OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & GAITHERSBURG, Md., US — November 7, 2025 — Leads & Copy —
Immunocore Holdings plc (Nasdaq: IMCR) has released data from its Phase 1 trial of IMC-I109V, a bispecific T cell receptor (TCR) candidate designed to eliminate hepatitis B virus (HBV)-infected hepatocytes expressing hepatitis B surface antigen (HBsAg) via T cell redirection.
The data, which were presented in a poster at The Liver Meeting, organized by the American Association for the Study of Liver Diseases, indicate that IMC-I109V is generally well tolerated at all evaluated doses and exhibits pharmacodynamic (PD) effects consistent with its mechanism of action.
According to the company, these effects include a reduction in HBsAg levels, the clearance of which is indicative of resolved hepatitis B infection.
David Berman, Head of Research and Development, stated that the dose-dependent decreases in serum HBsAg following a single dose of IMC-I109V are promising and show that a TCR-based approach to treating chronic HBV infection warrants further investigation.
Berman added that the data, along with the encouraging safety profile and antiviral activity seen in Immunocore’s ImmTAV candidate for HIV, reinforce the potential of the company’s platform to achieve functional cures for chronic infectious diseases.
The Phase 1 trial enrolled 20 participants in sequential cohorts, evaluating ascending doses (0.8 mcg; 2.4 mcg; 7 mcg; 20 mcg) of IMC-I109V, administered 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 of 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 its lowest point by day 8. Reductions meeting the predetermined threshold of ≥ 0.2 log10 IU/ml were seen in 4 individuals, with 2 out of 6 in the 7 mcg cohort and 2 out of 8 in the 20 mcg cohort. In 3 of these 4 participants, HBsAg remained below pre-dose levels throughout the follow-up period.
The company reported that 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 24 hours 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 (< 24 hours) 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 an extension of the hospital stay (<1 day). Subsequently, 2 participants received the 20 mcg dose with corticosteroid premedication as an additional precaution, and no SAEs occurred in these individuals.
Immunocore believes this first-in-human evidence of reductions in HBsAg via this novel mechanism supports further evaluation of IMC-I109V in multiple dose regimens.
IMC-I109V is designed to overcome HBV-specific T cell exhaustion by recruiting non-exhausted T cells to eliminate hepatocytes harboring covalently closed circular DNA or integrated HBV DNA.
ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells.
Immunocore is advancing clinical candidates to cure patients with HIV and hepatitis B virus (HBV). The company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. For the treatment of HBV, the company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.
Sébastien Desprez, VP Communications
T: +44 (0) 7458030732
E: sebastien.desprez@immunocore.com
Clayton Robertson / Morgan Warenius
T: +1 (215) 384-4781
E: ir@immunocore.com
Source: Immunocore Holdings plc
