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The issue isn't timelines--It is whether obtaining the $10 million, essentially a nondilutive financing of sorts, since it was an asset sale--will make a definitive difference. Successful ADHD results would be, but without any previous CX1739 ADHD data, and just a single pilot study for CX717, no one is assuming that. And AMPA is not the ADHD flavor of the month: Nicotinic alpha 7 is. Success would change everything, but they arent there yet. Absolutely no one has any expectations I can discern for sleep apnea. It would probably take surprisingly clean and clear results to capture attention. And I have no idea whether they have pushed the trial this far because 'having gone this far, we might as well finish it' or 'those anecdotal reports make completing the trial a worthwhile gamble.'
NeuroInvestment
FWIW Aiming; While everyone has the right to their opinion; so far as I can tell, people in the CNS area who have an opinion on the Cortex subject, would endorse what you said . The 'trust' issue was put to bed with the RD deal. Missing timelines is the rule rather than the exception in small biopharma.
NeuroInverstment
duplicate
OT: BVF
I was referring to the RD project only--and why that would separate out from SA from Biovail's commercial viewpoint. It has nothing to do with the rest of their portfolio. They're vertically integrated, so everything has a destiny in their marketing schema. AZ004, CX717 will be sold to hospitals. Wellbutrin and pimavanserin, to psychiatrists--maybe neurology if the PD psychosis indication pans out.. Now if their GDNF program ever gets anywhere, that would open up neurology, but that still wouldnt tap sleep labs per se. Fibiger is, as I said, constrained by the exclusion of anything that requires a huge PCP sales force. That leaves plenty of room for flexibility.
NeuroInvestment
If you think this is painful, try selling the company right now. And you seem to be overlooking the fact that the whole point of the RD deal was to give them the money to move ADHD forward. Thus your premise is incorrect.
Gfp: SA does not fit into the Biovail hospital sales strategy for which RD works. But the only absolute at the moment is that they don't want anything that would require a primary care sales force--and even that comes with a 'at least for now' caveat (this is as of Wednesday morning). I think they'd look at SA, at ADHD--because their strategy is to be opportunistic, not to fit a pre-conceived model of what indications to pursue. But everything has to fit the commercial strategy. SA could work. But it depends on what deals have or have not been completed as of the time that this hoped-for SA data comes out, whether they have the resources reserved to do the clinical trials needed for all of them. Would there be a conversation? Absolutely, but they have more conversations in a month than I have in a year.
NeuroInvestment
Getting back to Cortex: I am not spending much time agonizing over what Cortex will do if they have strong SA results. It would be nice to have that problem. The way it would sort out would be: They'd listen to offers for CX-1739. They would quantify what the cost would be to them of not developing and partnering CX-1739 for ADHD, but instead using a backup. Any partnering discussions regarding SA would include--If you want CX-1739, you have to make it worth our while to delay ADHD. They aren't going to divide the molecule by indications. Sometimes companies will divide a molecule by territory, generally licensing out Japan/Asia rights, partly because those markets require local trials, so they arent going to be relying on results from US trials by another licensee.
A more likely alternative would be: Selling an option to license CX-1739. The option would be contingent upon ADHD results. If positive, and in return for an upfront 'retainer', the potential licensee will have the option to partner CX-1739 for both indications for $XX million. There could even be an additional clause for the possible inclusion of sz/dep rights. Look at the AstraZeneca/Targacept agreements around 5619 as an example of deal flexibility.
It would be a nice problem to have.
NeuroInvestment
Rule out whatever you want. You might want do a little reading about the SEC, then get back to us.
NeuroInvestment
A contrary view: I would prefer for management to not buy shares now. Why? Because they can only buy shares if nothing is happening behind the scenes that would be material to the value of the shares. For example, during the drawn-out Biovail negotiations, they knew details of the transaction under discussion that would have made a stock purchase illegal. So I would still prefer that they not buy shares, because it at least leaves open the possibility that they are aware of something pertaining to the SA trial, or the sz/dep rights held by Merck, or something else entirely---that we don't know about. If they buy, it means nothing material is currently in play.
NeuroInvestment
OT: ACAD
Answers:
1) They do not have to produce a single-container combination drug. They could in the future if they want to. This is good news, because it allows psychiatrists to play with dose proportions--AND to use other antipsychotics if they prefer..
2) They do have to run a pimavanserin-only arm. This makes it a bit more expensive and complex. But they don't have to show anything other than its not as good as the combo. The vital thing is for the combo to do better than Risperdal--or for pimavanserin and a low dose of Risperdal do as well as a high dose of Risperdal by itself.
