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Blade
I'm traveling for a couple weeks, but i cansaythis:
1) Acadia did a great job with pima.
2) i know Allon very well, just had them present at a meeting i chaired, yesterday. The premise is good, a big pharma told me the allon molecule went thru their lab, and 'did everything they say it does.' But it isneurodegeneration/neuroprotection, and those scenarios have disappointed so often. On seat-edge from now tilyear-end.
NP
I am as well. My focus of late has been on other neuro events, but it is frustrating that Cortex could not get a receptive audience for their psychiatric/neurology assets. And based on my own experience in talking with companies, that says much more about the pharma industry than it does about Cortex. Once you get typecast, it's extraordinarily difficult to be perceived differently.
The same frustration is also true for the Respiratory Depression angle that they are trying to sustain. Every time I see another headline about the hazards of painkillers, I think about the potential for a combo analgesic/Ampakine--but partly because of the FDA being difficult about combos, no one has taken the risk--well, Biovail might eventually have approached that solution, but Valeant didnt want to be in the drug development business.
But because that need still exists, and no one has come up with a better idea, I'm still watching.
NP
You and Gfp are correct. Other than being broadly related to the glutamate system, the iGluR (of which AMPA receptors are one subset) and mGluR systems are very different, the latter working 'downstream' via second messenger pathways.
But it should also be noted that Merck, known to be very interested in mGluR strategies, had partnered with Addex on a mGluR4 program in Parkinson's, and then dropped the partnership late last year.
NP
OT: Intellect Neurosciences
I talked with CEO Daniel Chain in May at a conference, and he told me that they were shifting their emphasis from amyloid antibodies to tau antibodies (to which he refers in the PR). Their business model thus far has been establishing IP regarding targeting specific areas of beta-amyloid with antibody, then selling licenses to that IP to pharma. This IP will undoubtedly be for sale as well, but the market will be very limited; those who are not already pursuing mAbs for beta-amyloid are unlikely to jump in at this point.
NP
I don't know if there are any specific limitations to this grant, and there may be other people reading this thread who have hands-on knowledge of this, I do not.
But if you look at NIH regulations, they tend to allow a wide swathe of expenses--so long as they reflect a pro rated calculation of the amount attributable to the NIH project in specific (they differentiate between project-specific direct costs, e.g. the Phase IIb for dronabinol itself, and general 'indirect' costs). There are some exclusions--e.g. construction cannot be covered, and some salary cap limits. But with dronabinol going into Phase IIb, and CX-1739 waiting for its own funding, I think it's likely that a healthy chunk of Cortex's operating costs can be covered by the grant.
NP
From an investor and corporate recovery point of view, I'm satisfied that it is the best option available, and certainly beats the most likely alternatives, bankruptcy or a minimum price fire sale of assets. I had briefly noticed Pier Pharmaceuticals a couple of years ago, back in the Biovail era, but hadnt paid any attention since. The use of dronabinol (synthetic THC) in sleep apnea is something I have not looked at--yet. But the fact that they have a NIH grant of "almost" $5 million gives it some credence, most importantly, with the financial community. This should make it easier to obtain financing going forward for the CX1739 program.
Rebranding as a 'brain-based' respiratory disorder company is necessary. Cortex as a neurology/psychiatry company is seen as an old, even ancient, story, and I have been repeatedly frustrated by pharmas of various sizes whose thinking about Cortex became frozen with the safety signal from the high dose CX717 animal testing. This has been exacerbated by the fact that every Big Pharma exited from Ampakine-type compounds because they could not figure out the chemistry that would give them enough of a safety margin, and they figured if Lilly and Pfizer and Merck couldnt do it, why should they believe Cortex? And Cortex hasnt had the money to prove their merit. Servier's continued activity is irrelevant to the pharma perspective.
Perhaps Cortex will eventually consider changing their name to fully rebrand themselves, though they are now going to be playing to a relatively new audience once they have new Phase II data for CX1739 and/or dronabinol. I still think that a combo opioid using CX1739 would be a very useful approach to reducing opioid-induced RD. But I haven't been able to sell the concept to a couple of companies that should have been interested, and neither has Cortex. More data will help.
