AVA-NP-695

AVA-NP-695 is a highly potent, selective, and orally bioavailable small molecule inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), developed by Avammune Therapeutics for cancer immunotherapy. By inhibiting ENPP1, AVA-NP-695 prevents the hydrolysis of cyclic GMP–AMP (2'3'-cGAMP), thereby activating the cGAS-STING pathway and promoting interferon production and antitumor immune responses. Preclinical studies have demonstrated that AVA-NP-695 not only enhances immunomodulatory effects but also inhibits cancer metastasis by negatively regulating epithelial-mesenchymal transition (EMT). The drug has shown superior tumor growth inhibition compared to Olaparib and PD-1 inhibitors in syngeneic mouse models of breast cancer. It is being investigated as both monotherapy and in combination with other agents such as PARP inhibitors, anti-PD-L1 antibodies, paclitaxel, and radiation therapy. Its primary indications under investigation include solid tumors such as triple-negative breast cancer and metastatic osteosarcoma[1][2][3][4][5][6].