West Coast Editor

To build its pipeline of would-be drugs against central nervous system disorders, Intra-Cellular Therapies Inc. in-licensed a family of preclinical compounds from Bristol-Myers Squibb Co. for undisclosed terms.

New York-based ITI is paying BMS, also of New York, an up-front fee and development-based milestone payments, agreeing also to provide royalties if a marketed compound emerges from the set of candidates.

ITI could not be reached for comment.

The package from BMS complements an internal lineup of preclinical small-molecule therapies discovered by ITI, which is focused on signaling pathways inside nerve cells as elucidated by Nobel Prize-winning scientist and ITI co-founder Paul Greengard.

A professor at Rockefeller University (from which ITI has licensed a platform of technologies), Greengard's research found, among other things, that a protein called DARPP-32 might be what ITI called a "master checkpoint" for modulating neurotransmitters. The acronym stands for "dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000." (See BioWorld Today, Feb. 11, 2000; March 5, 2002; and Aug. 23, 2002.)

DARPP-32 bears a phosphate on threonine 34. The phosphoprotein maintains neuroreceptors, ion channels and other proteins in their phosphate-rich states, thus amplifying the nerve cell's response to neurotransmitters and making it possibly a fruitful area of investigation. Other DARPP-32 phosphoproteins, modified on sites other than threonine 34, play important roles in fine-tuning nerve cell activity, ITI said.

Using what the company calls its CNSProfile technology, ITI is tracking the biochemical changes that occur inside nerve cells after treatment with a drug by using antibodies to monitor neuronal signaling pathways before and after administering the compound. Specifically, the firm is taking aim at phosphoproteins (such as DARPP-32's phosphate on threonine 34) within the signaling pathways that are responsive to dopamine, serotonin and other neurotransmitters - and to novel antidepressants and antipsychotics that operate through the pathways.

ITI's first product in development is a small molecule for Parkinson's disease and, potentially, other CNS disorders.