During DNA replication in dividing cells, DNA mismatch repair (MMR) scans newly synthesised DNA to detect and correct errors. Components of MMR are genetically lost or mutated in up to 20% of patient tumours, notably in colorectal, endometrial, and gastric cancers. Tumours lacking MMR function harbour a characteristic genetic profile which includes high tumour mutational burden (TMB), microsatellite instability (MSI) and a resultant diversity of expressed mutated proteins recognised as foreign by the immune system. Patients with MMR-deficient tumours commonly benefit from checkpoint immunotherapy with remarkably improved clinical outcomes. NeoPhore was founded to test the hypothesis that transient inhibition of the MMR machinery in MMR-proficient tumours could elicit an immunogenic state, broaden cancer patient access to immunotherapy and thereby transform patient outcomes.
NeoPhore has validated this hypothesis in preclinical models.