COR Yahoo Message Board: Mon 4/3/2006
CX717 IS Snake oil
by: frogss12
Long-Term Sentiment: Strong Sell 04/03/06 07:22 am
Msg: 27225 of 27626
Don,t know about scientology but I do know about ADHD and I grew out of it in my early twenties,and have more than two formal qualifications.COR is currently being questioned by the feds as you insiders clearly know.What this stock does now is not my concern as long as the directors do as there told everyone will be fine.
Valium in a different wrapper.Tom Cruise has more money than you and access to more professional resources than most of you could dream of.Peasants trying to knock a man off the top of the hill.
Re: MAJOR OVERREACTION ...LOOK FOR RECO
by: daviddal66
Long-Term Sentiment: Strong Buy 04/03/06 09:49 am
Msg: 27265 of 27629
3 choices.
1. Something was hidden, toxic in animals and not disclosed--jail time and extremely unlikely.
2. Mild side effect--fda wants more testing.
3. They screwed up and didn't do enough animal testing, complete pathology ect . . .
I cannot figure it out. No problems with ORG24448. Weird, but thats biotech.
Disaster - maybe / maybe not
by: gfp927z 04/03/06 09:55 am
Msg: 27272 of 27629
Well, Murphy's Law strikes again. This is all part of the risk one takes in this sector, particularly with a brand new drug platform. The stock is obviously going to get creamed, but it remains to be seen whether there is actually a really dire problem or not. The FDA concerns are apparently with some animal data and not with any problems in the human trials.
Of course the most obvious concern one has with upregulating glutamatergic pathways is the risk of excitotoxicity (seizures), though this is much more a problem with the high impact approach. Being a low impact, CX-717 has had a very clean record as far as excitotoxicity is concerned, as far as we know. Perhaps they saw something in the longer term animal studies, or it could be something totally unrelated to excitotoxicity, perhaps related to the spectrin/calpain phenomenon. At this point it'as anyone's guess. We'll hear more from Cortex on it in the weeks to come.
Condolences to all longs, though we shouldn't pass final judgement just yet until we hear from Dr. Stoll and see the animal data that the FDA has concerns about.
One silver lining . . .
by: daviddal66
Long-Term Sentiment: Strong Buy 04/03/06 10:04 am
Msg: 27277 of 27630
Let's say that ampakine CX717 is on hold--the BOD might authorize a buyout on the cheap. It depends on the side effect in question. I'm just guessing. I don't get it, but sounds like the frog did. The buyout on the cheap would only apply if the side effect was a. mild and b. required another three to six month's of animal testing. The BOD might just take an offer--say at 5 and be done with it. Just my 2 cents. Still Dr. Stoll announced going to phase IIb studies ASAP--with plans on the board--the tox has been sent to the FDA--the FDA just reviews what Cortex did(and knows).
Re: One silver lining . . .
by: gfp927z 04/03/06 10:16 am
Msg: 27284 of 27630
Daviddal, This development with the FDA could turn out to be exceedingly dire, or the mother of all buying opportunities. Let's hope the FDA doesn't start digging through Org-24448's animal data also. I'll have to have a "neutral" opinion on the stock until we find out exactly what's going on.
Hopefully Neuro will chime in soon. I have to leave for work, but will be back tonight.
Gary Lynch
by: encinitan1999 04/03/06 10:24 am
Msg: 27291 of 27631
This is pure speculation, but I have to wonder if someone in Gary Lynch's lab (but not Cortex) was aware of an issue with animal data some time ago. Maybe this individual had a major greivance with Lynch. Maybe this individual tipped of the FDA. Is Lynch aware of a problem(s) that he was unwilling to disclose?
I don't have any direct connection with the Lynch lab, but I noticed that the lab web site has been shut down for the last two months.
I wonder if Lynch is in the process of resigning his position at UC Irvine based on the following observations: Another spinoff from Lynch's lab, Thuris (a virtual company), was aquired recently by a San Diego company that is a penny stock (Protein Polymer). A just published study in PNAS from Lynch and members of his lab lists his significant other (Christine Gall) as the contact person. Is Lynch aware of a problem(s) that he would not disclose?
Again, of course, this is all pure speculation.
I bought Cortex at the low 2s and am still holding. I am nauseous, which of course impairs thinking somewhat. Time for a Xanax.
Re: Disaster - maybe / maybe not
by: Neuroinv 04/03/06 10:27 am
Msg: 27295 of 27631
It's unlikely to have anything to do with preclinical seizure activity--because that's apparent when it happens. Cortex would have had to notify the FDA immediately, and the sleep dep trial would have been stopped.
For it to raise a question later: Perhaps its some histological change seen on a slide from one animal--but I must emphasize, I am just guessing here. It's the kind of thing that might come up in retrospect, and it might not be known what the cause is--but until they know if its a pattern, human trials are suspended--though in this case, sleep dep has already been completed.
It doesnt happen often, but I can recall a couple of instances. Pfizer's Lyrica was in Phase II when it was put on hold after they found a tumor in a preclinical trial animal. Pfizer eventually showed that there was no risk in humans, and Lyrica is approved in the US and EU. Back in 1997, the first NBIX/Janssen CRF-1 drug was in Ph II--and a dog showed liver enzyme changes. The drug was eventually dropped, although other CRF-1 drugs were developed and partnered with GSK, now in PhII.
There are other examples but none that come to mind 7:15am local time. Bottom line--we won't know how important this is at least until Cortex has received written detail from FDA and disclosed it--and maybe not then.
NeuroInvestment
Re: I hate to say this . . .
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 10:34 am
Msg: 27299 of 27632
Not at all. My point, and I obviously could be dead wrong, is that if Cortex completed their three month animal tox package to the FDA for review and had no concerns expressed public--declared that everything is swell on the partnering talks, this tells me it was probably mild in terms of side effect in animals. No insider sales. But a simple error of what was thought to be mild--and not serious side effect in animal toxicology. Again, the FDA decision may have blindsided Cortex, but the company already knew what the results were of their animal studies--unless I'm completely missing something.
Re: Call Stoll and request a conf. call
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:09 am
Msg: 27321 of 27633
sadly, wmg2, I agree. I believe Stoll made an honest mistake of believing what he thought was a minor side effect in animals(with an FDA dissent), and i believe he's making another honest mistake in not discussing the animal data in detail. Again, Cortex knows in detail--chapter and verse--the safety results in animals; they ran the studies and did the histo--not the FDA.
Re: Gary Lynch
by: jcpsy1
Long-Term Sentiment: Hold 04/03/06 11:14 am
Msg: 27327 of 27634
Didn't our mysterious urko have a critical comment about animal heads on the wall in Lynches lab, ax to grind? Plus bragging about following Cotman and possibly others around. His lurk-mode means something more than lurk perhaps. We have a da Vinci code-type plot in the making. Sad day, fellow longs.
I sent Dr. Stoll an email . . .
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:21 am
Msg: 27333 of 27634
urging him to have a conference call today to discuss their summary of the animal data--three month toxicology with CX717. If Cortex felt the side effect they saw was not material, find; everyone makes mistakes. I accept this. But the actions of the FDA clearly make the animal results material. To wait for 10 business days or whatever is unfair in the extreme. It would seem to me that a full--public vetting about the animal studies is in order. These are the two species. These are the histology slides. These were the potential problems. Maybe I'm missing something, but the letter and negotiations witht the FDA are vital--and Stoll cannot disclose these until they occur--ie the plan for advancement. But, with today's events, I feel strongly that the company has an obligation to its shareholders to have a 20-30 minute conference call--to lay the data on the table. I've urged him to hold such a conference call to disclose the animal data. I believe he's been a decent CEO, fair and honest. Mistakes happen, but mistakes can be made right.
Re: from 10-k
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:28 am
Msg: 27337 of 27636
Thanks, Jenkins, I think you nailed it. If this statement is correct:
"Each study examined the effects of very high (toxicological) daily doses of CX717 for ninety consecutive days. Each study included extra animals to assess whether any observed toxicological effects were reversible once dosing was stopped."
It could be--and probaly is--what is known as a 'failure of anticipation of the FDA's tough stance at very high dosages--maybe they wanted more animals included that were done.
