Replies to post #2873 on RespireRx Pharmaceuticals Inc (RSPI)

[gfp927z]

Here's that paper on Org-24448 and Org-26576. Though we don't know for sure if Org-26576 was originally from Cortex's labs or Organon's, I remember Neuro saying he was fairly sure it is covered under the existing partnership deal between Cortex and Organon (unlike the situation with Servier and S-18986) -

>>> Neuropharmacology. 2005 Aug;49(2):254-64.
Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by 14C-2-deoxyglucose autoradiography.Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. [e-mail]

AMPA receptor potentiating drugs (e.g. ampakines) enhance glutamatergic neurotransmission, and may have potential therapeutic consequences in CNS disorders. The neuroanatomical basis of action for these compounds is at present unclear. This study aimed to identify the effects of two novel ampakines, Org 26576 and Org 24448, on local cerebral glucose use (LCGU) in the mouse. C57BL/6J mice received Org 26576 (0.1, 1, 10 mg/kg i.p.) or Org 24448 (3, 10, 30 mg/kg i.p.) or vehicle and LCGU was assessed using 14C-2-deoxyglucose autoradiography. Both compounds produced dose-dependent increases in LCGU with specific regional activation at low doses. Org 26576 (1 mg/kg) produced significant increases in 9 of the 43 areas examined, including the anteroventral and laterodorsal thalamus, cingulate cortex, dentate gyrus and CA3 subfield of the hippocampus. Org 24448 (3 mg/kg) produced significant increases in LCGU in 4 of the 43 regions examined, including the dorsal raphe nucleus, medial lateral habenula, CA1 subfield of the hippocampus and median forebrain bundle. Furthermore, the increases in LCGU observed with both Org 26576 (10 mg/kg) and Org 24448 (10 mg/kg) were blocked by pre-treatment with the AMPA receptor antagonist NBQX (10 mg/kg). These data demonstrate that both Org 26576 and Org 24448 produce dose-dependent AMPA receptor mediated increases in LCGU and provide an anatomical basis suggestive that these drugs may be of use in the treatment of conditions such as depression or schizophrenia.

PMID: 15993447 [PubMed - indexed for MEDLINE] <<<

[gfp927z]

Misc late night ramblings --

If we assume that CX-717's dosing restrictions eliminate ADHD as an indication, that will probably mean that CX-717 will end up as an added element to the Neurodegenerative BP deal. It would make sense for the BP to want a low impact as part of the Neuro/high impact deal, especially considering the low impact/Aricept synergy for AD. The issue then becomes, with CX-717's somewhat tainted safety profile, the BP will probably also want a backup, and Cortex has both CX-701 and CX-1501 available. One of those could be kept by Cortex with the other going to the BP.

I'm starting to come around to the idea that even with puny upfronts, the Neurodegenerative deal could still be a major catalyst for Cortex's stock price, especially if the BP partner is a high profile household name. The usual suspects come to mind - Lilly, Glaxo, Sanofi-Aventis, Merck, Pfizer, Amgen, any of these would do nicely.

Assuming this Neurodegenerative BP deal doesn't happen until later in 2007, then we first need to get through a very unfavorable shelf financing and then a likely bad go/no go CX-717 announcement in late Feb/early March. The wildcard would be if Stoll can somehow pull off the Neuro BP deal in January - not completely impossible but definitely not something to count on. Of course the even bigger wildcard invloves the outside chance of much better than expected tox data on CX-717 (Feb/March), and a much better than expected dose liberalization decision by the FDA (May). I'm not expecting either of those CX-717 developments to happen however. So realistically, our chief upside hopes for 2007 rest on the Neuro BP deal with a big name partner.

So my prediction is that we continue wallowing in the muck for a number of months, until the BP deal is announced (perhaps mid-year). The stock is currently so cheap though, that we could see a modest January effect rebound, and/or a relief bounce after the financing. All eyes are on the new tox data however (late Feb/early March), so the sword of Damocles will still be hanging over the stock. Bottom line - we need to get some of the current myriad of uncertainties resolved.