Biotech Values

[DewDiligence]

VRUS Starts Phase-1 Trial of PSI-938

[PSI-938 is structurally and mechanistically similar to IDIX’s IDX184, but is about two years behind in development. VRUS’ grand scheme for HCV is to develop a dual-nucleoside regimen where the component nukes have complementary resistance profiles, and this is best accomplished by employing one pyrimidine analog and one purine analog. (The same idea was used by GILD in the HIV market to create Truvada.) RG7128 and PSI-7977, VRUS’ more advanced HCV polymerase inhibitors, are pyrimidine analogs, while PSI-938 (and the follow-on compound, PSI-879) are guanosine (purine) analogs. Of these drugs, only R7128 has been licensed to Roche; the others are wholly owned by VRUS.]

http://finance.yahoo.com/news/Pharmasset-Initiates-First-prnews-3701754589.html?x=0&.v=1

›Thursday April 8, 2010, 7:30 am

PRINCETON, N.J., April 8 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq:VRUS) announced today that dosing has initiated in a phase 1, single ascending dose (SAD) study in healthy volunteers with PSI-938, a third generation purine nucleotide analog polymerase inhibitor of hepatitis C virus (HCV). Pharmasset recently filed an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA).

"PSI-938 is our first purine nucleotide analog to move into clinical development," stated Dr. Michelle Berrey, Pharmasset's Chief Medical Officer. "As PSI-938's resistance profile is different from other nucleoside/tides in development for HCV and it has a different metabolic pathway from pyrimidine analogs, such as RG7128 and PSI-7977, we believe PSI-938 could be potentially combined with other nucleosides in development to deliver a pan-genotype regimen. We look forward to reporting the first antiviral data with PSI-938 in the third quarter of 2010."

Purine and Pyrimidine Analogs

Purine nucleoside/tide analogs have many of the benefits of pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7977, in that they have demonstrated in vitro activity across multiple HCV genotypes, have a higher barrier to resistance than other classes of HCV small molecules in development, and have a lower risk of drug interactions when combined with other direct acting antivirals targeting HCV. In addition, Pharmasset's purine analogs retain activity against the S282T mutation associated with in vitro resistance in other nucleoside/tide analogs in development, and are metabolized to the active triphosphate form through a different phosphorylation pathway than the pyrimidine analogs. Given these characteristics, Pharmasset's purine and pyrimidine analogs have the potential to be combined as part of a future treatment regimen.‹