COR Yahoo Message Board: Wed 4/5/2006
Re: 10k
by: aiming4_a_million (42/M)
Long-Term Sentiment: Strong Buy 04/05/06 01:21 am
Msg: 27886 of 28163
Gfp - what I was suggesting was that since Cortex has stated that they feel they are making good progress in developing a safe high impact Ampakine, and the calpain/spectrin problem would be most pronounced in a high impact Ampakine, doesn't that suggest that either calpain/spectrin isn't being found/perceived as a problem with the high impact Ampakine or that Cortex has found a way to engineer around it?
And if calpain/spectrin isn't causing a problem in the high impact Ampakine Cortex is developing, it is even less likely to be a problem in a low impact like CX-717?
The devil's advocate argument is that the calpain/spectrin problem perhaps may have just become recognized as a new problem with CX-717, while at the same time Cortex has made progress in mitigating the c/s problem with their high impact Ampakine. .. Aiming4.
Re: Toxicity
by: aiming4_a_million (42/M)
Long-Term Sentiment: Strong Buy 04/05/06 01:29 am
Msg: 27887 of 28163
Neuro - the discussion about liver enzyme changes is, I believe, the first time I've heard this mentioned in regards to Ampakines.
Is there any particular reason to think that Ampakines might be expected to have an adverse affect on the liver?... Aiming4.
Re: 10k
by: gfp927z 04/05/06 01:59 am
Msg: 27888 of 28163
Aiming, The big challenge with high impacts has been excitotoxicity. They have to get past the excitotoxocity hurdle first before worrying about calpain/spectrin, which would become a problem later, once longer term dosing is possible without inducing seizures.
Neuro, It appears that the nature of the calpain/spectrin phenomenon is not even well understood by researchers yet, much less decided upon as a key factor or not for Ampakines. I hope the current problem with CX-717 is something more easily remedied, but we can't dismiss anything at this point. Putting our collective heads in the sand isn't going to make this predicament go away any sooner unfortunately.
Re: Toxicity
by: Neuroinv 04/05/06 01:59 am
Msg: 27889 of 28163
Not Ampakines in specific. High doses of a lot of drugs can do that. It's an experiment one can actually do at home--buy a bottle of Tylenol, take 10-15 of them. That in itself can do permanent liver damage--if you down them with a couple of glasses of wine, near- certain. Get on a transplant list first. Some people have developed liver toxicity with four Tylenols--liver transplant level toxicity.
If Ampakines were prone to liver issues, we would have heard about that long ago--between CX516 and 717, not to mention 691--a couple thousand people have taken human-level doses. It's the dose/duration issue that the FDA is worried about--with every drug they look at. Too bad they don't worry about the ones already available on the shelf.
NeuroInvestment
OT-FDA strikes again
by: oldiesmd2002
Long-Term Sentiment: Strong Buy 04/05/06 08:29 am
Msg: 27891 of 28164
DSCO
http://biz.yahoo.com/pz/060405/96849.html
"Specifically, the FDA is requesting certain information primarily focused on the Chemistry, Manufacturing and Controls (CMC) section of the NDA. The information predominately involves the further tightening of active ingredient and drug product specifications and related controls. Consistent with previous review, the FDA does not have any clinical or statistical comments."
"Our previously submitted responses to the first Approvable Letter were accepted by the FDA as a complete response in October 2005."
Re: 10k (neuro, gfp)
by: gfp927z 04/05/06 09:38 am
Msg: 27896 of 28164
Bupaya, That's actually an old Servier trial (CX-516) that didn't go anywhwere. Their current large MCI Phase 2 is with their own AMPA upregulator (S-18986), a benzothiadiazide. This compound doesn't fall under the original Cortex/Servier licensing agreement, so they would have to do a new/updated agreement with Cortex if they ever want to commercialize S-18986.
I would love to be able to see/compare the 3 month animal tox data on Servier's S-18986, Lilly's LY-451395, Organon's Org-24448/CX-691, and Cortex's CX-717. It's hard to imagine any of those other compounds having cleaner tox profiles than CX-717. Of course the FDA probably hasn't evaluated S-18986, since Servier apparently hasn't used it in any US based trials. Lilly's Phase 2 AD trial with LY-451395 was halted several years ago (either by the company or by the FDA, we don't know which). And Org-24448 has been in various trials, a monotherapy Schizo trial (completed/near completed), and now a combo Schizo trial with the NIMH/TURNS which is just getting underway. As I recall, the dosing on the combo trial is at least 3 months, so 3 month tox data must have been supplied to the FDA. Whether or not they actually examined it in any depth (yet) is questionable though.
