Assembly Biosciences presented interim results from two Phase 2a clinical trials of ABI-H0731, a novel antiviral in development for the treatment of chronic HBV infection. The data were presented during a late-breaker oral session at The International Liver Congress, the Annual Meeting of the European Association for the Study of the Liver in Vienna, Austria. The oral presentation reviewed interim analyses from two ongoing double-blind, placebo-controlled Phase 2a studies of 731 in HBV subjects evaluating the potential benefit of combination with standard of care Nuc therapy. The studies explore the first two critical steps thought to be necessary for a direct acting antiviral therapy to achieve higher cure rates, including the ability to eliminate residual viremia and prevent new viral replication, and the prevention of new cccDNA generation. Interim analyses suggest faster and deeper declines in HBV DNA and HBV RNA are possible with combination therapy. The ABI-H0731-201 study enrolled 47 HBeAg positive and 26 negative subjects whose viral load was already suppressed on active Nuc therapy and the ABI-H0731-202 study enrolled 25 treatment naive HBeAg positive subjects. The primary efficacy endpoints are the log10 reduction in HBeAg or HBsAg at week 24 and the log10 reduction in HBV DNA at weeks 12 and 24. While 89 subjects have reached the 12 week interim endpoint across the two studies, few subjects on combination therapy have reached the 24 week endpoint. In Study 201, the interim analysis includes 65/73 subjects that have completed the week 12 assessments and 11 that have completed week 24. All subjects receiving 731 in combination with a Nuc had significant reductions in HBV RNA levels compared to the group receiving Nuc + placebo. Approximately 60% of subjects on combination therapy with quantifiable RNA at entry demonstrated RNA decline by week 16 compared to 0% on Nuc monotherapy. Additionally, DNA viremia was persistently detectable at the LOQ in all subjects on Nuc monotherapy, while several subjects on combination therapy showed a further reduction in HBV DNA to below the limits of a highly sensitive PCR assay. Reduction of residual viral replication may be a critical milestone for cure and does not occur on Nuc monotherapy. In Study 202, 24 treatment-naive subjects have completed week 12 assessments, and 12 have completed week 24. The combination of 731 + entecavir reduced both HBV DNA and HBV RNA significantly faster and deeper compared to ETV monotherapy as early as week 2. More subjects with liver inflammation at baseline experienced improvement on combination therapy. Blinded, pooled results across both studies indicate favorable safety and tolerability for 731 when combined with SOC Nuc therapy. Adverse events were mild, infrequent, and evaluated as generally unrelated to treatment. There were no treatment related discontinuations, no serious adverse events and no clinical AEs greater than Grade 2 observed. Lab abnormalities were mostly Grade 1, transient, and not thought to be related to drug. To date, across all clinical studies,731 has been dosed in over 150 subjects and has exhibited a favorable safety profile. Both studies are ongoing, with subjects receiving treatment through 24 weeks, and Assembly expects to report final data later in 2019. At the conclusion of 24 weeks of treatment, all subjects from both studies will have the opportunity to roll over to an open label combination extended treatment study for up to an additional year. The data generated over the course of these studies will help to inform timelines and Assembly's registration strategies for its core inhibitors.
