Arbutus Biopharma (ABUS) H.C. Wainwright 5th Annual Viral Hepatitis Virtual Conference summary

Strategic focus and development approach

• Focused on developing a functional cure for hepatitis B using a finite-duration combination therapy of antivirals and immunologics targeting at least a 20% functional cure rate.

• Three-pillar strategy: suppress HBV DNA, reduce hepatitis B surface antigen, and boost the immune system, using Imdusiran (RNAi therapeutic) and AB-101 (PD-L1 small molecule).

• Combination therapy is prioritized over monotherapy due to higher efficacy in achieving functional cure.

• Current standard of care requires lifelong treatment with low cure rates; the goal is to improve this with finite, more effective regimens.

Clinical trial design and rationale

• Imdusiran is being evaluated in two phase 2a proof-of-concept trials: IMPROVE 1 (with short-pulse interferon) and IMPROVE 2 (with immunotherapy VTP-300).

• Both studies are structured to first reduce surface antigen with Imdusiran, then introduce an immune booster.

• IMPROVE 1 uses interferon as the immune booster; IMPROVE 2 uses VTP-300, with or without nivolumab.

• The studies aim to identify the most effective regimen for progression to phase 2b.

Key clinical results and competitive positioning

• IMPROVE 1's best-performing cohort showed 33% of patients undetectable for surface antigen at end of treatment and after 24 weeks of nucleoside consolidation; in patients with baseline surface antigen <1000 IU/mL, this increased to 67%.

• IMPROVE 2 showed 84% of patients in the VTP-300 arm and 53% in the Imdusiran-alone arm were able to discontinue nucleoside therapy at week 48.

• Data compare favorably with competitors, with robust and sustained surface antigen loss.

• Additional data from new study arms and longer-term follow-up are expected in the fall.