Pumpers
by: gfp927z 04/05/06 10:19 am
Msg: 27902 of 28164
I can't help but think that some of these breathlessly enamored newcomers are employed by the warrant holders who didn't bail in the $5+ range. I figure probably half or so of the warrant owners were likely holding out for the Shift Work results/BP deal, and now they've become desperate. A large number of the warrants were priced in the $3.25 range, and are thus currently underwater. Pump away guys :o)
Re: Even when we know, we may not know.
by: ruengies3
Long-Term Sentiment: Strong Buy 04/05/06 10:59 am
Msg: 27909 of 28164
gfp,
Understood. Still, as we try to take our best guesses at the most likely impact on pps of the FDA letter, there are some possibilities we can pretty much rule out. As you've written, "It was serious enough in the FDA's view to justify halting the trials." So I think we have to assume it's highly unlikely that following release of the letter, COR (and those of you who actually understand the science) is not going to quickly conclude, "oh, yeah, we can fix that easy," and the price will suddenly soar.
Nor will COR, Neuro, you, etc. be able to quickly conclude, "oh s***, we're dead in the water."
My point then is that it seems most likely to me that either way, after we get the info from FDA, we'll be scratching our heads for a long time, with the result that the real impact on pps will likely be slow to occur (real as opposed to first-day-knee-jerk).
Taking a best guess on this matters because it informs our decisions on how invested we can afford to be as we await the letter.
I say all this to stimulate others' thoughts on the subject.
Re: Pumpers...rather daytraders!
by: gfp927z 04/05/06 11:02 am
Msg: 27910 of 28164
Anyoneofus, Near term, I can't see much of a sustained up move until we get something from Stoll, a conf call. And even if it turns out that there isn't a serious tox problem that jeapordizes the platform, the FDA has drawn its line in the sand, effectively putting Cortex in the FDA's doghouse. Once in that doghouse, it can be tough to get out (as DSCO demonstrated today).
Neuro said that an actual clinical hold by the FDA is fairly rare in the CNS area. The FDA isn't likely to quickly reverse course and suddenly become friendly to Cortex/CX-717. The scene is being set for a potentially long drawn out nightmare. That said, a less than dire conf call by Dr. Stoll next week could cause a nice big up move for the stock. We also can't rule out the possibility that BPs will see that the FDA's toxicity argument is full of BS (assuming that's the case), and decide to go ahead with the BP deal despite the current clinical hold. I just hate to see it when a company I otherwise would like gets on the wrong side of the FDA (as in DSCO, Epix, GTCB, etc).
Re: 10k
by: Neuroinv 04/05/06 11:32 am
Msg: 27914 of 28164
We know that it was preclinical, not clinical information, so it was not a clinical trial procedural issue.
I would not assume that Cortex is now on the 'wrong side' of the FDA. Were Stoll to make premature announcements and, in the FDA's view, take the discussion into the public arena, they would be. But he knows not to do that. I completely agree that the next communication is not going to completely resolve the issue--it will hopefully shed light on the process ahead. So long as Cortex works with the FDA behind closed doors and does what it is told to do, there will be no doghouse. And unless there is some dire issue beyond the level that I am currently projecting, at some point in the next few months the FDA will say that its concerns have been answered (and its tough cop street cred reaffirmed, though not quite in those words) and that the hold has been lifted. BPs may wait for that, but they will also be able--via their confidentiality agreements with Cortex--to have more access to the details. Depending on the content, if they perceive a clear path to putting this behind Cortex, they could pursue a final agreement before the hold is lifted.
But this is a middle of the road projection--no instant solution, no permanent damage. The next public disclosure by Cortex will probably make it somewhat--albeit not completely-- clearer whether it is on target or not.
NeuroInvestment
Here's what happened
by: lillyceo (54/M/Indianapolis, IN) 04/05/06 11:41 am
Msg: 27915 of 28164
We have been trying to pick up rights to the Ampakines for some time now. Unfortunately, the previous Cortex CEO carved up those rights to two other companies in other territories. we want them all and were not getting much co-operation. Compounding the problem further, the current CEO of COR, Stoll is playing hardball and wants more than we're willing to give. Plus, with the recent good results (a surprise to us) from the ADHD trial and subsequent share price appreciation, the price had doubled and new bidders had arrived. The situation was becoming desperate for us.
