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Bladerunner, OT - Concerning Satraplatin, I understand that the FDA is now questioning the validity of the endpoint itself used in the Satraplatin trial, with the FDA now saying that they previously expressed concerns to the company over the unorthodox endpoints. But did GPC have an SPA agreeing to those endpoints prior to the trial?
Ampakineman, The whole market's getting trashed lately, and small cap biotech has been weak for a while also. Cortex is starting to look more interesting to me though. I think Neuro's optimistic conclusion is likely correct - that the dose liberalization for AD PET likely signals further liberalization coming all around. Whether it's a strong signal or merely suggestive is of course debatable. Before "taking the plunge" again, I'd like to see more confirmation that higher dosing will be allowed for longer term studies and not just for a one day PET study. Other current uncertainties were/are the potential warrant share "unlocking" overhang, and now a somewhat wobbly general market. But "In chaos there is opportunity", right? Ah, the joys (and ulcers) of investing..
Jerry, If you're out there, any thoughts on the bio sector generally, and the current market overall? The global markets have been storming ahead for a year or so, with only a few pullbacks which quickly reversed. Do you see the current overall market downturn as temporary, or a prelude to more downside in the months ahead?
I thought this histo/artifact dosing business with Cortex would be resolved by now. Any near term plays you're looking at currently? In addition to Cortex, I've been looking at ArQule, Biomarin, Lifeway Foods, and SGX Pharma. I nibbled on each briefly, but then luckily unloaded the next day. Several of those stocks already had nice moves, but they appear to have run their course near term, and the general market appears to be deteriorating. I may just concentrate on Cortex until we get our pop. Any thought on support levels / entry points, from a technical perspective?
Tonyvanw, Since Neurology originally put the clinical hold in place, and then partially removed it last Fall with the dosing restrictions, shouldn't it first be Neurology to officially remove/reduce the overall dosing restrictions, not just for the AD PET trial as they have done, but generally? Then, based on that decision by Neurology, Psychiatric has to decide on the specifics of the proposed ADHD trial IND protocol.
What I'm trying to figure out is if once Neurology completes their review, Cortex will get an additional confirmation from them that removes/reduces the dosing restrictions generally (beyond the AD PET liberalization) - a development that would be material and require a new press release. Or will we just get a single press release when the IND is filed with Psychiatric, with a blurb included saying that everything is cool with Neurology (though perhaps without specifics)?
The timing of one's reentry into the stock will depend on the above. The scenario I'd rather not see would be if Cortex says nothing further about Neurology's final decision, and then just puts out a press release announcing the filing of the IND with Psychiatric. In that case we're left in the dark as to what Neurology's final ruling was, and we have to presume that the dose was sufficiently liberalized but we won't know that for sure. We'll only know it was likely favorable enough to justify Cortex's filing of the IND, but we won't know if the dosing limits were removed entirely, partially, modestly, etc.
Money4, Since Neurology hasn't yet completed their full evaluation of the tox data (as per the recent press release), I was just wondering if there will be another press release coming prior to the filing of the IND.
Another point about the Phase 2b IND protocol is that the Pharma who ultimately gets CX-717/ADHD may decide to file different Phase 2b INDs of their own anyway, and perhaps more than one (once/day dosing, BID dosing, various patient subsets (inattentive with/without hyperactivity), etc). So the Cortex IND may represent more of a general blueprint for the ultimate Phase 2b. What Cortex's IND approval means to investors though, symbolically, is that any remaining doubt about CX-717, its ability to be partnered, and indeed about Cortex's future as a company, are dispelled for good.
I wonder if after they complete their review, Neurology will give a final official decision to Cortex relating to the histo/artifact issue that will necessitate a separate press release from Cortex? Or perhaps that news will be combined in the press release announcing the filing of the IND with Psychiatric? Or perhaps the IND filing press release might not actually mention the details of Neurology's decision (it being assumed to be positive)? It would be nice to know some of the details of Neurology's dosing liberalization as early in the process as possible (BID and once/day dosing levels allowed, duration length of trial allowed, etc).
