NIH awards grant to Metaphore to study cancer co-therapy drug

August 01, 2001

St. Louis, Mo., August 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

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.

Kupper Parker Communications

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to