was able to defragment the Balkanized rights for neurodegenerative disease--they now have regained Servier's (outside North America) rights. Servier can try to develop one of the collaboratively-developed compounds to sell in their territory, but we believe they have a very small chance of success (their current lead, S18986, recently had its PhII trial in MCI halted due to toxicity, and is probably dead).And it would be in error to conclude that Servier had lost interest in AMPA modulators and simply relinquished them--such was not the case. More importantly, Cortex can now partner with a Big Pharma for neurodegeneration world-wide--including the high-impact compounds now in lead optimization. This is far more marketable than the slice of pie--North America--they could previously offer. This is a major development in terms of accessing a substantive BP partnership-the word 'worldwide' means a lot to major companies, and the earlier situation had been a deterrent to a Class A partnership.

Secondly, Cortex reported early mouse findings for both Fragile X and Huntington's. Not only did the high--impact CX929 normalize electrophyiological activity and BDNF levels, but it produced improved dendritic growth in the Fragile X model, and appears to be improving survival in HD mice. All mouse findings must be taken with salt, but this is exactly what one would hope to see.

There was essentially no real new news on the CX717/low-impact slate--still waiting until Jan/Feb to see if CX717 is viable for AD, ADHD, both, or neither. However, Roger Stoll stated that some company consultants still think that the cellular signal could be an artifact--this chapter is not yet closed.

Schönen Tag noch
Erbse

[Erbse1]

Kommentar des NeuroInvestor zu Cortex

Talk about bipolar years. In March Cortex was looking very healthy, based on surprisingly strong PhIIa ADHD data for CX717 and a bevy of advanced stage partnership discussions. A few weeks later, an ambiguous cellular finding in one monkey out of twelve caused CX717 to be placed on clinical hold by the FDA. The hold lasted about six months, but continued dosing limitations left a substantial cloud over CX717, Cortex's only clinical-stage compound. Other events during the year were eclipsed by these events: a DARPA-sponsored sleep deprivation Phase II failed, largely because DARPA's trial design included allowing subjects to nap.
More importantly, near year-end, Cortex took back its neurodegeneration rights from Servier, who had held them outside of North America. This will allow them to partner for Alzheimer's, Parkinson's, and other neurodegenerative disorders, on the basis of worldwide rights. The high-impact program is still a year away from the clinic, but preclinical testing with a prototype showed encouraging functional effects in models of Fragile X and Huntington's. By year-end, Cortex was near choosing a non-Ampakine program for inlicensing, with the worthy goal of diversifying to reduce risk, though the timing was suboptimal. Organon has still not released any of the data they have for Org24448 in schizophrenia, and it appears that they are very preoccupied with their post-Pfizer problems as they try to move towards spinning off from Akzo Nobel.
With this many key elements still unknown, projecting 2007 is more difficult for this company than for any other that we follow. Our best guess at this time is that the FDA will allow CX717 to resume ADHD testing at the necessary higher doses, which will then turn into a partnership encompassing CX717 and high-impacts, the former largely for ADHD (though Alzheimer's remains a target as well), the latter for Alzheimer's and Parkinson's. Cortex will finally be able to pick up where they left off last spring.

Schönen Tag noch
Erbse

[Erbse1]

Oh je Oh je, wie gehts nur weiter. Ich bin sehr ratlos. Cortex könnte nur ein Deal mit einem größerem Pharmapartner retten. Ich sehe eher schwarz. Im Augenblick leider nur noch ein Zockerwert.

Bin selber gespannt, wie es weiter geht.

Liebe Grüße
Erbse

Cortex Pharma to Sell Shares, Warrants
Wednesday January 17, 12:08 pm ET
Cortex Pharmaceuticals Shares Fall on Plan to Sell Warrants, Shares for $5.3 Million


IRVINE, Calif. (AP) -- Shares of Cortex Pharmaceuticals Inc. fell sharply after the drug developer said it will sell five million shares and warrants to buy about 3.3 million common shares for $5.6 million.


The warrants will have an exercise price of $1.66 per share and be exercisable at any time between the six-month anniversary of the deal's closing, which is expected to be Jan. 22, and the fifth anniversary.

Roth Capital Partners LLC acted as exclusive placement agent in the transaction. Cortex currently has about 35 million shares outstanding.

Cortex said it plans to use the proceeds to speed development of its Ampakine technology, licensing activities, working capital, capital expenditures and other general corporate purposes.

Cortex is focused on drug therapies for neurological and psychiatric disorders, and is developing a class of drugs called Ampakine compounds, which act to increase the strength of signals at connections between brain cells.

Shares fell 27 cents, or 20.3 percent, to $1.06 in midday trading on the American Stock Exchange.

[Erbse1]

Interessante E-Mail von Roger Stoll

An email from Dr. Stoll from today:

"David, The last thing you want to do is place the patents in the hands of a
bond holder or in someway leverage them as assets to cover some debt
financing. The risk of such an approach are clearly demonstrated by what
happened to DOV Pharmaceuticals. They are now banckrupt and the debtors
will shortly own all the assets. It was a huge disaster. If we had other
hard assets such as equipment and buildings, I would consider those, but we
do not. After Cortex struggled for 10 years without much success, we now
have a base of operation that can produce some success. We will soon be
making a submission to the FDA and hopefully get some relief for CX717.
Meanwhile our toxicology studies are underway for our backup compound CX701
and hopefully we will be able to materialize some interesting options for
clinical development through our licensing efforts. Additionally, we now are
approaching larger pharmaceutical companies to find a way to partner our
high impact program. We gave up on the bicifadine from DOV even though we
could have had it for development toward a neuropathic pain indication. You
will note that XLT obtained it. We could not rapidly enough secure the
financing for its development with an outside fund who was very interested
in supporting its clinical development, but needed a few more weeks to
finalize an agreement. DOV needed to get the deal done this past week. At
any rate, you would be amazed at how many ways we have looked at financing,
everything has it price, and there are no easy pathways. The best thing is
to move our internal programs as aggressively as we can and be alert to
other options which might enhance the profile of the business. Our
intellectual properties are the backbone of the business, and keeping that
intact is a priority. Roger

Roger G. Stoll, Ph.D
President Chairman and Chief Executive Officer
Cortex Pharmaceuticals, Inc
15231 Barranca Parkway
Irvine, CA 92618
949-727-3157 Ext 101"

[IchWeissDassIchNichtsWeiss]

wieder eine Antwort von Roger Stoll


John, We deliberately limited the financing to $5 - $6 million so that we did not have to use too much of our stock. We had to add some funds to be sure we had enough for a full year of activity, otherwise the auditors would have given us a “going concern” opinion which would be very unfavorable. So we added just enough funds to be sure that 2007 budget would not become an issue. We obviously feel that we should be able to improve the stock valuation over the coming year. If we do need to do another financing it would be later in the year and hopefully at a far better stock price. We have a significant number of events which I outlined in the recent meetings in NYC all of which can improve our position as a company; (a) submission of new toxicology data for CX717 to the FDA sometime at the end of February/early March, (b) bringing our backup compound CX701 through toxicology and into Phase I testing this year (c) having a possible in-license drug ready for Phase II development, and (d) establishing a research collaboration with big Pharma around the high impact compounds and getting our first high impact ready for clinical development by the end of this year. The research collaboration agreement should bring some money into the company, but it would not be a huge front-end payment since it is a preclinical deal and Cortex wants to retain some rights in the high impact arena. Obviously, if the FDA removes or alters the dosage limitation for CX717 sufficiently to allow us to pursue ADHD then not only should that provide a huge boost to our company and its stock, but also re-opens the door to a very significant licensing deal for that compound. Hope this helps. Roger

[Erbse1]

Nach langer langer Zeit nach der Ankündigung startet bald die Studie.

Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia

Purpose
The TURNS is a NIMH-funded contract for the evaluation of new compounds for the treatment of cognitive impairments in schizophrenia (HHSN 27820044 1003C; P.I.: Steve Marder, M.D.). Despite advances in the safety, tolerability, and effectiveness of antipsychotic medications for the treatment of schizophrenia, many patients continue to be plagued by impairments in social and work functioning. Persons with schizophrenia commonly show deficits in a number of areas of cognition that include impairments in attention, memory, and executive functioning (the ability and organize one’s behavior). Importantly, a large body of literature now shows a link between cognition and community functioning in schizophrenia. It is believed that treatments that improve cognitive deficits may lead to improvements in work and social functioning.

A promising approach to improve the community functioning of patients with schizophrenia is to develop new agents that treat the cognitive deficits of the illness. One type of pharmacological compound that has shown promise at improving cognition is a group of drugs called ampakines. These drugs are believed to improve the activity of a neurotransmitter system in the brain called the glutamate system. Increased activity of this system has been linked to improvements in cognitive functioning. The current study is an eight-week trial comparing two doses of the ampakine drug, Org 24448, that will be added to patients’ current atypical antipsychotic medication. One hundred thirty-five patients with schizophrenia, drawn from seven sites, will participate in the study. Cognition will be measured using a variety of paper-and-pencil and computerized measures from the consensus-derived NIMH-MATRICS cognitive battery. Psychiatric symptoms and the ability to perform community-based tasks of daily living will also be measured. Because previous trials with this drug and other similar drugs have detected lasting cognitive benefits, this trial will also repeat clinical assessments four weeks after completion of the study medication.

Schönen Tag noch
Erbse

[Erbse1]

Gestern war Konferenz. CX717 könnte doch noch klappen. Warten wirs ab. Schnell noch das Schaubild von der Konferenz.

Grüße
Erbse

[Erbse1]

Kommentar des NeuroInvestor

Online comment 2/22/07

Cortex was surprisingly definitive in their presentation at Roth Capital yesterday: the cellular 'signal' which has hamstrung the CX717 program since last April is a post-mortem artifact--it only occurs in tissue which is being prepared with a formalin-based fixative. If the same target tissue is instead frozen, the cellular signal is not seen, even when examined via electron microscope. Even the FDA will find it near-impossible to object to a resumption of full-dosage ADHD trials when the signal of concern only occurs after death. CEO Roger Stoll said quite bluntly--"I think we'll be able to get the dose limitation lifted by the FDA."

No hedging with anything like 'of course, the final decision will be up to the FDA...' Cortex will submit the full package to the FDA in mid-March, and we expect a 'go' decision from the FDA in May. It has been a long wait, but it appears that CX717, which has now been more thoroughly vetted than any other Phase II drug, is in fact safe, and will go back into ADHD, where the initial findings were so positive. It was also timely in that this occurred on the day that the FDA announced that all current ADHD drugs would have to include inserts detailing their safety risks. CX717 appears to have none of their side effect baggage. This will add to the program's lustre as a partnerhip candidate, in addition to the high-impact group, where a partnership is expected midyear. Cortex is now in a position to resume the upward trajectory that was so abruptly interrupted last April--which for those who lost track during the interim, had the share price over 5. We expect it back in--and perhaps above--that range during 2007.

[Erbse1]

Nochmal als Meldung von Cortex.

Update on Cortex's CEO Presentation at the Roth Capital Partners 19th Annual Conference
Friday February 23, 8:45 am ET


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR - News), presenting at the 19th Annual Roth Capital Partners Growth Stock Conference on Wednesday, February 21st, reported that it had generated data which indicated that the histopathological changes previously reported for its lead AMPAKINE® product candidate, CX717, occurred postmortem in the animal tissue. If similar tissue was rapidly removed from animals and placed in an appropriate buffered medium, the tissue showed no signs of any histopathological changes and was physiologically normal.
After earlier preclinical histopathological tissue results were reviewed by the FDA, the agency initiated a clinical hold for CX717 in March 2006. At the request of the FDA, Cortex conducted extensive additional animal toxicology studies during the summer of 2006 and in October 2006 the agency lifted the clinical hold, but placed significant dosage limitations on the use of CX717 in clinical trials. These limitations meant that Cortex could not proceed with further clinical assessments of CX717 in ADHD patients. CX717 had earlier demonstrated positive results in a pilot ADHD study in adult patients in a pilot Phase IIa study in March 2006. Cortex is planning to submit this new preclinical data to the FDA in March with a request to have the dosage limitations changed so that it can proceed to conduct further clinical trials of CX717 in adult ADHD patients. Dr. Stoll, the Chief Executive Officer of Cortex, cautioned that the final decision on the adequacy of the data to allow the Company to proceed clinically is up to the FDA.

Dr. Stoll also mentioned during his presentation that the FDA had just issued a notice that will require that all current manufacturers of ADHD drugs issue Patient Medication Guides that spell out the risks of the current medications with respect to cardiovascular and psychiatric adverse events observed with the currently approved therapies. Dr. Stoll noted that the potential for a new therapeutic approach to the treatment of ADHD is clear and, if clinically safe and effective, CX717 could meet many of the current market needs. Dr. Stoll reiterated that the 3-week study in adult ADHD patients randomized to either CX717 or placebo, in a cross-over design, was both clinically and statistically significant on both decreasing hyperactivity and increasing attention on the primary ADHD rating scale which is the primary measure by which all ADHD products are approved.

Another point made by Dr. Stoll during the presentation at the Roth Conference was that the most recent studies by Dr. Gary Lynch at UC Irvine using a high impact AMPAKINE drug, CX929, showed very encouraging results in transgenic mice with the Huntington's Disease gene. CX929 not only returned depressed levels of BDNF (brain derived neurotrophic factor) back to normal, restored long term potentiation and most recently showed significant improvements in behavioral effects in the transgenic mouse model.

The remaining topics covered by Dr. Stoll included an update on the low-impact AMPAKINE CX701 which Cortex anticipates commencing clinical trials by July 2007, the likelihood of a new research and development collaboration for its high-impact AMPAKINE compounds, and the in-licensing of a new Phase II non- AMPAKINE orphan drug.

[Erbse1]

Habe von der letzten Konferenz mal das Schaubild von der Pipeline kopiert.


Bin zwar ein großer Fan von Cortex und beobachte Cortex schon 6 Jahre, aber manchmal muß man sich fragen "Was haben die in der ganzen Zeit gemacht?" Da geht jede Menge Patentlaufzeit verloren.
Hoffen wir mal, daß jetzt nicht mehr alzu viele Probleme auftauchen und die FDA ihr ok für die Weiterentwicklung von CX717 gibt.

Die Patientenrekrutierung von ORG24448 bei Depression ist jetzt beendet worden.

"Org 24448 to Treat Depression

This study is no longer recruiting patients."

Quelle:http://www.clinicaltrials.gov/ct/show/NCT00113022?order=1

Schönes Wochenende noch
Erbse

[Erbse1]

Update vom NeuroInvestor
From NI March 07, posted 3/10/07

Cortex's CEO announced, with uncharacteristic confidence, that he believes that the evidence for CX717 will lead the FDA to lift dosing restrictions. The electron microscopy confirmed what the histopathological examination had indicated would be found in sections that were frozen--nothing at all. The cellular/structural anomaly is a post-mortem artifact, an interaction between high doses of CX717 and fixatives. This was presented on the day that the FDA ruled that all current ADHD drugs must include a pamphlet warning patients of their side effects. The irony should not be lost on the FDA, given that CX717 has shown no cardio or abuse risks thus far. The early data to us suggests that it will be better than Strattera, safer than stimulants. With Provigil having gone to the ADHD sidelines save for off-label use, CX717 could be the most promising ADHD medication in development. This will make Cortex rather popular, now that the spectre of dose limitation appears on its way out. Cortex still needs to file the data packet with the FDA, and the FDA will respond within 60 days, likely in mid-May. As irrational as the FDA can sometimes be, there is no reason to preclude CX717 from going into Phase IIb.

The share price responded healthily to the news, though some observers still want the official word from the FDA. The next few months will be extremely busy for Cortex: Besides the data submission, they have to file an IND with the Psychiatry diivision so that they can start ADHD trials again. They also have narrowed down the inlicensing choices to three, and could finalize something within the next month or two. Our preference would be that they hold off, our hope is that when they announce the licensing, it will become clear why they did not. Licensing talks regarding the hi-impact platform also continue, and an early 3Q deal could eventuate. But the big package would be for CX717, which we believe has more value right now for ADHD than anything else. The main question is how much else is rolled into that deal--from Alzheimer's to high-impacts. There is no CNS platform currently available that can match this one. It is also worth keeping an eye on Organon, given that they must make their case for a lofty IPO valuation, may have to say something about the Org24448 data in schizophrenia, and the enrollment-recently-concluded trial in depression. With 80-90% confidence that the FDA will do the right thing here, our target is 6.

Schönen Tag noch
Erbse

[Erbse1]

Partnerwechsel bei Cortex. Schering-Plough kauft die Pharma Sparte von Organon. Hoffen wir mal, daß die Ampakine unter Schering-Plough mehr Priorität genießen und in absehbarer Zeit entwickelt werden. Organon war eine Zumutung. Viele rechnen auch jetzt mit einer Übernahme von Cortex. Lassen wir uns mal überraschen.

Grüße
Erbse

[Erbse1]

Ausführungen von Cortex zu CX717 aus dem Quartalsbericht.

As reported earlier, the FDA released the clinical hold on CX717 in early October 2006, subject to specified dose limitations. Those limitations meant that Cortex could not proceed with further clinical development of CX717 as a treatment for ADHD. Cortex initiated three-month toxicology trials in rats and monkeys in order to obtain additional data. In February 2007, Cortex announced that the histopathological changes previously reported for CX717 occurred postmortem in the animal tissue. When similar tissue was rapidly removed from the animals and placed in an appropriate buffered medium, the tissue showed no signs of any histophathological changes and was physiologically normal. However, the same tissue subsequently exposed to the fixative solution rapidly began showing histopathological changes.

Cortex plans to submit the related results from these studies to the FDA in mid-March 2007 in order to request that the current dose range limitations on CX717 be raised to allow Cortex to initiate further clinical studies in ADHD. In early March 2007, Cortex submitted a letter to the FDA requesting a meeting to discuss the filing of an IND to conduct a Phase IIb study using CX717 and notified the agency that the data supporting this discussion will be filed by the end of March. The decision regarding the adequacy of the data to allow Cortex to proceed will be made by the FDA.

Schönen Tag noch
Erbse

[Erbse1]

Cortex's AMPAKINE CX717 Toxicology Data Package Submitted to FDA
Wednesday April 18, 8:31 am ET
Data Demonstrates that Specific Histopathological Changes Found in Animal Toxicology Studies Occurred Postmortem


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR - News), sent two large data packages to the Food & Drug Administration (FDA) today regarding the Company's lead Phase II AMPAKINE® product candidate, CX717. One data set went to the FDA's Division of Neurology Drug Products and the other went to the Division of Psychiatry Products. The original CX717 Investigational New Drug (IND) was filed with Neuropharmacological Division (now Neurology Division) for the treatment of Alzheimer's disease (AD) and the other data package went to the Psychiatry Division, where the Company intends to file a second CX717 IND for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The submitted data package provides clear evidence that the specific histopathological changes seen in animal toxicology studies, which previously caused the FDA to put CX717 on clinical hold, is a postmortem fixation artifact and is not found in the tissue of the animal when it is still living.

Dr. Roger Stoll, Chief Executive Officer of Cortex, stated, "When CX717 was removed from clinical hold on October 6, 2006 by the Neurology Division a dose was permitted for continuing a study in patients with AD, but that dose was too low to permit the assessment of the drug in patients with ADHD. Further information was needed to better understand the cause of the histopathological changes." Dr. Stoll added that, "We now have a substantial data base which clearly documents the fact that the histological changes of concern occur postmortem when the fixative solution is used to prepare the slides of the tissue specimens."

In early March 2006 Cortex reported in a small pilot Phase II study, that CX717 had demonstrated positive clinical and statistical results on the primary endpoint, the ADHD rating scale and the sub-scales related to attention and hyperactivity which are used for the approval of all currently available ADHD treatments. Consistent with all previous studies involving over 220 patients and healthy adults, this study demonstrated that CX717 was safe, well tolerated, and produced no increase in heart rate, blood pressure or other cardiovascular side effects. Cortex intends to cooperate fully with the FDA and the Company must now wait to hear from the agency regarding their willingness to approve higher dose levels for studying CX717 in adults with ADHD, and the Company's subsequent desire to proceed with a larger Phase IIb study for this indication.

[Erbse1]

Hallo Cortex Interessierte. Cortex CEO Roger Stoll beantwortete eine E-mail zum weiteren Ablauf bei der FDA.

Schönen Tag noch
Erbse

John, By regulation the FDA has 60 days to respond to our filing and set a meeting date. However, they do not have to agree to a meeting and may choose to simply answer the questions which we raised regarding the filing of an IND with the Psychiatric Division. If we can not get satisfactory responses, then a meeting would most likely occur. However, my optimistic sense is that they will generally concur with our suggestions and if such agreement is reached during the 60 day period, we may be requested to file the IND immediately. We are pretty much prepared to do so, but realistically we are all so busy with several other projects that we may need about 45 days to get a full IND filing into the FDA. That could occur before the 60 days are up or if other issues are raised some time beyond the 60 days. In the end, we will probably have a pretty good idea of the timeframe for proceeding with CX717 within the 60 period. So far the FDA has been reasonable and I do not anticipate any unusual problems at this point. Roger

[Erbse1]

Cortex and the University of Alberta Complete Patent License Agreement
Thursday May 10, 8:30 am ET
-- Rights Could Broaden the Use of AMPAKINE(R) Compounds to prevent Opiate- and Barbiturate-Induced Respiratory Depression --


IRVINE, Calif. and EDMONTON, AB--(BUSINESS WIRE)--The Board of Directors of Cortex Pharmaceuticals, Inc. (AMEX:COR - News) and TEC Edmonton on behalf of The Governors of the University of Alberta jointly announced that they have entered into an exclusive Patent License Agreement that could broaden the use of Cortex's AMPAKINE® technology to prevent and treat opiate- and barbiturate-induced respiratory depression. University of Alberta Professor Dr. John J. Greer has demonstrated in both in vitro and in vivo animal models that selected AMPAKINE compounds can enhance respiratory drive and breathing rhythm at the level of the brainstem. While it has been reported that only 0.5%-1.2% of total adverse drug events caused by prescription medications are respiratory in nature, these account for 25%-30% of drug-induced deaths. Opiates and barbiturates are the primary drugs classes responsible for these effects. These events usually occur during the dose adjustment period or when different central nervous depressants are taken together without checking with a pharmacist or physician.

"This filed patent application by Dr. Greer describes a method by which an AMPAKINE compound can reverse the respiratory depression associated with classes of commonly prescribed opiate analgesics, such as codeine, oxycodone, fentanyl, morphine, methadone, pentazocine, butorphanol, buprenorphine, and sedative drugs called barbiturates such as, phenobarbital. Dr Greer has demonstrated that the respiratory depression induced by these agents can be reversed or prevented with an AMPAKINE, without a reduction of pain relief or sedation," explained Roger G. Stoll, Ph.D., Cortex's Chairman, President and Chief Executive Officer. "This opens up the real possibility of combining an AMPAKINE compound with the commonly prescribed barbiturates or opiates to reduce the mortality caused by these adverse reactions."

Dr. Greer added: "Clinicians are currently concerned that the only means of countering opiate induced respiratory depression is to give an opiate receptor antagonist. This can lead to considerable problems managing pain. AMPAKINE compounds may allow for more effective use of opiate analgesics."

Under the terms of the Agreement, the University will receive an undisclosed upfront payment, milestones, and royalties, and Dr. Greer will get multiple years of support to expand this research.

About Dr. Greer, The University of Alberta and TEC Edmonton

Dr. John J. Greer is a Professor in the Department of Physiology, Faculty of Medicine & Dentistry, at the University of Alberta and Scientist of the Alberta Heritage Foundation for Medical Research. He is affiliated with the University's Centre for Neuroscience, the Perinatal Research Centre and the Women and Children's Health Research Institute. His research is directed toward providing fundamental insights into the development of the neuromuscular control of respiration. Dr. Greer's study of the effects of AMPAKINE compounds on respiration was published in the Dec. 15, 2006 issue of the American Journal of Respiratory and Critical Care Medicine.

Since 1908, the University of Alberta has remained committed to the pursuit of new knowledge and its dissemination to the world. As one of Canada's top research-intensive universities, it received over $420 million in externally funded research in 2006-07. The University is the largest research institution in the province of Alberta with nearly 13,000 academic and support staff and over 36,000 students at its campus located in the provincial capital, Edmonton. Its international reputation grows with many leading-edge achievements, including the "Edmonton Protocol" treatment for Type 1 diabetes, the pioneering work of the National Institute for Nanotechnology and the world's first antiviral treatment for hepatitis B.

TEC Edmonton acts as the technology transfer office for the University of Alberta. A joint venture created in 2004 by the University of Alberta and Edmonton Economic Development Corporation, TEC Edmonton is committed to providing investors with access to high-growth, advanced-technology opportunities in the form of new inventions, innovations or early stage ventures created in the Edmonton region.

Schönen Tag noch
Erbse

[Erbse1]

Neuer Kommentar des NeuroInvestor zur Jahreshauptversammlung und zur Übernahme von Organon.

On-line comment, 5/10/07
The very old Saturday Night Live skit (back when SNL was funny) 'Short Attention Span Theatre' came to mind as Cortex's recent price recovery sold off somewhat in the wake of a webcast presentation that had not one iota of bad news--but no immediate gratification either. The nearterm value drivers--FDA lifting of the CX717 dosing limits; corporate partnerships for CX717 and/or the neurotrophic 'hi-impact' portfolio could not be pulled out of a hat on cue. While momentum players quickly exited in their search for immediate reinforcement, all of these event will occur--the first, within the next six weeks, the other two before year-end--and NI's ongoing description of Cortex as being the single best partnering/acquisition target in the CNS space will look more prescient than it does at the moment. Cortex is doing its homework: expanding its range of molecules under development, demonstrating Ampakine value in such untreated but devastating disorders as Huntington's (where Amarin recently saw Miraxion fail in Phase III) and Rett's. They have also shown Ampakine value in restoring respiratory function in opiate overdose and Rett's--adding yet another potential use to the broad list already in place. NI's target for Cortex during 2007 has been maintained at 6. Though it would be superfluous to alter it at the moment, we expect that before the end of the year, that will look conservative.


On-line comment, 3/12/07
What does Schering-Plough's surprising--and seemingly exorbitant--acquisition of Organon mean for Cortex? That's not yet clear, but all the possibilities are favorable for Cortex, there is no cloud to accompany this silver lining.

1) Fred Hassan buying Organon from Akzo Nobel is like the hare making a purchase from the tortoise--watching Organon develop Org24448/CX717 has been like watching paint dry, an activity with which Akzo Nobel is well accustomed. No matter what Hassan does, he'll do it fast, not just faster than Organon, but more quickly than any other Big Pharma CEO would.

2) Is Schering-Plough really moving back into CNS? Given their complete lack of a CNS program, acquiring Organon's science/lab capabilities (which are not subpar) as well as some pipeline components, this would be an interesting first step. Asenapine is not the answer to anything, other than to analysts worried about SP meeting its quarterly earnings estimates in 2010...

3) Anytime someone pays $14.4 billion for anything (he could have had AstonMartin for under a billion), people are going to closely examine what was obtained with the money. This is going to get an unprecedented level of attention cast upon the Cortex/Organon partnership, and the Ampakine programs in schizophrenia and attention. This is an unmitigated boon for Cortex.

4) Schering-Plough could conceivably decide to not move into CNS, in which case the rights to sz and depression could conceivably be offered back to Cortex for future milestones/royalties, etc.

5) But if Fred Hassan is as smart as everyone says he is, he could round up his costs to an even $15 billion just by buying Cortex for $600 million. He would then have the best Ampakine program in the world, all indications, all territories, all the IP control. That would be as quick a way to get Schering-Plough into the CNS 'game' as there is. We are not predicting this..yet. But as the dust settles and SP looks at what it now has, this is an obvious step for consideration. SP could have Phase IIb going for the best next candidate for ADHD, and Phase III for what may be the next great generation of schizophrenia drugs. And that's before you even start talking neurodegeneration and the high impacts....Lilly has to be watching and wondering..the same with Merck, where Lilly's former neuro/Ampa chief is now running neuroscience.

This could get very interesting.

Schönen Tag noch
Erbse

[Erbse1]

Zur Information noch die Dia Bilder mit der Zusammenfassung vom Shareholder Meeting 2007.





Schönen Tag noch
Erbse

[Erbse1]

UC Irvine Researchers Reveal First Images Of Brain Changes Associated With Memory
5/16/2007


Source: University of California - Irvine
http://news.biocompare.com/newsstory.asp?id=183085

University of California, Irvine researchers have developed the first images of the physical changes in brain cells thought to underlie memory, a discovery that is already uncovering clues about memory loss linked to cognitive disorders.

Three decades of work by neuroscientists have established that a physiological effect known as long-term potentiation (LTP) encodes everyday forms of memory. In the Journal of Neuroscience today, a UC Irvine research team led by neuroscientists Christine M. Gall and Gary Lynch presents these unique images, which show that the size and shape of synapses were changed by LTP.

“The way is now open to mapping where in the brain memories are laid down,” said Lynch, a professor of psychiatry and human behavior. “Seeing memory-related physical changes to synapses means that we can at last use mouse models to test if the effects of retardation, aging and various cognitive disorders involve a specific, long-suspected defect in the connections between cortical neurons.”

Brain tissue collected from rats and mice was kept alive in specially constructed equipment. The researchers induced LTP by stimulating synapses with a rhythm known to be critical to memory formation. The brain slices were then sectioned and stained with one antibody that attaches to activated proteins involved with LTP and a second one that labels synapses. Newly developed microscopic methods were used to visualize and measure synapses that had both antibodies attached.

In addition to revealing new information about the formation of memory in the brain, this study and another published last month in the Journal of Neuroscience by the UC Irvine researchers have shown how LTP deficiencies accompany the memory loss seen during the early stages of Huntington’s disease, an incurable neurodegenerative disease characterized by disturbances to memory and learning.

Lynch, Gall and colleagues found that LTP structures encoding memory are defective in mouse models of Huntington’s disease. They discovered that these synaptic defects can be fully reversed through treatment with a brain growth factor released at synapses. Ampakines, a new class of drugs developed by Lynch at UC Irvine that are currently in clinical development for Alzheimer’s disease and ADHD, increase the levels of this growth factor and potentially emerge as therapy for the cognitive problems associated with Huntington’s.

The researchers are now working to see if such LTP defects are present in mouse models of common forms of human mental retardation.

Gall is a professor of anatomy and neurobiology. Lulu Y. Chen, Christopher S. Rex, Malcolm S. Casale and Danielle Simmons also participated in the studies, which were funded by the National Institutes of Health

[Erbse1]

Kommentar des NeuroInvestor zu Org24448

On-line comment, 5/23/07

Org24448--the Cortex (CX691) compound Organon has spent six or seven years developing in slow motion, has been pulled from its spot in the TURNS schizophrenia trial due to "seizures." We have been unable to obtain confirmation from Cortex, TURNS, or Jeffrey Lieberman, who stated this during a presentation at the American Psychiatric Association meeting. But we are going to go on the assumption that this is true. It would explain the sudden termination of the planned depression trials, and the fact that the TURNS trial never started to enroll. It is NI's working assumption that this must indicate a patient (s) with seizure activity sometime late in the schizophrenia monotherapy trial--or early in the planned polypharmacy trial in sz. Otherwise, Org24448 would never have been submitted for, and accepted by, TURNS.

What are the ramifications for Cortex?

1) This will revive some of the concerns that have dogged AMPA modulator programs throughout the past decade, and led to several Lilly programs demising. Due diligence by prospective partners would have involved a look at all animal and human data pertinent to epileptogenesis anyways. Obtaining information about this from Organon, during the Schering-Plough betrothal, will probably be slightly more difficult than achieving peace in the Middle East.

2) It does not necessarily say anything about CX717--which has not shown any epileptogenic risk in its tox vetting or in human trials. The tox issue--now shown to be an artifact--that had led to the dosing restrictions on CX717 would almost certainly not be related. This should not alter the anticipated lifting of the FDA restrictions, but it is not going to accelerate their processing of that huge data dossier.

3) It cuts both ways in terms of the Cortex 'portfolio.' It was nice to have a partnered molecule on the board as being in Phase II. But Organon was completely inadequate as a partner. If Org24448 is dead (and that is not definite, it could have been a single case without demonstrated causality), Schering-Plough will not start a program from scratch. This would leave the schizophrenia/depression rights up for sale, rights Cortex would love to reacquire, in order to package all rights to a partner. That is the silver lining to this development, though we expect that in the short run, this is going to amp up the anxiety regarding the FDA.

[Erbse1]

Antwort auf Beitrag Nr.: 29.440.744 von Erbse1 am 23.05.07 19:22:12

Ergänzung zum Kommentar vom NeuroInvestor

NI had posted a statement from Columbia's Jeffrey Lieberman that Org24448 was pulled from TURNS due to 'seizures.' We have now learned from a very credible source that this is not correct. No seizures have been reported with Org24448 (they would not have been expected with a low-impact). It was a false alarm from a high-profile expert in schizophrenia.

Machts mal gut
Erbse

[Erbse1]

In den nächsten Tagen steht die Entscheidung der FDA zu CX717 an. Da könnte es noch mal heftige Kursbewegungen geben. Ein positiver Entscheid könnte für Cortex vieles einfacher machen.

Weiterhin wird an neuen Anwendungsgebieten für die Ampakine gearbeitet. Alles allerdings noch in einem sehr frühen Stadium, doch für Langfristanleger durchaus interessant.

Schönen Tag noch
Erbse

AMPAKINE Compounds A New Potential Treatment For Respiratory Depression

Drug-induced respiratory depression is a life-threatening condition caused by analgesic, hypnotic, and anesthesia medications. Although it is a leading cause of death from the overdose of some classes of abused drugs, respiratory depression also arises during normal, physician-supervised procedures such as surgical anesthesia, post-operative analgesia, and as a result of normal out-patient management of pain from cancer, accidents, or illnesses.

The majority of adverse events occurring with these drugs take place during the dose adjustment period, when two or more central nervous depressants are taken together, or when patients take prescribed drugs in ways not intended by their physician.

Although only 0.5%-1.2% of total adverse drug events caused by prescription medications are respiratory in nature, these serious side effects account for 25%-30% of drug-induced deaths. Opiates and barbiturates are the primary drugs classes responsible for these effects. Opiates include the standard pain-killing drugs morphine, fentanyl, and codeine, as well as related products vicodin, hydrocodone, and oxycontin. Barbituates comprise the sedative drugs amobarbital, aprobarbital, butabarbital, pentobarbital, and others. Sleeping disorders are another common predisposing factor for respiratory depression, in this case known as sleep apnea.

Currently, the only way to counter opiate-induced respiratory depression is to administer opiate receptor antagonists, drugs that block the effectiveness of opiate analgesia. While this approach may prevent a serious side effect or even death, it dramatically reduces the effectiveness of drugs administered for management of severe pain.

Researchers at the University of Alberta (Edmonton, AB) and Cortex Pharmaceuticals (Irvine, CA) believe that AMPAKINE drugs may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

The drug tested in this study belongs to a novel class of molecules known as AMPAKINE compounds being developed by Cortex Pharmaceuticals, Inc. located in Irvine, California. AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA "Glutamate type receptor," which has been shown in rodent models to boost the brain's own protein for improving age-related deficits in memory mechanisms. In primate models AMPAKINE compounds have replicated the studies in rodents and in adults patients suffering from Attention Deficit Hyperactivity Disorder, significant clinical and statistical improvement in increase attention and decrease hyperactivity have been observed. The U. Alberta research provide evidence that another important AMPAKINE indication is to stimulate primitive areas of the brain called the pre-Botzinger Complex responsible for breathing, without causing side effects. The pre-Botzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties that have been identified in this brain region.

In a study published in 2006, Dr. John J. Greer of U. Alberta demonstrated that certain AMPAKINE compounds enhance the respiratory drive and breathing rhythm at the brain-stem level containing the pre-Botzinger Complex in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants.

Dr. Greer found that respiratory depression induced by these agents can be reversed or prevented in test animals with an experimental AMPAKINE drug, without a reduction of pain relief or sedation.

Greer and coworkers treated rats with the opioids analgesic fentanyl or the barbiturate sedative Phenobarbital, both commonly prescribed in the United States. Greer used a technique known as plethysmography, which measures blood flow throughout the body, to determine the level of respiratory distressed caused by the drugs. When drugged rats were treated with the AMPAKINE , the respiratory distress quickly resolved. The drug worked in both newborn and adult rats. Interestingly, the drug on its own did not affect blood flow in animals not treated with the sedative drugs, nor did administration of the drug cause noticeable arousal in the animals.

Greer concluded, in a study published in the September 20, 2006 issue of the American Journal of Respiratory Critical Care Medicine, that CX546, "effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response."

"These results open up the real possibility of combining an ampakine compound with commonly prescribed barbiturates or opiates to reduce the likelihood that life-threatening respiratory depression will occur," noted explained Roger G. Stoll, Ph.D., Chairman, President, and CEO of Cortex.

Cortex Pharmaceuticals has entered into a Patent Licensing Agreement with the University of Alberta for this new respiratory application for the use of AMPAKINE compounds. Under terms of the license Cortex will evaluate a number of novel low and high impact AMPAKINE compounds for a range of new respiratory applications, such as, respiratory depression induced by opiates and barbiturates to start and others to be named at a future time. In return, Cortex will provide the University with an undisclosed upfront payment, milestone compensation, and royalties from the commercialization of specific AMPAKINE drugs approved for any therapeutic and/or prophylactic indication associated with respiratory depression . Dr. Greer, who has successfully filed a patent for the use of AMPAKINE drugs for these respiratory indications, will receive multiple years of research support funding from Cortex.

Cortex focuses on novel drug therapies for neurological and psychiatric disorders. Its lead compounds belong to two classes of ampakines, which act on the brain's AMPA receptor. Approximately 85% of neurons that handle brain electrical activity do so through this receptor, which controls traffic of the neurotransmitter glutamate. Ampakine molecules bind to the AMPA receptor, causing its glutamate channel to remain open for a longer time period, thereby allowing more glutamate to enter the cell. As a result, ampakines cause amplification of signals at connections between brain cells.

The loss of these connections may be, in part, responsible for memory and behavior problems in Alzheimer's disease, neurological disorders, and even aging. Research data suggests that ampakine molecules may improve neurotransmitter deficiencies implicated in schizophrenia, Huntington's disease, fragile X syndrome, and Rhett's syndrome.

Cortex is developing two classes of AMPAKINE drugs: Low and High impact compounds. , CX717 is an example of a Low impact AMPAKINE drugs, which is currently in human clinical trials, and high-impact molecules which are currently in lead optimization and are currently being tested in transgenic animal models for a variety of neurodegenerative diseases . The two classes of AMPAKINE drugs operate at different binding sites on the AMPA-type glutamate receptor.

Cortex has partnered with several leading pharmaceutical companies for specific therapeutic applications of ampakines. The company has an alliance with Organon Biosciences (soon to be part of Schering-Plough) for AMPAKINE -based treatment of schizophrenia and depression, and with Les Laboratoires Servier.

The study of AMPAKINE drugs in respiratory depression opens a new chapter in the development of this class of therapeutics, and a potentially significant breakthrough in how medication for pain, analgesia, and sedation are used. "Ampakines may allow for improved safety and a more effective use of opiate analgesics and barbiturate sedatives," Dr. Stoll of Cortex observes, "two important classes of central nervous system drugs."

###

Contact: Mark Varney
Cortex Pharmaceuticals

Quelle: http://www.medicalnewstoday.com/medicalnews.php?newsid=73066

[bernie55]

ALLGEMEINE INFOS zur Zulassung neuer Arzneien


22.06.2007 - 09:28 Uhr

FTD: Das kann ja heiter werden

Die Zulassung neuer Arzneien ist für die Pharmabranche längst keine Kleinigkeit mehr. Regelmäßig lassen die Behörden Hoffnungsträger durchfallen und Börsenträume platzen. Künftig kommt es noch dicker.


Sanofi-Aventis ist fassungslos über die Ablehnung seiner Diätpille Acomplia bei der US-Behörde FDA. Begründung: psychische Nebenwirkungen.

GlaxoSmithKline fürchtet das Aus für das umsatzstarke Diabetesmittel Avandia. Risiko: Herzinfarkt.

Das neue Krebsmittel Vectibix vom weltgrößten Biotechkonzern Amgen findet nicht den Zuspruch der Kontrolleure bei der EU-Behörde Emea. Erklärung: Wirksamkeit zweifelhaft.

Drei Beispiele aus der jüngsten Vergangenheit - eine gemeinsame Wirkung: Aufruhr an der Börse. Die Aktienkurse der betreffenden Konzerne sackten nacheinander auf ein Zweijahrestief. Allen Beteiligten, den Managern, Analysten und Kontrolleuren steckt noch der Skandal um das Schmerzmittel Vioxx in den Knochen. Die Folge für den Hersteller Merck & Co. sowie die Branche waren Tausende Schadensersatzklagen, Imagekrisen und Milliardenverluste. Das mahnte zur Vorsicht. Im Jahr drei nach Vioxx zieht die Politik auf beiden Seiten des Atlantiks die Zügel nun noch fester an.

So feilten am Donnerstag in Washington US-Senatoren an letzten Details für ein Gesetz, das der FDA mehr Einfluss und Geld für zusätzliche Sicherheitskontrollen von Medikamenten gibt. Dazu zahlt die Industrie an die FDA Gebühren von rund 400 Mio. $ jährlich, weitere 225 Mio. $ bringt sie in den kommenden fünf Jahren für die FDA-Observierung von Neueinführungen auf. "Die Nation hat aus den Sicherheitsproblemen mit dem Diabetesmedikament Avandia gelernt", sagte der Vorsitzende des Kongressausschusses, John Dingell, vor wenigen Tagen. Zudem können Verstöße gegen Marketing- und Sicherheitsauflagen mit bis zu 100 Mio. $
Strafe geahndet werden.

Und auch die Emea kann nun härter durchgreifen. Die EU-Kommission hat am 15. Juni eine Verordnung in Kraft gesetzt die Verstöße gegen Emea-Regeln mit hohen Geldbußen ahndet - etwa, wenn Firmen Vorgaben ihrer Arzneimittelzulassungen nicht einhalten, Informationen zur Risikobewertung ihrer Produkte zurückhalten oder deren Nebenwirkungen gar nicht oder erst sehr spät melden.

"Sehr harte Sanktionen"

Die Höchstgrenze der Geldbußen liegt bei fünf Prozent des Jahresumsatzes des betroffenen Zulassungsinhabers. Zulassungsinhaber kann auch eine Konzerntochter sein. "Das dürfte zu ungerechten Bestrafungen führen", sagte Unternehmensanwalt Uwe Fröhlich vom Pharmakonzern Baxter. "Zufälligerweise oder sogar absichtlich kann ein besonders umsatzstarker oder umsatzschwacher Teil eines Konzerns Inhaber der Zulassung sein. Ein Schlupfloch könnten auch Vermarktungspartnerschaften unabhängiger Unternehmen bieten, von denen nur eines die Zulassung hält." Gerechter sei es, die Buße am EU-weiten Umsatz der Arznei festzumachen. "Das sind alles in allem sehr harte Sanktionen", sagt Anwalt Jörg Schickert von der Kanzlei Lovells in München. Er findet manches an der Verordnung unausgereift. "Es gibt noch Schwachstellen, darunter die Frage, wie die Abgrenzung zwischen einzelstaatlichen Strafmaßnahmen und EU-weiten Sanktionen geregelt werden soll."

Das für Zulassungen zuständige Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) habe in der jüngeren Vergangenheit einige Straf- und Bußgeldverfahren eingeleitet, mit unterschiedlichem Ausgang entsprechend der Beweislage, heißt es auf Anfrage. "Ob es in Zukunft wichtiger sein wird, derartige Instrumentarien zur Verfügung zu haben, lässt sich nur schwer einschätzen", so das BfArM. Die im Arzneimittelgesetz für Ordnungswidrigkeiten vorgesehenen Bußgelder von maximal 25.000 Euro seien vergleichsweise gering.

Die Verordnung (EG) 658/2007 zur Auferlegung von Geldbußen durch die Kommission ist ein neuartiges Sanktionsmittel, das es für von der Emea zugelassene Arzneimittel bislang noch nicht gab. "Die Industrie sollte schnellstmöglich alle Schwachstellen abklopfen und Verfahren aufsetzen, die zukünftig Verstöße vermeiden. Dies sollte auch dokumentiert werden", sagte der Anwalt Schickert.

Emea-Chef Thomas Lönngren zumindest will nie mehr einen Tag wie den 30. September 2004 erleben: Weder der Vioxx-Hersteller Merck & Co. noch die FDA-Kollegen hatten ihn frühzeitig über den geplanten Rückruf der Schmerzpille informiert. Die Börse wusste früher Bescheid als er. "Wir wollen von Konzernen so schnell wie möglich informiert werden", sagte er.



Autor/Autoren: Peter Kuchenbuch

http://www.finanztreff.de/ftreff/news.htm?sektion=topthemen&…

[Ackergaul]

Über ein Jahr ist CX717 schon auf HOLD und nun scheint sich wieder etwas zu bewegen - oder? 1 Jahr hat alleine Cortex benötigt die von der FDA geforderten Daten zu erstellen ud einzureichen. Die auffälligen Gewebestücke, die die FDA dazu bewegt haben den Trial anzuhalten, sind laut Cortex Berichten (April 07) erst NACH dem Tod der Tiere entstanden. Bestätigt die FDA dies, wird der Trial (und gleichzeitig die höhere Dosis - CX701) wieder freigegeben. Falls dies eintritt würde Cortex wieder sonnigeren Zeiten entgegen sehen und eine mögliche Partnerschaft scheint greifbar. Das andere "Falls" lasse ich mal lieber unter den Tisch fallen.
Der zweite Hoffnungsträger Org24448 hängt auch noch in der Phase II fest. Beim "Depression" Trial sind gerade alle Patienten eingeschrieben, der "Schizophrenie" Trial ist kurz davor "geöffnet" zu werden. Hoffnung liegt darin dass Schering-Plough nach der Übernahme von Organon auch mal ein wenig Tempo macht. Dies ist mein großer Kritikpunkt an Cortex: ZEIT. Unfassbar, dass ganze dauert und dauert, aber Fortschritte sind kaum zusehen. Das Cash reicht wohl noch bis etwa 2Q 2008, aber viel Forschungsarbeit ist mit den Mitteln nicht zu machen. Nichts desto trotz, ist zwar so oder so noch ein langer Weg bis in die (möglichen) schwarzen Zahlen, könnte aber ein sehr lohnender werden.

Ein älterer Bericht, beschreibt den Markt und die Möglichkeiten gut. Bedenkt man wie vielfältig das Einsatzgebiet der Ampakine ist, kann man verstehen weswegen Erbse hier so lange festgehalten hat...

http://www.adhs-schweiz.ch/ADHS_6d.htm
Kopf hoch, Leute
DIE WELTWOCHE Ausgabe 28/06

Müde werden wach, Dumpfe hell, Kluge kommen länger auf Ideen – und die beste Nachricht: mit Pillen, die erträgliche Nebenwirkungen haben.

Felix Hasler hat das Upgrade fürs Hirn getestet und ist überzeugt: Diese Drogen werden unser täglich Brot.

