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VRUS Starts Phase-1b Trial of PSI-7851 in HCV

[PSI-7851 is a nucleotide polymerase inhibitor (#msg-36688204). Unlike R7128, which is licensed to Roche, PSI-7851 is wholly owned by VRUS. As is the case for all FDA-sanctioned monotherapy trials in HCV, the duration of this phase-1b trial is limited to three days to avert the generation of resistant viral strains.]

http://finance.yahoo.com/news/Pharmasset-Initiates-Phase-1b-prnews-15473963.html

›Tuesday June 9, 2009, 6:30 am EDT

- PSI-7851 was generally safe and well tolerated in Phase 1a single ascending dose trial

- Further results from single ascending and multiple ascending dose trials are expected in second half 2009

PRINCETON, N.J., June 9 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS ) announced today that it had completed the single ascending dose study and begun dosing in a multiple ascending dose trial with PSI-7851, a nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. This study is designed to assess the safety, tolerability and antiviral activity of PSI-7851 over 3 days in HCV-infected individuals.

"We are encouraged by the safety and pharmacokinetics of PSI-7851 thus far," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "We believe PSI-7851, Pharmasset's lead second generation nucleotide, has the potential to be administered once a day at low milligram doses, while also continuing to demonstrate the many benefits nucleos(t)ides have over other classes of HCV direct acting antivirals, including a high barrier to resistance, pan-genotype potency, and ability to combine with other classes of compounds."

PSI-7851 Phase 1 Program Overview

The Phase 1 program is investigating the safety, tolerability and pharmacokinetics of PSI-7851 in healthy subjects following single doses (Phase 1a) and in patients chronically infected with HCV genotype 1 following repeat dosing for 3 days (Phase 1b). The Phase 1b study will additionally investigate hepatitis C viral dynamics and monitor for the development of drug resistance.

Subjects in the phase 1a single ascending dose study received single doses of PSI-7851 ranging from 25mg to 800mg or a matching placebo. Preliminary data from the phase 1a single ascending dose study demonstrated:

* No serious adverse events or discontinuations;
* No dose-related adverse events;
* No grade III / IV lab abnormalities;
* No clinically significant changes in vital signs or ECGs.

A Phase 1b multiple ascending dose trial has now been initiated in patients with chronic HCV genotype 1 infection. Subjects will be enrolled at multiple centers and randomized to PSI-7851 (8 per cohort) or placebo (2 per cohort). Based upon the results from the SAD study, the first dose of PSI-7851 to be tested will be 50mg once daily. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-7851 after repeat dosing over 3 days. The secondary objective is to evaluate the decrease in HCV RNA.

Results from both studies are expected in the second half of 2009.

About PSI-7851

PSI-7851 is a uridine nucleotide analog currently in development for the treatment of chronic HCV infection. PSI-7851 has demonstrated potent in vitro anti-HCV activity with EC50 values of 90 +/- 60 nM, which is approximately 15- to 20-fold more potent than Pharmasset's first generation nucleoside polymerase inhibitor, R7128. In vitro studies of PSI-7851 have not shown evidence of any mitochondrial or other cellular toxicities that may be associated with some nucleoside analogs. The half-life of the triphosphate in primary human hepatocytes is approximately 38 hours, which suggests the possibility for once-daily dosing. Like R7128, PSI-7851 has demonstrated in vitro activity against all of the most common HCV genotypes.

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 nucleos(t)ide analogs, a class of compounds which act to inhibit the enzymes required for viral replication. We currently have three clinical-stage product candidates: R7128, a nucleoside analog for chronic HCV infections, has initiated a Phase 2b clinical trial in combination with Pegasys plus Copegus through a strategic collaboration with Roche; PSI-7851, an unpartnered, next generation HCV nucleotide analog, which recently began Phase 1 clinical studies and Racivir, for the treatment of HIV that has completed a Phase 2 clinical trial.‹