Company: TVRD
Filing Date: 2025-01-27
Form Type: S-4/A
Source: 0001104659-25-006050
Chunk: 464

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-01-27
Form: S-4/A
Chunk 464
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 with a higher survival probability.

<div align='center'>STAT3 is Activated in Major Compartments of IPF-Affected Mouse and Human Lung Tissue</div>

Images on the right hand side were derived from Pedroza, M., Le, T.T., Lewis, K., Karmouty-Quintana, H., To, S., George, A.T., Blackburn, M.R., Tweardy, D.J. and Agarwal, S.K. (2016), STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation. The FASEB Journal, 30: 129 – 140. Western blot analysis of phospho-STAT-3 expression in human patients with mild and severe IPF. STAT-3 and GAPDH were used as controls (n ≥ 4). Phospho-STAT-3 band intensity was quantified using ImageJ analysis. Values are presented as the percentages of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), ± sem (n ≥ 4). *P ≤ 0.05 control vs. IPF. Western blot analysis using an antibody against phospho-STAT-3 in whole-lung lysates. STAT-3 and α-actin were used as controls. Phospho-STAT-3 band intensity was quantified using ImageJ analysis. Values are presented as the percentages of α-actin ± sem (n ≥ 4). *P ≤ 0.05 PBS vs. bleomycin (BLM).

Market Opportunity in IPF and Limitations of Existing Treatments

In the United States, approximately 150,000 individuals have IPF, while globally the number is estimated to be three million. Currently, there are two approved anti-fibrotic therapies for IPF, nintedanib (Ofev, marketed by Boehringer Ingelheim Pharma GmbH & Co. KG) and pirfenidone (Esbriet, marketed by Roche Holding AG).

The currently approved anti-fibrotic therapies target single mechanisms of IPF. Nintedanib is a tyrosine kinase inhibitor (TKI), that non-specifically targets kinases implicated in the pathogenesis of fibrotic tissue, while pirfenidone’s mechanism of action has not been established. Only approximately 25% of patients suffering from IPF are treated with nintedanib or pirfenidone. In