NP1867

NP1867 is an orally available, potent, selective covalent small molecule inhibitor of the DNA mismatch repair (MMR) protein PMS2, developed by NeoPhore as an immuno-oncology agent to induce a mismatch‑repair–deficient–like state in tumors.[3][5][8][9][14] By covalently targeting PMS2 within the MutLα complex, NP1867 functionally inhibits MMR, increasing tumor mutational burden and microsatellite instability and generating COSMIC mutational signatures characteristic of MMR-deficient cancers, which enhances neoantigen formation and sensitivity to immune checkpoint blockade in preclinical models.[3][5][8] The program is currently in preclinical development as a strategy to pharmacologically convert MMR‑proficient tumors into immunotherapy-responsive cancers across solid tumor indications.[4][5][7][9][11][13]