InterMune hepatitis compounds show preclinical promise

The drug candidates are small molecule inhibitors of the hepatitis C virus (HCV) NS3/4 protease. These molecules, which have been shown previously to be highly potent, metabolically stable and orally available, are part of InterMune’s protease inhibitor program.

InterMune and Array BioPharma scientists collaborated on the preclinical study. In vitro studies showed that the two compounds were stable on incubation with human liver cells and displayed a high degree of selectivity. Neither compound showed significant inhibition of cytochrome P450 isoforms (liver enzymes that break down toxins and other substances processed in the liver) or hERG channel-blocking activity (a complication that can lead to abnormal cardiac rhythm).

In preclinical models, both compounds showed concentrations in the liver in orders of magnitude above the EC50 level (the concentration that leads to 50% maximal response and a measure of the potency of a drug). The two compounds were well tolerated after seven days of dosing. No change in weight, abnormalities in clinical chemistries or hematology tests or mortality were observed.

“We were very encouraged to find that these two novel HCV NS3/4 protease inhibitors selectively targeted the liver, did not adversely impact the heart or liver and were well tolerated,” said Dan Welch, president and CEO of InterMune. “Based on these new data, we are moving these compounds into investigational new drug application (IND)-enabling toxicology studies in order to select the most appropriate clinical candidate.”