Or is Neurology only going to rule on the histo/artifact issue in general terms (thumbs up or down), with the actual dosing limit details left up to Psychiatric for ADHD, or to either division when additional INDs are filed for future indications?
Baal, Having the IND approved by Psychiatric will also be a major event. Cortex should hear more from Neurology over the next month also, since Neurology is still in the process of reviewing the tox data. Concerning when the IND for ADHD will be filed, in his NI update Neuro said - "Now Cortex can complete the IND application to Psychiatry--probably around the end of summer." <<<
Baal, First Cortex has to file the IND for the ADHD Phase 2b with the Psychiatric Division (hopefully filed by end of August or so, just a guess), then wait approx 30 days for a response (or if no response after 30 days, the IND is automatically approved as I understand it). Then Cortex has the choice to run the Phase 2b themselves, or license CX-717/ADHD to a BP. Odds are they'll license it to BP. A BP deal for CX-717/ADHD might conceivably occur around late '07/early '08, then it's up to the BP to do the Phase 2b and beyond.
Nerdseeksblonde, Thanks for the article. I hadn't realized that blocking the NMDA receptor could *increase* the activity of the AMPA receptor. It would be interesting to find out more about that mechanism -
>>> "It turns out that blocking NMDA increases the activity of another receptor, AMPA, and that this boost in AMPA is crucial for ketamine’s rapid antidepressant actions." <<<
Ombow, Concerning CX-717 and AD, it could possibly help alleviate memory loss in AD patients. It would likely be a palliative type treatment (like the current AD drugs), temporarily treating the symptoms. High impact Ampakines, on the other hand, hold the potential for strong disease modification - halting or even reversing the disease process, due to their upregulation of brain neurotrophins (BDNF, NGF, etc).
The way things are shaping up, CX-717 appears destined for the ADHD indication. For it to also be used for AD would require the licensing BP to also acquire Cortex's global Neurodegenerative rights in addition to the ADHD rights. Of course if a different BP gets the Neurodegenerative rights, they might conceivably also deal for a different low impact like CX-701 or CX-1501, in addition to the high impacts. Then that BP could run both high impact and low impact AD trials.
Moose, A BP will likely be the one to run the ADHD Phase 2b, and they'll have the resources to run a whole series of studies exploring both once/day and BID dosing at numerous dose levels, to find the optimum dosing regimen. It would have been nice to already have run a 500 mg BID cohort in the Phase 2a, but my concern at that time was that if 800 mg BID wasn't well tolerated, we'd wind up with no useful data from the trial. Luckily it was well tolerated.
Concerning the MTD, they ran the single dose up to 1600 mg and BID up to 800 mg, and called those the MTD's. But they never did get any serious adverse events, only things like headaches. They probably could have gone higher, but at that time I think they thought they'd never need to approach those doses therapeutically in humans anyway.
Moose, Neuro could better answer that one. I assume they run preclinical animal studies similar to those done for a single drug, but instead use several drugs in combination to look for combined tox effects, drug interactions, etc. One would think that running these type tests would be a good idea if they see a chance that CX-717 might be useful in that particular 3 way drug combination.
Namenda is more appropriate for later stage AD though, since the idea is to reduce glutamate toxicity/excitotoxicity that may be starting to occur once the disease has progressed (cellular destruction bringing about calcium imbalance at the synapses). Using an Ampakine (glutamate receptor (AMPA) upmodulator) in combination with memantine (glutamate receptor (NMDA) antagonist) might be contraindicated, theoretically at least.
It turned out that all 3 of those Phase 2a trial designs were flawed/potentially flawed to some degree, but lucky for us the ADHD trial worked out. My concern there was the lack of an intermediate dose cohort, since 800 mg BID is the BID Max Tolerated Dose, and one might have expected side effects/a high dropout rate. Luckily, 800 mg BID was well tolerated and the resulting data was excellent. The DARPA trial and the AD PET trial both turned out to have key design flaws, but at least we hit big with ADHD.
Moose, I think that just means the patients are taking an ACHase inhibitor (not that their AD condition had necessarily "stabilized" due to the effects of those drugs).
