Assembly Biosciences Begins Phase 1b Trial of ABI-4334 for Chronic Hepatitis B

On June 18, 2024, Assembly Biosciences, Inc. (Nasdaq: ASMB), a biotechnology firm focused on creating advanced therapeutics for severe viral diseases, announced that the inaugural participant has been administered a dose in the Phase 1b trial of ABI-4334. This next-generation capsid assembly modulator (CAM) candidate aims to treat chronic hepatitis B virus (HBV) infection.

Chronic HBV (cHBV) infection is a major global health issue, leading to chronic liver disease and liver transplants. The World Health Organization reported that more than one million deaths in 2022 were attributed to HBV-related causes. Current treatments often need to be administered for life, reducing the virus but not eliminating it, and achieving very low cure rates. CAMs are a class of direct-acting antivirals with two distinct mechanisms: they inhibit HBV DNA replication and prevent the formation of new cccDNA, which serves as the viral reservoir. ABI-4334 stands out as a highly potent next-generation CAM optimized to affect both these mechanisms.

In a Phase 1a study, ABI-4334 showed a favorable safety and pharmacokinetic (PK) profile when administered once daily to healthy participants. The exposure levels of ABI-4334 are projected to provide strong antiviral activity, significantly exceeding the protein-adjusted EC50 for both HBV DNA replication and cccDNA formation. In vitro tests have demonstrated that ABI-4334 has single-digit nanomolar potency against both mechanisms and can impact HBV DNA integration. The ongoing Phase 1b study aims to assess the safety, PK, and antiviral activity of ABI-4334 in individuals with cHBV infection over a 28-day treatment period.

Dr. Anuj Gaggar, Chief Medical Officer of Assembly Bio, expressed optimism about ABI-4334's potential, citing its high preclinical potency and the commencement of dosing in the trial. The 28-day placebo-controlled study will measure the effects of increasing doses of ABI-4334 on HBV DNA, refine the projected activity against cccDNA formation, and generate key safety data. Interim results from the study are expected later this year.

This Phase 1b trial, known as ABI-4334-102, is a randomized, blinded, and placebo-controlled dose-ranging study. It will evaluate the safety, PK, and antiviral activity of ABI-4334 in participants with cHBV infection who may be treatment-naïve or off-treatment and either positive or negative for hepatitis B e antigen (HBeAg). Up to five sequential cohorts of 10 subjects each will be enrolled, totaling up to 50 subjects, randomized in an 8:2 ratio between ABI-4334 and placebo. The treatment period will last 28 days.

The study aims to assess the safety, tolerability, and PK of ABI-4334, as well as changes in HBV DNA levels associated with the treatment. The trial's outcomes will inform dose selection for future clinical studies.

ABI-4334 remains an investigational product candidate that hasn't been approved anywhere globally, and its safety and efficacy are yet to be established. Assembly Biosciences is a biotech company dedicated to developing innovative small molecule therapeutics to tackle serious viral diseases and improve patient outcomes worldwide. Led by a skilled team in virologic drug development, the company is committed to addressing the chronic impacts of herpesvirus, hepatitis B virus (HBV), and hepatitis delta virus (HDV) infections.