Zunächst möchte ich einmal die Pipeline von Cortex Pharmaceuticals vorstellen. Am Mittwoch stehen sehr wichtige und auch wohl kursbewegende Nachrichten in der Anwendung Atemdepression an.
Doch erstmal die Pipeline von Cortex Pharmaceuticals
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Cortex Pharmaceuticals Amex:COR
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Zunächst möchte ich einmal die Pipeline von Cortex Pharmaceuticals vorstellen. Am Mittwoch stehen sehr wichtige und auch wohl kursbewegende Nachrichten in der Anwendung Atemdepression an.
Doch erstmal die Pipeline von Cortex Pharmaceuticals
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Im folgendem Schaubild ist die weitere Planung von Cortex abgebildet.
Cortex Pharmaceuticals, Inc. is a neuroscience company focused on the discovery and clinical development of AMPAKINE® molecules, a platform that represents a new approach to treating psychiatric and neurological disorders. AMPAKINE compounds are small drug-like molecules that positively modulate the AMPA–type glutamate receptor complex, amplifying the effect of glutamate at the synapse, leading to excitation of brain circuits.
AMPAKINE compounds fall into two categories: “low” and “high” impact compounds, defined by the site to which they bind on the AMPA receptor complex. Cortex’s lead low impact AMPAKINE, CX717, has demonstrated “Proof-of-Concept” in adult ADHD patients in a small pilot Phase IIa study. CX717 is currently being tested in two pilot Phase II studies. The first study is being performed in mild to moderate Alzheimer’s disease patients and will investigate changes in brain metabolism by PET imaging. The objective is to confirm acute PET Scan findings observed in an earlier study performed in non-human primates with memory and cognition impairment that were reversed by acute CX717 dosing. The second research program is evaluating the acute use of CX717 and in volunteers whose breathing has been depressed with the opiate, alfentanil.
Several follow-on molecules to CX717 have completed or are undergoing toxicology testing. The Company anticipates having up to three AMPAKINE compounds in clinical studies by late 2008.
Cortex’s business plan focuses on out-licensing internally developed AMPAKINE compounds for the very large CNS diseases such as ADHD, Alzheimer’s and Parkinson’s disease, while retaining the smaller indications and orphan diseases for internal development. The Company has already out-licensed two AMPAKINE compounds (Org24448 and Org26576) for the indications of schizophrenia and depression to Organon, which was acquired by Schering Plough in November 2007. Cortex remains eligible for milestone payments based upon further clinical development of those compounds, as well as for royalties on any ultimate sales.
Cortex’s patent portfolio includes submissions for over 250 Composition of Matter and Broad Use patents, with approximately 160 patents issued to date
AMPAKINE compounds fall into two categories: “low” and “high” impact compounds, defined by the site to which they bind on the AMPA receptor complex. Cortex’s lead low impact AMPAKINE, CX717, has demonstrated “Proof-of-Concept” in adult ADHD patients in a small pilot Phase IIa study. CX717 is currently being tested in two pilot Phase II studies. The first study is being performed in mild to moderate Alzheimer’s disease patients and will investigate changes in brain metabolism by PET imaging. The objective is to confirm acute PET Scan findings observed in an earlier study performed in non-human primates with memory and cognition impairment that were reversed by acute CX717 dosing. The second research program is evaluating the acute use of CX717 and in volunteers whose breathing has been depressed with the opiate, alfentanil.
Several follow-on molecules to CX717 have completed or are undergoing toxicology testing. The Company anticipates having up to three AMPAKINE compounds in clinical studies by late 2008.
Cortex’s business plan focuses on out-licensing internally developed AMPAKINE compounds for the very large CNS diseases such as ADHD, Alzheimer’s and Parkinson’s disease, while retaining the smaller indications and orphan diseases for internal development. The Company has already out-licensed two AMPAKINE compounds (Org24448 and Org26576) for the indications of schizophrenia and depression to Organon, which was acquired by Schering Plough in November 2007. Cortex remains eligible for milestone payments based upon further clinical development of those compounds, as well as for royalties on any ultimate sales.
Cortex’s patent portfolio includes submissions for over 250 Composition of Matter and Broad Use patents, with approximately 160 patents issued to date
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.
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.
Nach dem Stop durch die FDA von CX 717 bei der Anwendung ADHD rauschte die Aktie von COR in den Keller und hat sich immer noch nicht erholt. Außerplanmäßig tat sich ein neues Anwendungsgebiet (Atemdepression) auf. Die Ampakine wurden erfolgreich im Tierversuch getestet. Nun stehen am Mittwoch die ersten Ergebnisse einer Testphase 2a bei Menschen an.