Not enough info. FDA risk adverse
by: deathspiralwatcher (99/watching) 04/03/06 11:35 am
Msg: 27344 of 27636
Trying to game this situation right now is almost impossible. There is not enough information to do more than gamble or guess. What we know:
1. FDA issued a clinical trial hold based on questions about animal data.
2. The issues with the animal data are unknown to the public.
3. Cortex must have at least a rough idea of what the questions are. Liver enzymes, tummy aches, insommnia, etc. For reasons we can only guess they have chosen not to divulge this info at this time.
4. The FDA is risk adverse these days. The tysarbi MS fiasco really put them on edge. Probably didn't help about the trial in Great Britain where the human subjects all got very sick almost immediately.
Those are the facts as known today. Whether this clinical trial hold is a bump on the road or terminal or in between is anyone's guess. Myself going to wait for more visibility. Luck to all, IMHO
Re: Call Stoll and request a conf. call
by: Neuroinv 04/03/06 11:43 am
Msg: 27353 of 27637
Blade: If there were something clearcut from the 3month tox studies, you would be absolutely correct--everyone would have seen it. BP suitors get to look at everything. And Varney would not have come to a company if he knew a clinical hold was likely to happen.
It could well be an issue of interpretation and extrapolation: Note that the 10K mentioned the issue of showing that high-dose anomalies being correctible when dosing is stopped. Let's say two dogs given 5X the maximum human dose per kg (I am making this up, I have zero information as to what the actual content of the issue is) showed liver enzyme changes after three months. Taking them off the drug led to the enzyme levels going back towards normal after a month. Cortex and its BP suitors could look at the curve and say--it looks like its going back to normal. The FDA could say--but it's not back there yet, we want to know if it would get there, and how long it would take.
My point with this contrived illustration is that it is not a binary 'is there a toxic effect or isnt't there' situation.
What generally happens in these instances is that the FDA makes a quick call alerting a company that a letter is on the way, and that the hold is in effect. I don't believe those calls include much info, they certainly don't state what the FDA wants to see as a correction/clarification. The really big pharmas have people on staff whose sole job is as FDA liaison--in this kind of situation, they'd be calling and schmoozing to get all the detail they can ASAP. Small companies like Cortex can't afford that, so they have consultants that they hire to do the same. But until they get that information back, they'd be foolish to have a CC.
NeuroInvestment
Spoke to Stoll a little earlier this am
by: wmg2 (M/Palo Alto) 04/03/06 11:45 am
Msg: 27356 of 27638
Suggested a conference call to inform shareholders of what is known to date. He said that the FDA communicated to Cortex’s “Medical Director”. I assume this is Mansbach, not Varney. Stoll has not yet spoken with the FDA, though he, of course, plans to today.
His preference is to first speak with the FDA himself, prior to Cortex making any further public statements and would like to have the letter in hand. He will ask the FDA to expedite the letter so as not to have to wait the 7 to 10 days.
The FDA had to have addressed what the concern was with Cortex when the phone conversation took place. At least we are deserving of knowing what type of toxicity concern the FDA is questioning.
WMG2
Re: Just doubled my position
by: Neuroinv 04/03/06 12:55 pm
Msg: 27422 of 27640
It is a big deal--unless and until we learn otherwise. Which means 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) the aforementioned 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 is sociopathic enough to lie 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.
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.
NeuroInvestment
Re: Neuroinv...
by: Neuroinv 04/03/06 01:08 pm
Msg: 27432 of 27640
That was badly worded by the wire services. The sleep dep trial is already over, DARPA has the data. And the AD trial is hardly enrolling anyone. They were trying to say there was a hold on the sleep dep drug, not the sleep dep trial.
NeuroInvestment
Odd timing, animal, human trials, hold
by: deathspiralwatcher (99/watching) 04/03/06 01:21 pm
Msg: 27435 of 27640
Odd timing on this hold prompted by "animal data."
The usual clinical trial timeline is preclinical (tox, pharmokinetics, animal studies etc.) Followed by human phase 1, phase 11(a+b), phase 111, NDA.
We know that cor has done phase 1 and several phase 11s. Now, the FDA has questions about preclinical. Looking at the timeline, they should have had the preclinical data for a long time, months or years. And it didn't bother them enough to prevent CX717 from being tested in humans. Now, all of the sudden, it bothers them enough to issue a clinical hold.
This is odd looking timing. As to what it means, is anyone's guess. Myself, going to wait for more visibility. IMHO
Re: Odd timing, animal, human trials, ho
by: Neuroinv 04/03/06 01:29 pm
Msg: 27437 of 27640
It would almost certainly be from the three month tox study completed in the last few months--which would also have used some dose-levels far above those envisioned for humans. Whether any anomalies would be applicable to human dosing is another of those issues up for interpretation.
NeuroInvestment
Re: Neuroinv...
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 01:34 pm
Msg: 27442 of 27640
Neuro,
I just got off the phone with Roger Stoll. Nothing really new to report. COR is trying to speed up the reception of the letter from the FDA, using its contacts in Washington, D.C. Stoll feels there is no use in having a CC until he has the letter from the FDA in his hands. After receiving the letter, COR will attempt to get in touch with the person(s) at the FDA responsible for putting the clinical hold on CX717 and try to resolve the issues.
Stoll did make me aware of something that I didn't know: The FDA oftentimes has access to data that even the company does not have. So it could be that something that COR saw, but did not interpret as significant. Or, it can be something that the FDA has seen that the company was not aware of. (I don't have a clue about how the latter case is possible. Perhaps you could shed some light on that for me and for the board.)
Given how much in the dark that COR is about the situation, I'll reconsider my position on asking for an immediate CC. There really isn't much COR can say until the details are revealed in the letter.
Bladerunner
Re: Odd timing, animal, human trials, ho
by: learning2vest (62/M/Georgia)
Long-Term Sentiment: Hold 04/03/06 02:00 pm
Msg: 27459 of 27640
Have absolutely no personal knowledge of how the FDA conducts their approval process, but will share the my hunch after seeing today's news.
The "question";
Why would the FDA wait until now to order a halt based on animal data they have had for several years, and that they used to approve the move into human trials?
Best "answer" so far;
They did not do that. They must have received new data re the animal trials. I'm guessing that most of the animals that are used in pre-clinical trials live out normal lives. They may have endured multiple blood tests, and even biopsy's, during their active participation in multiple experiments, but maybe it's not until they expire that a detailed examination of all tissues can be performed.
Maybe detailed post mortem tissue examinations of some animal participants in the earlier trials, i.e., animals which only recently expired, showed signs of some abnormality which demanded further analysis.
Is the observation explained as being "just something in this animal's genetic makeup", or was it caused by something the animal was exposed to? Which experiment in this animal's "work history" do we attribute this to?
That is pure speculation by somebody totally unqualified to play such games, but it was good enough to justify this Cortex investor's desire to stay long. What's another year or so at this point??
My deepest Sympathies
by: frogss12 04/03/06 02:39 pm
Msg: 27477 of 27641
Horrible thing to happen to anyone.I never suspected a major gap down.However this is this industry Pharmacuticals and Biotech.They simply baffle people with BS,to often.In England last week 6 young lads nearly died from a drug trial.Two are still in a coma with massive swelling to their heads.
Invest with Dr.Frankenstien "not likely"
Looking back and ahead
by: farutti4toop (33/M/San Francisco) 04/03/06 02:46 pm
Msg: 27482 of 27641
On January 3, the first trading day of this year and a mere three months ago, COR opened at $2.28 and closed at $2.35 - still below where we are today.
If it were so obvious to the street that CX717 is "snake oil" or that COR is toast, there would be no price support at $2.50. As others have mentioned, today's trading volume includes a lot of buyers. A 51% drop may be precipitous, but it's hardly a free-fall.
C'mon, gang, this is a biotech company, a company with no earnings, a one-hit wonder, a virtual penny-stock, after all. Extreme volatility is too be expected - and not just to the up-side, for those of you who were expecting 20% increases every day.
And although no one could have predicted it, if you weren't at least considering the possibility that soemthing like this might happen, you were deluding yourself.
I lived through the Centocor debacle in 1992 -its shares went from $60 to $6 in one day, when the FDA halted testing of its flagship sepsis drug Centoxin. Yes, despite reams of promising data, it can and does happen.
