Axys Pharmaceuticals Advances Ulcerative Colitis Program Based On Encouraging Phase II Results.

Business Editors and Health/Medical Writers

SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--Jan. 10, 2001

Axys Pharmaceuticals, Inc. (Nasdaq:AXPH) announced today that it will advance its ulcerative colitis (UC) program based on encouraging Phase II results, as demonstrated in patient response and the achievement of certain clinical benefits. The Company said that it had completed its open-label Phase II clinical study of APC 2059 for the treatment of patients with moderate to severe flares of ulcerative colitis in late 2000. APC 2059 is a small molecule tryptase inhibitor that was delivered in this study by subcutaneous injection.

The data analysis included the safety and tolerability of APC 2059; 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; and an Investigators' Global Assessment (IGA) 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 11 on a scale of 12, with 0 being normal. The DAI measures parameters such as stool frequency, rectal bleeding, mucosal appearance by endoscopy and the physician's rating of disease activity. In this study, the dosage of APC 2059 was 20 mg delivered subcutaneously twice a day (sc bid), while patients continued their oral aminosalicylate therapy.

By the end of the Phase II study, there were 53 evaluable patients out of 56 total enrolled. The encouraging results of the study indicated:

-- APC 2059 delivered at 20 mg sc bid appeared to be safe and well-tolerated;

-- 51% of the evaluable patients had improvement indicated by a DAI reduction
of -- 4 (greater than or equal to 4);

-- 68% had a reduction in stool frequency;

-- 68% had a reduction in rectal bleeding;

-- 58% achieved "clinically significant benefit" as measured by the IGA;

-- 30% achieved a DAI -- 3 (less than or equal to 3), of whom 81% maintained
that response during the 2-week follow-up period;

-- 3 patients (out of 56) withdrew from the study, one for dizziness, one for
muscle weakness, and one was lost to follow-up early in the protocol.

"The results of this study encourage us to proceed further with the development of APC 2059 for ulcerative colitis," said Paul J. Hastings, President and Chief Executive Officer of Axys. "The improvements seen in moderate to severe UC patients already maintained on the current standard of aminosalicylate therapy indicate that APC 2059 may offer additional benefit for patients who might otherwise resort to an acute course of steroid treatment."

Hastings added that the positive results of this study warrant continuation of the clinical program into placebo-controlled Phase IIb/III clinical trials to further define the product profile, including dosage form, duration and frequency. He noted that the anti-inflammatory mechanism of tryptase inhibitors demonstrated in Axys' previous clinical trials in asthma and in a number of animal models of inflammation indicate that this class of compounds may offer a viable alternative to steroid therapy for patients who may become refractory to standard treatment.

Background

Ulcerative colitis, like Crohn's Disease, is an inflammatory disease of the colon from which approximately one-half million patients suffer, with males and females affected equally. 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 and a poor quality of life for the patients. Gross symptoms for ulcerative colitis include bloody diarrhea, fecal incontinence, abdominal pain and weight loss.

Current therapies include 5-ASA (aminosalicylic acid), steroids, immunosuppressive agents such as cyclosporine and, most recently, anti-TNF-(alpha) therapeutics -- all of which are targeted at reduction of intestinal inflammation. Although all of these therapeutic strategies offer increasing degrees of relief, a trade-off between their safety and efficacy often affects patients' ability to stay within a prescribed regimen. Patients are usually diagnosed before the age of 30 and despite standard drug therapy, 55 percent 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 may well be 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, in an inhaled version for the treatment of asthma. Those studies completed in the U.K. with Bayer AG demonstrated that a tryptase inhibitor 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 its partner Bayer AG are collaborating on the development of oral tryptase inhibitors for the treatment of asthma. However, APC 2059 is from a distinctively different chemical family than the compounds under investigation as oral therapies by Bayer AG.

Axys Pharmaceuticals, Inc., an integrated small molecule drug discovery and development company, 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 minority investments in affiliated businesses that leverage the Axys technologies. Currently, these companies include Discovery Partners International, Inc. (Nasdaq:DPII), a chemistry services company; DNA Sciences, a genetics 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 risk that clinical trials will not proceed as anticipated or may not be successful, 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 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.