SRI International Awarded National Institute of Allergy and Infectious Diseases Contract to Develop Oral Formulation for Anti-Radiation Drugs.

MENLO PARK, Calif. -- SRI International, an independent nonprofit research and development organization, today announced it has received a contract from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, for $931,000 to develop an oral formulation for calcium DTPA and zinc DTPA, two drugs approved for decorporation. Decorporation agents increase the rate of elimination or excretion of absorbed, inhaled or ingested radioactive contaminants.

Pentetate calcium trisodium diethylenetriaminepentaacetate (Ca-DTPA) and pentetate zinc trisodium DTPA (Zn-DTPA) are FDA-approved for inhalation or intravenous administration for the treatment of internal contamination from plutonium, americium or curium. DTPA is currently given only by intravenous injection or inhalation.

DTPA is an effective chelator (a substance that binds particular ions) of ingested radioactive materials, and is a potential medical countermeasure for defense against possible terrorist attacks. The U.S. Department of Heath and Human Services (DHHS) Office of Public Health Emergency Preparedness (OPHEP) intends to acquire intravenous and alternative formulations for Ca-DTPA and Zn-DTPA for the Strategic National Stockpile (www.bt.cdc.gov/stockpile/). The Strategic National Stockpile is part of a comprehensive government effort to develop and make available modern, effective drugs, vaccines and medical countermeasures to protect against attack by biological, chemical, or radiation/nuclear weapons or dangerous pathogens.

"Oral formulations of anti-radiation drugs will improve patient compliance with necessary treatment following exposure to a radioactive material," said SRI's Helen Parish, senior director, pharmaceutical sciences. "In a mass exposure situation, it will be safer, faster, and less expensive to administer DTPA if it can be provided orally."

In phase 1 of the project, SRI researchers will develop orally viable formulations for each of the DTPA compounds. Both Ca-DTPA and Zn-DTPA currently demonstrate negligible oral bioavailability. SRI will attempt to overcome the poor oral bioavailability of the drug using a combination of absorption enhancers and targeted delivery.

The most suitable formulations will be recommended for in vivo proof-of-principle studies. Pilot batches of candidate drug products will be manufactured and entered into accelerated stability studies since stability is essential for extended storage in stockpiles.

In an optional second phase of the study, SRI researchers will compare the bioavailability, pharmacokinetics, toxicology and efficacy of the oral formulations to intravenous formulations. Once the research studies are complete, it will be possible to begin nonclinical and clinical bridging studies necessary to demonstrate appropriate safety and plasma levels.

About SRI's Biosciences Division

The SRI Biosciences Division is a unique organization of nearly 200 people, with all of the resources necessary to take chemical and biological research programs from "idea to IND"(TM) -- from initial discovery to investigational new drug applications to start human clinical trials. The Biosciences Division performs basic research on disease mechanisms like an academic institution; drug discovery and the development of biologics like a biotechnology or pharmaceutical company; and full-service preclinical contract research and development like a CRO (contract research organization).

To date, SRI has developed nine drugs internally that have entered clinical trials, with several more currently undergoing preclinical evaluation. Marketed examples of these drugs include bexarotene and halofantrine. Additionally, working with government and industry partners, SRI has helped advance more than 100 drugs into clinical trials, and more than 30 drugs onto the market. Through collaborations with other divisions at SRI, Biosciences is also working at the interfaces of science to create technical platforms for the next generation of drug discovery and development in areas such as drug delivery, real-time diagnostics and systems biology.

About SRI International

Silicon Valley-based SRI International (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 60 years. The nonprofit research institute performs client-sponsored 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.