Folgend die Meldung zu dieser Präsentation:
Cortex to Provide Top Line Data for CX717 Clinical Trial for the Prevention of Opiate-Induced Respiratory Depression in Humans
— Presentation to be given at the Bank of Montreal’s Focus on Healthcare Conference on August 5-6, 2008 —
Irvine, CA (July 31, 2008) — Cortex Pharmaceuticals, Inc. (AMEX: COR, 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.
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:
www.bmocm.com/conferences/2008healthcare/default.aspx.
Sollten die Ergebnisse gut sein so eröffnen sich für Cortex ungeahnte Möglichkeiten. Negative Ergebnisse dürften wohl das Ende von Cortex bedeuten und sie würden das Schicksal vieler Biotechfirmen teilen und in der Bedeutungslosigkeit verschwinden.
Kurz gesagt: Die Gewinnmöglichkeiten sind ganz enorm, doch es droht auch der Totalverlust.
Zur weiteren Recherche noch die URL von COR:
www.cortexpharm.com/corporate/index.html
Weitere Postings gibts dann nach den erhofften positiven Nachrichten am Mittwoch
Grüße
Gurke
Folgend die Meldung zu dieser Präsentation:
Cortex to Provide Top Line Data for CX717 Clinical Trial for the Prevention of Opiate-Induced Respiratory Depression in Humans
— Presentation to be given at the Bank of Montreal’s Focus on Healthcare Conference on August 5-6, 2008 —
Irvine, CA (July 31, 2008) — Cortex Pharmaceuticals, Inc. (AMEX: COR, 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.
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:
www.bmocm.com/conferences/2008healthcare/default.aspx.
Sollten die Ergebnisse gut sein so eröffnen sich für Cortex ungeahnte Möglichkeiten. Negative Ergebnisse dürften wohl das Ende von Cortex bedeuten und sie würden das Schicksal vieler Biotechfirmen teilen und in der Bedeutungslosigkeit verschwinden.
Kurz gesagt: Die Gewinnmöglichkeiten sind ganz enorm, doch es droht auch der Totalverlust.
Zur weiteren Recherche noch die URL von COR:
www.cortexpharm.com/corporate/index.html
Weitere Postings gibts dann nach den erhofften positiven Nachrichten am Mittwoch
Grüße
Gurke
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. Es ist jetzt leider zu spät alle Einzelheiten über Cortex zu und das Themengebiet Atemdepression zu posten.
Doch bietet sich zur schnellen Recherche folgender link an:
www.wallstreet-online.de/diskussion/...icals-3#neuster_beitrag
Leider kann ich nicht mehr machen, nochmals darauf hinzuweisen. Die Ergebnisse werde ich selbstverständlich hier posten.
Grüße
Gurke
Doch bietet sich zur schnellen Recherche folgender link an:
www.wallstreet-online.de/diskussion/...icals-3#neuster_beitrag
Leider kann ich nicht mehr machen, nochmals darauf hinzuweisen. Die Ergebnisse werde ich selbstverständlich hier posten.
Grüße
Gurke
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.
Der erste Kommentar des Börsenbriefes NeuroInvestor läßt nicht lange auf sich warten. Ehrlich gesagt habe ich mir einen höheren Sprung ausgerechnet, doch jetzt stehen noch die RD1 Studie (bei 1500 mg) an und die unten erwähnte Partnerschaft. Ist halt noch etwas Geduld gefragt.
Grüße
Gurke
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
Grüße
Gurke
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
Einschätzung von Rodman&Renshaw. Sie warten doch 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.
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.
Zur besseren Übersicht habe ich mal das Schaubild der aktuellen Pipeline von COR neu überarbeitet.
(Verkleinert auf 92%) 
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
Gurke
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.
Grüße
Gurke
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.
Aktueller Kommentar des NeuroInvestor zur Situation von Cortex. In den nächsten Tagen erwarte ich die Ergebnisse der zweiten Atemdepressionsstudie.
Grüße
Gurke
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.
Grüße
Gurke
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.
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.
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.
Das schaut im Augenblick alles sehr gut aus für Cortex. Folgend der Kommentar des Börsenbriefes NeuroInvestor zu den heutigen Ergebnissen.
Liebe Grüße
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.
Liebe Grüße
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.
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
Gurke
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
Gurke
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.
(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.
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. CX 717 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
Gurke
1. CX 717 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
Gurke
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
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.
Tuesday January 27, 2009, 8:31 am EST
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.
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