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1PsychoGenics, Inc., Paramus, NJ, USA; 2Sunovion Pharmaceuticals, 84 Waterford Drive, Marlborough, MA, USA

Most of the neuropsychiatric disorders are polygenic and involve multiple neuronal circuits. Target-based approaches to CNS drug discovery have largely failed to deliver meaningful treatments. The SmartCube® system has been employed to phenotypically screen libraries of novel compounds with unknown mechanisms of action in vivo and identify potential CNS applications. The SmartCube® System combines behavioral neurobiological insights integrated with advances in robotics, computer vision and bioinformatics, to process and analyze massive temporal and vectorial datasets to detect the potential of compounds to treat psychiatric disorders. Compound testing is unbiased and high throughput, and using proprietary machine learning algorithms delivers complex behavioral signatures that are compared to a database of FDA-approved drugs.

In partnership with Sunovion Pharmaceuticals we screened a library of compounds using the SmartCube® System to identify novel, brain-penetrant drugs with unique behavioral profiles. Among the interesting compounds that have emerged is SEP-363856 which was identified as a lead compound with an antipsychotic-like profile in SmartCube®. SEP-363856 is unique as it does not interact with Dopamine D2. It has shown efficacy in rodent models of schizophrenia and it suppresses REM sleep. Similar to animal studies, Phase 1 clinical studies in humans showed good drug-like properties, REM suppression, and no EPS-like effects usually associated with D2 pharmacology. Phase 2 clinical studies are ongoing to evaluate SEP-363856 for the treatment of schizophrenia.