I am disappointed that the Ampakines never got a full shot at psychiatry/neurology. But nonstimulants in ADHD are less of an opportunity than they seemed to be seven years ago, and Shire has thrown guanfacine-SR into that niche. Schizophrenia, in terms of negative/cognitive symptoms, may be effectively addressed by nicotinic alpha 7 and glycine site modulators. Alzheimer's, with all the problems attached to mABs, may have its symptoms addressable via nicotinic alpha 7 (EnVivo) and 5HT-6 (Lundbeck), both of which had positive PhII data in recent months. The field is still open for neurodegeneration in PD and HD, but there, Ampakines have not had a full shot at showing what they can (or cannot) do.
NP
If that were the case, Biovail would not have licensed/acquired the RD program. Having said that, it is true that I have encountered pharma people who set their opinion in stone back in the day of the clinical hold, and have displayed no interest in updating/revising their opinion. Once there is a negative slant on a program, risk-averse pharma types don't want to take the chance. Biovail did thorough due diligence in assessing Ampakines, and went ahead with the deal--I don't know who else did DD, but I know at least a few that chose to not expend the effort.
NP
I forgot to mention Roche's R1678, a glycine transporter inhibitor (hence glutamatergic, as Ampakines would be considered to be). Phase III trials ongoing as both an adjunctive therapy and as a monotherapy.
NP
OT: Schizophrenia
Blade, the list omits EnVivo's nicotinic alpha7 drug EVP-6124, which is going into Phase III, and looks the best so far of the lot.
I've not been a big fan of the BioLineRx drug, and even at Cypress Bioscience, which had inlicensed it, there was disagreement within management as to the attractiveness of the compound. The 'Phase IIb/III' trial they are currently running has sites in India and Romania only. Which means that, even if the data is positive, some Big Pharma companies will not take it at face value. Indian psychiatric trials had their credibility undercut by AstraZeneca/Targacept's TC-5214 results, Romanian data may suffer from credibility concerns raised by Dimebon's Russian data. My current view is: If you want a potential Pharma licensee to take your CNS Phase IIb seriously, at least some of the sites have to be in the US or Western Europe.
NP
I guarantee you that Mark Varney is well aware of all this.
BTW--the head of AstraZeneca's iMed Neuro Unit, who orchestrated the acquisition of the assets from Link Medicine, is Mike Poole. Strangely enough, the former Chief Medical Officer of Link Medicine was named....Mike Poole. Coincidence? I think not....
NP
I am pretty sure your post has no relationship to anything I said in mine.
NP
It says he consulted in the past to Neurolixis. Now--as we already knew--he is in Capetown. As I expected, this is adding up to...nothing. Neither the euphoric (a buyout by JNJ) nor paranoid (a sellout of the shareholders) fantasies are anything more than that.
NP
It is possible I have missed something, but I think this speculation is off-target. Is there anyplace other than Corporate Wiki where Mark Varney is cited as the 'President' of Neurolixis? If there is, I havent seen it, and the CorpWiki site states its info is taken from the CA Sec State. That filing cites Varney as the 'registered agent' of Neurolixis--and I would wonder whether Wiki takes the only name linked to the company, and automatically labels them as 'President.' I didnt see anything about Les Street, so perhaps I have missed something, feel free to point me to it.
Neurolixis is not just a new shell for Cortex: Adrian Newman-Tancredi is a real person, I've corresponded with him, and his path crossed Varney's at Servier, they are friends. He has a 5HT-1a agonist program funded by MJFF, which is obviously not Cortex-sourced. Indeed, Neurolixis' description of their interests has only minor overlap with Cortex's portfolio.
As to JNJ, JNJ has extra space at their LaJolla R&D site which they are renting to small companies, partly in the hope of building early-stage relationships that will give them a leg up when it comes to eventual partnering. But these are not partnerships, and they do not have any legal rights to IP or anything else coming out of these incubated firms. Newman-Tancredi probably needed a CA business registration to rent that space from JNJ, and thus needed a CA-domiciled registered agent. He knows Varney, may have needed input on establishing ties in the area, Varney was able to provide those.
If someone has something beyond Corporate Wiki upon which this 'Presidency' is based, I'd like to see it. But otherwise, I believe that there is less here than seems to meet the eye.
NP
I do check in, but I don't know why you think I'd be an expert on 'liquidation'--it has seldom happened in CNS (Epix, Neurologix.....there must be other public companies, but they don't come to mind). And the involvement of the University of California further complicates things in the case of Cortex: I don't know at what point of 'liquidation' rights to IP revert to UC. This is as opposed to a sale of the Company, where there would be an orderly transfer, not a bankruptcy-triggered dispersal of assets.
