Transgene TG4050 sustains 100% disease-free survival at three years
Transgene and NEC Corporation have reported that all 16 patients treated with TG4050 in the Phase 1 arm of an ongoing randomised trial remained disease-free at a median follow-up of 41 months, a three-year landmark that the companies say strengthens confidence in their individualised neoantigen therapeutic vaccine approach. Three of 16 patients in the control arm experienced relapse over the same period.
The results accompany a peer-reviewed publication in Nature Communications, the first time comprehensive clinical and translational data from the Phase 1 study have appeared in a journal. The paper details vaccine-induced immune responses alongside the survival outcomes, adding mechanistic weight to the headline efficacy signal.
Immune response data
The translational analysis, which forms the core of the Nature Communications paper, found that neoantigen-specific CD8+ T-cell responses were detected in 73.3% of TG4050-treated patients, with a median of three responding neoantigens per responder. Crucially, those responses were maintained throughout the vaccination schedule and persisted for more than one year after the last dose, suggesting the vaccine is generating durable anti-tumour immunity rather than a transient immunological effect.
TG4050 encodes up to 30 patient-specific neoantigens identified by NEC's AI-powered neoantigen prediction system, which uses graph-based relational learning and proprietary HLA-binding models trained on two decades of biological data. The vaccine is built on Transgene's myvac Modified Vaccinia Ankara (MVA) viral vector platform, and a separate product is manufactured for each individual patient. The company reported no unexpected safety findings.
Alessandro Riva, chairman and chief executive of Transgene, said the sustained immune responses observed over time provide "important evidence that our individualised therapeutic vaccine approach can generate durable anti-tumour immunity." Christian Ottensmeier, professor at the University of Liverpool and the La Jolla Institute for Immunology and principal investigator on the trial, described the CD8+ T-cell data as supporting "the vaccine's ability to generate a targeted anti-tumour immune response" in a patient group with significant unmet need.
Market context and next milestones
The individualised neoantigen vaccine space has attracted considerable interest since the high-profile publication of early efficacy signals from mRNA-based neoantigen vaccines developed by Moderna and Merck in melanoma and other solid tumour types. Transgene and NEC's approach is differentiated by its use of an MVA viral vector rather than mRNA delivery, and by the adjuvant rather than neoadjuvant setting in which TG4050 is being tested. HPV-negative head and neck squamous cell carcinoma carries a poor prognosis after relapse, and no approved immunotherapy has demonstrated clear benefit as a monotherapy in the adjuvant setting, which gives the Phase 2 readout particular commercial significance if the efficacy signal holds.
The Phase 1/2 trial (NCT04183166) continues to enrol and treat patients. Transgene has flagged two near-term milestones: first immunological data from the Phase 2 cohort expected in the second half of 2026, and two-year disease-free survival data from Phase 2 due by the end of Q1 2028. Those readouts will be the primary test of whether the 100% three-year Phase 1 figure translates to the statistically powered randomised cohort. Investors and oncology clinicians will want to see overall survival trends and the consistency of the immune response data across the larger Phase 2 population before drawing firm conclusions about TG4050's commercial potential.