Heute hab ich was genommen. Ich bin hellwach, bester Laune und kann es kaum erwarten loszulegen. Hoch motiviert und zum Äussersten entschlossen, setze ich mich an den Computer, schreibe drauflos und stelle freudig fest: weit und breit keine Spur von Schreibstau.

Stimmt, so was ist nicht normal. Ursache meines ungewohnten Arbeitseifers sind zwei kleine Tabletten, die ich heute mit dem Frühstückskaffee heruntergespült habe. «Modafinil» steht auf der Packung. Eigentlich wurde das Medikament für Narkolepsie-Patienten entwickelt, für Menschen also, die auch am helllichten Tag plötzlich einnicken. Doch der Wachmacher wirkt auch bei Gesunden, sofort verfliegt jedes Bedürfnis nach Schlaf. Ich bin aufmerksamer, motivierter, effizienter – einfach besser als normal.

Medikamente für Gesunde, Doping fürs normale Hirn: Für die Pharmaindustrie eröffnet sich ein Milliardenmarkt, den sie bisher vernachlässigt hat. Mit dem gesunden Menschen lässt sich mindestens so viel Geld machen wie mit dem kranken. Smart drugs und brain boosters sollen unsere Leistung steigern und die Laune bessern, uns konzentrierter, wacher, schlauer machen.

Das neue Angebot an mentalen Kosmetika muss sich seine Nachfrage nicht lange suchen. Überfordert vom hoch getakteten Arbeitsalltag und überrollt von einer kaum mehr zu bewältigenden Informationsflut, sehnt sich das ermüdete Hirn nach dem Beistand pharmakologischer Helfer. Gar eine psychopharmakologische Revolution sieht das britische Office of Science and Technology auf uns zukommen. Die renommierte Denkfabrik, die auf wissenschaftlicher Grundlage gesellschaftsrelevante Entwicklungen abschätzt, hat sich unlängst im Auftrag der britischen Regierung mit der Zukunft der Hirnmedikamente beschäftigt. Sir David King, Projektleiter der Studie, wagt im Schlussbericht eine unbritisch verwegene Prophezeiung: «Wir stehen unmittelbar vor Entwicklungen, welche uns möglicherweise in eine Welt führen, in der wir Drogen nehmen, die uns helfen, zu lernen, schneller zu denken, zu entspannen, wirksamer zu schlafen oder sogar unsere Stimmung der unserer Freunde anzupassen.»

Mutter Natur hat uns betrogen

Tatsächlich hat diese Zukunft längst begonnen. Nach einer Studie, die das Fachmagazin Addiction veröffentlichte, haben an amerikanischen Colleges bereits sieben Prozent der Studenten zu verschreibungspflichtigen Stimulanzien wie Ritalin gegriffen, um ihre Leistung zu steigern. An einem College putschte sich gar ein Viertel der Studenten mit amphetaminartigen Substanzen für die Prüfung auf. Denn diese Tabletten machen nicht nur zappelige Kinder ruhiger und aufmerksamer, sie helfen auch den ganz normalen Studenten, sich besser zu konzentrieren.

An die Dopingmittel fürs Hirn heranzukommen, ist nicht schwer: Studenten mit echter Hyperaktivität geben gegen Bares gern etwas von ihrer Ritalin-Ration ab. Naheliegend darum die Frage, wie denn Schulen und Universitäten mit der steigenden Beliebtheit des pharmakologischen Hirn-Tunings umgehen sollen. Verbieten und Dopingkontrollen einführen, Pinkeltests vor der Prüfung? In den USA fordern das bereits einige Experten. Oder sollte man minderbegabte Schüler sogar gezielt mit den smart drugs fördern? Tatsächlich wurde schon vorgeschlagen, dass professionelle «Neuroedukatoren» auf «sensible und ethische Weise die Einführung der neurowissenschaftlichen Fortschritte ins Unterrichtswesen lenken».

Auch der prominente Neurowissenschaftler Michael Gazzaniga, Autor des Buchs «The Ethical Brain», mag im gezielten Einsatz von Pharmaka für den Leistungskick auf der Schulbank keine Unlauterkeit erkennen. Ganz im Gegenteil: «Auf eine gewisse Art wurden wir von Mutter Natur betrogen, wenn wir kein überlegenes Denkorgan mitbekommen haben. Mit unserer eigenen Erfindungsgabe zurückzumogeln, scheint eine gescheite Sache zu sein. Meiner Meinung nach ist das genau das, was wir tun sollten.»

Alles super, aber

Die Pharmaindustrie hat das Potenzial erkannt. Mit Hochdruck entwickelt sie alltags-taugliche Psychopharmaka zur Steigerung der Hirnleistung. Modafinil ist ein Ergebnis dieser Forschungen. Die Muntermacher sind seit mehreren Jahren ein internationaler Verkaufsrenner, und seit meinem heutigen Selbstversuch mit 200 Milligramm Modasomil – so der Markenname in der Schweiz – ist mir auch völlig klar, warum.

Die unscheinbaren Tabletten machen genau das, was man von ihnen erwartet: wach. Zudem fördern sie die Konzentration und liefern den notorisch fehlenden Motivationsschub. Erstaunlicherweise fühlt sich das durchaus natürlich an – etwa so, wie wenn man einen dieser seltenen richtig guten Tage erwischt hat. Keine Spur von der unangenehmen Getriebenheit und hektischen Unruhe, die Amphetamine mit sich bringen, oder dem nervösen Gezittere nach ein paar Tassen Kaffee zu viel. Modafinil führt noch nicht einmal zu nennenswerten Appetit- oder Einschlafproblemen. Soweit man bisher weiss, macht das Mittel nicht süchtig und führt nicht zu einer Toleranzbildung, die einen zur Einnahme immer höherer Dosen zwingt.

Kaum Nebenwirkungen also – das sei etwas qualitativ ganz Neues, sagt die Pharmakologin Barbara Sahakian von der University of Cambridge. Seit Jahren untersucht sie die neuropsychologische Wirkung von Leistungssteigerern fürs Hirn: «Bis vor kurzem hatten psychotrope Medikamente signifikante Risiken und waren deshalb nur attraktiv, wenn der Nutzen für den Patienten noch grösser als die Risiken eingeschätzt wurde.» Jetzt allerdings werde es möglich, die Kognition mit minimalen Nebenwirkungen pharmakologisch aufzubessern.

Eine gewisse Vorsicht scheint dennoch angebracht. Nicht zuletzt deshalb, weil die Wirkungsweise von Modafinil alles andere als verstanden ist. «Niemand weiss wirklich, wie es funktioniert», gibt Sahakian zu bedenken. Klar ist bisher lediglich, dass Modafinil in einem komplizierten, mehrstufigen Prozess die wachheitsfördernden Histaminneurone im Hypothalamus enthemmt.

Auch die Neurowissenschaftlerin Martha Farah von der University of Pennsylvania hat Einwände: «Bei keinem Medikament, ob für Therapie oder Tuning, können wir uns ganz sicher sein, dass nicht subtile, seltene oder langfristige Nebenwirkungen auftreten.» Definitiv geschadet hat Modafinil schon mal der Karriere der US-amerikanischen Sprinterin Kelly White – sie wurde 2003 mit Modafinil-Abbauprodukten im Urin erwischt und vom Internationalen Leichtathletikverband für zwei Jahre gesperrt.

Da Dopingkontrollen im Journalismus noch nicht üblich sind, kann ich zuversichtlich sein, mit meinem Selbstversuch ungestraft davonzukommen. So richtig erlaubt ist meine effizienzsteigernde Massnahme allerdings nicht: Es handelt sich um einen klassischen Fall von off-label-Gebrauch – der Verwendung eines Medikaments ausserhalb der gesundheitsbehördlichen Zulassung. Schliesslich bin ich kein Narkoleptiker, der seine Schlafattacken kurieren will.

Off-Label-Gebrauch von Medikamenten ist jedoch nichts Ungewöhnliches. So werden sicher nicht alle der zu Millionen verkauften Viagra-Tabletten zur behördlich genehmigten Versteifung bei diagnostizierter «erektiler Dysfunktion des Mannes» eingenommen. Genauso unwahrscheinlich ist, dass der Modafinil-Hersteller Cephalon den Rekordumsatz seines Blockbusters im Geschäftsjahr 2005 – 513 Millionen Dollar – allein mit der behördlich abgesegneten Versorgung von Tagesschläfrigen erwirtschaftet hat.

Es drängt sich die Frage auf, wer in Zukunft Zugang zu den neuen kognitiven Stimulanzien haben soll und wie sich dieser Zugang regulieren liesse. Das Militär vertraut schon lange auf kognitionsverbessernde Psychopharmaka. Im Zweiten Weltkrieg putschten sich amerikanische Soldaten noch mit Amphetaminen (go pills) auf, die aber nicht selten psychotisch und abhängig machten. Modafinil scheint da vorteilhafter zu sein. Amerikanische Militärpiloten sollen auf ihren Einsätzen im Irak schon routinemässig mit dem Wachmacher gedopt sein.

Doch was ist mit Zivilisten, die in ihrem Beruf äusserst wach und konzentriert sein müssen, zum Beispiel Tankerkapitäne? Hätte die Havarie des Öltankers «Exxon Valdez» 1989 und damit eine der grössten Umweltkatastrophen der Seefahrt per Stimulanziengabe verhindert werden können? Und wäre die Luftfahrttragödie von Überlingen nicht passiert, wenn Skyguide ihre Fluglotsen bei Nachtschichten mit Modafinil versorgt hätte? Menschliches Fehlverhalten aufgrund von Übermüdung kann fatale Folgen haben. Wäre es nicht ethischer, alle Berufsgruppen mit Fremdgefährdungspotenzial schon vorsorglich mit Wachmachern fit zu dopen?

Aber wo ist die Grenze? Firmenchefs könnten auf die Idee kommen, auch ganz normale Arbeiter pharmakologisch zu tunen, um die Effizienz ihrer Unternehmen zu steigern: 36-Stunden-Schichten, kein Problem dank Modafinil? Die Neurowissenschaftlerin und Bioethikerin Martha Farah schliesst nicht aus, dass Hirndoping eines Tages zwangsverordnet wird: «Was, wenn die Sicherung des Arbeitsplatzes davon abhängt, der Anwendung neurokognitiver Verbesserungsmethoden zuzustimmen?»

Vergessen war gestern

Und es wird nicht bei Konzentrationshilfen und Wachmachern bleiben. Die Pharmalabors nehmen sich immer neue Bereiche der kognitiven Leistungsfähigkeit vor. Cortex Pharmaceuticals bastelt beispielsweise an einem Mittel, das das Denken beschleunigen soll, uns also regelrecht schlauer machen könnte. Ampakine sollen die Signalübertragung zwischen Nervenzellen im Stirnhirn erleichtern, die Substanzen CX717 und CX516 werden bereits getestet. Auch der Markenname steht schon fest: «Ampalex» soll die Hochgeschwindigkeitspille fürs Hirn heissen.

Die neuste Entwicklung der Psychopharmakologen ist ebenfalls noch in der Testphase: die Pille gegen das Vergessen. Eine der Firmen, die an der chemischen Merkhilfe arbeiten, gehört Eric Kandel. Der Hirnforscher erhielt im Jahr 2000 den Nobelpreis für die Erforschung der molekularen Strukturen des Gedächtnisses. Mäusen hat er mit der Merkpille MEM 1414, welche das Wachstum der Synapsen im Hirn ankurbelt, schon zu einem verjüngten Gedächtnis verholfen.

Offiziell arbeiten die Forscher an dem Mittel, um die normale Vergesslichkeit im Alter zu bekämpfen. Die überalternde Gesellschaft in den industrialisierten Ländern mit ihrer zunehmenden Zahl von Demenzerkrankungen ist ein riesiger Zukunftsmarkt.

Im Jahr 2004 litten weltweit 18 Millionen Menschen an Demenzerkrankungen. Epidemiologen des britischen «Foresight»-Projekts gehen davon aus, dass im Jahr 2025 bereits 34 Millionen Demenzerkrankte zu erwarten sind, von denen 71 Prozent in den industrialisierten Ländern leben. (Was impliziert, dass sich ein Grossteil der Erkrankten die teuren neuen Medikamente auch wird leisten können.) Und die Behörden dürften die Pille gegen das Vergessen für Alte und Demente ohne Probleme zulassen.

Kein Risiko also für die Pharmaindustrie, dafür grosse Chancen auf zusätzlichen Umsatz: Denn auch die Merkpille hat das Zeug zum mentalen Muntermacher für jedermann. Schnell noch vor der Prüfung ein Buch reinziehen und zuverlässig abspeichern, flugs Vokabeln eintrichtern oder den Vortrag fix hochladen – wer träumt nicht davon? In ein paar Jahren könnte das Szenario Wirklichkeit werden, dann wird, meint Kandel, die Gedächtnispille auf dem Markt sein.

Der Fluch der Erinnerung

Doch ist es erstrebenswert, all die neuen Möglichkeiten bis zum Äussersten zu nutzen? Besser als normal zu sein, darin kann auch ein Fluch liegen. So werden Menschen mit fotografischem Gedächtnis ihre Erinnerungen oft nicht los, auch wenn sie sich nichts sehnlicher wünschen, weil ihr Hirn schier überquillt. Dieses Schicksal könnte auch dem hirngedopten Normalmenschen drohen, meint die Pharmakologin Barbara Sahakian: «Eines Tages könnten wir von Erinnerungen belastet werden, die wir eigentlich gar nicht wollen. Aber da wir dauernd pharmakologisch getunt sind, müssen wir uns einfach alles merken.»

Ich auf jeden Fall bin schon wieder ganz der Alte. Am Tag nach meinem Selbstversuch ist alles wie immer. Minutenlang blinkt das Cursorzeichen auf meinem Bildschirm nervig vor sich hin und wartet vergeblich darauf, dass ich einen halbwegs gescheiten Satz eingebe. Es ist also wahr – Modafinil hat auch keine Nachwirkungen.


Grüße

PS: Erbse, wenn ich hier was falsch geschrieben habe - schon mal Sorry vorab.

[Erbse1]

Hallo Ackergaul,
nett daß du hier postest. Nur ein kleiner Irrtum CX701 ist eine Nachfolgesubstanz. So wie es aussieht,ist Cortex mit CX701 schneller in Phase1, als die FDA den Antrag zu CX717 bearbeitet. Die Anwendungsgebiete von CX701 sind mir noch nicht bekannt. Die FDA hat nur CX717 auf hold gesetzt. Wir werden uns hier noch gedulden müssen. Hoffentlich nicht mehr so lange.
Grüße
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 30.325.979 von Erbse1 am 26.06.07 15:09:27

Ich bin über Umwege (wie das so üblich ist) auf Cortex gestossen. Alles momentan noch ziemlich neu für mich... Schuld ist eigentlich Mike Havrilla der auch für den Fool schreibt und der ist ein Riesen COR-Fan!

http://www.fool.com/investing/high-growth/2007/05/02/conside…
Consider Cortex
By Mike Havrilla May 2, 2007

Although Cortex's (AMEX: COR) attention deficit hyperactivity disorder (ADHD) drug, CX-717, was put on clinical hold, recent findings could lift the freeze and get the drug back on track for FDA approval.

Back in March of 2006, shares of Cortex approached $5 per share, after it reported positive results in a small clinical study of CX-717. Results showed that the drug was safe, effective, well-tolerated, and produced no increase in heart rate or blood pressure -- a major advantage over the majority of existing ADHD drugs (e.g. Ritalin and Shire's (Nasdaq: SHPGY) Adderall), which are strong stimulants with occasional cardiovascular side effects. Non-stimulant treatment options such as Lilly's (NYSE: LLY) Strattera carry other risks, such as suicidal thoughts and liver damage.

On April 18, Cortex submitted a data package to the FDA providing convincing evidence that the specific brain tissue specimen changes seen in animal toxicology studies -- which previously caused the FDA to put CX-717 on clinical hold -- are a postmortem fixation artifact unrelated to the drug, and are not found in the tissue of the animal while it is still alive. The FDA partially lifted the clinical hold on CX-717 last fall, but dosing restrictions in this ruling prevent Cortex from pursuing further studies for the lucrative ADHD indication.

With shares of Cortex currently changing hands at around $2.50, and a market cap of only $100 million, this news represents an excellent opportunity for speculative biotech investors. The FDA should respond to Cortex by mid-June, and will probably lift the current high-dose restriction imposed on CX-717. If the company gets this crucial endorsement from the FDA, it should quickly move back above its previous $5 per share.

The ADHD indication is pivotal to the future development of CX-717 and Cortex, because it opens the way to major partnership deals with larger biotech companies or big pharma. The treatment of ADHD represents a large, growing market in the United States, especially since currently approved drugs are riddled with major safety issues.

[Ackergaul]

http://alfin2100.blogspot.com/2007/06/getting-to-ampakines-h…
Getting to Ampakines--How Much Longer?
04 June 2007

Brain boosting drugs in the new Ampakine class are back in the news--this time in connection with the problem of respiratory depression from sedative/hypnotic drugs.

Researchers at the University of Alberta (Edmonton, AB) and Cortex Pharmaceuticals (Irvine, CA) believe that AMPAKINE drugs may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

The drug tested in this study belongs to a novel class of molecules known as AMPAKINE compounds being developed by Cortex Pharmaceuticals, Inc. located in Irvine, California. AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA "Glutamate type receptor," which has been shown in rodent models to boost the brain's own protein for improving age-related deficits in memory mechanisms. In primate models AMPAKINE compounds have replicated the studies in rodents and in adults patients suffering from Attention Deficit Hyperactivity Disorder, significant clinical and statistical improvement in increase attention and decrease hyperactivity have been observed. The U. Alberta research provide evidence that another important AMPAKINE indication is to stimulate primitive areas of the brain called the pre-Botzinger Complex responsible for breathing, without causing side effects. The pre-Botzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties that have been identified in this brain region.

In a study published in 2006, Dr. John J. Greer of U. Alberta demonstrated that certain AMPAKINE compounds enhance the respiratory drive and breathing rhythm at the brain-stem level containing the pre-Botzinger Complex in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants.

Dr. Greer found that respiratory depression induced by these agents can be reversed or prevented in test animals with an experimental AMPAKINE drug, without a reduction of pain relief or sedation.

Greer and coworkers treated rats with the opioids analgesic fentanyl or the barbiturate sedative Phenobarbital, both commonly prescribed in the United States. Greer used a technique known as plethysmography, which measures blood flow throughout the body, to determine the level of respiratory distressed caused by the drugs. When drugged rats were treated with the AMPAKINE , the respiratory distress quickly resolved. The drug worked in both newborn and adult rats. Interestingly, the drug on its own did not affect blood flow in animals not treated with the sedative drugs, nor did administration of the drug cause noticeable arousal in the animals.

Greer concluded, in a study published in the September 20, 2006 issue of the American Journal of Respiratory Critical Care Medicine, that CX546, "effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response."

"These results open up the real possibility of combining an ampakine compound with commonly prescribed barbiturates or opiates to reduce the likelihood that life-threatening respiratory depression will occur," noted explained Roger G. Stoll, Ph.D., Chairman, President, and CEO of Cortex.

Source

Ampakines hold out a promise for effective palliative treatments for Alzheimer's and other neurodegenerative disease. Currently, the Cortex drug CX717 is being held up by the FDA over toxicity concerns. Consequently the stock price of Cortex is currently quite low--trading below US $3 a share for over a year.

It is easy to see that should Cortex navigate through the labyrinthine bureaucracy of the FDA and reach approval for any of its Ampakines in development, that the stock price could rise rapidly.

Frankly, it is the potential for cognitive enhancement in normal people that fascinates me the most about the Ampakines. But the potential to make a substantial profit on a fairly small investment is also attractive. But do your own research before investing.

Here is more about Cortex' attempt to satisfy the FDA's concerns about possible toxicity of CX717 in animal studies.

Here is a recent report on a study that suggests that Ampakines might benefit Huntington's Disease patients, through their role in releasing BDNF in the brain.

[Erbse1]

Update des NeuroInvestor und neues Kursziel zu Cortex


(from NI July/August 07)

Cortex is still waiting for the FDA to read through the coffin-sized box of data sent to establish the fact that the 'tox finding' was an artifact. We expect the dose-restriction to be lifted--probably late in July, since the FDA tends to be late with everything, and they are prioritizing projects which have PDUFA mandated timeframes involved. That will allow the ADHD licensing auction to move ahead. The inlicensing process appears to be slow, which is a good thing. Cortex did sign an IP deal with University of Alberta regarding the use of Ampakines in respiratory depression. The CX701 IND is in queue, awaiting completion of animal tox report.Target is raised to 8.

On-line comment, 5/10/07

The very old Saturday Night Live skit (back when SNL was funny) 'Short Attention Span Theatre' came to mind as Cortex's recent price recovery sold off somewhat in the wake of a webcast presentation that had not one iota of bad news--but no immediate gratification either. The nearterm value drivers--FDA lifting of the CX717 dosing limits; corporate partnerships for CX717 and/or the neurotrophic 'hi-impact' portfolio could not be pulled out of a hat on cue. While momentum players quickly exited in their search for immediate reinforcement, all of these event will occur--the first, within the next six weeks, the other two before year-end--and NI's ongoing description of Cortex as being the single best partnering/acquisition target in the CNS space will look more prescient than it does at the moment. Cortex is doing its homework: expanding its range of molecules under development, demonstrating Ampakine value in such untreated but devastating disorders as Huntington's (where Amarin recently saw Miraxion fail in Phase III) and Rett's. They have also shown Ampakine value in restoring respiratory function in opiate overdose and Rett's--adding yet another potential use to the broad list already in place. NI's target for Cortex during 2007 has been maintained at 6. Though it would be superfluous to alter it at the moment, we expect that before the end of the year, that will look conservative.

Schönen Tag noch
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 30.470.186 von Erbse1 am 03.07.07 15:09:42

Ich gehe sogar davon aus, dass die FDA sich noch ein wenig mehr Zeit als Juli lässt... nichts desto trotz habe mich Ende der letzten Woche auch ein wenig in COR eingekauft. Ich denke die Ampakine-Story ist nach wie vor intakt.
Hier ist weiterhin Geduld angesagt, aber je mehr ich mich hier einlese desto besser wirds.

Grüße

[Erbse1]

Ich komme mir langsam vor wie zu Weihnachten. Warten auf das Christkind, oder auch warten auf die FDA Entscheidung
Mike Havrilla verkürzt mit seinem Artikel etwas die Wartezeit.

Machts mal gut
Erbse

Cortex Awaits the FDA's Decision Regarding ADHD Drug

Monday July 9, 5:18 am ET

Mike Havrilla submits: Cortex (AMEX: COR - News) and its investors are still waiting (patiently or otherwise) for the FDA to determine the fate of CX717 – specifically, the agency's willingness to allow for higher doses of the drug candidate to be studied in a Phase 2b trial in adults with ADHD. Back in March of 2006, shares of Cortex briefly traded above $5 per share, after it reported encouraging results among 22 adults with ADHD who completed the Phase 2a trial in the CX717 high-dose (800 mg twice daily) group. Since the low-dose (200 mg twice daily) group did not yield significant results in the same trial, the pending FDA decision is crucial to future commercial development potential of CX717 because of the urgent need for a safe, non-stimulant treatment option in the huge, growing market for the treatment of ADHD.
Specifically, the Phase 2a study demonstrated that CX717 was effective at the higher dose, well-tolerated, and produced no increase in heart rate or blood pressure, which is a major advantage over the majority of existing ADHD drugs which are strong stimulants such as Ritalin and Adderall. Non-stimulant treatment options such as Strattera have other risks, such as the potential for liver damage and suicidal thoughts. If Cortex receives clearance from the FDA to move on with the Phase 2b study for higher doses of CX717 in adult ADHD; it opens the way for a major partnership deal that could easily exceed the company's current market cap of just over $100 million.

Concerning the timeline for an FDA decision, Cortex submitted a data package to the agency on April 18 which provides concrete evidence that the specific brain tissue specimen changes seen in animal toxicology studies are a post-mortem fixation artifact unrelated to the drug and are not found in the tissue of the animal while it is still alive. This post-mortem fixation artifact previously caused the FDA to put CX717 on complete clinical hold until the agency partially lifted the hold on lower doses only last October. The CX717 dosing restrictions agreed upon in this ruling prevent Cortex from pursuing a Phase 2b study for the lucrative ADHD indication.

However, the exact timing of this FDA ruling is unclear, as original guidance from management placed a likely decision in about 60 days or around June 18. As that deadline passed with no ruling, it is apparent that the FDA is busy with higher priority deadlines such as the PDUFA dates for NDA filings, which would take precedence over the decision on CX717 since the clinical hold was already lifted last October and the current submission only involves a petition to allow for higher doses of the drug to be studied. With Cortex currently trading at a market cap barely above $100 million, the shares are poised to move much higher once the FDA lifts the high-dose clinical hold on CX717 due to the enormous commercial potential and need for a safe and effective non-stimulant ADHD drug treatment option. If the company gets this crucial endorsement from the FDA, it should easily eclipse its previous high of $5 per share.

Beyond the tremendous potential for CX717 in the treatment of ADHD, Cortex has other compounds in earlier stages of development. Studies of the company’s high impact Ampakine drug CX929 have demonstrated encouraging results in mice with the Huntington’s Disease gene. This compound has shown the ability to restore depressed levels of BDNF (brain derived neurotrophic factor) back to normal and has caused significant behavioral improvements in transgenic mouse models of Huntington’s Disease. Remaining near-term catalysts for Cortex beyond CX717 include the low-impact Ampakine CX701 which the company expects to move into Phase 1 clinical trials this month pending favorable preclinical toxicology results. Other objectives for Cortex include the possibility for a new research and development collaboration for its high-impact Ampakine compounds and the potential for in-licensing of a new Phase 2 non-Ampakine orphan drug.

Disclosure: Author has a long position in COR

[Ackergaul]

Mahlzeit,

war alles schonmal geschrieben, hier trotzdem noch eine Zusammenfassung der aktuellen Lage. Der Autor hat zwar kein Kursziel genannt, aber zwischen den Zeilen kann man auch einiges sehen...

http://www.winningwithadd.com/2007/07/cortex_awaits_decision…
Cortex Awaits Decision Regarding ADD Drug
July 14, 2007

Cortex (COR) and its investors are still waiting (patiently or otherwise) for the FDA to determine the fate of CX717 – specifically, the agency's willingness to allow for higher doses of the drug candidate to be studied in a Phase 2b trial in adults with ADHD.

Back in March of 2006, shares of Cortex briefly traded above $5 per share, after it reported encouraging results among 22 adults with ADHD who completed the Phase 2a trial in the CX717 high-dose (800 mg twice daily) group.

Since the low-dose (200 mg twice daily) group did not yield significant results in the same trial, the pending FDA decision is crucial to future commercial development potential of CX717 because of the urgent need for a safe, non-stimulant treatment option in the huge, growing market for the treatment of ADHD.



Ein bis zwei Monate Geduld, dann sollte hoffentlich eine positive Entscheidung der FDA folgen... hoffentlich!

Grüße

[Ackergaul]

früher als zumindest von mir erwartet:

http://www.reuters.com/article/topNews/idUKWNAS618720070717?…
Cortex gets OK to resume enrollment for Ampakine trials
Tue Jul 17, 2007 9:03AM EDT

Free practice account at FOREX.comJuly 17 (Reuters) - Cortex Pharmaceuticals Inc. (COR.A: Quote, Profile, Research) said it has received approval from U.S. regulators to resume enrollment for clinical trials of its drug candidate, Ampakine CX717, in Alzheimer PET-scan studies .

The trial will resume at all dose levels.

The study of Ampakine CX717, which was originally designed with doses of 200mg, 600mg and 1200mg, was placed on hold by the U.S. Food and Drug Administration due to concerns over some preclinical animal data. (Reporting by Shailesh Kuber in Bangalore)


Sollte der Startschuss für bessere Cortex-Zeiten sein. Bin weiterhin sehr hoffnungsfroh... Sehr schön - weitermachen!

Grüße

[Ackergaul]

Antwort auf Beitrag Nr.: 30.727.359 von Ackergaul am 17.07.07 15:10:35

Cortex Pharma To Restart Clinical Trial With AMPAKINE CX717 In Alzheimer-PET Scan Study - Quick Facts [COR]

7/17/2007 8:54:08 AM Cortex Pharmaceuticals, Inc. (COR) on Tuesday said that following review of the AMPAKINE CX717 data package sent to the Food & Drug Administration's Division of Neurology Products on April 17, 2007, the FDA responded that Cortex could immediately resume enrollment in the CX717 Alzheimer's positron emission tomography scan study at all requested dose levels. The agency had previously limited the dose levels such that the 600mg and 1200mg doses could not be administered.

The earlier dose limitations imposed by the FDA were related to concerns over data from preclinical animal studies and were not related to any findings from human clinical trials.

The company stated that the study was originally designed with doses of 200mg, 600mg, and 1200mg to be administered to the patients. The new protocol approved by the agency allows a return to the original dose levels, with the upper dose being 1200mg.

Further, Cortex said it plans to file a second IND for CX717 with the Division of Psychiatry Products during the third quarter of 2007 to allow the company to begin a Phase IIB study evaluating CX717 for the treatment of Attention Deficit Hyperactivity Disorder.

[Erbse1]

Kommentar des NeuroInvestor zu der Meldung.

Allen Cortex Fans noch einen schönen Tag
Erbse

The only trial within the Neurology section's purview is the Alzheimer's study, and they have OK'd all the dosing range Cortex wanted to use in that trial. That's as good as it could get. They can't OK a dosing range for ADHD that Cortex has not even defined or applied for yet, to an entirely different section of the FDA (Psychiatry). The reference to completing the tox review is IMHO a formality--'yes. we will read it when we get time, we'll let you know if we have any questions, but what we have read is sufficient to tell us there isnt a problem here, go ahead'. Now Cortex can complete the IND application to Psychiatry. Whether Psychiatry will go beyond the 1200mg dose--indeed whether Cortex will even ask for it, is yet to be determined. But they don't have to. This is enough to allow not only the Alzheimer's trial to resume in full--but more importantly, represents the 'clean bill of health' that is needed for the ADHD partnership discussions to go ahead.

This is as good as could have been hoped for.

NeuroInvestment

[Ackergaul]

Hi Erbse,

leider ist die Homepage von Cortex ein wenig unübersichtlich, um nicht zu sagen schlecht aufgebaut. Ich habe im vorigen Bericht die Pressemitteilung gepostet, dass im 3. Quartal ein IND zu ADHD bereits geplant ist (also vermutlich in 4-8 Wochen). Also ist davon auszugehen, dass bei AD (Alzheimer) dies bereits geschehen ist. Ist das soweit korrekt?
Das würde dann an eine anderen Stelle der FDA gehen. AD und EDS (Schlafkrankheit) in Richtung Neurological disorders und ADHD dann zu den Psychiatric disorders. Wurde zu EDS eigentlich auch ein IND gestellt?
ADHD scheint aus meiner Sicht die erste Option zu sein. Wäre wahrscheinlich am "einfachsten Durchzubekommen". Alleine vom Aufbau des Trials und der Zeit die dieser beansprucht.

CX717 ist in folgenden Phase 2 Trials:
- ADHD
- EDS
- AD

Nun ist wieder Tür und Tor geöffnet. Partnerschaften zu ADHD und AD scheinen bis Jahresende möglich. Wäre auch aus finanziellem Aspekt (cash-burn Rate) wünschenswert...


Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 30.732.256 von Ackergaul am 17.07.07 19:28:17

Hallo Ackergaul,
folgend die Pipeline von Cortex. CX 1501 ist mit Vorsicht zu genießen, da angeblich Probleme aufgetreten sind.

CX 717 wurde von der DARPA in der Anwendung Schlafentzug getestet. Allerdings war der Versuchsaufbau nicht sehr besonders und die Versuche sind gescheitert. Weitere Informationen hierzu findest du auf der Cortex Seite. Ob zu weiteren Anwendung bei Narkolepsie eine IND gestellt wurde, weiß ich nicht mehr. Ich glaub aber nicht. Geplant sind sie wohl später. Warscheinlich aber mit einer anderen Substanz. Was wo getestet wird hängt auch davon ab, welcher Wirkstoff auslizensiert wird und welche Bedingungen dann gelten. Das wird in nächster Zeit noch ganz spannend. Eine Auslizensierung der Low Impacts Ampakine wäre denkbar. Die High Impacts Ampakine könnten dann weitestgehend in Eigenregie entwickelt werden, doch Cortex hat gerade mal knapp 30 Leute. Da ist eine einzelne Anwendung schon eine Leistung. Es wird alles schon eine Weile dauern. Sollte ich weitere Informationen hierzu finden, werde ich sie dir posten.

Grüße
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 30.732.858 von Erbse1 am 17.07.07 19:57:27

Hi Erbse,

vielen Dank für die Hilfe!

Das mit dem Schlafentzug Tests habe ich mitbekommen. Anscheinend war (natürlich) das Militär anfangs stark interessiert. Nach wohl negativen Bericht der DARPA dann aber weniger. Wie auch immer, man hat hier noch multiple shots...
Der nächsten Auslizensierung steht wohl seit heuer nichts mehr im Wege.

Die "ofizielle" Cortex Mitteilung:

Cortex Pharmaceuticals, Inc. (COR) to Resume Clinical Trial with AMPAKINE(R) CX717 in Alzheimer-PET Scan Study after FDA Approves Protocol with Higher Doses of Drug
7/17/2007

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR), announced that following review of the AMPAKINE® CX717 data package sent to the Food & Drug Administration’s (FDA) Division of Neurology Products (DNP) on April 17, 2007, the FDA responded that Cortex can immediately resume enrollment in the CX717 Alzheimer’s positron emission tomography (PET) scan study at all requested dose levels. The study was originally designed with doses of 200mg, 600mg, and 1200mg to be administered to the patients. However, the agency had previously limited the dose levels such that the 600mg and 1200mg doses could not be administered. The new protocol approved by the agency allows a return to the original dose levels, with the upper dose being 1200mg.

Dr. Roger Stoll, Chief Executive Officer of Cortex, stated, “With the removal of the dose restrictions, the Company can now resume studying CX717 at all desired dose levels. This important double-blinded study will attempt to determine if we can duplicate the striking PET scan findings in non-human primates which correlated with increased cognitive performance published by Dr. Deadwyler in PLOS Biology in September 2005.” The clinical study is being performed in mild-moderate Alzheimer’s patients who are drug naïve or stabilized on cholinesterase inhibitors at the University of Michigan Medical Center. In animal studies cholinesterase inhibitors such as Aricept® and Reminyl® appear to enhance the effects of CX717.

The earlier dose limitations imposed by the FDA were related to concerns over data from preclinical animal studies and were not related to any findings from human clinical trials. The DNP plans to continue their review of the data package, but saw no reason not to permit the full resumption of the current AD-PET scan study. Cortex will continue to have further discussions with the DNP regarding the previously submitted toxicology package and additional requirements may be requested by the FDA.

Cortex intends to file a second IND for CX717 with the Division of Psychiatry Products (DPP) during the 3rd Quarter of 2007 to allow the Company to initiate a Phase IIB study evaluating CX717 for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Since the DNP was where the original clinical hold was issued and where the subsequent release of the clinical hold with dosage limitations was granted, Cortex recognized that a decision from that division of the FDA was needed before proceeding with a filing in another division (DPP) for the same drug product.

“We are gratified that all our hard work has succeeded in moving the development of CX717 forward and we have to thank some very diligent employees, consultants, and advisors for their help with this complicated issue,” added Dr. Stoll. “It is a credit to our researchers and our Company that an issue of such complexity could be unraveled and permit Cortex to proceed with the development of this new and novel treatment for some serious CNS diseases.”

[Ackergaul]

Moin, moin,

bin zwar kein Fan von R&R, hier trotzdem das Update:

Research Note from Rodman & Renshaw - First Take

Cortex Pharma (COR)
Rating: Market Outperform, Target Price: $4.50

CX717 Dosing Restriction Was Lifted on 17-July w/ brief spike before settling back to close below $3 per share the next day


• The FDA has lifted the dosing limitation on Cortex’s CX717 (Neurology division)
• Dosing of up to 1,200mg/day is allowed in the currently active Alzheimer’s study
• Cortex anticipates filing an IND for the Division of Psychiatry Products in 3Q07 (ADHD indication)--> remember that promising Phase 2a adult ADHD results were only observed at 1600 mg/day dose (800 mg twice daily); so yesterdays ruling is still positive, but not the definitive answer to moving forward to Phase 2b for ADHD
• Phase IIb ADHD study could get under way in 4Q07
• We believe that the drug is again partnerable and expect a licensing transaction by YE07
o The Alzheimer’s study originally included 200mg, 600mg, and 1,200mg doses of CX717.
However, the FDA’s dosing restriction had previously prevented Cortex from continuing
with the two upper doses. Lifting the restriction permits a return to the original dosing.
o This trial involves mild-to-moderate patients who are either drug-naïve or on
cholinesterase inhibitors at the University of Michigan Medical Center. In animals,
cholinesterase inhibitors like Aricept® and Razadyne® enhanced the effects of CX717.
o Cortex needed to get the green light from the Neurology division on dosing before submitting its ADHD Phase 2b IND to the Psychiatry division. Since the FDA division that originally restricted dosing has now deemed CX717 safe at all proposed doses, the Psychiatry division will be able to make its decision on CX717 in ADHD in that context.
• In the wake of this initial relaxing of the dosing restriction on CX717, we retain our Market
Outperform rating with a target price of $4.50 on Cortex shares.


Für mich ist Cortex zur Zeit ein klares BUY, gerade nach dem die FDA die 1200 mg Dosis für AD abgenickt hat. Man sollte nicht alles durch die rosarote Brille nun sehen, aber der Kursanstieg am Dienstag (durch die gestrigen Gewinnmitnahmen stark beschnitten) war - denke ich - alles andere als übertrieben.


Grüße

[Erbse1]

Update des NeuroInvestor zur aktuellen Lage. Sehr optimistische Einschätzung. Hoffen wir das Beste.
Grüße
Erbse

FDA Decision Announcement revised 7/19/07

The FDA decision was everything one could have asked for--a release of the dosing restrictions on CX717. At this time, the only trial within the Neurology section's purview is the Alzheimer's study, and they have OK'd all the dosing range Cortex wanted to use in that trial. That's as good as it could get. The dosing range for ADHD has not yet defined or applied for yet, to an entirely different section of the FDA (Psychiatry), but this opens to door to 1200mg, which gives them enough 'headroom' for a full Phase IIb in ADHD as well, though this will require submission and approval of the IND by Psychiatry this quarter. The current maximum preclinical tox exposure is 3 months, which will be the framework (depending on how much of a buffer Psychiatry wants) for determining how long the ADHD study can go for. The PR's reference to completing the tox review is in our opinion a formality--'we'll let you know if we have any questions, but what we have read is sufficient to tell us there isnt a toxicology/safety problem here, go ahead'. Now Cortex can complete the IND application to Psychiatry--probably around the end of summer. We expect that the IND will be approved, albeit perhaps with a modest limitation (4 or 6 weeks) on the duration of dosing.

This is enough to allow not only the Alzheimer's trial to resume in full--but more importantly, represents the 'clean bill of health' that is needed for the ADHD partnership discussions to go ahead.

This is most excellent news for Cortex. Given the inflation of deal valuations seen of late, the prospects for an Ampakine deal may well involve terms that could exceed those that might have been obtainable last year. The next 2 to 3 quarters will be fun to watch indeed. There is not a more valuable partnership/licensing/acquisition target in the CNS space than Cortex represents at this point.

Quelle: http://www.neuroinvestment.com/CORXcom.html

[Ackergaul]

Nun muss "lediglich" die Division of Psychiatry Products der FDA noch die Freigabe der 1600 mg/day Dosis zu ADHD CX717 freigeben. Dann wird sich der Kurs ein gutes Stück in Richtung 4 Dollar bewegen. Zumindest gehe ich davon aus, dass die DPP ebenso die Dosis absegnen will, wie Ihre Neurologen-Kollegen (DNP). Die Neurological Division hatte für die Alzheimer Tests die 1200 mg/day bestätigt.

Sind bis Jahresende noch ein paar schöne Ausblicke:
- Im 3. Quartal soll bereits das ADHD IND gestellt werden (Phase 2b Studie)
- bis Jahresende - VERMUTLICH! - eine Lizenz Partnerschaft


Geduld dann wird dass schon hier was...

[Erbse1]

Die Matrics Studie wurde beendet. Würde gerne einen Kommentar vom CEO Stoll hören.

Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia

This study has been terminated.
Study terminated at Sponsor's request.

http://www.clinicaltrials.gov/ct/show/NCT00425815?order=2

Zumindestens sollten jetzt mal langsam die Schizophrenie Ergebnisse veröffentlicht werden. Wie weit ist man mit dem add on Versuch mit Risperdal. Ehrlich gesagt, die gehen mir langsam auf den Keks.
Ackergaul, danke für deine Postings. Freut mich einen Mitstreiter gefunden zu haben.

Schönes Wochenende noch

Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 30.781.231 von Erbse1 am 20.07.07 20:58:23

Hi Erbse,

Terminated hört sich für mich erst einmal nicht gut an... Bevor Cortex zur Studie Stellung nimmt, sollte Organon aber vorher noch was zu den Ergebnissen sagen! Habe bei organon selber nichts gefunden. In der pipeline Übersicht, ist es immer noch in der Phase II:
http://www.organon.com/innovation/pipeline/index.asp

Das einzige was ich aktuell zu farampator gefunden habe war folgendes:
http://schizophreniabulletin.oxfordjournals.org/cgi/content/…
Schizophrenia Bulletin Advance Access published online on July 19, 2007

© The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [e-mail].


Recent Advances in the Development of Novel Pharmacological Agents for the Treatment of Cognitive Impairments in Schizophrenia
Robert W. Buchanan1,2, Robert Freedman3, Daniel C. Javitt4, Anissa Abi-Dargham5 and Jeffrey A. Lieberman6
2 Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 2128
3 Department of Psychiatry, University of Colorado Health Sciences Center
4 Department of Psychiatry, Nathan Kline Institute for Psychiatric Research, New York University School of Medicine
5 Department of Psychiatry, New York State Psychiatric Institute
6 Department of Psychiatry, College of Physicians and Surgeons, Columbia University

1 To whom correspondence should be addressed; tel: [phone]; fax: [phone]; e-mail: [e-mail].

Wayne Fenton was a major driving force behind the establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia (TURNS) project mechanisms. These projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified 3 drug mechanisms of particular interest: cholinergic, dopaminergic, and glutamatergic. The TURNS project is designed to select potential cognitive-enhancing agents and evaluate their potential efficacy in the context of proof of concept or clinical efficacy trials. This article reviews the rationale for these 3 approaches and provides an update on the development of therapeutic agents, which act through one of these 3 mechanisms.


Keywords: cognitive impairments / nicotinic receptors / dopamine / glutamate


Leider nicht gerade weiterhelfend...

Bis denn!

[Erbse1]

Antwort auf Beitrag Nr.: 30.794.058 von Ackergaul am 22.07.07 14:08:19

Hallo Ackergaul,
von Organon wirst du fast gar nichts finden und keine Informationen bekommen. Ich hoffe das Schering-Plough nach der Übernahme von Organon das Ampakine Programm in angemessener Zeit bearbeitet. Organon war eine einzige Zumutung. Sechs Jahre für eine Phase 2 und immer noch keine Testergebnisse veröffentlicht.
Cortex hat die Anwendungsgebiete Schizophrenie und Depression an Organon für nen Appel und nen Ei auslizensiert und Organon hat nichts besseres zu tun als ORG 24448 aus die Patentlaufzeit rauslaufen zu lassen. Ich hoffe, daß sich ein neuer Partner findet der mit dem nötigen Ernst an die Sache geht.

Was Org 24448 betrifft, soll diese Substanz bei kognitiven Defiziten wieder gestartet werden. Diese Information hat der NeuroInvestor ins Netz gestellt. Es sei denn Schering-Plough hat etwas anderes damit vor.
Wenn du dich für dieses Themengebiet interessierst kannst du dir auch mal Targacept anschauen. Die arbeiten an ähnlichen Gebieten wie Cortex nur an einem anderen Rezeptor. Nur haben sie im Unterschied zu Cortex mit AstraZeneca einen anständigen Partner und die Informationspolitik ist einfach gut.

http://www.wallstreet-online.de/community/thread/1105815-1.h…

Schönen Sonntag noch
Erbse

[Ackergaul]

Mal wieder was von Mike H. - der Artikel ist leider schon ein paar Tage älter. So viel wie der schreibt, ist anzunehmen, dass er hier gut investiert ist...


Cortex Waits to Hear Fate of CX717
Posted on Friday, July 6th, 2007 | In Biotech

Contributed by: Mike Havrilla (http://www.mikehav.com) -
Cortex (COR) and its investors are still waiting (patiently or otherwise) for the FDA to determine the fate of CX717 – specifically, the agency’s willingness to allow for higher doses of the drug candidate to be studied in a Phase 2b trial in adults with ADHD. Back in March of 2006, shares of Cortex briefly traded above $5 per share, after it reported encouraging results among 22 adults with ADHD who completed the Phase 2a trial in the CX717 high-dose (800 mg twice daily) group. Since the low-dose (200 mg twice daily) group did not yield significant results in the same trial, the pending FDA decision is crucial to future commercial development potential of CX717 because of the urgent need for a safe, non-stimulant treatment option in the huge, growing market for the treatment of ADHD.

Specifically, the Phase 2a study demonstrated that CX717 was effective at the higher dose, well-tolerated, and produced no increase in heart rate or blood pressure, which is a major advantage over the majority of existing ADHD drugs which are strong stimulants such as Ritalin and Adderall. Non-stimulant treatment options such as Strattera have other risks, such as the potential for liver damage and suicidal thoughts. If Cortex receives clearance from the FDA to move on with the Phase 2b study for higher doses of CX717 in adult ADHD; it opens the way for a major partnership deal that could easily exceed the company’s current market cap of just over $100 million.

Concerning the timeline for an FDA decision, Cortex submitted a data package to the agency on April 18 which provides concrete evidence that the specific brain tissue specimen changes seen in animal toxicology studies are a post-mortem fixation artifact unrelated to the drug and are not found in the tissue of the animal while it is still alive. This post-mortem fixation artifact previously caused the FDA to put CX717 on complete clinical hold until the agency partially lifted the hold on lower doses only last October. The CX717 dosing restrictions agreed upon in this ruling prevent Cortex from pursuing a Phase 2b study for the lucrative ADHD indication.

However, the exact timing of this FDA ruling is unclear, as original guidance from management placed a likely decision in about 60 days or around June 18. As that deadline passed with no ruling, it is apparent that the FDA is busy with higher priority deadlines such as the PDUFA dates for NDA filings, which would take precedence over the decision on CX717 since the clinical hold was already lifted last October and the current submission only involves a petition to allow for higher doses of the drug to be studied. With Cortex currently trading at a market cap barely above $100 million, the shares are poised to move much higher once the FDA lifts the high-dose clinical hold on CX717 due to the enormous commercial potential and need for a safe and effective non-stimulant ADHD drug treatment option. If the company gets this crucial endorsement from the FDA, it should easily eclipse its previous high of $5 per share.

