NIH Awards Grant to MetaPhore to Study Cancer Co-therapy Drug.

Business Editors/Health & Medical Writers

ST. LOUIS--(BW HealthWire)--Aug. 1, 2001

The National Cancer Institute of the National Institutes of Health (NIH) has awarded a six-month $104,000 Small Business and Innovation Research (SBIR) grant to MetaPhore Pharmaceuticals, Inc. to study a potential new co-therapy for advanced skin and kidney cancers.

The grant will help fund further pre-clinical studies that MetaPhore is conducting with one of the company's proprietary family of enzyme mimetics, as a co-therapy with interleukin-2 (IL-2). The mimetics replicate the catalytic activity of the natural enzyme superoxide dismutase (SOD), one of the body's primary defenses against free-radical damage to tissues and cells.

MetaPhore recently announced the successful completion of its first Phase I clinical trial with the SOD mimetic, M40403 (injectable), in normal healthy subjects. The drug candidate was shown to be safe and well tolerated. MetaPhore plans to proceed with a Phase II trial of M40403, as a co-therapy with IL-2, in small groups of patients with advanced skin and end-stage kidney cancers. The studies are the first clinical trials for MetaPhore's SOD mimetics, and are also significant because they represent the first time that a small molecule drug developed to mimic an enzyme's activity has been tested in humans, based on published records.

IL-2 is used to treat a number of cancers, particularly inoperable metastatic melanoma and metastatic renal cell carcinoma (RCC) for which it is approved. Approximately 80,000 cases of melanoma and RCC are diagnosed in the U.S. each year.

Use of IL-2 is limited, however, by potentially life-threatening side effects, including extremely low blood pressure (hypotension), particularly at the high-dosage level indicated for end-stage cancers. As a result, a majority of patients undergoing high-dosage IL-2 treatment currently require intensive care (ICU) intervention and many are unable to complete the full course of treatment.

Pre-clinical efficacy studies conducted by researchers with MetaPhore and the Huntsman Cancer Institute at the University of Utah showed that M40403 prevented the onset of IL-2 induced hypotension. In other studies, the mimetic also enhanced the anti-tumor effectiveness of IL-2.

"In combination with IL-2, and potentially other related cytokine cancer treatments, the SOD enzyme mimetic may offer end-stage cancer patients more effective therapeutic options with greatly improved side effect profiles," said Daniela Salvemini, MetaPhore's Vice President and Director of Pharmacology and Principal Investigator for the grant.

Dr. Salvemini will be joined in this project by co-investigator Dr. Wolfram Samlowski, of the Huntsman Cancer Institute.

Background

MetaPhore Pharmaceuticals is a privately held, St. Louis-based drug research and development company that is applying its proprietary enzyme mimetic technology to address the diseases and conditions associated with excessive superoxide free radical production. These include certain types of cancer, pain and inflammation, stroke, heart attack, autoimmune and neurodegenerative disorders, and complications of diabetes mellitus.

As part of the body's oxidative chemistry, SOD enzymes regulate normal levels of superoxide free radicals. In certain disease states, however, the body's immune system prompts an overproduction of superoxide and the natural enzymes are overwhelmed. In excess, superoxide free radicals have been shown to contribute to inflammatory processes, inhibit certain disease fighting mechanisms and deactivate a class of molecules that help maintain vascular pressure.

MetaPhore scientists pioneered the design and development of SOD enzyme mimetics. Previous attempts by the pharmaceutical industry to develop a naturally-derived SOD drug showed promise; however, use of the drug, a bovine form of SOD, was frustrated by the natural form's inherent instability and the body's reaction to its introduction.

The company's SOD mimetics are well suited for use as drugs because they have a low molecular weight, are highly stable and do not appear to elicit an immune response in the body. Furthermore, the chemical structure of the metal-based compounds can be easily optimized for application to different diseases and conditions.

In addition to cancer, MetaPhore is developing its family of enzyme mimetics as drug candidates for pain as well as other diseases and conditions associated with free radical damage.

"SOD mimetics have major medical potential, based on the growing body of research that links free radical-induced damage to numerous diseases and conditions. We can effectively replicate the beneficial action of the SOD enzyme in a stable and selective drug form, and also tailor specific mimetics for each disease state," said Dennis Riley, Senior Vice President of Research & Development at MetaPhore.

For more information, please visit www.metaphore.com.

Statements in this press release that are not strictly historical are "forward looking" statements as defined in the Private Securities Litigation Reform Act of 1995. The actual results may differ from those projected in the forward looking statement due to risks and uncertainties that exist in the company's operations, development efforts and business environment.