10068959Parallelised DNA encoded library screens with Artificial IntelligenceClosedCollaborative R&DInnovate UKProtein kinases are involved in almost all bodily function and changes in their activity can give rise to cancer and other diseases. Nevertheless, few drugs exist that target kinases as they are considered "difficult to drug" by leading experts. Recently, DNA Encoded Small Molecule Libraries (DELs) have attracted attention due to their ability to enable screening of trillions (~1,000,000,000,000) of potential drugs in a single experiment. While they would be exceptionally suited for discovering new drugs for hard-to-drug targets such as kinases, using them successfully remains difficult: DEL screens typically generate many potential drug candidates, but there is no easy way of developing one of them into a drug than is safe enough for human treatment. DeepMirror and Nuclera are developing disruptive new technologies to address these challenges. DeepMirror's software platform automates the development of machine learning models for drug discovery and suggests optimal lead candidates based on laboratory data such as DEL screens. Nuclera has developed the eProteinDiscoveryTM rapid protein prototyping system: an easy-to-use, pipette and forget, benchtop system that provides medium throughput numbers of proteins at microgram to milligram quantities for drug discovery applications. Combining these two technologies would enable a synergistic loop with which one could screen many different kinases in parallel, and then build AI models to select small molecules with low predicted cross-reactivity to test in the next screen, thus rapidly converging to the most promising small molecule leads. We are applying for the Biomedical Catalyst Grant to perform the essential R&D steps to upgrade and integrate our respective platforms for DEL screening execution and analysis. Our teams have deep and unique expertise in AI, protein synthesis, and laboratory experiments and we are supported by investors and advisors that hold senior positions in the pharma sector. The total taxpayer cost is estimated at £270k over the course of 23 months. If successful, our technologies will disrupt the early drug discovery phases for difficult-to-drug proteins, dramatically accelerating the development of new medicines against debilitating diseases such as cancer, with huge benefits for human health and the UK economy.