To be overly but accurately simplistic--if you sell now, you know what you'll get. If you are passive, it could go down to zero, or go up in response to a sale of the company or a resurrection.
NP
They fund dozens upon dozens of trials at various stages of discovery, preclinical, and clinical development. They are not monitoring the outcome of each one. There's doubtless some sort of result-reporting process after a trial has been wrapped up, and if a company wants more money, they have to justify why. They maintain a database of issued grants, but MJFF is not sending out press releases about animal studies.
NP
If they are negative, which the silence leads me to believe is the case, I'd figure on seeing it in a 10Q. They probably don't think it's material enough to justify the $1000+ it would cost to put it in a press release, have it vetted by their attorneys, and sent out.
NP
I think a more realistic description is that they are trying to continue to 'have' a bargaining position. I'm not sure "strengthen" is the right verb. The questions are: Does Samyang want to keep them on IV drip? and if so, in exchange for what? Although the second question may not matter, since the only answer would be--
whatever they want.'
NP
In the midst of so much chaos and uncertainty, your perseverative ignorance is a beacon of stability, serving to warn those with an interest in 'how things really work' to steer well clear.
NP
One can do almost anything on an outsourced basis--from chemistry (which they don't need) to preclinical and clinical development. There are numerous virtual and semi-virtual companies out there. Neuroscience at AstraZeneca is now going completely virtual, just as a large-scale example.
IF--and this is by no means assured--Cortex can outlicense programs on the basis of geography and/or by molecule, the lack of inhouse drug development capability would not prevent them from doing the same. it's the funding that is the limiting factor, not the inhouse resources.
NP
1) Samyang is certainly one of the financing options. But I have no idea whether they'd want to double down at this point.
2) Beyond the facetious response that a celebrity death from opioid OD would gather media attention? I don't understand why pain companies have not shown more interest, other than they don't want to acknowledge the dangers of their products, and don't want to contend with developing a combination drug. It can be done (e.g. GSK/Pozen's Treximet) but it's not easy, and they may not be sure that the commercial potential would justify the outlay (i.e., would payors actually cover the premium pricing of a branded combo drug over generic opioids?--you'd like to think that safety would be a compelling reason, but that shouldn't be assumed).
3) My recollection is that they have a IV-suitable compound, preferable to IV CX717. I don't remember the number. I don't think they need Les Street's expertise on this project.
4) I have no faith that doing more animal work would increase the chance of a licensing. If that were the case, they could try to get an option deal--'we'll give you $800K to complete preclinical testing, and we like the results, we'll exercise an option to buy the program for considerably less than you think it's worth.'
5) Recalling, reknocking: I am sure that Jim Coleman's life involves a lot of repetition.
NP
I didnt say no one could--I believe Cortex has. Servier apparently believes that the older one from Cortex is safe. Biovail believed they were safe. But some large pharmas have failed, which has left the class with the reputation of being too difficult to handle. Pharma is risk-averse for the most part, especially with thousands losing their jobs,so they shy away....
NP
I don't see #4 happening--because if there is capital available for investment in Cortex, it will come via #1 or #2. Whether they might then eventually do a reverse split to meet some minimum exchange requirement--I don't know, they don't tend to work out well: Look at StemCells' chart for the past year, they did a 10:1 reverse split last July....that's not a reassuring slope, though part of that is due to a couple of financings...
#3 would render everything else moot.
I am sure that they are looking at all variations on 1-3...
So far as I can tell, and I have approached a number of companies on this, Ampakines in CNS are considered an old story with unacceptable side effects (other companies have run into this, and to some eyes, if Pfizer and Lilly couldnt make a safe Ampakine, no one can). And ADHD is simply a dead area at the moment.
If there is a rescue story yet to occur, it probably revolves around respiratory depression/sleep apnea--I don't know the players there particularly well, but for them, AMPA modulation is a fresh story, with much less competition.
NP
OT:BDSI
I pay limited attention to the many opioid reformulations/repackagings out there--most large pharmas now tell me they aren't interested in them, but specialty pharmas like Endo are. Endo is smart and analgesia-focused, so their deal (even after the Phase III problem) does mean something.
