Company Overview

Cortex Pharmaceuticals, Inc. is focused on the discovery and clinical development of AMPAKINE® molecules. AMPAKINE compounds fall into two categories; low impact and high impact compounds, defined by the site to which they bind on the AMPA receptor complex. Cortex’s lead low impact AMPAKINE, CX717, has demonstrated “Proof-of-Concept” in adult ADHD patients in a pilot Phase IIa study.  CX717 is currently being tested in a pilot Phase II study in mild to moderate Alzheimer’s disease patients that will investigate changes in brain metabolism by PET imaging.  The purpose is to confirm acute PET Scan findings observed in an earlier study  performed in non-human primates with memory and cognition impairment that were reversed by acute CX717 dosing. This type of study also will allow the company to explore what the effective dose range for this drug is in humans before initiating longer term efficacy trials.  A second research program will evaluate the acute use of CX717 and possibly other AMPAKINE compounds in humans given analgesics and anesthetic agents which can cause respiratory depression.   Recent animal data suggests that acutely administered AMPAKINE compounds selectively activate AMPA receptors in the brain stem, which appear to prevent or reverse respiratory depression induced by inappropriate dosing of opiate analgesics or certain anesthetic agents without inhibition of their beneficial analgesic and sedative effects.  Several follow-on molecules to CX717 have completed or are undergoing toxicology testing.  The Company anticipates having two or more AMPAKINE compounds in clinical studies by late 2008.

Cortex’s business plan focuses on out-licensing internally developed AMPAKINE compounds for the very large CNS diseases such as ADHD, Alzheimer’s and Parkinson’s disease, while retaining the smaller indications and orphan diseases for internal development. The Company has already out-licensed two AMPAKINE compounds (Org24448 and Org26576) for the indications of schizophrenia and depression, respectively to Organon, which was acquired by Schering-Plough in November 2007.

Technology

AMPAKINE compounds facilitate the activity of the AMPA receptor, which are activated by the glutamate, to selectively amplifying brain circuits. Since AMPA receptors are expressed widely within the brain, AMPAKINE compounds may have wide utility in the treatment of neurological and psychiatric disorders. 

Cortex’s AMPAKINE platform technology is composed of two groups of compounds that we have designated as “low impact” and “high impact.” AMPAKINE compounds like CX614 and CX929 bind to the well characterized cyclothiazide binding site, and are referred to as high impact compounds.  In contrast, compounds like CX717, CX701, CX1739, Org24448 and Org26576 bind to a different modulatory site on the AMPA receptor complex and impact the response in unique ways. The low impact series of compounds are unique to Cortex and their partner Organon. Both types of compounds positively modulate the AMPA receptor function, but the high impact compounds also activate the expression of growth factors within the brain. This effect imparts these compounds with the potential for disease modifying activity.

Data from preclinical animal models suggest that AMPAKINE compounds might be effective in treating schizophrenia, depression, ADHD, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Fragile X. Recent work also suggests that AMPAKINE compounds activate respiratory drive in the brain stem to prevent or reverse respiratory depression induced by inappropriate dosing of opiates and barbiturates without inhibition of the analgesic and sedative effects.

Alliances

Cortex out-licensed to Organon the exclusive worldwide rights to Org24448 and Org26576 for the treatment of schizophrenia and depression. Organon was acquired by Schering Plough in November 2007. Based on this relationship,Cortex would receive developmental milestone payments and royalties on sales of these products.
  
In December 2006, Cortex terminated its five year research collaboration with Laboratories Servier on AMPAKINE research for the treatment of various neurodegenerative diseases in their Territory. With this termination, Cortex regained the worldwide rights for the use of all new AMAPKINE compounds for the treatment of neurodegenerative diseases and allows us to partner new compounds for such uses. At the termination, Servier selected three compounds developed during the previous 12 months of the research collaboration for its continued investigations. Should any of these three compounds be successful in reaching the market, Cortex will receive developmental and regulatory milestone payments and reasonable royalties on sales of such product(s) partnered.