Identification and Characterization of PPI-461, a Potent and Selective HCV NS5A Inhibitor with Activity Against all HCV Genotypes

Identification and Characterization of PPI-461, a Potent and Selective HCV NS5A Inhibitor with Activity Against all HCV Genotypes -

Reported by Jules Levin
EASL Apr 14-18 2010 Vienna Austria

Richard Colonno, Ningwu Huang, Margaret Bencsik, Eric Peng, Anja Huq, Qi Huang, Min Zhong and Leping Li Presidio Pharmaceuticals, San Francisco, CA, USA


AUTHOR SUMMARY
• HCV NS5A inhibitors belonging to several distinct chemical series identified following an extensive medicinal chemistry effort

• PPI-461 nominated as first clinical candidate
– Highly potent and selective inhibitor in HCV 1a and 1b replicon assays (EC50≤ 0.2 nM)
– Active against other major genotypes (EC50s 0.1-9 nM)
– Possesses desirable ADME and PK properties predictive of once daily dosing in humans
– Well tolerated in a battery of GLP toxicology studies

• Enabling studies completed and regulatory documents filed

• Anticipate initiation of clinical studies in near future