National Cancer Institute Selects SRI International's Novel AKT Inhibitor Drug for Further Development as a Cancer Chemopreventative

Novel Drug Shows Potent Oral Anti-Tumor Activity against Preclinical Tumor Models

MENLO PARK, California - Mar. 17, 2003 - The National Cancer Institute (NCI) has approved a cancer prevention drug developed by SRI International, an independent research and development organization, for inclusion in the NCI's "Rapid Access to Preventive Intervention Development" (RAPID) program. This is the first time an SRI drug candidate will be developed in the RAPID program, which is designed for the expeditious movement of novel drugs from the lab to the clinic.

"SRI expects that the drug, SR13668, will have three potential clinical applications: primary prevention for healthy, high-risk individuals to reduce the risk of developing cancer; adjuvant prevention for cancer survivors to suppress cancer indefinitely and thus prevent cancer recurrence; and single and combination agent therapy," said Glenn Rice, Ph.D., vice president of SRI's Biosciences Division.

The development of this drug candidate in the RAPID program will provide necessary data for its filing as an Investigational New Drug (IND) with the U.S. Food and Drug Administration (FDA). The RAPID program will assist SRI's development of the drug by providing preclinical and Phase I clinical development support with a goal of reaching Phase II clinical efficacy trials.

About SR13668
Cancer prevention drugs involve the use of natural or synthetic substances on a long-term basis to reduce the risk of developing cancer in apparently healthy individuals, or the chance of cancer recurrence. SRI has discovered and optimized through computer-aided structural analysis and rational design, a novel class of orally active analogues of dietary components whose effects include anti-proliferation, apoptosis and anti-angiogenesis. SR13668 exhibits potent tumor growth inhibitory activity and potently inhibits invasion. It is also active against tamoxifen-resistant cells and inhibits drug resistant tumors in vivo. Moreover, preliminary safety studies show that SR13668 is nontoxic and nonmutagenic at doses vastly exceeding required therapeutic levels.

SR13668 works through inhibition of the cell survival-promoting oncoprotein AKT. This oncogene has attracted much attention from researchers because of its central role in regulating cell proliferation and survival. It is abnormally activated in many human malignancies such as breast, prostate, lung, pancreatic, liver, ovarian and colorectal cancers. Increased activation is linked with tamoxifen resistance, drug and radiation resistance, and apoptosis resistance. AKT activation and overexpression has been shown to be tightly linked with increased invasion and angiogenesis signaling, and is correlated with poorer outcomes in human prostate and breast cancers.

"This oncogene appears to be an extremely important clinical target for inhibiting tumor drug resistance and invasion, either in the context of use as either an adjunctive chemopreventative or as a therapeutic drug," said Dr. Rice.

SRI senior organic chemist Ling Jong, Ph.D. and senior biochemist Wan-Ru Chao discovered the drug candidate. For her work in this drug class, Dr. Jong was awarded first place in the California Breast Cancer Research Program's Cornelius L. Hooper Award for Innovation of Research in Fall 2002.

About SRI International's Biosciences Division
SRI International's Biosciences Division works with government agencies and commercial pharmaceutical companies, large and small, to provide a broad range of preclinical discovery and development services, including medicinal chemistry, custom synthesis, efficacy and safety evaluations, pharmacokinetics and metabolism studies, analytical chemistry, and formulation design and production in a GLP and cGMP environment.

SRI announced in December 2002 that the NCI's Developmental Therapeutics Program selected SR16158, a novel breast cancer treatment agent discovered by SRI, for its competitive RAID (Rapid Access to Intervention Development) program. RAID is accelerating further preclinical development of this drug candidate to determine its efficacy against hormone-dependent breast cancer. More information about the RAPID and RAID programs can be found at http://www.cancer.gov.

About SRI International
Silicon Valley-based SRI International (http://www.sri.com) is one of the world's leading independent research and technology development organizations. Founded as Stanford Research Institute in 1946, SRI has been meeting the strategic needs of clients for more than 55 years. The nonprofit research institute performs contract research and development for government agencies, commercial businesses and private foundations. SRI is well known for its innovations in information technology, telecommunications, engineering, pharmaceuticals, chemistry, physics, and the public policy areas of education, health, and economic development. In addition to conducting contract R&D, SRI licenses its technologies, forms strategic partnerships and creates spin-off companies.