However, there's just too little information to make a reasoned judgment on what today's announcement means. Those who are doubling down are as likely to be right as those who are liquidating and running for the hills.
And me? I'm buckling my seatbelt, crossing my fingers, and hanging on for a wild ride.
The FDA and data access
by: Neuroinv 04/03/06 03:07 pm
Msg: 27497 of 27641
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--No, I dont buy the BP drive-the-price-down-to-get-a-better deal paranoid fantasy.
NeuroInvestment
Re: prxl
by: prxl (M/CA) 04/03/06 03:20 pm
Msg: 27504 of 27641
My point all along has been the following:
1) This notification is NOT a "non-event" that some people on the board have tried to emphasize.
2) Putting a trial on hold is a pretty significant regardless of future outcome.
3) Preclinical data is no less important than human data. I'm not saying it's MORE important, but it's no less important.
Today's news IS what it is. Disappointing, unfortunate, and with a future impact that is not fully known.
Why Not Tell Us?
by: jkhaynesx 04/03/06 03:26 pm
Msg: 27509 of 27641
The company must know considerably more than it has disclosed. Maybe there is a good reason why it has not provided a full disclosure of what is known so far, but I can’t imagine what it is. Waiting for another week allows the possibility of persons who may somehow have access to what is now known to trade unfairly, either as buyers or sellers.
I can’t recall any company getting in trouble for releasing material information too early.
JIM
Preclinical
by: Neuroinv 04/03/06 03:53 pm
Msg: 27528 of 27641
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
Re: If and when the FDA gives a green li
by: ggg7ggg
Long-Term Sentiment: Hold 04/03/06 03:59 pm
Msg: 27532 of 27641
I'm not so sure. I would imagine that this little situation has scared the beejeebees out of most, who will be grateful to sell on the way up, should this matter have a relatively quick and benign resolution.
I know that I now have a much greater respect for the risk in this little baby, in which I have way too much of my capital. I guess I am guilty of the "greed" factor, and now trying to control my "fear" impulses.
Re: NeuroInv Serious Questions
by: Neuroinv 04/03/06 04:02 pm
Msg: 27533 of 27641
1) The compound is far enough along that it would take an unredeemable (or at least, one that cannot be proven absent) safety issue to kill CX717 entirely.
2) No one can just 'make a few phone calls.' But, once the details are known, a BP could easily assess the time and risk involved in resolving it. If someone were eager enough, they could offer a risk-sharing agreement: 'we'll give you the deal that's on the table, withholding $15 million of the upfront payment to be paid as a milestone if/when the clinical hold is lifted. (I'm making up a number, again). They'd be gambling, but this is something BP is good at, looking at preclinical data, risk factors, regulatory concerns.
3) Organon trial--you mean if it failed? The Market is attributing little if any value to the Org24448 trial at this point. It would obviously become higher-profile if CX717 languishes for a while. Assuming it demised as well, Cortex would still have its IP, other low-impacts, and its high-impacts. They wouldnt go bankrupt. But we'd be discussing dilution and buyouts for two years. An ugly thought I am going to exile to the far reaches of my preconscious.
NeuroInvestment
Re: Why Not Tell Us?
by: laker9029 (49/M/Holland, OH)
Long-Term Sentiment: Hold 04/03/06 04:10 pm
Msg: 27540 of 27641
<The company must know considerably more than it has disclosed. Maybe there is a good reason why it has not provided a full disclosure of what is known so far,>
It would be foolhardy for Cortex to say anything until they know exacly what the issue is -- that includes restating their interpretation of animal study data. They need to recognize -- as they apparently do -- that the FDA must be handled with care - to attempt to refute or lessen the impact of the FDA "hold" would serve no meaningful purpose and might actually antagonize the FDA. As David mentioned, if Cortex had more cash, perhaps they could have done some serious schmoozing (relationship building) .. but that is not the case, so here we are.
My concern is that resolution will take at least 6 months, during which Cortex will be dead in the water -- unable to move agressively forward on any Ampikine development, while still hving to maintain their staff and without the R&D cash flow from Servier.
Re: Trading should of Halted
by: atshrugg 04/03/06 04:46 pm
Msg: 27556 of 27641
frogss - speaking of pending investigations- You don't think the SEC is going to be looking at todays action, and possibly at you? How is it you had the inside scoop a day, and then an hour before it went public? Why are you pumping hard 10 days ago and bashing hard last week. I'll give you this, you have large nads to be this blatant about manipulation on inside info. I would love to see your trade history over the past two weeks In any event Cortex really needs to take a look at the employees emails and any other internal communications they can get their hands on. The last thing they need now is an SEC problem.
Previous FDA holds
by: mjxspxdr9248 04/03/06 05:49 pm
Msg: 27570 of 27642
I attempted a search to try and get a feel for how long it takes for holds to be released if the company can please the FDA. It certainly varies on a case to case basis, but it seems pretty clear that it takes several months to clear things up. Here is a link to an anxiety medication that hit a similar snag. http://panicdisorder.about.com/b/a/2004_06_28.htm
It took the better half of a year to resolve this matter with the FDA. My search revealed a similar time frame for other drugs. I could not find an example of a drug where an animal study later came back to haunt a company in phase II trials.
While it is clear that trials for this drug are halted, I wonder if Cortex will or is even allowed to release the Sleep Dep Results. The trial is completed and should be fully analyzed.
Releasing these data, if positive, will certainly help to ease shareholders concerns in the short term. Also, if there are no adverse effects, as was the case in all of the previous trials, this would further ease concerns about the safety of the drug in the short term.
IMO, and I am definitely speculating, I do not think this is the end for CX-717. My guess is that the FDA noticed some problem in animals (increased liver toxicity) and realized that Cortex's protocol did not include analysis of this problem in the human trials. In the end (IMO), Cortex or a BP will be allowed to continue studying CX-717 in humans assuming that they adjust their protocol to monitor this potential problem in humans.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 06:35 pm
Msg: 27579 of 27642
mjx,
I have written to Dr. Scott Gottlieb at the FDA to protest the way in which this clinical trial hold was handled at the FDA. His email address is scott.gottlieb@FDA.HHS.gov
I don't want to get into some inane debate here about whether my letter to Gottlieb will have any effect, because I really don't know if it will. But I wrote to him. So there.
The halt to clinical trials that have successfully completed Phase II testing in human subjects without any adverse side effects based on much earlier animal toxicity studies seems to me patently unfair and ridiculous, and an exercise of what John Calfee recently cited as "regulatory bias" in the FDA's handling of drug development. See http://www.aei.org/publications/pubID.24130/pub_detail.asp
Bladerunner
Re: Previous FDA holds
by: Neuroinv 04/03/06 07:01 pm
Msg: 27583 of 27643
Blade--We don't know yet if this ("much earlier") is true. The data in question could have been from the recently completed three month tox study. But other than that, I tend to agree with you. There is no way that the event was so clearcut and blatant that they needed to do this highly publicized 'straight arm'--other than to show Congress that they are aggressively on the safety lookout.
And that's exactly what the FDA wants to do, to counter the complaints from Grassley and Sidney Wolfe, among others.
NeuroInvestment
Sad day
by: laddadg
Long-Term Sentiment: Strong Buy 04/03/06 07:47 pm
Msg: 27590 of 27643
I would love to write off this morning's sell-off as nothing more than an "over-reaction, but in all honesty, I cannot. The FDA order to halt further testing caught me completely off guard, and I am still trying to sort out the missing pieces. My first temptation this morning was to sell a portion of my considerable stake at market open (@ $3.40), but ultimately chose not to until I could get additional information. In retrospect, it was a poor decision - but one I must deal with.
The immediate question now is - do I sell @ $2.50 or continue to hold.
For me, the answer is simple. Despite the FDA announcement (which I concur is a significant cause for concern), the risk/reward still remains extremely attractive. The vast majority of the animal data is extemely good and has already been confirmed by Cortex and various BP partner candidiates. Based on these previous reviews, there were NO significant issues reported by anyone. I would assume that there MAY in fact be some minor side effects at huge dosage volumes, but I remain confident that these issues can be rectified in a short period of time.
