A-481

A-481 is an orally bioavailable small molecule immunomodulator developed by invIOs in collaboration with the Lead Discovery Center. It belongs to a novel class of compounds designed to selectively enhance the cytotoxicity of tumor-reactive T cells. A-481 acts by increasing T cell proliferation, upregulating activation markers such as CD25 and CD69, and stimulating the secretion of Th1 cytokines (IFN-γ, IL-2, and TNF-α) specifically in the presence of T cell receptor (TCR) ligation. This antigen-dependent mechanism is intended to provide potent anti-tumor immunity while minimizing the risk of systemic, non-specific immune activation. In preclinical studies using melanoma and breast cancer models, A-481 demonstrated significant tumor growth inhibition as a monotherapy and showed synergistic effects when combined with anti-PD-1 antibodies. The compound is being prepared for first-in-human clinical trials in solid tumors, which are projected to commence in 2025.