10115871Discovery of novel personalised therapies for genetically heterogeneous, immunotherapy resistant cancers.ClosedCollaborative R&DInnovate UKCancer is the leading cause of death in the UK, a significant and hard to tackle healthcare challenge. Whilst targeted and immune therapies are improving survival, large studies in tumour evolution reveal that the driver of poor patient survival is DNA chromosomal instability (CIN) and tumour heterogeneity. This instability progressively enables tumours to mutate and adapt to the body's defences, anticancer drugs, and radiotherapies. Enedra is a UK biotech initiated by a team of leading UK bioinformaticians that developed and created CASPAROV, a target discovery, tumour CIN classification and analysis platform. Through deep analysis of cancer DNA databases Enedra has identified key biological processes and proteins that become essential in highly evolved late-stage CIN tumours. These represent a novel drug target space where protein loss is both potent and selective for phenotypes which late-stage heterogenous cancers converge upon. Several of these processes bear clear signs of convergence through selection pressure from the immune system and in parallel are emerging as key mediators of immune evasion. Each target comes with its own clear genomic signature which allows the development of patient selection markers. The project will create assets in the form of a discovery platform, chemical equity and patient selection markers around these key protein targets and their families. As a result, the plan enables the establishment of the first therapies designed to treat incurable heterogeneous, evolving cancers, including those resistant to current immunotherapies, by exploiting new targets to overcome immune evasion.