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Dew, Dr. Tracy's many subscribers (a large number are Pharmas and institutions) don't subscribe for his price forcasts, but for his extremely detailed overviews and updates of the many neuro programs going on in the various neuro indications. To get some idea of the depth/breadth of these summaries, check out the March issue on Schizophrenia, which is available on his website in its entirety -
http://www.neuroinvestment.com/archives.html
Aslan, Here's an additional article on the deactivation vrs desensitization topic.
http://jpet.aspetjournals.org/cgi/content/full/303/3/1075
We may want to move further discussion over to the I-Hub Cortex board.
Aslan, From what I've read, there does seem to be some overlap between the deactivation and desensitization mechanisms, depending on the particular compound/compound family. Some articles (see link below) have discussed how Cortex's Benzamides act primarily via slowing receptor deactivation, while Cyclothiazide/Benzothiadiazides act primarily by inhibiting desensitization with only a small effect on channel deactivation. Other articles have indicated that within a compound family like Cortex's Benzamides, there is a range, with some compounds acting chiefly via deactivation, and others via a combination of deactivation and desensitization.
http://molpharm.aspetjournals.org/cgi/content/full/64/1/5
When considering seizure potential, in additon to the deactivation vrs desensitization mechanisms, the other related factor is the binding site where the particular compound acts. The high impact site where Cyclothiazide binds has been definitively located, and we now know that Lilly's LY-404187 (a Biarylproylsulfonamide) and Cortex's CX-614 (a higher impact Benzamide) also bind at this same high impact site.
Exactly how the deactivation/desensitization factor relates to the high/low impact binding site factor doesn't appear to be clear however (ie - whether action at the low impact site is primarily via deactivation, while at the high impact site is primarily via desensitization?)
One thing that is clear however, is that low impacts like CX-717 have shown virtually no excitotoxicity potential at all in the clinic, even at very high doses. The high impact approach has been problematic though, not only for Lilly (they halted their AD Phase 2 with LY-451395 last year reportedly due to excitotoxicity problems), but also preclinically for Cortex. According to Dr. Lynch, Lilly's Biarylpropylsulfonamides act at the high impact site in a massive way at very low doses, producing huge increases in currents in the cell. Cortex has been working diligently to produce a high impact with acceptable safety characteristics, and should have a lead compound ready to go into tox studies around year end or so.
One question I have is whether the excitioxicity induced by the high impact compound is itself triggering a protective neuronal response (the elevation of neurotrophins/BDNF)? If so, then some degree of excitoxocity would be a prerequisite for upregulating BDNF, and the trick will be to induce the excitotoxicity in a gradual way over a wider dose range.
Dew, Your chemistry quiz answer is - Zyprexa (thanks to Biowatch for the hint :o) They call Zyprexa "achiral", but looking at its structure, it isn't superimposible on its mirror image. Perhaps they mean that in the production of Zyprexa, only the one enantiomer is produced, so there's no need for separation (?)
Aslan2772, The low impact variety of Ampakines (CX-717, CX-691/ORG-24448) have extremely low excitotoxicity potential, even at very high dose (CX-717 hasn't shown any excitotoxicity potential at all). Excitotoxicity has been a problem with the high impact compounds being developed by competing companies however (Cyclothiazide derivatives, Biarylpropylsulfonamides). High and low impacts act at different binding sites on the AMPA receptor. The high impact site appears to be extremely sensitive (particularly to Lilly's Biarylpropylsulfonamides), so these types of compounds haven't had the level of dosing flexibility that would be required of a therapeutic drug. Also, high impacts like Cyclothiazide derivatives tend to act primarily by inhibiting receptor desensitization (which induces excitotoxicity) rather than by inhibiting receptor deactivation (a mechanism which induces less excitotoxicity).
The super-safe low impact compounds like CX-717 improve cognition and memory. The more problematic high impact approach (which strongly upregulates neurotrophin levels) will be needed for indications like Parkinson's, where neuroregeneration is the goal. For the high impact approach, the trick will be to find compounds that can induce excitotoxicity gradually enough, over a sufficiently wide dosing range, to allow for some dosing flexibility.
