AQUALUNG THERAPEUTICS, CORP — Department of Health and Human Services STTR Phase I: NHLBI

Description

PROJECT SUMMARYAcute Respiratory Distress SyndromeARDSis a devastatingly intense lung inflammatory disorder that annually afflicts more thanmillion individuals world widecases year in the U Swith an unacceptable mortality rate ofSubstantial clinical and biological heterogeneity within ARDS phenotypes has greatly impeded therapeutic developments to reduce mortalityAll therapies currently employed in ARDS management are genericThe critical care community suffers from a lack of tools that allow identification of ARDS sub phenotypes and individuals most likely to benefit from novel therapiesRecentlythe hyperinflammatory and low inflammatory ARDS sub phenotypes were identified that markedly differ in natural historiesclinical and biological characteristicsbiomarker profilesresponses to positive end expiratory pressureventilatorand organ failure free days and mortalityARDS severityPaOFiOratiothe severity of renal or hepatic failureor the extent of leukocytosis failed to distinguish the two phenotypesAs the mortality of the hyperinflammatory phenotype istimes greater than low inflammatory phenotypethis Phase I STTR will leverage substantial complementary expertise toiestablish a novel panel of ARDS biomarkersCRIT ICU Panelthat stratifies subjects at risk for ARDS into high and low mortality sub phenotypesand iidevelop a quantitative platform to allow assessment of these validated biomarkers upon patient entry into the ER or ICUOur preliminary biomarker data are strong and includeARDS relevant plasma biomarkers in andgtwell phenotyped ARDS subjects andcontrolsThe targeted biomarkers include cytokine chemokinesILILILbIL RAdual functioning cytozymes i ecytokine intracellular enzymesmacrophage migration inhibitory factorNAMPTvascular injury markersVEGFAS PRangiopoietinand the advanced glycosylation end product pathwayHMGBsoluble RAGESpecific Aimwill apply standard biostatistical approaches as well as novel neural network artificial intelligence analysis of this existing dataset to identify an optimal plasma derived CRIT ICU Panel which predicts ICU mortality in patients with sepsis or trauma who are at risk for development of respiratory failure and ARDSSpecific Aimwill develop an optimized and highly standardized Predictive Platform for the CRIT ICU biomarkers identified to be used in the clinical care settingFinallySpecific Aimwill conduct retrospective validation studies of the optimized CRIT ICU Panel in biobanked samples fromlarge cohortsan emergency room ARDS cohortPETAL Clinical Networknand a Spanish sepsis ARDS cohortnWe speculate that unique expertise within Aqualung Therapeutics CorpPAI Life Sciences IncInBios International Incand the University of Arizona Health Sciences will drive future prospective validation of the CRIT ICU Panel in patients at risk for ARDSPhase II STTRand lead to development of a true Point of Care test to accelerate clinical trial stratification strategiesand development of innovative ARDS therapeutics to reduce mortality in this devastating syndrome PUBLIC HEALTH RELEVANCEAcute Respiratory Distress SyndromeARDSis a devastatingly intense lung inflammatory disorder that afflicts more thanmillion individuals world wide each yearcases year in the U Swith an unacceptable mortality rate ofThe tremendous heterogeneity of ARDS has greatly impeded therapeutic developments to address ARDS mortality and all therapies currently employed in ARDS management are genericThe critical care community suffers from a lack of empirical data and tools that would allow identification of ARDS subphenotypes and potentially identify individuals most likely to benefit from novel therapiesThis Phase I STTR leverages substantial complementary expertise to establish a novel panel of ARDS biomarkersCRIT ICU Panelthat will be used to stratify subjects at risk for ARDS into high and low mortality sub phenotypes and develop a predictive platform to allow assessment of these validated biomarkers upon entry into the ER or ICUThis will accelerate the conduct of clinical trial stratification strategies and lead to more robust innovation in ARDS therapeutics to reduce mortality in this devastating syndrome