Assembly announces interim results from studies on ABI-H3733, ABI-4334

Assembly Biosciences announced promising interim efficacy, safety and pharmacokinetic results from two ongoing clinical studies of its investigational next-generation HBV core inhibitors, a Phase 1b clinical study of ABI-H3733 and a Phase 1a clinical study of ABI-4334. Phase 1b Study for 3733 – Study ABI-H3733-102: The ongoing Phase 1b clinical trial is a randomized, multi-center, double-blind and placebo-controlled study evaluating the safety, PK and antiviral activity of 3733. The dose selected for the first cohort was 50 mg. 50 mg Cohort Efficacy: As of the data cutoff date of December 18, 2022, dosing in the 3733 Phase 1b trial has been completed for all 10 patients in the first cohort of 50 mg. Nine of 10 patients enrolled were HBeAg negative, so efficacy data are provided for these patients. Interim efficacy results from this cohort at the data cutoff date include HBV DNA, HBV RNA and antigen measurements for all patients for the full 28-day dosing period. In the 50 mg cohort, six of eight patients receiving 3733 achieved HBV DNA less than the lower limit of quantification within 21 days, with a mean decline in HBV DNA over the treatment period of approximately 3.1 logs. Data on HBV RNA declines were limited due to low baseline levels in predominantly e-antigen negative patients. 25 mg Cohort Efficacy: The second cohort, evaluating a dose of 25 mg, is fully enrolled. Nine of 10 patients enrolled were HBeAg negative, so efficacy data are provided for these patients. In the five patients that have so far completed 28 days of treatment, the mean reduction in HBV DNA was approximately 1.9 logs. 50 and 25 mg Cohorts: Safety data reported here reflect data received for both cohorts through the data cutoff date. In these initial cohorts, all treatment-emergent adverse events and laboratory abnormalities reported were Grade 1 or Grade 2. Further, no AEs led to treatment discontinuation. The observed PK for the new tablet formulation of 3733 was consistent with predictions from preclinical studies, providing exposure equivalent to the liquid formulation evaluated in the Phase 1a study for 3733. As expected given the 28-day dosing period, limited changes in viral antigens were observed in both the 50 mg and 25 mg cohorts. Phase 1a Study for 4334 – Study ABI-4334-101: The Phase 1a clinical trial is a randomized, blinded and placebo-controlled study evaluating the safety, tolerability and PK of 4334 following single ascending dose and multiple ascending dose administration in healthy subjects. Dosing has completed for all eight subjects in the initial 30 mg single dose cohort. In this cohort, 4334 had a mean half-life of 24 hours, supporting once-a-day dosing. In this initial cohort, treatment-emergent AEs and laboratory abnormalities were mild to moderate and all were considered not related to study treatment. A dose of 100 mg has been selected for the second single-dose cohort. Dosing for the second cohort is complete and initial data from this cohort are anticipated in the first quarter of 2023.