Whodaman, Concerning the Cortex board - Yahoo has apparently had a technical problem.
Here's a link to the list of Lilly's clinical trials -
http://www.lillytrials.com/initiated/tas/initiated_cns.html
Rusbrn, It looks like LY-2140023 is a mGlu2/3 agonist (metabotropic glutamte receptor agonist), as opposed to Ampakines/AMPA Receptor Potentiators which are allosteric modulators of ionotropic glutamate receptors (AMPA receptors being a type of ionotropic glutamate receptor). Here's an excellent link which summarizes the different types of glutamate receptors -
http://www.bris.ac.uk/Depts/Synaptic/info/glutamate.html
One thing that struck me in viewing the list of Lilly neuro related clinical trials is the abundance of ADHD trials (20 trials), and lack of AD trials (only 1). They also have 10 Schizo related trials and 7 Depression related trials listed (some recruiting, some finished recruiting).
Dew, I see that Effexor is also a racemate, but it's probably still the wrong answer. I'll have to cheat now and search around the web to find out. Let me see, Epogen, Procrit, Zyprexa, Lipitor, Zocor, Norvasc, Plavix...
BTW, Isotechnika might be a company to check out further. I saw it mentioned in the news today, and I remember doing some DD on it several years ago (Icebrg/Erik from over on SI Investor had mentioned it back then as an promising company).
Dew, I think the answer to your chem quiz would be Prevacid, which is a racemic mixture as I recall (with Nexium being the later single enantiomeric version).
So do I get a prize? How about a few more stock tips (solid long term small/mid caps to hold for the next 5 years) Thanks :o)
Dew, I did some DD on Nuvelo last year, attracted by the presence of George Rathman who previously cofounded Amgen and Icos. I remember ARC-183 was early stage and seemed like a somewhat bizarre technology, being a piece of DNA that would bind directly to thrombin (?) I didn't get deep enough into researching the company to really understand how the approach worked however. What put me off Nuvelo was that their lead program Alfimerase (a thrombolytic clot dissolver) had to be administered via catheter directly to the site of the clot, which I thought sounded too complicated to be practical. Maybe I'll check them out again.
Dew, Yes, GTCB's very high risk doesn't come from the science as was the case with PARS and CTIC (clinical efficacy or lack of efficacy of the drug), but instead from the reluctance of politicians and regulatory bureaucrats to stick their necks out unnecesarily. By approving the world's first transgenic drug, they are putting their own necks on the chopping block if something goes wrong down the road. In a Mad Cow/SARS world, fear and perceptions can have more weight than logic and science. In such an environment, approving this first transgenic protein is a huge step, and the approval will open the door for many more drug products derived from animals. It's only natural for regulators to err on the side of extreme caution when making such a decision. They really have nothing to gain by rushing the decision, and a lot to gain by stalling as long as possible. Seeing that GTCB is such a tiny company with very limited resources, the regulators could easily just delay until GTCB runs out of money - then the regulator's problem goes away. While this underhanded scenario may not come to pass, I wouldn't put it past the buggers to try it.
All I'm saying is be careful not to put TOO many eggs into the GTCB basket. Odds-wise, one would have to say that it's probably 2 to 1 that there will be additional delays. It would be different if GTCB had plenty of cash to wait out the process, but I wonder just how long can they hold out financially.
Dew, Medicis has had a fine track record over the years, but I've been concerned about their recent entry into the breast implant area, due to the potential for lawsuits down the line. As a small part of a larger diversified portfolio, I figure it's still a good stock to own however.
Dew, I wonder what's going to happen now with GTCB? Are you still balls to the wall with that stock? I was tempted to nibble a little as a very short term trade, but thought perhaps the rebound this time might be muted. I guess you're a lot more of a gunslinger than I am. Be careful - remember what happened to PARS and CTIC.
