- In initial ABI-H3733 cohort of 50 mg in 28-day Phase 1b study, six of eight HBV patients on treatment reached lower limit of quantification for HBV DNA by day 21 and patients showed a mean reduction of 3.1 logs in plasma HBV DNA
- Initial ABI-4334 Phase 1a single-dose 30 mg cohort demonstrated pharmacokinetic profile supportive of once-daily oral dosing and provides early indication that ABI-4334's very high potency seen preclinically can be accessed clinically
- No serious adverse events or significant laboratory abnormalities including alanine aminotransferase (ALT) elevation were observed in either study
- Given potent antiviral activity in the initial 50 mg cohort, second 25 mg cohort ongoing in Phase 1b trial of ABI-H3733 to explore dose-response curve; 100 mg cohorts ongoing for both studies with further data expected in Q1 2023
SOUTH SAN FRANCISCO, Calif., Dec. 19, 2022 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage biotechnology company developing innovative, investigational therapeutics targeting hepatitis B virus (HBV) and other viral diseases, today announced promising interim efficacy, safety and pharmacokinetic (PK) results from two ongoing clinical studies of its investigational next-generation HBV core inhibitors, a Phase 1b clinical study of ABI-H3733 (3733) and a Phase 1a clinical study of ABI-4334 (4334).
“We are excited to see that these interim results from ongoing Phase 1 studies of our next-generation core inhibitors 3733 and 4334 are exceeding our expectations for key elements of the clinical profile we’re looking for to impact chronic HBV infection,” said John McHutchison, AO, MD, chief executive officer of Assembly Bio.
Assembly Bio specifically designed 3733 and 4334 to optimize potency against both new virus production (first mechanism) and formation of covalently closed circular DNA (cccDNA), the viral reservoir (second mechanism). Both compounds have demonstrated significantly increased potency preclinically against both mechanisms compared to first-generation core inhibitors. This increased potency, particularly against cccDNA formation, is critical to Assembly Bio’s HBV strategy to bring finite therapies and cures for those living with chronic HBV (cHBV) infection.
“In this first look at antiviral activity for 3733 in the Phase 1b study, we are seeing steep declines in HBV DNA at the low starting dose of 50 mg,” continued Dr. McHutchison. “The antiviral activity from this cohort against the first mechanism surpasses both what we demonstrated preclinically for 3733 as well as what we saw clinically in similar time frames with our first-generation core inhibitors at much higher doses. We are also highly encouraged by the initial pharmacokinetic data from our first-in-human clinical study of our most potent core inhibitor, 4334, which show the potential to reach high levels of activity against both mechanisms clinically at a low dose.”
Jason Okazaki, president and chief operating officer and CEO-elect of Assembly Bio, concluded, “With 100 mg cohorts of both 3733 (28-day dosing) and 4334 (single dose) underway, we are eager to see and share data in early 2023 that we anticipate will drive the optimal dose selection to maximize activity against both mechanisms of action. While early, we believe the interim results in both studies are an encouraging indication that the preclinical potency documented for our next-generation core inhibitors against the second mechanism of cccDNA formation will translate into the clinic with longer-term dosing.”
Complete results of these clinical trials, when available, together with ongoing nonclinical and chronic toxicity studies, will inform future clinical development planning for Assembly Bio’s next-generation core inhibitor programs.
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, 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 primarily of e-antigen negative patients. The study remains externally blinded, so individual patient data are not provided.
The dose selected for the first cohort was 50 mg. Given the potent antiviral activity observed at 50 mg, a 25 mg dose was selected for the second cohort to further explore the dose response curve of 3733. A dose of 100 mg has been selected for the third cohort, for which dosing is ongoing with initial data anticipated in the first quarter of 2023.
50 mg Cohort Efficacy (Viral Nucleic Acids):
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 (