Therapeutic Protein C Activator for Myocardial Ischemia

PROJECT SUMMARY Heart attackor acute myocardial infarctionAMIis a leading cause of death in the United Stateswith overvictims every yearThe most prevalent cause of AMI is progressive thrombotic coronary artery occlusionalso known as ST segment elevation myocardial infarctionSTEMIEarly therapy to promote heart reperfusion can dramatically improve outcomesWhile percutaneous coronary interventionPCIis preferred for early arterial recanalizationup toof patients present to hospitals without this capabilityand many STEMI victims must rely on thrombolytic therapy aloneHowevercurrent thrombolytics such as tissue plasminogen activatortPAare not fully effectiveand many patients are excluded from thrombolytic therapy altogether due to bleeding concernsConsequentlya major treatment gap exists for hemostatically safe antithrombotic and thrombolytic drugs that can be used alone or that can improve the efficacy of current treatments without increased bleedingTo directly address this needour company has been developing a firstin class antithrombotic agent for the safe treatment of heart attackThe product candidate is a bioengineered recombinant selective protein C activator enzyme that has potent antithrombotic effects without increasing hemorrhagic risksOur proprietary moleculeProCaseE WE thrombinhas been designed to act in part by increasing the surface concentration of the anticoagulantprofibrinolyticand cytoprotective enzymeendogenous activated protein CAPCat the site of developing blood clots via targeted cellular deliveryThis unique mechanism of action allows E WE thrombin to target pathological blood clots without disabling vital hemostasisIn primatesdoses as low asg kg are antithrombotic without systemic anticoagulation or any antihemostatic effectsAll of the critical milestones for our Fast Track SBIR Phase I II grant have been reached to justify progression to Phase IIB by demonstratingE WE thrombin is effective in a mouse AMI modelE WE thrombin safely interrupts vascular graft thrombo occlusion in primatesOur sensitive blood assay can measure drug exposure levels in plasmaandLimited repeat administration of E WE thrombin does not evoke an immune response in primatesOur Phase IIB aims that will support critical product development milestones are toDetermine the antithrombotic efficacy and hemostatic safety of combining E WE thrombin plus tPA in primatesComplete a bridging preclinical GLP toxicology study of E WE thrombin combined with tPAandTransfer E WE thrombin manufacturing to a facility capable of commercial scale productionWe are currently at a critical juncture for advancing E WE thrombin towards human trials to treat STEMIand ultimately all acute coronary syndromeACSpatientsThis SBIR Phase IIB Bridge Awardmatched by a combination of already secured and pending fundswill lead directly to the initiation of clinical trials investigating this unique and potentially life saving antithrombotic drug candidate PROJECT NARRATIVE Treating heart attack with andquot clotbustersandquotand other antithrombotic drugs increases the risk of serious bleedingconfining their usage to the hospital and selected patientsThe proposed preclinical research evaluates the therapeutic potential of a new emergency heat attack treatment that inhibits pathological blood clots by activating the endogenous antithrombotic and cytoprotective enzymeprotein Cinside blood vesselsThe drug candidate to be testedProCaseE WE thrombinis not expected to produce bleeding side effectsand may provide a safe addition to existing antithrombotic and thrombolytic treatments