On Aug. 27, 2020, Assembly Biosciences and Arbutus Biopharma announced that the companies have entered into a clinical collaboration agreement to evaluate Assembly’s lead hepatitis B virus (HBV) core inhibitor candidate ABI-H0731 in combination with Arbutus’ proprietary GalNAc delivered RNAi therapeutic AB-729 and standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy for the treatment of patients with chronic HBV infection.

A randomized, multi-center, open-label Phase 2 clinical trial will explore the safety, pharmacokinetics, and antiviral activity of the triple combination of HBV core inhibitor ABI-H0731, RNAi therapeutic AB-729 and an NrtI compared to the double combinations of ABI-H0731 with an NrtI and AB-729 with an NrtI. This clinical trial is projected to initiate in the first half of 2021 and enroll approximately 60 virologically-suppressed patients with HBeAg negative or positive chronic HBV infection. Patients will be dosed for 48 weeks, with a 24 week follow-up period. As part of the collaboration, the companies may add cohorts in the future, to evaluate other patient populations and/or combinations.

Assembly’s HBV portfolio includes three clinical-stage small molecule candidates, all of which are HBV core inhibitors that target multiple steps of the HBV lifecycle. In Phase 2 clinical trials, first-generation core inhibitor ABI-H0731 administered with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy has been well-tolerated, has shown statistically superior antiviral activity in HBV DNA suppression compared to NrtI therapy alone, and has demonstrated significant declines in HBV pgRNA that may indicate decreased cccDNA levels. In the ongoing Phase 2 open-label extension trial, Assembly has begun transitioning patients off combination therapy, to then monitor for sustained virologic response (SVR).