Validating Prodrug PRX-P4-003 approach in humans by phase 0 microdose study

Binge Eating DisorderBEDis the most common eating disorder and carries an elevated risk of medical complications due to uncontrolled overeatingIt can be treated effectively with stimulantsbut their known abuse and diversion risk is a persistent concernOur strategic approach is to build on the proven efficacy of stimulants in BED while reducing abuse potentialThe goal of this Fast Track SBIR project is to develop PRX Pas a saferfirst in classtherapy for BEDPRX Pis a novel prodrug that shows an unprecedented ability to reduce the risk of oral and parenteral abuse based on a well tolerated dopaminergic stimulantfencamfamineFCFThe unique structure of PRX Phas resulted in a prodrug with dual protection propertiesfirstlythis water insoluble prodrug is inactive in vivo following intravenous administration and secondly minimizes the potential for oral abuse due to delayed absorption propertiesThese protection properties were accomplished by chemically formulating the prodrug as a substrate specifically for pancreatic lipasewhich is overwhelminglyandgtlocated in the pancreatic duct and small intestinePraxis has compiled a substantial body of evidence in vitroin vivo and preliminary toxicology studies have demonstrated the feasibility of this Prodrug stimulant for further developmentSince the key clinical efficacy and safety parameters are generally well understood for parent and this class of drugsthe next critical determinant of success for the program is to confirm the exposure and other key pharmacokineticPKparameters ofFCF after oral dosing of the PRX Pin humansAfter a pre IND meeting with the FDA we obtained authorization to pursue a microdose pharmacokineticPKstudy under the Exploratory IND PathIn Phase I the aims are toScale up synthesis ofFCF and Prodrug PRX POptimize analytical assay forFCFDemonstrate linear PK of ParentFCF in a primate studyIn Phase II the aims are toDemonstrate safety ofFCF and PRX Pin Pre IND toxicity study in ratsValidate PRX Pas an orally viable prodrug in a clinical Phasemicrodose PK studySuccessful completion of this Fast Track SBIR project will provide key validation data in humans required for further non clinical and clinical advancement of PRX PSuccessful completion of this project will provide a safer treatment for binge eating disorderwhich affects nearlyMillion adults who are at a risk of serious medical complications due to uncontrolled eatingThis treatment is designed as an orally selective stimulant with potential to reduce both intravenous and oral abuseA major impact in the treatment of ADHDnarcolepsy and apathy in Alzheimer s Disease is also possible