At The Liver Meeting, Immunocore reported positive phase 1 data for its T-cell receptor (TCR) bispecific candidate, IMC-I109V. The results highlight encouraging early signs of antiviral activity and consistent pharmacodynamic effects in people with chronic hepatitis B virus (HBV) infection.
IMC-I109V is engineered to eliminate HBV-infected hepatocytes expressing hepatitis B surface antigen (HBsAg) by redirecting non-exhausted T cells toward infected cells. The Phase 1 study evaluated ascending single doses of the agent (0.8, 2.4, 7, and 20 mcg) in 20 participants. All individuals received a single IV infusion and were monitored through week 4 for safety, pharmacokinetics, and pharmacodynamic activity.
Across dose levels, IMC-I109V was generally well tolerated, with treatment-related adverse events largely limited to transient Grade 1–2 systemic symptoms following infusion. ALT elevations occurred as expected with the mechanism of action and resolved within two weeks. A single Grade 2 cytokine release syndrome event was observed in the 20 mcg cohort, resolving within hours and prompting the use of corticosteroid premedication in subsequent participants, which successfully prevented recurrence.
Pharmacodynamic effects became consistent at doses ≥ 7 mcg, with dose-dependent reductions in HBsAg and associated immune activation signals, including IL-6 elevations and transient ALT increases. Four participants—two each in the 7 mcg and 20 mcg cohorts—achieved ≥ 0.2 log10 declines in HBsAg, with reductions typically reaching their lowest point by day 8. Importantly, three of these individuals maintained levels below baseline throughout follow-up.
