Axys Pharmaceuticals Announces Key Milestone From Aventis; Lead Compound Series for Asthma Selected in Inflammation Program.

Health/Medical Writers

SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--Oct. 3, 2000

Axys Pharmaceuticals, Inc. (Nasdaq:AXPH) announced today the achievement of an important research milestone in its collaboration with Aventis (NYSE:AVE) on Cathepsin S, an enzyme believed to play a critical role in asthma. Axys indicated that a discrete collaboration compound synthesized by Axys had successfully demonstrated in vivo efficacy in a model of asthma, qualifying the compound and its analogs as a lead compound series. This family of compounds has been advanced into lead optimization, including pharmacokinetic evaluation, safety pharmacology, chemical scale-up, and formulation studies. Upon the successful conclusion of these activities, the Company believes that Aventis will formally nominate a clinical development candidate for the treatment of asthma.

Cathepsin S is a member of a large family of cysteine proteases, enzymes that are responsible for the cleavage and breakdown of other natural proteins in normal biological processes. In disease conditions, cysteine proteases can often be misregulated, providing an entry point for drug intervention. Cathepsin S has been highly associated with the processing and activation of the antigen receptor called MHC-II, essential for the initiation of both normal and pathological immune responses mediated by T-cells. Drugs designed to inhibit this enzyme could provide a novel method for control of antigen-induced response in multiple inflammatory diseases such as asthma, COPD, atherosclerosis and a variety of autoimmune and inflammatory diseases.

Approximately 10 months ago, Axys announced achievement of a milestone from Aventis (then Rhone-Poulenc Rorer) following the successful conclusion of in vivo efficacy proof-of-concept studies that confirmed the biological connection of Cathepsin S to the inflammatory process. These studies also showed that inhibiting Cathepsin S could provide a directed way to regulate the pathological imbalances in autoimmunity and inflammation.

"The milestone that we achieved this summer represents another success for the Company's preclinical research group. Moving this novel compound family into final optimization studies reflects the confidence of our partner, Aventis, that a candidate compound for the treatment of asthma will ready for formal nomination as a clinical development candidate in the near term. In addition to the proof-of-concept studies established at the end of last year, the latest studies confirm the potential for the use of the specific candidate in controlling asthma by oral administration," commented Michael C. Venuti, Ph.D., senior vice president, research and preclinical development, and chief technical officer at Axys Pharmaceuticals, Inc.

In December 1998, Axys and Aventis entered into a collaboration to discover and develop small molecule therapeutics that inhibit Cathepsin S. Under the terms of the agreement with Aventis, Axys and Aventis are collaborating on research and development of, among other things, orally bioavailable Cathepsin S inhibitors for asthma, atherosclerosis and rheumatoid arthritis. In addition to the two milestones met less than 18 months from the initiation of the collaboration, Axys remains eligible for a number of additional preclinical and clinical milestone payments.

The Aventis collaboration is one of three continuing small molecule research and development collaborative programs at Axys. In its collaboration with Merck, Axys received a proof-of-concept milestone in 1999 and continues preclinical activities to identify a clinical candidate. In partnership with Bayer AG, Axys has been seeking an oral tryptase inhibitor for the treatment of inflammatory diseases such as asthma, and is currently in a Phase II clinical trial of a tryptase inhibitor, APC-2059, for the treatment of ulcerative colitis. All three partnerships address major chronic diseases such as inflammation, osteoporosis, and asthma and are complementary to Axys' growing proprietary portfolio of oncology research programs.

Aventis (NYSE:AVE - news) is a world leader in life sciences. Focused on two core business areas -- pharmaceuticals and agriculture -- Aventis is dedicated to improving life through the discovery and development of innovative products in the fields of prescription drugs, vaccines, therapeutic proteins, crop production and protection, animal health and nutrition. With global corporate headquarters in Strasbourg, France, Aventis employs around 95,000 people in more than 120 countries and recorded pro forma sales in 1999 of 20.5 billion euros. Aventis was launched in December 1999 through the merger of Hoechst AG of Germany and Rhone-Poulenc SA of France.

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 the minority interest in Discovery Partners International, Inc. (Nasdaq:DPII) resulting from the merger of Axys Advanced Technologies into DPII earlier this year, 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.