Beyond the tremendous potential for CX717 in the treatment of ADHD, Cortex has other compounds in earlier stages of development. Studies of the company’s high impact Ampakine drug CX929 have demonstrated encouraging results in mice with the Huntington’s Disease gene. This compound has shown the ability to restore depressed levels of BDNF (brain derived neurotrophic factor) back to normal and has caused significant behavioral improvements in transgenic mouse models of Huntington’s Disease. Remaining near-term catalysts for Cortex beyond CX717 include the low-impact Ampakine CX701 which the company expects to move into Phase 1 clinical trials this month pending favorable preclinical toxicology results. Other objectives for Cortex include the possibility for a new research and development collaboration for its high-impact Ampakine compounds and the potential for in-licensing of a new Phase 2 non-Ampakine orphan drug.

Disclosure: The author has a long position in Cortex.

[Ackergaul]

http://alfin2100.blogspot.com/2007/07/on-losing-your-depress…
On Losing Your Depression Quickly
25 July 2007

Conventional antidepressants may require from a few weeks up to a few months to achieve their antidepressant effect, when they are effective. Depression is a very common condition worldwide, very expensive in terms of lost time and lost lives. A quicker way to lose one's depression would be quite useful.

A new study has revealed more about how the medication ketamine, when used experimentally for depression, relieves symptoms of the disorder in hours instead of the weeks or months it takes for current antidepressants to work. While ketamine itself probably won’t come into use as an antidepressant because of its side effects, the new finding moves scientists considerably closer to understanding how to develop faster-acting antidepressant medications – among the priorities of the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Ketamine blocks a receptor called NMDA on brain cells, an earlier NIMH study in humans had shown, but the new study in mice shows that this is an intermediate step. It turns out that blocking NMDA increases the activity of another receptor, AMPA, and that this boost in AMPA is crucial for ketamine’s rapid antidepressant actions. The study was reported online in Biological Psychiatry on July 23, by NIMH researchers Husseini K. Manji, MD, Guang Chen, MD, PhD, Carlos Zarate, MD, and colleagues.
...Almost 15 million American adults have a depressive disorder. During the long wait to begin feeling the effects of conventional medications, patients may worsen, raising the risk of suicide for some. Depressive disorders also affect children and adolescents.

By aiming new medications at more direct molecular targets, such as NMDA or AMPA, scientists may be able to bypass some of the steps through which current antidepressants indirectly exert their effects – a roundabout route that accounts for the long time it takes for patients to begin feeling better with the conventional medications.

While ketamine appears to achieve this, it is an unlikely candidate to become a new treatment for depression, because of the side effects it can cause in humans, including hallucinations. It is approved as an anesthetic by the Food and Drug Administration at much higher doses than those given in the study, but its use is limited because it may cause hallucinations during recovery from anesthesia.

Of course ketamine would be an absurd choice for routine antidepressant treatment--it is administered by injection, incapacitates an individual for a period of time, and often subjects an individual to horrific nightmares on emergence from the drug.

And yet if scientists and clinical researchers can learn from the effects of ketamine on the brain and on subsequent mental states, why not?

Ampakines are drugs under development by Cortex Pharmaceuticals (Amex: COR) that also affect the AMPA receptors. And like ketamine, some ampakines also have an antidepressant effect.

I suspect that we are due for a breakthrough in therapy for depression, given how long it has been since any significant progress has been made in that area of neuropharmaceutics. Looking at glutamate receptors in that regard can certainly not hurt. If we accidentally stumble across better therapies for Alzheimer's and other neurological conditions in the process, vive le serendipity!
;-)

Labels: Ampakines, depression


Wollen wir doch hoffen, dass der Durchbruch von Cortex kommt. Der kursiv dargestellte Text, stammt übrigends aus folgender Quelle:

http://www.eurekalert.org/pub_releases/2007-07/niom-fac07240…
Faster-acting antidepressants closer to becoming a reality

Experimental medication ketamine relieves depression in just hours -- Points to targets for new medications
A new study has revealed more about how the medication ketamine, when used experimentally for depression, relieves symptoms of the disorder in hours instead of the weeks or months it takes for current antidepressants to work. While ketamine itself probably won’t come into use as an antidepressant because of its side effects, the new finding moves scientists considerably closer to understanding how to develop faster-acting antidepressant medications – among the priorities of the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Ketamine blocks a receptor called NMDA on brain cells, an earlier NIMH study in humans had shown, but the new study in mice shows that this is an intermediate step. It turns out that blocking NMDA increases the activity of another receptor, AMPA, and that this boost in AMPA is crucial for ketamine’s rapid antidepressant actions. The study was reported online in Biological Psychiatry on July 23, by NIMH researchers Husseini K. Manji, MD, Guang Chen, MD, PhD, Carlos Zarate, MD, and colleagues.

“Our research is showing us how to develop medications that get at the biological roots of depression. This new finding is a major step toward learning how to improve treatment for the millions of Americans with this debilitating disorder; toward eliminating the weeks of suffering and uncertainty they have to endure while they wait for their medications to work,” said NIH Director Elias Zerhouni, M.D.

Almost 15 million American adults have a depressive disorder. During the long wait to begin feeling the effects of conventional medications, patients may worsen, raising the risk of suicide for some. Depressive disorders also affect children and adolescents.

By aiming new medications at more direct molecular targets, such as NMDA or AMPA, scientists may be able to bypass some of the steps through which current antidepressants indirectly exert their effects – a roundabout route that accounts for the long time it takes for patients to begin feeling better with the conventional medications.

While ketamine appears to achieve this, it is an unlikely candidate to become a new treatment for depression, because of the side effects it can cause in humans, including hallucinations. It is approved as an anesthetic by the Food and Drug Administration at much higher doses than those given in the study, but its use is limited because it may cause hallucinations during recovery from anesthesia.

Both NMDA and AMPA are receptors for the neurotransmitter glutamate, one of the chemical messengers that enable brain cells to communicate with each other. The glutamate system has been implicated in depression recently, leading to efforts to unravel its molecular machinery in search of abnormalities and of better targets for antidepressant medications.

This focus on the glutamate system is a departure from the thinking that led to currently available antidepressants, which are thought to relieve depression through a lengthy trickle-down process of biochemical reactions that affect the circuitry underlying depression.

The fact that NMDA and AMPA receptors are part of the glutamate system and that targeting them directly led to such rapid, sustained relief of depression-like behaviors in this study – and that a single dose of ketamine did the same in humans in the earlier study – suggests that they are probably the key targets for antidepressant medications.

“In any other illness of depression’s magnitude, patients aren’t expected to just accept that their treatments won’t start helping them for weeks or months. The value of our research on compounds like ketamine is that it tells us where to look for more precise targets for new kinds of medications that can close the gap,” said NIMH Director Thomas R. Insel, MD. “We’re making tremendous progress.”

To conduct the new study, researchers induced depression-like behaviors in mice; for example, the mice gave up after being forced to engage in hopeless tasks, such as prolonged swimming. A dose of ketamine reversed the depression-like behaviors for at least two weeks.

When the researchers gave the mice a substance that blocks the AMPA receptor beforehand, ketamine was not able to reverse the depression-like behaviors. The boost in AMPA thus appears to be a necessary ingredient for ketamine’s antidepressant effects.

In a related experiment, the scientists used two different compounds instead of ketamine to try to block just one part of the NMDA receptor, an even more precise target. These other compounds also reduced depressive behaviors, suggesting that it may be feasible to develop other fast-acting antidepressants without ketamine’s side effects.

“Today’s antidepressant medications eventually end up doing the same thing, but they go about it the long way around, with a lot of biochemical steps that take time. Now we’ve shown what the key targets are and that we can get at them rapidly,” said Zarate. “Ketamine probably can’t become the medication of choice, but this research is leading to some very real possibilities for a whole new generation of antidepressant medications.”


Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 30.854.150 von Ackergaul am 26.07.07 09:23:25

Danke an den NeuroInvestorzur Stellungnahme des unten geposteten Depressionsartikel. Zur besseren Anschaulichkeit füge ich unten das Cortex DIA von der Wechselwirkung mit Aricept bei.

The NIH piece has two interesting implications:
1) for depression, which I have paid much less attention to than schizophrenia (as did Organon). IF ketamine's action in depression is due to a subsequent increase in AMPA receptor activity, then an Ampakine might be a much safer route to doing so. It also implies that the effect is separate from neurogenesis, which some believe is the time-delayed route by which SSRIs have their effect on depression. It's separate, because it is fast, and neurogenesis takes a while.

2) for Alzheimer's. As we all know, patients on Namenda were excluded from the CX717 trial. While it was due to lack of preclinical combo data, there had always been an intuitive assumption that mixing a noncompetitive NMDA blocker (noncompetitive means it does not occupy the same space in the ion channel that glutamate does, which allows some normal glutamate activity to continue, probably the reason that Namenda is tolerated by patients, as opposed to competitive blockers like PCP and ketamine--the latter requiring great care in dosing) like Namenda would undermine the effect of Ampakines, whose effect on Ampa receptors includes increased opening of NMDA receptor controlled channels.

This implies that there is a feedback loop which causes Ampa activity to go up when NMDA activity goes down, and that this has a therapeutic downstream effect which I assume must be independent of NMDA gated channels. And perhaps this effect would be relevant to Alzheimer's as well as depression, and would allow CX717 to be effective in Alzheimer's even if given with Namenda. Since Namenda (along with Aricept) is the current regimen of choice in AD, this would greatly expand CX717's use in theory, since prescribers wouldnt have to choose between CX717 and Namenda. Whether there are other interactions, for better or for worse, between the two drugs, remains to be seen.

But--bottom line, it bodes well for Ampakines in both depression and Alzheimer's.

NeuroInvestment



Schönen Tag noch
Erbse

[Ackergaul]

Nur um des Formellen halber:
http://biz.yahoo.com/bw/070809/20070809005271.html?.v=1
Cortex hatte Halbjahres Zahlen gemeldet. Verlust wurde von 0,26 $ pro Aktie auf 17 Cent gesenkt. Dies begründet sich auf weniger Forschungsausgaben im CX717 Bereich. Wie bei vielen Biotechs, war es eigentlich ein Non-Event. Jedoch sollte dass Finanzielle noch beachtet werden, für die 6 Monate hat COR 6,7 Mil. $ ausgegeben. An Cash ist etwa 9 Mil. $ vorhanden. Alles andere als eine starke finanzielle Position. Eine Partnerschaft- / Lizenzmeldung wäre alleine aus diesem Grund erstrebenswert. Die einzige wichtige Meldung (wie schon vorher berichtet):
During the third quarter of 2007, the Company intends to file an Investigational New Drug Application for CX717 with the Division of Psychiatry Products of the FDA to allow Cortex to initiate a Phase IIb study with the compound as a treatment for Attention Deficit Hyperactivity Disorder. Prior to the FDA clinical hold on the compound, the Company announced positive statistical and clinical results with CX717 in a Phase IIa trial in adults with that indication.

Spätestens in 6-7 Wochen soll also das ADHD IND eingereicht werden. Unklar ist mir noch das Vorgehen der FDA bzw. der DPP. Wird die Freigabe der 1600 mg/day Dosis mit dem IND erteilt? Oder muss eine weitere Safety Studie absolviert werden? Ein fortführen der IIb Studie mit 2-mal täglich 200 mg wäre nutzlos oder soll etwa die zuletzt abgesegnete 1200 mg Dosis verwendet werden? Cortex hätte hierzu noch ruhig ein Wort verlieren dürfen...



Grüße

[Erbse1]

Hallo Cortex Freunde, es gibt jede Menge Abstrakte zu den Ampakinen. Ich erspare mir hier die Kopiererei, da vieles den Insidern schon bekannt ist, aber es gibt auch viel Neues. Zur Recherche kann man den folgenden link zum Neuroscience Meeting 2007 nutzen. Es ist wohl das weltweit größte Treffen seiner Art. Hier können auch alle anderen Abstrakte zu anderen Themen recherchiert werden.

Grüße
Erbse



http://www.abstractsonline.com/viewer/?mkey=%7BFF8B70E5%2DB7…

[Erbse1]

Ehre dem, dem Ehre gebührt.

Großer Artikel zu dem Cortex Pharmaceuticals Gründer Gary Lynch

Vierteilige Serie zu dem Thema Gedächtnis und Ampakine von der LA TIMES

TEXT: http://www.latimes.com/news/nationworld/nation/la-na-memoryf…

SICHERUNG TEXT: http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=118753500…

Wenns klappt gibt es Morgen die zweite Serie.

Grüße
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 31.222.249 von Erbse1 am 19.08.07 17:23:11

Zweiter Teil des Gary Lynch Artikel ist da.

Schönen Tag noch
Erbse

Gary Lynch's UC Irvine brain research lab struggles to map the elusive molecular underpinning of retention and recall.
By Terry McDermott : times staff writer, Second of four parts

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=118753500…

[Erbse1]

Teil drei und vier des Gary Lynch Artikels sind veröffentlicht.

TUESDAY: The lab begins an unparalleled run of success.

WEDNESDAY: The culmination. Can an actual memory inside the brain be seen?

LA TIMES: http://www.latimes.com/news/nationworld/nation/la-na-memoryf…

Sicherung: http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=118753500…

Schönen Tag noch
Erbse

[Erbse1]

Kapitalmaßnahme bei Cortex. Der Markt nimmt diese Meldung nicht gerade freundlich auf. Ich lasse mal alle Spekulationen und beobachte den weiteren Verlauf.

Cortex to Raise $14.2 Million in Registered Direct Offering
Quelle: http://biz.yahoo.com/bw/070824/20070824005265.html?.v=1

Schönes Wochenende noch
Erbse

[Coluche]

Antwort auf Beitrag Nr.: 31.286.135 von Erbse1 am 24.08.07 20:24:42

Hallo Erbse,

die Kapitalmarktmassnahme war absehbar, deswegen auch der Rückgang in den letzten WOchen auf das $2,5-Level, sie wurde in den US-Boards ja auch in den vergangenen Wochen ausführlich diskutiert.

Diese Reaktion ist für das Volumen völlig normal, wenn man die verwässerung bedenkt. Freilich für uns Aktionäre unschön, man hätte da auch jetzt erst einsteigen können.

Aber auf der anderen Seite muß man auch die Vorteile sehn. Cortex hat jetzt genügend Cash, um die nächsten zwei Jahre frei und ohne Druck agieren zu können. Das heißt, sie können sich in Ruhe ihre Partner aussuchen und stehen auf einer starken Verhandlungsposition.

Wenn man die Kapitalerhöhungen bei Allianz (2002) oder Alsthom ansieht, gabs da auch heftigste Kurseinbrüche. Aber der Kurs hat sich dann in den Folgejahren ver-x-facht.

Sehe die Sache in den nächsten Monaten sehr positiv. Man braucht halt bei diesem Investment einen langen Atem.

Viele Grüße

Coluche

[Ackergaul]

Antwort auf Beitrag Nr.: 31.289.403 von Coluche am 25.08.07 08:42:13

Es war nach den letzten Q-Zahlen klar, dass COR Cash benötigt. Aber das ist eine Verzweifelungstat 7,075 Mil. Aktien für 14,2 Mil. $ zu verkloppen (entspricht dann ja etwa 2,00 $ je Aktie = also Abschlag von 25 %). Den Schritt, zu diesem Zeitpunkt, verstehe ich einfach nicht.

Die FDA entscheidet noch über die Zulassung der höheren Dosis in ADHD. Dieser Markt ist etwa 1,5 Mrd. $ groß. Cortex CX717 scheint in der hohen Dosis genauso wirksam zu sein - aber wohl ohne die schädlichen Nebeneffekte - wie die Konkurrenz. Bestätigt die FDA dies (keine Nebenwirkung) UND gibt damit die 1600er Dosis frei, kann sich doch jeder ausrechnen, welcher Einfluss dies auf den Kurs hat!

Ergo: Warum (wenn man von CX717 überzeugt ist) nicht abwarten und den Kapitalschritt nach einer solchen Meldung durchführen? Warum?
Zudem stand eine mögliche Partnerschaftsmeldung für CX717 im Raum. Kommt so etwas zu Stande würden etwa 30 Mil. $ rüberfließen. Klingt für mich danach, dass keiner Interesse hat!

[Erbse1]

Hallo Ackergaul,
ich überlege auch mich von Cortex zu trennen und auf die watchlist zu setzen. Mit der Partnerschaft sehe ich das so ähnlich wie du. Ich denke mal, da wollten einige fürn Appel und Ei die Ampakine Technologie einlizensieren. Mir reichen da schon die jetzigen Partner Organon und Servier. 6 Jahre für eine Testphase 2b und immer noch keine Ergebnisse veröffentlicht. Das ist Verarschung von Cortex und der Aktionäre. Dann steht in einem Jahr die nächste Kapitalmaßnahme an. Das kann man sich gut von der Seitenlinie aus betrachten. Da stehen noch ca. 20 Millionen Warrents aus, der Kurs wird nicht mehr so schnell davonlaufen. Es ist im Augenblick sehr schwer an Geld zu kommen, aber ein Abschlag von 25% ist schon sehr heftig, zumal der Kurs vorher schon mächtig gedrückt wurde.

Es gibt wohl bald eine Konferenz mit der weiteren Entwicklung von Cortex vom CEO Stoll. Da bin ich sehr gespannt drauf.
Grüße
Erbse

[Erbse1]

Hallo coluche,
habe deinen Beitrag gerade erst gelesen. Cortex ist in der Tat für sehr langfristig eingestellte Gemüter. Ich halte Cortex jetzt schon über 6 Jahre. Doch da gibt es bessere Alternativen mit einer dicken Pipeline und genügend cash. Leider ist es so.
Ganz trennen von Cortex werde ich mich aber wohl nicht. Dafür ist die Aktie viel zu spannend.
Liebe Grüße
Erbse

[Erbse1]

Kommentar des Börsenbriefes NeuroInvestor zur Kapitalmaßnahme. Selbst hier kommt so langsam so etwas wie Kritik auf.

Cortex

(Financing deal 8/25/07)

I looked back over the past six months of financings for US traded, neuro-oriented companies without any products on the market--the best comparator group, and the only one I know.

Acadia Pharmaceuticals: (4/07) Sold 5.8 million shares at 15.50: the price was 15.02 when they announced the offering. So it was priced at market, which actually increased. No warrants. They sold after good ACP-103 news.

Corcept: (August 07): Sold 4.8 million shares at 2.10. The high on the previous trading day was 2.55, closed at 2.34. Thus the discount compared to the close was 10%. No warrants.

Curis (Aug 07): Sold 12.2 million shares and warrant units at 1.06/share, just above the previous day close of 1.03. So there were warrants, but no discount.

Memory Pharma (June 07): 694K shares sold to Stanley Medical Research at a 17% Premium to the 10 day average. No warrants.

Alseres: (Mar 07) Borrowed $15 million (debt has its own special risks) at 5% annual interest, convertible at 2.50 per share. Closing price previous day was 2.14.

Titan: (Mar 07) $25 million equity line of credit, shares to be sold at a 4-7% discount. No warrants.

Amarin (June 07): Sold 6.16 million shares at market price of May 31, plus warrants. Additional shares can be sold at 4% discount.

Bottom Line: No one gave a discount anywhere near the 25% Cortex did. 10% was the next worst, and that had no warrants attached. Warrants were used in a minority of cases, all of which involved much better pricing for the shares sold. Roger Stoll performed very well in handling the clinical hold issue, which was central to the survival of the company. But this financing should not have happened under these terms. The BOD should not have approved it. Roger needs better financial counsel--and better institutional investors. The lunatic fringe is calling this a 'scam.' No, that's ridiculous--but it is a painful mistake. Until the IND is filed AND accepted, the Market will understandably wonder whether this was a statement of diminished confidence in the IND's prospects at Psychiatry.

Schönen Sonntag noch
Erbse

[Erbse1]

Zwei Meldungen von Cortex

Cortex's CEO Roger Stoll to Speak at the Roth Capital Partners New York Conference on September 5, 2007

Kleiner Ausschnitt zu den jetzigen Wirkstofkandidaten von COR

>>>Dr. Stoll will also discuss recent new developments obtained from the University of Alberta in animal studies which demonstrate that both High and Low impact AMPAKINE® drugs are effective in overcoming the respiratory depression caused by opiate analgesic compounds. The potential for both acute and chronic applications of AMPAKINE drugs for the treatment of respiratory depression disorders may be realized due to these findings. The Company is currently assessing both CX717 and CX701 for rapidly moving forward with clinical trials for acute applications in respiratory depression.

Dr. Stoll will also provide an update on other clinical developments and strategies. Cortex plans to file an Investigational New Drug ("IND") application with the Psychiatric Drug Products Division of the FDA for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults in early September 2007. Also, as a result of the completion of the recently announced financing of Cortex, the Company anticipates developing both CX701 and CX1763 as clinical drug candidates. Cortex expects to file an IND for CX701 during the fourth quarter of 2007 and CX1763 is undergoing IND-enabling studies as well. Therefore, the Company is planning to have three AMPAKINE compounds in clinical development by mid-2008. Dr. Roger Stoll, the Chief Executive Officer and Chairman of Cortex stated that "having multiple compounds in our drug development pipeline has been a major objective for Cortex and with the recent financing we have the financial means to work toward a realization of those objectives for our Company during 2008. A more robust development pipeline will improve the chances for achieving clinical success.">>>

Quelle: http://biz.yahoo.com/bw/070830/20070830005441.html?.v=1

Zweite Meldung:
Cortex Completes $14.2 Million Registered Direct Offering

Quelle: http://biz.yahoo.com/bw/070830/20070830005439.html?.v=1

Schönen Tag noch
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 31.343.301 von Erbse1 am 30.08.07 15:50:06

Moin,

mir sieht es ein wenig danach aus, dass Cortex mittlerweile mehr auf die Karte CX701 als CX717 setzt. Ob Cortex irgendeine Sackgasse zu CX717 gesehen hat oder CX701 als überlegen ansieht? Mich würde vorerst beruhigen, wenn dass IND zum Phase IIb ADHD Trial beantragt wird. Sollte doch innerhalb September noch gelingen...

Eine Partnerschaftsmeldung sehe ich aktuell nicht, da der "Finanzschritt" ansonsten nicht gemacht wäre. Muss nicht am fehlenden Interesse gelegen haben, kann auch auf simple Dingen beruhen (z.B. der angebotene Preis für CX717 war Cortex zu gering).


Grüße

[Erbse1]

Hallo Ackergaul,
genau das ist ein Cortex Problem. Sie sind personell einfach unterbesetzt, um sinnvoll zu arbeiten. Es ist doch die Regel, daß Substanzen irgendwann auch scheitern können. Doch Cortex kann nicht zeitgleich genug Substanzen nachliefern, um die Pipeline zu füllen.
Ich beobachte Cortex jetzt über 6 Jahre und sie haben es bisher nicht geschafft eine Phase2b erfolgreich abzuschließen. Das liegt daran, daß nicht parallel die Substanzen entwickelt wurden. Sondern eben nur eine nach der anderen. So wird man dann irgendwann zum Spielball der Kapitalgeber.

Auch Org 24448 halte ich für gescheitert, bzw. gibt es mittlerweile einige Konkurrenzprodukte, die weiter in der Entwicklung sind. Sonst wäre bestimmt schon eine Meldung veröffentlicht worden.
Da laufen reihenweise die Patente ab.

Bin wirklich auf die Konferenz gespannt, da hören wir mehr zu den einzelnen Substanzen und Anwendungsgebieten.

CX717 müssen wir abwarten, sonst habe ich die gleiche Einschätzung wie du auch.

Schönes Wochenende noch
Erbse

[Ackergaul]

http://www.zangani.com/node/922
Orphan Neurological Diseases
Wed, 09/05/2007 - 14:21 — Zangani

Executive Summary
An orphan disease is defined in the US as a condition that affects fewer than 200,000 people nationwide. This includes diseases as familiar as cystic fibrosis, Lou Gehrig's disease, and Tourette's syndrome, and as unfamiliar as Hamburger disease, Job syndrome, and acromegaly, or "gigantism." Some diseases have patient populations of <100 subjects. Collectively, however, these diseases affect as many as 25 million Americans, according to the National Institutes of Health (NIH), and that makes them a serious public health concern.

New rare diseases are discovered every year. Most are inherited and caused by genetic mutations. Others can be acquired as a result of environmental and toxic conditions. As disparate as these disorders are, patients share many common frustrations. For example, 30% of people with a rare disease must wait up to 5 years to get an accurate diagnosis. Patients often must travel long distances to visit the few doctors knowledgeable about their illnesses, and the costs involved with diagnosis, treatment, and other related expenses can be exorbitant.

Before the passage of rare disease laws in the US, patients diagnosed with a rare disease were denied access to effective medicines because prescription drug manufacturers rarely could make a profit from marketing drugs to such small groups. Consequently, the prescription drug industry did not adequately fund research for orphan product development. Other potential sources, such as research hospitals and universities, also lacked the capital and business expertise to develop treatments for small patient groups. Despite the urgent health need for these medicines, they came to be known as orphans because companies were not interested in adopting them. This changed in 1983 when Congress passed the Orphan Drug Act (ODA). The ODA created financial incentives for drug and biologics manufacturers, including tax credits for costs of clinical research, government grant funding, assistance for clinical research, and a seven-year period of exclusive marketing given to the first sponsor of an orphan-designated product who obtains market approval from the FDA for that indication. Concomitantly, federal programs at the FDA and the NIH began encouraging product development, as well as clinical research for products targeting rare diseases. Thus far, the FDA has approved nearly 300 orphan drugs.

Europe has not been far behind. Within the last five years, 450 applications for orphan designation status (drugs for the treatment of rare diseases) have been submitted in the EU; 270 are currently being evaluated by the European Agency for the Evaluation of Medicinal Products (EMEA). 22 new orphan medicines for the treatment of life-threatening diseases have already received marketing authorization. Already, more than a million patients are estimated to have derived benefit from the 22 new orphan medicines.

We believe the total market for orphan drugs in 2006 reached ~$40 billion and could exceed $70 billion by 2010. In this sector, the current market for drugs aimed at treating orphan neurological indications could be as large as $7 billion. Given the projected increase in focus on niche disorders as the blockbuster business model wanes, we estimate that the total market for orphan drugs targeting neurological indications could exceed $15 billion by 2010. In the near-term, we expect the areas of narcolepsy, amyotrophic lateral sclerosis (ALS) and peripheral neuropathy to receive the greatest attention. We expect companies concentrating on targeting the pathological mechanisms underlying neurodegeneration in various disorders to record the greatest success. Among these firms, we believe that Cortex Pharmaceuticals (COR, Market Outperform), CytRx Corporation (CYTR, Market Perform) and Medivation (MDVN, Market Perform) are likely to become key players. Their platforms aim to increase cerebral arousal, reduce protein misfolding and attenuate mitochondrial dysfunction respectively, all of which are crucial aspects that impact neurological decline in a wide array of nervous system disorders. The orphan neurology therapeutic market could evolve to encompass approximately 20% of the total orphan drug market, with a wide range of smaller firms becoming involved. We believe that this market represents the best opportunity for emerging neurology-focused companies that have innovative insights into the molecular basis of rare neurological diseases. The opportunity could be lucrative, given the past history of orphan drugs and the proven richness of such products, with examples such as Cerezyme in Gaucher’s disease marketed by Genzyme (GENZ, Market Perform) attaining blockbuster status.

Cortex’s CX717, CytRx’s arimoclomol, and Medivation’s Dimebon? all represent novel agents with different mechanisms of action that are being developed to treat niche CNS disorders. These candidates could be the first new drugs to be approved in the near-term; as the harbingers of a new paradigm in CNS disease therapy, they could herald a new generation of therapeutics with a focus on rare diseases, which target the pathological mechanisms underlying such disorders at the cellular and molecular level. Promising privately held companies are also likely to achieve successes in the niche CNS disease sector. Private firms such as Antipodean Pharmaceuticals, EnVivo Pharmaceuticals, Faust Pharmaceuticals, Hunter-Fleming, and Trophos are all developing therapeutics for little-known diseases such as Friedreich’s ataxia, muscular dystrophy and ALS. These companies will likely generate significant interest, should their unique approaches towards the rare neurological diseases prove effective, and will bear watching.




Key Points
Orphan neurological diseases collectively represent a significant unmet medical need
Worldwide, orphan diseases currently afflict nearly 60 million people
Rare neurological disorders comprise nearly 20 million of the above, in our view
The current therapeutics market for orphan disorders exceeds $40 billion
We estimate that therapies for rare neurological diseases could represent a $7 billion market currently, rowing to over $15 billion by 2010
Rare neurological disorders are still underserved in terms of drug development
As the traditional ‘blockbuster’ drug development model loses steam, the ‘nichebreaker’ model will gain in prominence
Orphan-designated drug candidates have an approximately 20% average probability of approval, compared to the overall probability of only 10% for all drug candidates
Nearly 300 orphan drugs have been approved since the 1983 advent of the Orphan Drug Act
In the quarter-century since the Orphan Drug Act came into being, nearly twice as many orphan drugs as non-orphan drugs have been approved
On average, orphan drugs are approved 40% faster than non-orphan drugs
In this report, we discuss the current landscape of orphan drug legislation, the rare neurological diseases and highlight companies with drugs in advanced development
Finally, we examine in detail the firms with novel experimental drugs that address disease-specific pathways
In this report, we take a close look at who the winners could be . . . and highlight our "magic 20" - 10 publicly held firms and 10 private companies - to keep an eye on


http://www.zangani.com/files/2007-0905-orphan-diseases.pdf

[Ackergaul]

Antwort auf Beitrag Nr.: 31.479.051 von Ackergaul am 09.09.07 09:33:54

Bin mir nicht über den Wahrheitsgehalt der Meldung sicher, poste es trotzdem - also VORSICHT!:

http://www.mikehav.com/blog.html
Cortex Files CX-717 IND for Phase2b ADHD Study



-clock starts today for FDA's Psych Division standard 30-day review period of this key IND which will allow Cortex to pursue Phase 2b trial in over 300 patients at 20 US sites

-opens the way for partnership talks for huge market in ADHD for CX717 as a safer, non-stimulant treatment option with proven efficacy at 800 mg twice daily in Phase 2a trial

-FDA's Neuro Division has already cleared CX717 up to 600 mg twice daily in Alzheimer's study based on extensive tox studies which proved safety of CX717


Per SEC-Mitteilung und auf der Homepage ist davon nichts zu finden. Vielleicht kommt heute noch Licht ins Dunkle. Wäre zumindest ein Schritt vorwärts, den zweiten muss die FDA machn um die 1600er Dosis freizugeben!


Grüße

[Ackergaul]

Antwort auf Beitrag Nr.: 31.520.307 von Ackergaul am 11.09.07 08:26:45

also doch dass IND... Nun noch die Freigabe der 2 x 800er Dosis und vieles sieht gleich viel besser aus!
http://home.businesswire.com/portal/site/google/index.jsp?nd…
Cortex Files AMPAKINE CX717 IND for ADHD
— CX717 Blocks Fentanyl-induced Respiratory Depression Without Blocking Analgesic Effects —

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR) Chairman, President and CEO, Roger G. Stoll, Ph.D., announced at the Bear Stearns 20th Annual Healthcare Conference held in New York City that the Company has submitted the AMPAKINE® CX717 Investigational New Drug (“IND”) Application for the treatment of Attention Deficit Hyperactivity Disorder (“ADHD”) with the Division of Psychiatry Products of the Food and Drug Administration (“FDA”). Dr. Stoll mentioned that filing the IND was a high priority for both the Company and for patients with this affliction given the promising data generated last year in a small Phase IIa pilot study in this population. That study showed statistical significance for changes in the ADHD rating scale for CX717 without the cardiovascular and other side effects seen with the current stimulant-based treatments.

At the same conference, Dr. Stoll reported that in research recently conducted by Dr. John Greer at the University of Alberta, CX717 has demonstrated the ability of AMPAKINE drugs to block the risk of fatal overdose with the schedule II opioid, fentanyl, in rats due to respiratory depression, without inhibiting fentanyl’s analgesic effect. Dr. Stoll also announced that the Province of Alberta has just granted Dr. Greer an Advanced Education and Technology award of $322,800 in support of further research into the prevention and treatment of respiratory depression with AMPAKINE drugs, matching a similar amount funded by Cortex. The Company is planning to initiate the first study in this indication in humans early next year.

Dr. Stoll also discussed recent results in animal studies, where Low Impact AMPAKINE CX717 and High Impact AMPAKINE CX614 were found effective in overcoming the respiratory depression caused by fentanyl. The potential for both acute and chronic applications of AMPAKINE drugs for the treatment of respiratory depression disorders may be realized due to these animal findings.

With the recently announced financing, Cortex will be working to develop additional AMPAKINE clinical drug candidates. An IND for CX701 is anticipated to be filed during the fourth quarter of 2007, and CX1763 is undergoing IND-enabling studies as well. Therefore, Cortex is planning to have three AMPAKINE compounds in clinical development by mid-2008.

A replay of the presentation can be accessed by logging onto http://cc.talkpoint.com/BEAR002/091007a_sc/?entity=cortex and will be available for 30 days following the conference.

[Erbse1]

Weiterer Kommentar des NeuroInvestor zur letzten Konferenz.

Schönen Tag noch
Erbse

A major focus of the CC was the emerging possibility of low-impact Ampakines as adjuncts in opioid analgesia, preventing and/or ameliorating respiratory depression. It is an acute-care context which has a lot of appeal from a clinical development point of view--quicker, objective endpoints. The question is whether a single company will take on both ADHD and RD with a CX717 deal--one can see Cephalon, JNJ, Shire, Novartis, as companies with dual agendas therein. If CX717 were partnered away for ADHD but not RD, this might be the only context wherein the disgraced CX516 might have the opportunity of making a comeback. CX516 has lousy potency--at least as an oral drug--and a short half-life. The unanswered question is--if administered along with or following an opioid via injection/infusion, skipping the GI absorption barrier, does it have enough BBB penetration? There is lots of human data--600 or 700 humans have taken CX516, and some for extended periods, certainly enough to make a single infusion seem like a probably safe thing. The unknown is whether administering a fairly large bolus IV, for example, might be irritating to the vasculature, or involve some other side effect issue you wouldn't see with oral dosing. CX516 actually has a time advantage even over CX717, because of the extensive human testing database--and if Cortex does indeed partner CX717 (and perhaps CX701) I think CX516 might--might--be a backup option.Hopefully, Cortex will run a few rodents through an IV CX516 study just to see if they can get likely necessary levels and with acceptable side effects.

Two other Respiratory Depression points:

1) When thinking about risk, one risk is that a nonopioid analgesic (say a VR-1 or N-type CA channel blocker) is developed that has equal analgesic power. Nothing is beyond PhI at this point, but if that were to occur, the need for an RD therapeutic would likely vanish, neither of those approaches are thought to lead to RD (though it is still early). This argues against Cortex trying to take it all the way through, you don't want them holding an anachronism at the end.
2) On the other hand: Look at what New River accomplished with Vyvanse. It's not abuse-proof, but it is safer, with a lower risk of OD. Though it has a higher rate of side effects. Yet the prospect of this emerging as a competitor to Adderall XR so freaked out Shire that they paid $2.4 billion for NR (which also included an opioid). Far more than it deserved, but Shire was trying to protect its turf against a potentially safer competitor. Now--the corollary situation would be Cephalon. They are trying to protect their fentanyl franchise, Actiq being replaced by Fentora. If a competitor came up with an RD-proof fentanyl combo (and fentanyl itself is generic), that would pose the same threat to Cephalon and Fentora as Vyvanse did to Shire's Adderall. Now, Cephalon is not as dependent on Fentora as Shire is on Adderall XR, but still--they can't afford to have a clearly safer competitor come up against their fentanyl franchise. Hmmmm.

[Ackergaul]

Der Ausblick von Mike Havrilla:

Cortex (AMEX: COR) Near-Term Outlook
I think Cortex will start moving up again around Oct 10/11, assuming the IND is accepted to begin the Phase 2b trial in ADHD for CX717, which I give a 90% likelihood given Neurology's decision to allow resumption of all doses in the AD trial (up to 1200 mg). The new data on RD is a positive development as it replaces the need for in-licensing while providing an entire new set of indications for the company's own AMPAKINES. Beyond this CX701 should receive IND approval to begin Phase 1 trials & hopefully a partnership for CX717 in ADHD will occur in 1Q08 with a $50M upfront payment. I believe COR should trade back over $3 with IND approval & potential R&R upgrade and could see $6 within the next 6 months with a solid ADHD deal.

[Erbse1]

Update Pipeline 23. September 2007

[Erbse1]

Von der letzten Konferenz eine Zusammenfassung von gfp927z. Jetzt heißt es warten auf die Entscheidung.

1) Cash level - Near $21 mil at end of August.

2) IND for CX-717/ADHD Phase 2b was filed Sept 10th. FDA decision on the IND by approx Oct 10th.

3) ADHD Phase 2b is designed for approx 300 patients, and 20 clinical sites.

4) Cortex is in the process of hiring a permanent Chief Medical Officer to help with future clinical trials, protocols, etc.

5) CX-701 - IND for Phase 1 in Q4-07. The compound could target AD, EDS, or RD indications. CX-701 is more potent than CX-717, and has roughly twice the halflife in animals.

6) Respiratory Depression indication - Plans are underway for a pilot Phase 2a with CX-717 to start in early 2008. Cortex is talking to a clinical site in Europe to run the trial. Will likely involve Resp Dep from Fentanyl. The dosing period is only several days so the trial is quick and designed to give proof of concept. Other potential Resp Dep related indications include sleep apneas, resp dep associated with Retts, respiratory recovery from patients on ventilators, breathing problems associated with various neurodegenerative diseases like ALS, Parkinson's, spinal cord injury, and congenital hypoventilation syndrome.

7) The Alberta study indicated that both high and low impacts are effective in Respiratory Depression.

8) Dr. Stoll considers Respiratory Depression to be one of the most important opportunities to come along for Ampakines since he's been CEO. The acute nature of many of these RD conditions means a much shorter drug development timeline - he estimates a potential 3-4 year timeframe to file for FDA approval, which is much quicker than for chronic indications.

9) High Impact collaboration - most BPs also want CX-717, so these might ultimately be partnered with the same BP.

10) CX-717 Outlicensing interest - 5 or 6 companies interested, and term sheets are being put together. IND Phase 2b approval by Psychiatric will be critical in doing an optimum deal. Likely timeline to consumate deal - by end of Q1-08, or possibly sooner.

11) Studies indicate that CX-717 and Memantine/Namenda don't interact significantly, so AD patients on the Aricept/Namenda combo regimen will be allowed into the AD PET scan trial. This should help speed up enrollment considerably.

12) Patent related - There is some type of pending action that's going to occur in Jan 2008 involving the Lilly/Glaxo use patent challenge in Europe. Cortex is getting materials ready for that time. Either way the decision goes there will probably be appeals which could last several more years. On the comp of matter patent front, Cortex filed 2 high impact patents and 1 low impact patent this year, which when approved will extend patent life to 2027. The CX-717 comp of matter patent currently goes to approx 2017, plus an additional ~1.5 years beyond that.

13) Buyout/merger - Dr. Stoll wouldn't necessarily be averse to the idea if it was a good deal for Cortex.

14) Schering - CEO Hassan appears to want a presence in Psychiatric indications, so once the Organon buyout related activities are completed, Schering might possibly have some interest in partnering CX-717, along with the 5 or 6 other interested pharmas.

[Erbse1]

Kleiner Abstrakt zu den Ampakinen im Rett Syndrom

Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome.
Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM.
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

Rett syndrome (RTT) is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Although MeCP2 is thought to act as a transcriptional repressor of brain-derived neurotrophic factor (BDNF), Mecp2 null mice, which develop an RTT-like phenotype, exhibit progressive deficits in BDNF expression. These deficits are particularly significant in the brainstem and nodose cranial sensory ganglia (NGs), structures critical for cardiorespiratory homeostasis, and may be linked to the severe respiratory abnormalities characteristic of RTT. Therefore, the present study used Mecp2 null mice to further define the role of MeCP2 in regulation of BDNF expression and neural function, focusing on NG neurons and respiratory control.

We find that mutant neurons express significantly lower levels of BDNF than wild-type cells in vitro, as in vivo, under both depolarizing and nondepolarizing conditions. However, BDNF levels in mutant NG cells can be increased by chronic depolarization in vitro or by treatment of Mecp2 null mice with CX546, an ampakine drug that facilitates activation of glutamatergic AMPA receptors. Ampakine-treated Mecp2 null mice also exhibit marked functional improvement, characterized by restoration of normal breathing frequency and minute volume. These data demonstrate that BDNF expression remains plastic in Mecp2 null mice and raise the possibility that ampakine compounds could be of therapeutic value in the treatment of RTT.

[Ackergaul]

soviel Neues von Mike Havrilla. Ich denke, er sieht vieles zu "rosarot". Wenn es so stimmt, dass CX717 (bei ADHD) "nur" mit einer 1200er (nicht 1800) Dosis gestartet wird, ist dies sicher nicht positiv. Auch wenn die FDA hier leichter zustimmen wird!

Cortex Closes in on Key FDA Decision for CX717 IND

I think Cortex Pharma (AMEX: COR) will start moving up again by the end of this week or early next week at the latest, depending on the exact timing of FDA notification for the likely acceptance of the Company's IND to begin a Phase 2b trial in ADHD for CX717, which I give a 90% likelihood given FDA Neurology's decision to allow resumption of all doses in the AD trial (up to 1200 mg). Given the Neurology decision, Cortex should at least get the go-ahead for a 1200 mg dose, which is close enough to the 1600 mg dose that produced excellent results as a safe, non-stimulant treatment in a Phase 2a ADHD study in early 2006 and sent the stock up to around $6 per share.

Also, new data on potential to reverse opiate-induced respiratory depression (RD) without affecting pain relief is a positive development as it replaces the need for in-licensing while providing an entire new set of indications for the company's own AMPAKINES. Beyond this CX701 should receive IND approval to begin Phase 1 trials during 4Q07 & hopefully a partnership for CX717 in ADHD will occur in early 2008 with a $50M upfront payment.

Please view or download my free 8 page PDF stock report for Cortex:
http://www.mikehav.com/cor.pdf
BUY rating with EOY07 Price Range Target of $3- $4 and 9-12 month price range of $4 - $6

Also check out this Business Week Online article on CX717 & Cortex at the time of the Phase 2a results in early 2006 which compares the potential of CX717 to Strattera which recorded over $500 million in sales in 2005 as a non-stimulant option for ADHD, but carries warnings on its label for the potential of liver damage & suicidal thoughts.

[Ackergaul]

HARTER SCHLAG!

Cortex Pharma Says FDA Rejects Its Request To Study CX717 In Phase IIb ADHD Study - Quick FactsThursday, October 11, 2007; Posted: 08:55 AM

COR: Reject's Cortex's Request to Study CX717 to Phase IIb ADHD Study

*Cortex Pharma Says FDA's Psychiatric Division Rejects Company's Request To Study CX717 In Phase IIb ADHD Study

FDA's Psychiatric Division Has Rejected Cortex's Request to Study CX717 in Phase IIb ADHD Study

(RTTNews) - Cortex Pharmaceuticals Inc. (COR | charts | news | PowerRating) on Thursday said it was notified by the U.S. Food and Drug Administration on rejection of the company's Investigational New Drug Application for a Phase IIb study of CX717 in attention deficit hyperactivity disorder or ADHD.
The agency added that the denial is based on results of animal toxicology studies filed by the company. As a result, the company has requested that the Division of Psychiatry Products or DPP of the FDA inactivate its IND Application for ADHD. The company would be receiving the agency's formal notice on rejection of Investigational New Drug Application for a Phase IIb study of CX717.

The company said it intends to continue its plans to develop CX717 for the acute treatment of respiratory depression or RD and continue its study of CX717 in its Alzheimer's disease PET scan study.

[Erbse1]

Kurzer Kommentar des NeuroInvestor. Das dauert jetzt wieder seine Zeit, bis Cortex wieder aufgestellt ist. Das wird noch ganz schön bitter bei den nächsten Finanzierungsrunden.
Liebe Grüße
Erbse

The ADHD indication which had looked so promising for CX717, is dead. Psychiatry apparently made it clear that they would not consider opening themselves up to criticism from higher powers (e.g. Charles Grassley) for allowing clinical trials in ADHD with a drug where any safety questions had been raised--even if now answered in the negative. ADHD has effective albeit imperfect (safety problems) therapies already available. Ironically, neither Adderall, Ritalin, or Strattera would be allowed into the clinic today, given the contemporary climate of avoiding any risk of criticism. CX717 is still highly viable for the Respiratory Depression indication, and Cortex needs to accelerate European trials ASAP in order to establish human POC. CX701 will probably be the compound of choice for chronic disorders, though we would not bother with ADHD with another Ampakines for the time (years) being.
With the worst outcome having occurred with Psychiatry, the recent financing that we criticized quite strongly turns out to have been wise insurance. Without it, Cortex would not have been able to enter RD Phase II with CX717. With the money on hand, they can. Obviously, this scuttles all discussion of a major BP deal. The next opportunity for a partnership could come during 2H:08, when they have human POC data for Respiratory Depression. If it works as it did in animals, companies with heavy reliance upon opioid analgesics for revenue will be very interested.

[Erbse1]

Cortex Falls As FDA Rejects CX717 Phase IIb In ADHD

By Trista Morrison

Staff Writer

Shares of Cortex Pharmaceuticals Inc. plunged 59 percent after the FDA rejected a proposal for a Phase IIb trial of lead ampakine compound CX717 in attention deficit hyperactivity disorder.

"I think this could have grave consequences for Cortex, not because I don't believe in ampakines, but because the company may not be able to finance in the future," Rodman & Renshaw analyst Elemer Piros told BioWorld Today.

After hitting new 52-week lows, Cortex's shares (AMEX:COR) closed at 73 cents on Thursday, a loss of $1.07. The Irvine, Calif.-based company reported $8.7 million in cash and marketable securities as of June 30 and raised $14.2 million in a registered direct offering in August, but Piros said he doesn't expect any robust new clinical data between now and when that money will run out in about a year. He downgraded the stock to "underperform."

The FDA's rejection was based on results of animal toxicology studies that have long plagued the CX717 program. Toxicology concerns resulted in a clinical hold on the program last year, which was lifted by the FDA's Division of Neurology Products so Cortex could begin a trial in Alzheimer's disease. (See BioWorld Today, April 4, 2006, and Oct. 30, 2006.)

But the Division of Psychiatry Products, which oversees ADHD trials, proved harder to convince. Cortex submitted data indicating the animal toxicity issues were due to post-mortem tissue processing and showing that CX717 was well-tolerated in a previous Phase IIa ADHD trial, but the agency refused to approve the Phase IIb plan.

Cortex President and CEO Roger Stoll said the company is "unlikely" to try again with CX717 in ADHD, but that the Alzheimer's trial is moving forward and should be completed in mid-2008. The trial uses a dose that is five- to tenfold less than that required for ADHD, but Piros noted that the efficacy of such a low dose has not yet been proven in humans.

Stoll said Cortex also is planning initial European clinical trials to evaluate CX717 in the acute treatment of respiratory depression, which would use short-term rather than chronic dosing.

A backup compound known as CX701, which is more potent and has a longer half-life, is slated to begin European clinical trials this quarter. And CX1763, which has a mechanism conducive to use in neurodegenerative diseases such as Parkinson's disease and Huntington's disease, is scheduled to move into preclinical toxicology studies early next year.

