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.

Increase antigens

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 interference

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.

NeoPhore is headquartered in Cambridge, UK and was launched in November 2017 with an initial investment of £3M by Sixth Element Capital LLP. NeoPhore is a spin-out company of Cambridge-based PhoreMost Ltd, which collaborated with NeoPhore’s founders Professor Alberto Bardelli and Giovanni Germano to establish the new company’s innovative approach.

Clinicians see excellent immune responses for certain cancers that lack the mismatch repair ('MMR') genes targeted by NeoPhore’s approach.

Chronic mismatch repair loss causes massive increases of cancer neoantigens, and patients with mismatch repair deficiency respond well when treated with cancer immunotherapies called check point inhibitors ('CPIs').

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.

Contact us at info@neophore.com