EVAS THERAPEUTICS LLC — Department of Health and Human Services SBIR Phase I: NHLBI

Description

PROJECT SUMMARY ABSTRACTIschemic heart disease is the leading cause of death worldwide with acute myocardial infarctionMIas the primary culpritIn the USaboutpatients have heart attacks each year and of thesepatients dieReperfusion of infarct related artery by thrombolysis or percutaneous coronary interventionPCIimproves survival in patients with MIHoweveracute restoration of blood flow paradoxically also jeopardizes the myocardium in the first minutes of reperfusionTherapeutic interventions and pharmacological treatments during experimental MI in animal models could reduce infarct size up toUnfortunatelytranslation of these experimental animal results into human clinical settings has been largely unsuccessfulEVAS Therapeutics has developed a recombinant fusion proteinA Lthat can specifically bind to anionic phospholipids expressed on the membrane surfaces of ischemic endothelial cells and myocardiumand block coagulation and inflammatory cascades by inhibiting tissue factorTFpathway and cell signaling via protease activated receptorsPARand Toll like recetorsTLRsIn a rat MI modelA Ltreatment was shown to reduce infarct size by up towhich was the largest infarct size reduction ever reported in literatureA Ltreatment also ameliorated hemodynamic derangementneutrophil infiltration and cardiomyocyte apoptosisand decreased plasma levels of cTnITNFand sICAMbyandrespectivelywithout significant alteration of the coagulation parametersIn this Phase I proposalwe propose to expand preclinical development of A Lwith the following specific aimsGLP production of A LA non GLP bench process will be adapted for production of GLP grade A LVerify cardioprotective effect of A Lin a rat MI modelHuntington Medical Research InstitutesTheeffect of A Lon myocardial infarct size and no reflow will be determinedComparison of the cardioprotective effects of A Laloneheparin cangrelorandA Lcangrelorin arat MI modelUSouth AlabamaThe efficacy of A Lin salvaging ischemic myocardium will beassessed in a clinically relevant mannerCurrently there are no effective therapies to reduce myocardial infarct size after myocardial infarctionThrough this study we may provide a novel and simple pharmacological intervention to increase cardiomyocyte survivalreduce infarct size and improve the outcome after acute MIResults from this study will also provide critical data for IND filing and clinical development for MI patients undergoing PCI PROJECT NARRATIVENo effective therapies are currently available for reduction of infarct size after myocardial infarctionThis project will evaluate the efficacy of a Kuniz inhibitor Annexin V fusion protein for promotion of cardiomyocyte survivalreduction of infarct size and no reflowand improvement of outcomes in rat myocardial infarction models