Then one of my co-horts had a brilliant thought and an ingenious plan was devised. He contacted our agent at the FDA and gave him instructions. The call was made, and the results were beautiful on Monday. No one will touch this thing until the "issue" is resolved. Of course, we know there's no real problem, but thanks to the delay in informing Cortex and it's shareholders the details of the actual issue, speculation is running rampant that there's a serious problem.
This sequence of events has shifted the power back to us and Stoll is much more accomodating now. Sometimes you have to pull out the big guns. We're even getting more co-operation from those accross the pond.
Re: 10k
by: gfp927z 04/05/06 11:59 am
Msg: 27919 of 28164
Thanks Neuro. I'm assuming for now that at the least Cortex will need to do additional 3 month animal testing. I figure this process could take possibly 6-9 months (I assume BPs might also run their own 3 month animal tests).
The best outcome might be if the FDA argument is clearly BS (politically motivated ADHD related butt covering) and not a serious tox problem, the BPs will see right through it and go ahead with the BP deal. Let's hope the tox issue is either minor, or total BS. I'm not counting out the possibility that there is a serious tox issue that could jeapordize the viability of the entire platform however. I wish Stoll could say something before next week, but I guess there wouldn't be much point prior to his reading the full FDA letter.
Neuro, you were right - there's no such thing as a slam dunk in biotech, either clinically or regulatory-wise. The only thing reliable/predictable about this sector is its ability to induce ulcers. It does also have a consistent entertainment value for those with their money on the sidelines. One crazy sector.
Re: The lowest and best COR
by: gfp927z 04/05/06 12:17 pm
Msg: 27923 of 28164
Atshrugg, I'm with you on the corrupt FDA angle. The poster "lillyceo" from a few posts ago was obviously a BS artist, but his Lilly scenario is certainly quite plausible. With BP pipelines depleted and billions in future profits at stake, I wouldn't put anything past BPs. The way the FDA sits as judge, jury, and executioner over the industry, there is certainly the potential for massive corruption.
Lobbying influences on FDA
by: genericpharminvestor (46/M/New York, NY)
Long-Term Sentiment: Strong Buy 04/05/06 12:26 pm
Msg: 27926 of 28164
I have been in the generic development business for 20 years and have had many many interactions with FDA.
Make no mistake about it, the BP's have,and will continue to run interference with any new trials they possibly can in order to delay the furtherance of a program which may ultimately cause competition and/or declining sales for their products.
It is quite blatant, in fact. The worst offender over the years has been BMY, in my opionion, especially on the legal front. What they pay their lawyers to cause generic approval delays pales in comparision to their daily "take" on their Rx product sales. Therefore, their M.O. is always to push the Agency to the absolute limit with frivolous complaints and maneuvers before finally succumbing to threat of sanction.
Now, I have no idea if this is the case with COR, but for sure, it is a possibility, although I tend to believe the sentiment on this board that the Agency is flexing its public cop muscle in the effort to show it's personna on top of the caper for ADHD.
G.
Re: What am I missing? (layman's insigh
by: gfp927z 04/05/06 01:05 pm
Msg: 27928 of 28164
Bf3944, Just to clarify, the shorter term tox studies were done several years ago, being required prior to doing short-term human studies (the longest trial being the recently completed/reported 3 week ADHD Phase 2a study). All last year Cortex also ran longer 3 month animal tox studies in 2 species, which are a requirement for longer human trials of the type a BP partner would want to run (3 month long trials). These 3 month animal tox studies were completed approx late 2005/early 2006 (and took considerably longer than expected for some reason). This data was recently given over to the FDA for evaluation, and presumably it's in this 3 month data where the tox problem was seen that resulted in a clinical hold being placed on CX-717 by the FDA.
preclinical Liver Toxicity must be big
by: moosedogger 04/05/06 01:07 pm
Msg: 27929 of 28165
Here's the FDA's list of 2005 accomplishments by the agency (released last week).
Under the heading "Innovative Technology", they say they:
"....concluded an agreement with BG Medicine, a biotechnology research company, to collaborate on discovering signs of liver toxicity in the initial stages of drug development;....<<
Here's the rest of what they've done for us lately-
http://www.fda.gov/bbs/topics/news/2006/NEW01342.html
Neuro, how bad is bad, how good?
by: ardentmarr 04/05/06 01:41 pm
Msg: 27934 of 28165
The best case scenario is easy enough to imagine and goes something like; the FDA concern is an ensurance question that COR can easily clarify through the data, we move on in trials of our AMPAKINES in style and in riches.
