Axys Publishes Cancer Protease Structure.

Business Editors/Health & Medical Writers

SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--Sept. 26, 2000

Axys Pharmaceuticals, Inc. (Nasdaq:AXPH) announced the solution of the three-dimensional crystal structure of Cathepsin V, a protease believed to play a central role in the immune system, and which has been more recently associated with certain cancers.

The paper will be published in an upcoming issue of the journal Biochemistry, a publication of the American Chemical Society (ACS). An abstract of this paper is available on the ACS Publications website www.acs.org as an ASAP Article. In the paper, Axys scientists describe the atomic resolution (1.6 A) X-ray structure of the new therapeutic target, Cathepsin V, complexed with a highly potent inhibitor that delineates the important binding sites on the enzyme.

According to senior author John R. Somoza, Ph.D., "The structure of Cathepsin V is invaluable in helping design potent and selective inhibitors against this therapeutically-relevant protease. As we apply our chemistry and pharmacology expertise to this target, we hope to be able to identify lead compounds designed specifically for Cathepsin V for use in cancer therapy."

Cathepsin V belongs to a class of proteases called cysteine proteases, and has been shown to be expressed in excessive amounts in certain cancers. The Cathepsin V program forms part of Axys' focus on oncology and makes use of Axys' expertise in working with the papain family of cysteine proteases. Axys currently has programs focusing on the development of inhibitors of several papain family cysteine proteases, including Cathepsin K, Cathepsin S and Cathepsin B, which Axys is pursuing for oncology applications.

Michael C. Venuti, Ph.D., senior vice president of research and preclinical development and chief technical officer of Axys, added that Cathepsin V is only one of several therapeutic targets at Axys for which high-resolution structures have been obtained. He said that the company continues to garner value from its deep expertise in cysteine proteases, the proprietary technology used to identify inhibitors of these enzymes, as well as a broad base of related intellectual property. For example, in 1996, Axys solved the crystal structure of Cathepsin K, an enzyme believed to play an important role in the biology of osteoporosis. That work led to the solution of the crystal structure of Cathepsin S, a related enzyme believed to play a key role in inflammatory diseases such as asthma. The Cathepsin K program is now partnered with Merck (NYSE:MRK), while the Cathepsin S program's partner is Aventis (NYSE:AVE). In addition, the company is evaluating the inhibition of Cathepsin B as a potential new cancer treatment.

Three-dimensional, molecular maps of drug targets such as enzymes allow crystallographers to work closely with medicinal chemists in a structure-based drug design process that significantly accelerates drug discovery. Dr. Venuti noted that crystallography at Axys has enhanced the company's ability to quickly identify potent and specific inhibitors for a range of therapeutic targets being examined both in collaborative programs with pharmaceutical partners and in proprietary oncology research. He also indicated that Axys had successfully combined its expertise in molecular biology, the production and purification of large amounts of protein, and both genomics and proteomics of cathepsins to create structures of multiple members of families of inhibitors which bind to the complex enzymes being studied, and that in the case of Cathepsin K and S, in vivo proofs-of-concept with specific compounds have been achieved, and the programs are rapidly progressing toward the selection of specific clinical development candidates.

The authors of the paper entitled "The Crystal Structure of Human Cathepsin V" include John R. Somoza, Hangjun Zhan, Krista Bowman, Lily Yu, Kyle D. Mortara, James T. Palmer, James M. Clark and Mary E. McGrath.

Axys Pharmaceuticals, Inc. is an integrated small molecule drug discovery and development company. Axys has a broad pipeline of products for chronic therapeutic applications that are partnered with world-class pharmaceutical companies and a proprietary product portfolio in oncology. Axys is also building shareholder value through affiliated businesses that leverage the Axys technologies in order to provide capital for Axys' drug discovery and development programs. In addition to a minority interest in Discovery Partners International (Nasdaq:DPII) resulting from the merger of its combinatorial chemistry business Axys Advanced Technologies, with DPII and the subsequent IPO of DPII, Axys' technology leveraging businesses are: PPGx, a majority-owned pharmacogenomics company, and Akkadix Corporation, an agricultural biotechnology company.

Except for the historical information contained herein, this press release contains forward-looking statements that involve risks and uncertainties which could cause Axys' actual results to differ materially from those discussed here, including the risks inherent in early stage development and the reliance on the efforts of collaborative partners, the risk that Axys collaborations will not be successful, the risk that clinical trials will not proceed as anticipated or may not be successful, the risk that Axys will not be successful in entering into new collaborations, market risk associated with Axys' substantial ownership interest in Discovery Partners International, Inc., competition and marketing risk, and general economic conditions that may affect Axys' actual results and developments. Additional factors that could cause or contribute to such differences include, but are not limited to, those discussed in the sections entitled "What Factors Could Cause Our Results to Differ Significantly from Those You Might Expect?" and "What Other Matters Should Stockholders Consider with Respect to Axys?" in the Axys' SEC Reports, including Axys' report on Form 10-K for the fiscal year ended December 31, 1999.

For more information about Axys Pharmaceuticals, Inc., please visit the company's website at http://www.axyspharm.com.