Sanofi: Interim Data Validate Novel Profile of Investigational IL-2 THOR-707

Sanofi presented interim data on April 9, 2021, from a first-in-human trial of THOR-707 (SAR444245), an investigational interleukin-2 (IL-2) candidate. The findings, presented as a late-breaking poster at the American Association for Cancer Research (AACR) Annual Meeting, are consistent with preclinical studies and validate the drug's "not-alpha" profile.

The data suggest that THOR-707 may promote an anti-tumor immune response while avoiding certain side effects associated with the IL-2 receptor alpha subunit. The drug is being studied as a monotherapy and in combination with anti-PD-1 therapy, with initial activity observed, including partial responses in patients previously treated with anti-PD-1 agents.

THOR-707 is a precisely PEGylated version of IL-2, built on Sanofi's Synthorin™ technology platform. It is engineered to selectively expand tumor-killing T effector cells and Natural Killer (NK) cells via beta-gamma receptors, without binding to the alpha receptors that can trigger toxicity. This design aims to mitigate alpha-mediated immunosuppressive effects from regulatory T cells and eosinophil-mediated vascular leak syndrome, known challenges with traditional IL-2 therapies.

Interim results indicated an increase in CD8+ T cells and NK cells following dosing, an effect that appeared enhanced when combined with pembrolizumab (KEYTRUDA®). No significant increases in CD4+ regulatory T cells or eosinophils were observed, supporting the intended selectivity. No dose-limiting toxicities were observed up to the reported doses. Common, transient adverse events included flu-like symptoms, fever, and nausea. Vascular leak syndrome was not reported.