공시 • Jun 24
Assembly Biosciences Presents Data from HBV Core Inhibitor Programs At the International Liver Congress™ EASL 2021
Assembly Biosciences, Inc. announced data from its three clinical-stage core inhibitor programs, vebicorvir (VBR or ABI-H0731), ABI-H2158 (2158), and ABI-H3733 (3733), in an oral presentation and two poster presentations during the International Liver Congress™ 2021, the Annual Meeting of the European Association for the Study of the Liver (EASL), taking place virtually June 23-26, 2021. Assembly Bio’s Next-Generation HBV Core Inhibitors, 2158 and 3733: In an oral presentation, William Delaney, PhD, Chief Scientific Officer, describes data evaluating human plasma and estimated liver concentrations of VBR, 2158, and 3733 in relation to their respective protein-adjusted EC50 values in primary human hepatocytes. The intent of the analysis was to assess antiviral activity (assembly and release of new viral particles) and prevention of formation of new cccDNA of each of the three candidates. To date, core inhibitors have been inherently more potent against the formation of new virions (antiviral activity). Consequently, the company’s strategy is to optimize these next-generation candidates for greater potency against the generation of new cccDNA and employ both activities in combination regimens for maximal impact in patients. Plasma Cmin values for VBR, 2158, and 3733 are significantly above protein-adjusted EC50 values for antiviral activity, and plasma Cmin values of 2158 and 3733 are significantly above protein-adjusted EC50 values for cccDNA prevention. Concentrations for VBR, 2158, and 3733 are predicted to be enhanced in the liver by 18-fold, 5-fold, and 6-fold, respectively. Assembly Bio’s Lead Core Inhibitor, Vebicorvir: VBR is featured in two poster presentations during EASL, describing the efficacy, safety and resistance profile of virologically-suppressed patients with chronic HBV infection enrolled in the Phase 2 Studies 201 and Study 211 of VBR in combination with NrtI who discontinued treatment. Edward Gane, MBChB, MD, FRACP, MNZM, New Zealand Liver Transplant Unit at Auckland City Hospital in New Zealand, reported that combination therapy with VBR and NrtI for an extended period was well-tolerated and resulted in deep virologic suppression, but did not result in sustained virologic response in any patient who met prospective treatment stopping criteria. Post hoc analyses suggest HBcrAg level may be an important component when establishing stopping criteria for future trials. Patients were categorized as having lower or higher off-treatment viral load to enable a univariate logistic regression analysis to evaluate predictive factors. For HBeAg negative patients, entecavir use and HBcrAg<1.5 kU/mL at end of therapy were significant predictors of off-treatment lower viral load. For HBeAg positive patients, age less than 45 years was a significant predictor. Discontinuation of VBR+NrtI was well tolerated with limited adverse events and ALT elevations post-NrtI restart. Man-Fung Yuen, MD, PhD, Chief of Division of Gastroenterology and Hepatology at the Queen Mary Hospital in Hong Kong, described a post hoc analysis to investigate whether treatment-emergent core inhibitor substitutions were observed following discontinuation of VBR and NrtI. Sanger sequencing of HBV core and pol/RT was performed on HBV RNA for baseline samples and on HBV DNA for the first two consecutive off-treatment visits with HBV DNA >20 IU/mL. In vitro phenotyping assays were conducted for all novel substitutions observed in the core inhibitor binding pocket. The majority of patients had no core inhibitor substitutions and those that were observed had minimal impact on the in vitro antiviral activity of VBR. There was no emergence or enrichment of core substitutions observed in any patient. For patients who restarted NrtI, the presence of core inhibitor substitutions did not impact HBV DNA resuppression, nor did it impact the level of viremia off treatment.