Completion of IND-enabling studies required for first-in-human studies of a novel oral therapeutic agent for treating pulmonary fibrosis

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MDI Therapeutics is an early-stage pharmaceutical company developing a new class of small molecule inhibitors of plasminogen activator inhibitor-type 1 (PAI-1) (gene: SerpinE1) for the treatment of fibroproliferative diseases. Fibrosis is defined by the excessive accumulation of components of the extracellular matrix (ECM), such as collagen and fibronectin, in and around inflamed or damaged tissue, which can lead to permanent scarring, organ malfunction and, ultimately, death. Nearly 45% of all deaths in the developed world are attributed to some type of chronic fibroproliferative disease. In patients with acute and chronic fibrotic lung disease there is a marked induction of PAI-1. PAI-1 is best understood for its role regulating fibrinolysis and wound healing by inhibiting the tissue-type (tPA) and urokinase-type (uPA) plasminogen activators, which convert the zymogen plasminogen to the active enzyme plasmin. The role of PAI-1 as a primary regulator of wound healing, including in the lung, is consistent with its critical regulatory role in fibrosis. Wound healing is a natural repair process after injury that consists of overlapping stages, including hemostasis, inflammation, proliferation and matrix synthesis, and finally resolution. Disruption of this ordered process can result in impaired wound healing, leading to persistent inflammation and/or matrix synthesis and ultimately to a fibrotic syndrome. PAI-1, as a primary regulator of wound healing has been shown to impact all stages of wound healing, and accordingly to play a causal role in pulmonary fibrogenesis. MDI Therapeutics has developed a highly effective, orally active, small molecule inhibitor of PAI-1, MDI-2517, with demonstrated efficacy in multiple models of pulmonary fibrosis. The studies proposes here will provide critical IND-enabling data for this novel therapeutic necessary for filing an Investigational New Drug (IND) application prior to conducting first-in-human Phase 1 clinical studies of the first-in-class PAI-1 inhibitor (MDI- 2517) for the treatment of pulmonary fibrosis. Specific milestones include completion of key GLP safety pharmacology, pharmacokinetics and toxicology studies required for submission of an Investigational New Drug (IND) application for MDI-2517. The successful completion of these milestones will significantly advance this program toward commercialization by providing data necessary for the start of human Phase 1 clinical trials.