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

> **NIH NIH R44** · MDI THERAPEUTICS, INC. · 2022 · $1,000,618

## Abstract

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.

## Key facts

- **NIH application ID:** 10384244
- **Project number:** 1R44HL158435-01A1
- **Recipient organization:** MDI THERAPEUTICS, INC.
- **Principal Investigator:** James Craig Hartman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,000,618
- **Award type:** 1
- **Project period:** 2022-03-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384244

## Citation

> US National Institutes of Health, RePORTER application 10384244, Completion of IND-enabling studies required for first-in-human studies of a novel oral therapeutic agent for treating pulmonary fibrosis (1R44HL158435-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10384244. Licensed CC0.

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