Nonclinical development of Nervelight, an intra-operative peripheral nerve imaging agent

Inaboutmen elected to undergo radical prostatectomiesRPsEven with nerve sparingincontinence and or impotence can occur in up toof casesIn our SBIR Phase I grantwe showed in vivo Proof of Concept ofNervelighta peripheral nerve imaging agent comprised of a Near InfraRedNIRdyeDyomicsattached to recombinant human Nerve Growth FactorNervelight may spare nerves at risk in other cancer surgeriesi elymph node dissection for breast canceror oncological parotidectomiesHypothesisOur scientific hypothesis is that a single dose of peripherally administered Nervelight will localize bilaterally to cavernous nerves at risk in RPsOur commercial hypothesis is that we can translate this data into a commercial medical imaging agent to aid nerve sparing by showing that a single dose of Nervelightcan be visually detected in target nervesis safe in a GLP single dose acute toxicity studyandcan be produced to cGMP supporting an Investigational New DrugINDWe will test these hypotheses in these AimsAimWe will confirm effectiveness by showing bilateral localization in cavernous nerves in adultmale na ve rats after a single central injection in three pilot studiesnto identify preferred injection siteroute of administrationsub cutaneous or intra muscularand doseImmediately after euthanizationusing the Fluobeamwe will collect a single image of neurovascular bundle from inside the incisionUsing the approach established in our SBIR Phase Iwe will dissect left side target nerves to assess duration of effect in large tissue samplesFrom right side target nerves we will confirm visual observations from Fluobeam that Nervelight has localized to target nerves by comparing two sets of contiguous sectionsone set stained with nerve markersneuronal nuclear antigenNeuNPGPand the other set cryo preserved for NIR imagingAimUsing best siteroute and dose from Aimwe will determine dose in na ve male adult ratsnat two dose cohortslow from Aimand highX lowover eight timepointsnper timepoint groupboth dose cohortsWe will analyze withinand between group variances to statistical significance by quantifying pixels in target nervesand will assess fluorescence in a whole body distribution studyAimWe will assess safety per Guidancewith best route from Aimand intravenousIVroutein a GLP study of acutesingle dose toxicity to statistical significance in ratnand dognAimWe will complete a ChemistryManufacturing and ControlsCMCPlan by developing protocolsand bioanalytics for liquid formulation GMP product into hand filled vials for use in commercial syringesProject MilestoneUpon fundingwe will request a pre IND meeting to review our nonclinical planOur Project Milestone is to complete all nonclinical work to support and open an IND for a pivotal Phasesafety studynWe have the regulatoryclinicaland scientific team to conduct Phase III studies for commercialization