Assembly Biosciences presents data from HBV core inhibitor programs

Assembly Biosciences announced that data from its HBV core inhibitor programs and related research will be highlighted during four poster sessions - including two late-breakers - at the 2020 American Association for the Study of Liver Diseases The Liver Meeting Digital Experience. The posters include data from the company's HBV core inhibitor research and development programs, as well as a collaborative translational study using Assembly Bio's sensitive HBV nucleic acid assays. The Liver Meeting Digital Experience 2020 Presentations: The posters will be made available on the "Events and Presentations" page in the Investors section of assemblybio.com. Vebicorvir, Assembly Bio's Lead HBV Core Inhibitor: Poster Presentation 820: Analysis of the longer-term safety profile of the hepatitis B virus core inhibitor VBR in an open-label extension study: This poster includes data from a controlled comparison of 24 patients receiving placebo + nucleos(t)ide analogs for 24 weeks versus 95 patients receiving Assembly Bio's lead core inhibitor product VBR + NrtI for up to 1.5 years. Data support the differentiated safety profile and continued development of VBR combination therapy. Key Results: The safety profile of combination treatment with VBR+NrtI was similar to placebo+NrtI over a 24-week controlled-comparison and was stable with longer-term treatment of VBR+NrtI up to 1.5 years. Rashes without systemic involvement observed with VBR+NrtI treatment were predominantly Grade 1 resolving without VBR+NrtI interruption. There was no pattern of increased alamine aminotransferase and/or aspartate aminotransferase, indicative of hepatoxicity. Late-Breaking Poster LP37: Changes in viral antigens are more strongly associated with HBV pgRNA than HBV DNA in studies of vebicorvir and NrtI in treatment-naive patients with chronic HBV infection: This poster details the results of post hoc analyses of data from studies of VBR in treatment naive patients with HBeAg positive chronic HBV infection to better understand the correlations between changes in HBV DNA and pgRNA with those of other HBV antigens. Two approaches were used: correlation analyses with a Pearson's coefficient and a Mixed-Effects Model for Repeated Measures. These results demonstrate the importance of pgRNA as a meaningful biomarker for chronic HBV. Key Results: Changes in other HBV antigens are more strongly associated with the change in pgRNA compared with the change in HBV DNA. Correlations between pgRNA and HBeAg and HBcrAg were greater relative to the correlations with HBsAg, likely due to the substantial contribution of HBV integrants to HBsAg levels. A greater than2 log10 decline in pgRNA in patients receiving VBR + entecavir more significantly predicted the decline in the HBeAg and HBcrAg consistent with the second phase decline with core inhibitor treatment reflecting reduction in cccDNA pools. Assembly Bio's Next-Generation of Core Inhibitors: Late-Breaking Poster LP45: Amino acid substitutions in the inhibitor binding pocket of HBV core protein confer differential changes in susceptibility to three generations of HBV core inhibitors: This poster describes the in vitro resistance profiles of Assembly Bio's first-generation core inhibitor, VBR, and next-generation core inhibitor candidates ABI-H2158 and ABI-H3733. Researchers evaluated the antiviral activity of these candidates against known substitutions to the core inhibitor binding pocket. They also assessed whether these substitutions affect the ability of core inhibitors to block cccDNA formation as well as HBV replication through inhibition of pgRNA encapsidation. Key Results: 2158 and 3733 showed greater potency in terms of preventing cccDNA formation compared with VBR and had more favorable resistance profiles against a panel of substitutions. ETV retains activity against all tested core protein substitutions suggesting that combination therapy with NrtIs will prevent viral breakthrough due to pre-existence or potential emergence of core protein substitutions, consistent with the current clinical data. Use of Assembly Bio's Highly Sensitive HBV Assays to Characterize the Association of HBV with HCC: Poster 738: Persistently detectable serum HBV pgRNA is associated with subsequent HCC development in chronic hepatitis B patients receiving chronic NrtI treatment: In this poster, researchers detail findings from a case control study to assess whether residual HBV viraemia is associated with the development of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. The study evaluated 104 chronic HBV patients, 39% of whom had cirrhosis, on greater than or equal to 3 years ETV with unquantifiable HBV DNA by standard assays. Findings highlight the need for more potent viral suppression to further reduce the risk of HCC. Key Results: More sensitive assays revealed that patients still had ongoing replication as evidenced by detection of HBV DNA and pgRNA. More than 50% of chronic HBV patients on ETV with HBV DNAless thanLLOQ by standard assay had persistent viraemia as determined by a more sensitive HBV DNA assay. Detectable viral nucleic acids were associated with a higher 2-year risk of HCC development.