Arbutus Biopharma has made significant strategic shifts by discontinuing its involvement in COVID-19 research and RNA destabilizer programs, redirecting its focus towards hepatitis B. The company has abandoned AB-343, an oral therapy designed to inhibit the SARS-CoV-2 main protease, along with a combination therapy involving AB-343 and a potential nsp12 polymerase inhibitor. This decision came as a result of unfavorable pharmacokinetic findings in preclinical studies, prompting Arbutus to withdraw from COVID-19 endeavors.
A parallel move has been witnessed in the case of Arbutus’ RNA destabilizer, AB-161, which was also halted due to a pre-clinical toxicology discovery unrelated to peripheral neuropathy. Notably, AB-161 had progressed to a phase 1 trial for hepatitis B virus treatment, with no reported safety concerns in the study’s healthy participants.
These strategic shifts are expected to extend Arbutus’ financial runway until the third quarter of 2025. The company has a series of pivotal milestones on the horizon, including preliminary data from a phase 2a trial of the RNAi therapeutic imdusiran, in combination with Vaccitech’s antigen-specific immunotherapy VTP-300, targeting chronic hepatitis B virus. These initial results are anticipated in the fourth quarter of this year.
Following that, Arbutus plans to release preliminary data from a phase 1 trial of AB-101, an oral PD-L1 inhibitor. Despite facing a clinical hold from the FDA in April, the company has been granted permission to proceed with the trial in New Zealand, with data expected in the first half of next year. CEO William Collier has described AB-101 as “highly potent” and highlighted its efficacy against PD-L1 in cells from chronic HBV subjects, suggesting its potential in antiviral immune tolerance for chronic hepatitis B.
However, Arbutus faces legal challenges, as it has ongoing lawsuits against Moderna and Pfizer-BioNTech alleging patent infringement related to its lipid nanoparticle delivery system. The legal battle against Moderna is in progress, with a claim construction hearing scheduled for February 7, 2024.
These recent decisions to discontinue COVID-19 and RNA destabilizer programs mark the latest in a series of strategic adjustments for Arbutus. The company previously halted a phase 1 medication in 2019 due to safety concerns after two healthy participants developed acute hepatitis. Additionally, a preclinical hepatitis B candidate was abandoned less than six months later due to safety issues observed in animal studies. In November 2022, Arbutus also discontinued an oral capsid inhibitor from its pipeline.