Lignamed, LLC — Department of Health and Human Services STTR Phase I: NHLBI

Description

LignaMedLLC is developing LGMa novel medical device that will be administered via an FDA approved ex vivo lung perfusion deviceEVLPto improve lung function parameters of ex vivo donor lungs in advance of transplant surgeryPer FDA device regulations LGMwill be fully flushed and cleared from the donor lung prior to transplantThe major challenge with lung transplantation is the oxidative damage that occurs during lung storageThis reduces the availability of lungs for transplant andprimesthe donor lung to recruit polymorphonuclear neutrophilsPMNfrom the transplant recipientRecruited PMN adhere to the vessel wall of the newly transplanted lunggrafttransmigrate and release myeloperoxidaseMPOan enzyme stored in neutrophils and macrophages responsible for hypochlorous acid generation causing injury to the graftRecognizing the role of PMN in injury and eventual poor transplant outcomethe clinical strategy at present is to block PMN activation by a non specific immunosuppression regimen administered to the transplant recipientHoweverimmunosuppression therapy has severe side effectsLignaMed proposes the use of LGMa synthetic small molecule agent to adampen inflammatory pathways in the donor lung and binhibit MPO activation in recruited PMNPreliminary data show that LGMprotects human donor lungs but the mechanism of protection has not been elucidatedIn the proposed Phase I study we will determine the immunomodulatory properties of LGMto modulate the pro inflammatory phenotype of stored human and mouse donor lungscold storageAimand reduce PMN adherence and activation during warm reperfusion by monitoringexogenousPMN adherenceMPO inhibition and subsequent lung injuryAimIf data obtained from the proposed human and mouse donor lungs show a significant reduction in PMN recruitmentadherence and subsequent tissue injurywe will be enabled to proceed to Phase II with a full clinical and analytical evaluation of this agent for an eventual FDA approvalOur focus onpre treatmentof a donor organprior to transplantwith LGMconstitutes a paradigm shift from the current transplant related therapies LignaMedLLCis developing LGMas a device for use in lung transplantIn this application we propose to treat donor lungsrather than the current clinical practice of treating theliverecipientwith LGMa device which blocks a cascade of damaging signals on the donor lung that predispose it to beinginjuredafter transplantElucidation of the mechanism by which this protection occurs is the focus of this work