Replies to post #15902 on RespireRx Pharmaceuticals Inc (fka RSPI)

[gfp927z]

Rusbrn, There's usually a backup compound included in pharma deals, and the RD partner is probably going to be interested in exploring the lucrative chronic indications like sleep apnea, where CX-717's artifact trouble could reemerge as an approval problem. These new low impacts like CX-1739 are also a lot more potent than the CX-717 era compounds (CX-1739 being ~5 times more potent), so one would expect the RD partner to want at least one of the new compounds.

With so much riding on these new low impacts, one of the biggest question marks in my mind is - 1) whether they will share the high safety of the earlier benzofurazans, and 2) will they have similar efficacy in specific indications such as ADHD? As we know, there's a vast array of AMPA receptor subunit combinations in the different areas of the brain (4 subunits, plus 'flip' and 'flop'), and different Ampakine compounds hit the various subunit types in differing strengths/ proportions. We know there's a considerable variation in activity/efficacy/safety between different compounds within the benzofurazan sub-family of benzamides. While the new low impact compounds are presumably benzamides, they probably aren't benzofurazans (we investors don't yet know that for sure either way).

I'm still wondering how Dr. Street managed to suddenly discover all these new low impacts within months of his arrival at Cortex. The high impact 'breakthrough' apparently also coincided with Street's arrival. CX-717 had excellent activity in ADHD, and there's a reasonably good chance that other similar benzofurazans like CX-701, Org-24448 (or Org-26576), might also have good activity in ADHD. However, it's a much bigger jump to expect replicating CX-717's ADHD activity as you move to compounds from a new chemistry. Replicating the benzofurazan's very high degree of safety is not a given either.

[neuroinv]

Chronic use--as in sleep apnea. No one is worried about CX717 in acute use. But the shadow of the Artifact and the FDA means that they would want to have another one where there is no hint of problems with longterm use. CX701 might work given the use patent. However, the other issue is whether the partner has a veterinary program, in which case they want a second compound for that...., and thus would need at least three. However, I also don't think that Cortex is necessarily 'several years' away from having clinic-ready compounds beyond 1763 and 1739. Les Street has produced a bunch of them, so there are other options.

Re: Gfp's question about partnering and upfronts. Take the ADHD discussions we had back in the day, and build on those, since the potential markets are even bigger, and there is no current champion called 'Shire and the psychostimulants' that needs to be dethroned, or at least contended with. Bigger market, no competitors.

Last thought for Gfp: While I have no doubt the trials will happen, I agree that no one can take anything for granted about how they'll turn out, in spite of all the reasons for confidence. Because as we have learned several times, s--- happens. However, I don't think a 'feedback loop' will be a factor. The reason is John Greer from U. Alberta. All he does is respiration, and if there is anyone who knows the CNS controls for that system better than he does, let them step forward. If there was evidence for some type of feedback loop, he would have seen it, and it would have colored Cortex's trial planning. To put it another way--if Greer saw evidence of some type of feedback mechanism that would sabotage oral administration, we'd be hearing Cortex talk about initiating IV trials once the IV formulation is ready, not about oral trials. So there is reason to have 'free-floating anxiety' as they used to call it, based on the risks of the unknown that can always crop up, but I personally do not have anxiety tied to a specific issue.

NeuroInvestment