Immunocore Announces Clinical Trial Collaboration With Sanofi

Immunocore Holdings Plc recently announced it has entered into a clinical trial collaboration and supply agreement with Sanofi. Under the agreement, Sanofi will evaluate its precisely PEGylated, engineered version of IL-2, SAR444245, in combination with KIMMTRAK, Immunocore’s novel bispecific protein targeting gp100, in HLA-A*02:01 positive patients with advanced unresectable or metastatic skin cancers as part of Sanofi’s ongoing Phase 1/2 study.

Under the terms of the agreement, Sanofi will be responsible for clinical development and will assume all costs associated with the study, other than expenses related to the manufacturing and supply of KIMMTRAK for which Immunocore is responsible.

SAR444245 (formerly known as THOR-707), Sanofi’s product candidate, is a differentiated IL-2 engineered for specificity and selectivity towards CD8+ T cells and Natural Killer (NK) cells. The molecule has a single, targeted PEG-moiety irreversibly linked to a novel amino acid inserted at a precise location. This characteristic prevents SAR444245 from binding to CD25 (alpha-subunit) while preferentially binding to the beta/gamma IL-2 receptor subunits. Beta/gamma IL-2 receptor engagement has tuned IL-2 specificity for the robust proliferation of T-effector and NK cells, avoiding expansion of T-regulatory cells or eosinophils.

John Reed, MD, PhD, Executive Vice President and Global Head of R&D of Sanofi, said “We are excited to embark on this collaboration with Immunocore. The strong scientific rationale makes it compelling to investigate Immunocore’s KIMMTRAK, the first approved TCR therapeutic for a solid tumor, in combination with our engineered lymphokine, SAR444245. While we are actively studying SAR444245 as monotherapy and in combination with anti-PD-1 class checkpoint inhibitors and with approved immuno-competent monoclonal antibodies, the collaboration with Immunocore represents Sanofi’s first exploration of combining SAR444245 with a T cell engager. We are therefore very eager to explore this high potential combination in our ongoing multi-arm Phase 1/2 clinical study.”

David Berman, MD, PhD, Head of Research and Development at Immunocore, said “Immunocore has demonstrated that in vitro, IL-2 can enhance the activity of the ImmTAC platform, particularly in the context of tumor-associated inhibitory macrophages, and that metastatic uveal melanoma (mUM) patients with higher expression of IL2-beta and gamma, but not alpha, receptor have better overall survival (OS) on KIMMTRAK (presented at SITC 2021). We are pleased that Sanofi will test this hypothesis in their clinical trial in patients with metastatic cutaneous melanoma (mCM), a population with significant unmet medical need.”

In January 2022 and April 2022, the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively, approved KIMMTRAK (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Immunocore is currently planning a randomized study of KIMMTRAK with or without anti-PD1 therapy in patients with metastatic melanoma and anticipates initiating the trial in the fourth quarter of 2022.

KIMMTRAK is a novel bispecific protein composed 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 tumor cells. KIMMTRAK has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the US, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors.

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. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including five clinical stage programs in oncology and infectious disease, advanced pre-clinical programs in autoimmune disease and multiple earlier pre-clinical programs. Immunocore’s most advanced oncology TCR therapeutic, KIMMTRAK (tebentafusp-tebn), has been approved by the US FDA for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM) having demonstrated an overall survival benefit in a randomized Phase 3 clinical trial in metastatic uveal melanoma, a cancer that has historically proven to be insensitive to other immunotherapies.