BioNumerik Reports The Supercomputer Supported Discovery Of New, Non-Toxic Chemotherapy Protecting Agent

October 13, 1998

San Antonio, TX - October 12, 1998 -- BioNumerik Pharmaceuticals, Inc. today announced a key scientific publication in the October issue of the journal Seminars in Oncology which describes the discovery and mechanism of action of a new non-toxic, second-generation platinum protecting agent, known as BNP7787, which appears to substantially reduce the toxicity of platinum-type anticancer drugs, such as cisplatin and carboplatin.

Cisplatin and carboplatin are widely used in the treatment of a variety of common cancers including small cell and non-small cell lung cancer, ovarian, head and neck, and bladder cancer and many other tumors. However, the administration of cisplatin and carboplatin frequently results in clinically important toxicities, including kidney toxicity, vomiting, and bone marrow toxicity, that pose certain risks and adversely affect the quality of life of patients. BioNumerik investigators began their discovery efforts in this area with the idea that if it were possible to safely increase the total dose or the dose frequency of platinum drugs, this would lead to an increase in tumor response rates and could result in a substantial patient benefit. To date, several platinum protecting agents have been developed by others, but all have suffered from the problem of trading a reduction in platinum-associated drug toxicities for newly-introduced toxicities of their own.

The Seminars in Oncology paper, titled "Modulation of Platinum-Induced Toxicities and Therapeutic Index: Mechanistic Insights and First- and Second-Generation Protecting Agents," authored by Dr. Frederick H. Hausheer, et al., describes new information regarding the chemical basis for the antitumor and toxicologic effects associated with the administration of platinum-type drugs. BioNumerik's chemical, pharmacological and toxicological data, combined with that of other studies, suggest that nearly all of the major clinical toxicities associated with the administration of platinum type drugs can be explained by a common chemical mechanism.

A common feature of many first generation platinum protecting agents is the presence of reactive sulfur-containing chemical groups that can interact with platinum drugs in the blood plasma and can cause toxicity. BioNumerik has pursued the discovery and development of new second-generation platinum protecting compounds that are not highly reactive in the plasma, yet can undergo conversion inside normal cells to form a highly reactive compound that can selectively reduce platinum toxicity. These new compounds were developed based upon a series of supercomputer simulations developed at BioNumerik that involve new quantum mechanical methods capable of calculating the structural, electronic, thermodynamic and vibrational spectra properties of platinum type drugs and related species with far more accuracy than previously possible.

In the paper, BioNumerik researchers report preclinical animal data showing that BNP7787 can completely protect against cisplatin-induced kidney toxicity, vomiting and bone marrow toxicities while increasing cisplatin's antitumor activity. In these studies, tumor bearing animals receiving BNP7787 and cisplatin experienced an increase in complete tumor remissions and reduced toxicity compared to animals receiving the same dose of cisplatin alone. These studies have also shown that a single dose of BNP7787 substantially protects against cisplatin induced suppression of the bone marrow. It was also reported that, in preclinical testing, BNP7787 appears less toxic than table salt, making it non-toxic by pharmaceutical industry standards. BNP7787 is currently in Phase I clinical trials in the United States at the University of Chicago Medical Center and the Roswell Park Cancer Institute in Buffalo, New York and in Europe at the Free University Hospital in the Netherlands.

Richard L. Schilsky, M.D., Director of the University of Chicago Cancer Research Center and Principal Investigator for the University of Chicago BNP7787 Phase I trial indicated, "We are extremely pleased to have the opportunity to conduct Phase I trials on this exciting new drug. BNP7787 has great potential to increase the safety of platinum therapy and to provide meaningful increases in tumor response rates."

In commenting on the data, Dr. Frederick H. Hausheer, BioNumerik's Chairman & Chief Executive Officer stated: "This information represents an important new development in understanding the chemical mechanisms that underlie platinum drug toxicity and antitumor activity. Using this information, we hope to develop better drugs such as BNP7787. The reported preclinical studies demonstrate that BNP7787 appears to substantially protect against the common major toxicities of platinum chemotherapy and does not interfere with the antitumor activity of cisplatin. There also appears to be reproducible evidence of enhancement of cisplatin's antitumor effect by BNP7787. Preclinically, we have observed that BNP7787 can safely and effectively protect against very large increases in the dosage of cisplatin, including lethal doses of cisplatin. To our knowledge, no drug has ever been reported in preclinical models to achieve this level of protection against high doses of cisplatin."
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BioNumerik Pharmaceuticals, headquartered in San Antonio, Texas, is an emerging pharmaceutical company with an innovative, proprietary technology platform for the rapid discovery and clinical development of small molecule based pharmaceuticals for cancer.

BioNumerik is a leader in a powerful new area called "mechanism based drug discovery" which integrates medicine, quantum physics, synthetic chemistry, pharmaceutical sciences and Cray supercomputing. BioNumerik views its approach as a fourth generation technology relative to drug screening, automated screening and combinatorial chemistry, and rational drug design. BioNumerik believes its approach has the potential to greatly reduce the time to discover and bring new drugs into clinical development and to reduce the risk of failure in clinical development. In less than six years, the Company has rapidly advanced two compounds into human clinical trials and a third new compound into late preclinical development.

Editor's Note: This release is also available on the Internet at: http://www.noonanrusso.com
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Noonan/Russo Communications

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