- Prioritization of core inhibitor candidate ABI-4334 and pausing of core inhibitor candidate ABI-H3733 based on data to date from ongoing clinical Phase 1 studies of both candidates and chronic toxicology observation for ABI-H3733
- Phase 1a complete clinical data for all ABI-4334 dose cohorts expected in April 2023
- Advancing expanded research portfolio, with additional development candidate nomination anticipated in 2023 and IND/CTA submission for herpesvirus candidate ABI-5366 planned for the first half of 2024
SOUTH SAN FRANCISCO, Calif., March 22, 2023 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage biotechnology company developing innovative antiviral therapeutics targeting serious viral diseases, today provided an update on its investigational next-generation hepatitis B virus (HBV) core inhibitors, ABI-H3733 (3733) and ABI-4334 (4334), and reported financial results and recent highlights for the fourth quarter and year ended December 31, 2022.
“Last year, we accelerated our research pipeline and advanced our clinical pipeline of next-generation, highly potent HBV core inhibitors, 3733 and 4334,” said Jason Okazaki, chief executive officer and president of Assembly Bio. “While the clinical antiviral activity seen in HBV patients receiving 3733 in our Phase 1b trial is impressive, our objective has always been to prioritize the strongest candidate in a data-driven manner. Based on the data from our ongoing clinical and nonclinical studies, we are focusing on 4334 given its greater potency and encouraging clinical profile emerging from the initial cohorts in the Phase 1a study. We plan to evaluate and share data for the remaining multiple-dose cohort from that study in April.”
In the 100 mg cohort of 3733 in a 28-day Phase 1b study, all seven HBeAg negative chronic HBV (cHBV) patients that have completed dosing reached the lower limit of quantification for HBV DNA by day 21. In the Phase 1a study of 4334, all single-dose cohorts and the first multiple-dose cohort of 100 mg are complete. In these cohorts, 4334’s pharmacokinetic (PK) profile continues to be supportive of once-daily oral dosing and of providing exposures sufficient to potently inhibit both HBV DNA and covalently closed circular DNA (cccDNA) formation. No serious adverse events (AEs) or patterns of clinically significant AEs or laboratory abnormalities have been observed in either clinical study. However, a time-dependent toxicity in one species was observed in a nonclinical chronic toxicology study for 3733 that was not observed in the previous 28-day toxicology study.
“Beyond core inhibitors, we also achieved important research milestones in 2022, leveraging our virology expertise to broaden our discovery pipeline to include additional mechanisms of action targeting hepatitis B and hepatitis delta, as well as two programs outside of viral hepatitis targeting herpesviruses,” continued Mr. Okazaki. “We are thrilled with the progress of these programs, including the recent nomination of 5366, our first herpesvirus development candidate which we expect to move into the clinic for the potential treatment of patients who suffer from high-recurrence genital herpes during the first half of 2024. High-recurrence genital herpes is a disease for which current treatments are only partially effective and a new therapeutic hasn’t been approved in decades. We are excited at the opportunity to advance treatment options for this significant unmet medical need and expect to build upon our research progress with the nomination of a second development candidate from our expanded pipeline later this year.”
4334 and 3733 Clinical Data Updates
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. The objectives of the study include assessment of the proportion of subjects with AEs, premature treatment discontinuation due to AEs and abnormal laboratory results.
Dosing has been completed for all subjects in all single-dose cohorts (30 mg, 100 mg, 200 mg and 400 mg) and both multiple-dose cohorts of 100 mg and 200 mg, with data pending for the 200 mg multiple-dose cohort.
Based on data available for the single-dose and 100 mg multiple-dose cohorts through March 21, 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.
Through March 21, 2023, treatment-emergent AEs and laboratory abnormalities were mild to moderate and there were no patterns of AEs or laboratory abnormalities noted and no clinically significant ECG abnormalities reported.
A dose of 200 mg was selected for the second and final multiple-dose cohort. Dosing for this cohort is complete and data from this cohort are anticipated in April.
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, and has a distinct chemical scaffold from 3733.
Phase 1b Study for 3733 (Study ABI-H3733-102 and Nonclinical Toxicology Studies)
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, including changes in HBV DNA and other viral parameters associated with 3733 treatment in adults with cHBV infection who are treatment naïve or off treatment. Patients were randomized 8:2 between the new tablet formulation of 3733 and placebo for a period of 28 days. The patient population for the data included here consists of HBeAg negative patients. The study remains externally blinded, so individual patient data are not provided. Initial data for the 25 and 50 mg cohorts were reported in December 2022.
100 mg Cohort Efficacy (Viral Nucleic Acids), Safety and PK:
In the 3733 Phase 1b trial, as of March 21, 2023, enrollment was completed with 11 patients randomized to treatment. 10 of the 11 patients enrolled were HBeAg negative so efficacy data are not provided for the single HBeAg positive patient. Dosing has been completed for seven HBeAg negative patients receiving 100 mg 3733 and interim efficacy data are presented here for these seven patients. Interim efficacy results from this cohort include HBV DNA, HBV RNA and antigen measurements for the full 28-day dosing period.
In the 100 mg cohort, all seven HBeAg negative patients receiving 3733 who have completed treatment achieved HBV DNA less than the lower limit of quantification (