NeuroInvestment
That's my impression--actually it's very clear, if you look at the transcript of Biovail's CEO Bill Wells on their CC. This is not what they expected.
BUT--Even if the worst case scenario applies--single capsule formulation, pimavanserin-only arm--this is still doable. And I don't yet know if either of those is involved.
NeuroInvestment
OT: ACAD
Psychiatrists don't like to have the ratio of drug A to drug B decided by pre-packaging. They like to tweak the balance of dosing, and I think, rightly so--psych patients are so idiosyncratic.
Example: Lilly packaged Cymbalta and Zyprexa together as Symbyax, thinking this would be a good hedge against Zyprexa's patent expiration. Psychiatrists hated it---I talked to a Lilly person last year who told me their Symbyax prescriptions each month were in the dozens.
This pimavanserin news has been out since Biovail's CC, large holders could have dumped already if they wanted to. I've sent a query to someone, the answer will be informative as to just how much of a problem this is. I just don't know yet.
NeuroInvestment
OT: ACAD
Blade:
I had heard that on the Biovail CC a few days ago. I agree it is spin, but I'm not sure at what rpm. There is a whole office at the FDA dedicated to Combination Therapies, so I guess one could argue it's a well-defined path, but I don't buy that there's a clear advantage. Pretty much every epilepsy med approved over the past ten, twenty years has been as an 'adjunct', because they don't dare test them as monotherapies. So the Adjunct principle of 'Does adding Drug B to Drug A produce better results than Drug A alone' seems pretty clear to me. I had thought that it was a higher standard for combination therapy, that one had to show that Drugs A+B together are better than Drug A or Drug B alone. At some point I'll ask whether they have to utilize a pimavanserin-only arm.
If they do require another arm, then this was very high rpm spin.
I suspect that there may be more rigorous drug interaction testing for a combo drug--here is my question, and I havent gotten around to asking yet--will it be a fixed dose combo drug in one capsule (which would then need more testing regarding stability)? If so, the convenience would be offset by the fixed dose element. I'll let you know if I get an answer to that--I'm finishing a 450 page annual publication, so there are a lot of calls waiting to be made.
IMHO There was never a chance of the previous schizophrenia study being accepted as pivotal--it wasn't designed to be, so far as I knew. I always expected there'd be two trials--unless they used the same combo for Parkinsonian psychosis--received approval, and then tried to get a schizophrenia sNDA approved with one additional trial in sz....
NeuroInvestment
No. We're done on this. All relevant points have been discussed ad infinitum, approaching ad nauseum. You flatter yourself with the illusion that you are carrying a torch for righteousness, when in fact you're just looking to set fire to anything approximating rational analysis. I've got better things to do.
NeuroInvestment
I'm not sure if this meets criteria or not. But I had written it, so I'll submit it.
A. Six months ago: Cortex was operating on a month to month basis, the question was raised as to whether they would have to raise money at 5 cents a share, or go out of business. There were those who stated categorically that 'there is no deal'--it's over, gents...
The conclusion drawn by some subset of observers was that this situation reflected a lack of action and/or competence on the part of management, who should be derided harshly.
B. Now, Cortex has a year+ of cash. A possible $5 million milestone a year from now (just my guess), and the ability to run and complete the ADHD trial most of us have been eagerly awaiting for so long. There are wild cards to which no clear value can yet be attributed (SA, sz/dep rights).
The conclusion drawn by some subset of observers was that this reflects a lack of action and/or competence on the part of management, who should be derided harshly.
The difference between A and B is enormous: The difference between being on death's door, versus having control over their own fate, and the ability to obtain the clinical evidence that still stands to bring them the kind of partnership that most, albeit not all, Cortex observers have been waiting for since 2006.
And yet the view, for some, is essentially unchanged. For whatever reason. And it defies any logical analysis of the change of context. It's a waste of time to get into a debate about this. Minds are made up.
NeuroInvestment
OT:ACAD
There's an element of that--the decision to emphasize that over the schizophrenia area is still a little puzzling. But with sz being developed by their partner, PD psychosis is a worthwhile second indication.
NeuroInvestment
OT:ACAD
Blade:
1) They'd need a second successful Phase III.
2) I strongly suspect that Biovail has had input on the redesign--but Acadia carries the responsibility of making the PD trial work, so they have the last word.
