August 1, 2008 (Vol. 28, No. 14)

Firm’s Bioscience Division Conducts Internal Drug Discovery and Provides Research Services

Over 60 years ago, the groundwork for SRI International was laid when the trustees of Stanford University founded the Stanford Research Institute to support economic development. One of the Institute’s first projects was in collaboration with Chevron to find an artificial substitute for tallow and coconut oil used in soap making, which led to Procter & Gamble’s Tide. In 1970, the Stanford Research Institute became independent from Stanford University and it officially changed its name to SRI International in 1977.

SRI is organized into five divisions, each with an interdisciplinary approach to meeting client and partner needs. The biosciences division performs client-sponsored research and development for government agencies and private businesses and foundations. It boasts all the resources necessary to take a client’s program from an idea to an IND.

“We perform basic research like universities do,” says Walter Moos, Ph.D., vp of the biosciences division. Like biotechnology companies, the group performs drug discovery research to identify potential drug candidates. It also provides preclinical services on a contract basis and helps clients prepare and file INDs.

Researchers in the biosciences division focus on cancer, infectious diseases, immunology, inflammation, and neuroscience. About half the funding comes from the NIH, and a third comes from a variety of relationships with companies, including service contracts and broader partnerships. SRI International also develops drug candidates of its own. To date, SRI has helped advance more than 100 drugs into clinical trials, Dr. Moos reports.

Bridging the Valley of Death

“We perform a range of activities and we often find ourselves bridging the valley of death,” says Dr. Moos. He’s referring to the chasm faced by researchers who have great basic research pointing to a drug candidate but who do not know how to move to the product development stage or who lack the resources to do so. This problem particularly plagues basic researchers at universities. On the other hand, some companies excel at late-stage drug development but they lack innovative ideas. “SRI provides the missing link between basic research and later-stage drug development,” he explains.

Dr. Moos views the drug discovery process as a jigsaw puzzle that requires different skill sets, ranging from basic biology and chemistry to regulatory expertise. “When we partner with someone, each side plays to its unique strengths. SRI molds its skills to a partner’s, improving the chances of a successful outcome.”

Lead Projects

SRI International is a long-time contractor of the NCI; one of its projects included the synthesis of compounds in the NCI Carcinogen Repository, along with preclinical development.

For both government and private clients, SRI can discover new molecular targets and novel lead compounds, develop novel models for testing in vitro and in vivo efficacy, identify mechanisms of action, optimize leads, and create cost-effective syntheses, Dr. Moos says.

Some marketed and clinical-stage cancer drugs developed at SRI include Targretin®, a retinoid receptor ligand marketed by Eisai; tirapazamine, a hypoxic tissue-selective cytotoxin; TAS-108, a selective estrogen receptor modulator licensed to Taiho Pharmaceuticals; and PDX, an improved methotrexate being developed by Allos Therapeutics.

Two drugs in preclinical studies are: SR16157, a dual-acting sulphatase inhibitor and selective estrogen receptor modulator for the treatment of breast cancer, and SR13688, an oral drug that inhibits the oncoprotein AKT. SR13688, a natural compound derived from broccoli, is nontoxic and nonmutagenic at high doses, Dr. Moos notes.

“A natural product derivative may be safer than xenobiotics used in the past and present,” says Dr. Moos. AKT, an increasingly important clinical target, is overexpressed in a variety of human cancers, where it makes tumors resistant to chemotherapy and radiation.

SRI International also has a long history of moving drugs for infectious diseases forward, Dr. Moos reports. The first drug that SRI ever helped to send to market was halofantrine, an antimalarial compound.

In late 2007, the National Institute of Allergy and Infectious Diseases (NIAID) awarded SRI $15.5 million to develop a broadly based screening program for infectious diseases, including HIV and AIDS. SRI will provide preclinical services for new therapeutics, including toxicology and pharmacology screening.

“We work with NIAID, not only in drug discovery,” elaborates Dr. Moos, “but also to make new formulations and do clinical manufacturing to get drugs to the clinic.”

SRI’s infectious disease work also caught the attention of the Department of Defense. Programs are under way to speed the manufacturing of new vaccines and therapies for natural threats like bird flu and man-made biothreats.

Taking a Critical Path

SRI International has adopted some unique models for commercializing new drugs. In collaboration with the FDA and the University of Arizona, it set up the Critical Path Institute in Tucson. “This nonprofit works hand-in-hand with both the FDA and companies to tackle challenges in the later stages of drug development—what the FDA calls the critical path,” says Dr. Moos.

SRI will serve as a neutral third party to solve problems such as identifying patients who will best respond to a new drug to prevent clinical trial failures.

Researchers at and in collaboration with the Critical Path Institute are searching for biomarkers to predict drug response and reduce adverse side reactions. Critical Path’s goal is to bring more new therapies to market at reasonable prices by improving the time-consuming and inefficient processes involved in the clinical testing of drugs.

Neglected diseases like tuberculosis and malaria, which disproportionately impact billions of people in poorer nations, are also a focus at SRI. “Not many big pharmaceutical companies put real effort into these diseases,” comments Dr. Moos.

SRI established a new center for drug research in Harrisonburg, VA, known as SRI-Shenandoah Valley. The Center for Advanced Drug Research at the new facility will study host/pathogen interactions associated with neglected diseases. “We tap into these initiatives to benefit global health,” explains Dr. Moos.

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