InterMune announced today the presentation of preclinical data on the discovery and characterization of a number of potent and selective small molecule inhibitors of the hepatitis C (HCV) NS3/4 protease.
These molecules are part of InterMune's robust HCV protease inhibitor program and demonstrate promising potency, bioavailability and metabolic stability in preclinical models. The data were presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) being held in Boston this week.
According to the Centers for Disease Control an estimated 3.9 million (1.8%) Americans have been infected with HCV, of whom 2.7 million are chronically infected, and the prevalence of chronic HCV is increasing. Currently available therapies are insufficient, creating a need for the development of novel therapeutic approaches. Protease inhibitors represent a promising class of drugs for HCV, and the HCV NS3/4 protease is an attractive drug target because of its involvement in viral replication and suppressive effects on host response to viral invasion.
InterMune and Array BioPharma scientists worked in collaboration to discover novel small molecule inhibitors of the HCV NS3/4 protease. Compounds were designed using computational modeling techniques and optimized to achieve high potency. Preclinical plasma pharmacokinetic analysis following intravenous and oral administration was then used in conjunction with other in vitro assays and stability studies to optimize the compounds.
"We have discovered highly potent, metabolically stable, orally available small molecule inhibitors of the HCV NS3/4 protease," said Lawrence Blatt, Ph.D., Senior Vice President of Preclinical and Applied Research at InterMune, who presented the data. "Our preclinical data provide us with the rationale to further test these compounds with the goal of selecting the most appropriate candidate to take into the clinic for development as a treatment for patients with HCV."
In addition, InterMune and Array BioPharma announced the extension of their collaboration, which has focused on the discovery and development of small molecule drugs directed against HCV since 2002. Under this extension, Array will perform process research and cGMP scale-up through Phase I clinical trials of drug candidates resulting from the program. In addition, Array will create second-generation compounds as back-up candidates for the program.
"We are very excited by the progress we have made advancing our novel small molecule program and as a result we have extended our collaboration with Array BioPharma. This extended agreement provides a valuable opportunity to continue the development of novel HCV inhibitors, which we believe may one day prove to be an important component of treatment for HCV patients," said Dan Welch, Chief Executive Officer and President of InterMune. "In addition to our protease inhibitor program, we are advancing our robust and late stage HCV pipeline and growing our marketed brand, Infergen(R) (interferon alfacon-1) for HCV."