Assembly Biosciences, Inc. provided an update of results from the final multiple-dose cohort in the ongoing Phase 1a study of its investigational next-generation, highly potent hepatitis B virus (HBV) core inhibitor, ABI-4334 (4334), and announced it will evaluate partnering opportunities for its core inhibitor portfolio and prioritize its expanded virology pipeline. Assembly Bio's expanded virology research pipeline unveiled in 2022 focuses on differentiated programs against validated clinical targets for HBV/hepatitis delta virus (HDV) and herpesviruses. With the reprioritization of programs, Assembly Bio's estimated cash runway extends into the third quarter of 2024.

The Phase 1a clinical trial for 4334 (Study ABI-4334-101) is a randomized, blinded and placebo-controlled study evaluating the safety, tolerability and pharmacokinetics (PK) of 4334 following single ascending dose and multiple ascending dose administration in healthy subjects. The objectives of the study include assessment of the proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs and abnormal laboratory results. Dosing has been completed for all subjects in all four single-dose cohorts (30 mg, 100 mg, 200 mg and 400 mg), two multiple-dose cohorts of 100 mg and 200 mg and one food effect cohort at 200 mg (with data pending for the food effect cohort).

Based on data available for the single-dose and multiple-dose cohorts through April 17, 2023, 4334 continued to show a half-life supportive of once-a-day (QD) dosing. In addition, based on PK data from these cohorts and preclinical studies, daily minimum plasma trough concentrations (Cmin) are projected to achieve double-digit multiples over protein-adjusted EC50 for both antiviral activity and against cccDNA formation within the dose range studied in the Phase 1a study, with the 200 mg QD dose projected to achieve >30 times the protein-adjusted EC50 for cccDNA formation. Through April 17, 2023, treatment-emergent AEs and laboratory abnormalities were mild to moderate with the majority being mild, and there were no patterns of AEs or laboratory abnormalities noted to be associated with 4334 and no clinically significant ECG abnormalities reported.

4334 was internally discovered and developed by Assembly Bio and designed to optimize potency against both new virus production and formation of cccDNA, the viral reservoir.