Arbutus Biopharma provides update on HBV development programs

Arbutus Biopharma provided an update on its key HBV development programs. AB-506, the company’s second generation capsid inhibitor, has progressed through the healthy volunteer portion of a multi-component phase 1a/1b study in which it was demonstrated to be generally safe and well-tolerated after 10 days of dosing. This month, AB-506 will enter the 28-day HBV patient portion of the trial, where it will be evaluated both with and without a nucleoside analog. AB-452 is a novel, orally available RNA-destabilizer that has shown compelling anti-viral effects in multiple preclinical models. AB-452 is a new chemical entity acting via a novel mechanism and the company is taking the time needed to further characterize the compound following emerging nonclinical safety findings before initiating clinical studies. At present, this is expected to delay the initiation of the phase 1 program while the company completes the ongoing nonclinical studies. ARB-1467, an RNAi agent targeting HBV replication and antigen production, is currently in a 30-week study in HBV patients, in combination with tenofovir and PEG-IFN. To date, six HBV patients have enrolled and been treated. Three patients did not meet the predetermined response criteria at week 6 to proceed to PEG-IFN treatment as per protocol. Two patients have not yet progressed to the six-week analysis point to determine if the addition of PEG-IFN is warranted. One patient has responded strongly, with a 3.17 log reduction in HBsAg level at treatment week 14 of under 4 IU/mL having started with a baseline level of greater than 6000 IU/mL, indicating that this regimen may drive HBsAg levels to undetectable in some patients. The study remains open to enrollment and the company will provide periodic updates. AB-729. Arbutus is developing a second-generation RNAi agent, AB-729, a subcutaneously-administered GalNAc conjugate, targeting HBV. In preclinical models AB-729 exhibits potent and durable reductions in HBsAg. This agent is expected to enter clinical studies in Q2 2019 and may be combined with AB-506 in a clinical study in 2H 2019.

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