3) Uli Hacksell is an intelligent, pragmatic scientist. He and I have a running joke--well, it's a one way joke, Uli is a very serious guy--about his Swedish stubborn streak, which I can comment on, since I'm half Swedish in heritage, and have more than my share of it. It has not always served him well: Even when there was pretty clear evidence that the ACP-104 trial was doomed, Uli steadfastly maintained that it was not--until the data came in.
NeuroInvestment
Did I expect the share price to be higher than its current level, now that they have a year or more of cash, allowing them to reach critical developmental goals--as opposed to being on the brink of death? Sure. But I wouldn't judge it based on the first few weeks--be it Samyang playing around (which I am inclined to downplay as a factor)--or the anticipation of Samyang suppressing the price, leading other to do some selling beforehand, it just isn't that important. We no longer have to assess Cortex's prospects, even for survival, on a month to month basis.
NeuroInvestment
Samyang's US representative, who brokered the financing with Cortex, is someone (no, I had nothing to do with it) whose interests are very much aligned-to use that phrase again--with Cortex shareholders. Whether there was any maneuvering to keep the price within what they would consider an 'acceptable' range, I have no idea. But to the degree to which that individual might have any ongoing input, there would not have been a push on their part to squeeze everything out that they could.
NeuroInvestment
Partly OT:ACAD
Blade:
The funeral was premature. Biovail's response to that trial failure was interesting: They essentially told Acadia that Acadia could continue on with PD psychosis if they want, but if they fail again, Acadia eats the costs. Biovail has taken charge of the schizophrenia program, which does have 'hint of concept' data already--that's where their motivation is focused.
I certainly would not be betting against Fibiger--given his credentials, which you posted. As I noted earlier, I'll be very interested in seeing the protocol they come up with. Down the road, if they can improve the side effect profile of atypical antipsychotics, what they will then want to add to their portfolio, it seems to me, would be a drug that would deal with cognitive/negative symptoms.
Which is why the back story regarding the Merck-held rights for schizophrenia (and for depression, less importantly for the moment), and whether Cortex can regain them, is very much worth keeping an eye on. Not that there will be any comment during the process itself; it falls under the partnering 'cone of silence.'
NeuroInvestment
OT: ACAD
Blade:
Pimavanserin does have potential as a dose-sparing agent in schizophrenia, the target Acadia de-emphasized even though they had some hint of concept for it. They thought of PD psychosis as smaller, more manageable, less competitive. But sz is far larger and more lucrative, that's where Biovail is going to focus and will control clinical development. I'll be interested to see the dosing they choose, I suspect it will be higher than what Acadia utilized. It's not clear what else, if anything, Acadia has of value, but pimavanserin would be more than enough if the sz program works. Acadia's future rests on pimavanserin, just as Cortex's rests on CX-1739.
NeuroInvestment
Briefly (I'm traveling in the service of college tour rituals): Biovail sees exactly the opportunity you describe--using pimavanserin for dose-sparing, side effect reduction. That does not exclude Ampakines or something like them for cog/neg sx.
NeuroInvestment
Thanks for the information. I'm expecting 12-18 months, since they have to do Phase I, then Phase IIa. My guess is that if they decide to skip CX717, that the IV milestone would then transfer over to POC for CX1842. That's just a guess--but generally you don't want to lose a milestone just because a partner skips a step.
NeuroInvestment
Thanks. I'll send you a postcard from steerage.
NeuroInvestment
But it was Cortex being roadblocked by the FDA that provided much of the data that lets us know the circumstances under which the FDA applies roadblocks. At the time Laughren was new at the head of Psychiatry (actually, even having a separate Psychiatry division was new). Stoll 'not being a beginner' is irrelevant: The context itself was changing in ways neither Cortex nor their FDA consultants could predict, and Cortex became a prime Exhibit of that change.
NeuroInvestment
duplicate
Got that 20/20 hindsight working overtime tonight, I see. It's pretty easy to look at 2006 using 2010 knowledge and pretend that things were so clear at the time. Any suggestions on whether I should take a cruise on the Titanic when it makes its maiden voyage?
NeuroInvestment
So long as there is no smoking gun animal finding that could lead to a hearing where Grassley asks them 'how could you have allowed a drug to get through when it did this to (a monkey)'--the FDA will be neutral. They get plenty of flak around the abusability of pain and ADHD drugs, so there is some political pressure to find alternatives.
