Discovering drugs that create neoantigens
The immune system can both detect and fight cancer, but effective cancer immunity relies strongly on the presence of cancer neoantigens.
Continuous Neoantigen Creation
New ("neo") antigens are abnormal proteins that typically arise from DNA mutations that accumulate during tumour formation. Neoantigens appear foreign to the immune system and many are strong cancer antigens that stimulate immune responses to disease. However, cancer neoantigens often go undetected by the immune system simply because the the immune system response can fade over time, and in many cases cancers also only create a few weak neoantigens in the first place.
DNA Mismatch Repair Inhibitors
NeoPhore is discovering medicines that stimulate neoantigen creation in cancer cells marking them for attack by a patient's own immune system. NeoPhore’s drugs are designed to stimulate immunity directly at cancer's core, by interfering with DNA repair and forcing cancer to continuously produce neoantigens that will be detected by the immune system.
Recently, the CPIs Keytruda and Opdivo have both been approved for use in solid tumours that are deficient in MMR. This is a landmark event because it is the first time the FDA has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumour originated. It also represents strong clinical validation of NeoPhore's drug discovery strategy.
Lab research by NeoPhore’s scientific founders further supports this therapeutic approach: data recently published in the journal Nature (07 December 2017 Vol. 552, pages 116–120) shows that acute inhibition of specific mismatch repair genes causes continuous neoantigen generation in cancer cells, which in turn drives cancer immunity.
Relying on these newly discovered links between classical DNA repair genes and clinical efficacy, NeoPhore is pursuing novel, high-value approach for cancer drug discovery. NeoPhore's targeted approach to neoantigen creation stands out from competing methods: few mechanisms are as fundamental to cancer immunity or are as well-proven by both lab and clinical studies.
NeoPhore targets the dynamics of cancer neoantigen evolution and aims to make effective, well-tolerated medicines that will become a key part of the next-generation of cancer immunotherapies.