As we know, the main problem with the original design of the PET trial was that it didn't take into account that most AD patients would soon be taking Namenda in combination with the ACHase inhibitors, and Cortex hadn't done the preclinical work that would have been required to use an Ampakine with that combination. Also, Namenda is a glutamate antagonist (at the NMDA receptor), so using it with an Ampakine might not make much sense (theoretically at least).
Dew, Any thoughts on the activity with Barr today?
>>> Option traders turned their attention to the biotechnology industry amid speculation that private-equity buyers might be sizing up Barr Pharmaceuticals <<<
DFRAI, By any chance have you been able to verify that article/report recently posted on SGXP over on Yahoo? Howard Liang is with Leerink Swann. Any idea if the poster on YH has been a reliable source of info? Thanks.
It wouldn't be surprising to see some C-met deals coming. I recently started nibbling on both SGXP and ARQL, and figure that even without an imminent deal, they're likely good long term holdings.
>>> ARQL-OP-bet you see a decent trade in the stock in the next few weeks. Howard Liang expects SGXP (not rated) to announce a partnership on their preclinical C-met inhibitor this summer. Hearing there are 10 term sheets out for SGXP drug and shaping up to possibly be the richest preclinical biotech deal ever. ARQL's ARQ-197(c-MET inhib entering ph 2-pancreatic cancer mid:07) is currently partnered only in Jap. Expect the SGXP deal to significantly raise awareness of c-MET class and could be 9 bidders walking away from bidding looking to license a c-MET. T =$12. <<<
Ampakineman, I didn't mean to antagonize Neuro, only to point out what I saw as a disconnect between the info in the press release and his optimistic analysis. He has far more experience with how the FDA works, and fwiw I think in the end his conclusion will turn out to be correct. Being long a stock big can't help but affect one's judgement though, and from my experience the tendency is to get into a Pangloss "best of all possible worlds" mode that can be dangerous. The worst thing for a stock board is to have it turn into an "amen" echo chamber. We need to be continually critical of our assumptions, especially with so much money riding on the outcome.
OT - BTW, Anyone out there following the Satraplatin saga? Looks like it's getting interesting, with more fireworks to come. For pure entertainment value there's nothing quite like a binary event :o)
Money4, Neuro may not be trying to intentionally pump the stock, but when I read his commentary I couldn't help but think his views seemed heavily one sided, for whatever reason. Sorry about that, but that was my take so I said so.
I happen to agree with Neuro that the AD PET dose liberalization likely indicates a further liberalization coming across the board, but there are some sound arguments against assuming too much/too soon, so I presented them. No offense intended toward Neuro.
Horselover, I'll be the first to admit that I'm not always right, but I'll continue to keep a critical eye on this and any other stock I have interest in. Continual reevaluation of our assumptions is critical. Sorry for being a pain in the a**, but ideally there needs to be a counterbalance to rose colored optimism.
I'll go back on my medication now :o)
Ombow, I've got a bunch for the long haul that I've identified, dozens actually, both bio and non-bio. However I still need one more large 50% winner first, in order to be in a position to diversify properly. There are 5 stocks I'm currently looking at that might fit the bill (near term 50% potential) -
1) Cortex - this is an obvious choice. A 50% move would be to the mid-$4s, which should be easily attainable once we know CX-717/ADHD is going to happen.
2) Biomarin - a near term 50% might be a stretch, but their PKU med Kuvan is up for FDA approval in Q4, with extremely good chances. I figure the stock could move up to the mid 20s from its current 18 on that news. There is some uncertainty after that however, as they have some cardio related trial results in 2008 which could be dicey. They already have 2 drugs on the market though, ramping up revenues. Two hedge funds have reportedly taken a 5%+ position in Biomarin recently, and the company would be an attractive buyout candidate (one of their approved drugs is a 50/50 venture with Genzyme). I've been following them for almost as long as Cortex, though not nearly as closely.
3) ArQule - the C-Met cancer area is hot and will likely get hotter, and ArQule's compound is more selective than those from some competitors. The stock has had a nice pullback/consolidation and looks poised for some gains in Q3/Q4. A move from the current high $6s back up to the $9-10 area would give the 50% return.
