BioWorld International Correspondent

Addex Pharmaceuticals SA out-licensed one of its preclinical drug discovery projects to Ortho-McNeil Pharmaceutical Inc., a subsidiary of New Brunswick, N.J.-based Johnson & Johnson, in a deal that will garner it an undisclosed up-front payment and research funding for two years, plus additional payments for reaching scientific, clinical and regulatory milestones.

The program is focused on finding allosteric modulators of a particular G protein-coupled receptor (GPCR) target that has potential in anxiety, depression, Alzheimer's disease and schizophrenia.

Addex, of Geneva, is vying for leadership in an emerging field of drug discovery based on finding both positive and negative allosteric modulators of novel and known GPCR drug targets. The company hopes that compounds in that category - which bind at secondary sites on protein targets rather than at the site at which a natural ligand would bind - will have greater selectivity than agonists or antagonists that act at the primary or orthosteric site. The company has built up a set of tools for building functional assays and a compound library that is biased toward molecules with an allosteric mode of action.

"This deal is a very real validation of the concept of the platform," said Addex CEO Vincent Mutel. "There is a significant amount of manpower involved on both sides."

Johnson & Johnson Pharmaceutical Research and Development will be responsible for the J&J side of the agreement. The organizations will operate through a joint steering committee, which will supervise all aspects of preclinical and clinical development up to proof of concept.

Benzodiazepines, used in the treatment of anxiety disorders, offer the most obvious example of drugs acting via allosteric modulation - they mediate their effect via ion channels. Mutel, however, said there has, to date, been little systematic effort to find compounds that act in a similar fashion.

"It's a different type of pharmacology," he said. "These are special molecules in terms of their physico-chemical parameters."

The program that J&J licensed is at the lead-optimization stage.

"We were working on the target for one year," Mutel said. It has two others that are at a more-advanced stage of preclinical development. Its lead program, in anxiety, should reach the clinic later this year, Mutel said. It is based on the development of a negative allosteric modulator of the mGluR5 receptor. A second program, in schizophrenia, is focused on an undisclosed target.

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