Arbutus Biopharma’s EASL 2025 Data: A Turning Point in HBV Cure Strategies?

The European Association for the Study of the Liver (EASL) International Liver Congress 2025, taking place in Amsterdam from May 7–10, promises to be a landmark event for hepatitis B virus (HBV) research. Among the companies presenting groundbreaking data is Arbutus Biopharma (NASDAQ: ABUS), which will unveil advancements in its lead therapies: the RNAi candidate imdusiran (AB-729) and the oral PD-L1 inhibitor AB-101. These data could reshape the treatment landscape for chronic HBV, a disease affecting over 250 million people globally and responsible for 1.1 million annual deaths.

The Case for Imdusiran: Functional Cure and Beyond

Arbutus’s star asset, imdusiran, is an RNAi therapeutic designed to silence hepatitis B surface antigen (HBsAg) production in the liver. The therapy’s potential for a “functional cure”—defined as sustained suppression of HBV DNA and loss of detectable HBsAg post-treatment—has been a central focus of recent trials.

At EASL 2025, data from the IM-PROVE I study will highlight key insights:
- Baseline HBsAg Levels: Researchers found that baseline HBsAg levels, not other biomarkers like HBcrAg or HBV RNA, were the strongest predictors of functional cure after stopping nucleos(t)ide analogues (NAs). This suggests imdusiran’s efficacy may be most pronounced in patients with lower baseline antigen loads.
- Mechanistic Clues: A separate abstract (2043) reveals that rapid declines in HBV RNA during imdusiran’s lead-in phase correlated with eventual seroclearance. Even transient viral rebounds during combination therapy with interferon were linked to immune reactivation, offering clues about how to optimize treatment regimens.

The late-breaker presentation (LB25153), however, may be the most anticipated. This study explores imdusiran’s use alongside VTP-300 (a TLR8 agonist) and nivolumab (an anti-PD-1 antibody), aiming to achieve a “sterilizing cure” that eliminates all viral traces. If successful, this combination could redefine HBV treatment goals.

AB-101: A New Tool in the HBV Arsenal

While imdusiran targets viral production, AB-101 focuses on reigniting the immune system. As an oral PD-L1 inhibitor, it aims to counteract the immune suppression caused by HBV. Phase 1 data presented at EASL will emphasize its safety profile and pharmacodynamic activity:
- Tolerability: Single and multiple doses up to 40 mg were well-tolerated in healthy subjects, with no severe adverse events.
- PD-L1 Receptor Occupancy: Dose-dependent increases in PD-L1 binding were observed, with occupancy achieved at ≥10 mg. This suggests the drug could effectively block the PD-1/PD-L1 pathway, a critical checkpoint for T-cell activation.

Early data in chronic HBV patients show promise, though results from the ongoing Phase 1b cohort will be pivotal. If AB-101 can safely reduce HBsAg and HBV RNA levels when combined with imdusiran, it could become a cornerstone of combination therapies.

The Market Opportunity and Competitive Landscape

The global HBV therapeutics market is projected to grow at a CAGR of 10.2% through 2030, driven by rising awareness and unmet needs in functional cure strategies. Arbutus faces competition from giants like Gilead Sciences (GS), whose lenacapavir recently received FDA approval for HIV but has shown early HBV activity in trials. However, imdusiran’s RNAi mechanism and subcutaneous delivery—a rarity in HBV treatments—give it a unique profile.

Risks and Challenges

• Clinical Uncertainty: While the data are encouraging, functional cure rates remain low even in combination therapies. The IM-PROVE I study reported only five of six subjects achieved seroclearance, underscoring the need for larger trials.
• Regulatory Path: The FDA and EMA have yet to establish clear endpoints for “functional cure” approval, complicating the path to market.
• Financial Pressure: Arbutus’s cash reserves, though sufficient for 2025, depend on partnership deals or secondary offerings to fund late-stage trials.

Conclusion: A High-Reward, High-Risk Play

Arbutus’s EASL presentations are a critical inflection point. If the data confirm imdusiran’s role in functional cure and AB-101’s immune-boosting potential, the company could capture a significant slice of the $3.5 billion HBV therapy market. The late-breaker study’s focus on sterilizing cure—a first in the field—adds another layer of upside.

Investors should note, however, that the road to commercialization is fraught. The stock’s volatility—seen in its 40% drop in 2022 after a Phase 2 disappointment—reflects the high stakes. Yet with over 250 million patients in need, even modest success could deliver outsized returns. For risk-tolerant investors, EASL 2025’s data may mark the start of a new era for Arbutus and HBV treatment alike.

Data Points to Watch:
- Functional cure rates in imdusiran’s Phase 2b trial (expected by end-2025).
- AB-101’s Phase 2 efficacy data in HBV patients.
- Competitor pipeline updates, particularly from Gilead and Roche.

Stay tuned as Arbutus’s science moves closer to becoming medicine—and investors weigh the cure for HBV against the risks of a high-stakes biotech race.