What is the worst? Obviously a worst case involves the end of CX717..or does it? Is that still a possibility after initial success in ADHD and possibly the sleep dep study while the is the first 'concern' raised after all of the initial testing and clearances?
The likelyhood of a worst case scenario seems as likely as the best case scenario, highly unlikely. The simplest delineation suggests some middle ground concern which in turn, suggests CX717 progress is also likely.
This too is speculation, but educated guessing is all we have at the moment.
Re: What am I missing? (layman's insigh
by: gfp927z 04/05/06 01:52 pm
Msg: 27935 of 28165
Kiwi, That's an interesting idea (that the problem with the tox studies could conceivably be that they didn't dose the animals at sufficient multiples to justify using CX-717 at any higher doses than what we've already used, and Cortex/BPs want to go higher with the dose). The problem with this reasoning however is that if this were the reason for the clinical hold, the FDA wouldn't have put a blanket hold on all CX-717 trials, but only on any proposed trials where the human dose would be higher than what we've already done (the highest to date being 800 mg BID). But the clinical hold appears to be across the board, regardless of proposed dosing levels.
So, no the FDA's action had to be related to some other "concerns" that they saw in the tox data itself, not simply that we didn't dose the animals high enough to justify human dosing higher than what we've previously done.
Everybody should call FDA - NOT!
by: genericpharminvestor (46/M/New York, NY)
Long-Term Sentiment: Strong Buy 04/05/06 03:10 pm
Msg: 27945 of 28165
I am qualified to speak with the FDA and I advise against it at this time.
You people not in the industry have a sophomoric understanding of how these things must play out.
I can understand your frustration, but in the big picture of pharmaceutical timelines, 7-10 days is a nanosecond.
Lucky
by: go_cortex_go
Long-Term Sentiment: Hold 04/05/06 03:37 pm
Msg: 27949 of 28165
I just feel lucky for all longs that the FDA call didn't come BEFORE the release of ADHA results.
Can you imagine what would have happened in that senario? We probably might be looking at a penny stock now.
Couldn't complain about the timing.
gcg
Re: What am I missing (repro tox)?
by: jeskell 04/05/06 04:10 pm
Msg: 27952 of 28165
The following 10K section says that COR has initiated reproductive toxicology studies as well prior to ph IIb studies. I agree that it is most likely that some other toxicity (eg liver) is the reason for the hold but is there a possibility that there is something related to reproductive toxicity that is the reason for the hold.
Perhaps the FDA thinks that there may be problems with cx717 with regards to fetal developement or has seen data from other CNS drugs that have problems in this area.
Presumably the repro toxicity studies are with animals at this point so the FDA wouldn't necessarily have put a hold on those trials and I don't think that younger women have been in any of the phI/II trials to date.
From the 10K:
Additionally, we recently completed two separate three-month toxicology studies
for CX717, one with a rodent species and one with a non-rodent species, as
required by the guidelines of the FDA. 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. Full reports for each of these
three-month toxicology studies have been submitted to the FDA for review. We
also initiated reproductive toxicology studies of CX717 that are necessary to
include women of childbearing potential in future Phase IIb studies. We are
planning longer (e.g., six-month) general toxicology studies to support
clinical studies of greater than three months duration.
Re: What am I missing? (layman's insigh
by: Send me a message! horsetrader45
Long-Term Sentiment: Hold 04/05/06 04:13 pm
Msg: 27953 of 28165
Dr. Tracy's educated guess is probably better than most of ours.It's just that over the years that I have been invested in this company I have seen more curveballs than fastballs so I feel that we will probably be surprised again.
Whether its good or bad is anybody's guess.
Andy C.
Thoughts on Toxicology Data
by: sunshinecamesoftly2002 (49/M/nymetro) 04/05/06 06:53 pm
Msg: 27962 of 28165
Considering the Following
1. The purpose of the 3 month toxicology study is to identify possible areas of toxicity by using extraordinarily high dosing of a research compound (CX717).
2. These studies do commonly show toxicity b/o much higher then physiologic dosing used.
3. There is apparent great interest on the part of multiple large pharma in partnering for the use of ampakine technology and specifically cx717 even after their apparent access to the results of the 3 month preclinical animal toxicology data.
I beleive the FDA may just want Cortex to sent up a monitoring program in the human trial to evaluate if the toxicity found at extremely high doses is also identified in provision of physiologic dosing. If this is true...... the hold may not be a serious problem for Cortex.
