Clinical Trial of Enzyme Mimetic Compound for Oncology
St. Louis, MO, May 31, 2001 -- MetaPhore Pharmaceuticals, Inc. today announced that it has received FDA approval of its Investigational New Drug (IND) application to conduct clinical trials in the U.S. to evaluate M40403, one of its enzyme mimetic compounds.
MetaPhore has initiated a Phase I study to test the safety and tolerability and to determine the pharmacokinetics of the compound in normal, healthy human subjects, as a precursor to Phase II trials in which M40403 will be tested as a co-therapy with interleukin-2 (IL-2) for advanced skin and end-stage kidney cancers. This study is the first human clinical trial for MetaPhore and the company's proprietary family of enzyme mimetic compounds that effectively mimic the action of one of the body's primary free-radical fighting mechanisms, the natural enzyme superoxide dismutase (SOD)
In addition to cancer, MetaPhore is developing these compounds as drug candidates for pain and other diseases and conditions that have been associated with free-radical damage to tissues and cells.
"The opening of this IND marks a major step for MetaPhore and our SOD enzyme mimetic program. For many years, we have understood the free-radical fighting power of the body's natural SOD enzymes, but only recently have we been able to reproduce that benefit in a stable and selective drug form," said Denis Forster, Chief Operating Officer of MetaPhore. "These novel therapeutics have tremendous potential, based on the growing body of research linking free-radical mediated damage with a wide range of acute and chronic disease states."
Preclinical studies in animals, including several recently presented at the American Association for Cancer Research at the end of March, have shown that M40403 significantly improves the effectiveness of IL-2, an approved treatment for inoperable metastatic melanoma and metastatic renal-cell carcinoma. Approximately 80,000 cases of melanoma and renal-cell carcinoma are diagnosed in the U.S. each year.
IL-2 immunotherapy works by activating natural killer (NK) cells that have the ability to recognize and destroy many types of tumors. Its use 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.
In animal studies conducted by researchers at the Huntsman Cancer Institute at the University of Utah in Salt Lake City and at MetaPhore, the enzyme mimetic showed an ability to reverse and prevent the onset of an IL-2 induced blood-pressure drop. The studies also showed that the enzyme mimetic enhances the direct anti-tumor properties of IL-2 therapy.
"Based on these encouraging preclinical results, the SOD enzyme mimetic may offer improved therapeutic options for end-stage cancer patients, with a greatly reduced side-effect profile," added Dr. Wolfram Samlowski, one of MetaPhore's principal collaborators with the Huntsman Cancer Institute.
The natural SOD enzyme plays a central role in the body's oxidative chemistry, regulating normal levels of free-radical superoxide molecules. In certain disease states, however, the body's immune system prompts an overproduction of superoxide free radicals and the natural SOD enzymes become overwhelmed, leading to tissue and cell damage.
Free radicals also play a role in the body's natural blood-pressure regulatory system. In excess, superoxide free radicals deactivate a class of molecules, called catecholomines, that constrict blood vessels, resulting in hypotension (low blood pressure). By reducing the level of superoxide, the SOD enzyme mimetics have been shown to reverse hypotension and effectively restore blood pressure in several different animal models. These studies formed the basis for MetaPhore's exploration of its enzyme mimetics as a co-therapy with IL-2 cancer treatment.
Cancer research by other investigators has further revealed an excess of superoxide in surrounding tissues, paired with deficient amounts of SOD in the cancer cells themselves. In these states, superoxide also inhibits the activity of NK cells, thus hampering the effectiveness of immunotherapies such as IL-2. By selectively catalyzing the excessive superoxide in cancer states, the enzyme mimetic appears to work synergistically with IL-2 and, potentially other, cytokine-based immunotherapies.
MetaPhore Pharmaceuticals is a 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 production. In preclinical models, the primary drug candidates from this family of compounds has suggested the potential to combat such diseases and conditions more effectively and with fewer side effects than existing treatments by selectively catalyzing the removal of superoxide. The company's SOD enzyme 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.
For more information, please visit MetaPhore's web site at 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.
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For more information, contact:Punnie Donohue314-290-2014[email protected]
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