Development of TP-352 for the Treatment of Pediatric Non-alcoholic Steatohepatitis

ABSTRACTNon alcoholic fatty liver diseaseNAFLDrefers to a spectrum of diseases related to metabolic syndrome that are characterized by steatosisthe accumulation of fat within the liverNon alcoholic steatohepatitisNASHthe most aggressive NAFLD subtyperefers to the presence of inflammation and necrosis in a background of steatosisand is associated with hepatic fibrosisNASH is a serious health problem that can lead to serious long term health issuesincluding liver fibrosiscirrhosis and hepatocellular carcinomaIn the last few decadesNASH has emerged as one of the most common liver disorders amongst pediatric and adolescent patientsDespite affecting approximately two million children in the United Statesthere are currently no approved therapies for NASHTo answer this unmet medical needThetis PharmaceuticalsThetisproposes to develop magnesium L lysinate bis docosahexaenoateor TPas a safeoral therapy for resolution of NASH in pediatric patientsTPdelivers docosahexaenoic acidDHAan Omegapolyunsaturated fatty acidPUFAshown to have clinical efficacy for treatment of pediatric NASHTPovercomes the physico chemical and commercial deficits inherent to DHA to enable development of a safe and effective treatment for NASHIn this SBIR Fast Track projectThetis will complete the preclinical activities required for an investigational new drugINDsubmission to the FDA and initiation of clinical studiesThis goal will be achieved through the execution of five Specific AimsThe objective of Phase I is to obtain initial proof of concept by performing an efficacy studies using an established mouse model of NASHSpecific Aimand characterizing TPpharmacokinetics in miceSpecific AimThe objective of Phase II is to complete key commercially enabling preclinical activities required to initiate clinical studiesInitial efforts will focus on conducting a toxicological programSpecific AimOnce the efficacy and acceptable toxicity profile of TPare demonstratedThetis will manufacture good manufacturing practiceGMPcertified clinical trial material for the PhaseprogramSpecific AimUpon completion of this Fast Track SBIR projectThetis will have completed all requisite studies to submit an IND application and initiate Phaseclinical studiesAs indicated by letters of support from some of the country s leading NASH specialiststhis SBIR project is critical to enabling development of the TPprogram to address the unmet medical need in this vulnerable pediatric population NARRATIVE Non alcoholic fatty liver diseaseNAFLDis a chronic progressive disease characterized by hepatic fat accumulationsteatosisthat is quickly becoming the most common cause of liver disease in children and adolescents in Western countriesNon alcoholic steatohepatitisNASHthe most aggressive NAFLD subtyperefers to the presence of inflammation and necrosis in a background of steatosisAffecting nearly two million children in the United StatesNASH can lead to serious long term health problems including liver fibrosiscirrhosishepatocellular carcinomaliver failureliver related death and liver transplantationThere are currently no approved therapies for adult or pediatric NASHThetis Pharmaceuticals proposes to develop TPas a safeoral therapy for resolution of NASH in pediatric patients