Cortex Pharmaceuticals 3 ( Seite 26)

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.”

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.

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

Antwort auf Beitrag Nr.: 33.426.569 von Erbse1 am 20.02.08 18:11:51Hier 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

Antwort auf Beitrag Nr.: 33.427.203 von Erbse1 am 20.02.08 18:50:21Hier 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…

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

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…

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