The good news! At long last, we may be getting the warrant holders to finally exercise their warrants, thereby ridding ourselves of the overhang (as well as adding to our cash reserves). And if weak holders were looking for a valid reason to dump, they couldn't have found a better one than with this morning's news.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 07:55 pm
Msg: 27592 of 27643
Neuro,
I agree. My use of the pharse "much earlier" may be questionable. In any case, my own opinion is that when a drug has successfully--i.e. without serious side effects--completed some Phase II trials, then clinical trials should not be halted due to adverse effects found in (much?) earlier animal studies. There must be a better way to handle this than using the draconian "clinical hold" method. This is what I told Gottlieb. You may want to refer to Calfee's paper at AEI published just a couple of days ago about "regulatory bias" in the development--as opposed to the approval--process at the FDA. It's fairly safe to assume that Gottleib and Calfee are well-known to each other, since both are or have been associated with AEI. (The paper came out just two days before the FDA's decision to halt clinical testing of CX717. You'd better believe that I pointed out this interesting coincidence to Dr. Gottlieb. If there ever was an instance of Calfee's "regulatory bias" at the FDA, you could well argue that this was it in COR's case.)
You're right about COR not having an FDA liaison in its management system, but you can be well-assured that that situation has changed.
We can only hope that with von Eschenbach and Gotlieb now in charge, the regulatory and political climate will be undergoing a positive change. But the CNS division will probably will the last to hear about it. (lol)
We'll see how this plays out, but a three-six month delay seems almost certain, unless the FDA reverses itself which is very unlikely. I assume further animal toxicology studies will be needed, but perhaps only further clarification on studies already completed. Who knows at this point?
Bladerunner
Re: Previous FDA holds
by: DewDiligence 04/03/06 08:31 pm
Msg: 27599 of 27644
>I doubt the animal model would bring up an issue that was not already caught in human testing…<
You misunderstand the mathematical model that underlies animal testing: very high doses are administered to a relatively small population of animals to try to ferret out a side effect that might occur rarely in humans.
CX717 has been tested on how many humans? I think much less than 1,000. So how could you expect to find a side effect that occurs, say, once in 10,000 people in the human patients tested to date? The odds are you wouldn’t.
The mathematical model used by the FDA and other regulatory bodies says, “Look, we know you can’t test CX717 on thousands and thousands of patients in midstage human trials, but we still care about rare side effects. So we want you to test extremely high doses on animals on the theory that a rare side effect may show up in a much smaller sample size if the dose is raised by an order of magnitude or more.”
This is only a mathematical model that is not necessarily consistent with reality, but regulators have to have a method to evaluate safety in a drug like CX717 and, absent very large human trials, this mathematical model is the best method they have at their disposal.
Many drugs with a clinical hold end up doing fine and coming to market without even a black-box warning. CX717 may be perfectly safe for all we know today. However, the FDA’s mathematical model is presumably saying there is an issue to be addressed, and when it comes to safety the philosophy is guilty until proven innocent, as it should be.
So please hold your outrage against the FDA—they are simply doing their job.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 08:39 pm
Msg: 27601 of 27644
Thanks Curley. I think iepty has a point when he says that these things happen in drug development all the time, but when they happen to a microcap biotech with no FDA/regulatory liaison, the results can be quite devastating. In fact, having a liaison probably helps in preventing these kinds of things from happening. Given that COR doesn't have the wherewithal to have that kind of regulatory person, then I think all that Stoll can do is to try to get the letter in his hands as soon a s possible. I'm quite certain that the letter has already been written. I'm sure Gottlieb is aware that in an age of instant communication, there is no excuse for the FDA not giving a company "the letter" as soon as it puts the company's trials on clinical hold. At the very least, I would expect Gottlieb to try to make some changes in that procedure, and I, of course, suggested that to him. It wouldn't hurt to have others here drop him a line as well. scott.gottlieb@FDA.HHS.gov
Bladerunner
What the Delay Means
by: rdravin (56/M/NJ)
Long-Term Sentiment: Hold 04/03/06 09:57 pm
Msg: 27608 of 27644
So what does the FDA action mean?
1. Animal studies must be redone.
2. Clinical trials must be redone.
3. BP deal canceled and delay indefinitely.
3. Precious monetary reserves used up to complete steps 1, 2.
4. Additional pipe financing required.
5. Either panic sellout at $2.50/shr or
12 months of 1.8 - 2.25 range.
Good science vs poor capitalization. who wins??
Re: Previous FDA holds
by: Neuroinv 04/03/06 10:10 pm
Msg: 27613 of 27644
<<So please hold your outrage against the FDA—they are simply doing their job.>>
I have no problem with the FDA telling Cortex to not enroll more human subjects until this has been sorted out. But the process is inane. At the very least, there is no reason to wait 7-10 days for this mysterious letter. They require companies to submit NDAs in electronic form, the least they can do is provide Cortex with full info right up front via the same mechanism.
I had been annoyed as well that the clinical hold was vis-a-vis an AD study that is hardly enrolling anyone. Seemed like overkill, a quick phone call would have sufficed. But I had forgotten that Cortex was going to do a bioequivalence study between capsule and tablet formulations of CX717 quite soon. Based on that, which would have been quick to enroll, I am now more sympathetic to the concept that this had to be implemented in bureaucratic fashion. Now that it has, the FDA's obligation is to explain itself fully so that the Company can respond. This limbo period is totally unnecessary, and just leaves Cortex dangling, trying to get information behind a decision that has already been made and announced.
The FDA should indeed do its job. But it should be less sloppy about it.
NeuroInvestment
Re: Occam's Razor.......
by: duluoz04
Long-Term Sentiment: Strong Buy 04/03/06 10:49 pm
Msg: 27624 of 27644
After reading every damn post from today,
here's what I think...IMO, of course....
The FDA has found that at very high toxicity
there was some issue in the animal samples.
So, being that they are on full blast paranoia
at the moment, they issued this "strong armed"
notice which totally screwed the stock price,
obviously. I believe that because those at COR were(seemingly) so caught off guard here also makes me believe that this will not be a big issue, other than for our collective blood pressure to sky-rocket and also it taking longer for us to ge to double digits.
I say all of this using the occam's razor theory, which is listed below...
(website URL deleted - not sure it's safe - Aiming4)
So by the time all of the smoke (and i do empahsize SMOKE here) clears, we'll be
back on track, albeit probably a bit lower
in price than we were (3-4-5 instead of 5-6-7).
That's my take and I'm sticking to it!
Thanks to all those who posted good, honest
informative messages. All the other a-holes
are on ignore and there they shall remain.
GO COR
D
p.s. the 7-10 day waiting period on the mystery letter is absolutely criminal in my mind
Coincidence?
by: e_neurotech
Long-Term Sentiment: Buy 04/03/06 11:23 pm
Msg: 27630 of 27644
I hate to admit that I've gained some measure of cynicism as I try my best to gracefully age. Here we are on the verge of a promising BP deal, with positive clinical trial results... and then this. Hhmmm.
Surely all those big BP reps have stronger ties than COR with the folks at the FDA, surely they have friendly conversations. Hey, these are regular folks, right?
So, the BP guy meets some friend from the FDA, and over some stinking beer, drops a little hint: "Oh, yeah, we've been thinking about offering COR a deal, but then we took a look at their animal data and..."
Maybe there isn't a damn thing wrong with the animal data.
Point of reference: A few years ago, a local hospital got lots of unwanted publicity and a huge lawsuit when a surgeon removed the wrong leg from a patient. The publicity went on for weeks. There were newspaper and TV interviews with lawyers, hospital personnel,the patient's family. It went on and on, everything the hospital did was scrutinized, disected, hospital procedures revamped. You name it, they got it.
Now for the rest of the story: The patient was scheduled to have both legs amputated, one week apart. The surgeon removed the "wrong one" first.
There's more. The "inside" news is that a big conglomerate had been trying to buy the hospital for two years. The hospital's board had refused to negotiate.
The big conglomerate purposedly sought out an incident in the hospital that they could fully exploit (incidents happen all the time, folks) in order to bring the hospital board to their knees.
They succeeded.
Please don't tell me that the same could not possibly be happening here.
This FDA notice just tells me that Stoll has been playing hardball.
