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

Description

TITLEOptimization of LGMfor use as a device in lung transplantProject Summary Abstract LignaMedLLC is developing a novel small molecule deviceLGMthat will be utilized and administered via FDA approved ex vivo lung perfusionEVLPto improve lung function parameters of ex vivo donor lungs in advance of transplant surgeryPer FDA device regulations LGMwill be fully cleared from the donor lung prior to transplantThis work supports the efforts of the NHLBI to promote the prevention and treatment of lung diseases and enhance the health of individuals to live longer and more fulfilling livesand also addresses an NHLBI stated goal of expanding the donor lung poolChronic lung diseases affectmillion Americans and result in almostdeaths annuallyLung transplantation is the only life saving therapy for patients with certain types of end stage lung diseaseHoweverthe procedure has limited availability because not all donor lungs are safe for transplantationThis shortage of donor lungs results in the death ofpercent of lung transplant candidates awaiting transplantThis shortage arises in part from damage to donor lungs prior to and during preservation due to generation of reactive oxygen speciesROSand subsequent oxidative lung tissue damageThis damage is also linked to eventual primary graft dysfunctionPGDafter transplantationPGD arises from ischemia reperfusionI RInjury associated with storage and transplant maneuversAllograft quality combined with ROS and other oxidants produced with I R lead to direct damage that decreases the pool of transplantable lungsThusblocking ROS is a critical step in reducing ROS induced damageLignaMedandapos s novel device works through a unique three prong mode of action to impact reactive ROS via adirect free radical scavengingbactivation of the Nrfantioxidant response elementAREpathway and cdecrease of ROS production via inhibition of inflammasome and inflammatory cell influxneutrophilsmacrophagesLGMhas excellent drug like properties including desirable physiochemical properties and oral bioavailablePK PD studies in mouse and non human primates have shown good oralintravenous and subcutaneous distribution while studies in the EVLP model show excellent exposure to lung tissue with aerosolized drugWhen administered to miceLGMprevented radiation induced lung inflammation and fibrosis and improved lung function parameters and arterial blood oxygenationMoreover when administered via EVLP in pilot studies run in collaboration with DrChristieandapos s group at the University of PennsylvaniaLGMsignificantly improved rehabilitated lung function parameters in donor lungs that previously failed to meettransplant viableacceptance criteriaIn this Fast track SBIR proposalour Phase I aims will focus to characterize the kinetics of inhaled LGMIn Phase II we will validate the magnitude of the effect and determine safety in an expanded patient populationLignaMed has submitted a background and meeting request package to FDAlines NARRATIVE Lung transplantation is the only life saving therapy for patients with certain types of end stage lung diseaseHoweverthe procedure has limited availability because not all donor lungs are safe for transplantationThis shortage of donor lungs results in the death ofpercent of lung transplant candidates awaiting transplantLignaMed is developing LGMa small molecule medical device to improve the quality and number of donor lungs available for transplantLGMhas the potential to save livesdecrease healthcare costs and improve outcomes and quality of life for lung transplant patients