I am also reassured by the long hx of use of ampakine compounds for over a decade and other than exitotoxicty, not likely an issue here, they have been safe drugs.
sunshine
Re: 10k
by: aiming4_a_million (42/M)
Long-Term Sentiment: Strong Buy 04/05/06 01:21 am
Msg: 27886 of 28163
Gfp - what I was suggesting was that since Cortex has stated that they feel they are making good progress in developing a safe high impact Ampakine, and the calpain/spectrin problem would be most pronounced in a high impact Ampakine, doesn't that suggest that either calpain/spectrin isn't being found/perceived as a problem with the high impact Ampakine or that Cortex has found a way to engineer around it?
And if calpain/spectrin isn't causing a problem in the high impact Ampakine Cortex is developing, it is even less likely to be a problem in a low impact like CX-717?
The devil's advocate argument is that the calpain/spectrin problem perhaps may have just become recognized as a new problem with CX-717, while at the same time Cortex has made progress in mitigating the c/s problem with their high impact Ampakine. .. Aiming4.
Re: Toxicity
by: aiming4_a_million (42/M)
Long-Term Sentiment: Strong Buy 04/05/06 01:29 am
Msg: 27887 of 28163
Neuro - the discussion about liver enzyme changes is, I believe, the first time I've heard this mentioned in regards to Ampakines.
Is there any particular reason to think that Ampakines might be expected to have an adverse affect on the liver?... Aiming4.
Re: 10k
by: gfp927z 04/05/06 01:59 am
Msg: 27888 of 28163
Aiming, The big challenge with high impacts has been excitotoxicity. They have to get past the excitotoxocity hurdle first before worrying about calpain/spectrin, which would become a problem later, once longer term dosing is possible without inducing seizures.
Neuro, It appears that the nature of the calpain/spectrin phenomenon is not even well understood by researchers yet, much less decided upon as a key factor or not for Ampakines. I hope the current problem with CX-717 is something more easily remedied, but we can't dismiss anything at this point. Putting our collective heads in the sand isn't going to make this predicament go away any sooner unfortunately.
Re: Toxicity
by: Neuroinv 04/05/06 01:59 am
Msg: 27889 of 28163
Not Ampakines in specific. High doses of a lot of drugs can do that. It's an experiment one can actually do at home--buy a bottle of Tylenol, take 10-15 of them. That in itself can do permanent liver damage--if you down them with a couple of glasses of wine, near- certain. Get on a transplant list first. Some people have developed liver toxicity with four Tylenols--liver transplant level toxicity.
If Ampakines were prone to liver issues, we would have heard about that long ago--between CX516 and 717, not to mention 691--a couple thousand people have taken human-level doses. It's the dose/duration issue that the FDA is worried about--with every drug they look at. Too bad they don't worry about the ones already available on the shelf.
NeuroInvestment
OT-FDA strikes again
by: oldiesmd2002
Long-Term Sentiment: Strong Buy 04/05/06 08:29 am
Msg: 27891 of 28164
DSCO
http://biz.yahoo.com/pz/060405/96849.html
"Specifically, the FDA is requesting certain information primarily focused on the Chemistry, Manufacturing and Controls (CMC) section of the NDA. The information predominately involves the further tightening of active ingredient and drug product specifications and related controls. Consistent with previous review, the FDA does not have any clinical or statistical comments."
"Our previously submitted responses to the first Approvable Letter were accepted by the FDA as a complete response in October 2005."
Re: 10k (neuro, gfp)
by: gfp927z 04/05/06 09:38 am
Msg: 27896 of 28164
Bupaya, That's actually an old Servier trial (CX-516) that didn't go anywhwere. Their current large MCI Phase 2 is with their own AMPA upregulator (S-18986), a benzothiadiazide. This compound doesn't fall under the original Cortex/Servier licensing agreement, so they would have to do a new/updated agreement with Cortex if they ever want to commercialize S-18986.
I would love to be able to see/compare the 3 month animal tox data on Servier's S-18986, Lilly's LY-451395, Organon's Org-24448/CX-691, and Cortex's CX-717. It's hard to imagine any of those other compounds having cleaner tox profiles than CX-717. Of course the FDA probably hasn't evaluated S-18986, since Servier apparently hasn't used it in any US based trials. Lilly's Phase 2 AD trial with LY-451395 was halted several years ago (either by the company or by the FDA, we don't know which). And Org-24448 has been in various trials, a monotherapy Schizo trial (completed/near completed), and now a combo Schizo trial with the NIMH/TURNS which is just getting underway. As I recall, the dosing on the combo trial is at least 3 months, so 3 month tox data must have been supplied to the FDA. Whether or not they actually examined it in any depth (yet) is questionable though.