But one caution on this:
<<With only one drug for this indication currently in the market place sold by Reckitt Benckiser in the U.K., there seems to be room for other companies such as Biodelivery Sciences to enter>>
Reckitt Benckiser sells it everywhere (they're from the UK)--but Suboxone has lost patent protection. There may be a good reason no generic company has tried to enter this space, but RB was panicking a few years ago about the possibility of a generic, and if one did, that could be a real problem for a new branded entrant.
NP
Blade:
Please note, that comment was made in December. Since then, the Board has looked more like the trailer for the Three Stooges. As did many of the Republican debates. I just don't pay attention to those who think that their fantasies reflect reality to any degree (the Board, the debates, same thing).
RE: Cortex
If anyone licenses or acquires Ampakine technology, it will be a drug development deal, not discovery. If they don't think these molecules are good enough, they won't do the deal. So, Les Street had become an expensive luxury--and while in a perfect world, he could have stayed to execute tweaks as needed, Cortex couldn't afford it, and if future tweaks are needed by a partner, they will rely on inhouse chemists.
Cortex has explored all avenues, but the avenues are in constant motion. The shifts that could allow a change in outcome would be external--as I have quoted before, a Pharma BusDev head once described partnering as 'the stars coming into alignment'--not only regarding the asset, but the needs and priorities of licensing companies.
Things are constantly changing: For example, within a few months, AstraZeneca will have 40-50 CNS staff left, out of a couple thousand, but they actually predict they will increase their range of licensing activities in their new outsourced model. Does that make any difference vis-a-vis Ampakines? Probably not, but they are a moving target, and even they don't know how their priorities will sort out yet. The same is true, in smaller scale, for other companies.
The choice of indications change--and if someone previously uninterested in neurodevelopmental disorders decides that Fragile X is worth exploring, Cortex is out there, and might be of interest when they were not previously.
Cortex's task is to constantly monitor changes in strategy or even personnel, shifts in funding from MJFF and the like, putting themselves back in view every time there's a new set of eyes, or change in perspective. And they do that: those who ramble on about management's smug passivity have no idea what they are talking about.
Re ACAD: It looks like speculators ran it up, now they have gone on to speculate elsewhere, selling off in the process. Neither the rise nor the fall apparently had much to do with substance (with all due respect to the Allergan renewal and progress with Meiji Seika): Pimavanserin's Phase III results are still going to dictate Acadia's fate.
NP
Had Cortex been in the position of needing to create multiple iterations of low and high impacts, it would be a major loss. But in the current circumstances, his work there was done--it's no longer a case of molecular tweaks, he provided a modest portfolio of candidates. Now--if they were to obtain the resources to bring a couple programs ahead, and wanted to devise additional backup NCEs, or optimize them for some kind of desirable characteristic, then his absence would be salient. But that's not the case. Cortex's immediate prospects are not impoverished by his departure, it's a moot point at present. Even if their fortunes change, it would be moot for a couple of years, as they work with what they already have.
NP
Money continues to be "extremely tight." But Les Street left for an academic position at the University of Capetown. Makes sense--they don't need new chemical entities now, they need resources with which to develop the ones that they have.
As to Servier: They face massive French lawsuits in conjunction with their marketing of the diabetes/ obesity drug benflourex (it's the same heart-valve issue that killed fenfluramine and dexfenfluramine). Not only is there apparently the potential of jail time for the CEO/primary owner, Jacques Servier, but the weight of the hundreds of suits could pose fiscal jeopardy for Servier as a company: the French court has refused to combine all the suits into a class action, which eliminates the likelihood of a Wyeth-type class-wide settlement, as occurred with dexfenfluramine/Redux. At the very least, this is a major distraction for Servier, and makes investment in new programs more problematic.
NP
While I am sure they have talked to everyone, it's not as if that is a task that is ever finished. Other companies are always changing their priorities and licensing tactics, and the people executing these strategies are in flux as well. For example, I looked back at the 2011 purchasers of one of NIR's annual publications--who made that purchase between Dec 2010 and June 2011. To my surprise and dismay. half of them have been laid off by their companies. The downsizing in Pharma has been immense, which means small companies are always having to reintroduce themselves in the hope that the stars will line up at some point (that metaphor is not mine, it actually came from the head of BusDev for one of the largest pharma companies) between programs and motivations. So Jim Coleman is in the position of continually monitoring a landscape in perpetual change, and when someone with whom he thought he has a conversation underway leaves, he has to start over again.
