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

MDI Therapeutics是一家早期制药公司，正在开发一类新的小分子抑制剂 纤溶酶原激活物通道1型（派-1）（基因：SerpinE 1）用于治疗纤维增生性疾病。 纤维化由细胞外基质（ECM）的组分的过度积累定义，例如 胶原蛋白和纤连蛋白，在发炎或受损的组织内和周围，这可能导致永久性疤痕， 器官功能障碍最终导致死亡发达国家近45%的死亡是由一些 慢性纤维增生性疾病的类型。在急性和慢性纤维化肺病患者中， 派-1诱导。派-1被最好地理解为其通过抑制纤维蛋白溶解和创伤愈合来调节纤维蛋白溶解和创伤愈合的作用。 组织型（tPA）和尿激酶型（uPA）纤溶酶原激活剂，其将酶原纤溶酶原转化为 活性酶纤溶酶。派-1作为伤口愈合（包括在肺中）的主要调节剂的作用是 这与其在纤维化中的关键调节作用一致。伤口愈合是受伤后的自然修复过程， 包括重叠的阶段，包括止血、炎症、增殖和基质合成，最后 分辨率这种有序过程的中断可导致伤口愈合受损，导致持续性的创伤。 炎症和/或基质合成并最终导致纤维化综合征。派-1作为创伤的主要调节剂 已显示愈合影响伤口愈合的所有阶段，并因此在肺损伤中起因果作用。 纤维化MDI Therapeutics已经开发出一种高效、口服活性的派-1小分子抑制剂， MDI-2517，在多种肺纤维化模型中显示出疗效。这里提出的研究将 为这种新型治疗药物提供关键的IND支持数据，以便提交研究性新药（IND） 在进行第一类派-1抑制剂（MDI-1）的首次人体I期临床研究之前， 2517）用于治疗肺纤维化。具体里程碑包括完成关键GLP安全性 提交研究性新药所需的药理学、药代动力学和毒理学研究 (IND)MDI-2517的应用。这些里程碑的成功完成将大大推进这一进程。 通过提供启动人类1期临床试验所需的数据，实现商业化。

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.