Assembly Biosciences Announces Phase 1b Interim Results for ABI-4334 in Chronic Hepatitis B Trial

Assembly Biosciences, Inc., a biotech firm located in South San Francisco, has shared promising interim results from its ongoing Phase 1b clinical trial of ABI-4334, targeting chronic hepatitis B virus (HBV) infections. ABI-4334 is a next-generation capsid assembly modulator (CAM) under investigation for its potential to combat serious viral diseases.

The Phase 1b study commenced with a cohort receiving a 150 mg oral dose of ABI-4334 daily over a span of 28 days. The results demonstrated significant antiviral efficacy, with a marked decline in HBV DNA levels by an average of 2.9 log IU/mL among predominantly hepatitis B e antigen (HBeAg) negative participants. For those with initially detectable HBV RNA, a mean reduction of 2.5 log U/mL was observed. Despite these reductions, changes in viral antigens within the 28-day period were minimal, aligning with preclinical findings of ABI-4334's high potency.

The investigational drug's pharmacokinetic (PK) profile revealed a half-life conducive to once-daily dosing, with clinical exposure levels multiple times higher than what is deemed necessary for strong antiviral action and cccDNA formation inhibition. Safety evaluations from both cohorts indicated that ABI-4334 was well-tolerated, showcasing a favorable safety profile without severe adverse events or study drug discontinuations. Notably, two grade three laboratory abnormalities were recorded in the 150 mg cohort—one participant experienced an alanine aminotransferase elevation and another a total bilirubin increase. Both conditions resolved with continued treatment, whether with ABI-4334 or placebo.

Dr. Anuj Gaggar, Chief Medical Officer of Assembly Bio, expressed optimism over these findings, highlighting the strong antiviral activity of ABI-4334 in the initial cohort. He noted that while these are early results, they reinforce the molecule's potential to meet the targeted clinical profile. The primary aim of this Phase 1b study is to establish an initial efficacy and safety profile for ABI-4334 in patients with chronic HBV, which will inform future program directions alongside partner Gilead's assessments.

Currently, enrollment is underway for a second cohort, where participants will receive an increased dose of 400 mg of ABI-4334 daily. Given the antiviral activity observed in the first cohort, Assembly Bio anticipates that this will be the final cohort for this phase. Data from this group is expected to be available in the first half of 2025. Under a collaborative agreement, Gilead Sciences, Inc. holds the option to participate further in the development and commercialization of ABI-4334, contingent upon the successful completion and review of the Phase 1b study data.

The ABI-4334-102 study is a crucial step in evaluating the safety, pharmacokinetics, and antiviral activity of ABI-4334. It involves treatment-naive or off-treatment patients with either HBeAg positive or negative chronic HBV infection. The trial is designed with two sequential cohorts, each consisting of 10 subjects randomized in an 8:2 ratio to receive either ABI-4334 or a placebo for 28 days. While dosing for the initial 150 mg cohort is complete, data for the 400 mg cohort are being gathered, with safety data pooled and reported collectively.

Assembly Biosciences remains committed to pioneering small-molecule therapeutics aimed at altering the course of severe viral diseases and enhancing patient outcomes globally. This study marks a significant step in their mission to tackle chronic infections such as hepatitis B, with future data submissions planned for presentation at scientific forums.