Arris' Asthma Drug APC-366 Shows Promising Results.

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--April 30, 1995-- Arris Pharmaceutical Corporation (NASDAQ:ARRS) announced today that a preliminary analysis of the results of its Phase IIa trial of APC-366, an inhibitor of tryptase, a serine protease, serves to validate the Company's belief that tryptase is a promising target for the treatment of asthma.

The data confirm that both dosages of APC-366 evaluated had the effect of improving both the late and the hyperresponsive phases of asthmatic response in the allergen challenge model used in the study and thereby suggest a level of efficacy warranting further study.

The Phase IIa study was designed to accomplish two main objectives: first, to provide proof-of-concept for a therapeutic strategy that focuses on inhibiting tryptase as a treatment for asthma; and second, to determine whether APC-366 was a viable drug candidate for further clinical development.

The study used an allergen challenge model of asthma to evaluate the effect of APC-366 on the three phases of allergic, asthmatic response provoked by allergen inhalation.

Twenty subjects entered the study and received treatment. The subjects were mild-to-moderate asthmatics, male, and between the ages of 19 and 44. All subjects were tested prior to APC-366 or placebo treatment to establish a baseline against which the effects of APC-366 could be measured. The enrollment criteria for the trial required subjects to show a response to allergen challenge.

Subjects were divided into three treatment groups and treated in a double-blind fashion. Two of the groups received APC-366, and one received placebo. Subjects were dosed in the hospital with APC-366 at either 2.5 mg. or 5.0 mg. or with placebo, three times daily for a total of 13 doses.

An allergen challenge was performed after the 10th dose on day four of the study to evaluate the effects of the treatment on the early and late phase asthmatic response, and a histamine challenge was performed after the 13th dose on day five to measure the effect of treatment on the allergen-induced hyperresponsive state.

A total of 18 subjects completed the study. The study was conducted at two sites in the United Kingdom, at Guy's Drug Research Unit in London, under the direction of Dr. Tim Mant in collaboration with Dr. Tak Lee, and at the University of Southampton, under the direction of Professor Stephen Holgate.

The company indicated that positive results were most apparent when subjects within each treatment group were compared at baseline and after treatment. The subjects treated with APC-366 had less bronchoconstriction provoked by antigen after treatment with APC-366 than they did at baseline.

"The results are of a magnitude that suggests therapeutic relevance," indicated Jean Warner, M.D., Arris' vice president for medical affairs.

The company also reported that the results of the Phase IIa study paralleled results seen in earlier sheep models of asthma, specifically, an improvement in pulmonary function. In the Phase IIa study, FEV1, a well-established endpoint, was used to measure the amount of air a subject can forcefully exhale in one second.

In the late phase of asthmatic response to allergen, the study results demonstrated protection against allergen-induced bronchoconstriction, with a median improvement of more than 50% in the 5.0 mg., high dosage, group. In addition, in those subjects that demonstrated airway hyperresponsiveness at baseline, the study showed a protective effect against histamine provocation at both dosage levels.

"The data support our concept that tryptase inhibition has therapeutic utility in the treatment of asthma, and a conclusion that our clinical compound APC-366 has beneficial effects at both dosage levels. As a result, we are reviewing plans to further characterize APC-366 in studies which will focus on dose optimization and on potential delivery systems." Dr. Warner added.

... Patent Allowance on APC-366

In a related announcement, Arris indicated that the United States Patent and Trademark Office has issued a Notice of Allowance on its U.S. Patent Application 212,169, which relates to the tryptase inhibitor APC-366 and structural analogs thereof and the pharmaceutical compositions containing them and their uses as therapeutic agents. The company expects the Patent Office to proceed to issuance within the next four-to-six months.

Arris' collaborator in the development of tryptase inhibitors is Bayer AG of Leverkusen, Germany. APC-366 as well as other potential tryptase inhibitors are covered by the scope of that agreement and are subject to Bayer's rights of commercialization. There can be no assurance that the company's clinical trials will result in marketable products.

Arris Pharmaceutical uses an integrated drug discovery approach combining structure-based drug design, combinatorial chemistry and its proprietary Delta Technology to discover and develop small molecule therapeutics for existing markets where available therapies have significant limitations.

Arris' product development programs include: protease-based discovery programs targeting the inhibition of enzymes implicated in inflammatory and certain other diseases such as asthma, blood clotting disorders, arthritis, osteoporosis, cancer and various infectious diseases; and receptor-based discovery programs, including those designed to discover small molecule drugs that mimic therapeutically important proteins, such as EPO, hGH, G-CSF and TPO, and programs to develop drugs that modulate the activity of receptors involved in diseases such as cancer and diabetes.

CONTACT: Arris Pharmaceutical Corp., South San Francisco

Daniel H. Petree or Shari Annes, 415/829-1000

http://www.arris.com.