Axys Pharmaceuticals Announces Continuation of Phase II Study of Tryptase Inhibitor APC 2059 for the Treatment of Ulcerative Colitis.

Business Editors/Health & Medical Writers

SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--June 1, 2000

Interim Analysis of Data Warrants Study Continuance

Axys Pharmaceuticals, Inc. announced today that, after completing a planned interim data analysis of its Phase II clinical study of APC 2059 for the treatment of ulcerative colitis, it was continuing the Phase II study to its defined clinical endpoints later this year.

APC 2059 is a small molecule tryptase inhibitor delivered by subcutaneous injection. The interim analysis of 25 patients reviewed; the safety and tolerability of the drug; efficacy as measured by the Disease Activity Index (DAI), a clinically accepted measurement of the severity of ulcerative colitis; maintenance of the therapeutic benefit 14 days post-therapy; timing for onset of benefit; and an investigators' global assessment after the course of therapy was completed.

This study enrolled both male and female patients from 18 to 70 years of age who had at least six months history of ulcerative colitis, recurrent symptoms for at least two weeks at the time of first dose of APC 2059 despite the continued use of oral aminosalicylate (5-ASA) therapy, and a DAI score of between 6 and 9 on a scale of 12. The DAI measures parameters such as stool frequency, rectal bleeding, mucosal appearance by endoscopy and the physician's rating of disease activity. By the end of the current Phase II study, a minimum of 61 evaluable patients will have participated in the study. Axys expects the study will be completed by the end of this year.

Background

Inflammatory bowel disease (IBD) actually encompasses several diseases, most notably Crohn's Disease and ulcerative colitis, and has a significant impact on the quality of life for the patients. The etiology of the disease is unknown, but seems to relate to an intestinal overreaction to an environmental agent. Diffuse, superficial inflammation of the mucosal lining and sub-mucosal tissues of the colon is a characteristic of ulcerative colitis, resulting in a chronic cycle of remissions and flares. Gross symptoms for ulcerative colitis include bloody diarrhea, fecal incontinence, abdominal pain and weight loss.

The most reliable estimates indicate a total patient base of approximately one million in the United States for inflammatory bowel disease, with a relatively even distribution between Crohn's Disease and ulcerative colitis. Direct annual healthcare costs of IBD are approximately $700 million, and the total economic impact of both direct and indirect costs would approximate between $2 billion and $3 billion per year. Current therapies include 5-ASA (aminosalicylic acid), steroids, immunosuppressive agents such as cyclosporine and, most recently, anti-TNF-(alpha) therapeutics. Frustration with current therapies is mainly due to the trade-off between efficacy and safety, affecting especially patient compliance. Even on standard drug therapy, 55% of patients will require surgery within 10 years of diagnosis.

APC 2059 is a second-generation molecule that inhibits tryptase, an enzyme that is found in mast cells. Recent biological research strongly suggests that tryptase functions pathologically as a potent mediator of mast cell-related allergic inflammatory conditions. In the gastrointestinal tract, mast cell infiltration and tryptase activity have long been associated with several pathologies, including inflammatory bowel disease, caliginous colitis and gastrointestinal allergy. Significantly elevated tryptase secretion and enzyme activity have been measured relative to controls for ulcerative colitis. Taken together, these observations have suggested that ulcerative colitis is a mast cell and tryptase-mediated disease.

The Company had previously demonstrated the efficacy of tryptase inhibition in inflammatory disease with a first generation proof of concept molecule, APC 366, in an inhaled version for the treatment of asthma. Those studies, completed in the UK, demonstrated that APC 366 could alleviate symptoms associated with allergen-induced asthma, with statistically significant results in the reduction of the late airway response as measured against both baseline and placebo. Axys and Bayer AG have been collaborating on the development of tryptase inhibitors for the treatment of asthma for a number of years. Recently, Bayer AG halted development of the oral compound BAY 44-3428 due to toxicity. APC 2059 and BAY 44-3428 are from distinctively different chemical families. To date, APC 2059 has not demonstrated any dose limiting toxicity in either in vivo or clinical studies.

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, Inc., which recently acquired Axys Advanced Technologies, Inc., Axys' technology leveraging businesses are: PPGx, a majority-owned pharmacogenomics company, and Akkadix Corporation, a minority-owned 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 this or other 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, competition and marketing risk, the risk of unexpected difficulties and delays in the development of new technologies and in expanding its manufacturing capabilities, 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.