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Pharmasset Nominates PSI-938 as a New Nucleotide Analog Inhibitor of Hepatitis C for Preclinical Development
Date:7/7/2009

PRINCETON, N.J., July 7 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today the nomination of PSI-352938 ("PSI-938") as a lead development candidate from two series of purine analogs for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is a proprietary nucleotide analog polymerase inhibitor of HCV that is being advanced into studies required for submission of an Investigational New Drug (IND) application with the FDA or equivalent foreign regulatory application.

"PSI-938 is particularly interesting to us since it differs from our pyrimidine analogs, R7128 and PSI-7851, because it has a complementary resistance profile and is metabolized through a different phosphorylation pathway," stated Michael Otto, PhD, Pharmasset's Chief Scientific Officer. "These differences may prove to be particularly important as we explore combinations of nucleos(t)ides in clinical development in the future."

Purine nucleos(t)ide analogs have many of the benefits of pyrimidine nucleos(t)ide analogs, like R7128 and PSI-7851, in that they have demonstrated in vitro activity across multiple genotypes, a higher barrier to resistance than other classes of HCV small molecules in development, and the potential to be combined with other direct acting antivirals targeting HCV. In addition, these purine analogs are also active against the S282T resistant variant selected in vitro by the pyrimidine analogs, and are metabolized to the active triphosphate form through a different phosphorylation pathway than the pyrimidines. Given these characteristics, purine and pyrimidine analogs have the potential to be combined as part of a future treatment regimen.

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