SAN DIEGO, CA - (April 15, 1999) Privately-held Structural Bioinformatics Inc. (SBI) today announced the award of a USD $100,000 Phase I Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI), a division of the National Institutes of Health in Bethesda, MD, to develop non-peptide small-molecule antagonists targeting the HER2 gene product. The grant, entitled "Small Molecule HER2 Inhibitor Discovery" will enable SBI scientists to apply the Company's proprietary protein modeling and dynamic pharmacophore-based searching of existing and virtual combinatorial libraries to identify and synthesize putative small-molecule HER2 antagonists rapidly.

The HER2 gene (also known as "erbB2" or "neu") is amplified and overexpressed in nearly 30% of all human cancers and is associated with poor prognosis, chemoresistance, as well as aggressive and metastatic tumor growth. In 1998, a humanized monoclonal antibody to HER2 received Fast Track Product Status from the U.S. Food and Drug Administration (FDA) and, in 1999, was approved for the treatment of metastatic breast cancer, validating HER2 as an effective target for breast and possibly many other forms of cancer treatment. However, the difficulties associated with the administration of antibodies as therapeutic agents are well-known. Thus, a small-molecule, non-peptide orally-active HER2 antagonist would be a highly desirable therapeutic agent.

"We are very pleased to receive this SBIR grant from the NCI, which was awarded after a rigorous, peer-reviewed competitive selection process, and which addresses such a high-profile, therapeutically-validated protein target," remarked Dr. Seymour Mong, Ph.D., Vice President of Biotechnology of Structural Bioinformatics Inc. "The annual incidence of breast cancer alone in the U.S. is approximately 182,000 patients. We will be very happy indeed if SBI's research in this area makes even a small contribution to the alleviation of this devastating disease."

The goal of this Phase I SBIR grant is to identify a number of non-peptide small-molecule antagonists which target the HER2 gene product, a transmembrane tyrosine kinase protein belonging to the epidermal growth factor receptor family. SBI will use its patented and proprietary algorithms first to model the dynamic surface of the target protein and then to extract 3D-pharmacophore structural information which is used to computationally prescreen large-scale small-molecule compound libraries (both commercial and in-house generated virtual combinatorial libraries) for likely drug activity. A number of these compounds are then purchased or synthesized for biological testing. In previous projects, after a list of computational "hits" has actually been screened in biological assays to determine inhibition constants, the percentage of compounds meeting a pre-established level of antagonistic activity in vitro has ranged between 5 and 20%. SBI has successfully applied this technology to six clinically-important protein targets on behalf of three corporate pharmaceutical collaborators over the course of the last 18 months. In each case, multiple chemical series of antagonists were generated for each target in the viral protease, protein kinase, hormone and apoptosis areas.