CX717 IS Snake oil
by: frogss12
Long-Term Sentiment: Strong Sell 04/03/06 07:22 am
Msg: 27225 of 27626
Don,t know about scientology but I do know about ADHD and I grew out of it in my early twenties,and have more than two formal qualifications.COR is currently being questioned by the feds as you insiders clearly know.What this stock does now is not my concern as long as the directors do as there told everyone will be fine.
Valium in a different wrapper.Tom Cruise has more money than you and access to more professional resources than most of you could dream of.Peasants trying to knock a man off the top of the hill.
Re: MAJOR OVERREACTION ...LOOK FOR RECO
by: daviddal66
Long-Term Sentiment: Strong Buy 04/03/06 09:49 am
Msg: 27265 of 27629
3 choices.
1. Something was hidden, toxic in animals and not disclosed--jail time and extremely unlikely.
2. Mild side effect--fda wants more testing.
3. They screwed up and didn't do enough animal testing, complete pathology ect . . .
I cannot figure it out. No problems with ORG24448. Weird, but thats biotech.
Disaster - maybe / maybe not
by: gfp927z 04/03/06 09:55 am
Msg: 27272 of 27629
Well, Murphy's Law strikes again. This is all part of the risk one takes in this sector, particularly with a brand new drug platform. The stock is obviously going to get creamed, but it remains to be seen whether there is actually a really dire problem or not. The FDA concerns are apparently with some animal data and not with any problems in the human trials.
Of course the most obvious concern one has with upregulating glutamatergic pathways is the risk of excitotoxicity (seizures), though this is much more a problem with the high impact approach. Being a low impact, CX-717 has had a very clean record as far as excitotoxicity is concerned, as far as we know. Perhaps they saw something in the longer term animal studies, or it could be something totally unrelated to excitotoxicity, perhaps related to the spectrin/calpain phenomenon. At this point it'as anyone's guess. We'll hear more from Cortex on it in the weeks to come.
Condolences to all longs, though we shouldn't pass final judgement just yet until we hear from Dr. Stoll and see the animal data that the FDA has concerns about.
One silver lining . . .
by: daviddal66
Long-Term Sentiment: Strong Buy 04/03/06 10:04 am
Msg: 27277 of 27630
Let's say that ampakine CX717 is on hold--the BOD might authorize a buyout on the cheap. It depends on the side effect in question. I'm just guessing. I don't get it, but sounds like the frog did. The buyout on the cheap would only apply if the side effect was a. mild and b. required another three to six month's of animal testing. The BOD might just take an offer--say at 5 and be done with it. Just my 2 cents. Still Dr. Stoll announced going to phase IIb studies ASAP--with plans on the board--the tox has been sent to the FDA--the FDA just reviews what Cortex did(and knows).
Re: One silver lining . . .
by: gfp927z 04/03/06 10:16 am
Msg: 27284 of 27630
Daviddal, This development with the FDA could turn out to be exceedingly dire, or the mother of all buying opportunities. Let's hope the FDA doesn't start digging through Org-24448's animal data also. I'll have to have a "neutral" opinion on the stock until we find out exactly what's going on.
Hopefully Neuro will chime in soon. I have to leave for work, but will be back tonight.
Gary Lynch
by: encinitan1999 04/03/06 10:24 am
Msg: 27291 of 27631
This is pure speculation, but I have to wonder if someone in Gary Lynch's lab (but not Cortex) was aware of an issue with animal data some time ago. Maybe this individual had a major greivance with Lynch. Maybe this individual tipped of the FDA. Is Lynch aware of a problem(s) that he was unwilling to disclose?
I don't have any direct connection with the Lynch lab, but I noticed that the lab web site has been shut down for the last two months.
I wonder if Lynch is in the process of resigning his position at UC Irvine based on the following observations: Another spinoff from Lynch's lab, Thuris (a virtual company), was aquired recently by a San Diego company that is a penny stock (Protein Polymer). A just published study in PNAS from Lynch and members of his lab lists his significant other (Christine Gall) as the contact person. Is Lynch aware of a problem(s) that he would not disclose?
Again, of course, this is all pure speculation.
I bought Cortex at the low 2s and am still holding. I am nauseous, which of course impairs thinking somewhat. Time for a Xanax.
Re: Disaster - maybe / maybe not
by: Neuroinv 04/03/06 10:27 am
Msg: 27295 of 27631
It's unlikely to have anything to do with preclinical seizure activity--because that's apparent when it happens. Cortex would have had to notify the FDA immediately, and the sleep dep trial would have been stopped.
For it to raise a question later: Perhaps its some histological change seen on a slide from one animal--but I must emphasize, I am just guessing here. It's the kind of thing that might come up in retrospect, and it might not be known what the cause is--but until they know if its a pattern, human trials are suspended--though in this case, sleep dep has already been completed.
It doesnt happen often, but I can recall a couple of instances. Pfizer's Lyrica was in Phase II when it was put on hold after they found a tumor in a preclinical trial animal. Pfizer eventually showed that there was no risk in humans, and Lyrica is approved in the US and EU. Back in 1997, the first NBIX/Janssen CRF-1 drug was in Ph II--and a dog showed liver enzyme changes. The drug was eventually dropped, although other CRF-1 drugs were developed and partnered with GSK, now in PhII.
There are other examples but none that come to mind 7:15am local time. Bottom line--we won't know how important this is at least until Cortex has received written detail from FDA and disclosed it--and maybe not then.
NeuroInvestment
Re: I hate to say this . . .
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 10:34 am
Msg: 27299 of 27632
Not at all. My point, and I obviously could be dead wrong, is that if Cortex completed their three month animal tox package to the FDA for review and had no concerns expressed public--declared that everything is swell on the partnering talks, this tells me it was probably mild in terms of side effect in animals. No insider sales. But a simple error of what was thought to be mild--and not serious side effect in animal toxicology. Again, the FDA decision may have blindsided Cortex, but the company already knew what the results were of their animal studies--unless I'm completely missing something.
Re: Call Stoll and request a conf. call
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:09 am
Msg: 27321 of 27633
sadly, wmg2, I agree. I believe Stoll made an honest mistake of believing what he thought was a minor side effect in animals(with an FDA dissent), and i believe he's making another honest mistake in not discussing the animal data in detail. Again, Cortex knows in detail--chapter and verse--the safety results in animals; they ran the studies and did the histo--not the FDA.
Re: Gary Lynch
by: jcpsy1
Long-Term Sentiment: Hold 04/03/06 11:14 am
Msg: 27327 of 27634
Didn't our mysterious urko have a critical comment about animal heads on the wall in Lynches lab, ax to grind? Plus bragging about following Cotman and possibly others around. His lurk-mode means something more than lurk perhaps. We have a da Vinci code-type plot in the making. Sad day, fellow longs.
I sent Dr. Stoll an email . . .
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:21 am
Msg: 27333 of 27634
urging him to have a conference call today to discuss their summary of the animal data--three month toxicology with CX717. If Cortex felt the side effect they saw was not material, find; everyone makes mistakes. I accept this. But the actions of the FDA clearly make the animal results material. To wait for 10 business days or whatever is unfair in the extreme. It would seem to me that a full--public vetting about the animal studies is in order. These are the two species. These are the histology slides. These were the potential problems. Maybe I'm missing something, but the letter and negotiations witht the FDA are vital--and Stoll cannot disclose these until they occur--ie the plan for advancement. But, with today's events, I feel strongly that the company has an obligation to its shareholders to have a 20-30 minute conference call--to lay the data on the table. I've urged him to hold such a conference call to disclose the animal data. I believe he's been a decent CEO, fair and honest. Mistakes happen, but mistakes can be made right.
Re: from 10-k
by: daviddal66
Long-Term Sentiment: Hold 04/03/06 11:28 am
Msg: 27337 of 27636
Thanks, Jenkins, I think you nailed it. If this statement is correct:
"Each study examined the effects of very high (toxicological) daily doses of CX717 for ninety consecutive days. Each study included extra animals to assess whether any observed toxicological effects were reversible once dosing was stopped."
It could be--and probaly is--what is known as a 'failure of anticipation of the FDA's tough stance at very high dosages--maybe they wanted more animals included that were done.
