Company: TVRD
Filing Date: 2025-10-20
Form Type: S-1/A
Source: 0001104659-25-100896
Chunk: 182

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-20
Form: S-1/A
Chunk 182
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, TTI-101 demonstrated statistically significant improvement in lung function as compared to treatment with placebo (50mg/kg: 91.3; 25mg/kg: 92.7; 12.5mg/kg: 87.9 versus 94.9) (p<0.05) or with BLM alone (86.1) (p<0.05) as measured by SO2, where mice continued to experience loss of lung function.

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<div align='center'>**TTI-101’s Demonstrated Dose-Dependent PK exposure, PD and Improved Lung Function

TTI-101 Targeted a Multitude of Key Fibrotic Mediators in Human Ex Vivo Lung Slices from IPF Patients**</div>

Dr. Ivan O. Rosas is a nationally recognized expert in pulmonary and critical care medicine, currently serving as Chief of the Section of Pulmonary, Critical Care, and Sleep Medicine at BCM. In a preclinical study, published by McKenna et al, Dr. Rosas and his collaborators at BCM demonstrated that TTI-101 suppressed fibrotic markers that are not addressed with currently approved therapies (nintedanib and pirfenidone). In the study, the team used single-cell RNA sequencing on lung samples 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.

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<div align='center'>**By Target