NP3452

NP3452 is a first-in-class small molecule inhibitor of the DNA mismatch repair (MMR) protein PMS2, currently in preclinical development by NeoPhore. The drug is designed to treat mismatch repair-proficient (pMMR) tumors, which typically do not respond well to immune checkpoint inhibitors. By pharmacologically inhibiting the MMR pathway, NP3452 induces a transient mutator phenotype, leading to the accumulation of DNA mutations and the subsequent generation of novel neoantigens. This process is intended to increase the tumor's immunogenicity, effectively turning cold tumors hot and sensitizing them to the host's immune system and potentially synergistic immunotherapy treatments.