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Preclinical Study Finds Protease Inhibitor-Resistant HIV May Have,Reduced Potential to Develop Resistance to Panacos' Bevirimat

WATERTOWN, Mass.--(BUSINESS WIRE)--May 29, 2007 - Panacos Pharmaceuticals, Inc. (NASDAQ:PANC), a biotechnology company dedicated to developing the next generation of antiviral therapeutic products, today announced the results of a new study indicating that HIV resistant to Protease Inhibitors (PI) may have reduced potential for the development of resistance to the HIV maturation inhibitor bevirimat in laboratory assays. The study, carried out by scientists in Dr. Eric Freed's group at the HIV Drug Resistance Program at the National Cancer Institute, Frederick, MD, in collaboration with Panacos, was presented at the Cold Spring Harbor Laboratory's (CSHL) Retrovirus Conference held May 22-27, 2007 in Cold Spring Harbor, NY.

While resistance to bevirimat has not yet been reported in clinical studies, bevirimat-resistant HIV can be generated in the laboratory, as is the case with other HIV drugs. In previous studies where HIV was grown for several weeks in cell culture in the presence of bevirimat at suboptimal concentrations, mutations conferring resistance to bevirimat were found exclusively at or near bevirimat's target, the capsid-SP1 cleavage site in the HIV Gag protein. Cleavage of capsid from SP1, the final step in viral maturation, is mediated by the viral protease enzyme. Bevirimat inhibits this cleavage step by interacting with the capsid-SP1 junction in Gag, suggesting that pre-existing PI resistance mutations may have an impact on the development of bevirimat resistance.

In the new study, wild-type HIV, as well as HIV bearing major mutations conferring PI resistance, were grown in cell culture in the presence of bevirimat at suboptimal concentrations. Bevirimat resistance developed after several weeks in both wild-type and PI-resistant HIV, but took more than twice as long to develop in the PI-resistant virus. The bevirimat resistance mutation that appeared in PI-resistant virus was located at th
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