Pumpers
by: gfp927z 04/05/06 10:19 am
Msg: 27902 of 28164
I can't help but think that some of these breathlessly enamored newcomers are employed by the warrant holders who didn't bail in the $5+ range. I figure probably half or so of the warrant owners were likely holding out for the Shift Work results/BP deal, and now they've become desperate. A large number of the warrants were priced in the $3.25 range, and are thus currently underwater. Pump away guys :o)
Re: Even when we know, we may not know.
by: ruengies3
Long-Term Sentiment: Strong Buy 04/05/06 10:59 am
Msg: 27909 of 28164
gfp,
Understood. Still, as we try to take our best guesses at the most likely impact on pps of the FDA letter, there are some possibilities we can pretty much rule out. As you've written, "It was serious enough in the FDA's view to justify halting the trials." So I think we have to assume it's highly unlikely that following release of the letter, COR (and those of you who actually understand the science) is not going to quickly conclude, "oh, yeah, we can fix that easy," and the price will suddenly soar.
Nor will COR, Neuro, you, etc. be able to quickly conclude, "oh s***, we're dead in the water."
My point then is that it seems most likely to me that either way, after we get the info from FDA, we'll be scratching our heads for a long time, with the result that the real impact on pps will likely be slow to occur (real as opposed to first-day-knee-jerk).
Taking a best guess on this matters because it informs our decisions on how invested we can afford to be as we await the letter.
I say all this to stimulate others' thoughts on the subject.
Re: Pumpers...rather daytraders!
by: gfp927z 04/05/06 11:02 am
Msg: 27910 of 28164
Anyoneofus, Near term, I can't see much of a sustained up move until we get something from Stoll, a conf call. And even if it turns out that there isn't a serious tox problem that jeapordizes the platform, the FDA has drawn its line in the sand, effectively putting Cortex in the FDA's doghouse. Once in that doghouse, it can be tough to get out (as DSCO demonstrated today).
Neuro said that an actual clinical hold by the FDA is fairly rare in the CNS area. The FDA isn't likely to quickly reverse course and suddenly become friendly to Cortex/CX-717. The scene is being set for a potentially long drawn out nightmare. That said, a less than dire conf call by Dr. Stoll next week could cause a nice big up move for the stock. We also can't rule out the possibility that BPs will see that the FDA's toxicity argument is full of BS (assuming that's the case), and decide to go ahead with the BP deal despite the current clinical hold. I just hate to see it when a company I otherwise would like gets on the wrong side of the FDA (as in DSCO, Epix, GTCB, etc).
Re: 10k
by: Neuroinv 04/05/06 11:32 am
Msg: 27914 of 28164
We know that it was preclinical, not clinical information, so it was not a clinical trial procedural issue.
I would not assume that Cortex is now on the 'wrong side' of the FDA. Were Stoll to make premature announcements and, in the FDA's view, take the discussion into the public arena, they would be. But he knows not to do that. I completely agree that the next communication is not going to completely resolve the issue--it will hopefully shed light on the process ahead. So long as Cortex works with the FDA behind closed doors and does what it is told to do, there will be no doghouse. And unless there is some dire issue beyond the level that I am currently projecting, at some point in the next few months the FDA will say that its concerns have been answered (and its tough cop street cred reaffirmed, though not quite in those words) and that the hold has been lifted. BPs may wait for that, but they will also be able--via their confidentiality agreements with Cortex--to have more access to the details. Depending on the content, if they perceive a clear path to putting this behind Cortex, they could pursue a final agreement before the hold is lifted.
But this is a middle of the road projection--no instant solution, no permanent damage. The next public disclosure by Cortex will probably make it somewhat--albeit not completely-- clearer whether it is on target or not.
NeuroInvestment
Here's what happened
by: lillyceo (54/M/Indianapolis, IN) 04/05/06 11:41 am
Msg: 27915 of 28164
We have been trying to pick up rights to the Ampakines for some time now. Unfortunately, the previous Cortex CEO carved up those rights to two other companies in other territories. we want them all and were not getting much co-operation. Compounding the problem further, the current CEO of COR, Stoll is playing hardball and wants more than we're willing to give. Plus, with the recent good results (a surprise to us) from the ADHD trial and subsequent share price appreciation, the price had doubled and new bidders had arrived. The situation was becoming desperate for us.