Cortex's clinical data thus far have been mixed. Although CX717 has had toxicity issues, the Phase IIa ADHD trial showed that a high dose caused a positive trend in the ADHD Rating Scale and a statistically significant effect on the hyperactivity subscale compared to placebo (p=0.05). A subsequent trial of CX717 in alertness during night shift work didn't enhance cognitive performance but altered recovery sleep architecture.

A previous compound known as CX516 failed to meet its primary endpoint in a Phase IIb cognitive impairment trial. But Piros called the compound "silly" due to the fact that it required memory-impaired patients to take large doses four times daily, and he said Stoll was right to kill the program. (See BioWorld Today, Feb. 18, 2004.)

Piros said he is "still a fan" of the ampakine approach. Ampakines target AMPA receptors, a subtype of glutamate receptors involved in the long-term potentiation underlying memory and the excitatory stimulation that often is reduced in cognitive disorders. In a research note, Piros pointed out that Merck and Co. Inc.'s head of neuroscience research, Dennis Choi, told Fortune magazine that ampakines are one of the most promising approaches for memory enhancement.

Cortex's biggest problem, Piros said, has been its financial restrictions, which have forced programs to move forward in a linear fashion and never allowed "multiple shots on goal." He predicted that a partnership is unlikely at this stage, but he encouraged Cortex's management to "consider the sale of the company to a larger organization" that could fully exploit the technology.

Cortex has significant intellectual property covering AMPA modulation and has a partnership with NV Organon for schizophrenia and depression. French firm Les Laboratoires Servier has an option to license up to three neurodegenerative disease compounds from a partnership with Cortex that ended in late 2006.

For now, Stoll said his team is focused on trying to "define the best way to build Cortex." But he added that if an acquisition offer comes along, "we have to look at it."

[Erbse1]

Kommentar des NeuroInvestor zu COR

(from NI November, added 11/2/07)

Cortex was stunned, and its share price slashed by over 60%, when the FDA's Psychiatry Division rejected its IND for CX717 in ADHD. The FDA has yet to provide a written explanation, and all indications are that this is a politicaly-motivated decision--avoiding any risk of criticism, not scientifically-based. While Cortex is still trying to meet with Psychiatry to see if any headway can be made, they are now developing their European trial plans for Respiratory Depression using CX717, and preparing the IND for CX701. They hired a Lilly and XenoPort veteran to be their CMO, which indicates that they are not in retreat-mode. It also appears that Rodman & Renshaw is punishing Cortex for not using them as the main placement agent for the last financing: R&R revised its target to 30 cents (!) and is demanding that the company be sold (so that they can receive a broker commission). R&R's math contradicted itself in the telling, which is why we believe that this is punitive.

Weiterer Kommentar:

<<<But the epitome of the FDA's abject surrender to timidity was their rejection of Cortex's application to run a Phase II trial in ADHD with CX717. This is a drug which had recently been cleared by the Neurology section of the FDA for further clinical trials, since it had turned out that the anomalous cellular changes previously seen were post-mortem artifacts, in response to fixative. Good enough for Neurology, but not for Psychiatry, which flat-turned down Cortex's IND. Here is what appears to have happened: Given that ADHD is already treated by effective but highly flawed amphetamines and their relatives, the FDA simply did not want to deal with any possibility that some day, they might be criticized for allowing CX717 to be in a trial. Never mind that no actual toxicity has been found in humans or animals, and that the FDA could have overseen Phase II with whatever rigor they chose. Instead, they simply blew away CX717 as an ADHD candidate without checking to see if it has clinical utility or not. This safeguards marketshare for the established ADHD drugs, which have their own notable side effect and abuse issues. Like Blackwater, the FDA operates without any clear line of control by higher authority--save for Congress, which has a one-dimensional appreciation of the drug development issue. Companies considering bringing new chemical entities/mechanisms to the Psychiatry Division in the treatment of disorders with relatively useful current alternatives--like depression--should keep in mind that Psychiatry currently operates by this motto: 'The only good NCE is a dead NCE.>>>

Schönes Wochenende
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 32.260.601 von Erbse1 am 02.11.07 19:04:11

Kleine Zusammenfassung des NeuroInvestor zu den Zukunftsaussichten

Frankly, the only element that really perturbs me is the fact that R&R is not only not being supportive of their banking client, they give every indication of wanting to sabotage them.

Other than that--I am not sure I have ever, in 12 years, seen such a mispricing of a stock. The enterprise value, as you note, is--let's say somewhere between $5 and 8 million. Neurochem, whose anti-amyloid program has now failed in Phase III for two indications, has an enterprise value of $70+ million. Amarin, whose purified fish oil Miraxion failed in Huntington's, has an enterprise value of $12 million or so. If one looks at Cortex anew, you would see the following as of January 2008:

1) CX717 in Phase IIa for Respiratory Depression in Europe
2) CX717 in Phase IIa for Alzheimer's in the US
3) CX701 in Phase I in EU: ADHD, AD, EDS all potential targets
4) lead neurotrophic compound in preclinical stage, anticipating the clinic by year-end: potential disease modification for Alzheimer's, Parkinson's, Huntington's, Fragile X, possible neuroprotection in stroke/TBI
5) Cash for about 14 months
6) Better molecules than Schering-Plough has for the schizophrenia and depression indications, making a partnership possible
7) Use patents for Ampakines in most major indications other than what SP has, and Cortex will receive double digit royalties for sz and depression

That doesn't look like $5-8 million enterprise value to me. Neurogen might be the best comparator, and even with their stock having dove more than 50%, they still have an enterprise value of around $90+ million.

The wild card for nearterm valuation, as I have said before, is Schering-Plough. Once the Organon deal is completed at the end of the year, they may start being clearer about their intentions, and it would not be hard to see Cortex/Ampakines/sz+depression being included or implied.

NeuroInvestment

[Erbse1]

Heute war Konferenz. In aller Kürze die Milestones für die nächste Zeit.

[Coluche]

Nun ja, zumindest nach € hat Cortex das Ziel von R+R erreicht, wobei ich dieses Kursziel eine absolute Frechheit finde. Ähnlich dem, als die Deutsche Bank vor ca. 3 Jahren nach der KE von Alsthom(Kurs € 0,3) ein Kursziel von € 0,16 angegeben hat (3 Jahre später € 150 bzw. nach Split ca. € 4 - also mehr als verzehnfacht!).

Freilich ist die Lage bei Cortex nicht sehr rosig, aber bei der Bewertung, dem Potenzial, den Patenten und den Aussichten (bei genügend Cash) muß man nun eben ein paar mal tief durchatmen nach dem Motto von Dragoslav Stepanovic "Lebba geht weiter".

Angenommen, SP steigt ein mit entsprechenden Milestone-Vereinbarungen, wird der Kurs wieder in anderen Regionen sein. Und hier hat nicht nur SP Interesse. Zudem kann ich mir beim besten Willen nicht vorstellen, daß das Management von Cortex seine Share-Options, eigentlich der Hauptteil des Gehaltes und Absicherung für die Zukunft, so kampflos aufgibt.

Nach Regen kommt auch wieder die Sonne.

Viele Grüße

Coluche

[Erbse1]

Hallo liebe Cortex Freunde, im Augenblick steht nicht so viel an. Der weitere Ablauf von COR steht ja unten im Schaubild. Habe eine interessante Seite gefunden. Hier kann man sehr schön über das Gehirn und Alzheimer recherchieren. Das sind ja auch Themen, mit denen sich COR beschäftigt. Wünsche allen einen guten Rutsch ins neue Jahr und ganz besonders auch unserer Cortex viel Erfolg in 2008.
Machts gut
Erbse

Inside the Brain: An Interactive Tour



Start Tour: http://www.alz.org/brain/overview.asp

[Erbse1]

Kleiner Kommentar des NeuroInvestor aus einer vorherigen Ausgabe.

(from NI November, added 11/2/07)

Cortex was stunned, and its share price slashed by over 60%, when the FDA's Psychiatry Division rejected its IND for CX717 in ADHD. The FDA has yet to provide a written explanation, and all indications are that this is a politicaly-motivated decision--avoiding any risk of criticism, not scientifically-based. While Cortex is still trying to meet with Psychiatry to see if any headway can be made, they are now developing their European trial plans for Respiratory Depression using CX717, and preparing the IND for CX701. They hired a Lilly and XenoPort veteran to be their CMO, which indicates that they are not in retreat-mode. It also appears that Rodman & Renshaw is punishing Cortex for not using them as the main placement agent for the last financing: R&R revised its target to 30 cents (!) and is demanding that the company be sold (so that they can receive a broker commission). R&R's math contradicted itself in the telling, which is why we believe that this is punitive.

[Erbse1]

Aktuelle Ausgabe des NeuroInvestor

(from NI January 2008)

Comment 1: Having recovered from Neurology's imposition of a clinical hold on CX717, a hold that was lifted, with dose limitations subsequently removed as well, Cortex was battered when the FDA's Psychiatry Division refused to allow their IND for ADHD. As has been discussed at length in NI, the refusal appears to be fear-driven; the fear that the post-mortem artifact cleared in the eyes of Neurology might eventually prove to be a genuine problem, a risk they were not willing to take with ADHD. The stock price was savaged, a process inflamed by Rodman & Renshaw's call for the quick sale of the company, and a bizarre price target of 30 cents (!). On the positive side, CX717 and other Ampakines were found by a U. Alberta group to provide unique and highly specific activation of normal respiration via AMPA receptors in the pre-Botzinger Complex. The specific application would be in the treatment of analgesic-induced respiratory depression, where CX717 appears (in four species so far) to restore respiration without attenuating analgesia. A Phase IIa trial will begin this month in Germany. Cortex also made progress with other compounds, bringing CX701 close to its IND, and developing 'high-impact' neurotrophic compounds that are not epileptogenic (unlike many of the high impacts developed elsewhere, like Lilly). This opens the door to partnering for neurodegenerative conditions.


Comment 2: In the past two years, Cortex has had two setbacks, the CX717 artifact and the IND rejection, which have twice completely blown up solid share appreciation. Had the first not occurred, the second never would have, and the share price would be near 10. Every company has bad luck and unexpected setbacks, but Cortex seems to have had more than its share. Will this be the year their luck changes? Or are they forever snakebitten? With high probability of success with the respiratory depression program, and some resolution of Schering-Plough's Ampakine intentions, we believe that it will be the former, Of course, we have said that every year since 1946, or so it sometimes seems. Our target is 5; set low because Cortex also has the burden of swimming upstream against the wishes of their former banker, and because some degree of battle fatigure has set in. If they reach that price level, we suspect that they might be amenable to a buyout, and with a high-impact Ampakine now approaching the clinic by year-end, we cannot believe that there is not a Big Pharma out there smart enough to know a bargain platform when they see one.

[Erbse1]

Es geht wenn auch sehr langsam weiter mit ORG 24448. Bin gespannt wann hier Ergebnisse veröffentlicht werden.

http://www.clinicaltrials.gov/ct2/show/NCT00113022?term=2444…

Org 24448 to Treat Depression

This study has been completed.

Schönen Tag noch
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 33.158.645 von Erbse1 am 24.01.08 17:13:10

Etwas seltsam die Meldungen zu ORG24448. Jetzt werden wieder Patienten für die Studie gesucht. Na ja, wenigstens tut sich was.

Org 24448 to Treat Depression

This study is currently recruiting participants.

http://www.clinicaltrials.gov/ct2/show/NCT00113022?
term=24448&rank=1" target="_blank" rel="nofollow ugc noopener">http://www.clinicaltrials.gov/ct2/show/NCT00113022?
term=24448&rank=1

Am 19.2. präsentiert Cortex auf einer Konferenz: http://biz.yahoo.com/bw/080128/20080128005214.html?.v=3

Schönen Tag noch
Erbse

[Ackergaul]

Leider schon eine lange Zeit keine echten News mehr von COR vernommen. Die Roth Präsentation verlief anscheinend auch eher ohne News. Ich bin gespannt, ob Stoll wirklich auf der Suche ist einen Übernahmepartner zu finden oder nach Zusammenschlüssen Ausschau hält.
Es wird Zeit, dass die High Impact Ampakine vorangetrieben werden. Das AUS für CX717 in ADHD schmerzt noch sehr. Eigentlich verwunderlich, dass gerade aus Sicherheitsbedenklichen Gründen hier ein Veto seitens der FDA kam. Leider waren CX516 (Schizophrenie) und CX717 (als „Aufputschmittel“) wenig wirksam, aber doch zumindest bisher für Sicher befunden worden.

A Placebo-Controlled Add-On Trial of the Ampakine, CX516, for Cognitive Deficits in Schizophrenia.
Goff DC, Lamberti JS, Leon AC, Green MF, Miller AL, Patel J, Manschreck T, Freudenreich O, Johnson SA.
1Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.Neuropsychopharmacology (2008) 33, 465-472; doi:10.1038/sj.npp.1301444; published online 9 May 2007.
PMID: 17487227 [PubMed - in process]

Ampakine (CX717) effects on performance and alertness during simulated night shift work.
Wesensten NJ, Reichardt RM, Balkin TJ.
Department of Behavioral Biology, Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910-7500, USA. [e-mail]
INTRODUCTION: Round-the-clock operations in both military and civilian sectors have increased the need for alertness- and performance-maintaining strategies. The potential performance and objective alertness-enhancing effects of CX717 (a novel cognitive enhancer currently being tested in Phase II clinical trials) were evaluated using a simulated night shift work paradigm.
METHODS: In this randomized, double-blind, placebo-controlled, parallel groups design, 48 volunteers underwent 4 consecutive nights of simulated shift work. Each "shift" consisted of the following: at approximately 2145 (just prior to the start of each simulated night shift), volunteers ingested a single oral dose of CX717 200 mg, CX717 400 mg, CX717 1000 mg, or placebo (N = 12 per drug dosage). Performance, alertness, mood, and symptoms were then assessed from 2300 to 0700, followed by a polysomnographically monitored daytime sleep period from 0800 to 1200.
RESULTS: Performance and alertness significantly degraded across the simulated night shifts (P < 0.05). None of the dosages of CX717 reversed these effects (P > 0.05). CX717 exerted some effects on daytime sleep, most notably reduction of slow-wave sleep time (P < 0.05). CX71 7 caused very few side effects and none of those were serious or unexpected.
DISCUSSION AND CONCLUSIONS: At the doses tested, CX717 was not effective for reversing performance and alertness deficits associated with night shift work. Further work evaluating higher doses of CX717 may be warranted, as are studies in which CX717 effects are explored under other conditions (e.g., Alzheimer's dementia, attention deficit disorder).
PMID: 17955941 [PubMed - indexed for MEDLINE]

[Erbse1]

Hallo Ackergaul, es tut sich was bei den Ampakinen und ORGANON, seitdem sie übernommen wurden. Jetzt füllt sich doch langsam wieder die pipeline. Neue Studien bei Depression und ADHD mit ORG26576

Trial to Determine the Maximum Tolerated Dose (MTD,) Based on Safety and Tolerability, of Org 26576 in Patients With Major Depressive Disorder.
This study is currently recruiting participants.

http://www.clinicaltrials.gov/ct2/show/NCT00610649?term=2657…


Dose Finding Study in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
This study is currently recruiting participants.


http://www.clinicaltrials.gov/ct2/show/NCT00610441?term=2657…

Machts mal gut
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 33.334.533 von Erbse1 am 11.02.08 20:18:13

Hallo Cortex Freunde, ich muß mich noch mal zu den ADHD Studien und ORG-26576 melden. Meines Wissens nach waren bisher nur die Anwendungsgebiete Schizophrenie und Depression an Organon auslizensiert. Ich denke mal, daß wir bei ADHD mit Schering-Plough einen neuen Partner gefunden haben. Schering-Plough hat Organon letztes Jahr übernommen und ich hoffe, daß alle Konditionen unverändert übernommen wurden. Ansonsten haben wir in der nächsten Zeit noch eine Meldung von COR zu erwarten.
Gespannt bin ich jetzt auf die Konferenz von Cortex am 19.2. Sehr gut möglich, daß wir hier weitere Einzelheiten erfahren. Dies würde auch den Kursanstieg in den letzten Wochen plausibel machen.
Bin sehr gespannt auf die weitere Entwicklung.

Schönen Tag noch
Erbse

[Erbse1]

Jetzt haben wir die dritte Meldung zu ORG 24448

Org 24448 to Treat Depression

This study is ongoing, but not recruiting participants.

Die Phase 2 Versuche dauern jetzt mittlerweile 7 Jahre. Ich rechne nicht mehr damit daß ORG 24448 eine nenneswerte Rolle spielt. Bisher wurden keine Daten aus Studien veröffentlicht. Es ist sehr gut möglich, daß jetzt ORG 26576 die Hauptrolle bei Schering Plough übernehmen wird, da es ja auch wie ORG 24448 bei Depression getestet wird. Der Zeitrahmen für die Phase 2a bei ADHD und Depression ist abgesteckt und ich hoffe daß wir nicht mehr so lange auf die Ergebnisse warten müssen.
Durchaus interessant jetzt die Pipeline bei Cortex.
Demnächst vier Wirkstoffe in Phase 2a

ADHD
Depression
Respiratory Depression
Alzheimer disease imaging studies

Weitere Ampakine der High Impact Wirkstoffe in Entwicklung.

Mit so einer Pipeline werden andere Werte schon weit über der 100 Millionen Grenze bewertet. Cortex hat im Augenblick eine Kapitalisierung von knapp 40 Millionen.

@Ackergaul, ich bin mal gespannt welchen Wirkstoff COR einlizensieren will. Ich kann mir durchaus einen aus der mGlur Gruppe vorstellen, da hier von einer positiven Verstärkung bei Fragile X berichtet wird. Lynch hat sich hier ein Patent gesichert. Die Frage ist, ob auch hier Cortex Lizenznehmer sein kann. Das alles ist reine Spekulation meinerseits.

Ich sehe durchaus positiv in die Zukunft
Schönen Tag noch
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 33.345.470 von Erbse1 am 12.02.08 18:40:40

Hi Erbse,

ich bin gespannt, wie sich COR in 2008 entwickeln wird. Es sieht ja fast danach aus, dass irgendetwas positives in der Luft liegt. Dass es die 2 x 10.000 Aktienkäufe durch Stoll im Januar waren, ist zu bezweifeln. Aber für mich gibt es noch viele Fragezeichen.

Im September 2007 hatte COR etwa 21 Mil $ Cash. Bei etwa 1 Mil $ Cash-Burn pro Monat (wie zuletzt) wäre es nun noch 16 - 17 Monate hin, bevor die Kassen komplett leer sind. Dass CX717 (bei ADHD) dass "nicht sicher genug" der FDA erhielt, ist aus dem Grunde ärgerlich, da hiefür bestimmt ein (zahlungsfähiger) Partner hätte gefunden werden können. Organon hat nun die lizenzierten Ampakine von COR in einige II-er Phasen geführt, dies wirft aber - soweit ich weiß - kein Geld (Milestones) ab. Letztendlich ist COR wohl noch etwa 1 - 2 Jahre davon entfernt eines Ihrer Ampakine in eine Phase III zu bringen. Die High-Impact Ampakine sind allenfalls in der präklinischen Phase angekommen. Ein Partner muss also her... und vorher Einlizensierungen? Ich denke, dass dies vorher erst einmal auf Eis geschoben wird. Vielmehr glaube ich, könnte Schering-Plough eventuell noch eine Übernahme tätigen.

Zudem bin ich immer wieder enttäuscht, wie wenig Informationen COR herausgibt. Alleine schon der Punkt Pipeline. Wie sieht's hier aus? CX717 bei RD (respiratory depression) oder AD; die beiden von Org lizenzierten; CX701 bei all seinen Indikationen ebenso CX1501 - was läuft wirklich noch? Wohin richtet man mittlerweile das Hauptaugemerk (CX701?)? Wie sehen die Fortschritte hier aus? Aktuelle Daten?

Mal schauen, was Stoll aus dem Hut zaubert...

Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 33.370.560 von Ackergaul am 14.02.08 17:48:11

Hallo Ackergaul, bei Cortex brauchen wir sicher etwas mehr Geduld. Viel mehr kann eine 30 Mann Firma nicht auf die Beine bringe. Ich hab mal zur besseren Übersicht ein aktuelles Schaubild von der Cortex Pipeline gemacht. Es ist sehr gut möglich, daß Org24448 nicht mehr weiter entwickelt wird. Doch lassen wir uns mal überraschen.

[Ackergaul]

Antwort auf Beitrag Nr.: 33.390.913 von Erbse1 am 16.02.08 12:48:35

Spitze! Dass solltest Du mal COR zusenden, damit die auch mal wissen, wie man Daten sauber veröffentlicht!


Grüße

[Ackergaul]

Two New Independent Directors Join Chelsea Therapeutics
Source: CNNMoney.com (press release) (Original Article)

CHARLOTTE, N.C., Feb. 8, 2008 (PRIME NEWSWIRE) — Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that Roger Stoll, Ph.D., and Norman Hardman, Ph.D., have been appointed to the Company’s Board of Directors. Chelsea also announced the resignation of former Board member Jason Stein, MD. The additions of Drs. Stoll and Hardman to the Board increase the number of independent directors to six and the Board’s total membership to seven.

“The Board has been working diligently to identify qualified directors with specific experience in launching products, growing early stage pharmaceutical companies, and financing,” said Kevan Clemens, Chairman of the Board. “Roger and Norman are both industry veterans who bring excellent knowledge and diverse experience as senior managers and directors of large and small companies. Between them, they have brought over a dozen compounds to the market, grown substantive market share and accumulated significant M&A experience. The strong credentials of both of these gentlemen will be a great asset to Chelsea and we look forward to working with them to help us grow the Company and establish its commercial presence.”

“The Board would also like to thank Jason for his excellent service to Chelsea,” continued Dr. Clemens. “Jason has been a valuable member of our Board since the company’s inception in 2004. He was instrumental in the formation, initial funding and ongoing strategic guidance of the company. We have appreciated his dedicated service and wish him success in his new endeavors.”

[Erbse1]

Gestern war Konferenz. Ich konnte mir sie gestern nicht selber anhören. Deshalb hier eine Zusammenfassung von gfp927z.
Sieht so aus, daß sich alles etwas verzögert. Das war aber immer so bei Cortex. Nur jetzt wird langsam das Geld knapp.

1) Finances - The RD slippage will aggravate the cash problem considerably. At the $14 mil projected burn rate, there will be $9.1 mil left at the end of July, and $6.8 mil at the end of September. So Cortex will need to find new money by the end of Q3. The updated timeline for RD-1 results is in July, and RD-2 results by the end of June. That's going to cut it close to get a deal done, and Cortex's financial back will be to the wall in negotiations. Also, there could be some additional timeline slippage in the RD trials. So barring any other source of new cash, there's a good chance a financing will be needed prior to getting any proceeds from an RD deal.

2) Almost nothing mentioned on Schering's ADHD trial with Org-26576. The slide was updated to move Depression from Org-24448 to Org-26576, but nothing entered for ADHD.

3) CX-701 - goes to veterinary use, due to short patent life. However, CX-717 has the same short patent life problem, as do Org-24448, and very likely Org-26576.

4) There was a slide showing good RD rescue/reversal data in rats, in addition to the previously shown RD prevention/premedication data.

5) High impacts - CX-1837 - to start tox in Q2-08.

6) CX-1739 is 5 times more potent than CX-717.

7) AD PET study - more delays, now data pushed back to Q4-08. The 2nd trial (functional MRI) was removed from the milestone slide, so perhaps they've dropped it to save money (?)

8) No mention of the Euro patent event/decision that was supposed to happen around the end of January.

9) An IV form of CX-717 should be ready by Summer.

[Erbse1]

Der Vollständigkeit halber hier das Schaubild der Cortex Pipeline von der Roth Konferenz. Leider verzögert sich der ganze Prozess in der Anwendung Respiratory Depressionum ca 2 Monate. Die ganze Konferenz dreht sich aber um diese Anwendung. Kein Kommentar zu ADHD und ORG 26576. Geplant wird jetzt nur noch mit Wirkstoffen deren Patentlaufzeit bis 2027/28 geht. CX 701 soll nur noch in der Tiermedizin eingesetzt werden.

Grüße
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 33.426.569 von Erbse1 am 20.02.08 18:11:51

Hier noch den Kommentar des NeuroInvestor zu der gestrigen Konferenz.


Positive: Much, much bigger RD market than I had expected to hear, and the 15% incidence rate reported from anesthesiology would make prophylactic treatment much more acceptable (reimbursors are more likely to OK prevention of a bad event that happens 15% of the time than if it happens 1-3%). The sleep apnea aspect is even larger, and he noted they have some supportive animal data, and Big Pharma interest.

Also positive: that the animal data shows both rescue and prevention effects. The note that the animals not receiving CX717 died, as opposed to the CX717 animals still breathing normally, was a compelling example of the stakes involved.

And they finally have a high-impact lead candidate for tox studies: CX1837. That's something we've been waiting for...for a decade.

Mixed bag: Delay on the RD Phase IIa trials. It took a while for him to give some detail--German inquiries about manufacturing and chemistry--and to confidently state they expect to get started shortly. Until he did that, I was pretty anxious.So the bottom line is: trials delayed by bureaucracy, but likely to report two months after the initial timeline. It's not optimal, but is a lot better than 'we hope to work this out with the authorities, but we can't guarantee it...'

Presentation issues: He mentioned ADHD for Org26756 only in passing, didnt have it on the slide. That deserves more comment, even without getting into any SP info (i.e. that it is reassuring that Ampakines still are seen as viable for ADHD by the FDA)

When asked to explain 'high impacts', he led off by noting their 'seizure potential.' Not the take-home message I'd want to go out.

The inlicensing option, even if they are still looking at it, should be omitted from the presentation. It just sounds absurd when discussing a company which projects $3 million on hand by the beginning of 2009.

Overall: The RD prospects are better than I expected, there is a time lag, and he did sound tired. There was no bad news that should spur selling, but gratification (Phase IIa data ) is again delayed, so we'll have to see when the uptrend resumes.

NeuroInvestment

[Erbse1]

Antwort auf Beitrag Nr.: 33.427.203 von Erbse1 am 20.02.08 18:50:21

Hier noch eine Stellungnahme des Cortex CEO Roger Stoll auf die Anfrage eines Mitstreiters zur letzten Konferenz.

His reply:

What I said at the Roth meeting is what I can discuss publicly, things I did not say may have had a reason behind that decision which goes beyond simply not disclosing things to shareholders. Obviously, I must stay within the bounds of public disclosure and what I did say is (a) we have two studies in RD with CX717 filed in Germany (b) we can expect results in June/July from those two studies (which is a very short time in the world of pharmaceuticals), (c) we are developing an iv formulation of CX717 (d) CX1739 toxicology studies in two species are starting now and the results are expected in June, (e) we have five new composition of matter(COM) patents which extend patent life for our technology into the 2028 timeframe(including CX1739), and I said this was one of the most critical and positive events for the company since I joined Cortex. The future of the company rides very much on getting the extended patent life, since most of the existing library had a patent life of 2017-2018 and still require some substantial development time prior to getting approval for marketing (e) we are working on getting a high impact AMPAKINE® drug ready for toxicology trials later this year, and this is a big breakthrough for the company. Shareholders may have been disappointed with these items not being quicker, etc. but in our world of new chemical entity discovery the risks are very high and yet we have found a way to get a lead compound into Phase II and by year-end could have several compounds in clinical development with exceptionally long timeframes remaining for market life. If you want to do a license with larger pharmaceutical companies, they need to see a platform which can produce lots of potential drug molecules and excellent market life potential. So John by the end of this year we will have brought Cortex from a company with no money and a lead compound (CX516) which had a 45 minute half-life in man (could virtually never be a marketable drug), to a company which has a lead compound in Phase II development and several others ready for clinical development with a demonstrated proof of concept in humans for ADHD and hopefully for RD. Hopefully the stock price will react accordingly. Roger

Source: http://investorshub.advfn.com/boards/read_msg.asp?message_id…

[Erbse1]

Interessant von der letzten Konferenz sind noch die geplanten near term milestones



Bis vor einem Jahr wußte ich noch nicht einmal, daß es so etwas wie Atemdepression gibt und mit etwas Glück könnte diese Anwendung der Durchbruch für die Ampakine sein, die auch als erstes auf den Markt kommt. Die Bilder von den bisherigen Tierversuchen sind beeindruckend. Nur muß sich dies nun auch am Menschen bestätigen. Die Zeitplanung sieht das Ende der Studien 2a für die Monate Juni und Juli vor. Das ist für solche Studien sehr schnell. Bin sehr gespannt auf die Ergebnisse.

Sollten die Ergebnisse positiv ausfallen, so haben wir es hier mit einem Anwendungsgebiet mit geschätzen Umsatzzahlen von ca. 3 Milliarden $ zu tun. Hoffen wir mal, daß hier nichts Unerwartes seitens der Behörden eintritt. Pech genug hat Cortex bisher allerdings gehabt. In ca 5 Monaten sind wir alle schlauer.

Viele Grüße
Erbse

[Erbse1]

Hallo Cortex Freunde,
aus aktuellem Anlass poste ich noch mal den Abstrakt zu Atemdepression. Still und heimlich hat Cortex hier die Entwicklung vorangetrieben. Die Phase 2a Ergebnisse sollen hier schon im Juli vorliegen. Gute Ergebnisse könnten sehr positiv für die lange erwartete Auslizensierung sein. Die Frage ist nur, ob man hier auch die umstrittene Substanz CX717 nimmt, oder eine Weiterentwicklung. Eine sehr entscheidende Phase für COR.
Grüße
Erbse

Ampakines alleviate respiratory depression in rats.

Ren J, Poon BY, Tang Y, Funk GD, Greer JJ.
Department of Physiology, University of Alberta, 513 HMRC, Edmonton, AB, T6G 2S2 Canada.

RATIONALE: There is a need for improved therapeutic interventions to treat both drug- and sleep-induced respiratory depression. Increased understanding of the neurochemical control of respiration will help identify a basis for advances. Activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors positively modulates respiratory drive and rhythmogenesis in several brain regions including the pre-Bötzinger complex. Ampakines are a diverse group of small molecules that activate subsets of these receptors. OBJECTIVE: We determined whether the ampakine CX546 would enhance respiratory drive and rhythmogenesis across various stages of development and whether this ampakine could counter opioid- and barbiturate-induced respiratory depression. METHODS: Respiratory frequency and amplitude were measured in the following rat models: (1) perinatal in vitro brainstem-spinal cord, (2) neonatal in vitro medullary slice, (3) juvenile in situ perfused, working heart-brainstem preparation, and (4) newborn and adult in vivo. RESULTS: Administration of CX546 stimulated baseline respiratory frequency in perinatal in vitro preparations but not in older animals (greater than Postnatal Day 0). Furthermore, pharmacologic depression of respiratory frequency and amplitude was countered at all ages studied by the administration of CX546 in vitro, in situ, and in vivo. Significantly, CX546 countered opioid-induced breathing depression in all preparations, without altering analgesia as assessed by measuring the time to foot withdrawal in response to a thermal stimulus. CONCLUSIONS: CX546 effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response. These studies suggest that ampakines may be useful in preventing or reversing opioid-induced respiratory depression and identify the potential of ampakines for alleviating other forms of respiratory depression including sedative use and sleep apnea.

Quelle:http://www.ncbi.nlm.nih.gov/pubmed/16973981?ordinalpos=5&ito…

[Erbse1]

Cortex Receives Approval from German Regulatory Authority to Proceed with Two Clinical Trials for AMPAKINE(R) CX717 for the Acute Treatment of Respiratory Depression Due to Opiate Analgesics
Friday March 7, 8:30 am ET
CX717 Does Not Affect the Analgesic Properties of Opiates

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR, http://www.cortexpharm.com), has received approval from the German Federal Institute For Drugs And Medical Devices (BfArM) to initiate two AMPAKINE® CX717 clinical studies. These studies will assess whether the pre-administration of CX717 can prevent the development of respiratory depression (RD) induced by the potent Schedule II opiate agonist, alfentanil.

The first study is a single dose, randomized, double-blind, placebo-controlled, two-period crossover design in sixteen healthy subjects. The primary study objective is to determine if CX717 can prevent RD while preserving the underlying desired analgesic effect of alfentanil. Such affects have already been demonstrated in animals. Currently available opioid reversal agents, such as naloxone (Narcan®), also reverse the analgesic effect of opioids, which is a major drawback. Hence, an agent that enhances the safety of using opiate drugs by preventing the risk of RD, but preserves the analgesic effects of the opiates, can significantly improve pain management in patients.

The second study is a single dose, randomized, double-blind, placebo-controlled, two-period crossover design in twenty-four (eight subjects/dose) healthy subjects. Three different doses of CX717 will be assessed in this study, with the objective to determine an optimal dose for the prevention of RD in humans. The enrollment of patients will begin as soon as an additional approval from the German Federal agency that controls the use of opiate-type drugs is given.

Studies of CX717 in animal models have demonstrated that the drug can be used both to prevent and to rescue the animal from opiate-induced RD. It also has been shown that a dose response effect on RD can be obtained after oral administration in animal models. While the medical need for opiate drugs such as fentanil and alfentanil that permit maximal pain relief is clear, unfortunately there is a significant risk of inducing RD with these agents, which can be life threatening. Cortex believes that the acute use of a drug such as CX717 can improve the safety margin for giving powerful analgesics after painful surgical procedures and would provide a valuable tool for anesthesiologists and surgeons to optimize pain management in surgical patients. This would be especially true in high-risk surgical patients such as those over the age of sixty-five, those with a history of sleep apnea, respiratory illnesses or obese patients.

In his presentation at the February 19, 2008 Roth Capital Partners Conference, Dr. Roger G. Stoll, CEO of Cortex, estimated that Cortex should have preliminary results from one study by the end of the second quarter 2008 and the other by early in the third quarter 2008. A replay of Dr. Stoll’s presentation on the unique mechanism of action, market potential, and regulatory strategy for the use of CX717 to treat RD will be available until March 20, 2008 and can be accessed by logging onto http://www.wsw.com/webcast/roth16/cor/.

Schönen Tag noch
Erbse

[Erbse1]

Zu den Kurszielen von Rodman&Renshaw fällt einem wirklich nichts mehr ein. Deshalb hier das Posting des NeuroInvestor aus einem anderem Board. Die Umsatzschätzung zu Atemdepression könnt ihr aus folgendem Schaubid entnehmen.



Just in case anyone thought that R&R was done with their bizarre math, here's the important chunk from a note they sent out today:

<<Despite the envisaged short development pathway in respiratory depression, we continue to believe that no AMPAKINE® will approach a regulatory filing for at least 3-4 years. Estimates by Cortex that the market for a therapeutic against respiratory depression induced by opiates could exceed $3B may be optimistic.

We derive our 12-month price target of $0.30 per share based on 3x projected cash position (~$9MM) and dividing this by the 88MM shares outstanding at the end of 4Q08.

We reiterate our Market Underperform rating with a target price of $0.30 on Cortex shares.>>

One would think that the absurdity of valuing Cortex purely on a projected cash position and--88 million shares?--if the price is right, the shares out is almost twice what it should be--would have hit R&R by now. No value for any molecules, IP, etc. Let's consider the comment that the projection of a $3 billion RD market due to opiates 'may be optimistic.' They fail to note that sleep apnea not due to opiates is a big chunk of that projection. Besides, let's just say that the projection is off by a factor of 3. Call it $1 billion for the sake of easy numbers. Here's a game we can all play--calculate a revenue stream to Cortex from a partner's marketing of such a drug five years from now (OK, not even approaching a billion because of gradual market penetration, though with no competitors, that could go faster than is usual), and use any of the standard discounted earnings models to calculate an appropriate price per share then--discounted back to now.

I may get around to this later--but I can tell you this--it is a hell of a lot higher than 30 cents per share. Way higher. R&R's internal logic and math don't even approach adding up. One would think they'd be embarrassed. I have a premonition that a highly incendiary editorial may be published at month's end that will permanently burn my bridge to R&R. Companies with the kind of power they hold, should be held accountable for grotesquely wrong--due to an agenda or incompetence or both--statements that appear intended to do harm. This isn't just a difference of opinion about prospects, honorable people can disagree: this is malfeasance, deliberate or negligent.

NeuroInvestment

[Erbse1]

Habe mal das Schaubild der Cortex Pipeline nach der letzten Konferenz aktuallisiert. Cortex gestaltet gerade eine neue Homepage, die nach eigenen Angaben bald ins Netz gestellt wird. Deshalb hier der link nach Cortex.

http://www.cortexpharm.com/

[Erbse1]

Hallo Cortex Fans,
hier ein kleines Update aus der letzten COR Jahresmeldung. Zu den Atemdepressionen habe ich mal die zwei Schaubilder aus den Tierversuchen kopiert. Die Bilder sind schon beeindruckend. Hoffen wir mal, daß sich diese Versuche auch am Menschen bestätigen lassen. Bei einem negativen Ausgang dürfte Cortex es sehr schwer haben nochmal auf die Beine zu kommen. Das sollte allen klar sein.

>>>The company’s development plans for 2008 include two Phase IIa human clinical studies of Ampakine® CX717 as a potential acute treatment for respiratory depression.

As recently reported, Cortex has received approval from the German regulatory authority to proceed with both of these clinical trials. One study will evaluate whether the pre-administration of CX717 may prevent the respiratory depression induced by the opiate alfentanil, while preserving alfentanil’s pain relieving effects. A second study will seek to determine the optimal dose of CX717 in order to prevent respiratory depression. Related results from these studies are anticipated in late second quarter and early third quarter of 2008.

Cortex believes that CX717 may improve the safety margin for giving powerful pain relievers following surgical procedures, and thereby provide a valuable tool for anesthesiologists and surgeons to optimize pain management in their patients.

Studies of CX717 in animal models have demonstrated that the drug can be used both to prevent and to rescue the animal from opiate-induced respiratory depression. It also has been shown that a dose response effect on respiratory depression can be obtained after oral administration in animal models.

Cortex recently re-initiated its Phase IIa PET imaging studies with CX717 in Alzheimer’s disease. During 2008, Cortex also anticipates entering into Phase I human clinical trials with CX1739, a follow-on compound. Necessary toxicology studies for this compound are already underway and expected to be completed in June 2008.<<<

Cortex Prevention Atemdepression Studie



Cortex Reversal Atemdepression Studie

[Erbse1]

Antwort auf Beitrag Nr.: 33.705.648 von Erbse1 am 21.03.08 17:34:24

Folgend eine Beschreibung des Anwendunggebietes Atemdepression

Respiratory Depression

Respiratory depression represents a potentially life-threatening condition resulting from analgesic, hypnotic and anesthesia medications. The condition results in a depression of breathing that causes a reduced availability of oxygen to vital organs.

Respiratory depression is a leading cause of death from the overdose of some classes of abused drugs, but the condition also may arise during typical physician-supervised procedures such as surgical anesthesia, post operative analgesia and as a consequence of normal out-patient management of pain from illnesses or injuries. Events also may occur when two or more central nervous depressants are taken together or when prescribed drugs are taken in ways not intended by the physician. Sleeping disorders like sleep apnea are another predisposing factor for respiratory depression. Recent research estimates that the treatment market for respiratory depression may be approximately $1.2 billion in the U.S. alone.

Our own recently completed market research suggests that respiratory depression may occur during 10% to 15% of inpatient surgical procedures. Some of these respiratory depression events lead to death. The primary drug classes responsible for these effects are opiates and barbiturates. Opiates include standard pain medications such as morphine, fentanyl and codeine, along with vicodin, hydrocodone and oxycontin. Barbiturates include sedative drugs such as pentobarbital.

Currently, the only pharmacological method to counter respiratory depression induced by opiates is to administer opiate receptor antagonists such as naloxone (Narcan ® ), but those antagonists eliminate the analgesic activity of drugs administered for severe pain relief, which is a major drawback for using those agents.

In May 2007, we entered into an exclusive patent license agreement with the University of Alberta to potentially broaden the use of our A MPAKINE technology to prevent and treat opiate- and barbiturate-induced respiratory depression. The related patent application filed by Dr. John Greer of the University of Alberta describes a method by which an AMPAKINE compound can reverse the respiratory depression associated with classes of commonly prescribed opiate analgesics and barbiturates. Dr Greer has demonstrated in animal models that the respiratory depression induced by these agents can be reversed or prevented with an A MPAKINE , without a reduction of pain relief or sedation. We believe that this creates the opportunity to use an A MPAKINE compound in conjunction with commonly prescribed barbiturates or opiates to reduce the mortality caused by these adverse reactions. Preliminary animal data also suggests that an A MPAKINE compound may also reverse the respiratory depression effects of propofol (Diprivan ® ), a commonly used intravenous anesthetic agent.

[Erbse1]

Nachdem der Kurs in den letzten Tagen etwas unter Druck geraten ist spekulieren einige Aktionäre auf einen negativen Patententscheid. Deshalb folgend die Stellungnahme von Cortex und ein Kurzkommentar des NeuroInvestor.

We are aggressively pursuing patent protection of our technologies. We own or have exclusive rights (within our areas of product development) to more than 22 patent families comprising over 150 issued or allowed U.S. and foreign patents and over 100 additional U.S. patent applications and their international counterparts pending. Over 130 of these are composition of matter patents that cover hundreds of our compounds. These patents form the foundation of the Company’s business and the pharmaceutical industry in general. Additionally, we are consistently filing new disclosures and patents for new structures and new uses, and in 2007 we filed five new patent applications covering hundreds of new compounds. If these applications are granted as filed, they will provide patent protection for our new molecules through 2028.

One of our patents covers the method of use for our A MPAKINE compounds — as well as compounds made by others — and describes the mechanism by which A MPAKINE compounds may affect the treatment of memory and cognition. This patent issued to the University in the U.S. in 1999 and provides protection through 2016. We believe that this patent provides coverage in the U.S. that extends to both neurological disorders such as Alzheimer’s disease as well as psychiatric conditions with cognitive disturbances including depression, obsessive compulsive disorder, attention deficit disorder, and phobic disorders. Similar method of use patents have been issued to us in Mexico, Australia and New Zealand.

In November 2003, a similar patent was issued to the University by the European Patent Office (“EPO”) that provides protection through 2013. Upon issuance of the patent, an opposition was filed by Eli Lilly and Company. In August 2004, GlaxoSmithKline also filed an opposition. In cooperation with the University, we responded to the oppositions. An oral hearing took place at the EPO in late January 2008. A formal written decision has not yet been received from the EPO Opposition Division to provide clarity on the decision, although a verbal decision to revoke the patent was rendered at the hearing. Upon receipt of the written decision, which will give the reasons for the revocation decision, we will file a formal appeal. One of the reasons for the revocation cited at the hearing was a filing technicality related to matter added to the original patent application. The EPO decided that the parent application as filed did not provide sufficient basis for several terms that appeared in the final claims of the patent. The revocation decision does not take effect until any appeal is concluded, and that process will take several years to resolve.

We believe that the legal process related to our appeal of the revocation by the EPO may continue for most of the remaining life of the patent, given that the European patent expires in 2013. We do not believe that the European decision is material to the future of our A MPAKINE technology because of this patent’s limited life for commercial protection. Most importantly, we own a large portfolio of composition of matter patents with much longer patent lives that we believe are fundamental to pharmaceuticals in general and more critical to our commercial protection worldwide.

Because patent rules and regulations, and burden of proof requirements differ substantially between the U.S. and Europe, specifically in regards to the revocation reason cited by the EPO above, we believe that the decision by the EPO is not likely to impact the patent that has issued in the U.S.

Comment NeuroInvestment

Several years ago the patent meant something--but it was a depreciating asset, and as we discussed earlier, its current value is minimal. Given that Cortex's very survival has been called into question by R&R, and the RD trial is (once again) a critical 'binary' event. I believe that the current share price includes virtually no value for Cortex's IP, which means this patent decision should have no effect. Having said this, the share price will probably go ahead and slip tomorrow-- but it shouldn't.

NeuroInvestment

Warten wir mal alles gelassen ab.
Grüße
Erbse

[Erbse1]

Interessanter Artikel zu S18986. Diese Substanz wurde von COR an Servier auslizensiert. Allerdings habe ich die Information, daß die klinischen Versuche wegen toxikologischer Probleme unterbrochen wurden.

New drug may help rescue the aging brain

As people age, their brains pay the price — inflammation goes up, levels of certain neurotransmitters go down, and the result is a plethora of ailments ranging from memory impairment and depression to Alzheimer’s and Parkinson’s. But in a long-term study with implications to treat these and other conditions, researchers have found that an experimental drug, taken chronically, has the ability to stem the effects of aging in the rat brain.

The drug, temporarily designated S18986, interacts with AMPA (short for α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, or ampakine) receptors in the brain. These receptors transmit excitatory signals in the brain, and

researchers were interested in experimental AMPA-receptor drugs (such as S18986) for their neuroprotective abilities and for the way they temporarily boost memory. But rather than investigating the compound’s short-term effects, Alfred E. Mirsky Professor Bruce McEwen and his lab members made a far longer commitment: The scientists studied the drug’s impacts on middle-aged to elderly rats and found that, when administered daily over four consecutive months, it appeared to improve memory and slow brain aging.

“Nobody had ever looked at the long-term effects of these ampakines on the aging brain,” says McEwen, head of Rockefeller’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology. Short-term studies, he notes, had shown that the drug appears to improve aspects of memory, likely by temporarily ramping up AMPA receptors in the hippocampus — the brain’s memory and learning center. But McEwen, research assistant Erik Bloss and postdocs Elizabeth Waters and Richard Hunter found that, over the course of four months, S18986 changed the entire profile of the older rodents’ brains.

When compared to control animals that had received only sugar water, the drugged rats were not only more active and better at memory tests, but their brains showed physical signs of slowed aging. Neurons in the forebrain that produce acetylcholine, a neurotransmitter known to play a role in learning and memory, had 37 percent less decline. Dopamine-producing neurons, which are responsible for sustaining activity and motivation levels, slowed their decline by 43 percent. Levels of inflammation in the brain were also significantly lower. “Every marker we chose to look at seemed to indicate there was some preservation of function during aging with chronic treatment,” Hunter says. The drug appears to slow aging’s effects throughout the entire brain.

Dopamine is a motivation- and movement-related neurotransmitter in the brain, and its presence is necessary for maintaining normal activity levels — it’s the chemical that helps you get up off the couch and socialize or exercise. A severe loss of dopamine production causes Parkinson’s disease, “so this drug has the potential, perhaps, to block the progression of the disease,” Hunter says.

Not only that, but it could be helpful for much less severe conditions, too. As people age, it’s often harder for them to feel motivated to socialize or even eat, leading to depression and making latent conditions worse. “So maybe this drug isn’t going to be the one that prevents Parkinson’s,” Waters says, “but maybe it’s going to improve the quality of life as you age, so that up until the very end of your life you can sustain that quality and sustain a higher activity level.”

With such a variety of impacts on neurotransmitters, S18986 holds enormous potential. But so far, it’s only potential. The researchers hope to dig deeper to find out precisely how the drug works. “There’s a lot to be done,” Hunter says, “and this shows that there’s broad potential for these compounds.”



Age on the brain. An experimental drug, S18986, seems to counteract numerous symptoms of aging in rats. Animals given the drug daily for four months were active, with better memories and less inflammation in their brains. Dopamine-producing neurons in the forebrain of an 18-month-old drugged rat (top) are far more active than those in a normal rat of the same age.