NP
Actually, it's an example of a couple of things:
1) Sloppy thinking, which may be expected at a cocktail party. Sounds like they confused Ampakines and ketamine.
2) Premature closure based on #1. I just encountered a different example of this at a professional meeting a few days ago, where I spoke to someone with whom I have a good relationship. I had approached him and his company a few months ago, because their interests--I thought--were potentially, albeit obliquely, congruent with the Ampakines, and I had sent him a writeup for their BD&L group to review. I had heard back fairly quickly that they wouldn't look into it any further. He told me at this meeting that there was one inhouse scientist who had blocked consideration of a licensing. It was clear from the conversation that this scientist's negative view was based on some vague recollection of the CX717 toxicity flap. But when I said that the scientist's information was outdated and inaccurate, my friend told me that it didn't matter; there was a wall, and no one at the company is sufficiently motivated to try to overcome it. They have path of less resistance they can pursue.
Is this a 'marketing' problem? Not really. Cortex has spent four or more years trying to establish a different narrative for Ampakines, but with limited success--some people maintain a cognitive set based on the old information. With the thousands of licensing opportunities out there, people take a shortcut to parse the universe of possibilities down to a more manageable number. If Cortex had the capital to generate several tranches of new clinical data, that could start to undo the old perception, but they haven't had that option. It's akin to the problem the American auto industry had for so long, where even after they had started to turn around the design and quality issues that had led many to see them as second-rate compared to Japanese/German cars, they had to demonstrate (not just claim) improvement for a few years before they could substantially shift that perception.
So Cortex is stuck: They need to get data to change the perception, and they need to change the perception in order to fund the trials that would produce that data.
NP
OT:TRGT
Selling for well below cash, but I am worried about the large clinical trial costs they have taken on.In other words, with these substantial commitments, I believe they cite being down to around current cash level by end of year, which will wipe out that valuation premium.
TRGT also has an interesting preclinical compound for Parkinsonian dyskinesia--I don't remember the compound designation.
A huge question for TRGT--do they diversify outside of nicotinics now or not?
NP
After the first two trials failed, TRGT fell even lower--some of the angst got squeezed out then, though it had come back because some signal had been seen in the second trial, and there was a faint hope that these fixed dose trials might pick it up, since they had longer pt exposures. But no, and this will have some aftereffects:
1) It further casts psychiatric drugs as expensive gambles. However, Forest/Pierre Fabré just announced positive Phase III data for levomilnacipran, and there are three more treatment-resistant depression trials lining up to report in next three quarters: From Naurex, CeNeRx, and Euthymics Bioscience. If a couple of those do OK in Phase II, that could undo some of the damage--though I wouldn't try to sell a depression program to AZ over the next year--or two--or ever.
2) TC-5214 is a nonselective nicotinic receptor antagonist. It may cast some doubt on that mechanism and further doubt on the alpha4beta2 subtype antagonist mechanism, which has also not been panning out well for AZ/TRGT (mixed data). But it doesn't necessarily say anything about the nicotinic alpha 7 agonist programs from EnVivo, Targacept, Abbott, Proximagen.... Which is the approach I've been most interested in.
3) Companies are going to be very leery about Phase IIb data from unusual clinical populations (e.g. the Russian dataset for Dimebon, the India dataset for TC-5214). Both produced really impressive PhIIb results that did not predict Phase III outcome. Some of the clinical trial outsourcing that has been going on will now be brought back to the US and EU.
I'm presenting at a conference the next two days where the people who ran the TC-5214 Phase III program will be present. I'm sure it will be high on the topic list.
I totally agree that some of the money that AZ threw into FIVE Phase III trials could have been used to run Phase II trials for a number of other approaches to psychiatric disorders--Cortex's included. This 'all-in' strategy sets up binary events of huge consequence. The upcoming bapineuzumab dataset is another example of the same thing.
NeuroPerspective
(this is the only place I haven't changed the name, done everywhere else almost a year ago).
1) Preclinical prep work is actually expensive--I'd guess it'd be over $1 million to get CX1846 ready, and that doesn't include reinstating the infrastructure they've had to cut.
