A-687

A-687 is an orally bioavailable small molecule immunomodulator developed by invIOs in collaboration with the Lead Discovery Center. It belongs to a novel class of low molecular weight compounds designed to selectively enhance the cytotoxicity and proliferation of tumor-reactive T cells. The mechanism of action is characterized by its selectivity; A-687 induces T cell activation, including the expression of markers such as CD25 and CD69 and the secretion of Th1 cytokines (IFN-γ, IL-2, and TNF-α), only upon T cell receptor (TCR) ligation. This antigen-dependent activation profile is intended to focus the immune response on the tumor microenvironment while potentially minimizing systemic off-target effects. In preclinical murine models of B16-SIY melanoma and EO771 breast cancer, oral administration of A-687 demonstrated significant tumor growth inhibition and enhanced T cell infiltration. As of early 2024, the compound is in preclinical development, with first-in-human trials in solid tumors anticipated to begin in 2025.