NeuroInvestment
There is a muddying of distinctions here: Your post supposes that all ampakines are considered to have potential in all these indications. As I have posted in the past, Lynch believes that different ampakines may activate different AMPA receptors localized in different areas of the brain, having different functions. So the class of Ampakines may be relevant to all of these areas, but a single ampakine molecule is (if he is right) not likely to be.
Look at the range of potential indications listed for the nicotinic receptor drugs Targacept partnered with GSK and AstraZeneca. Alzheimer's, sz, dep, ADHD, smoking cessation, pain, Parkinson's....
NeuroInvestment
in general, those parents who are seeking medications for their children with ADHD, who are reluctant to utilize psychostimulants, will not be perturbed by the lack of an Ampakine 'buzz.' It's actually a selling point, due to the lessened risk of abuse. It would allow it to be sold on Schedule IV, where a MD can call in a scrip for months at a time, instead of a psychostimulant's Schedule II, where each month, a new handwritten scrip must be given to the patient/parent.
We are not competing with the 'buzz', we're trying to provide an alternative, one that improves attention and hyperactivity.
NeuroInvestment
I addressed pretty much all of these points during my past few posts.
NeuroInvestment
Is what possible--that Alseres has that much debt? I don't know their debt structure details--I do know that they go on month by month via an infusion of another 500,000-1 million by Robert Gipson, who is approaching being a majority owner. He apparently likes their Altropane Phase III PD imaging program, which is pretty much a waste of time and money. A company's debt overhang becomes critical when the debt comes due--which is why, for example, Epix Pharma went bankrupt last year, and why Elan had to sell a chunk of itself to JNJ.
<<I don't understand why the fear/explanation was; without this deal, Corx was about to go under. These early stage biotech's can trade forever. There will almost always be a route to stay in existence>>
I could list close to fifty private and public CNS companies which have gone out of business over the past six years. If you presume that a company's only motivation is to limp on for the sake of management salaries, I suppose that some find a way to linger. But that assumes a cynical version of reality.
if you want a "serious/competent nearterm driver" for Cortex, there is only one over which Cortex has control, and has a clear reason to anticipate success: ADHD. Any other scenario would involve ]a leap of faith, a hope that events will luckily fall into place. So they had to obtain the resources that allow them to make that happen--albeit without any guarantee of success (probability yes, guarantee no). Playing out the string was a hypothesis advanced by some as a raison d'etre for Cortex, but if you do not assume that would have been sufficient from their perspective, then they had to generate enough cash to make a critical mass event happen. Other things could happen--SA, HI--but ADHD will happen. Whether it turns out in such a way that validates the time and money put into it--we will see when the data comes out.
NeuroInvestment
With all respect to Dew, he has a well-earned appreciation for the efficacy of stimulants for ADHD, as he has discussed elsewhere. But with what I think is an premature dismissal of nonstimulant options. Dew has made the correct statement here in the past that Strattera is not going to be an adequate benchmark for efficacy, Cortex must beat Strattera, the leading nonstimulant ADHD med ($500-600 million sales per year)--because Strattera isnt very good. Even Lilly admits privately it only helps 20% of patients who use it. The only nonstimulant drug added since 2006 is Shire's SR guanfacine, which involves a couple weeks of sedation before it has a beneficial effect. Parents aren't going to like being told: 'Your child will get worse, before he/she gets better.'
Cortex does not have to match stimulants in efficacy--there are still a lot of parents who refuse psychostimulants for reasons that are both good and bad. They simply have to provide a better nonstimulant option, and that should access a market potentially worth in the $500 million range. Will that get them the $50 million upfront that was rumored back in 2006? Probably not: The mean upfront payment for CNS Phase IIa data programs (Hint of concept obtained), 2006-9, was $27.7 million.
My guess is that RD licensing, royalties retained, would have gotten them $3-5 million with that same HOC. An ADHD package will be much closer to that mean cited above. And if they could package sz and dep rights to form a psychiatry portfolio for CX-1739? That would be worth considerably more.
NeuroInvestment
1) 2001-9: 16 discovery stage CNS alliances in my database. Six had upfront payments disclosed, nine had 'total milestones' disclosed (most milestones are never paid, I mention them in that they sometimes sound good in the press release):
Average upfront payment: 30.66 million
Range: 2-65
Average cited milestone potential: 160.8 million
Range 20-359
Closest example:
NeuroSearch/Lilly 2009: $20 million upfront, $320 million potential milestones
That covered modulators of undisclosed CNS ion channels, a NeuroSearch specialty. I suspect that NeuroSearch had more comprehensive IP to include, such as information about the targets modulating these channels, and proprietary methods of measuring drug effects on the channels, beyond the compounds, which may have come from both companies. Based on this, a Cortex deal would probably be somewhat smaller upfront, but there would be annual R&D support payments.