2) Chris Fibiger, Biovail's CSO, is now CSO of MedGenesis Therapeutix, working on infusing GDNF into Parkinson's brains under pressure, to improve penetration. When he was at Amgen, he did a lot of work with GDNF in PD, so this is another of his priorities.
3) So far as partnering goes: Pretty much every company I contacted about a RD/SA partnership had already been contacted by Cortex.
Here's a new statistic: in 2011 Merck reviewed over 8000 licensing opportunities. That's just to give some color to the context, which is immensely competitive. I agree with Enemem that it is stunning that none of the analgesia companies have picked up the RD/SA program.
4)MJFF gave Ceregene $2.5 million towards their Phase IIb PD trial, which was followed by a $11.5 million financing. The fact MJFF would put that much into a clinical trial (they fund lots of animal work) was undoubtedly a factor in being able to raise the funds. The hope is that Cortex might be able to follow the same path.
NeuroInvestment
A few thoughts:
1) Reversal/regeneration of neurodegeneration would be an unexpected boon, but in an aged population, just slowing progression would be terrific, and has yet to be accomplished.
2) Servier does not appear to have started Phase II. For symptomatic treatments, they've gone as short as four weeks in the past, for disease-slowing, six months.
3) If either UCI/Lynch or Cortex had seen evidence of low-impacts producing enough BDNF to be disease-modifying, they would have been all over it....they haven't pursued the tough nut of high-impacts for the exercise...
4) There is a world of difference between the safety window for Parkinson's compared to ADHD. Look at some of the programs currently in Phase IIa or IIb testing, using neurosurgically implanted cells and/or viral vector gene therapy: Ceregene, NeuroNova, Neurologix.
5) I'm still hoping for nonhuman primate PD data in the next couple of months, if distinctly positive, perhaps turning into MJFF support for human testing (they've paid for some of Ceregene's clinical testing for CERE-120).
6) Big Pharma isn't generally interested in licensing platforms, unless it's a discovery stage platform they can a junior partner develop. They want a lead compound and a backup or two....
NeuroInvestment
OT: Bexaretone
Athero:
You are absolutely right that my first response was to be cynical and skeptical. We've cured a lot of mice, no humans. But interestingly, I polled a number of my Alzheimer's contacts, some of whom are prominent in the field. While they are also cautious about the mouse-human translation obstacles, they are unusually impressed by the combination of biomarker and functional changes shown in this paper. The best part is that it isn't a long path to sorting out whether it will work in humans. Usually, we hear about these findings for a drug that has yet to even be tried in humans, where there is no data regarding safety, and it will be years before we know if it really works. While bexaretone's chronic dosing safety and tolerability have yet to be established, it's not the leap of faith usually required. I've been in touch with the Case Western Reserve group that is spinning this out into a private company--they will be starting a human POC trial within the next month. So, while I am still cynical, this deserves watchful attention, even if not overt optimism.
Postscript: Immediately after I posted this here and blogged a version of it, I heard from a very high-profile AD expert who did indeed say the animal data looked 'too good to be true.' And when things look that way in CNS, they almost always are. But as I said above, there's a bit more room for cautious hope here than is usually the case.
NeuroInvestment
Even Big Pharma companies are wary of autism, because it is so heterogeneous (hence, 'Autism Spectrum Disorder') and the pathophysiology is not clear. Most companies that have an interest are going after Fragile X first, since it is genetically defined as a population, and has a partial overlap with autism, with the hope of then going after autism if they prove their principle. But Cortex already ran into a problem using a very low-impact with Fragile X (CX516)--have not been able to get funding for testing with a better low-impact or (optimally) to prepare a high impact for the clinic (Increasing BDNF corrects defects in a mouse model of Fragile X). With mGluR5 antagonists currently one of the favored approaches (Novartis, Roche, Seaside). Cortex did fund UC animal studies showing combining an Ampakine combined with mGluR5 antagonists increased BDNF production in the brain, and has the IP for that combination. That IP might eventually have value to a competitor who has successfully developed a mGluR 5 drug, but that hasn't happened yet.
