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

Rhea-AI Summary

Immunocore (Nasdaq: IMCR) presented Phase 1 single‑ascending‑dose data for IMC-I109V at AASLD The Liver Meeting on November 7, 2025. The bispecific TCR candidate showed a manageable safety profile and pharmacodynamic activity consistent with its mechanism, including dose‑dependent reductions in HBsAg at doses ≥ 7 mcg, with HBsAg nadirs typically by day 8. Four participants met the predefined ≥ 0.2 log10 HBsAg reduction threshold. Treatment‑related adverse events were mostly transient; one Grade 2 cytokine release syndrome at 20 mcg resolved with treatment.

The company plans further evaluation in multiple‑dose regimens.

Positive

• Dose‑dependent HBsAg reductions observed at doses ≥ 7 mcg
• 4 of 20 participants met ≥ 0.2 log10 HBsAg reduction threshold
• HBsAg nadirs typically reached by day 8 post‑dose
• Short serum half‑life (< 24h) with rapid resolution of TRAEs

Negative

• One Grade 2 cytokine release syndrome (SAE) at 20 mcg requiring corticosteroids
• ALT elevations Grade 1–3 occurred, indicating transient liver enzyme increases
• Only 4 of 20 participants met predefined HBsAg PD threshold (limited responder rate)

Insights

Infectious disease immunotherapy expert

Phase 1 shows early antiviral signal with manageable, short‑lived toxicity; supports further multi‑dose study.

IMC-I109V produced dose-dependent pharmacodynamic activity at doses ≥ 7 mcg, including predefined reductions in serum HBsAg in 4 participants (2/6 at 7 mcg, 2/8 at 20 mcg), with nadirs typically by day 8. Safety findings included transient systemic symptoms in 8 participants, ALT elevations that resolved to ≤ Grade 1 within 14 days, and one Grade 2 cytokine release syndrome in the 20 mcg cohort that resolved quickly with supportive care; bilirubin and prothrombin stayed within normal ranges and the serum half‑life was reported as <24h.

The business and clinical mechanism is clear: a TCR bispecific (ENVxCD3) that redirects T cells to HBsAg‑positive hepatocytes to achieve HBsAg clearance, a marker of resolved infection. Key dependencies and risks are safety on repeat dosing and reproducibility of HBsAg declines across a larger sample; the single‑dose design and small numbers limit assessment of durability and frequency of meaningful declines.

Concrete items to watch over the next 6–18 months include results from planned multiple‑dose cohorts, rates of sustained HBsAg loss beyond day 28, incidence of ALT/IL‑6 linked transaminitis or CRS on repeat dosing, and whether corticosteroid premedication alters PD activity. These data will determine whether the program advances into larger efficacy studies.

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 (<1 day). Subsequently, 2 participants received the 20 mcg dose with corticosteroid premedication as an additional precaution. No SAEs occurred in these individuals.

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.

The Company believes this first-in-human evidence of reductions in HBsAg via this novel mechanism supports further evaluation of IMC-I109V in multiple dose regimens.

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About ImmTAV molecules and infectious diseases

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. This is known as ‘functional cure’. 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.

About Immunocore

Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including numerous active clinical and pre-clinical programs​ in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

Forward Looking Statements

This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate”, “aim”, “continue”, “target” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the therapeutic potential, including tolerability, safety profile and antiviral activity, of Immunocore’s product candidates, including IMC-I109V; the potential of the Company’s bispecific TCR technology platform to offer a new approach for the treatment of certain chronic infections, including a T cell receptor-based approach to treating chronic HBV infection; expectations regarding the design, progress, timing, enrollment, randomization, scope, expansion, funding, and results of the Company’s existing and planned clinical trials, those of the Company’s collaboration partners or the combined clinical trials with the Company’s collaboration partners; and the Company’s goals to develop and commercialize product candidates based on its KIMMTRAK platform alone or with collaboration partners; the expected submission of clinical trial applications; the potential regulatory approval, expected clinical benefits and availability of the Company’s product candidates; and the Company’s expectations regarding the payment of sales-related rebate accruals in the second half of 2025. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company’s business, financial position, strategy and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes in inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict in the Middle East, and global geopolitical tension; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of Immunocore’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore’s filings with the Securities and Exchange Commission, including Immunocore’s most recent Annual Report on Form 10-K for the year ended December 31, 2024 filed with the Securities and Exchange Commission on February 26, 2025, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.

Contact Information

Immunocore

Sébastien Desprez, VP Communications
T: +44 (0) 7458030732
E: sebastien.desprez@immunocore.com
Follow Immunocore on LinkedIn: @Immunocore

Investor Relations

Clayton Robertson / Morgan Warenius
T: +1 (215) 384-4781
E: ir@immunocore.com

FAQ

What did Immunocore announce for IMC-I109V at AASLD on November 7, 2025 (IMCR)?

Immunocore reported Phase 1 single‑dose data showing manageable safety and dose‑dependent reductions in HBsAg, with PD activity at doses ≥ 7 mcg.

How many participants showed meaningful HBsAg reduction in the IMCR IMC-I109V Phase 1 trial?

Four of 20 participants met the predefined ≥ 0.2 log10 IU/ml HBsAg reduction threshold (2/6 at 7 mcg; 2/8 at 20 mcg).

What safety events occurred with IMC-I109V in the IMCR Phase 1 study?

Treatment‑related adverse events were mostly transient; one participant at 20 mcg had Grade 2 cytokine release syndrome that resolved with supportive care and corticosteroids.

When did HBsAg reductions occur after dosing with IMC-I109V in the IMCR study?

HBsAg reductions typically reached a nadir by day 8 after a single IV infusion.

What is Immunocore’s next step for IMC-I109V (IMCR) after the Phase 1 single‑dose results?

The company plans further evaluation of IMC-I109V in multiple‑dose regimens based on observed PD activity and tolerability.