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

Strategic focus and approach

• Aims to develop a finite-duration combination therapy for chronic hepatitis B, targeting at least a 20% functional cure rate.

• Employs a three-pillar strategy: suppress HBV DNA, reduce surface antigen, and boost immune response.

• Pipeline includes Imdusiran (RNAi therapeutic) and AB-101 (PD-L1 small molecule) to address these pillars.

• Combination therapy is prioritized over monotherapy due to superior potential for functional cure.

• Functional cure is defined as undetectable HBV DNA and surface antigen for 24 weeks off all therapy.

Clinical development and trial updates

• Imdusiran demonstrated significant reduction in surface antigen and HBV DNA in phase 1b, with evidence of HBV-specific immunology.

• Two phase 2a trials (IMPROVE 1 and IMPROVE 2) are ongoing, testing Imdusiran with interferon and VTP-300, respectively.

• IMPROVE 1's best cohort showed 33% of patients undetectable for surface antigen at end of treatment and after 24 weeks of nucleoside consolidation; this rose to 67% in patients with low baseline antigen.

• IMPROVE 2 interim data: 84% of VTP-300 arm and 53% of Imdusiran-alone arm discontinued nucleoside therapy at week 48.

• Additional data from new trial arms and longer-term outcomes expected in the fall at major liver conferences.

Mechanistic insights and future plans

• Imdusiran is a GalNAc-conjugated siRNA that blocks all HBV RNA transcripts, mainly reducing surface antigen.

• AB-101 is a liver-targeted small molecule PD-L1 inhibitor designed to minimize systemic immune activation.

• Phase 1 data for AB-101 show promising safety and target engagement; multiple ascending dose studies are underway.

• Plans to combine Imdusiran with AB-101 depend on safety and biomarker data from ongoing studies.

• The company is preparing for a larger phase 2b trial, with regimen selection guided by maturing phase 2a data.