Immunocore Holdings plc has registered a Phase 1 first-in-human clinical trial (NCT07493122) for IMC-S118AI, a bispecific soluble TCR–PD-1 agonist fusion protein, in adults with Stage 3 Type 1 Diabetes. The trial, posted on ClinicalTrials.gov on March 25, 2026, with an anticipated start date of April 1, 2026, represents the first clinical test of Immunocore's ImmTAAI platform — an inversion of the same TCR-based bispecific technology underlying KIMMTRAK (tebentafusp), the company's approved therapy for metastatic uveal melanoma. Where KIMMTRAK activates T cells to kill tumor cells via an anti-CD3 effector domain, IMC-S118AI suppresses autoreactive T cells at the pancreatic beta-cell surface via PD-1 agonism. No other clinical-stage program currently combines beta-cell-specific TCR targeting with localized PD-1 agonism for T1D, positioning IMC-S118AI as a first-in-class candidate in autoimmune diabetes.
The study is a randomized, single-masked, sequential dose-escalation trial comprising single ascending dose and multiple ascending dose cohorts, with a planned enrollment of 154 participants. Eligible adults are aged 18 to 45, must carry the HLA-A*02:01 allele, have a body mass index of 18 to 25 kg/m², and show evidence of residual beta-cell function. Exclusion criteria include non-T1D forms of diabetes, prior immunomodulatory therapy for T1D, cardiovascular disease, and malignancy history. Primary endpoints are safety-focused: treatment-emergent adverse events measured over 45 weeks, serious adverse events over 60 weeks, clinically relevant changes in laboratory parameters, vital signs, and electrocardiograms, and dose interruptions or discontinuations over 21 weeks. Secondary endpoints include the area under the curve of serum C-peptide after a two-hour mixed-meal tolerance test at Week 25 — a direct measure of beta-cell function — plasma concentrations of IMC-S118AI over 21 weeks, and anti-drug antibody formation over 31 weeks. IMC-S118AI is administered as a solution for infusion or injection; specific dose levels have not been disclosed. The trial has a data monitoring committee. Primary completion is estimated for November 2030. The trial is not filed under a US FDA IND based on available data; no regulatory designations have been reported.
IMC-S118AI was developed internally by Immunocore using its ImmTAX platform, which originated from soluble TCR research conducted at the University of Oxford in the 1990s by Bent Jakobsen, subsequently commercialized through Avidex Ltd and briefly held by MediGene AG before Immunocore's founding in 2008. The molecule's TCR arm is affinity-enhanced to recognize preproinsulin peptide 15–24 presented on HLA-A*02:01 on beta cells, while the effector arm agonizes PD-1 on nearby autoreactive T cells. Preclinical work published in JCI Insight (Bossi et al., 2021) reported that ImmTAAI molecules inhibited IFN-gamma release with an IC50 of approximately 29 pM and suppressed T cell-mediated beta-cell killing with an EC50 of approximately 22 pM, with activity dependent on beta-cell tethering rather than systemic PD-1 engagement. Validation in live human pancreas tissue slices was conducted in collaboration with the University of Florida Diabetes Institute and the Network for Pancreatic Organ Donors with Diabetes. Eli Lilly entered a clinical trial collaboration and supply agreement with Immunocore in February 2024, though this is not a licensing arrangement and Immunocore retains full ownership of the asset.