[Erbse1]

Cortex Initiates Enrollment in Opiate Induced Respiratory Depression Clinical Trial in Germany Today

Monday March 31, 8:29 am ET

Goal is to Determine If CX717 Can Prevent Respiratory Depression without Affecting Analgesic Properties of Opiates


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR, http://www.cortexpharm.com), was notified by the German regulatory agency which approves the use of narcotic drugs that it can proceed with the trial which will use alfentanil, an opiate analgesic. With this approval the enrollment of subjects into the dose response study evaluating the ability of CX717 to prevent respiratory depression caused by opiate analgesics has begun. The study is a placebo controlled, double blinded, cross-over design with three doses of CX717compared to placebo. Depending on the pace of subjects being enrolled, Cortex at this point believes that top-line data will be available from this study by the end of June, 2008.

Currently, the only available means of preventing respiratory depression induced by the combination of multiple opioids medications like fentanyl, morphine and codeine in the operating room is either to have the patients re-intubated in order to attach them to a respirator or to utilize opioid reversal agents, such as naloxone (Narcan®). Intubation is a costly procedure and may lead to additional days of hospitalization. The use of. naloxone, a narcotic antagonist, eliminates the analgesic effect of the opioid medication as well as countering the respiratory depression, which is considered a significant drawback to its use.

If the German AMPAKINE® studies are successful, pre-surgical or post- surgical administration of CX717 could potentially improve the safety margin for giving these powerful analgesic agents, which would provide a valuable tool for anesthesiologists and surgeons to optimize pain management in surgical patients. This would be especially true in high risk surgical patients such as those over the age of sixty-five, those with a history of sleep apnea, respiratory illnesses or obese patients. Further information about the design of the two clinical studies which the Company is conducting in Germany can be obtained by reading the press release on the initial approval by the BfArM issued on March 3, 2008.

[Ackergaul]

Antwort auf Beitrag Nr.: 33.766.257 von Erbse1 am 31.03.08 14:42:01

Es gab schon 2006 eine Hypoventilation Studie von Cortex. Damals noch mit CX546 als Wirkstoff:
http://www.med.ualberta.ca/research/documents/JunArticle.pdf

Unter http://www.uni-duesseldorf.de/awmf/ll-na/020-001.htm kann man möglicherweise ableiten, dass gut 1 % der Bevölkerung als Therapieziel in Frage kommen. Natürlich werden nur die schwereren Fälle behandelt...

Obstruktives Schlafapnoe-Hypopnoesyndrom (OSAHS): Pro Stunde Schlaf mindestens 5 Ereignisse pharyngealer Obstruktionen mit Hypopnoen (Abnahme der Atmungsamplitude/-frequenz mit nachfolgendem Abfall der Sauerstoffsättigung um mindestens 3% oder einem nachfolgendem Arousal4) oder Apnoen (mindestens 10 Sekunden dauerndes vollständiges Sistieren der Atmung); Hypersomnie oder (selten) Insomnie.5 Epidemiologie: mindestens 1 % der Bevölkerung, Verhältnis Frauen/Männer: ca. 1:2.

Hypoventilation und Apnoe werden anscheinend therapeutisch gleich behandelt, ist aber nicht dasselbe... Nur mal so nebenbei, in Deutschland mit über 80 Mil. Einwohnern wären dies rund 800.000. Sind es 3 bis 5 % die hiervon behandelt werden, ergäbe dies ungefähr 30.000. Kosten für CX717? 100 $ im Monat?
Nehmen wir 100 $ monatlich an, wäre ein Umsatz von knapp 35 Mil. $ im Jahr alleine hier in DE möglich...


Aber bis dahin ist es noch ein langer Weg...



Grüße

[Erbse1]

Insiderkauf durch den COR CEO Stoll von 20.000 Stück in dieser sensiblen Phase. Ich denke mal Stoll will uns damit sagen, daß alles nach Plan läuft, nachdem der Kurs in den letzten Tagen wohl etwas geschwächelt hat. Bis zu den Ergebnissen sind es jetzt noch in etwa 8 Wochen. Im Mai ist noch die Jahreshauptversammlung. Sonst gibts nicht viel Neues zu vermelden. Also, dann Daumen drücken bis Ende Juni.
Grüße
Erbse

[Erbse1]

Die Jahresversammlung wird übertragen. Den link bitte aus der folgenden Meldung entnehmen.

Grüße
Erbse

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR, http://www.cortexpharm.com/), a neuroscience company focused on developing novel AMPAKINE® drug therapies for psychiatric disorders, neurological diseases, and drug induced respiratory depression, will web cast presentations from its annual shareholder meeting scheduled for Wednesday, May 14, 2008, at 10:30 a.m. PDT (1:30 p.m. EDT), at the Fairmont Newport Beach Hotel, 4500 MacArthur Boulevard, in Newport Beach, California.

During the informal part of the meeting, Cortex will update shareholders on recent developments, updates for the two Phase II clinical trials evaluating CX717 in opiate-induced respiratory depression currently being conducted in Germany, the market research conducted on respiratory depression, and other preclinical developments underway at the company.

[Erbse1]

Antwort auf Beitrag Nr.: 34.075.722 von Erbse1 am 12.05.08 14:56:16

Tut mir Leid, hab den link unterschlagen

Investors may access the live web cast through the Cortex website at http://www.cortexpharm.com/ beginning at 10:30 a.m. PDT on May 14, 2008. The web cast will be available for replay through May 29, 2008, at http://www.InvestorCalendar.com.

[Erbse1]

Zwei neue Abstrakte zu unserem Themengebiet:

The substrates of memory: Defects, treatments, and enhancement.
Lynch G, Rex CS, Chen LY, Gall CM.
Department of Psychiatry and Human Behavior, University of California, Irvine CA, United States.

Recent work has added strong support to the long-standing hypothesis that the stabilization of both long-term potentiation and memory requires rapid reorganization of the spine actin cytoskeleton. This development has led to new insights into the origins of cognitive disorders, and raised the possibility that a diverse array of memory problems, including those associated with diabetes, reflect disturbances to various components of the same mechanism. In accord with this argument, impairments to long-term potentiation in mouse models of Huntington's disease and in middle-aged rats have both been linked to problems with modulatory factors that control actin polymerization in spine heads. Complementary to the common mechanism hypothesis is the idea of a single treatment for addressing seemingly unrelated memory diseases. First tests of the point were positive: Brain-Derived Neurotrophic Factor (BDNF), a potent activator of actin signaling cascades in adult spines, rescued potentiation in Huntington's disease mutant mice, middle-aged rats, and a mouse model of Fragile-X syndrome. A similar reversal of impairments to long-term potentiation was obtained in middle-aged rats by up-regulating BDNF production with brief exposures to ampakines, a class of drugs that positively modulate AMPA-type glutamate receptors. Work now in progress will test if chronic elevation of BDNF enhances memory in normal animals.



The AMPA modulator S 18986 improves declarative and working memory performances in aged mice.
Marighetto A, Valerio S, Jaffard R, Mormede C, Muñoz C, Bernard K, Morain P.
aBordeaux 1-University, CNRS UMR 5228, Center of Cognitive and Integrative Neurosciences, Avenue des facultés, Talence bServier International Research Institute, 6 Place des Pléiades, Courbevoie, France.

The aim of this study was to further characterize the memory-enhancing profile of S 18986 a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. S 18986 was studied in two mouse models of age-related memory deficits, using radial maze paradigms involving long-term/declarative memory and short-term/working memory. Aged mice exhibited severe deficits when compared with their younger counterparts in the two behavioural tests. S 18986 at the dose of 0.1 mg/kg selectively improved aged mouse performance in the test of long-term/declarative memory flexibility and exerted a beneficial effect on short-term retention of successive arm-visits in the short-term/working memory test. This study confirms the memory-enhancing properties of S 18986 and, in line with emerging data on multiple AMPA modulators, highlights the relevance of targeting AMPA receptors in the development of new memory enhancers.

[Erbse1]

Für Interessenten der Jahreshauptversammlung hier der link zur Veranstaltung

http://www.investorcalendar.com/IC/index.asp

Schönen Tag noch
Erbse

[Ackergaul]

Es geschehen noch Zeiten und Wunder! Cortex Homepage präsentiert sich im neuen Glanz... http://www.cortexpharm.com/index.html

Zudem wurde auch endlich eine aktuelle Übersicht der laufenden Trials hinzugefügt


Die letzte Roth Präsentation (Feb 08) ist ebenfalls einsehbar:
http://www.cortexpharm.com/pdfs/Roth_Conference_Feb2008-f.pd…


Viel vergnügen beim stöbern

Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 34.094.554 von Ackergaul am 14.05.08 20:10:40

Erst mal der Hammer vom SHM:

Stoll hört als Chef auf. Varney kommt.

Aus aktuellem Anlass die Pipeline, wie sie für die nächste Zeit geplant ist



Sonst lief alles nach Plan. Genehmigte Shares von 75Mill. auf 105 Mill. erhöht.

Ich wünsche Roger Stoll alles Gute für seine Zukunft. War ein sehr schwerer Job mit vielen Hindernissen. Gut gemacht.

Liebe Grüße
Erbse

[Erbse1]

Zum SHM noch ein kleiner Kommentar des NeuroInvestor. Jetzt ist erst mal Warten auf die Atemdepression Ergebnisse angesagt. Dauert ja nicht mehr so lange.
Grüße
Erbse

A few impressions on the SHM:

1) The transition to Mark Varney as CEO has always been the underlying plan--no one forced Stoll to do anything.The fact that they announced it now makes me think that there has been no hint of failure (that doesn't necessarily mean there is a hint of success) from Germany. If Varney thought the company was about to blow up, he might have demurred.

Well, I would.

2) The mood amongst Cortex management was positive, not ebullient. I don't think they know anything for sure yet. Pierre Tran had come back from Germany, and he made a joke at some point, and if anyone has a sense from watching the patients, he would.

3) Stoll actually did make reference to the share price and believing that it's very undervalued--not that I expected anything else, but it's not as if he didnt acknowledge the current situation. His presentation was as usual, which is in the midrange for execs. There are some who are flashy but sleazy, there are some who are totally boring, he's in neither group--but you have to have interest in the data he's showing. Spoonfeeding and cheerleading is not his style. There are just a few CEOs who stand out in their presenting, Don deBethizy of Targacept is one example. But the issue here is not presenter style--put deBethizy up there presenting the same pending binary scenario, and the stock will do exactly the same thing. Varney is also very lowkey--but I'm more interested in the fact he got Street and Tran to join up.

4) Other important points: CX1739 is not delayed, it's finishing its tox work, and they clearly expect it to be in the clinic 3Q.

I asked specifically whether anything had caused a caution flag on the first high impact, CX1837. There has not been, but it's still early in the tox testing process.

There is no use patent on ADHD, which accounts for SP going ahead without a license. Stoll made a half-hearted reference to the cognition patent perhaps applying, but he more importantly indicated that there is some prior art (must be vis-a-vis attention specifically) that prevented a use patent for ADHD. So Cortex's leverage there is strictly molecule-based.

NeuroInvestment

[Ackergaul]

Antwort auf Beitrag Nr.: 34.096.762 von Erbse1 am 15.05.08 07:38:18

Wenn ich mein Statement abgeben darf:
- für mich siehts danach aus, dass der CX717 RD Trial um möglicherweise ein ganzes Quartal nach hinten geschoben wurde (Ergebnisse sollten doch Ende Juni kommen)
- Viele klinische Trials hört sich sehr gut an. Klar ist die Kosten werden dadurch höher ausfallen. Leider sind die meisten in Phase I und geben (zumindest aus meiner Perspektive) dann wenig Auskunft über die potentielle Wirksamkeit. Vielleicht bringt der CX717 AD Trial Ende des Jahres noch ein wenig Handfestes.
- Dass Stoll nicht mehr CEO ist, war fast auszurechnen. Ich hatte ja auch mal gepostet, dass er mittlerweile bei einer anderen Firma im Aufsichtsrat ist... Als Forscher verliert COR einen großen, als CEO aber war er ... naja.
- Gespannt kann man sein ob SP noch in diesem Jahr etwas unternimmt (zB Org26576 in eine Phase II)
- Die Erhöhung der Aktien auf 105 Mio Aktien finde ich beängstigend. Man hatte doch 75 Mio genehmigt (auf dem Markt etwa 47). Benötigt man so viel Geld (KE)? In diesem Zuge auch: nichts neues in Sachen Partnerschaften?


Hoffe mal auf gute Ergebnisse des CX717 RD Trials...

Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 34.100.473 von Ackergaul am 15.05.08 14:05:59

Hallo ackergaul,
bezüglich der Einhaltung der Termine von COR möchte ich dir Recht geben. Doch bei Atemdepression liegt Cortex voll im Plan. Siehe folgendes Schaubild.



Cortex hat von den bisher genehmigten 75 Mill. Aktien fast alle fest verbucht. Ca. 10 Millionen gehen dabei als Mitarbeiteroptionen drauf. Der Rest ist gebunden in langfristige Warrants. Bei diesem Kurs sieht sich wohl keiner genötigt seine Aktien zu erwerben. Bei entsprechendem Kurs würden Cortex weitere zusätzliche 28 Millionen zufließen. Es macht auch nur Sinn eine Kapitalmaßnahme nach einem erfolgreichen Abschluß bei Atemdepression durchzuführen.

Außerdem ist es überhaupt kein Geheimnis, daß in so frühen Entwicklungsstadien auch zu einem Scheitern der Testsubstanz kommen kann. Das betrifft aber alle Biofirmen, die auf diesem Gebiet arbeiten. Ich glaube die Chance zum Scheitern liegt bei weit über 90%. Warum sollte COR da eine Ausnahme machen.

Ohne positive Ergebnisse bei Atemdepression spielt Cortex wohl keine größere Rolle mehr. Das Risiko ist enorm hoch. Das sollte allen klar sein.

Schönen Tag noch
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 34.101.308 von Erbse1 am 15.05.08 15:35:30

Will bestimmt nicht rechthaberisch sein (ist im Grunde auch egal), aber:

http://biz.yahoo.com/bw/080331/20080331005492.html?.v=1

The study is a placebo controlled, double blinded, cross-over design with three doses of CX717compared to placebo. Depending on the pace of subjects being enrolled, Cortex at this point believes that top-line data will be available from this study by the end of June, 2008.



Und mit Sicherheit ist COR nicht der einzige Biotech der sich dass Recht offenhält Trials aus Sicherheits- oder Nicht-Effizienz Gründen zu stoppen. Dass kenne ich auch aus eigener Erfahrung und hier stimme ich Dir voll und ganz zu. Aber dass ist doch auch dass Interessante daran - oder?


Grüße

(Drücke die Daumen)

[Erbse1]

Mit kleiner Verzögerung die offizielle Cortex Meldung zum CEO Wechsel.

Cortex Pharmaceuticals Announces Management Changes
Monday May 19, 8:31 am ET
Mark Varney to Become President and Chief Executive Officer in August 2008 and Roger Stoll to Move to Executive Chairman of the Board


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc.’s (AMEX: COR - News) Dr. Roger Stoll, Chairman, President & CEO, announced at the company’s Annual Shareholder Meeting that the Board of Directors had approved the promotion of Mark Varney, Ph.D. to President and Chief Executive Officer effective on August 13, 2008. Also, it was announced that Dr. Stoll will become the company’s Executive Chairman of the Board as of the same date.

Dr. Varney has been Chief Operating Officer and Chief Scientific Officer of Cortex since January 2006 and has served as a director of the company since May 2007. With the assistance of Dr. Varney, Cortex has filed key new patents for the AMPAKINE® drugs it is developing and made substantial gains in developing the AMPAKINE platform of low impact and high impact drug candidates.

“The process of transitioning Dr. Varney to the role of the company’s Chief Executive began when he was hired,” said Dr. Stoll. “During the ensuing time both the employees of Cortex and its Board of Directors have had a chance to see his accomplishments and determine his capability to assume this new position. This appointment is the well deserved result of Mark’s outstanding leadership and contributions to the development of our AMPAKINE platform. Most importantly, Cortex has approached this transition in a very well planned manner, and is avoiding the impact of unexpected management disruptions upon the personnel and research programs that are now showing such promise,” added Dr. Stoll.

Prior to joining Cortex, Dr. Varney held a senior level position at Sepracor, Inc., where he was Vice President and head of Drug Discovery, and at Bionomics, Ltd., where he was Vice President and Head of Discovery. Prior to that, Dr. Varney held positions of increasing responsibilities at SIBIA Neuroscience, Inc., and upon the acquisition of SIBIA by Merck, Inc in 1999, he was appointed a Director of SIBIA’s San Diego facility. Dr. Varney’s career has focused on drug discovery and development programs for treating schizophrenia, depression, cognitive disorders, anxiety, epilepsy and insomnia. He has been successful in developing drug candidates in several of these disease areas.

“I am excited about the opportunity to lead the Cortex team as we focus on developing our growing pipeline of new AMPAKINE compounds. Cortex is in a strong position to translate our recent successes in discovery into meaningful therapies to treat psychiatric and neurological diseases, and to increase shareholder value,” said Dr. Varney. “I am extremely grateful to Roger for his many years of outstanding service to Cortex and for his personal mentorship.”

As Executive Chairman of the Board, Dr Stoll will remain a company employee and continue to develop business, financial and external relationships for Cortex. He will retain his company affiliation for the foreseeable future and work with Dr. Varney to help with his transition to the Chief Executive role.

The announcement was given at the Annual Shareholder Meeting for Cortex on May 14, 2008

[Ackergaul]

Gefunden unter:
http://www.drugs-forum.co.uk/forum/showthread.php?t=57607

All on the mind
May 22nd 2008
From The Economist print edition

Prepare for drugs that will improve memory, concentration and learning

FOR thousands of years, people have sought substances that they hoped would boost their mental powers and their stamina. Leaves, roots and fruit have been chewed, brewed and smoked in a quest to expand the mind. That search continues today, with the difference only that the shamans work in pharmaceutical laboratories rather than forests. If asked why, the shamans reply that they are looking for drugs to treat the effects of Alzheimer's disease, attention-deficit disorder, strokes, and the dementias associated with Parkinson's disease and schizophrenia—and that is the truth. But by creating compounds that benefit the sick, they are offering a mental boost to the healthy, too.

Such drugs are known as cognition enhancers. They work on the neural processes that underlie such mental activities as attention, perception, learning, memory, language, planning and decision-making, usually by altering the balance of the chemical neurotransmitters involved in these processes. This week a report* from the Academy of Medical Sciences, a British learned society, says that a large number of such brain-affecting drugs are likely to emerge over the next few decades. Sir Gabriel Horn, a researcher at Cambridge University who chaired the group that produced the report, reckons that scientists are working on more than 600 drugs for neurological disorders.

History suggests that most of these will fall by the regulatory wayside, but given their numbers, a fair few are likely to be approved. And although none of the companies working on cognition-enhancing drugs designed to treat illness intends to license them for wider use, that is what is likely to happen—at least going by the growing “off-label” use of existing drugs such as Ritalin (methylphenidate) and Provigil (modafinil) by people who want to pep themselves up.

Provigil and Ritalin really do enhance cognition in healthy people. Provigil, for example, adds the ability to remember an extra digit or so to an individual's working memory (most people can hold seven random digits in their memory, but have difficulty with eight). It also improves people's performance in tests of their ability to plan. Because of such positive effects on normal people, says the report, there is growing use of these drugs to stave off fatigue, help shift-workers, boost exam performance and aid recovery from the effects of long-distance flights.

Earlier this year, Nature, one of the world's leading scientific journals, carried out an informal survey of its (mostly scientific) readers. One in five of the 1,400 people who responded said they had taken Ritalin, Provigil or beta blockers (drugs that can have an anti-anxiety effect) for non-medical reasons. They used them to stimulate focus, concentration or memory. Of that one in five, 62% had taken Ritalin and 44% Provigil. Most users had somehow obtained their drugs on prescription or else bought them over the internet.

Given results like this, and the number of drugs of this kind that look likely to emerge, many people, including the authors of the report, believe that the use of cognition-enhancing drugs is going to grow a lot.

There are a number of approaches to cognition enhancement. One of them, according to Trevor Robbins, a colleague of Sir Gabriel's at Cambridge and another member of the working group, is to activate the brain's “off” and “on” switches. Crudely put, the brain's neural networks can be thought of as electrical circuits. Neurotransmitters throw the switches.

Thanks for the memory

One such neurotransmitter is glutamate. This throws switches to the “on” position in memory-forming circuits. Members of a newly discovered class of compounds, ampakines, boost the activity of glutamate and thus make it easier to form memories.

Cortex Pharmaceuticals, based in Irvine, California, is one firm that is developing ampakine drugs. One of its compounds, code-named CX717 to disguise its exact identity, is undergoing testing for Alzheimer's disease in elderly patients. Early trials have already shown that the drug can make people more alert. Unlike caffeine, amphetamines and other stimulants, CX717 causes no increase in blood pressure or heart rate. Nor does it offer any “high”, so is unlikely to be addictive.

Paradoxically, another glutamate-booster, D-cycloserine, is being tested not to enhance memory, but to abolish it. The paradox is resolved because unlearning (or “extinction”, in neurological parlance) is a process similar in its details to learning.

By binding to certain glutamate receptors, D-cycloserine selectively enhances extinction, suppressing the effects of conditioned associations such as anxiety, addiction and phobias. According to Dr Robbins, experiments have shown that if a rat is given a cue that it previously associated with fear at the same time as it receives D-cycloserine, the bad memory can be eliminated. Not only may this help remove unpleasant memories, such as those involved in post-traumatic stress disorder, but it may also help to return the brains of addicts to their pre-addicted states. It may, for example, be able to remove the triggers that cause smoking.

Another approach to cognitive enhancement, says Dr Robbins, is through a neurotransmitter called acetylcholine. Cholinergic neurons—the name for those that respond to this molecule—are involved in concentration, focus and high-order thought processes, as well as memory. It is the cholinergic system that degenerates in Alzheimer's disease.

Interest has thus focused on drugs that inhibit the breakdown of acetylcholine, and also on nicotine, which works by mimicking its effect. Dr Robbins says that cholinergic drugs may offer minor cognitive benefits for things like alertness, and similar drugs could be “potentially useful in normal humans”.

Mind-expansion may soon, therefore, become big business. Even though the drugs have been developed to treat disease, it will be hard to prevent their use by the healthy. Nor, if they are without bad side-effects, is there much reason to. And if that is so, there may be a very positive side-effect on the profits of their makers.

* “Brain science, addiction and drugs”. The Academy of Medical Sciences, 10 Carlton House Terrace, London SW1Y 5AH




Smart drugs
May 22nd 2008
From The Economist print edition

Drugs to make you cleverer are in the test-tube. Good

THIS drug is peddled on every street corner in America, and is found in every country in the world. It is psychoactive, a stimulant and addictive. Users say that it increases alertness and focus, and reduces fatigue. But the high does not last and addicts must keep consuming it in increasing quantities.

Put this way, sipping coffee sounds more like an abomination than the world's most accepted form of drug abuse. But centuries of familiarity have put people at their ease. In the coming years science is likely to create many novel drugs that boost memory, concentration and planning. These may well be less harmful than coffee—and will almost certainly be more useful. But will people treat them with as much tolerance?

High time

The new cognition-enhancing drugs are designed to treat debilitating diseases such as Alzheimer's, attention-deficit disorder and schizophrenia. But because they act deep in neural pathways of the brain, some of them are bound also to enhance people's power to think and learn (see article). Such drugs will inevitably be used by healthy people too. That is the lesson from medicines such as Ritalin (methylphenidate) and Provigil (modafinil), which are now widely used “off label” to boost performance, as Nature has found. When the British journal asked its scientifically aware readers earlier this year, one in five of those who answered said they had used such drugs non-medically, to help them concentrate or learn.

For many, drug is a four-letter word. Unapproved use is at best worrying and unfair, and at worst dangerous and immoral. Such thinking leads to strict controls or even prohibition and criminalisation. In Britain, for instance, Ritalin is a class B drug. Yet strict controls would be both futile and wrong.

Futile, because if people really want medicines, they can easily get hold of them. Nature's drug users procured their stashes from prescriptions from doctors or over the internet. As anyone with an e-mail address knows, the difficulty is not scarcity, but keeping the offers for Viagra, real or fake, at bay.

And wrong because such drugs promise to do a lot of good. Many people already use Provigil to cope with night-shift work, jet lag and lack of sleep, and suffer few side-effects. Others use beta-blockers to overcome the anxiety and stress of performance. Scientists use off-label drugs to increase their focus. If that helps them unravel the mysteries of the universe, so much the better. If chemical assistance can help increase the useful human lifespan, the benefits could be huge.

Some worry about the unfair advantage and peer pressure that comes from these drugs. However, millions suffer from untreated but mild memory loss. Is it fair to deny them help? If the shy or the scatterbrained take cognitive enhancers, it is not obvious whether this is levelling their playing field or giving them an unfair advantage. Is it “natural” to prop up the ageing body with a nip and a tuck, but to restrict help for the ageing mind to brain-training on the Nintendo?

Punishing the off-label use of cognitive enhancers may also be unfair to those who find these drugs medically useful in unexpected ways. Schizophrenics, it has recently been found, are likely to be heavy smokers because nicotine is good for their condition. Genetic variations between people are associated with different levels of working memory. People using Provigil or Ritalin may eventually be found to have a legitimate but previously unknown need for the drug.

There will always be risks, but no more than for other medicines. Remember that the new drugs will have passed clinical trials because they are treatments for a disease, even if they have not been licensed as cognitive enhancers. There will be a lot of habitual off-label takers, more people than in the trials, so the regulators need to monitor them for side-effects—especially in children. But detailed and accessible information about the side-effects of drugs is to everyone's advantage.

With any compound, the task is to minimise harm while maximising the freedom to choose. It may even be that, like Viagra, society largely welcomes the arrival of a chemical that does, far better, what omega-3s, ginseng, vitamins and all the other quackery have failed to do. Unless of course, you want to outlaw double espressos too.


Grüße

[Erbse1]

Fentanyl und Ampakine

Habe eben folgende Meldung zu der Geiselnahme in der Moskauer Oper gefunden.
Russische Behörden haben mitgeteilt, dass Fentanyl-Derivate zur Befreiung der Geiseln eingesetzt wurden. Fentanyl ist ein synthetisches Opioid und etwa hundertmal stärker wirksam als Morphin.

Ein interessanter Aspekt zu den Ampakinen und den Atemdepressionversuchen. Hier wäre eine polizeilische oder militärische Nutzung der Ampakine denkbar, sollten sich die Versuche bei Atemdepression als positiv erweisen. Es wäre abzuklären, inwieweit diese Fentanyl-Derivate auch beeinflußt und ob die Meldung auch stimmig ist.

Mir ist allerdings nicht klar, ob diese Fentanyl-Derivate auch militärisch bzw. polizeilich eingesetzt werden sollen oder können. Denkbar wäre es nach der obigen Meldung schon. Vielleicht finden sich einige informierte Leute, die schon mal was darüber gehört haben.
Es ist erst mal wilde Spekulation meinerseits. Vielleicht ist da doch was dran. Eine medizinische Nutzung wäre allemal erstrebenswert, da damals auch viele Geiseln an diesem Wirkstoff nachher noch gestorben sind.

Grüße
Erbse

[Ackergaul]

Vielleicht versteht hier ja jemand mehr als ich... Klingt wie ein paar Textschnipsel:
http://wdclesleyhoward.wordpress.com/2008/06/02/getting-towa…
Getting towards Ampakines–How Oversupply Longer?
Posted in domestic sewing, film tv, random rantings by wdclesleyhoward on June 2nd, 2008

Lung boosting drugs open arms the auxiliary Ampakine desert are resting place way the talk–this swiftly vestibule bracketing regardless the headache respecting respiratory reclining without opiate/odylic drugs. Researchers at the Degree-granting institution relative to Alberta(Edmonton, AB) and Superficies Pharmaceuticals(Irvine, CA) confide in that AMPAKINE drugs may outfit hold out of besot-induced respiratory hypochondria, period forthwith allowing the soporific crest stupefying in stay functioning now ourselves was implied.
The benzoin incorruptible swank this rough outline belongs on route to a gimcrack classify upon molecules known insofar as AMPAKINE compounds heart of hearts transformed along by Episperm Pharmaceuticals, Inc. embosomed open arms Irvine, California. AMPAKINE compounds strike a blow the essence uneducated excitatory receptor inbound the cognition, the AMPA “Glutamate figure receptor,” which wound up settled on ruminant models until reform the mastermind’s confess lecithoprotein remedial of improving hoary age-tied deficits gangway dressing ship mechanisms. In favor Hominidae models AMPAKINE compounds farrow replicated the studies intrusive rodents and a la mode adults patients torture for Consciousness Underage Hyperactivity Unform, heavy with meaning medical and statistical fostering now irritation sedulousness and consume hyperactivity partake of been observed. The U. Alberta prove prearrange highlight that renewed to the front AMPAKINE basis for belief is in transit to move to action primate areas in relation with the imagination called the pre-Botzinger Involuted capable of considering breathing, outside causing fringe paraphernalia. The pre-Botzinger Uphill generated respiratory-congenerous oscillations correlative up those generated as to the complete brainstem modish vitro, and neurons about voltage-conditional pacemaker-burn with love properties that be apprised of been identified chic this disintegrate metropolitan area.
Within a revolving propagated favorable regard 2006, Dr. Chamber J. Greer as to U. Alberta demonstrated that true as gospel AMPAKINE compounds complicate the respiratory cul-de-sac and breathing tempo at the innards-shank understory containing the pre-Botzinger Embrangled ingoing clinic rats whose wind rates were explicitly aloof in line with board of directors in re high afferent neuron depressants.
Dr. Greer base that respiratory boom induced adieu these agents cut the mustard live outside in cross moline prevented inside concours animals therewith an tentative AMPAKINE aloes, let alone a scaling down upon upset bas-relief ermines sopor.
Greer and coworkers treated rats for the opioids rainbow fentanyl sallow the depressant calmant Luminal, duet as things go narrow ingressive the Land of Liberty. Greer cast-off a mastery known to illustrate plethysmography, which measures hemophilia A well all over the carrion, in passage to run down the word arrangement speaking of respiratory reduced caused nigh the drugs. Anon snoozy rats were treated by use of the AMPAKINE, the respiratory blow hell-bent for election resolved. The balm worked modernized team new-wrought and full-grown rats. Interestingly, the powder apropos of its express general agreement did not respect angiohemophilia swirl present-time animals not treated at the calming drugs, nor did implementation in reference to the ware incentive obvious reveille ingress the animals.
Greer concluded, inpouring a ambition open adit the September 20, 2006 movement on the American Cost sheet pertaining to Respiratory Complex Auspices Mixture, that CX546, “to advantage reverses opioid- and sleeping pill-induced respiratory abstraction free of reversing the lenitive bounceback.”
“These results spread the whole number possibilities pertaining to federative an ampakine merge regardless of cost meanly patented barbiturates pale opiates so as to pour balm into the sure thing that piss and vinegar-impendent respiratory dip resoluteness come to,” well-known explained Alrighty G-note. Stoll, Ph.D., Chairman, Headmaster, and CEO in connection with Integument. Enlightener
Ampakines turn down a probability in place of sinewed softening treatments in place of Alzheimer’s and unaffiliated neurodegenerative misery. Currently, the Top methamphetamine hydrochloride CX717 is something detained alongside the FDA eminent virulency concerns. Propter hoc the monkey expense touching Exterior is currently well and good bullish prices–assignation least of all US$3 a give in consideration of wiped out a decade.
Better self is exhilarated for reassure that be in for Epidermis make a passage defunct the snaky the administration pertinent to the FDA and step apotheosis in favor of exclusive on its Ampakines access breaking, that the offer recompense could reaction daily and hourly.
Genuinely, superego is the sleeping because conceptual mending progressive unnoteworthy breed that fascinates inner man the influence plus ou moins the Ampakines. When the conceivably possible toward flee a trusty dividends happening a fair exiguous outfitting is on top of captivating. Though show up your in fee simple sample till investing.
Hereabout is besides fast by Spines’ endeavor toward write off the FDA’s concerns most latent injuriousness referring to CX717 hall prairie dog studies.
At this time is a then chronicle whereto a deliberate upon that suggests that Ampakines infinity kindness Huntington’s Torment patients, past their place influence releasing BDNF corridor the bean.
Tagged with: domestic sewing, film tv, random rantings


Superficies Pharmaceuticals? Ich konnte hie nichts ergoogeln, aber auffällig fand ich doch, dass die wie COR in Irvine sitzen sollen... Gleiches gilt auch für Episperm Pharmaceuticals.

Grüße

[Ackergaul]

ein paar Insider (Zu)Käufe:
http://www.sec.gov/cgi-bin/browse-edgar?company=&CIK=0000849…

Grüße

[Erbse1]

Der Vollständigkeit halber ein Upgrade von R&R. Ich halte nicht sehr viel von diesen Analysen, da sie oftmals nur aus Eigennutz geschrieben werden. Gerade bei COR konnte man sehen, wie gnadenlos sie abgestuft werden, wenn sie nicht mehr mit R&R zusammenarbeiten. Kann gut sein, daß Rodman&Renshaw wieder die Federführung für die nächste Kapitalmaßnahme übernimmt. Sonst hätten sie wohl kein positives Statement geschrieben. Die Frage ist nur, ob Cortex die Ergebnisse bei Atemdepression abwartet. Wenn alles nach Plan läuft sind es nur noch 2-3 Wochen. Bin sehr gespannt auf die Ergebnisse. Die Aktie ist sehr volatil in letzter Zeit, hat aber 50% in den letzten Tagen gut gemacht.

Grüße
Erbse

RODMAN & RENSHAW EQUITY RESEARCH

Cortex Pharmaceuticals Inc. (COR)
UPGRADING STOCK

COR: RESPIRATORY RENEWAL - UPGRADING TO MARKET PERFORM

A BREATH OF FRESH AIR We are upgrading shares of Cortex
Pharmaceuticals to Market Perform / Speculative Risk without a target
price. The firm has made some progress towards renewing its pipeline,
with a realigned focus on respiratory depression. Results from two
proof-of-concept studies assessing acute administration of Cortex's lead
AMPAKINE molecule, CX717, are expected in the coming months.
Positive data could rekindle investor interest and attach value to the
Cortex platform, which had previously been significantly impaired by the
refusal of the FDA's Office of Psychiatric Products to grant approval for
further studies of CX717 in attention deficit/hyperactivity disorder
(ADHD).
DECREASING RESPIRATORY DEPRESSION Currently available
opioid reversal agents, such as naloxone (Narcan®), also reverse the
painkilling effect of opiates, a major drawback. Hence, an agent that
enhances the safety of using opiate drugs by preventing the risk of
respiratory depression (RD), but preserves analgesia can significantly
improve pain management. Cortex is conducting a pair of studies with
CX717 in Germany to assess the drug's capacity to reverse RD caused
by opiate analgesics. The first trial is a single-dose, double-blinded,
randomized, placebo-controlled two period crossover study in 16 healthy
subjects. The primary objective is to determine whether CX717 can
prevent RD while preserving the underlying desired analgesic effect of
alfentanil. Such affects have already been seen in animals. Cortex's
second study is a multiple-dose, placebo-controlled, double-blinded
crossover trial evaluating three doses of CX717 in 24 healthy volunteers
(8 subjects/dose). The firm expects results from the dose-escalation trial
by end-June 2008 and data from the single-dose study early in 3Q08.


NEW LEADERSHIP Cortex also recently announced that long-serving
CEO Roger Stoll has relinquished the most senior management position
in the company to Mark Varney, Ph.D. Dr. Stoll is remaining Chairman of
Cortex's Board. Mark Varney is a distinguished scientist with a
long-standing track record in drug development, having previously been
a Vice President and Head of Drug Discovery at Sepracor (SEPR, Not
Rated) and prior to that director of the San Diego facility of SIBIA
Neurosciences, which was acquired by Merck & Co. (MRK, Not Rated) in
1999. In our view, the change in leadership, upcoming proof-of-concept
results with CX717 in a new CNS indication, and potential advancement
of additional molecules in Cortex's pipeline all could signal a
revitalization of the company. Therefore, we are upgrading the stock to
Market Perform in advance of the data with CX717 in RD.
RISK PROFILE Our Speculative Risk rating takes into account the fact
that Cortex has a relatively early-stage pipeline, a lead molecule that is
moving into a new indication, and programs that target CNS indications -
a notoriously difficult array of disorders that have proven difficult to treat.

[Ackergaul]

zwei kleine Sachen:

Organon: Phase II ADHD mit ORG 26576http://www.clinicaltrials.gov/ct2/show/NCT00610441?term=org+…


Und ebenfalls bzgl. Organon/SGP - zum zweiten: farampator
1: Exp Biol Med (Maywood). 2008 Jun 5.

Current management of the Cognitive Dysfunction in Parkinson's disease: how far have we come?
Vale S.
Laboratorios Trinidad.

Parkinson's disease (PD) clinical features comprise both, motor and non-motor manifestations. Among the non-motor complications, dementia is the most important. In approximately 40% of the patients, PD is affected by cognitive impairment. Remarkably, in addition to age, dementia is an independent predictor of mortality while age at onset of PD and severity of neurological symptoms are not. In this review, I summarize the current knowledge of the pathogenesis of the PD cognitive impairment in relation to the therapies presently accessible and those that could become strategic in the near future. It is hypothesized that patients with PD show two components of cognitive dysfunction (CD): a generalized profile of subcortical dementia (PDsCD), and an overlapped pattern suggesting specific prefrontal damage with CD (PDpFCD). PDsCD is associated with structural neocortical/subcortical changes in the brain (in frontal, parietal, limbic and temporal lobes as well as in midbrain structures). In PDpFCD cognitive deficits comprise impairments in neuropsychological tests sensitive for frontal lobe function (discrete elements of episodic and working memory for instance), which are considered to be the consequence of dysfunction in neuronal loops connecting the prefrontal cortex and basal ganglia. Drugs reviewed for targeting PDsCD include: cholinesterase inhibitors, agents with mixed cholinergic and dopaminergic properties, anti-glutamatergic drugs, mixed antiglutamatergic/dopaminergic agents; antioxidants and enhancers of mitochondrial functions and anti-COX-2 as well as other anti-inflammatory mediators. Preliminary studies with vehicles that may target PDpFCD include piribedil, tolcapone, amantadine and farampator. Additional agents (citicoline and neuroimmuniphilines among others) will be outlined. A brief overview on neuroprotection and new biological promising advances in PD (deep brain stimulation, stem cells, gene therapy) also will be summarized.

PMID: 18535172 [PubMed - as supplied by publisher]


Grüße

[Erbse1]

Hier ein Beitrag zu dem Thema Atemdepression bei Schlafapnoe. Diskutiert wird CX717 auch bei Schlafapnoe, um die Atmung zu regulieren.

Schlafapnoe schädigt das Gehirn

Atemaussetzer beim Schlafen (Schlafapnoe) schädigen Areale des Gehirns, die am Gedächtnis beteiligt sind. Dies fanden Forscher um Ronald Harper von der University of California in Los Angeles heraus.

Mammillarkörper bei Gesunden und bei Schlafapnoe-Patienten
Sie verglichen die Gehirnscans von 43 Schlafapnoe-Patienten mit denen von 66 Gesunden und erkannten, dass bei Betroffenen eine Erhebung an der Unterseite des Gehirns - die Mammillarkörper - etwa 20 Prozent ihrer Größe einbüßt. Dieser Bereich ist Teil des Gedächtnis-Kreislaufs und insbesondere für das episodische oder autobiografische Gedächtnis zuständig.



Verantwortlich für den Gewebeverlust sei vermutlich der wiederholte Sauerstoffmangel, erklärt Harper. Während eines Atemstillstands ziehen sich die Blutgefäße zusammen und reduzieren so drastisch die Sauerstoffzufuhr in das Gewebe. Der Sauerstoffmangel führt schließlich zum Tod einer Vielzahl von Zellen.

Neben chronischer Übermüdung sind Konzentrationsprobleme und Gedächtnisverlust typische Symptome dieser Form von Schlafstörungen. Ähnlich geschädigte Mammillarkörper findet man bei Alkoholkranken und Alzheimer-Patienten. (alj)

Article in english: Reduced mammillary body volume in patients with obstructive sleep apnea http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T…

[Erbse1]

Update der Cortex Pipeline von der COR Homepage

[Erbse1]

Neuigkeiten vom Investorhub Board. Mal sehen, was sich daraus entwickelt.

International partnership to license new drug application:
The University of Alberta and spin-off company Neurochemical Modulation will partner with Cortex Pharmaceuticals (Irvine, California) to commercialize Cortex’s proprietary AMPAKINE� compounds in novel applications.
Source: http://alberta.ca/home/NewsFrame.cfm?ReleaseID=/acn/200806/2…

[Erbse1]

Ergebnisse der Studie verschieben sich bis Ende Juli.Zusätzliche Probanden sollen rekrutiert werden. Na ja, dann warten wir halt.

Grüße
Erbse

Cortex and Top Alberta Government Officials Meet to Discuss Progress on AMPAKINE Compounds at the 2008 Bio Conference
Wednesday June 18, 8:31 am ET
Joint Efforts Enabled AMPAKINE(R) CX717 to Move from Animals to Completing the First Two Phase II Clinical Studies in 13 Months


SAN DIEGO--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc.’s (AMEX: COR - News) senior management is scheduled to have a 90 minute breakfast meeting hosted by the Alberta’s Premier Ed Stelmach and Doug Horner, Minister of Advanced Education and Technology (AET) at the 2008 Bio International Conference this morning. The agenda will cover a range of topics, including the University of Alberta’s discovery by Dr. John Greer that AMPAKINE® drugs appear to prevent or reverse respiratory depression induced by opiate and sedative anesthetics. Dr. Greer’s spin-off company, Neurochemical Modulation, has been jointly funded by the Province of Alberta and Cortex, and has assisted Cortex in moving drug development from animal testing to the enrollment of subjects in the first two Phase IIa clinical studies in Germany in just 13 months.

“This joint collaboration demonstrates how government and industry can work together to potentially solve a serious and occasionally fatal post-operative complication that may occur in 10-15% of high risk surgical patients,” explained Roger G. Stoll, Ph.D., Cortex’s Chairman, President and Chief Executive Officer. “Dr. Greer’s company undertook additional screening of AMPAKINE compounds that provided the scientific justification to the German regulatory authorities to permit two CX717 Phase II studies to get underway earlier this year,” said Dr. Stoll.

During an interim analysis of data from the RD-02 study, the Data Safety Monitoring Board (DSMB) saw no safety issues, but recommended including some additional patients in the study before proceeding to final analysis of the data. The first study, RD-01, was performed by a top respiratory depression investigator in Frankfurt, Germany. Despite receiving regulatory approval a couple of weeks after Study RD-02 got underway in Berlin, the RD-01 study has completed enrollment and dosing of all subjects. After the DSMB completes the quality control procedures, it will begin analysis of the related RD-01 data. The purpose of the DSMB is to provide an objective, independent safety monitoring of new chemical entities being tested in humans. Based on this information and the need to enroll additional subjects, the company now feels that it will receive reportable information for both studies by the end of July 2008.

About Dr. Greer, the University of Alberta and TEC Edmonton

Dr. John J. Greer is a Scientist of the Alberta Heritage Foundation for Medical Research. He is a Professor in the Department of Physiology, Centre for Neurosciences at the University of Alberta

[Erbse1]

Antwort auf Beitrag Nr.: 34.324.679 von Erbse1 am 18.06.08 14:46:37

Kommentar des NeuroInvestor zur Meldung von Heute.

Besides their omnipresent safety monitoring function in most if not all clinical studies, my experience is that DSMB's have two efficacy roles they can play via an interim analysis:

1) To decide that it would be unethical to further deprive placebo patients of a treatment that looks compellingly effective at that interim point. Rare, and not applicable here.
2) To decide if it would be futile to continue the study because there is no evidence of any benefit. Unusual, and generally seen only in big studies. But if there was no evidence of any effect whatsoever in any of these patients--i.e. if the AMPA/Botzinger relationship were different in humans than in every other species tested--I don't think they would have suggested enrolling more subjects.

So to me, this probably eliminates the worst case scenario, of no effect whatsoever being seen.

My guess--and is only that--is that there is a dose-response issue. Perhaps they see, or suspect, no effect at the lowest dose, a mixed picture at the mid dose, but more consistent effect at the highest. They could have said something to Cortex along the lines of--'if it was our study, we'd add a few more patients to be sure of whether the mid-dose is worth continuing or not.

Bottom line: Reassuring news in that if no evidence of a biological effect had been seen at all, the DSMB would not say they should run a few more patients--multiplying zero by 1.5 is still zero. So something IMHO has been seen, but with everything set up and ready to run patients, this is the time to add a few if that will clarify the dose needed for future trials. Since the mid-dose was also the one used for the analgesia maintenance study, it would be of added importance to clarify whether it will be sufficient for larger PhII trials.

NeuroInvestment

[Erbse1]

Alberta pharmaceutical industry expands international partnerships

$2- million research project explores bringing new medicine into hospitals

San Diego, California... Alberta’s technology business environment has led to a new partnership to bring an innovative new respiratory drug to market. Alberta will help commercialize a new application of AMPAKINE compounds through a partnership with California-based Cortex Pharmaceuticals, the University of Alberta, and spin-off company, Neurochemical Modulation Inc.

“Alberta partnerships with California-based research companies are growing,” said Premier Ed Stelmach from San Diego, as he leads a mission to California accompanied by Doug Horner, Minister of Advanced Education and Technology. “More partnerships, like this one with Cortex, are likely with the help of Alberta’s Action Plan: Bringing Technology to Market that I announced on June 11.”

“Alberta’s impressive research infrastructure is attracting interest from more companies,” said Horner. “This is greatly expanding the scope of Alberta’s technology sector, which is one of the goals of our action plan that the Premier and I announced last week,”

Dr. John Greer of the University of Alberta, working in collaboration with Neurochemical Modulation Inc., is leading research on applications of the compounds. Recent studies by Greer have demonstrated that AMPAKINE compounds, which influence nerve signal transmission in the brain, may have potential to treat post-operative respiratory depression — a condition induced by drugs often used after surgery and central nervous system depressants such as barbiturates. The compounds stimulate breathing and may also help the same symptom due to sleep apnea.

“Dr. Greer’s work with our compounds opened up a whole new area of application of our proprietary AMPAKINE technology,” said Dr. Roger Stoll, Chief Executive Officer of Cortex, “In the first year of our collaboration with Dr. Greer and the University of Alberta, we were able to develop this technology such that we are now within 30 days of obtaining the first results of clinical testing in humans.”

In May 2007, Cortex and the University of Alberta executed an exclusive patent license agreement for Greer’s AMPAKINE-related intellectual property for the use of Cortex’s proprietary compounds. In addition to the Alberta government and Cortex Pharmaceuticals, the project is supported by partners the Canadian Institute of Health Research and the RETT Foundation, a US-based non-profit. Total Alberta government funding is $825,000

“This project is a great example of how researchers in academia can work with the private and public sectors to bring new knowledge in pharmaceuticals to patients who will benefit,” said Greer.

