A repurposed molecule as an oral therapeutic to improve vascular flow in sickle cell disease

PROJECT SUMMARY Problem to be SolvedSickle cell diseaseSCDis a global health issue that affects approximatelyAmericans and overmillion people worldwideAs a chronic and multifactorial diseaseit is characterized by a persistent milieu of oxidative stressinflammationrecurrent and painful episodes of sickle crisisand chronic vasculopathyThe disease places significant financial stress on the United States Healthcare systemwith annual costs exceeding $billionEach year in the U Sthere are approximatelyemergency room visits by patients seeking treatment for pain crisis and other disease related complicationsThere remains an unmet need for new interventions that ameliorate chronic vasculopathy and reduce the frequency and severity of pain crisesProduct and Long term GoalPHDis a small molecule with an excellent safety profile in humans and is being repurposed by Nanometicsd b aPHD BiosciencesPHDas a chronic oral therapeutic to improve vascular flowreduce the frequency of pain crisesand ameliorate organ damage in SCD patientsTechnological InnovationPHDcan act by several mechanisms to improve vascular flow and preliminary studies have demonstrated that a single intraperitoneali pdose causes statistically significant improvements in the hemodynamic parameters of BerkeleyBERKmice under ambient conditions and hypoxiareoxygenation challenged NY DD micePhase I ObjectivesThis Phase I SBIR project aims to demonstrate the feasibility of oral doses of PHDas a safe and effective therapeutic in BERKPhase II studies will be guided by feedback from a preinvestigational new drug meeting with the Food and Drug AdministrationCommercial OpportunityTreatment options for SCD are limited and there remains a significant need for new drugs to improve patient outcomesAs infant death rates decrease in developing countriesthe target market is expected to rise dramatically over the nextyears CSR To whom it may concernApplication titleA repurposed molecule as an oral therapeutic to improve vascular flow in sickle cell diseaseOpportunity TitlePHSOmnibus Solicitation of the NIHCDCand FDA for Small Business Innovation Research Grant ApplicationsParent SBIRRRPhase I SBIR Research Grant Applications Please assign this application to the followingNational Heart Lung and Blood InstituteNHLBISmall BusinessHematology ZRGVH FHematology Small Business ActivitiesSBIR STTRSpecial Emphasis Panels This proposal aims to further the development of PHDas a repurposed oral therapeutic for sickle cell diseaseSCDPHDhas an impressive safety record in all human clinical studies and preliminary results have demonstrated that a single intraperitoneali pdose improved the hemodynamic properties in two rodent models of SCDThis Phase I SBIR proposal aims to demonstrate the feasibility of PHDas an oral therapeutic for SCD using the Berkeley mouse modelPlease make secondary assignment to NCATSPlease make tertiary assignment to NIDDK