Not enough info. FDA risk adverse
by: deathspiralwatcher (99/watching) 04/03/06 11:35 am
Msg: 27344 of 27636
Trying to game this situation right now is almost impossible. There is not enough information to do more than gamble or guess. What we know:
1. FDA issued a clinical trial hold based on questions about animal data.
2. The issues with the animal data are unknown to the public.
3. Cortex must have at least a rough idea of what the questions are. Liver enzymes, tummy aches, insommnia, etc. For reasons we can only guess they have chosen not to divulge this info at this time.
4. The FDA is risk adverse these days. The tysarbi MS fiasco really put them on edge. Probably didn't help about the trial in Great Britain where the human subjects all got very sick almost immediately.
Those are the facts as known today. Whether this clinical trial hold is a bump on the road or terminal or in between is anyone's guess. Myself going to wait for more visibility. Luck to all, IMHO
Re: Call Stoll and request a conf. call
by: Neuroinv 04/03/06 11:43 am
Msg: 27353 of 27637
Blade: If there were something clearcut from the 3month tox studies, you would be absolutely correct--everyone would have seen it. BP suitors get to look at everything. And Varney would not have come to a company if he knew a clinical hold was likely to happen.
It could well be an issue of interpretation and extrapolation: Note that the 10K mentioned the issue of showing that high-dose anomalies being correctible when dosing is stopped. Let's say two dogs given 5X the maximum human dose per kg (I am making this up, I have zero information as to what the actual content of the issue is) showed liver enzyme changes after three months. Taking them off the drug led to the enzyme levels going back towards normal after a month. Cortex and its BP suitors could look at the curve and say--it looks like its going back to normal. The FDA could say--but it's not back there yet, we want to know if it would get there, and how long it would take.
My point with this contrived illustration is that it is not a binary 'is there a toxic effect or isnt't there' situation.
What generally happens in these instances is that the FDA makes a quick call alerting a company that a letter is on the way, and that the hold is in effect. I don't believe those calls include much info, they certainly don't state what the FDA wants to see as a correction/clarification. The really big pharmas have people on staff whose sole job is as FDA liaison--in this kind of situation, they'd be calling and schmoozing to get all the detail they can ASAP. Small companies like Cortex can't afford that, so they have consultants that they hire to do the same. But until they get that information back, they'd be foolish to have a CC.
NeuroInvestment
Spoke to Stoll a little earlier this am
by: wmg2 (M/Palo Alto) 04/03/06 11:45 am
Msg: 27356 of 27638
Suggested a conference call to inform shareholders of what is known to date. He said that the FDA communicated to Cortex’s “Medical Director”. I assume this is Mansbach, not Varney. Stoll has not yet spoken with the FDA, though he, of course, plans to today.
His preference is to first speak with the FDA himself, prior to Cortex making any further public statements and would like to have the letter in hand. He will ask the FDA to expedite the letter so as not to have to wait the 7 to 10 days.
The FDA had to have addressed what the concern was with Cortex when the phone conversation took place. At least we are deserving of knowing what type of toxicity concern the FDA is questioning.
WMG2
Re: Just doubled my position
by: Neuroinv 04/03/06 12:55 pm
Msg: 27422 of 27640
It is a big deal--unless and until we learn otherwise. Which means 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) the aforementioned 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 is sociopathic enough to lie 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.
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.
NeuroInvestment
Re: Neuroinv...
by: Neuroinv 04/03/06 01:08 pm
Msg: 27432 of 27640
That was badly worded by the wire services. The sleep dep trial is already over, DARPA has the data. And the AD trial is hardly enrolling anyone. They were trying to say there was a hold on the sleep dep drug, not the sleep dep trial.
NeuroInvestment
Odd timing, animal, human trials, hold
by: deathspiralwatcher (99/watching) 04/03/06 01:21 pm
Msg: 27435 of 27640
Odd timing on this hold prompted by "animal data."
The usual clinical trial timeline is preclinical (tox, pharmokinetics, animal studies etc.) Followed by human phase 1, phase 11(a+b), phase 111, NDA.
We know that cor has done phase 1 and several phase 11s. Now, the FDA has questions about preclinical. Looking at the timeline, they should have had the preclinical data for a long time, months or years. And it didn't bother them enough to prevent CX717 from being tested in humans. Now, all of the sudden, it bothers them enough to issue a clinical hold.
This is odd looking timing. As to what it means, is anyone's guess. Myself, going to wait for more visibility. IMHO
Re: Odd timing, animal, human trials, ho
by: Neuroinv 04/03/06 01:29 pm
Msg: 27437 of 27640
It would almost certainly be from the three month tox study completed in the last few months--which would also have used some dose-levels far above those envisioned for humans. Whether any anomalies would be applicable to human dosing is another of those issues up for interpretation.
NeuroInvestment
Re: Neuroinv...
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 01:34 pm
Msg: 27442 of 27640
Neuro,
I just got off the phone with Roger Stoll. Nothing really new to report. COR is trying to speed up the reception of the letter from the FDA, using its contacts in Washington, D.C. Stoll feels there is no use in having a CC until he has the letter from the FDA in his hands. After receiving the letter, COR will attempt to get in touch with the person(s) at the FDA responsible for putting the clinical hold on CX717 and try to resolve the issues.
Stoll did make me aware of something that I didn't know: The FDA oftentimes has access to data that even the company does not have. So it could be that something that COR saw, but did not interpret as significant. Or, it can be something that the FDA has seen that the company was not aware of. (I don't have a clue about how the latter case is possible. Perhaps you could shed some light on that for me and for the board.)
Given how much in the dark that COR is about the situation, I'll reconsider my position on asking for an immediate CC. There really isn't much COR can say until the details are revealed in the letter.
Bladerunner
Re: Odd timing, animal, human trials, ho
by: learning2vest (62/M/Georgia)
Long-Term Sentiment: Hold 04/03/06 02:00 pm
Msg: 27459 of 27640
Have absolutely no personal knowledge of how the FDA conducts their approval process, but will share the my hunch after seeing today's news.
The "question";
Why would the FDA wait until now to order a halt based on animal data they have had for several years, and that they used to approve the move into human trials?
Best "answer" so far;
They did not do that. They must have received new data re the animal trials. I'm guessing that most of the animals that are used in pre-clinical trials live out normal lives. They may have endured multiple blood tests, and even biopsy's, during their active participation in multiple experiments, but maybe it's not until they expire that a detailed examination of all tissues can be performed.
Maybe detailed post mortem tissue examinations of some animal participants in the earlier trials, i.e., animals which only recently expired, showed signs of some abnormality which demanded further analysis.
Is the observation explained as being "just something in this animal's genetic makeup", or was it caused by something the animal was exposed to? Which experiment in this animal's "work history" do we attribute this to?
That is pure speculation by somebody totally unqualified to play such games, but it was good enough to justify this Cortex investor's desire to stay long. What's another year or so at this point??
My deepest Sympathies
by: frogss12 04/03/06 02:39 pm
Msg: 27477 of 27641
Horrible thing to happen to anyone.I never suspected a major gap down.However this is this industry Pharmacuticals and Biotech.They simply baffle people with BS,to often.In England last week 6 young lads nearly died from a drug trial.Two are still in a coma with massive swelling to their heads.
Invest with Dr.Frankenstien "not likely"
Looking back and ahead
by: farutti4toop (33/M/San Francisco) 04/03/06 02:46 pm
Msg: 27482 of 27641
On January 3, the first trading day of this year and a mere three months ago, COR opened at $2.28 and closed at $2.35 - still below where we are today.
If it were so obvious to the street that CX717 is "snake oil" or that COR is toast, there would be no price support at $2.50. As others have mentioned, today's trading volume includes a lot of buyers. A 51% drop may be precipitous, but it's hardly a free-fall.
C'mon, gang, this is a biotech company, a company with no earnings, a one-hit wonder, a virtual penny-stock, after all. Extreme volatility is too be expected - and not just to the up-side, for those of you who were expecting 20% increases every day.
And although no one could have predicted it, if you weren't at least considering the possibility that soemthing like this might happen, you were deluding yourself.
I lived through the Centocor debacle in 1992 -its shares went from $60 to $6 in one day, when the FDA halted testing of its flagship sepsis drug Centoxin. Yes, despite reams of promising data, it can and does happen.