Aiming, FWIW I added a few more names to that list of bio stocks for the longer term, bringing the total to 15 stocks - Kos Pharma, Idenix, and Medicis. Owning smaller positions in many different bio stocks has some definite advantages.
Bocephus, At the Sept 8th Roth Conf, Dr. Stoll said there should be an interim analysis of the AD data in around a month. No additional details were given, but from my notes I see that Cortex is presenting at an AD conference on October 6-7, so perhaps they'll present some interim data then. The enrollment has apparently gone a little slower than expected, but the trial only has 12 patients plus a number of age matched normal controls, so it shouldn't take very long. It's a 3 period crossover design, comparing 2 doses of CX-717 given as a single dose (200 mg and 600 mg) with placebo. Outcome measures are PET scans measuring regional changes in glucose utilization rates in the brain, plus a fairly comprehensive battery of neuropsychometric tests to see if we can pick up on these single doses any difference in performance on drug relative to placebo.
It's already been clearly demonstrated that CX-717 causes increased glucose utilization in the hippocampus and cerebral cortex in Dr. Deadwyler's primates, so there is good reason to expect good results in the PET scan portion of the human study also. The only real question in my mind is how much measureable cognitive improvement a single dose of CX-717 will bring about. I would have preferred to see a multidosing study over several days, since that would have provided more useful data, but if we get at least some indications of improvement from a single 600 mg dose, that will be a good sign.
Aiming, I've been waiting for a retracement in COR (a reload opportunity), but so far no luck. Without the Yahoo board available, the numerous bashers who always show up ahead of clinical results haven't been able to disseminate their usual fear/doubt. We've got to get the Yahoo board operational soon! :o)
If Swissi was around, he'd undoubtedly be fretting over the extremely narrow Bollinger bands, with much angst and handwringing. The stock has been stubbornly resistant to any movement in either direction. I have my modest core position, but have been planning to reload sometime prior to the AD results in October. We need another Canadian fund dumping type event to get us down near $2 again, otherwise I'll just start buying again gradually over the next few weeks.
Some issues I see -
1) The timeline slippage of Shift Work into early 2006 might possibly hold up a BP deal, although on the other hand, it looks like ADHD is moving along well, with results on track for year end. Of the two indications, Shift Work may matter less to BPs, since they already have the good Sleep Dep data to look at.
2) The cash situation will start to get really tight around Feb/March however (Dr. Stoll said approx $14 mil remaining at year end, so I figure we probably drop under $10 mil around March). I still think a pre-BP deal PIPE would be a good idea, giving us more leverage with BPs, and hedging against the possibility of ambiguous ADHD results. At the last Conf call, Dr. Stoll flatly said no to a PIPE in 2005 however, so perhaps it might occur in early 2006. Trying to negotiate a deal as critical as this one while running on fumes doesn't seem like a prudent idea.
3) Will BPs demand both CX-717 and CX-727, or only CX-717? Neuro discussed the possibility that a mid-tier BP might only require CX-717, while a large BP would probably insist on having both compounds. This is actually a very important consideration, since not having CX-727 available will add considerably to the time delay of getting into the clinic with the in-house program.
4) The lack of a compelling orphan indication. This has been bothering me for some time, since Frag-X would probably be better suited for a higher impact, and memory loss post-ECT has always struck me as a somewhat screwy indication. Narcolepsy would be the best, but as Neuro has pointed out, a BP won't cede control of that indication (though perhaps a mid-tier might?), and the trials required would be larger than I had previously thought, since Provigil is already approved for the indication. I'm not sure what the solution here is. I just don't like the indications that are available for in-house development very much. Of course, a buyout would solve that problem nicely, but the "Balkanization" of the Ampakine rights (especially Organon's) complicates that scenario.
