EOS-448, our Anti-TIGIT antibody (co-developed and co-commercialized with GSK)

EOS-448 is an anti-TIGIT human immunoglobulin G1, or IgG1, antibody that we are developing to inhibit the immunosuppressive activity of TIGIT. TIGIT is a cell surface receptor expressed on multiple immune cells, including CD8+ T cells, natural killer, or NK, cells and T regulatory cells, or Tregs, a cell population that inhibits the immune response and, in the context of cancer, promotes tumor growth by inhibiting the activation and proliferation of effector T cells and NK cells. TIGIT has also been shown to be a mediator of resistance to existing CPIs, including anti-PD-1.

We have designed EOS-448 to engage with the immune system in multiple ways. First, it binds with high affinity to TIGIT, thereby breaking the immunosuppressive interaction between TIGIT and its ligands. In preclinical studies, we also showed that EOS-448 had superior binding to TIGIT and functional potency compared to a number of clinical-stage anti-TIGIT antibody equivalents. Furthermore, as we have chosen to design our anti-TIGIT antibody as an IgG1 antibody, the constant region of the antibody can activate FcγR on macrophages, dendritic cells and NK cells in the tumor microenvironment.

This activation of these cells augments the anti-tumor immune response but also triggers Antibody Dependent Cellular Cytotoxicity or ADCC response to those cells which expressed the highest levels of TIGIT, the Tregs. We have shown preclinically and in patients that EOS-448 causes the ADCC killing of Tregs.