Breaking News

Assembly Biosciences (ASMB) announced the appointment of Nicole White, PhD, as Senior Vice President of Pharmaceutical Development and Manufacturing. Prior to joining Assembly Bio, Dr. White headed Process Chemistry at Gossamer Bio (GOSS).

Assembly Biosciences and Door Pharmaceuticals announced that the companies have signed an exclusive, two-year collaboration and option agreement focused on the development of a novel class of hepatitis B virus core protein modulators. Door Pharmaceuticals' innovative discovery platform targets functions of core protein distinct from viral assembly and that have the potential to interfere with viral nucleic acid including cccDNA transcription, providing a strong complement to Assembly Bio's current portfolio. Under the terms of the agreement, Door Pharmaceuticals will build upon its previous efforts to lead and conduct new discovery research, which will be funded by Assembly Bio. In return for an up-front payment and success-based milestones and royalties, Assembly Bio will be granted an exclusive option to license compounds arising from the collaboration and will be responsible for the continued development and commercialization of optioned compounds. Financial details were not disclosed.

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.

Assembly Biosciences provided an update on the ongoing open-label Phase 2 extension study, or Study 211, of vebicorvir in patients with chronic HBV infection. Study 211 is exploring whether sustained virologic response, or SVR, could be achieved after discontinuing therapy in virologically-suppressed patients who had received at least 12-18 months of combination treatment with core inhibitor VBR and a nucleoside analogue reverse transcriptase inhibitor, or NrtI. Study patients who met the treatment stopping criteria discontinued therapy and have been assessed monthly for safety and relapse. The study has not achieved meaningful SVR rates as 39 of 41 patients have now relapsed. Among the patients who have discontinued treatment, 22 of the 23 with HBeAg negative HBV have relapsed, defined as off-treatment quantifiable HBV DNA by the COBAS TaqMan assay. Sixteen of these patients relapsed at post-treatment Week 4, three at post-treatment Week 12, and three patients at post-treatment Week 16. Among the HBeAg positive patients, 17 of 18 relapsed at post-treatment Week 4. Assembly Bio continues to collect and analyze study data and intends to submit more detailed findings to a future medical meeting. Assembly Bio's Phase 2 trials, Study 201 and 202, demonstrated that the addition of VBR to NrtI therapy achieved a more rapid and deeper level of viral suppression than seen with NrtI alone and with a similar safety and tolerability profile. Based on these data, Assembly Bio has reached agreement with the Chinese regulatory body, National Medical Products Administration, Center for Drug Evaluation, and continues discussions with the FDA, on a Phase 3 registrational program for VBR plus NrtI as a chronic suppressive therapy for certain patient populations with chronic HBV infection. The company expects to initiate Phase 3 CST trials in the first half of 2021 in collaboration with BeiGene for the partnered China territory as part of the global registration program. Assembly Bio also continues to advance ABI-H2158 and ABI-H3733, which have demonstrated in preclinical studies 10-fold and 40- to 50-fold higher potency, respectively, than VBR in inhibiting the formation of new cccDNA. A multi-center, randomized, placebo-controlled Phase 2 trial is evaluating 2158 with entecavir versus placebo with entecavir in treatment naive HBeAg positive patients with chronic HBV infection. Additionally, a Phase 1 trial of 3733 is evaluating safety, tolerability, and pharmacokinetics following single ascending dose and multiple ascending dose administrations in healthy subjects. During the first half of 2021, Assembly Bio also intends to initiate a Phase 2 trial to evaluate the triple combination of VBR, Arbutus Biopharma's RNAi therapeutic AB-729 and NrtI in patients with chronic HBV infection. Combining multi-drug regimens with non-overlapping mechanisms has the potential to generate higher response rates in certain HBV patient populations and potentially shorten their duration of treatment. The Company also anticipates initiating a triple combination study in the first half of 2021 to evaluate the addition of interferon to VBR and NrtI.