Topline Phase 1b Data Support Once-Daily Oral ABI-4334’s Potential for Chronic HBV

Assembly Biosciences has announced positive topline efficacy, safety, and pharmacokinetic (PK) results from a phase 1b study evaluating ABI-4334, an investigational next-generation capsid assembly modulator (CAM), in patients with chronic hepatitis B virus (HBV) infection.1

According to a June 25, 2025, press release, a favorable safety and tolerability profile, as well as pharmacokinetics supporting once-daily oral dosing, continued to be observed in the final 400 mg dose cohort, similar to that previously reported for the 150 mg dose cohort.1

“We are pleased to see that our most potent CAM, ABI-4334, achieved our target clinical profile with strong antiviral activity in both cohorts,” said Anuj Gaggar, MD, PhD, chief medical officer of Assembly Bio.1 “These data support the ability of ABI-4334 to effectively inhibit viral replication at the lower 150 mg dose, while offering the potential to dose higher for purposes of maximizing inhibition of cccDNA formation. We believe that maximizing direct antiviral activity and inhibition of cccDNA formation will be important components of regimens targeting cure of chronic HBV infection, and that achieving cure will likely require combination approaches with additional mechanisms still being explored by the field.”

ABI-4334-102 (Study 102) was a randomized, blinded, placebo-controlled, dose-ranging phase 1b clinical study that evaluated the safety, PK, and antiviral activity of ABI-4334. The study was conducted in treatment-naive or off-treatment participants with HBeAg positive or negative chronic HBV infection. A pair of cohorts consisting of 10 subjects each were randomized in an 8:2 ratio to receive ABI-4334 at 150 mg (cohort B1), 400 mg (cohort B2), or placebo daily for a 28-day treatment period.1

Interim safety, PK, and efficacy results from the 150 mg dose cohort of ABI-4334-102 clinical study were announced in December 2024 and showed ABI-4334 was well-tolerated with a favorable safety profile and half-life supporting once-daily oral dosing. In the first 150 mg dose cohort, ABI-4334 showed strong antiviral activity with a mean reduction of 2.9 log IU/mL in plasma HBV DNA over 28 days of treatment.2

In the latest data from the cohort evaluating a 400 mg oral daily dose, potent antiviral activity was observed over the 28-day treatment period similar to that previously reported for the 150 mg dose cohort. According to the release from Assembly Biosciences, the relationship between ABI-4334's observed antiviral activity and its exposure profile was consistent with having reached full engagement of the first mechanism of action for CAMs, inhibition of viral replication, at the lower 150 mg dose.1

In the predominantly HBeAg negative participants, a mean decline in HBV DNA of 2.9 and 3.2 log10 IU/mL were observed over 28 days in the participants receiving 150 mg and 400 mg, respectively. In the subset of participants with detectable HBV RNA at baseline, mean declines in HBV RNA of 2.5 and 2.3 log10 U/mL were observed over 28 days in the participants receiving 150 mg and 400 mg, respectively.1

Investigators noted slightly higher than dose-proportional increases in clinical PK exposures were observed from 150 mg to 400 mg, as measured by maximum concentration (Cmax) and area under the curve (AUC). Based on PK data from these cohorts and preclinical studies, daily minimum plasma trough concentrations (Cmin) at both dose levels achieved double-digit multiples over protein-adjusted EC50 for both antiviral activity and cccDNA formation.1

Additionally, safety and PK data from the 400 mg cohort continue to support a once-daily oral dosing profile, while reaching exposure levels at greater multiples of the target exposure anticipated to fully engage a second mechanism of action of CAMs, inhibition of formation of the viral reservoir, cccDNA.1

As described in the press release, under the collaboration agreement between Assembly Bio and Gilead Sciences, Gilead has the right to opt in to an exclusive license for further development and commercialization of ABI-4334 after reviewing the phase 1b option data package to be delivered by Assembly Bio following completion of this study.1

“These results will support discussions on potential next steps for ABI-4334 with our partner Gilead as they evaluate their option to the program,” Gaggar said.1

References

1. Assembly Biosciences. Assembly Biosciences Reports Positive Topline Results from Phase 1b Clinical Trial of Next-Generation Investigational Capsid Assembly Modulator ABI-4334 in Chronic Hepatitis B. June 25, 2025. Accessed June 25, 2025. https://www.globenewswire.com/news-release/2025/06/25/3105003/16259/en/Assembly-Biosciences-Reports-Positive-Topline-Results-from-Phase-1b-Clinical-Trial-of-Next-Generation-Investigational-Capsid-Assembly-Modulator-ABI-4334-in-Chronic-Hepatitis-B.html

2. Assembly Biosciences. Assembly Biosciences Reports Interim Phase 1b Results from Clinical Trial Evaluating Next-Generation Capsid Assembly Modulator Candidate ABI-4334 in Chronic Hepatitis B. December 26, 2024. Accessed June 25, 2025. https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-reports-interim-phase-1b-results-clinical