4) Lifeway Foods - The only non-bio on my short list, they are a small co (mkt cap ~200 mil) but are the dominant player in their dairy related health food niche (including Kefir, their flagship drinkable yogurt product). They bought out their only real US competitor in '06. If all goes well I figure they have 5-10 bagger potential over the next 5 years. Dannon has a 20% stake, and Lifeway could eventually get bought out. They're growing fast, and are currently doubling their production capacity. The stock had a recent big move, and has so far stayed stubbornly high, so finding a good entry point may be a challenge.
5) ? Mystery Bio Company ? - This one is a thinly traded microcap, so I'm not going to mention it until I have my position. They've had a recent up move and I'm waiting for a pullback.
A few longer term plays -
1) Medarex - I don't see them moving up 50% in the near term, but longer term they look like a no-brainer. At last count there were 34 drug candidates in clinical trials using a Medarex MAB. They could eventually get bought out like competitor Abgenix did.
2) GTCB - the US regulatory road ahead may be rocky for a while, and could induce some ulcers for investors along the way, but this could be a long term 10+ bagger. This is one of Dew's favorites.
I have several dozen more like Sigma Aldrich, Elbit, etc. One of my favorites, a gambling stock called Penn Gaming, unfortunately just got munched before I could take a position.
Another, Alnylam, just got a huge BP deal for their RNAi technology, before I could get a position. Hopefully a win with Cortex will help fund some long overdue portfolio diversification :o)
Thanks Ombow. A conference call will be great. Thanks again :o)
Neuro, You've said that Cortex is your largest position, and of course you've been touting it for years in your NI publication. It would be perfectly understandable for you to be rabidly pro Cortex since it's in your financial and professional interest.
You have more access to Cortex's mangement than any of us here on I-Hub. I just thought you may have heard something from your contacts at Cortex that made you so extremely confident in your NI update. To me your conclusions seem to go way beyond what's in the press release.
Neuro, I take it you spoke to someone at Cortex after the press release came out?
Thanks Ombow. Yes, the longer view is the preferred approach. I'm still trying to amass enough funds to be able to diversify and take the more sensible longer view. I think I've gotten past "bet the farm on one stock", and have now graduated to a "bet the farm on 3-4 stocks" approach. Success there will hopefully enable a much broader long term strategy. Of course with a bio stock it's tough to be long term under even the best of circumstances, since a clinical/regulatory landmine can go off at any time.
Here's the recent NI update that was posted on I-Hub earlier this week (see below), including such phrases as - "clean bill of health", "everything one could ask for", "as good as it could get", "most excellent news", "there is not a more valuable partnership/licensing/acquisition target in the CNS space than Cortex represents at this point." I've been accused of occasionally pumping, but I'm just an amateur. Just kidding Neuro, but you have to admit it does seem a little over the top based on the limited info in the press release :o) -
>>> Neuroinvestment: COR has "clean bill of health"
new posting: FDA Decision Announcement revised 7/19/07)
The FDA decision was everything one could have asked for--a release of the dosing restrictions on CX717. At this time, the only trial within the Neurology section's purview is the Alzheimer's study, and they have OK'd all the dosing range Cortex wanted to use in that trial. That's as good as it could get. The dosing range for ADHD has not yet defined or applied for yet, to an entirely different section of the FDA (Psychiatry), but this opens to door to 1200mg, which gives them enough 'headroom' for a full Phase IIb in ADHD as well, though this will require submission and approval of the IND by Psychiatry this quarter. The current maximum preclinical tox exposure is 3 months, which will be the framework (depending on how much of a buffer Psychiatry wants) for determining how long the ADHD study can go for. The PR's reference to completing the tox review is in our opinion a formality--'we'll let you know if we have any questions, but what we have read is sufficient to tell us there isnt a toxicology/safety problem here, go ahead'. Now Cortex can complete the IND application to Psychiatry--probably around the end of summer. We expect that the IND will be approved, albeit perhaps with a modest limitation (4 or 6 weeks) on the duration of dosing.
