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Overview and Mechanism of Action

An innovative multi-specific T and NK cell engager technology that selectively activates the immune response within the tumor microenvironment.

Our technology displays several distinctive features:

  • Dual engagement of T cells and NK cells to mount an optimal anti-tumoral immune response
  • A tumor-restricted activation through a cleavable capping system
  • Carefully selected Tumor Associated Antigens (TAA) allowing cost-effective and patient-centric development

IM1240 is a conditionally-activated tri-specific antibody that engages both T cells and NK cells to mount a strong, localized immune response within the tumor microenvironment. The third arm of the lead compound specifically targets the Tumor Associated Antigen (TAA) 5T4, that is expressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness and poor clinical outcomes. The compound is distinguished from other products targeting 5T4+ tumors both by its dual engagement of T cell and NK cells and by the cleavable capping technology, which confines the compound’s therapeutic activity to the tumor microenvironment, and thereby is expected to increase the therapeutic window in patients.

The benefit of the dual T cell/ NK cell activation was demonstrated in cytotoxicity assays against various 5T4+ cancer cells lines, where the 5T4xCD3xNKG2A format was much more potent than the 5T4xCD3 variant (A).

The relevance and robustness of the cleavable capping system was investigated in xenograft models using immune-competent mice. As shown below, sustained tumor regression (Breast cancer MDA-MB-231 5T4+/HLA-E+) was achieved with the tribody harboring a cleavable cap. The effect was superior to a variant with no cap, illustrating the detrimental effect of peripheral engagement tumor-irrelevant T cells. As expected, the efficacy was completely lost using a variant with non-cleavable cap blocking the CD3 arm of IM1240 (B).



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