The safety and antiviral activity of CRV431 is built on a robust set of clinical data from chemically-related cyclophilin inhibitors. Naturally occurring cyclosporine A has been used for more than 30 years in the field of organ transplant due to its immunosuppressive properties, and cyclophilin inhibitors such as alisporovir (developed by DebioPharm and acquired by Novartis) achieved clinical safety and efficacy against hepatitis C virus. CRV431 has undergone extensive medicinal chemistry to shed its immunosuppressive activity and optimize its potency and target selectivity, which dramatically increases its therapeutic window for treating hepatitis B.
CRV431 inhibits HBV replication by simultaneously blocking several specific interactions of HBV proteins with host cell cyclophilins, which the virus uses to propagate infection and avoid detection by the cell’s natural antiviral mechanisms. There is also evidence that it blocks the entry of HBV into cells, stimulates an interferon-mediated antiviral immune response, and directly reduces inflammation and fibrosis, a major contributor to cirrhosis and development of liver cancer in chronic hepatitis B patients.
CRV431 has a clearly distinct and complementary mechanism of action, as compared to ContraVir’s clinical stage HBV drug TXL™, which the company believes can act as a cornerstone molecule for a future combination HBV curative treatment.