Selection of a lead candidate for the development of a novel anti-inflammatory therapeutic

PROJECT SUMMARY/ABSTRACT 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.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.