By Vicki Brower

Special To BioWorld Today

CoCensys Inc. and Warner-Lambert Co. have expanded their November 1995 collaborative agreement for glutamate receptor antagonists to include a second class of receptor antagonists -- modulators of the AMPA receptor.

The original two-year agreement focused on the discovery of sub-type specific N-Methyl-D-Aspartate (NMDA) receptor antagonists, second-generation compounds that block the activity of one specific class of glutamate receptor.

According to the new agreement, Warner-Lambert, of Morris Plains, N.J., will make a $7 million equity investment in CoCensys, contribute up to $16.5 million in milestone payments if all key targets are met, and also pay royalties on compounds that result from the collaboration.

As a result of the new agreement, CoCensys will have about $19 million in cash and cash equivalents by the beginning of 1998, which is about 1.5 years of cash with its current burn rate, said spokesperson Christi Foster.

This month, CoCensys divested itself of its 60-person sales and marketing team, which was acquired by Watson Pharmaceuticals Inc., of Corona, Calif., for about $9 million, and which cut its annual burn rate by about $3 million. CoCensys said the transaction would enable it to focus on its ongoing research and development efforts, but also call upon the team once it had more need for a sales and marketing force.

The extension of the Warner-Lambert deal caps a year of ups and downs for CoCensys. In July, the Irvine, California-based company reported positive Phase II results with its drug, ganaxolene, in children with uncontrolled epilepsy. A synthetic version of naturally occurring neuroactive steroids, called epalons, ganaxolene binds to the gamma-aminobutyric acid (GABAA) receptor complex, which is a major inhibitory or calming complex in the brain. These results mirrored earlier European trial data; the drug is continuing Phase II trials in adults with epilepsy and recently completed a Phase II in migraine patients. CoCensys expects to make deals for the drug in both indications in early 1998.

However, in April, Novartis returned rights to licostinel (ACEA-1021), CoCensys' lead glutamate receptor antagonist for stroke and head trauma, after Phase I data showed some patients suffered kidney toxicity. Since then CoCensys has been conducting further preclinical studies with a lower dose of the compound, an antagonist to the glycine site of the NMDA receptor, and probenicid to block the drug from entering the kidneys.

Cocensys plans to announce new preclinical data this weekend at the annual meeting of neuroscientists in New Orleans. With cleaner data, the company expects to re-partner the compound in the near future, Foster told BioWorld Today.

In May, CoCensys licensed its anxiety therapeutic, Co 2-6749, and related backup compounds to Wyeth-Ayerst for $59 million, including an up-front licensing fee of $5 million and $5 million of convertible preferred stock. For this compound, also based on epalons, Wyeth-Ayerst is funding all clinical development costs and will pay royalties. A second deal, for co-development and co-promotion, with CoCensys' CCD-3393 and related epalons, was struck in May 1996 with G.D. Searle & Co., of Skokie, Ill., for $80 million, for insomnia.

The company expects to forge two new partnerships by early next year for its epilepsy and migraine drug, Foster said. *

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