Targeting Neutrophil Extracellular Traps for Acute Lung Injury

ABSTRACT Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are life- threatening conditions with no FDA-approved pharmacologic therapy. More than 200,000 people suffer from ALI/ARDS annually in the US. They are primarily ICU patients who suffer secondary organ injury to the lungs as a result of trauma, transfusion, burns, infection, sepsis, hemorrhagic shock, smoke inhalation, or oxygen exposure. ALI/ARDS has demonstrated mortality rates as high as 40% as well as significant long-term morbidity. ALI/ARDS pathogenesis is characterized by neutrophilic inflammation and the release of Neutrophil Extracellular Traps (NETs). Neutrolis’ founding team has deep understanding of the biology and pathology caused by NETs. NETs are lattices of high-molecular weight chromatin filaments complexed with toxic proteins. In ALI/ARDS, NETs accumulate in alveolar cavities and capillaries of the lung and prevent blood oxygenation. Neutrolis has developed a lead candidate for therapeutic targeting of NETs. In this research proposal, Neutrolis will generate information on non-clinical properties and formulation of its lead that are required for the pre-IND meeting with the FDA. Specifically, the key outcomes of these aims are to determine the most effective route of administration. Neutrolis will assess an intravenous and inhalational method of drug delivery for treatment of ALI, and characterize their (1) efficacy dose, (2) pharmacological (PK/PD), and (3) toxicological properties. In summary, Neutrolis is well positioned to bring its proprietary developmental lead for treating ALI into the clinic. Given that NETs are abundant in acute and chronic inflammatory diseases, Neutrolis aims to ultimately address the multiplicity of inflammatory conditions, offering hope and relief to millions of suffering patients worldwide.NARRATIVE Acute Lung Injury (ALI) is a potentially fatal disease with no available drug treatments. In the US, over 200,000 people develop ALI each year. Thus, ALI/ARDs represents an unmet medical need which urgently requires new treatment options. Neutrolis, a biotech company in Cambridge, Massachusetts, develops therapeutics against acute inflammatory diseases and proposes NTR-10, its lead candidate, for the direct treatment for ALI.