Company: TVRD
Filing Date: 2025-02-14
Form Type: 424B3
Source: 0001104659-25-014310
Chunk: 474

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: 424B3
Chunk 474
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 established efficacy endpoint for IPF clinical trials. Patients suffering from IPF have demonstrated an annual decline of approximately 5% in FVC in placebo-treated groups of randomized control trials, while real world evidence suggests many patients decline more rapidly. According to a study titled “Three-Month FVC Change: A Trial Endpoint for Idiopathic Pulmonary Fibrosis Based on Individual Participant Data Meta-analysis” by Fasihul A. Khan, et al., meta-analyses of pooled patient data from twelve placebo cohorts from IPF clinical trials have demonstrated a median three-month decline of 2.3% in FVC. Additionally, there was a 15% increased risk for mortality per 2.5% relative FVC decline. Data further demonstrated that three-month declines in lung function, as measured by FVC, are highly predictive of 12-month change and represent major implications for overall disease progression and prognosis for patients suffering from IPF.

STAT3 plays a critical role as a central mediator underlying the pathogenesis of fibrosis in IPF. pY-STAT3 levels are often elevated in human lung tissue samples of patients suffering from IPF, driving the development and progression of fibrosis through clotting and coagulation, inflammatory cell migration, myofibroblast proliferation, ultimately leading to ECM deposition.

STAT3 is activated in the three major compartments of the lungs associated with IPF. Elevated levels of pY-STAT3, as measured immunolocalization expression by immunohistologic staining, have been observed in human lung tissue samples of patients suffering from IPF and not observed in non-fibrotic, healthy control lungs. Specifically, pY-STAT3 was observed in the alveolar epithelial cells, alveolar fibroblasts and alveolar macrophages. High STAT3 expression in these compartments correlates with higher mortality in patients suffering from IPF, whereas low STAT3 correlates with a higher survival probability.

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<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