Arbutus Biopharma announces clinical data for AB-729 trial

Arbutus Biopharma announced that clinical data for AB-729, an RNAi therapeutic, and preclinical data for AB-161, a next-generation oral HBV specific RNA destabilizer, were presented as late-breaker oral presentations at the Global Hepatitis Summit 2023 in Paris. Principal investigators for the AB-729-001 clinical trial, presented data on nine patients with chronic hepatitis B virus infection, or cHBV, who completed 48 weeks of treatment with AB-729, and 24 weeks later met protocol-defined criteria to also stop nucleos(t)ide analogue, or NA, therapy. Two patients have restarted therapy – one at the investigator’s request after the week 20 visit which was previously presented at AASLD in November 2022, and one that met the protocol-defined HBV DNA criteria to restart NA therapy after the week 36 visit. In the 78% of patients that remain off NA therapy for 44-64 weeks, HBV DNA remains low and HBsAg remains below baseline. No adverse effects or ALT flares have occurred in these patients during follow-up. Professor Yuen also presented post-treatment follow-up data for the seven HBV DNA negative, HBeAg positive patients enrolled in the same trial. The mean log10 change from baseline in HBsAg was -2.57 IU/mL at week 48 and -1.86 IU/mL at follow-up week 48. Mean log decline in HBeAg was greater than1.0 log10 at the last follow up visit, even though HBeAg was low at baseline in some patients. One patient achieved both HBsAg and HBeAg less than the lower limit of quantitation with detectable anti-HBs antibodies. Two other patients achieved either HBsAg or HBeAg less thanLLOQ during the trial. AB-729 is currently being evaluated in two Phase 2a clinical trials, one in combination with an HBV antigen-specific immunotherapeutic and another with pegylated interferon alfa-2a, or IFN. Both of these trials will report preliminary data this year. At the same congress, Angela Lam, VP of Biology at Arbutus Biopharma, presented preclinical antiviral data and mechanism of action profiling of AB-161, a potent small-molecule HBV RNA destabilizer being developed as an orally administered antiviral agent for the treatment of cHBV infection. The data show that AB-161 provides robust anti-HBV activity including suppression of HBV RNA and HBsAg production in vitro and in vivo. In AAV-HBV infected mice, AB-161 reduces circulating HBsAg levels in a dose-dependent manner. Data from the mechanism of action studies show that AB-161 promotes viral transcript degradation and reduces viral proteins and viral replication. Preclinical pharmacokinetic data and repeat dose toxicology studies show enhanced liver concentrations and lack of peripheral neuropathy.