Preclinical development of AST-004 for astrocyte-mediated treatment of TBI.

PROJECT SUMMARY Traumatic brain injuriesTBIincluding concussionsare an area of significant unmet need with no approved therapeutics and a national burden of$billion annuallyTBI is the global leading cause of post injury death and disabilityand overmillion Americans sustain a TBI each yearThe tremendous incidence and long term consequences of TBI highlight the considerable epidemic at handand the need for neuroprotective treatmentsAstrocyte Pharmaceuticals Incis developing a proprietary small molecule pharmaceutical agent for acute administration to TBI patients that will dramatically improve the survival of neuronsaffected brain tissueand the long term neurological deficits that have been linked to TBIThe proprietary approach at Astrocyte Pharmaceuticals differs significantly from historical neuroprotective attempts in that it focuses on a non neuronal cell typethe astrocytewhich has only recently received broader attention as an important cellular target for successful therapeutic researchMolecular activation of astrocytes enhances multiple healing mechanisms including protection against edemaglutamate excitotoxicity and oxidative stressPhase I studies identified a lead candidateASTwhich demonstrates significant neuroprotective benefits in murine and porcine TBI models without side effects at a reasonable dosing regimenThe goal of this SBIR Phase II project is to advance this promising TBI therapeutic to an IND and a first in human Phase I clinical trial through the completion of critical path preclinical activitiesThe project aims toperform FDA required toxicology and safety pharmacology studies in rats and dogsconduct required in vitro studies to characterize ASTandapos s liver metabolism and potential for drug drug interactionsanddevelop the manufacturing process for the IV formulation of ASTand manufacture drug product for a first in human clinical trialSuccessful completion of this project will lead to an IND submission with the FDA and a subsequent first in human Phase I clinical trial PROJECT NARRATIVE Traumatic brain injuriesTBIincluding concussionsaffect overmillion Americans each yearand TBIs are a leading cause of death and disabilityCurrentlythere are no FDA approved pharmaceutical treatments for TBIAstrocyte Pharmaceuticals Incaims to develop the first TBI therapeutic to limit neuronal damage and the physicalcognitiveand emotional complications associated with TBI