Personalized precision dosing of biologic therapies in oncology

AbstractRituximabisamonoclonalantibodymAbamongthetopbestsellingdrugswithglobalsalesestimatedtoexceed$ BinRituximabisindicatedtotreatconditionsincludingchroniclymphocyticleukemiaCLLBcellnonHodgkinandapos slymphomaandvariousautoimmunedisordersPopulationpharmacokineticstudieshaverevealedconsiderabledifferencesinthefinallevelsofrituximabfoundinthebloodafteracourseoftherapyandtheselevelscorrelatewiththerapeuticoutcomesWith current dosing regimensa substantial fraction of the patients may not be receiving anefficaciousdoseDuringclinicaldevelopmentlaboratorybasedtestsareusedtomonitorrituximablevels in patientsbut these tests are not available to physicians after approvalCurrentlythere are nopointofcarePOCtests available to monitor the levels of rituximab in patientsThe goal of this projectis to develop low cost POC devices that provide a quantitative measure of rituximab levels in bloodThese tests will help physicians personalize the dosing of patients and identify early rituximab treatmentfailures resulting from low drug levelsOur core enabling technology platform is based on mimetopepeptidestermed VeritopesTMthat mimic the cognate ligand of a given mAb and specifically bind at theantigenbindingsiteVeritopesTMarecheaprobustandsimpletointegrateintolateralflowimmunoassayLFAthatthenenablesinexpensivePOCtestingInpreliminarystudieswedemonstratedthefeasibilityofVeritopeTMbasedLFAforthequalitativedetectionofrituximabtrastuzumaband bevacizumab levels in biologic fluids as well as the potential to develop quantitativetestsIn this Phase II projectwe will complete the development of a CLIAwaivable rituximab monitoringtest that can be performed at the POC from a single drop of bloodWe will integrate the LFA strips intosingleusedisposabledigitalLFAreaderdevicesthatcanprovidequantitativeanalysisoftheteststripsThese devices will be validated in a clinical trial in partnership with UCSD Moores Cancer Centerusing blood samples from patients treated with rituximabThe data generated during this Phase II studywill be incorporated in our technical data package to submit to FDA for clearance of our devicewhichwill be the first FDA cleared device for biologic drug monitoring at the POCThis innovative product will fulfill of an unmet clinical need for a rapidcost effectiveand accurate dosemonitoring assayPrecision dosing through datadrivenpersonalized regimens will improve treatmentoutcomes and maximize the efficient use of this and other monoclonal antibody therapeuticsSummaryRituximab is a monoclonal antibody used to treat many types of cancer and autoimmune disordersbutthereisgrowingevidencethatsomepatientsarenotreceivingenoughofthisagentwhengivenstandarddosesThisprojectwillfinalizedevelopmentandfullyvalidatesimplelateralflowassaydevices that can measure within minutes how much rituximab is present in a patient s blood