# Myocardin-related transcription factor (MRTF) pathway modulators as a novel, disease-modifying oral medicine for idiopathic pulmonary fibrosis (IPF)

> **NIH NIH R43** · ONCOARENDI THERAPEUTICS, LLC · 2024 · $241,125

## Abstract

Abstract
 The overall objective of this project is for OncoArendi Therapeutics (OAT) to develop a myocardin-related
transcription factor (MRTF) pathway inhibitor as a novel, disease-modifying oral medicine for
idiopathic pulmonary fibrosis (IPF), with superior medical benefit and improved safety and tolerability
compared to current treatments. The main goal of this Phase I proposal is the selection of a compound to
enter IND-enabling studies.
 IPF is a chronic, progressive and fatal fibrotic lung disease, with a median survival of 3-5 years after
diagnosis. Current treatment options for IPF are limited with minimal efficacy and significant tolerability issues.
It is estimated that about 5 million people worldwide suffer from IPF. Thus, IPF represents a serious, common
disease with a massive unmet medical need for new medicines that will improve morbidity and mortality.
 Literature reports have provided evidence that the MRTF pathway is critical to the initiation and progression
of fibrosis, and underpins the various processes that are responsible for fibrosis. One of the current standard-
of-care treatments for IPF, pirfenidone, inhibits MRFT activation, albeit in very high concentrations. Thus,
selective and potent MRTF pathway inhibitors offer an innovative strategy to attenuate fibrosis. OAT has
identified MRTF pathway inhibitors, with the most potent compound, OAT-5116, having an IC50 of 50 nM in the
primary screening assay, involving inhibition of MRTF/SRF dependent luciferase assay on transfected HEK293
T cells. OAT-5116 is >1000-fold more potent than pirfenidone (IC50 >100 µM) in this assay. The two key Aims
of this proposal are: Specific Aim 1: Lead Optimization to identify a Clinical Development Candidate
(CDC). A detailed Medicinal Chemistry strategy has been developed to synthesize and test novel analogs of
the current chemical pharmacophore, and address the developability liabilities of the lead compound, OAT-
5116, including poor oral pharmacokinetic profile in rodents, high plasma protein binding, and hERG potassium
channel inhibition. All the relevant in vitro and in vivo biological and DMPK assays have been established.
The ultimate goal of these studies is the selection of a CDC compound with the appropriate biological,
chemical, DMPK and developability characteristics to progress into IND-enabling studies. Specific Aim 2:
Effects of the CDC in the Bleomycin-induced Model of IPF in Mouse. The dose-response effects of oral
administration of the CDC compound will be examined in the bleomycin-induced pulmonary fibrosis model in
mouse, the gold-standard rodent model of IPF. The compound will be administered using a therapeutic
treatment paradigm and its effects will be compared with those of oral pirfenidone, a current treatment for IPF.
 The results from this Phase I application will expand the scientific rationale for an MRTF pathway
inhibitor as an innovative, disease-modifying oral therapy for IPF, and lay the foundation for the ...

## Key facts

- **NIH application ID:** 10918422
- **Project number:** 1R43HL174237-01
- **Recipient organization:** ONCOARENDI THERAPEUTICS, LLC
- **Principal Investigator:** Adam Golebiowski
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,125
- **Award type:** 1
- **Project period:** 2024-05-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918422

## Citation

> US National Institutes of Health, RePORTER application 10918422, Myocardin-related transcription factor (MRTF) pathway modulators as a novel, disease-modifying oral medicine for idiopathic pulmonary fibrosis (IPF) (1R43HL174237-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10918422. Licensed CC0.

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