Curadel, LLC — Department of Health and Human Services SBIR Phase II: 102

Description

PROJECT SUMMARY ABSTRACTImage guided surgery using invisible near infraredNIRlight is in the midst of a renaissanceMultiple commercial imaging systemsincluding Curadel s state of the art FLAREsystemare available for preclinicalveterinaryand human surgeryHoweverthe ultimate success of the field will depend on innovative NIR fluorophores that solve important clinical problemsCuradel has invented a novel family of NIR fluorophores termedzwitterionicMore preciselythey are geometrically balancedelectrically neutralpolyionic polymethine indocyaninesZwitterionic NIR fluorophores exhibit extremely low non specific binding and uptake in normal tissues and organs after a single intravenous injectionyet have extremely high extinction coefficientquantum yieldand signal strengthBecause of these propertieszwitterionic NIR fluorophores create the highest possible signal to background ratioSBRThere are two immediate clinical uses for zwitterionic NIR fluorophores that make them so attractive commerciallyFirstthey can be conjugated in one chemical stepthrough either N hydroxysuccinimideNHSesterstetrafluorophenylTFPestersor maleimide to any cancer targeted small moleculepeptidomimeticantibodyproteinor nanoparticle thus creating a targeted NIR fluorescent contrast agent for cancer surgerySecondwhen injected in their simplest carboxylic acid formzwitterionic NIR fluorophores exhibitrenal clearance and elimination into urineThis causes the ureters to become NIR fluorescent for several hours after a single intravenous injectionthus providing surgeons with the ability to avoid the ureters during cancer surgeries of the abdomen and pelvisUreter damagewhile uncommonleads to extraordinarily high cost and patient morbidityBecause of its clinical potentialZWwas deemed a high value asset by the NCI s Experimental TherapeuticsNExTProgram and was accepted into the first in human tractIn consultation with the FDAthe NExT Program paid for a complete two species toxicology packagea genotoxicity packageand mutagenicity packageall of which were negativesee AppendixBecause of ZWand Curadel s drug portfolio of overunique chemical entitiesthe most important companies in the field of surgery have visited usand most are interested in investment and or distributionThe message we have receivedthoughis consistentinvestment will only come after first in human clinical trials of ZWare completedIn this direct to PhaseD PSBIR applicationour approach to solve our current dilemma is systematiccGMP manufacturing of ZWunder ISOaseptic fill finish including lyophilization under ISOthen a PhaseAB clinical study at our major academic collaboration sitethe Leiden University Medical CenterLUMCin the NetherlandsCompletion of the aims will position Curadel to execute a sizeable distribution investment deal with a major player in the surgical spaceand thus cross thevalley of death