Immunocore presents Phase 1 data for hepatitis B candidate at AASLD’s The Liver Meeting

Single ascending dose data show IMC-I109V has manageable safety profile and antiviral activity

IMC-I109V is a bispecific T cell receptor targeting a peptide derived from HBsAg that is presented by HLA-A*02:01 on the surface of infected hepatocytes

(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & GAITHERSBURG, Md., US, November 7, 2025) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, has today announced data from its Phase 1 trial of IMC-I109V, a TCR bispecific (ENVxCD3) candidate designed to specifically eliminate HBV-infected hepatocytes expressing hepatitis B surface antigen (HBsAg) via T cell redirection.

The data, presented in a poster at The Liver Meeting, organized by the American Association for the Study of Liver Diseases, show that IMC-I109V is generally well tolerated in all evaluated doses and exhibits pharmacodynamic (PD) effects consistent with its mechanism of action, including reduction in HBsAg levels, clearance of which is indicative of resolved hepatitis B infection.

“Dose-dependent decreases in serum HBsAg following a single dose of IMC-I109V are promising and show that a T cell receptor-based approach to treating chronic HBV infection warrants further investigation,” said David Berman, Head of Research and Development. “These data – alongside the encouraging safety profile and antiviral activity seen in our ImmTAV candidate for HIV – reinforce the potential of our platform to achieve functional cures for chronic infectious diseases.”

The trial enrolled 20 participants in sequential cohorts evaluating ascending doses (0.8 mcg; 2.4 mcg; 7 mcg; 20 mcg) of IMC-I109V, given as a single IV infusion on day 1. Each dose was assessed for tolerability and PD activity, defined by either a ≥ 0.2 log10 reduction in serum HBsAg or by predefined increases in alanine aminotransferase (ALT) or serum IL-6 levels. Escalation to the next dose level was permitted for any dose that was deemed tolerable but was associated with PD activity in less than half the participants in a cohort.

Participants were evaluated for safety, tolerability, pharmacokinetics (PK) and PD activity up to week 4.

At doses ≥ 7 mcg, consistent PD activity was observed, including a dose-dependent decrease in HBsAg, which typically reached a nadir by day 8. Reductions meeting the predetermined threshold of ≥ 0.2 log10 IU/ml were seen in 4 individuals, 2/6 in the 7 mcg cohort and 2/8 in the 20 mcg cohort. In 3 of these 4 participants, HBsAg remained below pre-dose levels throughout follow-up. Reductions in HBsAg levels coincided with immune activation (IL-6 elevations) and transient elevations in ALT, which were expected based on the mechanism of action.

Treatment-related adverse events (TRAEs) were observed in 8 participants, including transient systemic symptoms (mostly Grade 1-2) in the 24h following infusion. ALT elevations (Grade 1-3), resolved to ≤ Grade 1 within 14 days. Bilirubin and prothrombin values remained within normal ranges throughout the study. The rapid resolution of all TRAEs was consistent with the short serum half-life (< 24h) of IMC-I109V.

One of 8 participants in the 20 mcg cohort developed Grade 2 cytokine release syndrome (fever, transient hypoxia and transient hypotension) within 4 hours of the end of infusion. This event responded rapidly to supportive treatment and corticosteroid therapy, resolving within 4 hours. Although dose-limiting toxicity criteria were not met, this event was classified as a serious adverse event (SAE) due to extension of the hospital stay (