Validation of targets for therapeutic intervention in NASH

Direct to Phase II SBIRValidation of targets for therapeutic intervention in NASHABSTRACT Non alcoholic steatohepatitisNASHis part of the progressive disease spectrum of non alcoholic fatty liver diseaseNAFLDa public health crisis affectingof typediabetics andof obese individualsGlucoseand insulin regulated de novo lipogenesis in the livera critical step in the disease processis severely compromised in cellular hepatocyte systems typically used for drug discovery and developmentdue to dedifferentiation in vitro and the requirement for supra physiological levels of insulinX in vivoand glucoseX in vivoto sustain viabilityThisalong with the use of mouse models that do not mimic human disease pathogenesishelps explain the unfocused target landscape in NASH with overdrugs in preclinical clinical development without consensus on optimal human targetsand resulting high failure ratesHemoShear Therapeutics is a biotechnology company that utilizes a patented technology to recreate human liver diseasesIn a previous SBIRR DKwe developed a multi cellular NASH system that recapitulates key elements of the diseaseincluding similar transcriptomic and metabolomics signatures observed clinically in human biopsies from NASH patientsThis system has been accepted for publication in a high impact journalJCI Insightand in multiple presentations at AASLD Liver Meetingsreceiving three Presidential AwardsMore thancompoundsincluding many currently in clinical trialswere evaluated in this NASH system using a combination ofomics and functional endpoints to create a rich data set for target identificationUsing this datasetwe have performed a gap analysis to gain a deeper understanding of the relative strengths and weaknesses of the current industry pipeline and importantly identified three promising targets that require further validation for future development of therapies for NASHThe purpose of this Directto Phase II SBIR is to further validate these targets in the HemoShear NASH system and in an animal model of NASH and to develop the functional target assays necessary to launch a small molecule drug discovery program!