National Cancer Institute Awards SRI International an R33 'Fast-Track' Grant for Innovative Drug Toxicology Models

SRI Researchers Explore Advanced In Vitro Modeling Systems for Liver Toxicity

MENLO PARK, California - July 14, 2003 - SRI International, an independent contract research organization, has been awarded a two-and-a-half-year exploratory/developmental R33 grant by the National Cancer Institute, a component of the National Institutes of Health, to develop innovative in vitro assays using hepatobiliary (liver) cell systems. The assays will be developed to identify toxicological profiles and predict safety of potential therapeutics for cancer and other diseases.

SRI's novel approach is to build assays around multicellular systems with good survival in culture and the capability to model liver injury and response. SRI has developed a modified technique that extends liver cell viability to 10 days or more, instead of the current two to three days, in combination with classical biomarkers to predict the relative toxicity and target cell specificity of liver toxicants. This advance allows researchers to perform longer-term cell incubations in studying chronic liver exposures and effects such as fibrosis. SRI's approach builds upon techniques for improved slice preparation and culture conditions identified by Alison Vickers, Ph.D., of the Novartis Institute for Biomedical Research.

"We believe SRI's approach can lead to better-informed predictions on the nature and severity of liver damage in humans," said Charles Tyson, Ph.D., director of SRI's Advanced In Vitro Toxicology program and the project's primary investigator. "Performing these assays in vitro facilitates extrapolation of adverse effects in animals to humans before clinical testing, for better confidence in lead drug selection," he continued.

The grant stems from work performed by SRI under an R21 grant that began in 2002. SRI received the follow-on R33 grant after it successfully demonstrated the feasibility of its approach. Because this phased-grant mechanism expedites the NCI's review of scientifically meritorious applications that indicate high potential for commercialization, it is characterized as a "fast-track" award process. It is given for applications that the NCI expects to have a high-risk proof of principle (the R21 stage) followed by a second, larger, scale-up or developmental phase (the R33 stage). The total amount of SRI's R21/R33 phased award is approximately $1.82 million, which represents 100 percent of the total costs for this project effort.

SRI has another R21 research grant under way to devise model systems for predicting pulmonary (lung) toxicity.

About SRI International and SRI's Biosciences Division
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. In addition to conducting contract R&D, SRI licenses its technologies, forms strategic partnerships and creates spin-off companies.

SRI'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.