Sanofi and Immunocore Pair High Potential Molecules for Metastatic Skin Cancers

On Friday, Immunocore and Sanofi announced a clinical trial collaboration and supply deal. Under the deal, Sanofi will study its SAR444245 in combination with Immunocore’s KIMMTRAK in HLA-A*02:01 positive patients with advanced unresectable or metastatic skin cancers in an ongoing Phase I/II trial.

SAR444245 is Sanofi’s precisely PEGylated, engineered form of Interleukin-2 (IL-2) which has specificity and selectivity toward CD8+ T cells and Natural Killer (NK) cells. It has a single, targeted PEG-moiety linked irreversibly to a novel amino acid inserted at a precise spot, which prevents the drug from binding to the CD25 alpha-submit while preferentially binding to the beta/gamma IL-2 receptor subunits.

KIMMTRAK (tebentafusp) is a novel bispecific protein targeting gp100, a lineage antigen expressed in melanocytes and melanoma. It is the first molecule developed using the company’s ImmTAC technology platform that redirects and activates T cells to recognize and kill tumor cells.

KIMMTRAK is well-regarded, having received Breakthrough Therapy Designation, Fast Track designation and orphan drug designation from the U.S. Food and Drug Administration, Accelerated Assessment from the European Medicines Agency and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. It is approved in the U.S. for metastatic uveal melanoma and was also approved for that indication in Europe on April 4.

“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),” Dr. David Berman, M.D., Ph.D., head of Research and Development at Immunocore stated. “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.”

Under the deal, Sanofi will handle clinical development and all costs for the study except for expenses associated with manufacturing and supply of KIMMTRAK, which Immunocore will be responsible for.

“We are excited to embark on this collaboration with Immunocore,” Dr. John Reed, M.D., Ph.D., executive vice president and global head of R&D for Sanofi, said. “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.”

He added, “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 I/II clinical study.”

In 2021, Sanofi presented interim, early-stage data on SAR444245 (previously THOR-707) as a monotherapy and in combination with an anti-PD-1 checkpoint inhibitor. The initial activity was observed, with three confirmed partial responses, including patients who had previous anti-PD-1 therapy.

At the time, Reed said, “THOR-707 has a potentially best-in-class profile and reinforces the promise of our Synthorin technology platform to overcome difficult targets with precision biology. The activity observed both as single agent and with an anti-PD-1 further strengthens our belief that as a unique not-alpha IL-2, THOR-707 could become a backbone of future immuno-oncology therapies.”