2) If Merck wants to be in the Ampakine field, they need better molecules, Cortex has them. My guess is they do not, and they have nothing to lose by licensing them back to Cortex--for low-mid single digit royalties on eventual products, perhaps. They don't have anything to gain from burying them.
NeuroInvestment
In terms of practical interest, I think you can remove Sanofi-Aventis; Merck (if they were interested in Ampakines, they might show some interest in the ones they already have, and Schoepp isnt an Ampakine guy); Novo Nordisk isn't in CNS; Lilly hasnt done anything in AMPA recently, they went mGluR as well; I don't know about BI, but they appear to be looking elsewhere. Takeda seems highly unlikely. NeuroSearch has so many collaborations going, and is so focused on finishing Huntexil testing, that I think they'd be unlikely as well. AC Immune licensed an AMPA drug partly because they thought the fact it came from the discoverers of Dimebon gave it extra credibility. So much for that.
Servier is most likely.
GSK, Pfizer. Maybe--but Pfizer's new head of neuroscience just jumped ship for AstraZeneca, so they are leaderless and probably fraught with angst about whether to continue the Dimebon Phase III testing.
Dark horse: Lundbeck.
NeuroInvestment
It will probably provide you with a sense of contrarian satisfaction to know that I strongly doubt that anyone in the neuropharm industry would concur with your conclusion that the anticipation of RD royalties in 2016 and onward would provide stronger value enhancement to Cortex's share price than anticipation of, and consummation of, an ADHD partnership in 2011--provided that they show good results in Phase IIa. That is the obvious but crucial caveat.
NeuroInvestment
1) Yes, but he gave the OK to SP running an ADHD trial with Org26576. No artifact=no problem that I would foresee with CX-1739.
2) Cortex was cutting all expenses to the bone--now they have the money to do their compound stability studies. They couldnt afford it before.
3) BTW--I left out Lundbeck from the roster of companies interested in AMPA approaches to sz.
4) I'm not certain which study MV was referring to. Here is a Yale study which used both Lilly and Pfizer compounds to correct working memory deficits associated with the ketamine sz model--I think he was referring to animal data:
<< Behav Brain Res. 2010 Mar 25. [Epub ahead of print]
Prevention of ketamine-induced working memory impairments by AMPA potentiators in a nonhuman primate model of cognitive dysfunction.
Roberts BM, Holden DE, Shaffer CL, Seymour PA, Menniti FS, Schmidt CJ, Williams GV, Castner SA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510; VA Connecticut Healthcare System, West Haven, CT 06519.
Working memory impairments are a core aspect of schizophrenia, yet current medicines do not address such cognitive dysfunction. We have developed a model of these working memory deficits by acutely disrupting glutamatergic synaptic transmission by administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine in the nonhuman primate. The current studies evaluated the effect of positive allosteric modulators (“potentiators”) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the working memory and behavioral effects of ketamine. AMPA receptors mediate fast excitatory synaptic transmission throughout the brain and play a critical role in the activity-dependent regulation of NMDA receptors. We find that positive modulation of AMPA receptors with LY451646 (0.1-1.0mg/kg, SC) and structurally-distinct PF-4778574 (0.01mg/kg, SC) robustly ameliorates ketamine-induced working memory impairments without altering behavioral effects of acute ketamine we consider related to positive- and negative-like symptoms. These results support AMPA receptor potentiators as a potential adjunctive treatment for cognitive impairment associated with schizophrenia (CIAS). >>
NeuroInvestment
I appreciate the thought, Ombow, but my serendipitous meeting with Greer only benefited me in developing my appreciation for the prospects. Greer and Cortex were already either partnered or near signing when I encountered Greer at SFN. Give Jim Coleman credit, for recognizing the opportunity when Greer approached them with his animal data. As to Biovail--to the modest extent to which I facilitated that process, I do take a lot of satisfaction--the right place, at the right time (finally).
NeuroInvestment
I didnt take his response that way--it was more 'why are you taking up time asking a question you know that I am not going to answer?' To which my response would be that, indeed, useful light was shed on that issue a little later in the CC.
