# Novel compounds for the treatment of systemic sclerosis-associated interstitial lung disease

> **NIH NIH R44** · EYDIS BIO, INC. · 2024 · $1,182,632

## Abstract

PROJECT SUMMARY / ABSTRACT
Systemic sclerosis interstitial lung disease (SSc-ILD) is a progressive orphan disease highlighted by pulmonary
fibrosis leading to a high mortality rate. Currently, there are only two FDA approved SSc-ILD therapies (OFEV
and ACTEMRA), both of which have limited efficacy and are mired with safety issues, warranting the
development of novel therapeutic targets to treat SSc-ILD. Our preclinical work has identified TGFβ-activated
kinase 1 (TAK1) as a key signaling element in fibroinflammatory signaling observed in pulmonary fibrosis. TAK1
plays a critical role in facilitating activation of protein kinase-mediated signaling pathways implicated in the
pathogenesis of SSc-ILD, and as a result has emerged as a novel target for regulating SSc-ILD mediated
inflammation and fibrotic signaling. Our recent discovery of the takinib scaffold has identified a highly selective
(selectivity score = 0.037), potent (IC50 = 2.5nM), and orally bioavailable (%F = 98%) small molecule inhibitor of
TAK1 (HS-276). Preclinical studies have demonstrated that TAK1 inhibition attenuates critical TGFβ fibrotic
signaling in human-derived fibroblasts, as well as limits pro-inflammatory cytokine signaling in activated human
macrophages. Furthermore, HS-276 significantly reduced bleomycin-induced pulmonary fibrosis, in vivo. Here,
we will build upon these foundational proof of concept studies and further develop HS-276 for the treatment of
SSc-ILD. In order to successfully further develop our program, this project includes the following Specific Aims:
Aim 1: In vivo pharmacodynamic studies with HS-276 in two distinct murine lung fibrosis models: (Bleomycin
and Tsk1/+). Aim 2: HS-276 safety in bacterial and fungal opportunistic disease models. Aim 3: Completion of
key GLP safety and toxicology studies required for submission of an IND. Following successful completion of
these aims we will be poised to advance HS-276 towards Phase I clinical trials for the treatment of SSc-ILD.

## Key facts

- **NIH application ID:** 10920991
- **Project number:** 1R44HL170834-01A1
- **Recipient organization:** EYDIS BIO, INC.
- **Principal Investigator:** TIMOTHY A HAYSTEAD
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,182,632
- **Award type:** 1
- **Project period:** 2024-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920991

## Citation

> US National Institutes of Health, RePORTER application 10920991, Novel compounds for the treatment of systemic sclerosis-associated interstitial lung disease (1R44HL170834-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10920991. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*