Flossie Wong-Staal, Ph.D., CSO and executive vp research at ItherX, says that the conference is happening at a good time for her company. “We just licensed a compound that failed as an anti-inflammatory that has great potential in the HCV space. It already has a good safety profile in over 250 human subjects and is highly potent against HCV entry (EC50 in the picomolar range). This drug is now ready for a proof of concept clinical study in HCV patients.
“Our back-up candidates exhibit EC50 of <1 nM and a >10,000-fold therapeutic window in our assays has been shown using both genotype 1 and genotype 2 HCV. All the entry inhibitors act additively with the current standard of care as well as an HCV protease inhibitor,” says Dr. Staal. “Furthermore, the compounds are equally potent against a protease mutant virus that is resistant to the protease inhibitor. This class of compounds can add significantly to a drug cocktail targeting multiple steps of the viral life cycle, with the goal of completely eliminating virus infection.”
Dr. Wong-Staal will talk about developing entry inhibitors for HCV. “We’ve developed different programs for targeting virus entry at different points. ITX5081 and its back-up compounds target a known HCV receptor, SR-B1. We have a series of compounds that target the HCV virus envelope. This is at the lead-optimization stage. A third program is based on a new receptor for HCV that we have discovered and shown to be essential for HCV infection of liver cells.
“This target is amenable to both biologics and small molecule drug development. Unlike HIV, which utilizes one of two alternative co-receptors for virus entry, HCV engages multiple receptors in series, and it appears that blocking any of these receptors would affect virus inhibition. Furthermore, such inhibitors should be able to work synergistically with each other, as well as with inhibitors using other modes of action.”