The interesting thing about the Merck rights is that they are of absolutely no use to anyone else, there's no market. Only Cortex is bound by their old Organon contract, and none of us know the details of what the partner has to do to sustain their end of the bargain. Everyone else can go ahead as the various use patents expire. So Merck can't auction them off; they don't want them; and I suspect that somewhere in the contract there is language that says that you can't just shove this in the drawer and forget about it. Organon and SP both did clinical trials--if Merck doesn't, at what point can they be charged with 'abandonment?' I don;'t know the answer, and I was not going to run into a stone wall by asking it during the CC. Merck is now going through the programs it doesn't want to keep, and once they decide what goes into the culled pile, then they'll decide what they want to do with the rejectees. Some things they'll try to outlicense, in theory that could include Org26576--but it's not that compound Cortex wants, it's just the right to use Ampakines in sz/dep (although the data might be useful in figuring a strategy going forward).
I think they'll get the rights back, but it's not like there is a lot to negotiate, it's more a case of trying to get Merck's attention ( it occurs to me that sometimes you need an attorney to do that, and now Cortex has the money for one, if they so choose). Perhaps Cortex can promise to pay them a 1% royalty on future sales, so that Merck feels like they get something....
NeuroInvestment
You are undoubtedly correct on the SA issue--there isn't much to lose by waiting it out. But I had heard from a non-Cortex source that fourteen patients had been completed as of mid-January, and if enrollment is now indeed near-standstill; patience just is not my strong suit. I am sure MV would make the same point you did.
Sz/dep: The fact that MV subsequently made reference to trying one of the CX2007 series low impacts in sz and depression confirms that hypothesis. Schizophrenia is the area where cognition enhancement is currently the hottest, and if MV had a molecule that could be used in both ADHD and sz.....If Cortex had a molecule with HOC/POC in both ADHD and sz....that would be quite the scenario.
Biovail has to contend with the same trial design and execution issues that Cortex did, but they have the benefit of all Cortex's data and travails. They have to do IND-preparation, safety testing--I'm not sure how far along Cortex was with the IV form of CX717, which has not been in humans. I'd put this one into the 'maybe twelve to eighteen months' category unless and until I get some clarification from Biovail. They are also trying to work on another trial for pimavanserin in sz, plus prepare a Phase II for their GDNF/CED in Parkinson's, so RD may not be their number one priority. But they need to sort out which molecule they are going to emphasize for RD, so they need to figure out whether they run with CX717 IV or not....
I'll probably ask them in a couple months, when the smoke clears from their hyperactivity.
NeuroInvestment
You're right, some of the individual investors asked some excellent questions.
Re: High impacts.... He mentioned Pfizer himself, so that's an obvious one. GSK has an Ampakine in PhI, sz is their first emphasis. Servier could be the most likely, most desirous (not desirable, but they may offer more money)--since they may see a couple Big Pharmas getting ahead of them in an area they have long-pursued.
Cypress Biosciences ran a study a few years ago with Organon, testing Remeron in-if I recall correctly--a combination therapy in sleep apnea. They did a pretty large study, and the combination failed. It was a serotonergic strategy, like the one BTG is pursuing with a combo treatment.
His point was that if you just have people be pre-screened, then do one sleep study night, then have some treatment for a month or two, before coming back for a post-drug sleep study, it's a lot easier than a trial where they have to do three sleep study nights in quick succession. Of course, it also means that patients with a lot of inherent variability can get into the trial, which can muddy the results. So did the combo fail because it doesnt have an effect, or because the effect was obscured by SA variability? Vivus also ran their SA study this way, extended duration, indeed they had to, since it was the loss of weight that most likely caused the apnea episodes to diminish. And that trial did work.
So instead of using rigorous screening to give the study some power, you can increase treatment duration and the sample size to try to do the same thing. They couldnt afford to run a 200pt study with CX1739.
My only area of disagreement with their plan, which I think is well done, is that I'm not sure I'd drag out the SA study longer. Fourteen patients over fifteen months--I'd be sorely tempted to break the blind now and see if there's a signal....if you can't see anything at 14, will you be likely to see much at 20?
All in all, it sounds to me like they've thought it all through very thoroughly. Even the willingness to wait on relisting rather than going for it ASAP suggests that they have a very logical sequence in mind. SA is still the wild card. But ADHD is the most probable driver of value. Had they demanded royalties on RD, maybe they would have gotten $3-4 million upfront, which would have precluded doing the ADHD study without another financing. An ADHD partnership in the next 18-24 months trumps royalties in six or seven years so far as impact on Cortex's valuation is concerned.
NeuroInvestment