NeuroInvestment
Virtually no one expected this last Dimebon trial to do any better than the others. I don't think Pfizer or Sanofi are where the potential partner for a program like Cortex's may yet be found. I moderated a panel of Big Pharma BusDev heads in November, and asked them how important it is for a potential licensing candidate to have a 'champion' within the larger company, someone with a an interest in the mechanism--"No champion, no deal" was the emphatic response. Servier is the only company at present with such an internal interest in Ampakines, and as such, would only be bidding against themselves. But there are some smaller companies (small in comparison to the majors) that might eventually be open to another neurodegeneration option. Biogen-Idec has built a dominant presence in MS, and has defined neurodegeneration as a major focus going forward. Lundbeck has licensed a range of Parkinson's programs and is building a presence there. Both those companies are focused on mechanisms that have some genetic marker (e.g. LRRK) that at the least might define potential responder populations. I don't know if even "regenerative" would reach their threshold for assessment, but that's the kind of company I'd be focusing on, not Big Pharma. And before someone says 'Hey, why didn't Cortex management think of this?'--I have zero doubt that they have, and will again.
NeuroInvestment
OT: Sanofi
At his JPM presentation, Viehbacher did not mention the brain, CNS, or 'neuro' even once in his overview, other than when referring to MS, which Sanofi categorizes as immunological rather than neurological. He highlighted diabetes, vaccines, emerging markets, and the "growing pet segment." The problem from his point of view would be that the biomarkers that give him (and many other CEOs) a potentially-illusory sense of security do not, for the most part, exist in validated form in CNS. Which keeps CNS out of his and Sanofi's top tier of interests.
NeuroInvestment
The funding environment has been bleak--the relevant sidebar in NP January was titled 'Starvation Rations in the NeuroGulag'--total 2011 neuro partnering/funding resources were down 23% from a bad 2010, 53% lower than what was seen in 2006.
I was also at JPM and the concurrent Biotech Showcase meeting down the street. Here is an anecdote to illustrate just how messed up some Big Pharma companies are: GSK's CEO gave a twenty minute presentation on GSK--and not once did he use the terms 'drug' or 'pharmaceutical.' Some of these companies aren't even sure they want to be identified with the pharma industry, let alone invest in it. And the recent spate of industry-academic collaborations, which are a cheap way to eliminate the biopharm middle man, is at best complementary, it does not replace small company R&D focus.
Re: Cortex
I have not had any luck getting a couple of pain companies to be interested in the RD angle, but I don't have good contacts there. They should be interested, and I have no doubt that Varney/Coleman have repeatedly touched base with all of them-- it's been frustrating.
The key to any value from the MJFF animal testing is whether any reference is made to 'regenerative' effects. That is what stood out in the Lilly results a decade ago, and would differentiate these animal data from the many 'protective' reports that have come from other preclinical studies. That is what I think would be required to make Ampakine animal data of interest to other companies beyond Servier.
NeuroInvestment
Athero:
<<until we have disease disease modifying intervention.... what is thepoint>>
To the degree to which a biomarker can identify pre-symptomatic, pre-plaque, prodromal Alzheimer's, it could greatly help in validating a disease-modifier. There's a school of thought that to show disease-modification, you have to intervene before a patient is on the slippery symptomatic slope. But you have to know who would eventually get AD, in order to show that your drug stopped or slowed the process.
I'm not endorsing this particular biomarker candidate--but where I used to be cynical about the value of diagnostic tools when there isn't a therapy to then be deployed, I now have an appreciation for the potential value of early identification.
NeuroInvestment
1) If the animal data in PD is as positive as that long-ago Lilly study might predict, MJFF would probably fund IND-preparation, possibly Phase I. MJFF funds a lot of trials, and that in itself might not spur much change in the stock price. But it could depend on what is seen and said: Lilly's rodent data indicated 'regeneration', and that would be more impactful than 'protection.' MJFF funds a much smaller array of Phase II trials (e.g. Ceregene's gene therapy Phase II)and that might get more attention. But this is jumping ahead: First we have to wait for Cortex's academic collaborator to finish the rodent trial.
2) I see no evidence that the Servier PhII has started--the ony Alzheimer's trial I see active at present from them is for a H3 antagonist (symptomatic treatment).
3) A successful Phase I might increase interest from Servier. It would take a successful Phase II to get much interest from companies not presently involved in AMPA modulation.
NeuroInvestment
This is like watching Herman Cain and Rick Perry debate foreign policy.
Exception: Gfp's summary was pretty on-target. And BTW--many thanks to Aiming for his longterm contribution to keeping this Board sane and productive.
NeuroInvestment