This is enough to allow not only the Alzheimer's trial to resume in full--but more importantly, represents the 'clean bill of health' that is needed for the ADHD partnership discussions to go ahead.
This is most excellent news for Cortex. Given the inflation of deal valuations seen of late, the prospects for an Ampakine deal may well involve terms that could exceed those that might have been obtainable last year. The next 2 to 3 quarters will be fun to watch indeed. There is not a more valuable partnership/licensing/acquisition target in the CNS space than Cortex represents at this point. <<<
Bladerunner, Well, the crux of things is Neurology's view of the histo/artifact issue. If they've signed off on that not being a problem, then we're likely in the clear all around. Their liberalization of the AD PET dosing is suggestive that they're leaning that way, but not conclusive (since the phenomenon only occurs with long term dosing, and the AD PET trial is short term dosing).
If Neurology has effectively given the "clean bill of health" for the histo/artifact issue generally, then everything else should fall into place - longer term dosing, Psychiatric's decision for ADHD IND, etc.
Dr. Tracy's NI update seemed in my view "over the top" optimistic, and I assume he's spoken to Dr. Stoll or someone at Cortex since the press release came out (he posted that he had made some phone calls). If Neurolgy has indeed given CX-717 a "clean bill of health" vis-a-vis the histo/artifact issue, it would be nice for us commoners to find out too, if not officially then via a wink/nod type confirmation.
Ombow, I guess a simpler, more direct way to ask my question would be -
Do you have reason to believe that Neurology has effectively laid to rest the histo/artifact issue (laid to rest sufficiently to likely allow longer term dosing at higher dose levels)? Or does Neurology's dose liberalization for the single day AD PET study still leave unanswered their stance on the histo finding/artifact issue (since the artifact phenomenon only occurs with longer term dosing)?
In other words, have we indeed gotten a "clean bill of health" from Neurology vis-a-vis the histo/artifact issue?
Thanks again Ombow.
Hi Ombow, I was wondering if you might be able to use your informal access to Dr. Stoll via email to ask him a brief question? I was interested in getting some idea on how confident he is at this juncture that *longer term* dosing at the higher dosing levels might be allowed by the FDA (not for any particular indication, just generally). The press release info is limited to Neurology allowing higher doses on the one day AD PET study, but does he have reason to expect/conclude they may also allow higher levels for longer dosing periods?
What I'm trying to get a read on is whether Neurology has concluded (or is leaning that way) that the histo finding/artifact issue is no longer an obstacle to allowing *longer term* dosing at higher levels.
While he may not be able to say anything more than what was in the press release, I figure it can't hurt to ask. Even a vague reassurance would be helpful for us "Corheads". Thanks Ombow!
Patco, "The stock moved up and down like a sweaty porno
star."
I'd like to use that as the opening line in my novel about bio investing :o)
MarketFest, >>> "there is no advantage to holding the stock when a warrant holder can participate in any upside by simply holding the warrants" <<<
Or they can just excercise the warrants, sell the stock, take the $1+ per share profit, and move on. Hopefully many/most will see the potential for further upside and sit tight with the warrants. The presence of the warrants does represent a pps barrier, until we get a massive move up on heavy volume. Hopefully once all these warrant shares are cleared out someday, we won't have to do any more financings with warrants attached.
Thanks Neuro.
Novice787, Concerning the outstanding warrants, here's a general overview -
PIPE #1 (8-03) ~3.3 mil warrants, exercise price $2.55. Last I checked there were ~1.8 mil of these remaining, though more have likely been excercised since then. I'll have to check the latest SEC filings for the exact amounts left.
PIPE #2 (1-04) ~4.5 mil warrants, exercise price $3.25. The last I checked there were ~3.9 mil of these still outstanding, but the figure has likely changed since then.
PIPE #3 (12-04) ~2.1 mil warrants, exercise price $3.00. Last figure I have was 1.77 mil remaining.
PIPE #4 (1-07) ~3.26 mil warrants, excercise price $1.66. These are the ones we have to worry about at the moment. Can be exercised starting 7-22-07. As you can see, these are well in the money. I'm not sure exactly how long after the excercise that they can be sold, immediately or perhaps several days? I'm not sure.
