Maxim Caspase Inhibitor Protects Against Liver Apoptosis in Preclinical Study.

Business Editors & Health/Medical Writers

BIOWIRE2K

SAN DIEGO--(BW HealthWire)--Feb. 26, 2001

Maxim Pharmaceuticals (Nasdaq:MAXM)(SSE:MAXM) announced the publication of a preclinical study demonstrating that its investigational caspase inhibitor CV1013 protected critical cells of the liver from programmed cell death in a mouse model, providing further insight into the mode of action of this family of compounds.

The publication, "Protection Against TNF-Induced Parenchymal Cell Apoptosis during Endotoxemia by a Novel Caspase Inhibitor in Mice," appeared in the November 15, 2000 issue of Toxicology and Applied Pharmacology (volume 169, pp. 77-83).

Caspases are key enzymes that modulate and carry out the cellular signaling pathways involved in programmed cell death, also known as failure due to cell death. Compounds such as CV1013 that can inhibit caspases may potentially form the basis for new drugs for endotoxic shock and other degenerative diseases. CV1013 is a member of one of several novel families of caspase inhibitors identified to date by Maxim through its proprietary apoptosis drug discovery program.

In this study, mice were administered galactosamine and endotoxin (Gal/ET), chemical agents that are used to induce endotoxemia resulting in liver failure due to cell death. Doses of 10 or 1 mg/kg of CV1013 administered 3, 4.5, and 5.5 hours after Gal/ET greatly reduced the amount of liver cell apoptosis in treated animals relative to animals not receiving CV1013. All mice treated with CV1013 survived with little or no liver injury after Gal/ET administration. In contrast, all control animals died within 12 hours of Gal/ET administration due to shock and liver failure. Biochemical data are consistent with the hypothesis that CV1013 inhibited primarily caspase 8, thereby blocking the initial intracellular signal that would be expected to lead to apoptotic cell death and liver failure.

"Maxim's live-cell, high-throughput screening technology forms the basis for our caspase modulator program that is generating a rapidly growing portfolio of compounds," said Larry G. Stambaugh, CEO and president of Maxim Pharmaceuticals. "Studies such as these highlight the potential of this program, and we are continuing our efforts directed toward preparing our most promising compounds for clinical development and/or corporate collaborations."

Maxim Pharmaceuticals is a late-stage pharmaceutical company developing advanced drugs and therapies for cancer and infectious diseases. Ceplene(TM) (histamine dihydrochloride), the company's lead product candidate, is undergoing Phase III cancer clinical trials in 12 countries for malignant melanoma and acute myelogenous leukemia, in addition to Phase II trials in hepatitis C and advanced renal cell carcinoma. The company has also developed product candidates based on its MaxDerm(TM) technology that are designed for the treatment of medical conditions for which topical therapy is appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions. Lastly, Maxim is developing small-molecule inhibitors and activators of caspases, key enzymes that modulate and carry out the cellular signaling pathways involved in programmed cell death, also known as apoptosis. Compounds that can either inhibit caspases or induce caspases may form the basis for important new drugs for a wide variety of disease targets, such as cancer, cardiovascular disease and other degenerative diseases.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy and intended utilization of Ceplene, MaxDerm and the caspase modulator compounds, and regarding the Company's preclinical studies and clinical trials. Such statements are only predictions and the Company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in more advanced research or in clinical trials, the risk that the Company's high-throughput screening technology will not generating promising compounds as rapidly as anticipated, and the risk that the Company will not obtain approval to market its products. These factors and others are more fully discussed in the Company's periodic reports and other filings with the Securities and Exchange Commission.

Note: Ceplene(TM), MaxDerm(TM), and the Maxim logo are trademarks of the company.

Editor's Note: This release is also available on the Internet at: http://www.maxim.com.