MICROVASCULAR THERAPEUTICS LLC — Department of Health and Human Services SBIR Phase II: NHLBI

Description

Three ultrasound contrast agentsDefinityOptisonand Lumasonare FDA approved forechocardiography in the U SDefinity currently has overmarket shareDefinity s dominance in the marketis due to its ease of administration via IV infusion and robust ultrasound contrastDefinityhas shelflife ofyears and must be stored under refrigerated conditionsDefinity has an unpleasant side effect of back pain inaboutof patientsIn some groupse gpatients with sickle cell diseasethe rate of side effects is muchhighere gaboutThe most likely etiology of the back pain is complement activationDefinity is stabilizedby three phospholipids one of which is dipalmitoylphosphatidic acidDPPAThe investigators in this proposalhave shown that DPPA shortens the storage life of Definity and likely causes the side effect of the back painMicrovascular TherapeuticsMVThas discovered that not only is DPPA the most rapidly hydrolyzed lipid inthe Definity formulation but that DPPA also accelerates the hydrolysis of the other lipidsWhen DPPAhydrolyzes it forms lysoPAa potent stimulating molecule causing inflammation likely responsible for theadverse side effectsMVT has invented a stableneutral MBMVTCompared to DefinityMVTisfour times more resistant to hydrolysisIn a model of complementmediated renal retention MVThad fewerbioeffects than Definitywhich should translate into significantly less adverse eventsEchocardiography inpigs shows that MVTis comparableif not superior to Definityin providing LV opacification andmyocardial perfusion contrastMVT has received guidance from the FDA that MVTcan be developedvia thebpathwayno additional animal studies are requiredan accelerated clinical programcan be used to lead to approvalMVTwill serve as a platform for development of theranosticsSpecific AimsGMP manufacture MVTfile INDDose ranging study involunteersbolus andinfusionDefinity vs MVTPivotal study inpatients with suboptimal echocardiogramssignificantimprovement in LV border delineation in andgtof subjectsFile NDARationaleMVTis an improved productPerfluoropropane is the API and the lipids are excipients in theproductThebpathway allows for an accelerated approval pathway for such productsUpon NDAsubmissiontypicalmonth review period by the FDA before approvalThe development pathway will yieldidentical label claims as those for DefinityAdditional label claims can be pursued later or in parallelExpected outcomes of researchDevelopment of an FDA approved improved perflutren productMVTwith longer shelflifepotential for room temperature storage and terminal sterilizationincreasing safety of theproductand decreased adverse side effectsSince the product is electrostatically neutralMVTwill alsoserve as a robust platform for development of molecular imaging targeted ultrasound contrast agentsand theranostic agentsUltrasound is one of the most common imaging examinations and has advantages of absence of ionizing radiationportability and relatively low costUltrasound contrast agents are used to improve the accuracy of ultrasound and Definityperflutrenis the worldandapos s leading ultrasound contrast agent but perflutren has to be refrigerated and has a side effect of back painThe investigators have developed a newimproved perflutren for room temperature storage with decreased side effects