AFFINERGY, LLC — Department of Health and Human Services SBIR Phase I: NIAID

Description

SUMMARY ABSTRACT Inoverorgan transplants were performed in the United Statesan increase ofover the pastyearsOrgan transplantation requires lifelong immunosuppression to prevent rejection of the transplantTacrolimusa macrolide antibioticis one of the most effective immunosuppressantswith andgtof solid organ transplant recipients receiving it as part of their maintenance immunosuppressionTacrolimus has a narrow therapeutic windowwith sub therapeutic levels putting patients at risk for rejection and supra therapeutic levels leading to toxicityIn addition to significant pharmacokinetic variabilityit is also estimated that andgtof patients are non adherent to their immunosuppressant regimensignificantly increasing graft rejection and failure rates and increasing the financial burden on the US healthcare systemBecause transplant recipients require a lifetime of immunosuppressionany methods that facilitate improved dosing and rapid detection of non adherence are of great clinical utilityBecause tacrolimus levels cannot be ascertained at the point of caredetection of non therapeutic levels in the outpatient setting is challengingPatients must either attend a separate lab appointment ahead of their routine follow up visits or they have levels drawn on the day of their visitIn the formeran extra burden is placed on the patient to attend an additional appointment while the latter precludes analysis of levels prior to the patient s appointmentDelays in medication management or identification of patient non compliance place the patient at risk for graft rejectionsub therapeutic levelsor drug associated toxicitiessupra therapeutic levelsTo address this technical hurdleAffinergy plans to develop a point of care lateral flow assay that will enable frequentaccurate and affordable monitoring of tacrolimus levelsWe have already generated a proprietary capture reagent and identified several detection reagent candidates that bind with nanomolar affinity to tacrolimusAt the conclusion of Phase Iwe will have a prototype lateral flow assay with established limits of quantitationIn Phase IIwe will scale up production of our assayoptimize performance characteristicsestablish storage conditionsdetermine stability and evaluate our assay using transplant recipient blood specimensSuccessful completion of this project will lead to improved long term maintenance of patients receiving tacrolimus for immunosuppression and ease the burden on both patients and providers PROJECT NARRATIVE Tacrolimus concentration must be closely monitored in transplant recipients as a part of their lifelong immunosuppressionHoweverpatients receiving tacrolimus in the outpatient setting must have blood levels shipped out or drawn the day of their visitleading to unacceptable delays in dosage adjustmentIn this FastTrack applicationwe propose to develop a novel peptide based sandwich assay to facilitate rapidaffordablepoint of care measurement of tacrolimus concentration in biological fluids