# Development of a small molecule inhibitor of PAI-1 for the treatment of diffuse cutaneous systemic sclerosis

> **NIH NIH R44** · MDI THERAPEUTICS, INC. · 2020 · $746,985

## Abstract

This project will provide critical preclinical data for a novel therapeutic small molecule inhibitor of
plasminogen activator inhibitor 1 (PAI-1) as a potential treatment for diffuse cutaneous systemic
sclerosis with associated interstitial lung disease (dcSSc-ILD). SSc is a devastating disease of
unknown etiology with no currently approved disease-modifying treatments; lung fibrosis
(interstitial lung disease, ILD) is the leading cause of mortality in dcSSc. In this phase II
application we will further develop a highly innovative first in class therapeutic, MDI-2517. PAI-1
is the physiologic inhibitor of tissue and urokinase plasminogen activator (tPA and uPA). In
normal physiology PAI-1 regulates processes such as fibrinolysis and wound healing. However,
elevated expression of PAI-1 is associated with fibrotic diseases of the lung, kidney, heart, and
importantly for this application, with SSc. This association has led to the recognition that PAI-1
contributes directly to pathology, and that its inhibition may be an effective approach to treat
fibrotic disease. MDI Therapeutics has identified a highly effective, orally active, small molecule
inhibitor of PAI-1 with efficacy in multiple models of fibrotic disease, including pulmonary fibrosis
and SSc. The studies described in this Phase II application will provide critical safety and
toxicology data as well as in vivo comparator studies with current treatment options. There are
two Specific Aims with clearly defined Milestones aimed at advancing MDI-2517 toward filing an
Investigational New Drug (IND) application and subsequently conducting first-in-human Phase 1
clinical studies which will be funded in Phase III by securing private venture capital investment.

## Key facts

- **NIH application ID:** 10004564
- **Project number:** 5R44AR074318-03
- **Recipient organization:** MDI THERAPEUTICS, INC.
- **Principal Investigator:** James Craig Hartman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $746,985
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004564

## Citation

> US National Institutes of Health, RePORTER application 10004564, Development of a small molecule inhibitor of PAI-1 for the treatment of diffuse cutaneous systemic sclerosis (5R44AR074318-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004564. Licensed CC0.

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