Washington Editor

Locus Pharmaceuticals Inc. is lending its kinase-related drug discovery capabilities to a research agreement with Ono Pharmaceutical Co. Ltd.

Locus, a drug design and development firm based in Blue Bell, Pa., will apply its computational technologies, as well as its capabilities in chemistry, biology and crystallography, to design and develop preclinical drug candidates for Ono.

The companies did not disclose financial or other terms of the multiyear collaboration. The efforts are targeting an unnamed protein kinase selected by Osaka, Japan-based Ono.

Robert Dickey, Locus' chief financial officer, told BioWorld Today that the deal demonstrates to potential partners that the "knowledge we've accrued is of value." In particular, the arrangement leverages Locus' internal drug development capabilities with an underlying knowledge of kinases. Because there are more than 500 structurally related kinases, a small molecule often requires high selectivity for the intended target, and Locus is active in that space.

Already, the privately held company has used its computational approaches and algorithms in internal kinase efforts, of which a p38 program focused on non-ATP inhibitor drugs for inflammation has a lead series undergoing optimization. In addition, it has kinase-related collaborations such as an ongoing agreement with Eli Lilly and Co., of Indianapolis.

In the Ono program and others, Locus starts by modeling a protein's crystal structure and its movement and then comes up with a binding-site map through the use of an in silico collection of 40,000 molecular fragments and a Linux-based supercomputer cluster. Then the company computes the binding affinity of molecular fragments to sites and links the fragments to computationally assemble virtual drug candidates.

The result is a virtual library of drug candidates that exceeds the size and diversity of any physical screening library by orders of magnitude - more than 10 billion compounds, Dickey said. "The diversity, chemically speaking, of what we're able to create far exceeds any [traditional] screening library."

Notably, Locus has incorporated its computational approaches "in a very integrated fashion" with in-house capabilities in chemistry, biology and crystallography, Dickey said, to create a preclinical drug development platform. That, he added, "iterates between computational design and synthesis in our labs."

Dickey declined to specify a timeline for producing candidates for Ono.

Locus, a 6-year-old company, last reported raising money in late 2001, when it brought in $40 million via a Series D round of financing. Last summer, the company was in the midst of trying to raise more.

The company also is looking to develop its own compounds. In addition, Locus recently filed its first investigational new drug application for LP-261, its lead oral oncology compound. A planned Phase I study is designed to evaluate the safety and pharmacokinetic profile of LP-261 in patients with advanced metastatic tumors or blood cancers, as well as refractory cancer that has progressed despite chemotherapy.

Earlier-stage projects include a program to develop multi-kinase inhibitors, a heat-shock protein 90 program that is being conducted in collaboration with the National Cancer Institute and a gp41 program for HIV/AIDS. Locus also has entered various drug design and development collaborations with a number of pharmaceutical partners.

Ono's R&D priorities are focused on prostaglandins, enzyme inhibitors, neuroscience and cellular signaling.

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