PROJECT SUMMARY The high rate of failure in CNS drug discovery, in particular of the first-in-class therapeutics with new modes of action, highlights a clear unmet need to improve the success rate in drug discovery for rare diseases and psychiatric disorders. One well-known issue is the high cost, high risk, and low development time for drug development, time, and costs that most of the 10,000 rare disorder patients and support organizations cannot afford to support or wait for. Another important issue is the lack of clear targets for many for most rare diseases, which are complex and may require polypharmacology. Phenotypic screening platforms are well-suited for drug repurposing of drug in a target-agnostic manner. Suitable proven in vivo phenotypic screens, however, are scarce with the exception of PsychoGenics SmartCube® platform, which has been developed in the past few years for drug repurposing approaches using behavioral data, combining reference drugs’ signatures, and comparing them against disease animal models’ signatures. Our aim for this Fast Track project is to create a similar repurposing platform based on EEG data, using our eCube® fast EEG platform. To do this we will assess in eCube® several animal models of rare disease to create a small database, increase our reference drug EEG database, and use a novel algorithm, called Drug EEG Signature Analysis (DESA) to compare the two datasets and generate at once a multitude of hypotheses for potential drug repurposing. These hypotheses to be evaluated empirically using such models of disease. If our Phase I proof of concept project is successful, we will use the Phase II period to get the platform ready for commercialization. If successful, this platform will be an innovative and unique drug repurposing platform, offered as fee-for-service or used in drug development by PGI and its partners.