10111848Grey Wolf Therapeutics: Advancing next-generation immunotherapies through targeting of novel cancer-associated antigens induced by a First-In-Class ERAP1 inhibitor for the treatment of colorectal cancer.ClosedCollaborative R&DInnovate UKCancer is the leading cause of death worldwide, with the global economic cost of cancer estimated at £930 billion in 2021\. In the UK, 1 in ~18 people will be diagnosed with colorectal cancer(CRC) in their lifetime. Microsatellite-stable CRC (MSS-CRC) represents ~85% of all CRC cases and 95% of advanced metastatic CRC(mCRC) which has a very low 5-year survival rate of 10%. Early-stage MSS-CRC is treated by surgical resection of the tumour with or without adjuvant chemotherapy. Additional targeted therapies such as anti-VEGFR, anti-EGFR and BRAF inhibitors may be given to patients with advanced MSS-CRC, however, they only help a small fraction of the patient population. Unfortunately, immunotherapies such as immune checkpoint inhibitors(ICIs) have shown limited or no efficacy in MSS-CRC cancers, most likely as a result of their 'immune-cold' phenotype with low-tumour mutation burden and neoantigen generation. Grey Wolf Therapeutics (GWT) is pioneering a next-generation approach to cancer immunotherapy that's based on inhibition of ERAP1\. In this project, GWT will accelerate the progression and expand the therapeutic potential of their novel inhibitor as well as identifying and validating a separate treatment modality. Project outputs are expected to transform the reach of immuno-oncology therapies, addressing the significant unmet healthcare need within the majority of cancer patients who don't respond to first-generation immunotherapies, in particular MSS-CRC, representing ~1.6m cases globally (34,850 UK). This project brings together world-leading expertise in immuno-oncology, antigen discovery, pre-clinical development, molecular immunology, biotech development and commercialisation within the UK. The project team is also supported by a wide range of advisors including world leading researchers, driving rapid development and exploitation post-project.