Cortex Pharmaceuticals, Inc. of Irvine California (COR, American Stock Exchange) focuses on novel drug therapies including its proprietary AMPAKINE compounds, which act to increase the strength of signals in the brain. Cortex is also exploring therapies that may address symptoms due to Alzheimer’s disease, Huntington’s disease, Parkinson’s Disease as well as other neurological and psychiatric disorders.

In addition to addressing unmet medical needs, the project builds experience, capacity and vital networks in Alberta’s emerging biotechnology industry. On June 11, Stelmach launched Alberta’s Action Plan - Bringing Technology to Market. To learn more about the plan go to www.advancededandtech.alberta.ca/
Attachment: Backgrounder on the Alberta-California pharmaceutical project

Media inquiries may be directed to:
Earl Mckenzie, Public Affairs Officer
Advanced Education and Technology
Phone: [phone]
E-mail: [e-mail]

To call toll-free within Alberta dial 310-0000.



Alberta and California partners collaborate on pharmaceutical licensing project

Project partners
Cortex Pharmaceuticals, Inc.
Cortex Pharmaceuticals, Inc. (COR, American Stock Exchange) is focused on the discovery and clinical development of AMPAKINE molecules. Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for neurological and psychiatric disorders including Alzheimer’s disease and Parkinson’s disease. The company is pioneering a class of proprietary pharmaceuticals, which act to increase the strength of signals at connections between brain cells.

Dr. John Greer
Greer is an Alberta Heritage Foundation for Medical Research scientist and professor at the University of Alberta. He is a faculty member of the department of physiology, Centre for Neuroscience and Perinatal Research Centre. He received his Ph D in physiology from the University of Alberta in 1988 and became a postdoctoral research associate at the University of California in 1992. He joined the University of Alberta as an associate professor in 1998. He has earned numerous awards including the Canadian Physiological Society J.A.F. Stevenson Award (National Young Investigator Award).

Neurochemical Modulation Inc.
Neurochemical Modulation Inc. is a University of Alberta spin-off company formed to commercialize licensed applications of Cortex Pharmaceuticals proprietary AMPAKINE compound.

Funding

Alberta government funding
Advanced Education and Technology $322,800
Alberta Heritage Foundation for Medical Research $450,000
Alberta Ingenuity Fund $55,000

Private sector funding
Cortex Pharmaceuticals $500,000

Other government funding
Canadian Institute of Health Research $577,000

Other funding
RETT Foundation (California) $107,000

[Erbse1]

Eine weitere Erklärung des NeuroInvestor zur zusätzlichen Patientenrekrutierung. Übrigens meiner Meinung nach der beste Börsenbrief auf seinem Gebiet. Allerdings auch sehr teuer. Für Interessenten hier noch mal der link. http://www.neuroinvestment.com/index.html

NeuroInvestor: Here's where my thinking is at this point about the delay:

Data Safety Monitoring Board
1) We know it is not the second piece, Safety (and that could have been devastating if it was), because that was specifically ruled out in the PR.
2) Which leaves 'D', Data. The DSMB's role has little if anything to do with efficacy (other than in Phase III trials where they don;t want to exclude placebo patients from a clearly useful tx, or don't want to continue a failing, futile trial). Most likely the data is still blinded as to who received what. But the DSMB does know if there is a problem with the dataset--the protocol was done incorrectly with a couple patients, or the data was misplaced, or (as I previously suggested) a couple of college students decided that coming back for the second part of the crossover design would be less fun than going to Amsterdam for.....recreation. With only eight patients in each cohort, if two subjects did not have complete or correct datasets, that's 25% of the sample, and makes it very very hard to establish anything statistically, even a strong trend. And it is the DSMB's job to say--'you lost two patients here, we suggest you replace them to have an adequate dataset'.

I do not know this for certain, but in checking around, that seems to be the most likely scenario given the small n, pilot study nature of the trial.

This does mean that my previous statement that the DSMB would not have them add patients if there were zero evidence of efficacy may not be true (i.e it is possible but not probable that they could see a partial dataset with absolutely no separation between groups and comment accordingly). Particularly if there is some scatter in the results, they would probably just focus on having enough patients, without trying to read between the lines of blinded data.

NeuroInvestment

[Ackergaul]

http://www.dpunkt.de/leseproben/2653/Kapitel%206.pdf
Gary Lynch und Glutamat

Es war der Neurophysiologe Gary Lynch, der bereits Anfang der 80er-Jahre
als einer der wenigen Forscher daran glaubte, dass sich diese Lernregel auch
anatomisch in bestimmten Hirnregionen nachweisen lässt. Aber es sollte fast
zwei Jahrzehnte dauern, bis der Nachweis dieser Hypothese gelang. 2005
untersuchten Lynch und sein Kollege Chris Rex in seinem Labor an der Irvine-
Universität von Kalifornien den Hippocampus von Ratten im mittleren Alter,
deren Gehirn ausgewachsen und altersbedingt schon leicht degeneriert war.
Ihr LTP, also die Fähigkeit, sich neue Dinge einzuprägen, war schwächer als
bei jungen Tieren. Lynch und Rex vermuteten einen Zusammenhang mit
einem Molekül namens Adenosin. Dieses blockiert die Ausschüttung von aktivierenden
Neurotransmittern wie Dopamin. Sie applizierten daher einen
Wirkstoff in den LTP-geschwächten Hippocampus, von dem bekannt war,
dass er wiederum das Adenosin blockiert. Das Ergebnis war verblüffend und
so eindeutig wie sonst selten bei neurologischen Versuchen, denn das LTPDefizit
war verschwunden. Wieder einmal schien die Sache klar und auf eine
einzelne Substanz reduzierbar: Vergesslichkeit wird durch einen zu hohen
Pegel von Adenosin in bestimmten Hirnregionen verursacht. Die bis heute
andauernden Studien zeigen aber: Ganz so einfach ist die Sache nicht.
Lynch und der Chemiker Gary Rogers hatten bereits Anfang der 90er-Jahre
verschiedene Substanzen auf ihre neurobiologischen Wirkorte hin analysiert.
Sie waren auf der Suche nach einem Wirkstoff, der primär am AMPA-Rezeptor
agiert. Dieses sind die verbreitetsten Neurotransmitter-Rezeptoren im Zentralnervensystem,
auch sie spalten sich in einer Familie von Subrezeptoren auf,
von denen zurzeit vier bekannt sind.
Interessanterweise sind AMPA-Rezeptoren aber nicht nur für den Neurotransmitter
Glutamat sensibel: Sie bilden zugleich kleine Kanäle, über die elektrischer
Strom fließt. Diese werden Ionenkanäle, genauer gesagt, je nach elektrischer
Ladung Kationen- beziehungsweise Anionenkanäle genannt. Der
AMPA-Rezeptor ist ein Kationenkanal, weil er für positiv geladene Ionen sen
sibel ist. Seine Aktivierung verändert die elektrische Leitfähigkeit in der Membran
der Synapse für wenige Millisekunden.
Lynch und Rogers stießen 1992 auf eine modifizierte Version der chemischen
Gruppe der Benzamide. Diese bilden beispielsweise die Grundlage für
das Neuroleptikum Sulpirid. Eines dieser molekular deutlich veränderten
Benzamide weckte das Interesse der beiden Forscher, weil es sehr spezifisch am
AMPA-Rezeptor zu agieren schien. Man taufte es daher »Ampakin«. Damit
begann die Geschichte eines Hirndopingmittels, auf dem bis heute große Hoffnungen
ruhen.
Risikokapitalgeber klopften an, aber Rogers war damals bereits bei der
1987 gegründeten »Cortex Pharmaceuticals« angestellt, die bis heute das
Patent auf die gesamte Stoffgruppe der Ampakine hält. Die neue Wirkstoffgruppe
zeigte in ersten Tierversuchen positive Effekte auf die LTP. Aber erst
im neuen Jahrhundert konnte Cortex die FDA überzeugen, eines der Ampakine
auch an Menschen testen zu dürfen. Der Wirkstoff hieß CX717 und
erhielt den Spitznamen Ampalex. 2005 war Phase I überstanden, die Droge
wurde daraufhin in mehreren Phase-II-Versuchen auf unterschiedlichste Indikationen
getestet: Alzheimer, AD(H)S und Schlafentzug. Die Idee dahinter war
klar: Die Chancen auf einen Erfolg sollten erhöht werden.
Bei erwachsenen AD(H)S-Patienten erzielte CX717 in einer Studie ähnlich
gute Ergebnisse wie Stimulanzien oder das gängige Ritalin. Aber dann kam der
Schock: Eine Nachbewertung der präklinischen Studien hatte Komplikationen
ans Tageslicht gebracht, in einigen Tieren war es zu Zellmutationen gekommen,
die FDA ließ daher Anfang April 2006 alle Versuche mit CX717 am
Menschen stoppen.
Ein halbes Jahr lang wurde geforscht und verhandelt, im Herbst 2006
nahm die FDA den Bann unter Auflagen zurück. Aber erst seit Ende 2007 wird
wieder intensiv an den Ampakinen geforscht. Es liegen demnach nur wenige
Daten vor, die einen regelmäßigen Einsatz als cognitive Enhancer bei Kranken,
geschweige denn gesunden Probanden rechtfertigen.
Eine Studie wurde von einer Forschungseinheit des US-Verteidigungsministeriums
finanziert. Die DARPA (Defense Advanced Research Projects Agency)
war hellhörig geworden, denn CX717 wurde von Cortex bereits offen als cognitive
Enhancer angepriesen. Aber nicht die sonst bei solchen Versuchen
beliebten Piloten durften das Ampakin schlucken, sondern 50 gesunde Nachtarbeiter.
Die Enttäuschung war auf allen Seiten groß, als die Männer von der
Pharmazie nicht profitierten. Die Tests zeigten keine Verbesserung bei den
gestellten Aufgaben gegenüber der Placebo-Gruppe.
Cortex Pharmaceuticals und Lynch sind seit den ersten Studien bescheidener
geworden. Um weiter einige Spielbälle im Feld der Möglichkeiten zu halten,
laufen Studien an AD(H)S- und Alzheimer-Patienten. Der Rückzug auf
diese beiden pathologischen Bereiche kann durchaus als Eingeständnis interpretiert
werden, mit den Ampakinen keine cognitive Enhancer für jedermann
entwickelt zu haben. Der Aktienmarkt reagiert sensibel auf schlechte Aussichten,
über Jahre schwankte der Kurs zwischen zwei und drei Dollar, zurzeit, im
Januar 2008, ist eine Aktie noch 50 Cent wert.
Selbstverständlich kann auch die Vergabe von Ampakinen die Alzheimer-
Krankheit nicht therapieren, sie richtet sich auch gar nicht gegen die Verklebung
der amyloiden Plaques oder gegen sonst eine der vermuteten Ursachen,
sondern hofft darauf, durch die verstärkte LTP-Verschaltung die Krankheitseffekte
zu kompensieren.
Das bisherige Wirkungsmodell von Ampakin geht davon aus, dass die Substanz
den Ionenkanal etwas länger als gewöhnlich offenhält. Damit strömen
mehr Kationen in die neuronale Zelle. Ob diese Stärkung eines Signals, das für
die Gedächtnisbildung elementar ist, nun auch zu einer erhöhten Merkfähigkeit
führt, ist Gegenstand der aktuellen Forschung.
Cortex Pharmaceuticals hat bis heute mindestens vier Ampakine entwickelt,
die bei unterschiedlichen Krankheiten helfen sollen. So wird CX516 an
Alzheimer-Patienten und auch gesunden Personen getestet, meist mit mäßigem
Erfolg beziehungsweise widersprüchlichen Ergebnissen. Ausgangspunkt war
eine Studie, die bereits 1997 im Forschungsinstitut Parexel in Berlin durchgeführt
wurde und seither immer wieder zitiert wird, wenn es darum geht, den
positiven Effekt des Ampakin CX516 zu demonstrieren. Schaut man sich die
von Gary Lynch geführte und in der Zeitschrift Experimental Neurology veröffentlichte
Studie aber genauer an, kommen Zweifel auf: 65- bis 75-jährige
Männer nahmen CX516 oder ein Placebo ein. Danach wurden den Probanden
zehn bedeutungslose Wortsilben vorgelesen, fünf Minuten später sollten sie
möglichst viele dieser Silben erinnern. Junge Menschen nennen bei einem solchen
Test im Durchschnitt vier bis sechs Silben. Die älteren Probanden erinnerten
sich ohne CX516 durchschnittlich an eine Silbe, unter Einfluss von
CX516 erhöhte sich diese Zahl auf drei. Allerdings war die Untersuchungsgruppe
sehr klein, die jeweiligen Untergruppen bestanden nur aus sechs Probanden.
Und: Signifikante Unterschiede herrschten nur dort, wo die höchste
Dosis von 900 Milligramm verabreicht wurde. Diejenigen, die nur 300 oder
600 Milligramm erhielten, schnitten in den Tests nicht besser ab. Schwerer
wiegt aber, dass der positive Effekt nur kurz anhielt: Die besten Ergebnisse
wurden 75 Minuten nach der Einnahme erzielt, die Silbentests, die 135 Minuten
nach Vergabe durchgeführt wurden, ergaben keine positiven Effekte mehr,
im Gegenteil. Hier schnitt die Placebo-Gruppe besser als die anderen ab.
Die Studie wurde gleichwohl als Erfolg gefeiert, nur ein paar Monate später
veröffentlichte das gleiche Journal eine Anschlussuntersuchung, die am
Karolinska-Krankenhaus in Stockholm durchgeführt wurde. Die dortige
Abteilung für klinische Neurowissenschaft genießt internationales Ansehen,
der Studienleiter Martin Ingvar, heute Leiter des Instituts, erweiterte die Testbatterie
erheblich. Wieder durften gesunde Männer CX516 zu sich nehmen,
in dieser doppelblinden Studie waren sie zwischen 20 und 35 Jahre alt. Wieder
war die Gruppe mit 12 Wirkstoff- und 12 Placebo-Probanden sehr klein.
Gering war auch die Dosis im Vergleich zur Vorgängerstudie, nämlich nur 300
Milligramm. Die allerdings wurde über fünf Tage verabreicht.
In einem der visuellen Tests zeigte man den Männern Fotografien und die
dazugehörigen Biografien von Personen, die sie später wieder richtig zuordnen
sollten. In weiteren Tests mussten sie Gerüche wiedererkennen, am Bildschirm
durch ein Labyrinth finden, Arten und Positionen von Spielkarten wiederfinden
und sich in ihren motorischen Fähigkeiten prüfen lassen.
Die Ergebnisse geben aus gleich mehreren Gründen zu denken. Zum einen
ergab der visuelle Biografie-Test einen sehr hohen Wiedererkennungswert.
Sowohl die Placebo- als auch die Wirkstoffgruppe erkannten zwischen 10 und
11 der 12 Items innerhalb von zehn Minuten wieder. Wartete man länger,
nämlich 24 Stunden, verschlechterte sich der Wert in beiden Gruppen. Über
die Nacht hatten viele der Probanden den Zusammenhang zwischen den Fotos
und den Lebensläufen vergessen. In der Placebo-Gruppe erinnerte man durchschnittlich
nur noch 6,5 Items. In der CX516-Gruppe waren es im Schnitt 7
Items. Die Studie nennt dies einen »signifikanten Unterschied«, angesichts der
Teilnehmerzahl von 12 Personen eine mehr als gewagte Aussage.
Auch bei der Geruchserinnerung schnitt die Wirkstoffgruppe besser ab,
allerdings galt dies nicht für alle Stoffe, sondern nur für eine Gruppe von speziellen
Gerüchen, die bekannt dafür sind, dass sie zumeist schwierig erinnert
werden. Klarer waren die Ergebnisse beim Labyrinthtest. Hier schnitten die
Wirkstoff-Probanden allerdings nicht an den eigentlichen CX516-Tagen, sondern
erst am vierten, dem Ausstiegstag, besser ab. Im Karten- und motorischen
Test schließlich kam es zu keiner Vervollkommnung individueller Fähigkeiten.
Mehr noch: Die Studie erweckt an dieser Stelle den Eindruck, dass eine eingehendere
Analyse sogar negative Effekte hervorgebracht hätte.
Selbst wenn man die Ergebnisse für valide halten würde, ist ihre Aussagekraft
für die Praxis des cognitive Enhancements widersprüchlich. Denn
CX516 bewegt die unterschiedlichen Gedächtnissysteme zu unterschiedlichen
Zeitpunkten auf verschiedene Weise. Die Verfasser der Studie versuchen
es positiv zu wenden, indem sie konstatieren, dass die »Effekte des Ampakin
CX516 nicht auf bestimmte kortikale Systeme beschränkt« seien. Mit der
vorsichtigen Hoffnung, dass die Beeinflussung des AMPA-Rezeptors »zumindest
einige Aspekte des Gedächtnis steigern« könnte, gleitet man aus dem
Aufsatz heraus.
Seither wird immer mal wieder ein Aufsatz veröffentlicht, der ein Ampakin
an gesunden Probanden testet, aber zum einen sind die Untersuchungseinheiten
meist erschreckend klein, zum anderen die Ergebnisse ähnlich widersprüchlich
wie in der eben analysierten Studie. So stellten Elke Wezenberg und
ihr Team von der Radboud-Universität im niederländischen Nijmegen fest,
dass der Ampakin-Einfluss auf das Arbeitsgedächtnis nicht nur von der Art
des angewendeten Tests abhängig ist: In ihrer Untersuchung verlief nur einer
von sieben Gedächtnistests unter Ampakin-Einfluss signifikant besser.
Von den Medien angeheizt wuchs zwischen 2000 und 2005 die Hoffnung,
den grundlegenden Mechanismen des Langzeitgedächtnisses auf der Spur zu
sein. Biotech-Startups mit klangvollen Namen wie »Memory Pharmaceuticals
« und »Helicon Therapeutics« waren entstanden. Dort ging man zwar
anderen Spuren nach, das Ziel aber war dasselbe: die Verbesserung von Lernleistung
durch die Pharmakologie. Das Interesse der Medien wuchs, 2004 meldete
der Scientific American in einem Artikel über die Bemühungen der Firmen:
»Tuning für das gesunde Hirn – es steht real in Aussicht.«
Durch die ersten, oft auf statistisch tönernen Füßen stehenden Erfolge
bestätigt, lehnte man sich weit aus dem Fenster. Lynch äußerte gegenüber der
Technology Review: »Das Argument, geistige Prozesse wären unter dem
Druck der Evolution optimiert worden, hat mich nie überzeugt.« Und weiter:
»Die Modulation der AMPA-Rezeptoren stellt eine völlig neue Strategie für
das cognitive Enhancement dar.« Bis heute entwickeln Lynch und Cortex
immer neue Ampakine, die in Tierversuchen darauf getestet werden, welchen
Einfluss sie auf die Merkfähigkeit nehmen. Je nachdem, welches Zwischenoder
Endergebnis eine Studie gerade zeigt, oszilliert der Aktienkurs der Firma
Cortex. Ein Phänomen, das von anderen pharmazeutischen Biotechnologiefirmen
bekannt ist, die ihr Geschäftsmodell auf einen oder wenige Wirkstoff-
Kandidaten bauen.

[Erbse1]

Antwort auf Beitrag Nr.: 34.351.562 von Ackergaul am 23.06.08 10:22:17

Hallo Ackergaul,
es ist schön noch mal aus alten Cortex Zeiten zu lesen. Nicht immer ganz richtig der Artikel, ist aber auch egal. Es wäre schön etwas zum aktuellen Stand zu lesen. Ich freu mich über jeden, der über Cortex schreibt. Leider müßen wir uns einen Monat länger in Geduld üben. Der Kurs hat erst mal einen kleinen Dämpfer erhalten. Doch das spielt absolut keine Rolle. Sind die Ergebnisse bei Atemdepression positiv, gehts mächtig hoch. Ich beteilige mich nicht an den Spekulationen, denn ich habe absolut keine Ahnung zu der zusätzlichen Rekrutierung. Sind die Ergebnisse negativ, gehts halt mächtig runter. Danke Ackergaul für die kleine Cortex Retrospektive.

Grüße
Erbse

[Erbse1]

Interessanter Artikel von Spiegel Online. Zu Cortex möchte ich allerdings einwenden, daß es in der Regel 10 Jahre dauert, bis ein neues Medikament auf dem Markt ist. Bei Schwierigkeiten, die zwischendurch auch auftreteten können und in vielen Fällen auch eintreten, kann es auch schon einige Jahre länger sein. Am Beispiel Cortex kann man das sehr schön sehen. CX 516 war leider zu schwach und nicht tauglich. CX 717 zeitweise durch die FDA ausgesetzt und schon sind fünf sechs Jahre Entwicklungs- und Forschungsarbeit vorbei. Allerdings hat Cortex jetzt noch das Schwein, das CX 717 bei Atemdepression getestet wird. Hier hat Cortex ein riesiges Glück gehabt, daß sich ganz unverhofft ein neues Anwendungsgebiet auftat. Sollten die Versuche positiv sein, so könnte eine Zulassung wohl in ca. 3-4 Jahren in Betracht kommen. Eine off label Anwendung mit CX 717 bei ADHD und kognitiven Störungen bietet sich dann an. Zumindestens bis die dritte Generation an Cortex Substanzen erfolgreich getestet werden kann.
Jetzt sind es noch ca. 3-4 Wochen bis zu den verzögerten Ergebnissen. Also durchhalten und Daumen drücken.

Grüße
Erbse

Die gedopte Elite
Von Veronika Szentpétery

Große Teile der Bevölkerung helfen schon heute ihrer Hirnleistung chemisch auf die Sprünge – mit zugelassenen Medikamenten oder illegalen Drogen. Künftig dürfte die Auswahl noch größer werden - denn Pharmaunternehmen wittern einen gewinnträchtigen Zukunftsmarkt.

Der IT-Spezialist will sich über die Zeit retten: "Er kommt seit fünf Jahren. Gerade gestern war er wieder da und wollte für weitere zwei Jahre fit gemacht werden. Danach will er in den Ruhestand gehen", erzählt Professor Hinderk Emrich, Leiter der Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie an der Medizinischen Hochschule Hannover (MHH). Der Betroffene sei einerseits ein sehr leistungsstarker Mensch, andererseits von Depressionen und Angstzuständen geplagt. Eigentlich, sagt Emrich, hätte er schon lange nur eingeschränkt arbeiten dürfen, "aber er wollte die Familie ernähren". Sein Patient griff zu Opiaten und Medikamenten. Fünf Jahre lang hielt er damit den Druck aus, dann brach er zusammen und suchte Hilfe bei Emrich.


Für Emrich bedeuten solche Fälle ein ethisches Dilemma: "Soll ich ihm helfen oder ihn nur wieder fit machen?" Helfen hätte bedeutet, den Patienten für mehrere Wochen aus seiner Stresssituation herauszuholen. Aussetzen kam für den Mann allerdings nicht infrage – er wollte einfach nur wieder funktionieren. Emrich bestellte den Computerprofi schließlich für ein paar Tage in die Klinik, verschrieb ihm Medikamente gegen die Depression, die Angstzustände, die Schlafstörung und auch zur Leistungssteigerung, die ihn arbeitstauglich machen sollten, verknüpfte die Pharmabehandlung aber mit einer psychiatrischen Beratung. "Könnte er angstfrei leben, bräuchte er weniger Behandlung. Trotzdem will er sogar mehr leisten als andere. Es ging tatsächlich nicht nur um Symptomlinderung, sondern auch um Leistungssteigerung", sagt Emrich.

Leistungssteigerung ist das Stichwort: Während der aktuelle Suchtbericht der Bundesregierung Medikamentenmissbrauch noch hauptsächlich als Problem alter Menschen darstellt, berichten Emrich und andere Ärzte von einer zunehmenden Zahl von organisch weitgehend gesunden Spitzenkräften, die nach Mitteln verlangen, mit denen sie noch besser werden oder das hohe Niveau dauerhaft halten können. Das gilt anscheinend vor allem für Leute vom Fach: In einer – nicht repräsentativen – Umfrage der Fachzeitschrift "Nature" gab jeder fünfte Forscher an, schon mit Hirndoping experimentiert zu haben, zwölf Prozent betreiben es regelmäßig.

Das Bedürfnis, dem eigenen Gehirn chemisch auf die Sprünge zu helfen, ist alles andere als neu: Kaffee und Energiegetränke zum Wachbleiben, Traubenzucker für die Konzentration, Alkohol zum Entspannen und pflanzliche Präparate bei leichten Gedächtnisstörungen und Gemütsschwankungen sind so verbreitet wie gesellschaftlich akzeptiert. Dazu kommen in bestimmten Branchen illegale Drogen wie Kokain oder die Aufputschmittel Speed oder Ecstasy. Die beiden letzteren sind Derivate des einst als Anti-Asthma-Mittel entwickelten Amphetamins (siehe Grafik). Für Nachschub in dieser Richtung scheint gesorgt zu sein: Die Pharmaindustrie, immer auf der Suche nach lukrativen neuen Mitteln, bereitet laut einer Erhebung des Pharmaunternehmens Novartis nicht weniger als 600 neue Medikamente für bessere kognitive Fähigkeiten bei Krankheiten wie Alzheimer vor.

Noch ist das sogenannte Neurodoping hierzulande nicht die Regel. Doch Psychiater berichten, dass die Grenze zwischen Medikamenten und Drogen sowie zwischen krank und gesund verschwimmt – ähnlich wie zuvor schon der Unterschied zwischen Wiederherstellungs- und Schönheitschirurgie oder Erektionsstörungen und dem Wunsch, allzeit sexuell bereit zu sein. Müdigkeit und mangelnde Konzentration werden zu Symptomen, die es zu beheben gilt. Die Online-Foren sind voll von experimentierfreudigen Menschen, die sich Tipps geben, mit welchem Medikament es sich am besten lernen, am längsten arbeiten und am zuverlässigsten Prüfungsangst ausschalten lässt, zuweilen in beängstigend sorgloser Kombination.

In Deutschland werden Medikamente, die in die Gehirnchemie eingreifen, zwar restriktiv gehandhabt – sie fallen wegen Suchtgefahr meist unter das Betäubungsmittelgesetz, sodass sich verschreibende Ärzte ohne triftige medizinische Gründe für den Einsatz strafbar machen würden. Doch es ist keine allzu große Herausforderung, die sogenannten smart pills in Online-Apotheken aus Indien oder Panama zu finden und zu bestellen.

Wohl auch deshalb hat sich der weltweite Umsatz mit einem Medikament des US-Unternehmens Cephalon seit dem Jahr 2000 von 70 Millionen Dollar auf 850 Millionen Dollar mehr als verzehnfacht: Provigil (in Europa: Vigil) wurde zur Bekämpfung der Schlafkrankheit Narkolepsie entwickelt, unter der aber etwa in den USA nur 0,05 Prozent der Bevölkerung leiden. Trotzdem liegt der US-Umsatz bei 800 Millionen Dollar – das lässt sich kaum damit erklären, dass das Mittel inzwischen auch gegen die Folgen von Schichtarbeit und nächtliche Atemaussetzer zugelassen ist. Tatsächlich warb Cephalon in einer Ärzte-Broschüre dafür, dass sich Provigil auch für andere Schlafstörungen eignet, bis die Aufsichtsbehörde FDA diese Praxis Anfang 2007 unterband. Dafür erreichte das Unternehmen in diesem März, dass Vigil in Deutschland nicht mehr unter das Betäubungsmittelgesetz fällt, weil kein Suchtpotenzial nachgewiesen wurde.

Akademiker haben die Vorzüge solcher Medikamente jedenfalls längst entdeckt. Die Neuropsychologin Barbara Sahakian von der University of Cambridge wurde darauf aufmerksam, als sie zu einer Konferenz nach Florida flog und sich über ihren spät liegenden Vortragstermin ärgerte: "Da fragte mich ein befreundeter Wissenschaftler: Möchtest du etwas von meinem Provigil haben?" Er nehme es regelmäßig gegen die Zeitverschiebungsmüdigkeit. Sahakian lehnte ab, erfuhr aber später von immer mehr Kollegen, die das Mittel nehmen, um dem Jetlag zu entgehen oder um länger arbeiten zu können. In der "Nature"-Umfrage lag unter den dopenden Forschern Ritalin – ein Amphetamin-Derivat – mit 62 Prozent vorn, gefolgt von Provigil, das 44 Prozent zu nutzen angaben.

Verlässliche Zahlen darüber, welche Berufs- oder Altersgruppen zu welchem Anteil Neurodoping betreiben, gibt es kaum. Interessanterweise aber scheinen deutsche Leistungsträger bislang weniger auf moderne Brain-Booster zu setzen als auf ältere Medikamente – und schlicht auf Illegales. MHH-Psychiater Emrich etwa beobachtet nach eigenem Bekunden seit rund zehn Jahren, dass die Zahl der Menschen zunimmt, die ihr Leben nur noch mithilfe von Medikamenten oder Drogen wie Kokain bewältigen. Um dem Druck standhalten zu können, schlucken sie tagsüber Antidepressiva und abends Benzodiazepine – Medikamente wie Valium, die angstlösend und muskelentspannend wirken.

Fast schon notorisch ist der Konsum von Kokain und anderen Aufputschmitteln in kreativen Branchen wie der Werbung. Emrich bestätigt den Verdacht, verweist aber darauf, dass auch ganz gewöhnliche Manager nicht selten dem weißen Pulver zugeneigt sind. "Es soll die Leistung und die Kreativität steigern", erklärt Emrich. Zudem könne man es über Jahre hinweg konsumieren, ohne dass es Außenstehenden auffällt.

Hoffen auf die schnelle Lösung

Auch Bernd Sprenger, Chefarzt der auf Suchterkrankungen und Burnout spezialisierten privaten Oberbergklinik in Wendisch Rietz, sieht heute mehr kokainabhängige Manager vor sich als früher – mittlerweile etwa 30 im Jahr, wie er sagt. Seine Klinik, idyllisch gelegen am Glubigsee eine knappe Autostunde südöstlich von Berlin, befindet sich in einem Erholungsgebiet. Links und rechts von ihren Gebäuden stehen Häuser eines Ferienparks. In der Klinik, die früher auch ein Hotel war, herrschen sanfte Pastelltöne vor, alle Patientenzimmer liegen auf der Seeseite.

Sprenger erklärt engagiert. Und was er zu erzählen hat, passt ins Bild: In die Klinik kommen nur wirklich ernste Fälle – und selbst die haben häufig die Vorstellung, dass ein paar Tabletten sie in ein paar Tagen schon wieder fit machen. "Es ist ein Zeitgeist-Phänomen. Wir sind technisch denkende Menschen – ich muss es packen, notfalls mit chemischen Krücken. Problem – Pille – gelöst", sagt Sprenger. Diese Haltung sei nicht nur "bei der Funktionselite" zu erkennen: "Das geht quer durch den Garten. Wir sehen auch viele Lehrer, Polizisten, Ärzte, Mittelständler – und auch mal einen Beamten aus dem Auswärtigen Amt oder einen Vorstand eines Dax-Unternehmens." Was die Leute nehmen? "Längst nicht immer illegale Drogen", sagt auch Sprenger, "Ich nenne es Alltagsdoping: Alkohol, Nikotin und legale Medikamente. Dazu gehören Benzodiazepine, also Beruhigungsmittel wie Valium, die haben ein hohes Suchtpotenzial." Dann erst kommen illegale Drogen wie Kokain und Ecstasy. Auch Smart Pills seien längst nicht so verbreitet wie in den USA, die Deutschen seien da eher "medizinskeptisch".


Die Pharmaindustrie hat massive wirtschaftliche Interessen


Wer erst einmal bei Sprenger gelandet ist, muss von der Hoffnung auf eine schnelle Lösung ohnehin Abschied nehmen. Akut Abhängige werden zunächst in einem der Intensivzimmer zur Entgiftung untergebracht. Das Suchtmittel wird sorgsam herunterdosiert, parallel dazu findet die Entwöhnung statt. Es sei ein Irrglaube, dass das Burnout-Syndrom oder Stress durch ein paar Pillen zu beheben sei, merkt der Chefarzt an. Symptome ließen sich zwar chemisch-technisch lindern, aber der Grundzustand selbst nicht. "Diese Bescheidenheit stünde der Medizin gut an", sagt Sprenger und zielt damit nicht nur auf Kollegen mit locker sitzendem Rezeptblock, sondern auch auf die Pharmaindustrie: "Die hat massive wirtschaftliche Interessen. Wenn die Patente auslaufen, suchen sie für die Medikamente neue Indikationen." Pharmavertreter, die ihm immer wieder Werbung als Wissenschaft verkauft und Nebenwirkungen heruntergespielt hätten, kämen bei ihm seit 15 Jahren nicht mehr ins Büro.

Es geht aber längst nicht mehr nur um überarbeitete Manager und überehrgeizige Forscher. Einen viel größeren Markt machen alte Menschen aus. Für diese Zielgruppe schuf die Pharmaindustrie bereits den Krankheitsbegriff "mild cognitive impairment", die leichte Gedächtnisstörung. Tatsächlich steht aufgrund des immer genaueren Verständnisses der molekularen Grundlagen des Lern- und Erinnerungsvermögens zu erwarten, dass die nächsten Medikamente, die auch beim kognitiven Aufrüsten von Gesunden eine Rolle spielen werden, aus der Neuroforschung stammen werden.

Viele Medikamente, die die kognitiven Fähigkeiten zum Beispiel von Demenzkranken verbessern sollen, verstärken die Wirkung von Botenstoffen (Neurotransmittern) an den Verbindungen (Synapsen) zwischen Nervenzellen. Auf diese Weise sollen die Schaltkreise für Aufmerksamkeit, Lernen und Gedächtnis positiv beeinflusst werden. Ein Ansatzpunkt ist etwa der Botenstoff Acetylcholin: Damit er länger wirkt, hemmen Medikamente wie das Alzheimer-Mittel Donepezil das Acetylcholin abbauende Enzym Cholinesterase. Erste Tests mit Piloten, die nach Einnahme von Donepezil im Flugsimulator bessere Ergebnisse erzielten, waren vielversprechend, doch das Mittel löste auch Übelkeit aus.

Ohnehin könnten die Effekte auf Dauer zu gering sein, denn die kognitive Leistung lässt sich über die Neurotransmitter-Schiene nicht linear steigern. Vielmehr gilt eine Glockenkurve: Es existiert ein Dosis-abhängiges Optimum, ein Zuviel oder Zuwenig an Botenstoffen hingegen mindert ihre Wirkung. Zudem variieren die Idealwerte für die Botenstoffe je nach kognitiver Aufgabe, sodass die Verbesserung einer Fähigkeit wohl immer auf Kosten einer anderen gehen wird. Auch viele der neuen Hoffnungsträger in den Wirkstoffpipelines der Pharmaindustrie konnten die in sie gesetzten Hoffnungen bislang nicht erfüllen. Die US-Unternehmen Helicon Therapeutics und Memory Pharmaceuticals etwa setzen nicht bei den Synapsen an, sondern bei den mit Lernen in Verbindung gebrachten Molekülen innerhalb der Neuronen. So sollte zum Beispiel die Produktion des Proteins CREB angekurbelt werden; als Transkriptionsfaktor reguliert es Gene, die die Verstärkung von synaptischen Verbindungen zwischen den Neuronen bewirken. Doch die Enzymhemmer, die für den CREB-Anstieg sorgen sollten, taten dies nicht an den richtigen Stellen – und seither hört man von den Substanzen nicht mehr viel. Auch die mit vielen Vorschusslorbeeren bedachten Ampakine von Cortex Pharmaceuticals, die das Gedächtnis über die Glutamatrezeptoren im Gehirn verbessern sollten, haben nicht überzeugt.

Allerdings ist es nicht ungewöhnlich, dass scheinbar vielversprechende Kandidaten bei der weiteren Prüfung durchfallen. Angesichts von 600 potenziellen Hirndoping-Pillen ist zu erwarten, dass einige davon besser wirken als die heutigen. Wird es also eines Tages normal sein, Wach- und Schlaumacher so selbstverständlich einzunehmen wie Aspirin? "Das wird so kommen", sagt MHH-Professor Emrich, "jeder muss das moralisch selbst entscheiden. Aber sonst müsste man Alkohol auch verbieten, das ist ja auch ein gutes Schlaf- und Beruhigungsmittel." Vorausgesetzt, dass kein Schaden für den Betroffenen selbst oder andere entsteht und die Nebenwirkungen gering bis vertretbar sind, spricht nichts dagegen, seinem Gehirn mit Medikamenten auf die Sprünge zu helfen, findet auch Burnout-Experte Sprenger. Nur: "Das Dumme ist, es gibt dieses Medikament nicht." Denn zumindest die heute verfügbaren Neurodoping-Pillen haben alle ihre Nebenwirkungen.

Langfristig wird sich der Trend wohl trotzdem nicht aufhalten lassen. Denn wie die Beliebtheit selbst illegaler Hirndopingmittel zeigt, sind nicht unerhebliche Teile der Bevölkerung bereit, für bessere Leistung Gefahren in Kauf zu nehmen und sogar Gesetze zu brechen. Die ärztlich kontrollierte Verschreibung zugelassener Pharmazeutika auch an nicht Kranke wäre so gesehen das kleinere gesellschaftliche Übel. Letztlich müsste dann tatsächlich jeder selbst entscheiden, wie viel er aus seinem Gehirn herausholt – und ob er es womöglich so weit kommen lassen will, dass er den erholsamen Spaziergang am See nicht aus Vergnügen, sondern als Patient einer Burnout-Klinik macht.

Quelle: http://www.spiegel.de/wissenschaft/mensch/0,1518,druck-56080…

[Erbse1]

Kommentar des NeuroInvestor zu Cortex aus der letzten Ausgabe.

Cortex Pharmaceuticals: Commentary

(from NI July/August 2008; added 7/9/08)

Surely having run through many of its proverbial, feline nine lives, Cortex came back strongly during the 1H:08 based on anticipation of the potential for Ampakines in treating and/or preventing respiratory depression. But the results from the first German Phase IIa trial were delayed to the end of July, when the analgesia-maintenance trial will also have data released. The use of a drug preventing RD has at least $1 billion potential in analgesia contexts, while company-sponsored market study suggested that sleep apnea as an indication could more than triple that potential. Our view is that there are two aspects: Nearterm, there is a (primarily) hospital-based market for a RD-preventative. RD's incidence is quite a bit higher than we had initially thought, apparently approaching 13%. But the second, longerterm application would be in chronic outpatient use: The analgesia company that combines an Ampakine (probably not CX717) with their opioid analgesic, and can market it as a safer painkiller for severe pain, will have a distinct advantage where competition has tended to revolve around extending the duration of release and discouraging abuse. We expect that companies with prominent pain franchises are going to be avid bidders for the RD program, as much to keep it out of a competitor's hands as to have it themselves. Assuming trial success, which is probable but not assured, that partnership should take care of Cortex's perennial cash flow problems.

In terms of its core business, which remains neuropsychiatric, Cortex also has made progress in broadening and deepening its pipeline. CX1739 is nearly ready for Phase I, with CX1942 (a CX1763 prodrug) going into full toxicology studies. CX1739 could be in Phase II for ADHD and Alzheimer's within nine months. Schering-Plough has moved Org26576 (which falls under the Cortex partnership) into Phase II trials in both depression and ADHD, with data coming in early 2009. Perhaps more importantly, the neurotrophically 'high-impact' CX1837 could be in Phase I during 2Q:09 as well. In terms of addressing the neurodegenerative disorders that were Cortex's original raison d'être, that is a potential landmark event. We would be surprised if this does not yield a neuro/psychiatric partnership with a Big Pharma within the next 6-12 months, but we have said that before.

[Erbse1]

Die Studie bei Depression mit Org 24448 wurde ausgesetzt. Hab leider noch keine näheren Informationen.

Org 24448 to Treat Depression

This study has been suspended.

Quelle: http://www.clinicaltrials.gov/ct2/show/NCT00113022?term=ampa…

[Erbse1]

Das Militär meldet sich jetzt auch wieder mit CX 717 mit einem Schlafreduktionsprogramm.

Night of the Living Meds
The U.S. military's sleep-reduction program.

By William Saletan
Posted Wednesday, July 16, 2008, at 8:01 AM ET
You don't have to worry anymore about the possibility of an arms race in pharmaceutical enhancement of combat troops. It's already here.

The evidence is laid out in "Human Performance," a report commissioned by the Pentagon's Office of Defense Research and Engineering. The document, issued by a defense science advisory group known as JASON, was published earlier this year. It was flagged by Secrecy News and came to Slate's attention through Wired's military blog, Danger Room.

The report is unclassified because there's nothing earth-shattering in it. Indeed, it debunks some fanciful brain-augmentation scenarios. What it offers instead is a level-headed account of how cognitive performance-enhancement technology is already entering military practice. The gateway application for this technology isn't sensory acuity or information processing. It's sleep reduction.

According to the report, "The most immediate human performance factor in military effectiveness is degradation of performance under stressful conditions, particularly sleep deprivation. If an opposing force had a significant sleep advantage, this would pose a serious threat." Consequently, "the manipulation and understanding of human sleep is one part of human performance modification where significant breakthroughs could have national security consequences."

That's the theory. But it's not just a theory, the report notes; it's a proven pattern in military history.

Sleep deprivation is known to have significantly harmful impact on physical performance, alertness, and the ability to perform complex cognitive tasks. In planning their campaigns, battlefield commanders have to weigh carefully the negative impact on the effectiveness of their forces of extended periods of wakefulness and combat. In addition, under appropriate conditions on the tactical battlefield, sleep deprivation and exhaustion can be and has been exploited militarily as a specific mechanism to weaken opposing forces. This observation … is illustrated by accounts of General George Patton's almost legendary pattern of driving his army with extreme aggressiveness in World War II, based on his stated conviction that it was the way to reach his goal more rapidly and with fewer casualties. The point is to maximally exploit the state of exhaustion of one's enemy. It seems intuitive that, in combat between two armies at comparable levels of sleep deprivation, the advantage is with the force on offense in its ability to stress the opposition's state of exhaustion.

Deprivation. Degradation. Exhaustion. Harmful impact. All of these terms imply a deficit, a reduction from normal performance. This is another reason why sleep modification is the gateway app for cognitive military enhancement. We can tell ourselves and the rest of the world that we're not really making our troops superhuman; we're just restoring their natural powers. In the report's words:

If we take as a given that soldiers on the battlefield will always need to undergo sleep deprivation, sometimes severe, and given that such sleep deprivation leads to large performance degradation, it follows that any method for improving how soldiers behave under sleep deprivation will have significant consequences for either our own forces or an adversary that learns to solve this problem.

In concrete terms, sleep modification will save lives. This is the trump card for any controversial biotechnology. The report calculates:

[T]he maximum casualty rate depends strongly on the individual's sleep need, τ0. Hence any effort to improve human performance to minimize τ0 for given tasks can lead to a significant decrease in the casualty rate, of [about] 20 percent. … Suppose a human could be engineered who slept for the same amount of time as a giraffe (1.9 hours per night). This would lead to an approximately twofold decrease in the casualty rate. An adversary would need an approximately 40 percent increase in the troop level to compensate for this advantage.

Massively reduced casualties—how could anyone oppose that? In the face of these numbers, sleep modification, if practical, ceases to be an option. It becomes an obligation. Foregoing it begins to feel as derelict as failing to supply our troops with adequate body armor.

But is it practical? Will it harm our brave young men and women? Relax. Our brave young men and women are already doing it. The report notes:

The use of supplements, primarily to ameliorate sleep deprivation and to improve physical performance, is report[ed] to be common among US military personnel. This behavior is a cultural norm in the US and is recognized, but not endorsed, by the US military. For instance the PX at most military bases stock popular supplements.

The part about the military not "endorsing" these chemicals is pretty rich. The armed forces are up to their eyeballs in research on drugs to facilitate sleep reduction. The report cites a recent study, conducted by the Military Nutrition Division of the U.S. Army Research Institute of Environmental Medicine, which

involved tests of the effects of caffeine on performance for a group of Navy SEALS, following 72 hours of intense training activity with almost total sleep deprivation. A variety of metrics were used, including computer-based tests of reaction speed and mental acuity, psychiatric self-assessment surveys, and marksmanship tests. The test was to determine the optimal caffeine dose to ameliorate the effects of fatigue and stress.

The study concluded that caffeine "significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness."

But caffeine was only the beginning. "The US military … has a long-standing effort in tracking and evaluating popular supplements," says the report. "To date, 86 proposed ergogenic and cognitive aids have been evaluated." These apparently include "amphetamines and modafinil," which "are known to be effective for combating the effects of sleep deficit." But the hot target now is a class of chemicals called ampakines. On this subject, the report cites several studies funded by the Defense Advanced Research Projects Agency, particularly a paper called "Facilitation of Task Performance and Removal of the Effects of Sleep Deprivation by an Ampakine (CX717) in Nonhuman Primates." The report notes that the study found

a clear improvement in performance, correlated with changes in fMRI patterns, when the monkeys were treated with ampakines. … Repeating the tasks with sleep-deprived monkeys that had been administered ampakines … restored performance to levels comparable to or better than those for well-rested monkeys without ampakine treatment.

Clearly, we're well on our way to systematizing sleep reduction. But we don't want to be accused of starting the pharmaceutical arms race. So let's blame it on somebody else. Let's say we're doing this research not to enhance our troops, but to prepare for the possibility that our enemies will enhance theirs first. Accordingly, the report advises the armed forces to

Monitor enemy activities in sleep research, and maintain close understanding of open source sleep research. Use in-house military research on the safety and effectiveness of newly developing drugs for ameliorating the effects of sleep deprivation, such as ampakines, as a baseline for evaluating potential activities of adversaries.

There you have it: To make the world safe from sleep reduction, we're working night and day on the world's most advanced program in sleep reduction. You can rest easy, knowing our troops are wide awake.

Source: http://www.slate.com:80/id/2195466/

[Erbse1]

Neue Patentanmeldung mit Servier. Wird hier eine alte Partnerschaft wiederbelebt? Dieses Patent ist wohl aus der dritten Generation Ampakine von Leslie Street, mit denen man sich mehr Erfolg verspricht. Da werden wohl in nächster Zeit noch einige Patentanmeldungen erfolgen, um auch zeitmäßig von dem Patentschutz zu profitieren. Leider gerät man bei den alten Patentanmeldungen ein wenig in Zeitnot, deshalb sind wohl einige neue Wirkstoffe und Weiterentwicklungen zum Patent angemeldet worden.

Ich rechne damit, daß in den nächsten zwei Wochen die Ergebnisse der Tests bei Atemdepression veröffentlicht werden. Man sollte dann Cortex etwas genauer verfolgen.

Grüße
Erbse

3-SUBSTITUTED-[1,2,3]-BENZOTRIAZINONE COMPOUND FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES

Abstract of WO2008085506

This invention relates to the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for higher order behaviors. These brain networks are involved in cognitive abilities related to memory impairment, such as is observed in a variety of dementias, and in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia and affective disorders. In a particular aspect, the present invention relates to a compound useful for treatment of such conditions, and methods of using this compound for such treatment.

Quelle: http://v3.espacenet.com/results?sf=a&DB=EPODOC&PA=cortex+pha…

[Ackergaul]

Hi Erbse,

hast Du eigentlich etwas zu den toxicology results der High Impact Ampakine gehört bzw. mitbekommen? Soweit was ich in der Roth Präsentation gelesen habe, sollten die bis Ende 1. H 08 erschienen sein.
Ist ja immerhin auch noch ein großer Hoffnungsschimmer...

