Personalized precision dosing of anti-TNF biologic therapies

Project SummaryBiologics are increasingly used in the treatment of autoimmune and inflammatory diseasesMonoclonal antibodymAbdrugs that target tumor necrosis factor alphaTNF asuch as Remicadeinfliximabare blockbuster drugs global sales of infliximab were close to $ B inHoweverpost approval studies have revealed inefficiencies in the use of these anti TNF a biologicssome patients do not respond to mAb therapies upon inductionwhereas others lose response over timePrimary causes of dosing inefficiency include a rigid dosing schedule and the frequent development of anti drug antibodyADAresponses in treated patientsThe clinical data strongly point to the need for therapeutic dose monitoring of mAb drugs to ensure an optimal therapeutic window in every patientWhile laboratory based test methods are availablethere are no point of care tests for measuring the concentration of either infliximab or ADAsThe goal of this project is to develop lateral flow immunoassaysLFAsfor rapid measurement of free infliximab and ADA levels in finger stick blood samplesOur proprietary technology uses small peptide mimeticsVeritopesof the antigen as a specific capture reagentOur tests are based on ligand binding activityand are thus expected to detect the parent mAb druginfliximabas well as new biosimilarsinfliximab dyybinfliximab abdaWe previously qualified the technical feasibility of Veritope based LFAs for the detection of rituximab concentration in patient serumThe objectives of this project are togenerate Veritope specific for infliximab and implement the peptide in a LFA for the measurement of free infliximab levels in blood at the point of careDemonstrate ADA detection for infliximab using a complement point of care LFA that incorporates an initial acid dissociation stepandvalidate free drug and ADA LFA using patient samplesThese innovative products will fulfill of an unmet clinical need for a rapidcost effectiveand accurate dose monitoring assayPrecision dosing through data drivenpersonalized regimens will improve treatment outcomes and maximize the efficient use of infliximab Project NarrativeInfliximab is a monoclonal antibody used to treat Crohn s disease and ulcerative colitisbut there is growing evidence that some patients are not receiving a therapeutic dose of this agent when given standard dosesThis project will finalize development and fully validate simple lateral flow assay devices that can measure within minutes how much infliximab is present in a patient s blood