Research and Development

A Novel Drug to Combat HIV/AIDS

Sequoia has discovered a family of molecules with outstanding potency against HIV and multi-drug-resistant HIV. These novel protease inhibitors are effective against HIV isolated from sera of patients who were no longer responding to highly active anti-retroviral therapy.

The strategy for discovering this series of compounds was to design an HIV protease inhibitor that was likely to remain potent even as mutations arose. To design such an enzymatic inhibitor, we wanted to be able to discriminate between the invariant and variant atomic contact points within the active site of the enzyme. The core of this discovery program is a computational algorithm that determines the invariant, essential atomic contact points. This platform technology is called Resistant-Repellent™ and uses information derived from families of targets to determine the essential atomic contact points. The result of these efforts has yielded a potent HIV protease inhibitor that is expected to enter clinical trials in 1H07.

A Novel Pharmacokinetic Enhancer

To enhance the half-life of our HIV protease inhibitor, as well as other therapeutics, we designed a series of small molecules that interfere with specific isozymes of the cytochrome P450 system. These PKEs have no anti-viral properties, and have no known therapeutic indications of their own, but enhance the effectiveness of co-administered or co-formulated drugs. Sequoia’s PKEs have applications in several therapeutic areas in addition to HIV/AIDS such as HCV and cancer. The first of these PKEs is expected to enter clinical trials in 2H07.