Ich weiß, das dies irrsinnig schwer ist, aber:
Wass erwartest Du von den kommenden CX717 RD Ergebnissen?
Das Handelsvolumen war in den den letzten Wochen ruhig / normal. Deutet darauf, dass wohl noch nichts im Vorfeld nach außen gelangt ist...

Grüße

[Erbse1]

Antwort auf Beitrag Nr.: 34.550.778 von Ackergaul am 21.07.08 13:53:10

Hallo Ackergaul,

als nächstes soll CX 1739 (oder ein Ampakin aus der gleichen Wirkstoffgruppe)in die Klinik. Es ist ein Low Impact Wirkstoff und wohl in weiten Teilen die gleichen Anwendungsgebiete bedienen wie CX 717. Warscheinlich soll damit unter anderem auch die Anwendung ADHD belegt werden, da hier CX 717 noch immer durch die FDA gestoppt ist und auch wohl nicht mehr in Frage kommt. Nach meinen Informationen soll dies in allernächster Zukunft geschehen.

Von den High Impacts soll CX 1837(oder eins mit einer anderen Bezeichnung) gegen Ende des Jahres klinisch geprüft werden.Die toxikologischen Tests sollen bis dahin beendet sein. Leider ist es so, daß hier Cortex die anvisierten Termine nicht einhalten kann. Dies ist leider ein Problem vieler Biotechs.

Zum besseren Verständniss poste ich mal den Unterschied von Low und High Impacts Ampakinen. Sie sind in der Wirkungsweise vollkommen verschieden.



Technology

AMPAKINE compounds facilitate the activity of the AMPA receptor, which are activated by the neurotransmitter glutamate, the most prominent excitatory neurotransmitter in the human brain. The AMPAKINE compounds interact in a highly specific manner with the AMPA receptor, lowering the amount of neurotransmitter required to generate a response, and increasing the magnitude and/or duration of the response to any given amount of glutamate. Cortex believes that this selective amplification of the normal glutamate signal may eventually lead to utility in the treatment of neurological diseases and disorders characterized by depressed functioning of the glutamatergic pathways in the brain.

Cortex’s AMPAKINE technology is composed of two groups of compounds that are designated as “low impact” and “high impact”.

AMPAKINE compounds like CX614 and CX929 bind to the well characterized cyclothiazide binding site, and are referred to as high impact compounds. In contrast, compounds like CX717, CX701, Org24448 and Org26576 bind to a different modulatory site on the AMPA receptor complex and impact the response in unique ways. Both types of compounds positively modulate the AMPA receptor function; low impact compounds increase the amplitude of the neuronal action potential, while the high impact compounds generally increase both the amplitude and the half-width of the neuronal action potential. Additionally, the high impact compounds activate the expression of certain genes in the neuron, including neurotrophins such as Brain Derived Neurotrophic Factor (“BDNF”). BDNF mediates the differentiation and survival of neurons by providing the necessary trophic support, and modulates synaptic transmission and plasticity. We believe that this action of AMPAKINE molecules imparts these compounds with the potential for disease modifying activity, since deficits in BDNF have been observed in psychiatric disorders, such as; anxiety, depression, and ADHD, and neurodegenerative disease such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Fragile X.

Although low impact AMPAKINE compounds do not significantly enhance neurotrophic factors, they are able to improve the strength of the synaptic connections through their potentiation of the AMPA receptors

Zu den Ergebnissen bei Atemdepression werde ich keine Spekulation abgeben. Ich habe bei Prognosen schon zu oft daneben gelegen. Ich erhoffe mir schon einen positiven Ausgang sonst wäre ich nicht investiert. Sollten die Ergebnisse keine Wirkung zeigen, dürfte es Cortex sehr sehr schwer haben nochmals auf die Beine zu kommen. Dies ist erst mal alles was ich dazu sagen kann.

Liebe Grüße
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 34.551.247 von Erbse1 am 21.07.08 14:37:30

Verstehe ich voll und ganz... Obwohl es nicht nur ein Schwarz oder Weis Ergebnis werden muss. Persönlich rechne ich mit einem besseren Ergebnis - aber kein überragendes. Wenn es ein sehr gutes Ergebnis werden sollte, könnte der nicht gerade kleine Sleep Apnea Markt auch offen stehen.

Dann noch ein eher (unwichtigeres?) abstract:

1: Behav Neurosci. 2008 Jun;122(3):535-48. Links
Glutamate receptor-mediated restoration of experience-dependent place field expansion plasticity in aged rats.
Burke SN, Maurer AP, Yang Z, Navratilova Z, Barnes CA.
Evelyn F. McKnight Brain Institute, Life Sciences North Building, Room 384, University of Arizona, Tucson, AZ 85724, USA.

Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally induced expression of neuronal plasticity uses an NMDAR-dependent, LTP-like mechanism and could be used by hippocampal networks to store information. Aged spatial memory-impaired rats exhibit defective experience-dependent place field expansion plasticity. One possible explanation for this aged-associated deficit is alterations in glutamatergic function. In fact, both NMDAR- and AMPAR-mediated field excitatory postsynaptic potentials in CA1 decrease with aging. The current study investigated whether modulation of either AMPA or NDMA receptor activity could restore this experience-dependent plasticity by prolonging AMPAR activity with the ampakine CX516 and modulating the NMDAR with the noncompetitive antagonist memantine. The spatial firing characteristics of multiple CA1 pyramidal cells were monitored under both treatment conditions as aged rats repeatedly traversed a circular track. Compared to the saline baseline condition, acute administration of memantine, but not CX516, reinstated experience-dependent place field expansion. Taken together, these data suggest that pharmacological manipulation of the NMDAR can improve the function of hippocampal networks critical to optimal cognition in aging. (Copyright) 2008 APA, all rights reserved.

PMID: 18513124 [PubMed - in process]


Grüße

und ich drücke natürlich die Daumen!

[Erbse1]

Antwort auf Beitrag Nr.: 34.552.099 von Ackergaul am 21.07.08 15:49:28

Hallo Ackergaul,
hier noch mal die Pipeline von der letzten Präsentation, wie sie von Cortex geplant war. CX 1837 ist aus der High Impact Wirkstoffgruppe. Alle anderen sind Low Impact Ampakine.



Man liegt demnach voll im Plan. Ich bin jetzt wirklich gespannt auf die Ergebnisse. Lange genug haben wir ja gewartet. Danke fürs Daumen drücken.

Grüße
Erbse

[Erbse1]

Hallo Ackergaul,

gut daß du die High Impact Ampakine angesprochen hast. Bei Fragile X tut sich auch wieder was, wenn auch erst vorklinisch. Das dauert schon seine Zeit bis ein neuer Wirkstoff getestet werden kann. Da gehen ja Jahre ins Land. Die High Impact Ampakine sollen bei Fragile X wirkungsvoller sein, als das ehemalige getestete CX 516.
Hier wird sich zeigen, ob die High Impact Wirkstoffe auch den Erfolg haben, wie man sich es verspricht. Es wäre schon riesig, wenn das klappen würde. Ma verspricht sich hier jede Menge Erfolg bei Anwendungsgebiete wie,

- Angststörungen
- Depression
- ADHD
- Huntington's disease
- Parkinson
- Fragile X

Damit wäre Cortex die nächsten 20 Jahre beschäftigt. Wäre toll, wenn sie hier einen kapitalkräftigen Partner finden können. Aber warten wir jetzt erst mal die Ergebnisse bei Atemdepression ab. Da kann man nur hoffen, daß es auch klappt.

Grüße
Erbse


TREATMENTS IN CATEGORY 3

(directly strengthening the
connection by replacing reduced AMPA activity)

Ampakines
Ampakines activate AMPA receptors, which show lower activity
in the weak connections in FXS. These drugs can also help bring
AMPA receptors back to the surface of the connections where
they are deficient because of the mGluR overactivity.
Ampakines activate BDNF (brain derived neurotrophic
factor) which has been shown to improve connectivity in the
fragile X mouse. A single ampakine, CX516, was studied
in a phase II placebo-controlled trial in humans with FXS.7
This drug did not help the treated group as compared to the
placebo group, but there were no substantial side effects. It
appeared that in just the individuals co-treated with an
antipsychotic, the CX516-treated group showed more
improvement than with the placebo.
Since antipsychotics increase the activity of ampakines,
and CX516 was subsequently shown to be a very weak
ampakine, this suggests that ampakines may well be helpful in
FXS, but stronger forms are needed. There is a stronger
ampakine, CX717, in phase II clinical trials, but CX717 does
not have much effect on BDNF, and it is felt that other
stronger ampakines that robustly activate BDNF would be
best for FXS. These are being studied in the fragile X mouse
but are still in preclinical studies.

http://www.fragilex.org/FQ_July_2008_Issue_31_status_report.…

[Ackergaul]

erst einmal sollten nun in den nächsten 14 Tagen die Ergebnisse hierzu gemeldet werden:

Cortex initiates enrollment in respiratory depression trial
1st April 2008
By Staff Writer

Cortex Pharmaceuticals has received approval from the German regulatory agency to proceed with the trial which will use alfentanil, an opiate analgesic. With this approval the enrollment of subjects into the dose response study evaluating the ability of CX717 to prevent respiratory depression caused by opiate analgesics has started.

The study is a placebo controlled, double blinded, cross-over design with three doses of CX717 compared to placebo. Depending on the pace of subjects being enrolled, Cortex at this point believes that top-line data will be available from this study by the end of June, 2008.

If the German Ampakine studies are successful, pre-surgical or post- surgical administration of CX717 could improve the safety margin for giving these analgesic agents, which would provide a valuable tool for anesthesiologists and surgeons to optimize pain management in surgical patients. This would be true in high risk surgical patients such as those over the age of sixty-five, those with a history of sleep apnea, respiratory illnesses or obese patients.


Grüße

[Erbse1]

Die Spannung steigt. Die Ergebnisse der ersten Studie werden nächste Woche präsentiert.

Cortex to Provide Top Line Data for CX717 Clinical Trial for the Prevention of Opiate-Induced Respiratory Depression in Humans

Thursday July 31, 8:31 am ET
Presentation to be given at the Bank of Montreal's Focus on Healthcare Conference on August 5-6, 2008


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR, http://www.cortexpharm.com) Chairman, President and CEO, Roger G. Stoll, PhD, will speak at the Bank of Montreal’s Focus on Healthcare Conference taking place August 5-6, 2008, at the Millennium Broadway Hotel in New York City. Dr. Stoll will present in Room #4 on Wednesday, August 6th at 9:30 AM (EDT). He will discuss the initial top line results from the first of two studies in normal volunteers to evaluate the use of AMPAKINE® CX717 to prevent opiate-induced respiratory depression. The study, CX717- RD-02, was performed at a clinical research unit in Berlin, Germany.
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A second respiratory depression study, CX717-RD-01, began enrollment several weeks after the Berlin study. The clinical phase of that study has been completed and data management and analysis is currently underway. The top line results from that study will be provided at a later date.

Dr. Stoll will also provide an update on other compounds in Cortex’s AMPAKINE® platform that are currently being prepared for human testing. The updates will provide the current status of developments for CX1739, CX1942, and CX1837.

The conference presentation will be webcast and available for a period of thirty days after the conference by logging on to:http://www.bmocm.com/conferences/2008healthcare/default.aspx…

[Erbse1]

Es wäre einfach zu Schade nicht noch einmal auf die Veröffentlichung der Ergebnisse morgen am 6 August hinzuweisen. Ich erwarte ganz enorme Kurssprünge. Cortex hat die Konferenz vorher angekündigt und ich erwarte nicht, daß hier schlechte Ergebnisse präsentiert werden. Es sei denn, der CEO Stoll wäre ein Sadist. Trotzdem kann ich auch nicht ausschließen, daß schlechte Ergebnisse präsentiert werden, doch halte ich die Warscheinlichkeit für sehr gering.
Jetzt wird es spätestens Zeit, sich mit Cortex zu beschäftigen. Leider kann ich jetzt auch nicht mehr machen.

Grüße
Erbse

[Erbse1]

Antwort auf Beitrag Nr.: 34.647.552 von Erbse1 am 05.08.08 08:19:49

Cortex's AMPAKINE Molecule CX717 Has Positive Effects in Opiate-Induced Respiratory Depression in a Phase IIa Clinical Study


Wednesday August 6, 8:31 am ET


Correlation with Animal Studies Demonstrates AMPAKINE Compounds Can Prevent Opiate-Induced Respiratory Depression


IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (AMEX: COR - News) reported that top-line data from its first Phase IIa study in opiate-induced respiratory depression (RD) demonstrated that a single oral dose of 2100mg of AMPAKINE® CX717 achieved statistical significance over placebo on the primary endpoint measure. These results are being presented at the Bank of Montreal Capital Markets Focus on Healthcare Conference in New York City on Wednesday morning, August 6, 2008 at 9:30AM (EDT) by Dr. Roger G. Stoll, President & CEO of Cortex. This placebo controlled, double-blind, randomized two-way crossover trial (RD-02) was performed by Parexel’s clinical research unit in Europe. In this study, eight (8) volunteers per dose group each received either 900mg, 1500mg, or 2100mg of CX717 or matching placebo that was orally administered two hours before each subject received an intravenous infusion of the opiate agonist, alfentanil. The primary performance measures were derived from a CO2 re-breathing procedure that measured the breathing response of the subject to increased CO2 levels in the presence of alfentanil. The primary measure, the minute expiratory volume (VE) at 55mgHg CO2 (VE55), was reversed by 2100 mg CX717 in comparison to placebo (p<0.03).
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No reliable responses were seen in the 900mg and 1500mg CX717 groups, but procedural problems were detected by the Data Safety Monitoring Board (DSMB) for this study, which was authorized by the protocol to monitor safety and responses on an interim basis. Corrective procedural changes were instituted before the initiation of the last group of subjects in the 2100mg segment of the study.

“While we initiated this study using oral doses of CX717 and had only eight subjects per treatment group, we were pleased to obtain statistical significance using such small study groups,” said Dr. Roger Stoll the CEO of Cortex. The primary objective was to simply verify that the mechanism, which was seen functioning in animal studies, would also be operative in humans. Substantial investments were required to develop an intravenous dosage form of CX717, including formulation development and stability studies for such a dosage form as well as two species toxicology trials. The Company now feels that it can proceed with such studies. Cortex recently received verification of three months of accelerated stability for the experimental intravenous formulation of CX717 and plans to initiate toxicology trials in the fourth quarter 2008.

A second respiratory depression study has been performed by a group in Frankfurt, Germany. This study uses a single dose of 1500mg of CX717 and focuses on both the respiratory depression and the analgesic effects associated with alfentanil. The analysis of the data has been initiated and related results should be reported within a few weeks. Studies of CX717 in animal models by Dr. John Greer at the University of Alberta have shown that the AMPAKINE drugs do not interfere with the analgesic effects of opiates.

Cortex continues to advance other AMPAKINE compounds, particularly those newer compounds that have potential patent lives to 2028. It will also be reported at the BMO Capital Markets conference that Cortex has initiated human phase one safety and kinetic trials with CX1739 in normal volunteers. Assuming successful Phase I human trials with this compound, the Company plans to rapidly pursue the Attention Deficit-Hyperactivity disorder indication for CX1739 in the second half of 2009. The Company will also report on an initial animal trial with CX1942, a unique pro-drug analog of another low impact AMPAKINE drug that is highly water soluble, ideally suited for an intravenous dosage form. This compound rapidly hydrolyzes to the parent AMPAKINE drug in vivo. CX1942 has shown exceptionally rapid results in reversing respiratory depression due to intravenously administered fentanyl in rats. The Company plans to initiate toxicology studies with this unique analog during the last quarter of 2008.

High impact AMPAKINE compounds from recent patent applications are also being advanced with a focus on neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, as well as orphan drug indications like Huntington’s and Fragile X disease.

[Erbse1]

Antwort auf Beitrag Nr.: 34.660.442 von Erbse1 am 06.08.08 15:00:44

Der erste Kommentar des NeuroInvestor

Cortex got the POC they needed to have for a partnership.

I don't think 'the Market' has yet paid much attention, let alone worried about any uncertainties. You had day traders who jumped in at the bell, and when the momentum stopped in the 1.11-1.12 range, they decided to exit. It's August 6, a lot of people aren't around, and the assistants at the desks probably don't have the authority to do anything major.

The R&R note that I expect in the next 24-48 hours will be important, as much as I hate to say that.

As I mentioned last night, I was hoping Roger would make a positive statement about partnership prospects, and he did. A partnership will include both CX717 and CX1942--the question in my mind is which other low impact will be included for future ongoing oral use....including CX1739 would set back ADHD etc., unless they carved out non-RD uses--which they possibly could, the markets are totally separate.

Just to throw out some figures: Given that they can license RD worldwide, I'd like to see something in the $30 million range upfront plus a couple years research support (I'm not going to get into Biobuck milestones and royalties here). I'm aware of recent deals with more upfront, albeit generally for either more clinically advanced programs or those with a wider range of indications covered, but I'd rather be conservative here.

But I have also previously noted that a company like Cephalon has major interests in both analgesia and ADHD, so it is possible a deal could cover a wider swathe of low-impact indications, while still leaving Cortex with high-impacts/neurodegeneration for inhouse development.

NeuroInvestment

[Erbse1]

Antwort auf Beitrag Nr.: 34.662.337 von Erbse1 am 06.08.08 17:47:08

Einschätzung von Rodman&Renshaw. Sie warten auch lieber die zweite Studie ab.

<<Cortex stated positive top-line data from a Phase 2a study of its lead drug candidate, the AMPAKINE® compound CX717, in respiratory depression induced by opiates. The firm reported that the highest dose of CX717, 2100mg, showed a statistically significant positive impact (p<0.03) on depression of breathing. This placebo controlled, double-blind, randomized two-way crossover trial (RD-02) was performed in Europe. Eight volunteers per dose group each received 900mg, 1500mg, or 2100mg doses of CX717 or placebo, orally administered two hours before receiving an intravenous infusion of the opiate agonist, alfentanil. The primary performance measures were derived from a carbon dioxide (CO2) re-breathing procedure that measured the breathing response of the subject to increased CO2 levels in the presence of alfentanil.No reliable responses were seen at the 900mg and 1500mg doses, but procedural problems were detected in these groups. Corrective procedural changes were instituted for those patients receiving the 2100mg dose.

A second respiratory depression study (RD-01) was performed by a group in Frankfurt, Germany. This study uses a single dose of 1500mg of CX717 and aims to show that CX717 can reverse respiratory depression without reversing analgesia. Data analysis is ongoing and results are expected within a few weeks.

Based on the results from the first Phase 2a study reported today, we are cautiously optimistic regarding the potential of CX717 in treatment of respiratory depression associated with opiate administration. This is an estimated $1.3B market worldwide. However, we note that in this study, the 1500mg dose was not active – although this may have been due to procedural problems for which we have no clarity at this time.

This dose is the same as that being used in the second Phase 2a trial. We are currently uncertain as to whether the 1500mg dose will show efficacy in the second trial, based on the results reported today.

Cortex aims to start tox studies for i.v. CX717 in 4Q08, and also has three backups (patent-protected to 2028), which do not have the histopathological signal that originally arose with CX717 in animal testing:
*
o CX1739, which has entered Phase 1 clinical testing and is slated to be developed for attention deficit/hyperactivity disorder (ADHD) in 2H09
o CX1942, an orally available and intravenous formulation-ready water-soluble pro-drug of CX717, which will be the designated backup in the respiratory depression indication
o CX1837, a “high-impact” compound to address neurodegenerative conditions – this molecule has an encouraging therapeutic window, without the seizure risk associated with earlier candidates

We continue to believe in the therapeutic potential of the AMPAKINE® platform. However, in our view, Cortex will need to show definitive proof-of-concept in respiratory depression and validate the technology with a high-profile partnership. The firm is also trying to initiate ADHD trials with CX717 in Europe – this will bear watching.

In anticipation of the results from the second respiratory depression study, we maintain our Market Perform rating without a target price on Cortex shares.>>

[Erbse1]

Zur besseren Übersicht habe ich mal das Schaubild der aktuellen Pipeline von COR neu überarbeitet.

[Erbse1]

Wäre schön, wenn diese Abstracte sich auch irgendwann am Menschen bestätigen könnten. CX 516 ist bei Alzheimer schon lange als zu schwach potent ausgemustert. Geplant ist von COR bei den neurodegenerativen Erkrankungen auf die High Impact Wirkstoffe zu setzen.
Grüße
Erbse

Ampakine CX516 ameliorates functional deficits in AMPA receptors in a hippocampal slice model of protein accumulation.

Kanju PM, Parameshwaran K, Sims C, Bahr BA, Shonesy BC, Suppiramaniam V.
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

AMPAkines are positive modulators of AMPA receptors, and previous work has shown that these compounds can facilitate synaptic plasticity and improve learning and memory in both animals and humans; thus, their role in the treatment of cognitive impairment is worthy of investigation. In this study we have utilized an organotypic slice model in which chloroquine-induced lysosomal dysfunction produces many of the pathogenic attributes of Alzheimer's disease which we have previously shown.

Our previous work demonstrated that synaptic AMPA receptor function is impaired in hippocampal slice cultures exhibiting lysosomal dysfunction leading to protein accumulation. The present study investigated the effect of the AMPAkine CX516 on AMPAR-mediated synaptic transmission in this organotypic slice-culture model, as well as the CX516 induced modification of single channel AMPA receptor properties. In whole cell recordings from CA1 pyramidal neurons in chloroquine-treated slices we observed a significant decrease in AMPAR-mediated mEPSC frequency and amplitude indicating synaptic dysfunction. Following application of CX516, these parameters returned to nearly normal levels.

Similarly, we report chloroquine-induced impairment of AMPAR single channel function (decreased probability of opening and mean open time), and significant recovery of these properties as well following CX516 administration. These results suggest that AMPA receptors may be potential pharmaceutical targets for the treatment of neurodegenerative disease, and highlights AMPAkines in particular as possible therapeutic agents.

[Erbse1]

Aktueller Kommentar des NeuroInvestor zur Situation von Cortex. In den nächsten Tagen erwarte ich die Ergebnisse der zweiten Atemdepressionsstudie.

Grüße
Erbse

Cortex Pharmaceuticals: Commentary

Cortex presented Phase IIa data for CX717 in Respiratory Depression. The highest dose (2100mg) hit statistical significance in its effect on RD, even though only seven patients were assessed. The two lower doses did not produce valid data due to 'procedural errors', which does not reflect well on the CRO that did the trial. Had the DSMB not stepped in and revised the execution of the last and highest dose, the trial might have produced a false negative result. But this does provide the POC Cortex needed: the animal models were indeed predictive of human response, even though the experimental model itself had to be revised to meet human subjects safety standards. This makes CX717 and its IV version (and IV successor CX1942) a unique competitor for the highly problematic use of naloxone in cases of opiate induced RD. Adding in the potential of an oral adjunct that prevents RD in ongoing opiate analgesia, which would provide a distinct competitive advantage for the analgesia company marketing it, and one can expect an active partnering environment. Discussions have clearly already been underway, and Cortex's understated CEO was unusually optimistic in discussing prospects for a deal, A second Phase IIa trial will report in the next few weeks, and could potentially (assuming that group carried out the protocol correctly) add to the POC, including the demonstration of analgesia-maintenance.

NI's take is that over the next four months, Cortex will be choosing from three options:
1) A RD only deal for CX717, CX1942, and a low-impact-yet-to-be-named
2) A low-impact deal which covers RD and ADHD, which takes CX1739 as well. Otherwise, Cortex will bring CX1739 into ADHD trials next year.
3) A buyout offer. For example, Cephalon looks like a rational choice given their strong interests in both analgesia and ADHD. They need to update and upgrade their portfolio due to patent expirations. Over Cephalon's history, their preference appears to be to acquire rather than to license. There have been exceptions, but the license for Provigil was followed by the acquisition of Lafon, Actiq was via acquisition, so was their oncology franchise.

In any of these scenarios, Cortex's chronic cash problems will be alleviated, and (unless acquired outright) they will have the resources to develop their 'high-impact' neurotrophic platform for Alzheimer's, Parkinson's, and Huntington's. The recent damage done to the primacy of the amyloid hypothesis will raise the value of such 'ideology-free' strategies for AD--i.e. approaches that do not depend upon a specific causal model for therapeutic effect. RD, ADHD, and neurodegeneration together make for a company valuation far above the $37 million where they started the day.

[Erbse1]

Kleiner Abstract zu CX691. Interessant scheint noch, daß GlaxoSmithKline hier die Ampakine testet. Vielleicht der Partner für den europäischen Markt.

Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat.

Woolley ML, Waters KA, Gartlon JE, Lacroix LP, Jennings C, Shaughnessy F, Ong A, Pemberton DJ, Harries MH, Southam E, Jones DN, Dawson LA.
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK, [e-mail].

RATIONALE: Positive allosteric modulators of the glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment. OBJECTIVES: The objective of the study was to investigate the effect of an AMPA positive modulator, CX691, (1) in three rodent models of learning and memory, (2) on neurochemistry in the dorsal hippocampus and medial prefrontal cortex following acute administration, and (3) on brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat hippocampus following acute and sub-chronic administration. RESULTS: CX691 attenuated a scopolamine-induced impairment of cued fear conditioning following acute administration (0.1 mg/kg p.o.) and a temporally induced deficit in novel object recognition following both acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Acute CX691 (0.1, 0.3 and 1.0 mg/kg, p.o.) increased extracellular levels of acetylcholine in the dorsal hippocampus and medial prefrontal cortex and dopamine in the medial prefrontal cortex. Sub-chronic administration of CX691 (0.1 mg/kg, p.o.) elevated BDNF mRNA expression in both the whole and CA(1) sub-region of the hippocampus (P < 0.05). CONCLUSIONS: Collectively, these data support the pro-cognitive activity reported for AMPA receptor positive modulators and suggest that these compounds may be of benefit in treating disorders characterised by cognitive deficits such as Alzheimer's disease and schizophrenia.

[Erbse1]

Ampakine Abstracts Neuroscience Meeting 2008

Effects of Ampakines on hippocampal CA1 pyramidal neurons

Ampakines enhance axonal outgrowth by cortical neurons

Inhibition of XII inspiratory output by μ-opioid receptors is presynaptic and alleviated by ampakines

A nootropic drug Ampakine(CX-717)potently modulates synaptic AMPA receptor single channel properties

http://www.erbse.vm-elsig.de/form/base/YaBB.pl?num=122191222…

[Erbse1]

Cortex's AMPAKINE Compound, CX717, Achieves Primary Endpoints in Second Phase IIa Respiratory Depression Study in Germany

Monday October 6, 8:31 am ET
CX717 Prevents Opioid-Induced Respiratory Depression While Maintaining Analgesia

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) reported that top-line data from its second Phase IIa study in opioid-induced respiratory depression (RD) demonstrated that a single oral dose of 1500mg of the AMPAKINE® compound CX717 achieved statistical significance (p = 0.005) over placebo on the primary endpoint measure of spontaneous basal respiration without affecting opioid-induced analgesia. This placebo-controlled, double-blind, randomized two-way crossover trial (CX717-RD-01) was performed by one of the leading experts in the field, Professor Jörn Lötsch at the Institut für Klinische Pharmakologie, Johann Wolfgang Goethe-Universität in Frankfurt, Germany.

In this study, sixteen volunteers each received either 1500mg of CX717 or matching placebo that was orally administered two hours before each subject received an intravenous infusion of the opioid, alfentanil. The primary performance measures were the basal breathing rate, and the minute expiratory volume (VE) at 55 mmHg CO2 (VE55), and the lack of effect on analgesia. CX717 prevented the reduction in basal breathing rate induced by alfentanil, in comparison to placebo (p = 0.005). The degree of the reversal of the basal respiratory rate was similar to that obtained with the opioid antagonist, naloxone (Narcan®). At the same time, the analgesic properties of alfentanil were maintained in an acute pain model in the presence of CX717, whereas naloxone blocked the analgesic properties. The effect of CX717 on the VE55 numerically trended toward reversing, but did not reach statistical significance.

In August 2008, Cortex reported that in its first Phase IIa study in opioid-induced RD, 2100mg CX717 significantly reversed the VE55 measure of respiration. Spontaneous basal respiration was not an endpoint in the first Phase IIa study. “The primary objective of these two studies was to verify that this novel mechanism of action observed in animals would translate to humans,” commented Mark A. Varney, President and CEO, “and we are pleased to see statistically significant effects with a single oral dose in these small proof of concept clinical studies.” Dr. Varney went on to say, “AMPAKINE compounds may positively impact the ability of caregivers to optimize pain management for patients, as well as provide Cortex with a potentially large partnering opportunity and a good revenue stream when commercialized.”

The incidence of RD in a clinical setting related to opioid administration has been estimated to be up to 17% when oxygen desaturation is used as the indicator. Professor Lötsch added, “There are still fatal outcomes after opioid administration even under controlled conditions in the clinical setting. The data from this study supports the possibility of using CX717 in the clinic to avoid life-threatening adverse effects associated with opioids.”

These human results replicate data from animal studies generated by Dr. John Greer at the University of Alberta, which showed the utility of CX717 and other AMPAKINE compounds to prevent and treat opioid-induced RD without affecting their analgesic properties. Dr. Greer stated, “These advances will help patients whose pain cannot be treated effectively with opioids due to the unwanted side effect of a depression of breathing. Administration of AMPAKINE compounds can overcome this problem and lead to a significant improvement in pain management, as well as guard against deaths caused by opioid overdose. We are now extending our preclinical studies to determine whether AMPAKINE molecules can help the breathing problems in prematurely born babies and in adults with sleep apnea. This has been, and continues to be, an extremely productive collaboration with Cortex that is resulting in the translation of our basic scientific discoveries to clinical applications.”

Cortex plans to continue the development of AMPAKINE compounds in opioid-induced RD. An intravenous dosage form of CX717 is being finalized, and a follow-on compound, CX1942, a water soluble pro-drug of a novel AMPAKINE compound with improved potency over CX717, will shortly enter preclinical development for RD. Additionally, a novel AMPAKINE molecule, CX1739, is currently in Phase I clinical trials and is targeted to begin Phase II clinical trials for ADHD in Q2 2009.

[Ackergaul]

Antwort auf Beitrag Nr.: 35.435.586 von Erbse1 am 06.10.08 14:39:27

ich denke ein sehr gutes Ergebnis, mit dem nicht unbedingt zu rechnen war. Nachdem die 900er und 1500er Dosis des 1. Phase IIa nicht dieses Ergebniss brachte.
Obs jetzt in eine Phase IIb oder direkt III geht, bleibt abzuwarten. Vielleicht ist das Interesse von BIG Pharma auch wieder geweckt...


Grüße

[Erbse1]

Das schaut doch alles sehr gut aus im Augenblick für Cortex. Hier der Kommentar des NeuroInvestor zu den heutigen Daten.

Liebe Grüße
Erbse

Cortex and Respiratory Depression
Cortex Pharmaceuticals reported very solid efficacy data from their second trial of CX717 in respiratory depression, showing that the drug both prevents RD and (iunlike naloxone, the current treatment for opioid-induced RD) preserves analgesia. This will allow anesthesiologists to not have to subject patients to unmedicated post-surgical pain if respiratory depression occurs--and it occurs far more often than we had ever thought. The incidence varies by setting, and Cortex reports it may be as high as 17%, we think it can be safely estimated as being in the low double-digits--enough to be a safety, quality of care, and liability issue. Given that the data suggests this risk can be avoided via prophylaxis with CX717, we believe that once commercialized, CX717 (or a second-generation Ampakine) will become the new standard-of-care, because no anesthesiologist or hospital will want to justify a patient exposed to either the risk of death or of physically traumatizing and dangerous levels of pain.

Respiratory depression is not something with which NI was familiar when the concept of Ampakine usage therein was first floated last year. But it is familiar to front-line ER docs and surgeons. We witnessed this first hand when speaking with John Greer, who has pioneered the work in this area, at a professional meeting. During the 30 minutes we spoke in front of his poster, three MDs came up at various points, and spontaneously expressed the wish that they had CX717 in their armamentarium. By a rough calculation of the number of crash carts and surgical suites that would have to be equipped with CX717 in the US, NI's estimate a few months back was that just this market alone would be worth $700-800 million annually in the US (due to expirations, restocking would be necessary at least yearly). Cortex and Greer are also looking at the possibility that CX717 might be the first drug to directly address the respiratory issues in sleep apnea, which would jump the annual potential two to three fold, at least.

But beyond this, the Ampakine/RD scenario has one additonal, huge area of potential: the licensing company could develop a combination opioid/Ampakine drug which, via any delivery modality, would be differentiated from all other opioid formulations by this safety margin--the impossibility of inducing respiratory depression. In a nociceptive pain market where the gold standard opioids are almost indistinguishable from each other, and major efforts are going into various permutations of altering duration of effect and vulnerability to abuse, this would represent a unique marketing advantage--and one that no generic could approach for many years.

There is no competing MOA on the horizon, and indeed the role of AMPA circuits in the respiratory Pre-Botzinger Complex may be uniquely suited to this role. We expect that these very clear, clean data will stimulate a very competitive bidding situation vis-a-vis a partnership for Cortex.

[Erbse1]

Neue Patentanmeldung bei sexueller Dysfunktion bei Frauen. Die Anwendungsgebiete für Ampakine sind sehr vielfältig. Doch wenn es überhaupt entwickelt werden soll. Bis zur Marktreife dauert es sehr sehr lange.

TREATMENT OF FEMALE SEXUAL DYSFUNCTION BY COMPOUNDS THAT POSITIVELY MODULATE AMPA-TYPE GLUTAMATE RECEPTORS

http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2008118644&F…

Schönen Tag noch
Erbse

[Erbse1]

Cortex's AMPAKINE(R) Research in Opioid-induced Respiratory Depression Makes Windhover's Top 10 List of Neuroscience Projects Available for Partnering

Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) announced that Mark Varney, Ph.D., President & CEO, will present at the Windhover Information’s 3rd Annual Therapeutic Area Partnershipsconference to be held at the Loews Philadelphia Hotel on November 3-5, 2008.

The selection committee included Marc Wortman, Ph.D., associated with Windhover’s In Vivo and Start Up publication and Dr. Harry Tracy, President of NeuroInvestment, a leading independent neuroscience analyst. "Selected companies were evaluated using a strict set of judging criteria and represent what our committee considered the most attractive neuroscience opportunities the industry has to offer,” said Roger Longhorn, Managing Director of Windhover Information. After reviewing many promising neuroscience projects, the committee selected Cortex’s AMPAKINE® research program on opioid-induced respiratory depression as one of the Top Ten Projects for potential licensing. Acute post-operative respiratory depression extends hospital stays and is associated with a disproportional mortality rate. As a selected company, Cortex has been invited to make a presentation on its lead Phase II product candidate, CX717.

Dr. Varney commented, "Being selected as one of the Top 10 Neuroscience Projects by Windhover Information is a great honor and tangible evidence of what has been accomplished over the past 14 months with our AMPAKINE program. We are all excited about the results seen to date with CX717 that indicate the compound may optimize pain management with opioids without exposing surgical patients to the increased risk of respiratory depression.”
The web-link for the conference is listed below:

http://www.windhover.com/ezine/html/TA08Projects.htm?utm_sou… TA08&utm_mediu

(Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)

CX717 is an AMPAKINE molecule with good safety and efficacy. Earlier this week, Cortex issued a press release reporting the second positive Phase IIa, placebo-controlled, double-blind, randomized two-way crossover trial. In this study, a single oral 1500 mg dose of CX717 was administered two hours before the infusion of the potent opioid, alfentanil. CX17 prevented the reduction in basal breathing rate induced by the opioid in comparison to placebo (p = 0.005). The degree of the reversal of the basal respiratory rate was similar to that obtained with the standard opioid antagonist, naloxone. At the same time, the analgesic properties of alfentanil were maintained in an acute pain model in the presence of CX717. The trial was performed by one of the leading experts in the field, Professor Jörn Lötsch at the Institut für Klinische Pharmakologie, Johann Wolfgang Goethe-Universität in Frankfurt, Germany.

About Windhover

Windhover Information Inc (www.windhover.com), an Elsevier company, has led the field in providing analysis of the healthcare industry to decision-makers at all levels since the founding of its flagship publication, IN VIVO, the Business & Medicine Report, in 1983. Windhover provides its information and analysis in many formats, including print, electronic databases, international conferences and webinars.

[Erbse1]

Folgend eine kurze Zusammenfassung der erwarteten Ereignisse von COR, die in der nächsten Zeit anstehen.

1. Im 4.Quartal Fertigstellung der 2a PET Scan Studie mit CX 717 bei Alzheimer. Es sieht so aus, daß hier auf die Substanz CX 1739 gewechselt wird.

2. Gegen Ende des Jahres Fertigstellung der 2a Studie mit ORG 26576 bei Depression. Es bleibt zu hoffen, daß Schering - Plough nach der Übernahme von Organon eine verbesserte Informationspolitik verfolgt und die Daten auch veröffentlicht.

3. Im 1. Quartal 2009 Fertigstellung der 2a Studie mit ORG 26576 bei ADHD. Schering - Plough macht diese Studie in Eigenregie. Bisher sind die Anwendungsgebiete Depression und Schizophrenie an Schering - Plough auslizensiert. Bei dem Anwendungsgebiet ADHD wird seitens Cortex ein Partner gesucht. Kann gut sein, daß Schering-Plough nach dieser Studie Vertragspartner wird.

4. Ende 1. Quartal 2009 Fertigstellung der Phase 1 Studie mit CX1739 und anschließend Start im 2. Quartal einer Phase 2 Studie bei ADHD. CX1739 ist für mehrere Anwendungsgebiete vorgesehen.

5. In nächster Zeit Fertigstellung der vorklinischen Phase der Substanzen CX1942 CX1796 und dem High Impact Wirkstoff CX1837.

6. Quartal 1 2009. Partnerschaften oder Auslizensierungen hauptsächlich bei den Anwendungsgebieten ADHD und Atemdepression. Cortex hat noch ca. für gut ein halbes Jahr Geld. Entweder steht eine neue schmerzhafte Kapitalmaßnahme an oder eine wünschenswertere Auslizensierung. Lassen wir uns mal überraschen. Wer einige Millionen übrig hat und ein lohnendes Investment sucht, der kann sich ja mal bei Cortex melden.

Das wars erst mal im Großen und Ganzen

Grüße
Erbse

[Erbse1]

Happy Halloween all ihr Cortex Freaks

[Erbse1]

Nach erfolgreicher Atemdepressionstudie hier die Patentanmeldung. Bin mal gespannt drauf, ob demnächst auch das Anwendungsgebiet Schlafapnoe von Cortex bearbeitet wird. Bis dahin haben sie aber noch die schwierige Aufgabe an genügend Finanzen zu kommen. Es wird nicht einfach.

METHOD OF INHIBITION OF RESPIRATORY DEPRESSION USING POSITIVE ALLOSTERIC AMPA RECEPTOR MODULATORS

Abstract of US 2008261962 (A1)

The invention is directed to a method for alleviating respiratory depression in a subject as a result of disease of pharmacological agents such as opiates, opioids or barbiturates. The invention also discloses pharmaceutical compositions for use with the method, the composition containing in combination, an analgesic, anaesthetic, or a sedative and a positive allosteric AMPA receptor modulator in an amount sufficient to reduce or inhibit respiratory depression caused by the analgesic, anaesthetic, or sedative.

Quelle: http://v3.espacenet.com/publicationDetails/biblio?KC=A1&date…

[Erbse1]

Folgend die geplanten Milestones für das Jahr 2009.Ein neues Anwendungsgebiet ist mit Schlaf Apnoe geplant. Die Frage ist nur, ob Cortex das mit oder ohne Partner machen will. Eine Kapitalmaßnahme um die 50-60 Cent macht absolut keinen Spaß und das Geld ist schnell verbrannt. Signifikante Ergebnisse sind erst für Ende 2009 geplant. Man könnte das ganze auch gut von der Seitenlinie aus betrachten, wenn nicht doch eine Partnerschaft in Frage kommt. Es geht alles sehr langsam bei Cortex.
Grüße
Erbse

[Erbse1]

Noch ein kleiner Auszug des Börsenbriefes NeuroInvestor zu Cortex Pharmaceuticals

The Breathtaking Potential of Ampakines in Respiration
(from NI November)

Cortex Pharmaceuticals reported very solid efficacy data from their second trial of CX717 in respiratory depression (RD), showing that the drug both prevents RD and (unlike naloxone, the current treatment for opioid-induced RD) preserves analgesia. This means that anesthesiologists would not have to subject patients to completely unfettered post-surgical pain if respiratory depression occurs--and it occurs far more often than we had ever thought. The incidence varies by setting, and while Cortex has data indicating it may be as high as 17%, we more conservatively estimate it as being in the low double-digits. Certainly this is enough to constitute a safety, quality of care, and liability issue. Since it now appears that this risk can be completely avoided or alleviated via an Ampakine, we believe that once commercialized, an Ampakine will become the new standard-of-care: No anesthesiologist or hospital will want to explain why a patient was left exposed to either the risk of death or of physically traumatizing and dangerous levels of pain.

Respiratory depression is not something with which NI was at all familiar when the concept of Ampakine usage therein was first floated last year, and initially our view was that this was at most, a very secondary niche indication. What transformed our view was an anecdotal experience, but one with some impact. At a professional meeting in late 2007, we serendipitously happened to encounter John Greer, who has pioneered the work in this area, at a poster session he was presenting on his preclinical work with Ampa modulation and RD. During the 30 minutes we conversed in front of his poster, three MDs came up at various points, and spontaneously expressed the wish that they had CX717 in their armamentarium--"We could really use something like this.' As it turns out, RD is indeed a familiar and troubling worry for front-line ER docs, surgeons, and anesthesiologists/anesthetists, a large market unhappy with having to choose between respiratory function and pain when RD occurs.

After a rough calculation of the number of crash carts and surgical suites that would have to be equipped with an Ampakine for RD rescue or prophylaxis in the US, our estimate a few months back was that just this market alone would be worth $700-800 million annually in the US (due to expirations, restocking would be periodically necessary). Cortex and Greer are also looking at the possibility that CX717 might be the first drug to effectively address RD due to other agents, like Propofol or barbiturates, for which there is no current 'antidote.' The animal data indicates that it works with that type of RD, indeed it appears to be a potential remedy for RD due to many different causes. Perhaps most enticingly, Cortex is working to ascertain whether Ampakine modulation may address the respiratory issues in sleep apnea, which would jump the annual potential manyfold.

The Ampakine/RD scenario has one additional, major area of commercial potential: producing a gold-plated market leader amongst the gold standard opioid analgesics. The company which licenses Ampakines for RD (and Cortex controls this IP for many years) could develop a combination opioid/Ampakine drug which, via any delivery modality, would be differentiated from all other opioid formulations by this safety margin; the impossibility of inducing respiratory depression. In a nociceptive pain market where opioids are almost indistinguishable from each other. Currently, major efforts are going into various permutations of altered duration of effect and vulnerability to abuse; this safety profile would represent a unique marketing advantage, one beyond the reach of generic competition for many years.

At worst, the opioid RD rescue market alone is worth $700 million annually. The numbers climb steeply if one includes an opioid combo drug application, and would skyrocket if it turns out that Ampakines constitute the first direct (rather than treating secondary fatigue) pharmacotherapy for sleep apnea--since that taps a market that may reach eighteen million people in the US alone. The sleep apnea POC remains to be shown, but there are published studies wherein electrical stimulation of the hypoglossal nerve produced clear improvement in sleep apnea patients, due to the effect upon tone in the musculature of the tongue. If AMPA receptors in the dorsal medulla trigger similar activation of that nerve, it could be a straightforward route to correcting sleep apnea. While 5HT-4 and adenosine receptors have been suggested as targets for respiration control, the role of AMPA circuits may be uniquely suited to these indications, there is no competing MOA that has yet emerged. These strikingly clear data, and surprisingly large-scale prospects, should stimulate a very competitive bidding situation vis-a-vis a partnership for Cortex and RD.

[Erbse1]

Hallo liebe COR Freunde,
die Rekrutierung des ADHD Versuches scheint jetzt schon fertig zu sein.

Dose Finding Study in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
This study is ongoing, but not recruiting participants.

http://www.clinicaltrials.gov/ct2/show/NCT00610441?term=2657…

Bleibt abzuwarten, ob Schering - Plough die Ergebnisse auch veröffentlicht. Bin mal gespannt darauf, ob es Cortex gelingt rechtzeitig an Geld zu kommen. Eine Auslizensierung wäre schon wünschenswert. Zu dem Kurs traue ich mich gar nicht mehr überhaupt etwas zu schreiben. Ich hatte mir da nach den erfolgreichen Atemdepressionsstudien doch einiges mehr erwartet.
Machts mal gut
Erbse

[Ackergaul]

Wünsche schöne Weihnachtstage!

Grüße

[Erbse1]

Die nächste Phase2 Studie bei Depression ist jetzt komplett. Auch hier müssen wir die Ergebnisse abgewartet werden. Federführend war hier nicht Schering-Plough sondern das National Institute of Mental Health . Demnach warten wir nun auf vier Ergebnisse von verschiedenen Studien.

1. CX717 Pet Scan bei Alzheimer
2. Org 24448 bei Depression
3. Org 26576 bei Depression
4. Org 26576 bei ADHD

Ansonsten bin ich sehr enttäuscht von dem Kursverlauf von Cortex. Auch von der Ankündigung Roger Stolls schnell einen Partner zu präsentieren ist bisher nichts zu sehen. Leider arbeitet Cortex sehr langsam. Es ist sehr gut möglich, daß bald das Geld ausgeht. Cortex hat sich wohl von den Anwendungsgebieten Kognitive Defizite verabschiedet und fokussiert kommende Entwicklungen auf die Anwendungsgebiete Atemdepression und Schlafapnöe. Vielleicht verliere ich auch etwas zu früh die Geduld. Ich betrachte Cortex nur noch von außen und setze sie auf meine Watchlist. Sollte ein finanzkräftiger Partner auftauchen, so überlege ich einen Widereinstieg. Leider ist es so, es gibt bessere Biotechwerte mit einer guten Pipeline und vor allem mit mehr Kapital. Eine Übernahme bei dem wenigen Kapital wäre eine Option. Die Chancen für die Pipeline sind nicht von der Hand zu weisen. Dazu gehört aber noch eine finanziell abgesicherte Planung. Ich laß mich mal überraschen.

Allen Cortex Mitstreitern einen guten Rutsch und ein erfolgreiches Jahr 2009
Grüße
Erbse

[Erbse1]

Kleiner Artikel zu dem nächsten Anwendungsgebiet der Ampakine von Cortex

Grüße
Erbse

(Business Wire) The Greek word “apnea” literally means “without breath.” Sleep apnea is a common sleep disorder characterized by short pauses in breath during sleep. Each episode lasts long enough so that several breaths are missed, with such episodes occurring repeatedly throughout sleep.

There are three types of apnea: obstructive, central, and mixed; with obstructive being the most common. Despite differences in the root cause of each type, those suffering from sleep apnea stop breathing repeatedly during sleep, sometimes hundreds of times during the night, and often for a minute or longer.

Sleep apnea is a surprisingly common condition: according to the National Institutes of Health, the disorder affects more than twelve million Americans, making it as common as adult diabetes.

