Pharmasset Selects Investigational HCV Polymerase Inhibitor PSI-879 for Preclinical Development

Pharmasset, Inc. recently announced that it has chosen its experimental hepatitis C virus (HCV) polymerase inhibitor PSI-352879 (or PSI-879 for short) -- a purine nucleotide analog -- as a candidate for further preclinical development. PSI-879, as well as the company's other investigational nucleoside/nucleotide analogs, may potentially be suitable for use in combination regimens with other directly-targeted oral anti-HCV drugs now in the pipeline.

Below is an excerpt from a Pharmasset press release describing the compound and planned research. (Note: Purine analogs mimic the adenine and guanine nucleotide building blocks of genetic material, while pyrimidine analogs mimic cytosine and thymine nucleotides).

Pharmasset Nominates PSI-879 as a New Nucleotide Analog
Inhibitor of Hepatitis C for Preclinical Development

Princeton, NJ -- October 6, 2009 -- Pharmasset, Inc. (Nasdaq: VRUS) announced today the nomination of PSI-352879 (PSI-879) as a second development candidate from two series of purine analogs for the treatment of chronic hepatitis C virus (HCV) infection. PSI-879 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-879 employs a different prodrug technology than our lead purine nucleotide, PSI-938. We plan to submit an IND for PSI-938 in the first quarter of 2010" stated Michael Otto, PhD, Pharmasset's Chief Scientific Officer. "We now are in a position to have two opportunities to develop a purine and pyrimidine nucleoside/tide combination. We believe in addition to being used in combination, our nucleoside/tide analogs also have the potential to be combined with other classes of direct acting antivirals for HCV."

Preclinical data demonstrate that purine nucleotide analogs have many of the benefits of pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7851, by demonstrating 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.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV) and, secondarily, on the development of Racivir for the treatment of human immunodeficiency virus (HIV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase thus inhibiting viral replication.

We currently have three clinical-stage product candidates. RG7128, a nucleoside analog for chronic HCV infections, is in a Phase 2b clinical trial in combination with Pegasys plus Copegus and is also in INFORM studies, the first studies designed to assess the potential of combinations of small molecules without interferon and ribavirin to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage candidates are PSI-7851, an unpartnered, next generation HCV nucleotide analog which has completed Phase 1 clinical studies and Racivir, for the treatment of HIV, which has completed a Phase 2 clinical trial.

For more information, visit http://www.pharmasset.com.

10/09/09

Source
Pharmasset, Inc. Pharmasset Nominates PSI-879 as a New Nucleotide Analog Inhibitor of Hepatitis C for Preclinical Development. Press release. October 6, 2009.