Immunocore, Gadeta ink agreement to develop first gamma delta TCR ImmTAC for solid tumours

Immunocore Holdings plc, a commercial-stage biotechnology company, and Gadeta B.V., an innovative clinical-stage biopharmaceutical company, announced that they will collaborate on the first ?d ImmTAC for solid tumours, including colorectal cancer.

“Immunocore pioneered TCR therapy with the launch of Kimmtrak and we continue to push the edge of TCR science, including researching non-HLA restricted TCR therapies, both internally and through collaborations that complement our platform,” said David Berman, head of research and development of Immunocore. “We are very pleased to collaborate with Gadeta to combine their expertise in gamma delta TCRs with our scientific, development, and commercialization capabilities to deliver new TCR therapies.”

“Gadeta is excited to work with Immunocore on bringing these novel, soluble ?d-TCRs to patients with solid tumours,” said Marcel Zwaal, chief executive officer of Gadeta. “This agreement shows the potential of Gadeta’s new tumor targeting mechanism and it provides us with an opportunity for maximizing the impact of our suite of technologies for T cell related therapies, including the NOVA ?d-TCR discovery platform.”

Gamma delta T cells are an important subset of immune cells that sit on the boundary of the innate and adaptive immune systems. They patrol the body using their T cell receptors to scan for cellular alarm signals, some of which are not HLA restricted, such as modified cell surface proteins or protein clusters caused by cancer or pathogens. Gadeta has identified a portfolio of novel, first-in-class, ?d-TCRs. One of those, referred to as ‘201, specifically recognizes a non-HLA restricted alarm signal on the surface of cancer cells. Gadeta is developing ‘201 TCR in its proprietary TEG (T Cells Engineered to Express a Defined Gamma Delta TCR) cell therapy platform as GDT201. Pre-clinical data for GDT201 show promising results across a wide range of colorectal cancer cell lines and the product will be evaluated in a Phase 1 trial for a range of solid tumour indications, slated to start in H2 2023. GDT201 remains fully owned by Gadeta.

Under the terms of the agreement, Immunocore and Gadeta will collaborate on ‘201 ?d-TCR target discovery, and Immunocore will have the option to develop ImmTAC therapies derived from the ‘201 TCR as part of the research collaboration. Immunocore has an option for an exclusive license to further research, develop and commercialize an ImmTAC candidate from the collaboration. Gadeta is eligible to receive upfront, near-term option fee and research milestone payments. If Immunocore exercises its option for an exclusive license, Gadeta is eligible to receive development milestone and commercial milestone payments and is also entitled to receive royalties on sales of the product.

Kimmtrak is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Kimmtrak specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumour cells. 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.

IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of Kimmtrak compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A 02:01-positive adult patients with previously untreated mUM. Kimmtrak demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring Kimmtrak, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

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, and infectious disease.