PEEL Therapeutics, Inc. (PEEL) is pioneering a novel approach to prevent morbidity and mortality associated with inflammatory disease through the inhibition of neutrophil extracellular traps (NETs). NETs are lattices of decondensed chromatin decorated with histones and antimicrobial proteins extruded by polymorphonuclear leukocytes (PMNs) to trap and kill microbes. While regulated NET formation contains infection, dysregulated NET formation leads to inflammatory tissue damage and vascular injury. NETs have been implicated in human diseases characterized by inflammation, including sepsis, stroke, diabetes, and heart disease. The ability of NET- inhibitory factors (NIFs) to block PMN-dependent NET formation makes this newly described class of endogenous peptides a promising therapeutic modality for diseases caused and/or exacerbated by NET-dependent inflammatory events. In this Phase I SBIR, PEEL will quantify and compare the biological activity and pharmacokinetics of two NIFs in vitro and in vivo. The lead NIF peptide will move forward in the development of a novel anti-NET therapeutic. After completing these SBIR Phase I tasks, PEEL Therapeutics will be in an excellent position to advance its new and patented NIF-based therapeutic to further preclinical studies. These efforts by PEEL Therapeutics hold the potential to disrupt and improve the treatment approach to both acute and chronic inflammatory diseases. Public Health Relevance Statement PROJECT NARRATIVE Dysregulated inflammation leads to significant disease-associated morbidity and mortality, contributing to more than 30 million annual deaths worldwide. PEEL Therapeutics, Inc. is an emerging biotech that specializes in delivery of peptides and proteins to treat serious human diseases and has licensed novel peptides with unique biological properties to block inflammation as potential therapeutic agents for multiple inflammatory diseases. Development of novel strategies for inhibiting the molecular mechanisms of dysregulated immune response that lead to tissue and vascular damage has the potential to save millions of lives and profoundly impact human suffering from these inflammatory diseases.
Project Terms: inhibitor/antagonist ; inhibitor ; Anti-Inflammatory Agents ; Anti-Inflammatories ; Anti-inflammatory ; Antiinflammatories ; Antiinflammatory Agents ; antiinflammatory ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biology ; Biotechnology ; Biotech ; Blood Vessels ; vascular ; Cell Count ; Cell Number ; Chemotaxis ; Chromatin ; High Pressure Liquid Chromatography ; HPLC ; High Performance Liquid Chromatography ; High Speed Liquid Chromatography ; Cessation of life ; Death ; Diabetes Mellitus ; diabetes ; Disease ; Disorder ; DNA ; Deoxyribonucleic Acid ; Enzyme-Linked Immunosorbent Assay ; ELISA ; Fluorescence ; Half-Life ; Heart ; Heart Diseases ; Cardiac Diseases ; Cardiac Disorders ; heart disorder ; Histones ; Human ; Modern Man ; In Vitro ; Infection ; Inflammation ; intravenous injection ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Methionine ; Morbidity - disease rate ; Morbidity ; mortality ; Mus ; Mice ; Mice Mammals ; Murine ; neutrophil ; Blood Neutrophil ; Blood Polymorphonuclear Neutrophil ; Marrow Neutrophil ; Neutrophilic Granulocyte ; Neutrophilic Leukocyte ; Polymorphonuclear Cell ; Polymorphonuclear Leukocytes ; Polymorphonuclear Neutrophils ; Norleucine ; Legal patent ; Patents ; Peptides ; Peritonitis ; Phagocytosis ; Drug Kinetics ; Pharmacokinetics ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Proteins ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Tissues ; Body Tissues ; Universities ; Utah ; Work ; Caymans ; Measures ; Protein-arginine deiminase ; peptidylarginine deiminase ; protein-L-arginine iminohydrolase ; base ; Blood specimen ; Blood Sample ; improved ; Acute ; Phase ; Biological ; Ensure ; Licensing ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; Therapeutic ; Therapeutic Agents ; Inflammatory ; Deposit ; Deposition ; Rivers ; Nature ; peptide A ; Hour ; Immunes ; Immune ; Event ; Pattern ; extracellular ; experience ; success ; novel ; Treatment Factor ; Prevention ; Modality ; Pathogenesis ; Position ; Positioning Attribute ; Nervous System Injuries ; Nervous System damage ; Neurological Damage ; Neurological Injury ; Neurological trauma ; neurotrauma ; Nervous System Trauma ; Pharmacodynamics ; Modeling ; Property ; drug development ; Co(beta)-cyano-7''-(2-methyl)adeninylcobamide ; factor A ; preventing ; prevent ; Data ; in vivo ; Clinical Trials Design ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Molecular ; Enzyme Inhibition ; Development ; developmental ; Pathway interactions ; pathway ; pre-clinical ; preclinical ; preclinical study ; pre-clinical study ; Sepsis ; blood infection ; bloodstream infection ; novel strategies ; new approaches ; novel approaches ; novel strategy ; Neonatal ; antimicrobial ; anti-microbial ; Microbe ; human disease ; comparative ; mouse model ; murine model ; commercialization ; therapeutic development ; therapeutic agent development ; novel therapeutic intervention ; new therapeutic approach ; new therapeutic intervention ; new therapeutic strategies ; new therapy approaches ; novel therapeutic approach ; novel therapeutic strategies ; novel therapy approach ; in vitro activity ; comparative efficacy ; compare efficacy ; screening ; peptide drug ; therapeutic peptide ; live cell imaging ; live cell image ; live cellular image ; live cellular imaging ; experimental study ; experiment ; experimental research ; Injections ; polymicrobial sepsis ; cecal ligation puncture ; CLP model ; CLP mouse model ; Cecal ligation perforation ; preservation ; lead candidate ; stroke model ; pharmacokinetics and pharmacodynamics ; PK/PD ; vascular injury ; injury to the vasculature ; coronavirus disease ; COVID ; CoV disease ; corona virus disease ; chronic inflammatory disease ;