Then one of my co-horts had a brilliant thought and an ingenious plan was devised. He contacted our agent at the FDA and gave him instructions. The call was made, and the results were beautiful on Monday. No one will touch this thing until the "issue" is resolved. Of course, we know there's no real problem, but thanks to the delay in informing Cortex and it's shareholders the details of the actual issue, speculation is running rampant that there's a serious problem.
This sequence of events has shifted the power back to us and Stoll is much more accomodating now. Sometimes you have to pull out the big guns. We're even getting more co-operation from those accross the pond.
Re: 10k
by: gfp927z 04/05/06 11:59 am
Msg: 27919 of 28164
Thanks Neuro. I'm assuming for now that at the least Cortex will need to do additional 3 month animal testing. I figure this process could take possibly 6-9 months (I assume BPs might also run their own 3 month animal tests).
The best outcome might be if the FDA argument is clearly BS (politically motivated ADHD related butt covering) and not a serious tox problem, the BPs will see right through it and go ahead with the BP deal. Let's hope the tox issue is either minor, or total BS. I'm not counting out the possibility that there is a serious tox issue that could jeapordize the viability of the entire platform however. I wish Stoll could say something before next week, but I guess there wouldn't be much point prior to his reading the full FDA letter.
Neuro, you were right - there's no such thing as a slam dunk in biotech, either clinically or regulatory-wise. The only thing reliable/predictable about this sector is its ability to induce ulcers. It does also have a consistent entertainment value for those with their money on the sidelines. One crazy sector.
Re: The lowest and best COR
by: gfp927z 04/05/06 12:17 pm
Msg: 27923 of 28164
Atshrugg, I'm with you on the corrupt FDA angle. The poster "lillyceo" from a few posts ago was obviously a BS artist, but his Lilly scenario is certainly quite plausible. With BP pipelines depleted and billions in future profits at stake, I wouldn't put anything past BPs. The way the FDA sits as judge, jury, and executioner over the industry, there is certainly the potential for massive corruption.
Lobbying influences on FDA
by: genericpharminvestor (46/M/New York, NY)
Long-Term Sentiment: Strong Buy 04/05/06 12:26 pm
Msg: 27926 of 28164
I have been in the generic development business for 20 years and have had many many interactions with FDA.
Make no mistake about it, the BP's have,and will continue to run interference with any new trials they possibly can in order to delay the furtherance of a program which may ultimately cause competition and/or declining sales for their products.
It is quite blatant, in fact. The worst offender over the years has been BMY, in my opionion, especially on the legal front. What they pay their lawyers to cause generic approval delays pales in comparision to their daily "take" on their Rx product sales. Therefore, their M.O. is always to push the Agency to the absolute limit with frivolous complaints and maneuvers before finally succumbing to threat of sanction.
Now, I have no idea if this is the case with COR, but for sure, it is a possibility, although I tend to believe the sentiment on this board that the Agency is flexing its public cop muscle in the effort to show it's personna on top of the caper for ADHD.
G.
Re: What am I missing? (layman's insigh
by: gfp927z 04/05/06 01:05 pm
Msg: 27928 of 28164
Bf3944, Just to clarify, the shorter term tox studies were done several years ago, being required prior to doing short-term human studies (the longest trial being the recently completed/reported 3 week ADHD Phase 2a study). All last year Cortex also ran longer 3 month animal tox studies in 2 species, which are a requirement for longer human trials of the type a BP partner would want to run (3 month long trials). These 3 month animal tox studies were completed approx late 2005/early 2006 (and took considerably longer than expected for some reason). This data was recently given over to the FDA for evaluation, and presumably it's in this 3 month data where the tox problem was seen that resulted in a clinical hold being placed on CX-717 by the FDA.
preclinical Liver Toxicity must be big
by: moosedogger 04/05/06 01:07 pm
Msg: 27929 of 28165
Here's the FDA's list of 2005 accomplishments by the agency (released last week).
Under the heading "Innovative Technology", they say they:
"....concluded an agreement with BG Medicine, a biotechnology research company, to collaborate on discovering signs of liver toxicity in the initial stages of drug development;....<<
Here's the rest of what they've done for us lately-
http://www.fda.gov/bbs/topics/news/2006/NEW01342.html
Neuro, how bad is bad, how good?
by: ardentmarr 04/05/06 01:41 pm
Msg: 27934 of 28165
The best case scenario is easy enough to imagine and goes something like; the FDA concern is an ensurance question that COR can easily clarify through the data, we move on in trials of our AMPAKINES in style and in riches.