Anyway, I've now assembled modest long term positions in 12 small/mid cap bio stocks. Here's my updated list of the "dirty dozen" - Atherogenics, Biomarin, Celgene, Cortex, Cubist, Discovery Labs, Exelixis, MGI Pharma, Pain Therapeutics, Protein Design Labs, Senomyx, and Vertex. These modest/medium size positions I plan to just hold on to for the long haul and not trade (might have some additional shorter term trading positions in these stocks from time to time however, while maintaining the core position). For exposure to larger bio/pharma companies (Genzyme, Gilead, Teva, Sepracor for example), I may just use a mutual fund.
OT, Article - Psychopaths may make the best financial traders -
http://aolsvc.news.aol.com/business/article.adp?id=20050919144609990015
AlohaDan, Yes, from the recent Conf calls it sounds like they're getting the manufacturing issues straightened out, and the CEO seems very knowledgeable. They're based very close to where I live, so I may drive over and check them out. The company certainly seems worthy of a medium size/modest long term position.
Rstor1, Thanks for the list. Also, anyone out there following Atherogenics (AGIX), Exelixis (EXEL), or Discovery Labs (DSCO)? I've done some early DD, and they have been mentioned as potential buyouts targets. Any opinions appreciated. Thanks.
Aiming, SCGator, Thanks. Yes it's odd since all the other boards I follow on Yahoo are functioning normally.
I've been trying to keep up to speed on more stocks lately, plus digging into some new ones. The next "big" news for Cortex should be the interim AD results in October. The PET scan portion of the study should be a slam dunk (relatively speaking), since we've already seen clear increases in regional brain glucose utilization in Dr. Deadwyler's primates. The only real question will be how much cognitive improvement a single dose of CX-717 will show in the battery of cognitive psychometric tests they'll also be giving. The high dose is 600 mg, so there's a good chance of seeing at least indications of cognitive improvement after a single dose, which when combined with the PET scan data should give BPs some idea what CX-717 can do. I personally would have preferred seeing the trial designed to have dosing for at least several days or a week.
So it looks like the plot thickens for GTCB. I wasn't that surprised over the additional 4 month delay, since I always considered continued regulatory foot dragging to be the primary risk with the stock (made more serious by the company's lack of cash). At least they did raise some additional money over the summer, which turned out to be a wise move. There's a chance that GTCB could tank under a dollar, as happened earlier this year, followed by a decent rebound. Trying to catch that rebound might be something to consider, although for me that would violate one of my basic trading principles - to never short term trade a stock that you aren't willing to own for the longer term (since if the trade goes badly you're stuck with it). I'm just not willing to own GTCB through the entire regulatory process, so I probably won't try to trade it. After the last big drop under a buck, GTCB came roaring back quickly, but this time the rebound might be considerably less vigorous.
Aiming, Have you had trouble posting over on the Yahoo board?
I haven't been able to get a message to post over there for a week or so. Just curious if you've had the same problem.
Dew, PGS, Thanks for the input. Martek, Imclone, and Kos all look very interesting. Thanks for your opinions on Celgene (I only have a very small position). I've been trying to diversify.
As you said, mid-caps with products on the market and in late stage trials should be the place to be right now. That BP repatriated money needs to go somewhere, plus BPs need to replenish their pipelines. Do you think the bigger names like Genzyme, Gilead, Sepracor, will eventually be in play as takeovers, or are the smaller mid-caps like Imclone the better bets?
Any additional mid-cap names you or other posters could mention for further DD would be appreciated. Thanks again.
PGS, Just wondering if you still like Telik's chances with Telcyta and Telintra?
Dew, board, OT - I've been looking for some new long term ideas and was wondering if anyone would care to list a few of their favorites for the long haul (not trading stocks, but small and mid-caps you would put away untouched for 5 years or more).
(So far my list includes - Biomarin, Celgene, Cortex, Cubist, MGI Pharma, Pain Therapeutics, Protein Design Labs, Senomyx, and Vertex). GTCB could be included if they can successfully get through the regulatory process. Any other ideas? Thanks.
BTW, another company mentioned in that article which you might want to check out is Protein Design Labs, which I also have a long term position in. They have the potential to be a great long term holding.
