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

Description

PROJECT SUMMARYMortality rates in intensive care unitsICUsare unacceptably high and are directly related to the duration of mechanical ventilation that is required to support patients with respiratory failureFor exampleacute respiratory distress syndromeARDSis a vexing acute inflammatory lung disease requiring mechanical ventilatory support as the result of severe hypoxemia and respiratory failureThe estimatedARDS cases yrU Sexhibit a mortality rate ofwith ventilator induced lung injuryVILIa potent stimulus for lung inflammation and release of multiple inflammatory cytokinesknown as cytokine storma significant contributor to ARDS severity and mortalityVILI may also ensue in mechanically ventilated patients with respiratory failure in intensive care unitsICUseven when ARDS is not presentAs no clinical therapeutic intervention in the ICU has significantly addressed VILIthere remains a serious unmet need for effective preventive therapies for VILIAqualung Therapeutics scientists have identified nicotinamide phosphoribosyltransferaseNAMPTas a novel upstream therapeutic target in the development of VILIand have developed human monoclonal antibodiesFabs or fragment antigen bindingdesigned to neutralize circulating extracellular NAMPTor eNAMPTGiven the lack of approved VILI therapiesALT seeks to improve ICU outcomes by developing the human monoclonal FabeNamptorTMas an innovative strategy to reduce or eliminate VILItargeting circulating eNAMPTeNamptorTM will be given prophylactically at the time of intubation in critically ill ICU patients receiving mechanical ventilationa marked advantage compared with prior ICU strategiesWe expect that eNamptorTM will reduce or eliminate VILI incidence and severityreduce the number of days ICU patients require mechanical ventilationreduce healthcare costsand improve ICU survivalWith this backgroundthe goal of this STTR Phase I II Fast Track application is to evaluate NAMPT neutralizing pegylated and non pegylated human monoclonal eNamptorTM Fab candidates for efficacy in attenuating eNAMPT induced NFkB in vitro signaling and preclinical murine VILI in vivo modelsSTTR Phase IIn additionwe will conduct pharmacokinetic pharmacodynamic and toxicology studies with lead eNamptorTM Fab candidates in rat and canine modelsSTTR Phase IIThis STTR Phase I II Fast Track application represents a collaboration between a biotech startup companyAqualung Therapeutics Corporationan academic entityUniversity of Arizonaand a private companyGennova Biopharmaceutical LtdTogetherwe will address a serious and important unmet need by validating eNamptorTM as a viable VILI therapeutic approachWe anticipate these efforts will lead to submission of a IND application to the FDA to promote eNamptorTM as a therapeutic strategy for VILI in man PUBLIC HEALTH RELEVANCEAcute respiratory distress syndromeARDSis a devastating inflammatory lung diseaseestimatedcases per year in the United Stateswith an unacceptable high mortality rate ofMechanical ventilation directly contributes to de novo lung injury in ARDS patients as well as in mechanically ventilated ICU patients with respiratory failureestimatedU Scases yrdue to a condition known as ventilator induced lung injuryVILIDespite recent advances in care of the critically illthere remains a need for therapeutic options to address the extremely harmful consequences of VILIThis Fast Track Phase I II STTR seeks to utilize a novel therapeutic strategy targeting extracellular NAMPT to reduce VILI morbidity and mortality