What is the worst? Obviously a worst case involves the end of CX717..or does it? Is that still a possibility after initial success in ADHD and possibly the sleep dep study while the is the first 'concern' raised after all of the initial testing and clearances?
The likelyhood of a worst case scenario seems as likely as the best case scenario, highly unlikely. The simplest delineation suggests some middle ground concern which in turn, suggests CX717 progress is also likely.
This too is speculation, but educated guessing is all we have at the moment.
Re: What am I missing? (layman's insigh
by: gfp927z 04/05/06 01:52 pm
Msg: 27935 of 28165
Kiwi, That's an interesting idea (that the problem with the tox studies could conceivably be that they didn't dose the animals at sufficient multiples to justify using CX-717 at any higher doses than what we've already used, and Cortex/BPs want to go higher with the dose). The problem with this reasoning however is that if this were the reason for the clinical hold, the FDA wouldn't have put a blanket hold on all CX-717 trials, but only on any proposed trials where the human dose would be higher than what we've already done (the highest to date being 800 mg BID). But the clinical hold appears to be across the board, regardless of proposed dosing levels.
So, no the FDA's action had to be related to some other "concerns" that they saw in the tox data itself, not simply that we didn't dose the animals high enough to justify human dosing higher than what we've previously done.
Everybody should call FDA - NOT!
by: genericpharminvestor (46/M/New York, NY)
Long-Term Sentiment: Strong Buy 04/05/06 03:10 pm
Msg: 27945 of 28165
I am qualified to speak with the FDA and I advise against it at this time.
You people not in the industry have a sophomoric understanding of how these things must play out.
I can understand your frustration, but in the big picture of pharmaceutical timelines, 7-10 days is a nanosecond.
Lucky
by: go_cortex_go
Long-Term Sentiment: Hold 04/05/06 03:37 pm
Msg: 27949 of 28165
I just feel lucky for all longs that the FDA call didn't come BEFORE the release of ADHA results.
Can you imagine what would have happened in that senario? We probably might be looking at a penny stock now.
Couldn't complain about the timing.
gcg
Re: What am I missing (repro tox)?
by: jeskell 04/05/06 04:10 pm
Msg: 27952 of 28165
The following 10K section says that COR has initiated reproductive toxicology studies as well prior to ph IIb studies. I agree that it is most likely that some other toxicity (eg liver) is the reason for the hold but is there a possibility that there is something related to reproductive toxicity that is the reason for the hold.
Perhaps the FDA thinks that there may be problems with cx717 with regards to fetal developement or has seen data from other CNS drugs that have problems in this area.
Presumably the repro toxicity studies are with animals at this point so the FDA wouldn't necessarily have put a hold on those trials and I don't think that younger women have been in any of the phI/II trials to date.
From the 10K:
Additionally, we recently completed two separate three-month toxicology studies
for CX717, one with a rodent species and one with a non-rodent species, as
required by the guidelines of the FDA. 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. Full reports for each of these
three-month toxicology studies have been submitted to the FDA for review. We
also initiated reproductive toxicology studies of CX717 that are necessary to
include women of childbearing potential in future Phase IIb studies. We are
planning longer (e.g., six-month) general toxicology studies to support
clinical studies of greater than three months duration.
Re: What am I missing? (layman's insigh
by: Send me a message! horsetrader45
Long-Term Sentiment: Hold 04/05/06 04:13 pm
Msg: 27953 of 28165
Dr. Tracy's educated guess is probably better than most of ours.It's just that over the years that I have been invested in this company I have seen more curveballs than fastballs so I feel that we will probably be surprised again.
Whether its good or bad is anybody's guess.
Andy C.
Thoughts on Toxicology Data
by: sunshinecamesoftly2002 (49/M/nymetro) 04/05/06 06:53 pm
Msg: 27962 of 28165
Considering the Following
1. The purpose of the 3 month toxicology study is to identify possible areas of toxicity by using extraordinarily high dosing of a research compound (CX717).
2. These studies do commonly show toxicity b/o much higher then physiologic dosing used.
3. There is apparent great interest on the part of multiple large pharma in partnering for the use of ampakine technology and specifically cx717 even after their apparent access to the results of the 3 month preclinical animal toxicology data.
I beleive the FDA may just want Cortex to sent up a monitoring program in the human trial to evaluate if the toxicity found at extremely high doses is also identified in provision of physiologic dosing. If this is true...... the hold may not be a serious problem for Cortex.
I am also reassured by the long hx of use of ampakine compounds for over a decade and other than exitotoxicty, not likely an issue here, they have been safe drugs.
sunshine
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