Company: TVRD
Filing Date: 2025-10-07
Form Type: S-1/A
Source: 0001104659-25-097519
Chunk: 178

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-07
Form: S-1/A
Chunk 178
---
 from untreated IPF patients and those treated with current approved therapies. They mapped the transcriptional landscape across 40 pulmonary cell types and observed ~60% of IPF-associated dysregulated genes were not addressed by either approved drug, which they termed the “IPF therapeutic gap.” They further identified STAT3 as a dominant regulatory transcription factor both in untreated IPF samples and in the “IPF therapeutic gap.” In addition, ex vivo analysis of human lung slices demonstrated TTI-101 outperformed nintedanib and pirfenidone in observed reversal of gene expression changes across IPF-relevant cell types.

Notably, of the many pro-fibrotic genes downregulated, TTI-101 robustly repressed PDE4B, the target of nerandomilast, which recently reported positive Phase 3 data in IPF patients. Along with the preclinical animal data, we believe this data further substantiates TTI-101 as a target a multitude of key fibrotic mediators that have been singularly targeted by previous IPF therapeutics.

<div align='center'>105</div>

#### By Targeting STAT3, TTI-101 Demonstrated to Downregulate Genes of the “IPF Therapeutic Gap” in Ex Vivo Human Lung Slices​We believe our findings further support TTI-101 as a therapeutic product candidate for IPF as we were able to impact multiple mechanisms associated with the critical components of deposition and degradation in the pathogenesis of IPF.Clinical Development of TTI-101 for IPFPhase 1 TTI-101 Healthy Volunteer Drug-Drug Interaction Clinical TrialPrior to the initiation of our ongoing Phase 2 clinical trial of TTI-101 in IPF, we completed a Phase 1 healthy volunteer clinical trial in the United States to determine the safety, tolerability and PK potential of a drug-drug interaction with IPF standard of care therapies (nintedanib and pirfenidone). The clinical trial enrolled 41 healthy volunteers, all of whom received 1,200 mg/day of TTI-101 in addition to nintedanib or pirfenidone.No severe adverse events (“SAEs”), were reported in this clinical trial. The most frequent treatment-emergent adverse events (“TEAEs”), were predominantly mild in severity and resolved on study with no change in therapy. One subject withdrew early due to a severe non-serious adverse event of pneumonia, which was deemed by the clinical trial investigator to be possibly related to T