Just to update the clinical timeline for Cortex, based on info from the 9-8-05 Roth Conference presentation -
AD trial - Interim analysis in October.
ADHD trial - Results approx year end.
Shift Work trial - Results in early 2006.
Aiming, By the way, if you get the chance, you might want to update the regulatory timetable posted for Cortex on I-Hub. The updated timeline based on info from the recent Cortex presentation is -
1) An interim analysis of AD data in October (instead of data in September).
2) ADHD results by year end.
3) Shift Work results in early 2006.
Aiming, Nice article. That's the first article I can remember mentioning Cortex as a takeover play (other than Dr. Tracy discussing that possibility in his NI newsletter). I'll have to check out the other stocks mentioned in the article. I already own a few they mentioned - a decent position in Cubist, and a smaller one in Vertex.
Looks like Celgene will get a boost today from the FDA panel vote on Revlimid. I generally try to avoid cancer stocks, but have a small position in Celgene. Some others I own modest long term positions in include Biomarin, MGI Pharma, PTIE, and Senomyx.
If you haven't seen it yet, Dr. Tracy has his March issue on Schizophrenia available in its entirety on his website. I tried to post a link over on the Yahoo board but something seems to be amiss with Yahoo lately. The Schizophrenia issue is an excellent overview.
I'm actually thinking about taking a VERY small token position in GTCB. I figure it might dip before the October deadline which could give a good entry point. It's so cheap and the upside is potentially so massive that one has to consider owning a little (plus if they're successful, Dew can't say I missed the boat entirely :o) Another regulatory delay is quite possible however, and it doesn't look like the company's finances will allow for much more waiting.
Aiming, I'm not going to go hog wild with PTIE, but I figure a medium sized position makes sense. Still, I don't want to be in it with much when the IBS results come out.
With the trial results coming so close together, I figure they should be able to release whichever one they want to first. If the SEC was to ever question the timing, PTIE can say for example that even though the IBS trial completed first, the Oxytrex trial was easier/quicker to analyze since they already had previous experience from the first Oxytrex trial (or some similar explanation). The time required to analyze the data for the different trials gives them a lot of leeway.
Logically, one would expect the good results first, since that should greatly overshadow the bad results that followed. The sigh of relief from good Oxytrex results will be huge, and the stock could conceivably double from its extremely low valuation. Bad/mediocre IBS results coming the next week might not have that much downside effect since most people gave IBS little chance anyway, and who cares when you've now got Oxytrex "in the bag". They could do it the other way around, but good first seems more likely. Of course BOTH results might be bad, so another way to play it would be to wait and then buy super cheap, placing hopes solely on Remoxy. I'm not going to go hog wild with a huge position either way after watching what happened with PARS, CTIC, Elan, etc. The only stock I have enough confidence in to get in really big is Cortex, and then just as a trade associated with clinical results. The key risk is no BP deal and a PIPE/in-house Phase 2b, which wouldn't be all that bad in the grand scheme of things (especially if the alternative is say getting only $25 mil while losing both CX-717 and CX-727). I have a decent position in Cubist, which even after the runuup still looks undervalued. My days of loading up to the max on one stock are gone however (except short term with Cortex, and then only if I can get a really good entry point). PTIE as part of a diversified bio portfolio makes sense.
Aiming, PTIE is actually very tempting, since it's so ridiculously cheap, and Remoxy and Oxytrex both have decent chances of ultimately reaching the market. I actually began establishing a position about a week ago, figuring there could be a modest bounce on the Remoxy news (which I thought would come out later in the month, but instead came a little early). I figure Remoxy has a good chance, and Oxytrex has a reasonably good chance too, which combined with the ultra-low valuation could eventually make PTIE a homerun stock.
A key factor in deciding when to buy though, is whether the IBS results will come out before the Oxytrex results, or vice versa. At Friday's presentation, Barbier said that Oxytrex enrollment had been completed back in Q2 (I must have missed that original PR, though I remember the completion of IBS enrollment was announced 6-21-05). He also said on Friday that they expect to have Oxytrex results in Q4 "sometime between Thanksgiving and the year end holidays", and IBS results "toward the end of this year".