Certain factors increase the risk of sleep apnea, such as being male, overweight, and over the age of forty, but sleep apnea can strike anyone at any age, including children. The vast majority of sufferers go undiagnosed and untreated. Untreated, sleep apnea can lead to high blood pressure and other cardiovascular diseases, memory problems, weight gain and diabetes, impotence, and headaches.

A special consideration for sufferers of sleep apnea concerns the use of anesthetic agents during surgery and narcotic analgesics (pain relievers) after surgery. Many drugs and agents used during or after surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards.

Researchers at the University of Alberta and Cortex Pharmaceuticals, a neuroscience company based in Irvine, California, believe that a novel class of molecules known as AMPAKINE compounds may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA-type glutamate receptor. Dr. John J. Greer of the University of Alberta demonstrated that certain AMPAKINE compounds stimulate primitive areas of the brain called the pre-Botzinger Complex that controls breathing, without causing side effects.

In animal models, AMPAKINE compounds were shown to enhance the respiratory drive and breathing rhythm in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants.

AMPAKINES could one day allow for improved safety and a more effective use of opiate analgesics and barbiturate sedatives, two important classes of central nervous system drugs. For more information, visit www.cortexpharma.com.

[Erbse1]

Cortex Receives UK Regulatory Approval to Initiate a Clinical Study in Sleep Apnea With Its AMPAKINE CX1739
Tuesday January 27, 2009, 8:31 am EST
Yahoo! Buzz Print Related:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) announced that the UK’s Medicines and Healthcare product Regulatory Agency (MHRA) gave it permission to proceed with the clinical development of CX1739 in subjects with moderate to severe sleep apnea. The study will be conducted in a UK sleep unit using a double-blind, placebo-controlled design in 20 subjects.

Sleep apnea is a chronic disorder characterized by pauses in breathing during sleep, with the most common type being obstructive sleep apnea. Each episode, called an apnea, lasts long enough so that one or more breaths are missed. Such episodes occur repeatedly throughout sleep and may result in significantly reduced blood oxygenation. If left untreated, sleep apnea can lead to an increased risk of stroke, heart attacks, hypertension, obesity and Type II, maturity onset diabetes, as well as an increased risk of accidents due to excessive sleepiness. The National Institute of Health estimates that over 12 million American adults have sleep apnea. There is currently no drug treatment option available for sleep apnea and the market is considered a multi-billion dollar opportunity in North America alone.

“CX1739 has been very well tolerated in Phase I healthy volunteer studies, and we are excited to be able to proceed with an efficacy study in sleep apnea,” said Dr. Mark Varney, President and Chief Executive Officer of Cortex. “We anticipate starting subject enrollment in February and completing the study in the second quarter of 2009.”

Data obtained from animal studies have demonstrated that AMPAKINE compounds can specifically stimulate breathing by activating regions in the brain stem. In 2008, Cortex announced positive results of two clinical studies that demonstrated the AMPAKINE CX717 could prevent the depression of breathing induced by an opioid analgesic. Further analyses of these clinical studies also showed that CX717 reduced both the number and duration of apnea events caused by the opioid. Studies in animals suggest that CX1739 is approximately three times better than CX717 at reversing breathing depressed by opioids. CX1739 also stimulates another brain region that regulates muscle tone in the upper airways. “Our hypothesis is that by stimulating breathing and increasing muscle tone in the upper airways, CX1739 will be effective in maintaining breathing throughout the night in sleep apnea patients,” commented Dr. Varney.

[Erbse1]

Schön und gut der folgende Beitrag. Leider fehlen im Augenblick Geld und Partner die Geschichte auch erfolgreich durchzuführen. Ich selber bin genau wegen dieser Thematik vor 9 Jahren auf Cortex aufmerksam geworden. Leider haben sie bis jetzt so gut wie gar nichts auf die Beine gekriegt. Die Schuldfrage lassen wir mal außen vor.
Grüße
Erbse

Studies in Animals Demonstrate AMPAKINE Molecules Reverse Memory Loss in Huntington's Disease
Friday March 6, 2009, 7:51 am EST
Print Related:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) announced that preclinical studies from the laboratory of Professor Gary Lynch at the University of California Irvine, one of the scientific founders of the company, demonstrated that AMPAKINE® molecules show promise in the treatment of memory loss in Huntington’s disease. The studies were performed in mice harboring the genetic mutation found in humans that is responsible for Huntington’s disease. The related results demonstrated that treating mice with CX929, a High Impact AMPAKINE, produced dramatic increases in the brain’s chemical processes for creating and storing memories. These studies were published in the early online version of the prestigious, peer-reviewed journal, Proceedings of the National Academy of Sciences (PNAS).

Huntington's disease is a progressive, hereditary brain disease that affects men and women alike, and affects 30,000 patients in the U.S., with another 150,000 at risk. It is caused by the death of specific brain cells and is characterized by the gradual development of involuntary muscle movements, progressive deterioration of cognitive processes and memory (dementia), and severe behavioral disturbances. The memory impairments include altered organization, generally slowed processing of information by the brain, and executive function – that is, the ability to plan, abstract thinking and multi-tasking.

“One protein in particular, brain-derived neurotrophic factor (BDNF), is reduced in Huntington’s disease. We know that BDNF plays an essential role in maintaining the health of the brain,” commented Professor Lynch. “And our studies now demonstrate that we can restore levels of BDNF by treating mice with an AMPAKINE, which reverses the memory impairments.”

Mark A. Varney, President and CEO stated that, “Professor Lynch’s studies in mice support the rationale for Cortex to develop AMPAKINE molecules to address the memory deficits in patients suffering from Huntington’s disease. Also, the link to BDNF may play an important role in other neurodegenerative diseases such, as Alzheimer’s Disease.”

[Erbse1]

Cortex jetzt mit neuem Partner.

Merck to buy Schering-Plough for $41.1B
http://sanjose.bizjournals.com/sanjose/stories/2009/03/09/da…

Mit Merck habe ich mich noch gar nicht beschäftigt. Keine Ahnung, was das für eine Auswirkung auf das Ampakine Programm hat. Meine Hoffnung war immer noch, daß Schering-Plough Cortex einmal übernehmen könnte. Die Kapitalisierung ist sowieso nur noch ein Witz und Cortex in wenigen Wochen pleite, wenn sich nicht bald was Entscheidendes tut.

Grüße
Erbse

[Erbse1]

Das schaut nicht gut aus. Kein Geld. Keine Partner.

Cortex Pharmaceuticals Announces Corporate Restructuring and Workforce Reduction
Thursday March 19, 2009, 8:35 am EDT
Print Related:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) announced a significant restructuring of its organization which involved a reduction of personnel by approximately 50%. The workforce reduction is in addition to other capital preserving initiatives, including the reduction of salaries for the Company’s Executive Officers. Because of the continuing uncertainty in the capital markets and the global economy, Cortex took steps to reduce its monthly spending requirements to align its current resources with its strongest near-term opportunities. Cortex will focus its efforts on the development of its clinical programs involving CX717 and CX1739, which it believes will have the greatest opportunity for creation of shareholder value. At the same time it has significantly reduced basic research efforts in early, non-clinical stage programs.
“This restructuring is an absolute necessity in the light of the current financial climate,” said Mark Varney, Ph.D., President and CEO of Cortex. “I would like to express my gratitude for the contributions and commitment of our outstanding employees who were impacted by the workforce reduction. However, we need to ensure that Cortex can continue to advance its promising pipeline compounds. In the near term, these programs have the potential to address three very large markets of ADHD, sleep apnea and respiratory depression. Obviously, over the longer term we plan to continue to develop additional applications in Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders.”

Currently, Cortex has four programs in clinical or preclinical development representing diverse chemical structures and market opportunities. These programs include:


CX717: one of Cortex’s Low Impact AMPAKINE® drugs that achieved proof-of-concept in opioid-induced respiratory depression. Current efforts are focused on the development of an intravenous dosage form of CX717.
CX1739: an AMPAKINE compound that is currently in a Phase II sleep apnea study, with expected completion around mid-2009. A Phase II study in ADHD in adult patients is planned to be initiated around mid-year in the US.
CX1942: a unique AMPAKINE pro-drug with enhanced water solubility which is approximately 5-6 times as potent as CX717 and has potential in both i.v. and oral respiratory depression applications and sleep apnea. Cortex plans to advance the compound into toxicology and Phase I clinical trials over the next year, when additional capital becomes available.
CX2007: A compound in a new chemistry space, with a longer half-life than other compounds that will be advanced for the treatment of ADHD and Alzheimer’s disease, when additional capital becomes available.

“Given the current state of the capital markets, we will continue to evaluate all options for raising cash, including licensing, partnering, and other strategic options. Cortex is currently working diligently to secure several out-licensing and partnering opportunities, which if and when completed, will provide a significant infusion of capital,” stated Mark Varney.

[Erbse1]

Jetzt wirds aber bitter. Da kann man nur hoffen, daß Cortex bald einen Partner findet. Vielleicht schaffen sie ja noch die Phase 2 Studie.
Grüße
Erbse

Cortex Announces Financing

Tuesday April 14, 2009, 10:49 pm EDT
Print Related:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Amex: COR) announced that it has obtained a commitment to purchase shares of a newly-designated series of convertible preferred stock pursuant to a registered direct offering to a single institutional investor, representing gross proceeds of approximately $1.5 million. Subject to certain ownership limitations, the preferred stock is convertible into shares of Cortex at the option of the investor at a price of $0.17 per share.

The investor will also receive warrants to purchase 6.9 million shares of Cortex’s common stock. The warrants have an exercise price of $0.3401 per share and, subject to certain ownership limitations, are exercisable after the six-month anniversary of the closing of the transaction and before the third anniversary of such initial exercise date. The closing of the offering is expected to take place on or before April 17, 2009, subject to the satisfaction of customary closing conditions, including the final approval for listing of the shares of common stock (including shares of common stock underlying the convertible preferred stock and the warrants) on the NYSE Amex Equities Market. Cortex plans to use the net proceeds from the offering for working capital and other general corporate purposes.

A shelf registration statement (File No. 333-155749) relating to these securities has been declared effective by the Securities and Exchange Commission. Rodman & Renshaw, LLC, a subsidiary of Rodman & Renshaw Capital Group, Inc. (Nasdaq: RODM), acted as the exclusive placement agent for the transaction.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. Any offer of these securities will be solely by means of a prospectus included in the registration statement and any prospectus supplement that may be issued with respect to such offering. Copies of the final prospectus, including the prospectus supplement when filed, can be obtained at the Securities and Exchange Commission’s website, www.sec.gov, or from Rodman & Renshaw, LLC at 212.536.0550

[Ackergaul]

Antwort auf Beitrag Nr.: 36.968.967 von Erbse1 am 15.04.09 05:35:38

Im letzten Quartal über 3 Millionen Dollar verbrannt. Rechnet man nun pro Monat etwa 0,8 Millionen Dollar (Reduzierung auf Grund Restrukturierung) Verlust, kommt Cortex allenfalls bis Mitte Mai noch. Cash und die verschleuderbaren Wertpapiere waren nämlich so ungefähr 4,3 Mil. $...
Ob die Sleep Apnea Resultate von CX1739 noch Rechtzeitig helfen (Mitte 09)? Partnerschaften und Verhandlungen zu 717 sind schon ewig angekündigt und nichts bei rum gekommen. Sieht leider überhaupt nicht gut aus...

[Erbse1]

Antwort auf Beitrag Nr.: 36.973.224 von Ackergaul am 15.04.09 17:02:55

Hallo Ackergaul,
ich seh es genau so wie du. Nur ein Wunder kann Cortex noch retten. Interessenten sollten einen möglichen Konkurs abwarten und die gesamte Ampakine Patente für einige Dollar aufkaufen. Schade eigentlich, aber manchmal läufts halt so.

Grüße
Erbse

[Ackergaul]

Antwort auf Beitrag Nr.: 36.973.693 von Erbse1 am 15.04.09 17:56:59

ASM hatte sich zuletzt ja noch 1,5 Mil $ gesichert, so dass man wohl auf jeden Fall bis Juni / Juli Geld hat. Dann sollten die Ergebnisse zu CX1739 (hoffentlich) heraus sein. unter folgender Seite ist ein Interview zu CX1739 zu hören:
http://www.sleepreviewmag.com/podcast/files/20090422.asp

The Pill to Treat Sleep Apnea
Special guest: Mark A. Varney, PhD

Mark A. Varney, PhD, is president and CEO of Cortex Pharmaceuticals Inc. Cortex Pharmaceuticals Inc is proceeding with clinical development of CX1739, a pharmaceutical for the treatment of sleep apnea. The UK's Medicines and Healthcare product Regulatory Agency gave Cortex Pharmaceuticals permission to proceed with the clinical development of CX1739 in subjects with moderate to severe sleep apnea. The study will be conducted in a UK sleep unit using a double-blind, placebo-controlled design in 20 subjects.

Sleep Review acknowledges Clayton Sleep Institute for their generous sponsorship of the Sleep Review Soundcast.


Deutet für mich darauf dass CX717 nicht zu verpartnern ist und die (letzte) Hoffnung nun auf CX1739 liegt...


Grüße

habe übrigends noch nicht reingehört...

[Erbse1]

!

Dieser Beitrag wurde moderiert.

[Erbse1]

Cortex Receives Notice of Non-Compliance from NYSE Amex for Continued Listing Requirements

On Friday May 22, 2009, 4:03 pm EDT
Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Amex: COR) reported that it has received notice from the NYSE Amex LLC indicating that the company is not in compliance with certain of the Exchange’s continued listing standards. Specifically, the notice indicated that the company is not in compliance with Sections 1003(a)(i), 1003(a)(ii) and 1003(a)(iii) of the NYSE Amex Company Guide regarding stockholders’ equity and losses from continuing operations and/or net losses; and Section 1003(a)(iv) of the Company Guide in that its financial condition has become so impaired that it appears questionable, in the opinion of the Exchange, as to whether the company will be able to continue operations and/or meet its obligations as they mature.

In order to maintain its listing, Cortex has the opportunity to submit a plan of compliance by June 18, 2009, advising the Exchange of action it has taken or will take, that would bring it into compliance with Section 1003(a)(iv) of the Company Guide by November 18, 2009 and with Sections 1003(a)(i), 1003(a)(ii) and 1003(a)(iii) of the Company Guide within a maximum of 18 months, or by November 18, 2010 (the “plan period”). Cortex intends to make a timely submission of its plan to the NYSE Amex.

The Exchange will evaluate the submitted plan and determine whether the plan includes a reasonable demonstration of an ability to regain compliance with the continued listing standards within the specified timeframes, in which case the plan will be accepted. However, there can be no assurance that such plan will be accepted by the Exchange.

If the submitted plan is not accepted by NYSE Amex, or if the plan is accepted but Cortex is not in compliance with the continued listing standards within the appropriate time periods, or if Cortex does not make progress consistent with the plan during the plan period, the company may become subject to delisting proceedings. If the NYSE Amex staff determines that it will initiate delisting proceedings, Cortex may appeal the decision at a hearing with the exchange.

Prior to submitting its plan and while the plan is under review by the NYSE Amex, Cortex expects that its common stock will continue to trade without interruption on NYSE Amex; however the trading symbol for the company’s common stock will have an indicator (.BC) added as an extension to signify noncompliance with the continued listing standards. The .BC indicator will remain as an extension on the company’s trading symbol until Cortex has regained compliance with all applicable continued listing standards. The NYSE Amex website will also include Cortex on a list of issuers that do not comply with the continued listing standards.

Currently patient enrollment is underway in Cortex’s clinical trial of CX1739 in patients with moderate to severe sleep apnea. This pilot study in patients was undertaken based on promising animal data generated by Dr. John Greer at the University of Alberta. Chronic sleep apnea can lead to serious long-term consequences such as cardiovascular disease, stroke and diabetes. Also, recent studies with Cortex’s High Impact AMPAKINE molecules in animal studies demonstrated that CX1837 produced marked increases in the rate and extent of recovery of motor function following brain damage induced by a stroke in mice. In another study, CX929 exhibited a mood stabilizing effect in mice, suggesting the potential for treating bipolar disorder. The company currently has two compounds in clinical development: CX1739, which is targeted for sleep apnea and ADHD, and i.v. CX717 for treatment of drug-induced respiratory depression.

Cortex currently is actively engaged in on-going discussions related to strategic alternatives, including licensing, partnering and M&A opportunities. At some time in the future, Cortex may also seek to raise additional capital through the sale of debt or equity. There can be no assurance that any of these aforementioned discussions will result in a transaction.

[Ackergaul]

wen es interessiert:
http://journals.lww.com/anesthesiology/Fulltext/2009/06000/A…

Ampakine CX717 Protects against Fentanyl-induced Respiratory Depression and Lethal Apnea in Rats

Abstract
Background: The use of fentanyl as a potent analgesic is contradicted by marked respiratory depression among a subpopulation of patients. The commonly used approach of reversing fentanyl-induced respiratory depression with μ-opiate receptor antagonists such as naloxone has the undesirable effect of blocking analgesia. Here, the authors report a clinically feasible pharmacological solution for countering fentanyl-induced respiratory depression via a mechanism that does not interfere with analgesia. Specifically, to determine if the ampakine CX717, which has been proven metabolically stable and safe for human use, can prevent and rescue from severe fentanyl-induced apnea.

Methods: Plethsymographic recordings were performed from young and adult rats. Varying doses of fentanyl were administered either intraperitoneally or intravenously to induce moderate to life-threatening apneas. CX717 was administered either before or after fentanyl administration. In addition, phrenic nerve recordings were performed from in situ working heart brainstem preparations from juvenile rats.

Results: Preadministration of CX717 markedly attenuated fentanyl-induced respiratory depression. Postadministration of CX717 rescued animals from a lethal dose of fentanyl. Significantly, CX717 countered fentanyl-induced depression of respiratory frequency without suppressing analgesia. The effective dose of CX717 was in the range deemed safe on the basis of clinical trials examining its efficacy for cognitive disorders. In situ, fentanyl-induced depression in respiratory frequency and amplitude was alleviated by CX717.

Conclusions: CX717 is an agent that enhances the safety of using opiate drugs while preserving the analgesic effects. This advancement could significantly improve pain management in a variety of clinical settings.

........



Grüße

[Erbse1]

S18986 ist von Cortex an Servier auslizensiert

The AMPA receptor positive allosteric modulator, S18986, is neuroprotective against neonatal excitotoxic and inflammatory brain damage through BDNF synthesis.

Destot-Wong KD, Liang K, Gupta SK, Favrais G, Schwendimann L, Pansiot J, Baud O, Spedding M, Lelièvre V, Mani S, Gressens P.
Inserm, U676, Paris, France; Université Paris 7, Faculté de Médecine Denis Diderot, Paris, France; PremUP, Paris, France.

Brain lesions induced in newborn mice by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-willardiine (acting on AMPA-kainate receptors) mimic some aspects of periventricular white matter lesions and neocortical grey matter damage observed in human neonates at risk for developing cerebral palsy. The neonatal mouse brain can be sensitized to excitotoxic damage by IL-1beta exposure similar to that observed in the human situation. Positive modulators of AMPA receptors have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. However whether they can also act as a neuroprotectant in neonatal brain damage has yet to be defined. Therefore the present study uses a well-defined rodent model of neonatal excitotoxic brain lesions to assess the neuroprotective effects of S18986, a positive allosteric modulator of AMPA receptors, as well as its mechanisms of action. In this model, S18986 provided a dose-dependent and long-lasting protection of developing white matter and cortical grey matter against an excitotoxic insult and also when this was combined with a sensitizing inflammatory insult. Neuroprotective effects of S18986 in cortical grey matter involved decreased necrotic and apoptotic cell death. S18986-induced neuroprotection against NMDA receptor-mediated brain lesions was blocked by inhibitors of ERK and PI3 kinase-Akt pathways. S18986 effects were abolished by a neutralizing anti-BDNF antibody and real-time PCR confirmed the stimulation by S18986 of BDNF production in the neonatal brain. The present study provides strong experimental support for the role of S18986 as a candidate molecule for therapy in cases of excitotoxic perinatal brain lesions and identifies BDNF as a key mediator of this S18986-mediated neuroprotection.

[Erbse1]

Ampakine CX717 protects against fentanyl-induced respiratory depression and lethal apnea in rats.
Ren J, Ding X, Funk GD, Greer JJ.
Department of Physiology, Division of Neuroscience, University of Alberta, Edmonton, Alberta, Canada.

BACKGROUND: The use of fentanyl as a potent analgesic is contradicted by marked respiratory depression among a subpopulation of patients. The commonly used approach of reversing fentanyl-induced respiratory depression with mu-opiate receptor antagonists such as naloxone has the undesirable effect of blocking analgesia. Here, the authors report a clinically feasible pharmacological solution for countering fentanyl-induced respiratory depression via a mechanism that does not interfere with analgesia. Specifically, to determine if the ampakine CX717, which has been proven metabolically stable and safe for human use, can prevent and rescue from severe fentanyl-induced apnea. METHODS: Plethsymographic recordings were performed from young and adult rats. Varying doses of fentanyl were administered either intraperitoneally or intravenously to induce moderate to life-threatening apneas. CX717 was administered either before or after fentanyl administration. In addition, phrenic nerve recordings were performed from in situ working heart brainstem preparations from juvenile rats. RESULTS: Preadministration of CX717 markedly attenuated fentanyl-induced respiratory depression. Postadministration of CX717 rescued animals from a lethal dose of fentanyl. Significantly, CX717 countered fentanyl-induced depression of respiratory frequency without suppressing analgesia. The effective dose of CX717 was in the range deemed safe on the basis of clinical trials examining its efficacy for cognitive disorders. In situ, fentanyl-induced depression in respiratory frequency and amplitude was alleviated by CX717. CONCLUSIONS: CX717 is an agent that enhances the safety of using opiate drugs while preserving the analgesic effects. This advancement could significantly improve pain management in a variety of clinical settings.

[Erbse1]

Noch ein Abstract. Cortex wird nur noch mit 9 Millionen $ bewertet und ich wollte mir mal davon meine Rente finanzieren. So geht es manchmal im Leben.
Schering Plough hat nur noch ADHD und Depression in der Pipeline. Kognitive Defizite bei Schizophrenie wird nicht mehr aufgeführt.
Schlafapnöe Trial läuft sehr langsam und so droht eine weitere schmerzhafte Kapitalmaßnahme. Interessenten kriegen bald alle Patente für einige Dollar.
Trotzdem mal die Augen aufhalten, falls doch eine Partnerschaft vermeldet wird.
Grüße
Erbse

Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation.
Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M.
Neurobiology, University of Southern California, Los Angeles, California 90089, USA.

Brain-derived neurotrophic factor (BDNF) stimulates local dendritic mRNA translation and is involved in formation and consolidation of memory. 2H,3H,6aH-pyrrolidino[2'',1''-3',2']1,3-oxazino[6',5'-5,4]-benzo[e]1,4-dioxan-10-one (CX614), one of the best-studied positive AMPA receptor modulators (also known as ampakines), increases BDNF mRNA and protein and facilitates long-term potentiation (LTP) induction. Several other ampakines also improve performance in various behavioral and learning tasks. Since local dendritic protein synthesis has been implicated in LTP stabilization and in memory consolidation, this study investigated whether CX614 could influence synaptic plasticity by upregulating dendritic protein translation. CX614 treatment of primary neuronal cultures and acute hippocampal slices rapidly activated the translation machinery and increased local dendritic protein synthesis. CX614-induced activation of translation was blocked by K252a [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester], CNQX, APV, and TTX, and was inhibited in the presence of an extracellular BDNF scavenger, TrkB-Fc. The acute effect of CX614 on translation was mediated by increased BDNF release as demonstrated with a BDNF scavenging assay using TrkB-Fc during CX614 treatment of cultured primary neurons and was blocked by nifedipine, ryanodine, and lack of extracellular Ca(2+) in acute hippocampal slices. Finally, CX614, like BDNF, rapidly increased dendritic translation of an exogenous translation reporter. Together, our results demonstrate that positive modulation of AMPA receptors rapidly stimulates dendritic translation, an effect mediated by BDNF secretion and TrkB receptor activation. They also suggest that increased BDNF secretion and stimulation of local protein synthesis contribute to the effects of ampakines on synaptic plasticity.

PMID: 19587275

[Erbse1]

Wird Zeit daß Merk Schering-Plough mal die Daten zu den ORG 26576 Studien veröffentlichen. Ein wenig Klarheit würde allen nutzen. Unten noch einen Abstract zu diesem Thema.
Leider weiß ich im Augenblick nichts mehr zur patentrechtlichen Position. Wenn ORG 26576 mal zugelassen wird, schaut Cortex ganz lböd aus der Wäsche, da die Patentzeit abgelaufen ist. Es ist bei Cortex fast alles schief gelaufen, was eben geht. Doch das ist Biotech.
Grüße
Erbse

Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus.
Su XW, Li XY, Banasr M, Koo JW, Shahid M, Henry B, Duman RS.
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, 06508, USA.

RATIONALE: Currently available antidepressants upregulate hippocampal neurogenesis and prefrontal gliogenesis after chronic administration, which could block or reverse the effects of stress. Allosteric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators (ARPs), which have novel targets compared to current antidepressants, have been shown to have antidepressant properties in neurogenic and behavioral models.
OBJECTIVES: This study analyzed the effect of the ARP Org 26576 on the proliferation, survival, and differentiation of neurons and glia in the hippocampus and prelimbic cortex of adult rats.

MATERIALS AND METHODS: Male Sprague-Dawley rats received acute (single day) or chronic (21 day) twice-daily intraperitoneal injections of Org 26576 (1-10 mg/kg). Bromodeoxyuridine (BrdU) immunohistochemistry was conducted 24 h or 28 days after the last drug injection for the analysis of cell proliferation or survival, respectively. Confocal immunofluorescence analysis was used to determine the phenotype of surviving cells.

RESULTS: Acute administration of Org 26576 did not increase neuronal cell proliferation. However, chronic administration of Org 26576 increased progenitor cell proliferation in dentate gyrus (~40%) and in prelimbic cortex (~35%) at the 10-mg/kg dosage. Cells born in response to chronic Org 26576 in dentate gyrus exhibited increased rates of survival (~30%) with the majority of surviving cells expressing a neuronal phenotype.

CONCLUSION: Findings suggest that Org 26576 may have antidepressant properties, which may be attributed, in part, to upregulation of hippocampal neurogenesis and prelimbic cell proliferation.

[Erbse1]

Ob Cortex im letzten Augenblick nochmal die Kurve kriegt. Diese Kapitalmaßnahmen zu diesem Kurs sind bitter, aber nicht mehr zu vermeiden.

Cortex Pharmaceuticals Announces Financing
IRVINE, Calif., Jul 30, 2009 (BUSINESS WIRE) -- Cortex Pharmaceuticals, Inc.
(NYSE Amex: COR) reported that it has entered into a definitive agreement with a
single institutional investor related to a private placement of its newly
designated Series F convertible preferred shares. The financing will provide
proceeds of approximately $2.0 million to Cortex. A total of 4,029 shares of its
preferred stock and warrants to purchase 6,060,470 shares of Cortex common stock
will be issued for gross proceeds of $4.029 million, of which $2.029 million
will be placed in escrow for certain payments upon conversion of the preferred
stock described below. The preferred stock has a stated value of $1,000 per
share and is convertible into Cortex common stock at the option of the investor
at $0.3324 per share. The warrants have a three year term and an exercise price
of $0.2699 per share. An aggregate of 12,120,939 shares of Cortex common stock
is issuable upon conversion of the preferred stock.

Additionally, if the convertible preferred stock is converted prior to July 29,
2014, Cortex has agreed to pay the holder an amount from escrow equal to
approximately $504 per share of preferred stock converted. The closing of the
financing is expected to take place on or before August 3, 2009, subject to the
satisfaction of customary closing conditions.

Cortex plans to use the net proceeds from the financing to meet the company's
working capital needs and for general corporate purposes. Cortex is currently
enrolling patients in a pilot Phase II clinical trial of CX1739 for the
potential treatment of sleep apnea. Additionally, it has multiple discussions
underway related to strategic relationships with other companies and it believes
that this funding will support its continued business activities in these areas.

[Erbse1]

Cortex Receives NYSE Amex Staff Determination
Press Release
Source: Cortex Pharmaceuticals, Inc.
On Friday August 21, 2009, 8:30 am EDT
Companies:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Amex (COR)) reported that it has received a delisting notification from the NYSE Amex LLC indicating that it has not accepted the Company’s plan to regain compliance with the Exchange’s continued listing standards, as submitted by the Company in June. Specifically, the notice indicated that the Company is not in compliance with Sections 1003(a)(i), 1003(a)(ii) and 1003(a)(iii) of the NYSE Amex Company Guide regarding stockholders’ equity and losses from continuing operations and/or net losses; and Section 1003(a)(iv) of the Company Guide in that its financial condition has become so impaired that it appears questionable, in the opinion of the Exchange, as to whether the company will be able to continue operations and/or meet its obligations as they mature.

The Company plans to appeal this determination and request a hearing before a listing qualifications panel. Such a hearing is anticipated to be scheduled within 45 days of the hearing request. During the appeals process, the Company expects that its common stock will remain listed on the Exchange.

There can be no assurance that the listing qualifications panel will grant the Company’s request for continued listing of its common stock. In the event that the Company’s common stock is delisted from the Exchange, the Company believes that its common stock will be eligible to trade or be quoted on alternative markets, such as the Over the Counter Bulletin Board or the Pink OTC Markets, Inc. (commonly referred to as the “pink sheets”).

Currently patient enrollment is underway in Cortex’s clinical trial of CX1739 in patients with moderate to severe sleep apnea. This pilot study in patients was undertaken based on research by Dr. John Greer at the University of Alberta. Chronic sleep apnea can lead to serious long-term consequences such as cardiovascular disease, stroke and diabetes. Also, recent studies with Cortex’s High Impact AMPAKINE molecules in animal studies demonstrated that CX1837 produced marked increases in the rate and extent of recovery of motor function following brain damage induced by a stroke in mice. In another study, CX929 exhibited a mood stabilizing effect in mice, suggesting the potential for treating bipolar disorder. The Company currently has two compounds in clinical development: CX1739, which is targeted for sleep apnea and ADHD, and intravenous CX717 for treatment of drug-induced respiratory depression.

[Ackergaul]

bin mal gespannt, auf die nächsten zwei, drei Wochen...
Laut dem Rodman & Renshaw CC, sollten die Sleep Apnea Daten zu CX1739 noch diese Woche erscheinen. Vermutlich wird dies mal wieder nach hinten rutschen.
COR hatte Probleme mit der Studie, auf Grund screening Fehler und auch auf Grund fehelnder Akzeptanz der Patienten 3 Nächte durchzuhalten (???). Klingt nach den üblichen COR Problemen. Mal schauen wie die Ergebnisse aussehen werden.
Wenn Cash in der Kasse ist wird CX1739 auch bei ADHD getestet. Ebenso CX717 (wenn Cash da ist), bei respiratoy depression dann in i.v. Form.

COR ist am Schwimmen, geht aber (noch) nicht unter. Ob ein partner gefunden werden kann?

[Erbse1]

Antwort auf Beitrag Nr.: 38.076.117 von Ackergaul am 29.09.09 13:10:56

Hallo Ackergaul,
du bist wohl einer der die Cortex noch hoch hält.

Ich gehe nicht mehr in Cortex rein. Bei Atemdepression dürfte Cortex irgendwann mit einem Wirkstoff erfolgreich sein.
Große Bedenken habe ich bei den Daueranwendungen ADHD und Schlafapnöe. Eine der gravierende Nebenwirkung von den Ampakinen sind halt Schlafstörungen, so daß hier zumindest große Schwierigkeiten bei Daueranwendungen sehe.
Mir ist das Risiko einfach zu hoch, sollten auch die 3 Tage Tests bei Schlafapnöe erfolgreich verlaufen.
Außerdem hat Cortex so gut wie kein Geld mehr und es stehen jede Menge Kapitalmaßnahmen an. Da wird verwässert ohne Ende.

Der Stop von der FDA hat Cortex das Genick gebrochen. Leider kann ich im Augenblick nichts positiveres sagen. Cortex ist trotzdem immer noch meine Lieblingsaktie, auch wenn sie bisher nicht zum Erfolg beigetragen hat.
Grüße
Erbse

[Ackergaul]

bin bei COR nur mit einem Auge am beobachten dran...
Die Rodman & Renshaw Präsentation habe ich nur mitgenommen, da ich dort auch die von ASM verfolgt hatte.


Grüße

Kapitalmaßnahmen könnten geringer ausfallen, wenn ein (finanzkräftiger) Partner endlich gefunden werden dürfte!

[lisa46]

lebt diese Unternehmung noch?!

[Erbse1]

Antwort auf Beitrag Nr.: 38.247.536 von lisa46 am 25.10.09 02:39:46

Hallo lisa46,
noch lebt Cortex. Doch das Leben hängt an einem seidenen Faden. Geld ist so gut wie gar keins mehr vorhanden. In nächster Zeit stehen wohl die Ergebnisse zu Schlafapnöe an. Wenn nicht bald irgendwas verpartnert oder auslizensiert wird, hat Cortex wohl nicht mehr so lange.
Rege diskutiert wird Cortex auf dem Investorhub Board. Ich bin schon länger nicht mehr in Cortex investiert.

http://investorshub.advfn.com/boards/board.aspx?board_id=325…

Grüße
Erbse

[Erbse1]

Das war auch keine Überraschung mehr, mit dieser Meldung. Verfolge Cortex nur noch aus Sympathie. Sie ist mir sehr ans Herz geachsen. Ich wünsche ihnen jetzt mal gute Ergebnisse bei der Schlafapnöe Studie und einen Guten Partner.
Grüße
Erbse

Cortex Receives Delisting Notification from NYSE Amex
Companies:Cortex Pharmaceuticals Inc.
IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (NYSE Amex: COR) announced that it has received notification from the NYSE Amex LLC indicating that, due to the Company’s non-compliance with certain continued listing standards as previously reported, the Exchange intends to delist the Company’s common stock from the NYSE Amex effective as of the close of business on Friday, December 11, 2009. Cortex appealed an earlier delisting determination by the NYSE Amex, but was unable to regain compliance within the allotted timeframe provided by the Exchange.

Upon the Company’s delisting of its common stock from the NYSE Amex, the Company believes that its securities will be eligible for quotation on the OTC Bulletin Board. Cortex intends to continue to comply with its Securities and Exchange Commission filing obligations.

Cortex Pharmaceuticals, Inc.

Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for treating psychiatric disorders, neurological diseases and brain-mediated breathing disorders. Cortex is pioneering a class of proprietary pharmaceuticals called AMPAKINE® compounds, which act to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer’s disease. Many psychiatric diseases, including schizophrenia, occur as a result of imbalances in the brain’s neurotransmitter system. These imbalances may be improved by using the AMPAKINE technology. For additional information regarding Cortex, please visit the Company’s website at http://www.cortexpharm.com

[KillingJoke]

Antwort auf Beitrag Nr.: 38.536.001 von Erbse1 am 09.12.09 14:44:11

Seit gestern ein neues Kürzel:
CORX.OB

Kurz nach Eröffnung zu 0,10 USD gab es einen sagen wir "Schwächeanfall" zwischen 09:40 und 09:44 Uhr, in dem Aktien unter 10 Cent (low bei 7 Cent!) gehandelt wurden. Den Rest des Tages fristete Cortex ein Niveau bei 12 Cent.
Vor 3 bis 6 Monates stand Cortex noch relativ stabil zwischen 0,20 und 0,30 USD. Seit dem verfolge ich die Aktie so am Rande.

Trauriger Kursverlauf und intakter Abwärtstrend.

[Erbse1]

Antwort auf Beitrag Nr.: 38.569.201 von KillingJoke am 15.12.09 13:11:42

Hallo Killing Joke,
es sollten bald die Ergebnisse zu Schlafapnöe kommen. Ich kann es nicht begründen, doch irgendwie hab ich kein gutes Gefühl. Es dürfte sowas wie die letzte Chance für Cortex werden. Doch auch hier befürchte ich, daß so schnell kein Partner gefunden wird.
Ich habe mich vom CEO Stoll in die Irre führen lassen, da er einen baldigen Abschluß bei Atemdepression ankündigte. Mein Vertrauen in diese Aussage war sehr teuer für mich und alle die daran geglaubt haben. Doch ich sollte nicht meckern.

Grüße und schönen Tag
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.574.611 von Erbse1 am 16.12.09 06:28:29

Cortex ist auf dem (unterirdischen) Niveau vielleicht doch noch für eine Überraschung gut?

[Erbse1]

Antwort auf Beitrag Nr.: 38.586.610 von KillingJoke am 17.12.09 13:33:21

Hallo Killing Joke,
könnte schon sein. Doch auch mit sehr viel Risiko. Kaum noch Geld. Haben Schwierigkeit mit der Studie. (Sollte schon fertig sein). Handel nur unter Schwierigkeiten möglich. Zumindestens bei etwas größeren Stückzahlen.

Bei Erfolg der Schlafapnöe Studie und der Partnerschaft, die schon lange angekündigt wurde sicher ein großes Potential. Sollte die Finanzierung gesichert sein, könnte man wieder reingehen. Eine Alternative zu den jetzigen ADHD Medikamenten mit weniger Nebenwirkungen wäre nicht schlecht. Ich warte aber erst mal ab.

Grüße
Erbse

[KillingJoke]

Antwort auf Beitrag Nr.: 38.592.414 von Erbse1 am 18.12.09 04:58:58

Bin seit Montag 14.12. long, weil nach dem Amex-Delisting mein Abstauberlimit am OTC Bulletin Board gegriffen hat.

Könnte jetzt die kleine Position mit einem schnellen Gewinn verkaufen oder den begonnenen Trade mental in ein Kurzzeit-Invest wandeln - und auf die unwahrscheinlich(en) guten News warten.

Bin noch unentschieden.

[Erbse1]

Antwort auf Beitrag Nr.: 38.595.564 von KillingJoke am 18.12.09 13:10:16

Hallo KillingJoke,
wir haben bald Weihnachten. Mögen deine Wünsche in Erfüllung gehen.
Wünsche dir viel Glück.
Grüße
Erbse

[Erbse1]

IRVINE, Calif.--(BUSINESS WIRE)--Cortex Pharmaceuticals, Inc. (OTCBB (CORX)) announced that it has completed a private placement of $1.5 million in principal amount of a convertible promissory note with a single institutional investor, Samyang Optics Co., Ltd. (“Samyang”) of Korea.
The note accrues interest at the rate of 6% per annum and may be converted into Cortex’s common stock at Samyang’s option at any time after April 15, 2010 and if not converted may be subject to repayment at its maturity date on January 15, 2011. This investment is part of a fund created by Samyang which is targeted at strategic investments in several US biotech companies over the next twelve months.

The number of common shares issuable upon conversion of the note shall be based upon the greater of market price per share at closing or a 15% discount to the market price of the common stock at the conversion date. Upon conversion of the note, Cortex is obligated to issue to Samyang two-year warrants to purchase additional shares of the Company’s common stock representing 40% of the number of common shares issued upon conversion of the note. The exercise price for such warrants would represent a 40% premium to the price per share at which the common stock is issued upon conversion of the note.

Cortex plans to use the net proceeds from the private placement for general corporate purposes to support ongoing development of its AMPAKINE® compound platform.

“We appreciate Samyang’s timely financial support and the decision to invest in Cortex by their Chief Executive Officer, Mr. Sang Yoon Rhee,” stated Mark A. Varney, Cortex President and CEO.

The securities were offered to an accredited investor in reliance on an exemption from the registration requirements of the Securities Act of 1933, as amended (the “Securities Act”). The securities have not been registered under the Securities Act or any state securities laws and the securities may not be offered or sold absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws. This press release does not and will not constitute an offer to sell or the solicitation of an offer to buy any securities and is being issued under Rule 135c under the Securities Act.

Cortex Pharmaceuticals, Inc.

Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for treating psychiatric disorders, neurological diseases and brain-mediated breathing disorders. Cortex is pioneering a class of proprietary pharmaceuticals called AMPAKINE® compounds, which act to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer’s disease. Many psychiatric diseases, including schizophrenia, occur as a result of imbalances in the brain’s neurotransmitter system. These imbalances may be improved by using the AMPAKINE technology. For additional information regarding Cortex, please visit the Company’s website at http://www.cortexpharm.com

Samyang Optics Co., Ltd.

Samyang, located in Masan, Korea, is a developer of optical lenses and a range of applications for closed circuit television systems used extensively in highly important security settings such as casinos, banks, as well as government and commercial building structures. Samyang’s securities are publicly traded on the Korean stock exchange.

[KillingJoke]

Antwort auf Beitrag Nr.: 38.750.812 von Erbse1 am 16.01.10 15:10:15

Der neue Geldgeber aus Seoul ist eine für Investments in Biotechfirmen recht untypische Firma.
http://www.syopt.co.kr/

[truthwatch]

Scope

- Provides key company information for business intelligence needs
- Gives information on the company’s major recent financial deals including mergers & acquisitions, asset transactions, PE/VC deals, equity offerings, debt offerings, partnerships and licensing agreements.
- Data is supplemented with details on the company’s history, key executives, business description, locations and subsidiaries as well as a list of products and services and the latest available company statement.

Reasons to buy

- A quick "one-stop-shop" to understand the company.
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- Understand and respond to your competitors’ business structure, strategy and prospects through.
- Understanding the key deals which have shaped the company.

http://www.pr-inside.com/cortex-pharmaceuticals-inc-pharmace…

[Erbse1]

Erst mal posten, dann lesen. Es geht weiter für Cortex, da dürfte es heute einen Freudensprung geben.
Glückwunsch, wenn noch einer drin ist.
Grüße
Erbse

Cortex Sells Selected AMPAKINE Compounds and Rights to Respiratory Depression Indication to Biovail

Purchase Price of $10 Million and up to $15 Million Clinical Development Milestones

IRVINE, Calif., Mar 26, 2010 (BUSINESS WIRE) -- Cortex Pharmaceuticals, Inc. /quotes/comstock/11k!corx (CORX 0.17, 0.00, 0.00%) announced that it has entered into an agreement with Biovail Laboratories International SRL ("Biovail") in which Biovail acquired certain AMPAKINE compounds and the rights to the patent filing for respiratory depression and vaso-occlusive crises associated with sickle cell disease. The transaction with Biovail includes a purchase price of $10,000,000 and additional payments of up to $15,000,000 based upon defined clinical development milestones.

The agreement includes the transfer of rights to Biovail for certain AMPAKINE compounds, including the Phase II compound CX717, the preclinical compounds CX1763 and CX1942, and the injectable dosage form of CX1739 and the indication of respiratory depression. Specifically, the agreement allows Cortex to retain its rights to non-injectable dosage forms of CX1739 for all uses outside of respiratory depression. Biovail will allow Cortex to continue to pursue the treatment of sleep apnea for which a clinical trial is currently underway.

The transaction follows the earlier results from two of the Company's Phase IIa studies in which administration of CX717 prevented the onset of respiratory depression induced by an opioid, while preserving the opioid's pain-relieving effects. "We are pleased that Biovail has recognized the potential of our AMPAKINE technology," commented Mark A. Varney, Ph.D., President and CEO of Cortex. "We believe the technology may ultimately be useful in reversing or preventing respiratory depression in patients undergoing surgical procedures."

Cortex retains all rights to the non-acquired AMPAKINE compounds for treatment of neurodegenerative diseases and psychiatric diseases which historically have been part of its portfolio. "As a result of this transaction, we will be in the position to continue the oral Phase IIa sleep apnea trial with CX1739 and to initiate a Phase II clinical trial for the treatment of ADHD very soon," commented Mark A Varney. "Additionally, we are pushing ahead to develop the CX2007 and CX2076 series of compounds and move one of those analogs into the clinic as soon as possible."

[Erbse1]

Antwort auf Beitrag Nr.: 39.221.995 von Erbse1 am 26.03.10 12:21:30

Kommentar NeuroInvestor

There are no royalties, because this is a sale of those compounds, albeit with a license for these respiratory indications only. Cortex went for more money upfront, rather than waiting for royalties from sales in 2016 and beyond. There are very modest milestones along the way, but the story is the upfront payment, and what Cortex did not have to give up: CX-1739, sleep apnea, and the high impacts. Back when we discussed the RD indication, and as time went on, the conjecture was on upfront payments in the $5 million range. With their cash dwindling again, and along with it, Cortex's leverage, I was becoming worried that if there was a RD deal, they'd receive even less, $3-4 million, and would have to throw in SA for nothing.

So if you believe, as I do, that CX-1739 in ADHD (and perhaps in sz, depending on what Merck ends up doing with that license, which at the moment seems to be in limbo), and the high impacts, are the most important Cortex components, this deal gives them enough cash--when one also figures on some warrant conversions--to get that the project with the most nearterm leverage accomplished, an ADHD trial.

Count me as someone who is extremely happy with this Biovail transaction.

NeuroInvestment

[KillingJoke]

Antwort auf Beitrag Nr.: 39.223.036 von Erbse1 am 26.03.10 14:14:36

Hallo Erbse,

bin noch drin. Weiß aber nicht, ob ich der lebende Beweis bleiben werde, dass jemand mit Cortex mal 100% Gewinn gemacht hat - ist schliesslich nicht realisiert.

Die 9 Mio tun Cortex erstmal gut. Der Kommentar vom NeuroInvestor ist auch interessant, weil er besagt, dass die Komponente auch weniger Geld hätte einbringen können.

[Erbse1]

Antwort auf Beitrag Nr.: 39.233.631 von KillingJoke am 29.03.10 07:36:27

Hallo Killing Joke,
das ist leider alles sehr knapp gestrickt mit dem Geld.
Das reicht jetzt erst mal einige Monate. Man kann jetzt in Ruhe die Ergebnisse der Schlafapnöe Studie abwarten(die sollte schon Ende letzten Jahres fertig sein) Doch wer soll dann die neuen ADHD Studien finanzieren. Es sind weitere Verpartnerungen notwendig.

Außerdem hab ich meine Bedenken wegen der Nebenwirkungen der Ampakine bei den Daueranwendungen bei ADHD und Schlafapnöe.

Eine Einzelanwendung bei Atemdepression ist sicher denkbar, doch diesen Schatz hat Cortex jetzt ohne Umsatzbeteiligungen aus der Hand gegeben.
Ich geh nicht mehr rein, auch wenn hier kurzfristig noch einige Gewinne möglich sind.
Grüße
Erbse

[truthwatch]

Findet Cortex einen großen Investor um die 'clinical trials' noch in diesem Sommer zu beenden, wäre hier noch ein gutes Geschäft möglich. Man verspricht sich sehr viel von CX1739, dessen Eigenschaften auf eine rasche Markteinführung hindeuten. Es gibt wohl mehrere Interessenten, die sich unter strengen Auflagen beteiligen würden. Eine Entscheidung dazu wird wohl erst nach Beendigung der klinischen Studien zu CX1739 getroffen.

Dennoch lohnt sich momentan ein Einstieg kaum, da der letzte Kursanstieg kaum reale Substanz aufweist. Kurzfristig sind weitere Verluste zu erwarten. Auf Jahressicht gesehen, kann es jedoch zu enormen Kursgewinnen kommen. (Bei erfolgreichen Studien zu CX1739 sind Kurse von bis zu 1,50 EUR realistisch -> 800 bis 900%)