However, there's just too little information to make a reasoned judgment on what today's announcement means. Those who are doubling down are as likely to be right as those who are liquidating and running for the hills.
And me? I'm buckling my seatbelt, crossing my fingers, and hanging on for a wild ride.
The FDA and data access
by: Neuroinv 04/03/06 03:07 pm
Msg: 27497 of 27641
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--No, I dont buy the BP drive-the-price-down-to-get-a-better deal paranoid fantasy.
NeuroInvestment
Re: prxl
by: prxl (M/CA) 04/03/06 03:20 pm
Msg: 27504 of 27641
My point all along has been the following:
1) This notification is NOT a "non-event" that some people on the board have tried to emphasize.
2) Putting a trial on hold is a pretty significant regardless of future outcome.
3) Preclinical data is no less important than human data. I'm not saying it's MORE important, but it's no less important.
Today's news IS what it is. Disappointing, unfortunate, and with a future impact that is not fully known.
Why Not Tell Us?
by: jkhaynesx 04/03/06 03:26 pm
Msg: 27509 of 27641
The company must know considerably more than it has disclosed. Maybe there is a good reason why it has not provided a full disclosure of what is known so far, but I can’t imagine what it is. Waiting for another week allows the possibility of persons who may somehow have access to what is now known to trade unfairly, either as buyers or sellers.
I can’t recall any company getting in trouble for releasing material information too early.
JIM
Preclinical
by: Neuroinv 04/03/06 03:53 pm
Msg: 27528 of 27641
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
Re: If and when the FDA gives a green li
by: ggg7ggg
Long-Term Sentiment: Hold 04/03/06 03:59 pm
Msg: 27532 of 27641
I'm not so sure. I would imagine that this little situation has scared the beejeebees out of most, who will be grateful to sell on the way up, should this matter have a relatively quick and benign resolution.
I know that I now have a much greater respect for the risk in this little baby, in which I have way too much of my capital. I guess I am guilty of the "greed" factor, and now trying to control my "fear" impulses.
Re: NeuroInv Serious Questions
by: Neuroinv 04/03/06 04:02 pm
Msg: 27533 of 27641
1) The compound is far enough along that it would take an unredeemable (or at least, one that cannot be proven absent) safety issue to kill CX717 entirely.
2) No one can just 'make a few phone calls.' But, once the details are known, a BP could easily assess the time and risk involved in resolving it. If someone were eager enough, they could offer a risk-sharing agreement: 'we'll give you the deal that's on the table, withholding $15 million of the upfront payment to be paid as a milestone if/when the clinical hold is lifted. (I'm making up a number, again). They'd be gambling, but this is something BP is good at, looking at preclinical data, risk factors, regulatory concerns.
3) Organon trial--you mean if it failed? The Market is attributing little if any value to the Org24448 trial at this point. It would obviously become higher-profile if CX717 languishes for a while. Assuming it demised as well, Cortex would still have its IP, other low-impacts, and its high-impacts. They wouldnt go bankrupt. But we'd be discussing dilution and buyouts for two years. An ugly thought I am going to exile to the far reaches of my preconscious.
NeuroInvestment
Re: Why Not Tell Us?
by: laker9029 (49/M/Holland, OH)
Long-Term Sentiment: Hold 04/03/06 04:10 pm
Msg: 27540 of 27641
<The company must know considerably more than it has disclosed. Maybe there is a good reason why it has not provided a full disclosure of what is known so far,>
It would be foolhardy for Cortex to say anything until they know exacly what the issue is -- that includes restating their interpretation of animal study data. They need to recognize -- as they apparently do -- that the FDA must be handled with care - to attempt to refute or lessen the impact of the FDA "hold" would serve no meaningful purpose and might actually antagonize the FDA. As David mentioned, if Cortex had more cash, perhaps they could have done some serious schmoozing (relationship building) .. but that is not the case, so here we are.
My concern is that resolution will take at least 6 months, during which Cortex will be dead in the water -- unable to move agressively forward on any Ampikine development, while still hving to maintain their staff and without the R&D cash flow from Servier.
Re: Trading should of Halted
by: atshrugg 04/03/06 04:46 pm
Msg: 27556 of 27641
frogss - speaking of pending investigations- You don't think the SEC is going to be looking at todays action, and possibly at you? How is it you had the inside scoop a day, and then an hour before it went public? Why are you pumping hard 10 days ago and bashing hard last week. I'll give you this, you have large nads to be this blatant about manipulation on inside info. I would love to see your trade history over the past two weeks In any event Cortex really needs to take a look at the employees emails and any other internal communications they can get their hands on. The last thing they need now is an SEC problem.
Previous FDA holds
by: mjxspxdr9248 04/03/06 05:49 pm
Msg: 27570 of 27642
I attempted a search to try and get a feel for how long it takes for holds to be released if the company can please the FDA. It certainly varies on a case to case basis, but it seems pretty clear that it takes several months to clear things up. Here is a link to an anxiety medication that hit a similar snag. http://panicdisorder.about.com/b/a/2004_06_28.htm
It took the better half of a year to resolve this matter with the FDA. My search revealed a similar time frame for other drugs. I could not find an example of a drug where an animal study later came back to haunt a company in phase II trials.
While it is clear that trials for this drug are halted, I wonder if Cortex will or is even allowed to release the Sleep Dep Results. The trial is completed and should be fully analyzed.
Releasing these data, if positive, will certainly help to ease shareholders concerns in the short term. Also, if there are no adverse effects, as was the case in all of the previous trials, this would further ease concerns about the safety of the drug in the short term.
IMO, and I am definitely speculating, I do not think this is the end for CX-717. My guess is that the FDA noticed some problem in animals (increased liver toxicity) and realized that Cortex's protocol did not include analysis of this problem in the human trials. In the end (IMO), Cortex or a BP will be allowed to continue studying CX-717 in humans assuming that they adjust their protocol to monitor this potential problem in humans.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 06:35 pm
Msg: 27579 of 27642
mjx,
I have written to Dr. Scott Gottlieb at the FDA to protest the way in which this clinical trial hold was handled at the FDA. His email address is scott.gottlieb@FDA.HHS.gov
I don't want to get into some inane debate here about whether my letter to Gottlieb will have any effect, because I really don't know if it will. But I wrote to him. So there.
The halt to clinical trials that have successfully completed Phase II testing in human subjects without any adverse side effects based on much earlier animal toxicity studies seems to me patently unfair and ridiculous, and an exercise of what John Calfee recently cited as "regulatory bias" in the FDA's handling of drug development. See http://www.aei.org/publications/pubID.24130/pub_detail.asp
Bladerunner
Re: Previous FDA holds
by: Neuroinv 04/03/06 07:01 pm
Msg: 27583 of 27643
Blade--We don't know yet if this ("much earlier") is true. The data in question could have been from the recently completed three month tox study. But other than that, I tend to agree with you. There is no way that the event was so clearcut and blatant that they needed to do this highly publicized 'straight arm'--other than to show Congress that they are aggressively on the safety lookout.
And that's exactly what the FDA wants to do, to counter the complaints from Grassley and Sidney Wolfe, among others.
NeuroInvestment
Sad day
by: laddadg
Long-Term Sentiment: Strong Buy 04/03/06 07:47 pm
Msg: 27590 of 27643
I would love to write off this morning's sell-off as nothing more than an "over-reaction, but in all honesty, I cannot. The FDA order to halt further testing caught me completely off guard, and I am still trying to sort out the missing pieces. My first temptation this morning was to sell a portion of my considerable stake at market open (@ $3.40), but ultimately chose not to until I could get additional information. In retrospect, it was a poor decision - but one I must deal with.
The immediate question now is - do I sell @ $2.50 or continue to hold.
For me, the answer is simple. Despite the FDA announcement (which I concur is a significant cause for concern), the risk/reward still remains extremely attractive. The vast majority of the animal data is extemely good and has already been confirmed by Cortex and various BP partner candidiates. Based on these previous reviews, there were NO significant issues reported by anyone. I would assume that there MAY in fact be some minor side effects at huge dosage volumes, but I remain confident that these issues can be rectified in a short period of time.