The way I figure it, they'll probably release data first from whichever of the two trials was successful (assuming one of them is successful). So if one likes Oxytrex's chances (as I do, to a reasonable degree at least), it's probably safe to start buying PTIE over the next several months. Then, after the big move up on good Oxytrex results, one could unload to avoid the negative reaction to the bad IBS results (though if Oxytrex results were good, people won't care so much about IBS). Then one could reload again for the longer term (or else just do a 1/2 long, 1/2 trading position approach). If they decide to release whichever trial results were good first (which would seem logical), then that considerably lowers the risk of being blindsided by bad IBS results.
Anyway, that's my take. Getting even one approval (say Remoxy or Oxytrex), would make this is a billion dollar company (over a triple from the current valuation). And the science here, while clever, is not of the exotic variety that captures the imagination but has a low probability of success (gene therapy, cancer cures, etc). This looks like a good long term bet IMO, and worthy of at least a modest/medium size position.
OT - Aiming, Here's a link to a Low Dose Naltrexone related site. They have some very interesting info which may help us in figuring PTIE's chances in their IBS trial -
http://www.lowdosenaltrexone.org/
The NY physician who has been dosing his autoimmune, cancer, and HIV patients with Naltrexone has apparently seen excellent results using 4.5 mg of Naltrexone, which he has found to be the optimum dose. He's dosed many autoimmune patients (among them 400 with MS), plus 300 cancer patients, and 350 HIV patients with seemingly outstanding results (I say seemingly since these are not controlled studies - no blind / no placebo control. Sort of like PTIE's IBS pilot study you might say, only on many more patients). He saw maximum activity at 4.5 mg, with a therapeutic range of 1.75 to 4.5 mg of Naltrexone. He notes that doses under 1.75 mg may be too low to produce any effect at all, and doses above 4.5 may begin to block endorphins for too long and interfere with its effectiveness.
PTIE's PTI-901 is only a 0.5 mg dose of Naltrexone, so a potential key problem for PTIE's IBS Phase 3 trial could be that they're dosing way too low - far below the therapeutic dose as found by the NY physician. Of course we don't know the actual dose PTIE is using in the Phase 3, but unless they're giving 3-9 pills per day, they may be underdosing bigtime. So this is another reason to be highly suspicious of the IBS trial.
Thanks Dew. Yes, the IBS indication looks like a real bio graveyard. My strategy with PTIE will probably be to wait until after the (likely bad) IBS trial results are out of the way, and then re-evaluate the chances for Remoxy and Oxytrex.
Good luck with GTCB in October. These high risk binary events are definitely not for me anymore. After narrowly dodging the PARS and CTIC fiascos, I've become a lot more risk averse. It's fun to watch from the sidelines though.
Aiming, OT - One of the reasons for the low valuation of PTIE appears to be a general lack of info/guidance from the company. Part of this is probably due to having 3 different programs going at once, but also there aren't enough Conf calls, and not enough time in the Q+A portions of Conf calls to get the detailed trial info/details out to investors (or maybe we're just spoiled by Dr. Stoll, who stresses the technical aspects in great detail, perhaps to a fault). And at investor conference of course, the Q+As aren't usually webcast to the general public at all. It could also be that Barbier prefers not to discuss the details, since it would reveal the lack of normal-sized Phase 2s (IBS), the somewhat unorthodox design of Phase 3s (Oxytrex), the lack of proper drug formulation (Remoxy), etc. In any event, while the very low stock valuation translates potentially into a huge upside for the stock (an easy double/triple), as an investor it's very difficult to figure the odds without having adequate information.
