Assembly Biosciences, Inc. announced completion of patient enrollment in two Phase 2a studies with ABI-H0731, a potent core inhibitor, for the treatment of HBV. The studies are ongoing, and the company anticipates reporting interim results from both studies during Second Quarter of 2019. ABI-H0731-201 is a Phase 2a “viral antigen” proof-of-concept study that enrolled HBeAg positive and negative patients whose viral load is already suppressed on active nucleos(t)ide (‘Nuc’) therapy. The enrolled patients continue their ‘Nuc’ therapy and were randomized 3:2 to either placebo or ABI-H0731 for six months. This study is designed to evaluate the effectiveness of ABI-H0731 in inhibiting the generation of new covalently closed circular DNA (cccDNA). Based on previous studies, inhibition of new cccDNA generation while existing cccDNA decays should manifest as a decline in viral antigens HBsAg and HBeAg. ABI-H0731-202 is a Phase 2a “viral load” study that enrolled treatment-naïve HBeAg positive patients and is designed to evaluate the de novo combination of ABI-H0731 and ‘Nuc’ therapy (entecavir) to ‘Nuc’ monotherapy alone. This study is designed to assess the benefit of combination therapy by comparing the relative rates of HBV viral load declines over six months. At the end of six months, patients from both studies have the opportunity to rollover to an open label combination (ABI-H0731 + Nuc) and continue treatment for up to an additional year. The data generated over the course of the Phase 2a studies will help to inform timelines and registration strategies for this novel class of HBV therapies. The U.S. Food and Drug Administration (FDA) recently issued draft guidance for HBV drug development1 reviewing development considerations for direct acting antiviral approaches such as Assembly’s core inhibitors. In addition to ‘731, Assembly continues to advance its deep pipeline of potent HBV core inhibitors with ABI-2158, its second core inhibitor, in an ongoing Phase 1a study in healthy volunteers. Data from this study is expected to be available in the first half of 2019. The company is planning to advance its third core inhibitor, ABI-H3733, into clinical trials in 2019.