Assembly Biosciences doses first participant in Phase 1b trial of ABI-4334

Assembly Biosciences announced that the first participant has been dosed in the Phase 1b trial of ABI-4334, a next-generation capsid assembly modulator candidate in development for the treatment of chronic hepatitis B virus infection. Chronic HBV infection is a leading cause of chronic liver disease and liver transplants globally, with the World Health Organization estimating that over one million people died in 2022 from HBV-related causes. Current treatments are lifelong and reduce, but do not eliminate, the virus with very low cure rates. CAMs are direct-acting antivirals with two distinct mechanisms of action, inhibition of HBV DNA replication and prevention of the formation of new cccDNA, the viral reservoir. ABI-4334 is a highly potent next-generation CAM with a potential best-in-class profile and has been specifically optimized to target both mechanisms. In a Phase 1a study, once-daily oral dosing with ABI-4334 demonstrated a favorable safety and pharmacokinetic profile in healthy participants, with ABI-4334 exposure levels projected to achieve strong antiviral activity and double-digit multiples over protein adjusted EC50 for both HBV DNA replication and cccDNA formation. In vitro, ABI-4334 has shown single-digit nanomolar potency against both mechanisms of action and the ability to impact HBV DNA integration. The Phase 1b study that is currently enrolling will evaluate safety, PK and antiviral activity in individuals with cHBV infection over a 28-day treatment period.