On the surface, Remoxy would seem to be very low risk, but as far as I can tell, Barbier hasn't really explained to investors what the regulatory pathway to approval is (the nature of the 2nd Phase 3 for example). He apparently suggests that they are in discussions with the FDA about getting an SPA established for Remoxy, but there is skepticism about this. The other big question mark creating uncertainty around Remoxy is the lack of info on its formulation, which apparently is still being changed even though it's in Phase 3 (what the heck is that all about?). No one (at least on the Yahoo board, for what that's worth), seems to know much about the subject, and Barbier apparently hasn't explained what's going on.
The bearish view of this lack of communication from the company is that they might want it that way, to cover their tracks and downplay shortcomings in trial size, design, drug formulation, etc.
I don't know. It's tempting to own some PTIE stock for when the Remoxy Phase 3 results come out sometime in September, but I'm not sure these results will be all that surprising (against placebo). I may decide to just wait til later in the year, until after the (hopefully) disappointing IBS results, and then re-evaluate the situation. Then you might be able to get in in the $4s. I have at least a reasonable amount of confidence in Oxytrex, and Remoxy looks like a very likely winner (need to get answers to the re-formulation question though). Ah, the joys of biotech investing ...
Aiming, One lesson from the PARS experience is to never put a large amount of faith in a small Phase 2 study, and PTIE's IBS study wasn't even a Phase 2 but only a self described "pilot study" of 50 patients. And it was open label to boot, which would tend to maximize the already high placebo effect, since there was no doubt in the patient's minds that they were getting the active drug. There was a reported 76% response rate (this figure was based on only 42 patients however). What we need to find out is what the placebo response rate has been for other IBS trials (we know it's high, but how high?). Even if the typical placebo response rate turns out to be in the 50% range however, we still can't trust the 76% PTI-901 figure as being reproduceable in the Phase 3. In my mind, there's no way to justify placing a sizeable bet on PTIE based on the IBS indication. If the IBS results are inconclusive or outright bad however, which is quite possible, then it could provide a good buying opportunity if one believes in Remoxy and/or Oxytrex.
Dew, Board, Just wondering if anyone has previous experience following Irritable Bowel Syndrome clinical trials? I understand that the placebo effect is very high in IBS trials generally, since the condition apparently has a complex etiology, and a high psychological component. Anyone have experience following this indication? I'm trying to get an estimate on what the typical IBS trial placebo response rate might be. Thanks!
Aiming, OT - Concerning PTIE, I'm still getting up to speed on the company, so I may just sit it out for now. The company's PR from June 8th says the top line Remoxy results will be released in the 3rd quarter, ahead of schedule, so that would be by the end of September. Problem is, that trial was against placebo, so the results aren't going to be particularly revealing (pain med vrs sugar pill). On the other hand, there does seem to be an amazingly high placebo effect in these pain trials generally, as evidenced by the Oxytrex Phase 2 (where placebo reduced pain by 21% vrs Oxycodone's 24%), and the 1st Oxytrex Phase 3 (where placebo reduced pain by 32% vrs Oxytrex BID's 43%). Even considering that, these first Remoxy results should hardly be in doubt, so the market reaction to their release may be muted. The bigger question is what type of trial will the 2nd Remoxy trial be - against Oxycodone/Oxycontin, or against placebo again? One would expect it to be against Oxycodone/Oxycontin, but apparently the company hasn't revealed anything yet about the design. Either way though, Remoxy does look like an eventual "slam dunk" (relatively speaking). I just wonder how much pop there will be from these 1st Phase 3 results. The gnawing concern over the upcoming IBS and Oxytrex results may continue to overshadow any momentary positive feeling from these rather meaningless Remoxy results.
The IBS and Oxytrex results will be exceedingly important though, and based on them, the stock will either skyrocket to the heavens, or plunge into the sea. Looking at these -
IBS - This IBS study is against placebo, and in the earlier pilot study, they reportedly saw a 76% response rate. Sounds good, but the red warning flags are abundant here -- 1) There was no real Phase 2, only a VERY small pilot study (50 patients), 2) that study was open label. The high placebo effect reportedly seen in IBS trials generally is a big concern. I'm going to do some additional digging to try to determine just how high the placebo effect has been in previous IBS trials with other drugs. Of the three indications, IBS easily looks the most risky.
