Arbutus Biopharma Corporation (Nasdaq: ABUS) announced that five abstracts, including one late-breaker, have been accepted for presentation at the upcoming European Association for the Study of the Liver (EASL) Congress 2025. The event will take place May 7-10, 2025, in Amsterdam, Netherlands, where the company will showcase new data on its investigational hepatitis B therapies.
The presentations will focus on imdusiran (AB-729), an RNAi therapeutic, and AB-101, an oral small-molecule PD-L1 inhibitor, both being developed to address chronic hepatitis B (CHB), a disease affecting over 250 million people worldwide.
Imdusiran Shows Promise for Functional Cure
Four of the five abstracts will detail findings from studies of imdusiran, Arbutus's lead candidate designed to reduce all HBV viral proteins and antigens. The data comes from the IM-PROVE I trial, which evaluated imdusiran in combination with pegylated interferon alfa-2a (IFN) and nucleos(t)ide analogue (NA) therapy.
Professor Man-Fung Yuen will present findings characterizing CHB subjects who achieved functional cure or HBV DNA suppression after completing the combination therapy and discontinuing NA treatment. This represents a significant advancement in the field, as functional cure remains an elusive goal in hepatitis B treatment.
Another presentation by Dr. Emily P. Thi will highlight how rapid loss followed by transient increases in HBV RNA during treatment with imdusiran and pegylated interferon is associated with HBsAg seroclearance. According to the abstract, subjects who achieved functional cure showed rapid HBV RNA decline during the imdusiran lead-in phase, with 5 of 6 subjects reaching undetectable HBV RNA levels during this period.
"The transient elevations in HBV RNA observed during the interferon treatment period were associated with further HBsAg decline and loss in some functional cure subjects," noted the abstract summary.
A late-breaking poster presented by Dr. Grace Lai-Hung Wong will address the off-treatment antiviral efficacy and safety of repeat dosing of imdusiran followed by VTP-300 with or without nivolumab in virally-suppressed, non-cirrhotic CHB subjects.
AB-101: Novel Oral PD-L1 Inhibitor Shows Promising Early Results
The remaining abstracts focus on AB-101, Arbutus's oral PD-L1 inhibitor designed to allow for controlled immune checkpoint blockade while minimizing systemic safety issues typically associated with immune checkpoint antibody therapies.
Dr. Emily P. Thi will present first-in-human pharmacokinetics and pharmacodynamics data showing that AB-101 was safe and well-tolerated in both single- and multiple-dose administrations in healthy subjects. The clinical plasma profile indicated rapid distribution into tissues, mirroring profiles seen in preclinical efficacy models with high liver biodistribution and target engagement.
Professor Edward J. Gane's presentation will cover preliminary safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of AB-101. Early data shows that single doses up to 40 mg and repeat doses up to 40 mg QD for 7 days were well tolerated in healthy subjects, with dose-responsive increases in PD-L1 receptor occupancy observed at doses ≥ 10 mg.
Addressing a Significant Global Health Burden
Chronic hepatitis B represents a substantial unmet medical need despite available vaccines and current treatment options. The World Health Organization estimates that approximately 1.1 million people die annually from complications related to chronic HBV infection.
Imdusiran targets hepatocytes using Arbutus' novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology, enabling subcutaneous administration. Clinical data generated thus far has shown imdusiran to be generally safe and well-tolerated, while providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA.
AB-101 works through a different mechanism, mediating re-activation of exhausted HBV-specific T-cells from CHB patients. The compound is currently being evaluated in a Phase 1a/1b clinical trial.
Looking Toward Future Development
Arbutus is currently reviewing development plans for a Phase 2b clinical trial of imdusiran combined with IFN and NA therapy, building on the promising results seen in earlier studies.
The posters will be available to conference attendees at the start of the EASL meeting on May 7, 2025, and will subsequently be accessible on Arbutus' website. The presentations represent important progress in the company's mission to develop a functional cure for chronic hepatitis B, a goal that has eluded researchers for decades.
The EASL Congress serves as a critical platform for sharing advances in liver disease research and treatment, making it an ideal venue for Arbutus to showcase its progress in developing novel therapies for this challenging viral infection.
