Next Generation Drugs for Bipolar Depression and Maintenance

Project SummaryThe goal of this program is to discover the next generation of drugs for bipolar depression and maintenanceBPDa brain disorder that affectsmillion adult AmericansExisting drug classes are relatively ineffective and very few new modes of actionMOAshave been developed in the pastyearsThis is duein partto the lack of predictive preclinical BPD disease models and the biopharma industry focus on drugging single molecular targetsOur scientific premise is that first in class drugs will be discovered by testing novelcustom designed privileged chemotypes using a proven behavioral profiling method and ex vivo imaging of the forebrain circuits implicated in BPDWe successfully employed this targetagnostic strategy to discover and optimize novel clinical drugs for psychiatric illnessone is currently in Phasetrials for schizophrenia and another is in Phaseclinical trialsWe founded Blue Oak Pharmaceuticals in order to further advance this research paradigm and discover the next generation of drugs for BPDOur research planAimDevelop abehavioral mapfor BPD reference drugs and screen the Blue Oak privileged chemotype libraryWe will utilize the SmartCubetechnology to generate deep behavioral profiles of the existing BPD drugs combinationsOur library of novel candidate privileged chemotypesdesigned to be CNS active and drug likewill also be screened to identify profiles similar to the reference BPD drugsAimMap brain circuit activity to prioritize lead chemotypesA lead chemotype with a novel MOA will be selected that is inactive at known molecular targets for existing BPD drugs but modulates mesolimbic mesocortical dopamineglutamate and GABAergic pathwaysAimOptimize clinical candidate sClinical candidate swill be achieved by maximizing in vivo efficacyoptimizing ADME properties and establishing intellectual propertyAn important translational medicine goal is to identify compounds that enhance EEG gamma power as a biomarker for use in Phaseclinical studiesTo execute this program effectivelywe will utilize theresearch networkmodel that we have developed over the pastyearsThis world class team includes Blue Oakdrug hunterswho are experts in systems neurobiologymedicinal chemistry and informaticsWe will enable our research strategy with established partners that have cutting edge technologies in behavioral profilingsynthetic chemistry and brain imagingOur clinical and business advisors have proven track records in drug development and commercializationThis program will generate several paths that transform therapeutics for brain disordersBPD clinical candidate swith translational medicine biomarkers and improved safetyefficacy profilesPharmacological tools for identifying cellular pathways and novel target sinvolved in BPDPrivileged chemotypes and a behavioral profiling database that provides excellent starting points foradditional drug discovery programs for other brain disorders Project Narrative This proposal aims to discover the next generation of drugs for bipolar depression and maintenanceBPDa brain disorder that affectsmillion adult Americans and imposes a significant medicalsocial and economic burdenUnfortunatelyexisting drug classes are relatively ineffective for most patients and very few new therapeutic mechanisms have been developed in the pastyearsBlue Oak will combine a unique chemistry platform with an in vivo systems neurobiology strategy of behavioral and brain circuit profiling to discover the next generation of drugs for BPD that have new modes of action and improved efficacy and safety profiles