Oxytrex, The comfort here is that in the Phase 2, Oxytrex BID reportedly reduced pain by 40%, vrs 24% for Oxycodone, and 21% for placebo. Sounds good right? Problem is, the Oxytrex BID cohort had a considerably higher dropout rate for some reason (45 out of 103 patients) vrs Oxycodone (32 out of 104). That left only 58 patients remaining in the Oxytrex BID group vrs 72 in the Oxycodone group. That difference *might* conceivably have contributed to the favorable outcome for Oxytrex BID. Also, this was a relatively small trial. The other obvious question in the Phase 2 was why Oxytrex didn't show any improvement in side effects over Oxycodone (however this could have been partly due to the short duration of the trial - only 3 weeks). Then there's the 1st Oxytrex Phase 3. The pain relief was supposedly equal, but it really wasn't - Oxycodone was actually somewhat better with 47% reduction vrs 43% reduction for Oxytrex BID. Seeing approximately equal pain relief would actually be expected, since the trial design allowed patients to titrate themselves until they were comfortable and free of pain. The company stressed the fact that the Oxycone BID patients only had to titrate themselves with 34.7 mg vrs 39.0 mg for Oxycodone, but they choose to ignore that the pain reduction for the Oxycodone group was 47% vrs 43% for Oxytrex BID (preferring to call pain relief "the same").
I don't know, I'm getting some PARS/CTIC-like vibes here, so I may just take a wait and see approach. Remoxy looks like the clear winner, but I'm not sure its Phase 3 results (against placebo) will be enough to dispel the pervasive angst over the upcoming IBS/Oxytrex data. That said, the upside is truly gigantic if either the IBS or Oxytrex data is good (but then it also depends on which comes out first). Caution and a modest position might be in order here. (Unless of course you name is DEW, in which case go ahead and make a huge bet on a phenomenally risky stock - balls to the wall! Yahoo!! (Of course I'm just kidding DEW, you would NEVER do that would you?) :o)
Aiming, Dew, OT - Just wondering if you've seen the Smith Barney analyst comments/info on PTIE? You can get them for free by registering on the Smith Barney website, or I could e-mail them to you if you're interested.
My interest in PTIE is being rekindled as we approach year end. As you know, PTIE will be reporting the top-line results from their 3 different Phase 3 trials over the next 4 months. Along with GTCB (the high risk there being regulatory/political), PTIE seems to be among the most hugely undervalued late stage companies out there. The market cap is only around $275 mil, with 3 programs targeting large ($Bil/year) indications about to report Phase 3 results, and approx $80 mil in cash.
The Smith Barney analyst's comments are worth checking out if you haven't seen them. They bring up some critical issues I hadn't previously been aware of.
Aiming, Just to update the clinical trial calender you posted for Cortex's Phase 2a trials -
1) AD trial results should be in September.
2) Shift Work results by year end.
3) ADHD trial results in early Q1 2006.
Dew, The new thread is the same idea with some fresh input. BTW, you might want to reconsider Senomyx, the creator of taste modulators and flavor enhancers. Not quite as boring/mundane as we thought -- they just signed another collaboration, and the stock has been on a tear (I sold way too early, as usual). The stock is probably overvalued at the moment, but they could be a company with staying power, or even a munch candidate for a more traditional food additive company. Also, any thoughts on Cubist? Their pipeline is thin, but Cubicin looks like a big winner, and they've been mentioned as a potential takeover target. I know you don't like Pain Therapeutics, but Oxytrex and Remoxy appear to have decent/good chances of being approved, and the stock looks hugely undervalued. I'll be watching GTCB closely this Fall, though they still seem like a very risky choice with their cash depleted and further delays quite possible.
Dew, Just wondering if you have any ideas on potential takeover candidates? There's a new munch thread over on SI -
http://www.siliconinvestor.com/subject.aspx?subjectid=55818