The good news! At long last, we may be getting the warrant holders to finally exercise their warrants, thereby ridding ourselves of the overhang (as well as adding to our cash reserves). And if weak holders were looking for a valid reason to dump, they couldn't have found a better one than with this morning's news.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 07:55 pm
Msg: 27592 of 27643
Neuro,
I agree. My use of the pharse "much earlier" may be questionable. In any case, my own opinion is that when a drug has successfully--i.e. without serious side effects--completed some Phase II trials, then clinical trials should not be halted due to adverse effects found in (much?) earlier animal studies. There must be a better way to handle this than using the draconian "clinical hold" method. This is what I told Gottlieb. You may want to refer to Calfee's paper at AEI published just a couple of days ago about "regulatory bias" in the development--as opposed to the approval--process at the FDA. It's fairly safe to assume that Gottleib and Calfee are well-known to each other, since both are or have been associated with AEI. (The paper came out just two days before the FDA's decision to halt clinical testing of CX717. You'd better believe that I pointed out this interesting coincidence to Dr. Gottlieb. If there ever was an instance of Calfee's "regulatory bias" at the FDA, you could well argue that this was it in COR's case.)
You're right about COR not having an FDA liaison in its management system, but you can be well-assured that that situation has changed.
We can only hope that with von Eschenbach and Gotlieb now in charge, the regulatory and political climate will be undergoing a positive change. But the CNS division will probably will the last to hear about it. (lol)
We'll see how this plays out, but a three-six month delay seems almost certain, unless the FDA reverses itself which is very unlikely. I assume further animal toxicology studies will be needed, but perhaps only further clarification on studies already completed. Who knows at this point?
Bladerunner
Re: Previous FDA holds
by: DewDiligence 04/03/06 08:31 pm
Msg: 27599 of 27644
>I doubt the animal model would bring up an issue that was not already caught in human testing…<
You misunderstand the mathematical model that underlies animal testing: very high doses are administered to a relatively small population of animals to try to ferret out a side effect that might occur rarely in humans.
CX717 has been tested on how many humans? I think much less than 1,000. So how could you expect to find a side effect that occurs, say, once in 10,000 people in the human patients tested to date? The odds are you wouldn’t.
The mathematical model used by the FDA and other regulatory bodies says, “Look, we know you can’t test CX717 on thousands and thousands of patients in midstage human trials, but we still care about rare side effects. So we want you to test extremely high doses on animals on the theory that a rare side effect may show up in a much smaller sample size if the dose is raised by an order of magnitude or more.”
This is only a mathematical model that is not necessarily consistent with reality, but regulators have to have a method to evaluate safety in a drug like CX717 and, absent very large human trials, this mathematical model is the best method they have at their disposal.
Many drugs with a clinical hold end up doing fine and coming to market without even a black-box warning. CX717 may be perfectly safe for all we know today. However, the FDA’s mathematical model is presumably saying there is an issue to be addressed, and when it comes to safety the philosophy is guilty until proven innocent, as it should be.
So please hold your outrage against the FDA—they are simply doing their job.
Re: Previous FDA holds
by: bladerunner1717
Long-Term Sentiment: Hold 04/03/06 08:39 pm
Msg: 27601 of 27644
Thanks Curley. I think iepty has a point when he says that these things happen in drug development all the time, but when they happen to a microcap biotech with no FDA/regulatory liaison, the results can be quite devastating. In fact, having a liaison probably helps in preventing these kinds of things from happening. Given that COR doesn't have the wherewithal to have that kind of regulatory person, then I think all that Stoll can do is to try to get the letter in his hands as soon a s possible. I'm quite certain that the letter has already been written. I'm sure Gottlieb is aware that in an age of instant communication, there is no excuse for the FDA not giving a company "the letter" as soon as it puts the company's trials on clinical hold. At the very least, I would expect Gottlieb to try to make some changes in that procedure, and I, of course, suggested that to him. It wouldn't hurt to have others here drop him a line as well. scott.gottlieb@FDA.HHS.gov
Bladerunner
What the Delay Means
by: rdravin (56/M/NJ)
Long-Term Sentiment: Hold 04/03/06 09:57 pm
Msg: 27608 of 27644
So what does the FDA action mean?
1. Animal studies must be redone.
2. Clinical trials must be redone.
3. BP deal canceled and delay indefinitely.
3. Precious monetary reserves used up to complete steps 1, 2.
4. Additional pipe financing required.
5. Either panic sellout at $2.50/shr or
12 months of 1.8 - 2.25 range.
Good science vs poor capitalization. who wins??
Re: Previous FDA holds
by: Neuroinv 04/03/06 10:10 pm
Msg: 27613 of 27644
<<So please hold your outrage against the FDA—they are simply doing their job.>>
I have no problem with the FDA telling Cortex to not enroll more human subjects until this has been sorted out. But the process is inane. At the very least, there is no reason to wait 7-10 days for this mysterious letter. They require companies to submit NDAs in electronic form, the least they can do is provide Cortex with full info right up front via the same mechanism.
I had been annoyed as well that the clinical hold was vis-a-vis an AD study that is hardly enrolling anyone. Seemed like overkill, a quick phone call would have sufficed. But I had forgotten that Cortex was going to do a bioequivalence study between capsule and tablet formulations of CX717 quite soon. Based on that, which would have been quick to enroll, I am now more sympathetic to the concept that this had to be implemented in bureaucratic fashion. Now that it has, the FDA's obligation is to explain itself fully so that the Company can respond. This limbo period is totally unnecessary, and just leaves Cortex dangling, trying to get information behind a decision that has already been made and announced.
The FDA should indeed do its job. But it should be less sloppy about it.
NeuroInvestment
Re: Occam's Razor.......
by: duluoz04
Long-Term Sentiment: Strong Buy 04/03/06 10:49 pm
Msg: 27624 of 27644
After reading every damn post from today,
here's what I think...IMO, of course....
The FDA has found that at very high toxicity
there was some issue in the animal samples.
So, being that they are on full blast paranoia
at the moment, they issued this "strong armed"
notice which totally screwed the stock price,
obviously. I believe that because those at COR were(seemingly) so caught off guard here also makes me believe that this will not be a big issue, other than for our collective blood pressure to sky-rocket and also it taking longer for us to ge to double digits.
I say all of this using the occam's razor theory, which is listed below...
(website URL deleted - not sure it's safe - Aiming4)
So by the time all of the smoke (and i do empahsize SMOKE here) clears, we'll be
back on track, albeit probably a bit lower
in price than we were (3-4-5 instead of 5-6-7).
That's my take and I'm sticking to it!
Thanks to all those who posted good, honest
informative messages. All the other a-holes
are on ignore and there they shall remain.
GO COR
D
p.s. the 7-10 day waiting period on the mystery letter is absolutely criminal in my mind
Coincidence?
by: e_neurotech
Long-Term Sentiment: Buy 04/03/06 11:23 pm
Msg: 27630 of 27644
I hate to admit that I've gained some measure of cynicism as I try my best to gracefully age. Here we are on the verge of a promising BP deal, with positive clinical trial results... and then this. Hhmmm.
Surely all those big BP reps have stronger ties than COR with the folks at the FDA, surely they have friendly conversations. Hey, these are regular folks, right?
So, the BP guy meets some friend from the FDA, and over some stinking beer, drops a little hint: "Oh, yeah, we've been thinking about offering COR a deal, but then we took a look at their animal data and..."
Maybe there isn't a damn thing wrong with the animal data.
Point of reference: A few years ago, a local hospital got lots of unwanted publicity and a huge lawsuit when a surgeon removed the wrong leg from a patient. The publicity went on for weeks. There were newspaper and TV interviews with lawyers, hospital personnel,the patient's family. It went on and on, everything the hospital did was scrutinized, disected, hospital procedures revamped. You name it, they got it.
Now for the rest of the story: The patient was scheduled to have both legs amputated, one week apart. The surgeon removed the "wrong one" first.
There's more. The "inside" news is that a big conglomerate had been trying to buy the hospital for two years. The hospital's board had refused to negotiate.
The big conglomerate purposedly sought out an incident in the hospital that they could fully exploit (incidents happen all the time, folks) in order to bring the hospital board to their knees.
They succeeded.
Please don't tell me that the same could not possibly be happening here.
This FDA notice just tells me that Stoll has been playing hardball.
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