Neuro, Concerning Org-24448 and the TURNS trial - you heard that the reason for the decision was "there was some other animal tox issue"? I don't like the sound of that, considering what we just went through with Org-24448's sister compound CX-717. Any additional grapevine info on what type of animal tox issue? Thanks!
Alertmeipp, Thanks. The question I'd like to ask Dr. Stoll is whether he has had any indication from Neurology if they might allow longer term dosing at the higher levels, for something like a 6 week AD trial for example, theoretically speaking. I realize an official IND would need to be filed for Neurology to respond to, but perhaps the Neurology Division has informally indicated to Dr. Stoll that they would generally be amenable to allowing a longer term trial at higher dosing. If this would be the case, then we would have a defacto complete lifting of the dosing restrictions for long term dosing, at least from Neurology's perspective for indications under their purview. That would be plenty evidence for me to extrapolate a likely lift from Psychiatric for ADHD (from a bio-wagering perspective).
Neuro, Just wondering what you make of the comment in the press release that "additional requirements may be requested by the FDA"? By "requirements" could they mean the FDA may conceivably want even more tox studies? Thanks.
>>> "Cortex will continue to have further discussions with the DNP regarding the previously submitted toxicology package and additional requirements may be requested by the FDA." <<<
Enemem, Yes, that makes sense, and is basically Neuro's argument too. Another view (from the dark side) :o) could be that the FDA might be planning to shoot down longer term dosing and is throwing Cortex a consolation bone with the AD PET decision. But there goes my oveactive imagination again. Yes, neurotic is an accurate description, but being paranoid has gotten me this far in bioland with increasing success. Or maybe it's just been luck (probably).
Truth be told, I've about had it with large scale bio betting anyway. The bio sector will quickly wipe out anyone who isn't at least moderately paranoid. I really can't describe large scale bio-betting as fun, unless one enjoys ulcers and sleepless nights. I can't wait to be able to get back to a more diversified approach. One reason I'm so frustrated is that I just want this whole Cortex uncertainty over with - enough already. Looks like another several months to go though. I don't know how some of you guys have been with this stock for 10, 15 years. 5 has been more than enough for me thanks.
Well 15th post of the day, so see ya'll later..
Neuro, I just don't see how you can draw that conclusion so confidently since it requires a considerable leap of faith. Your argument appears to rest on the presumption that the FDA wouldn't have liberalized the AD PET dose unless they were also planning to liberalize the dose all around, the rationale including various FDA public relations perceptions related to their thoroughness and safety, etc as you elaborated in a previous post. That's fine, but face it, the conclusion involves a leap of faith, so presenting it as a virtual done deal sounds a little bit like one of my ill advised slam dunk pronouncements. That said, I think you're conclusion will turn out to be correct BTW.
Neuro, >>> Where he and I parted company was ... that there is still a hold or dose-limit in place. <<<
How can you say that there isn't still a dosing restriction in place for long term dosing when the FDA hasn't yet given the OK for higher long term dosing?
Aiming, >>> *if* what the FDA determined was that the histo problem was caused by fixative and was an artifact, doesn't that decision clear the way for trials of any length? <<<
Yes, it should, but we don't know that Neurology has come to that conclusion yet. They may have, or are leaning that way, etc, but liberalization of the PET study dose is only suggestive. "Circumstantial" evidence I suppose would be the legal term.
Aiming, The press release said that Neurology hasn't yet completed their full analysis of the data. They could allow dose escalation for the AD PET study prior to deciding on the histo finding issue because the histo finding/artifact phenomenon is technically not an issue for a one day study. What would be an issue for a single day study was getting the dose multiple significanlty higher in the repeated acute animal tox studies than what had been initially been reached, and Cortex successfully accomplished that.
That said, Neuro's point about Neurology allowing any dose liberalizations at all if they weren't strongly leaning toward giving CX-717 a totally clean bill of health all around makes sense. The thing is, it's tea leaf reading, and we seem to be doing way too much of that with this stock for my taste, especially considering that Murphy seems to be Cortex's middle name (as in Murphy's Law). So I remain cautious.