Company: TVRD
Filing Date: 2025-10-07
Form Type: S-1/A
Source: 0001104659-25-097519
Chunk: 172

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-07
Form: S-1/A
Chunk 172
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 observed. We have received pre-IND feedback from the FDA that our data package to date is sufficient to support a clinical trial of TTI-109 in oncology. We submitted an IND application for TTI-109 in June 2025.

<div align='center'>TTI 109: Prodrug of TTI 101 and Next Generation STAT3 Inhibitor</div>

Idiopathic Pulmonary Fibrosis

Background on Idiopathic Pulmonary Fibrosis

IPF is a rare, chronic, debilitating interstitial lung disease characterized by inflammation, progressive fibrosis and lung damage of unknown cause. As IPF progresses, it leads to thickening and stiffening of the lung tissue and eventually the inability of the lungs to transfer oxygen into the bloodstream. Patients suffering from IPF experience a poor quality of life and struggle with their daily routine due to constant shortness of breath, fatigue and weakness. In most patients suffering from IPF, the cause of death is IPF itself. Moreover, IPF is also associated with respiratory and non-respiratory comorbidities such as chronic obstructive pulmonary hypertension, obstructive sleep apnea, lung cancer, ischemic heart disease and gastro-esophageal reflux. Patients suffering from IPF have a poor life expectancy, and it is estimated that the five-year mortality rate of patients suffering from IPF ranges from 60% to 80%.

FVC, a measure of pulmonary function, is an important monitoring and prognostic tool for patients suffering from IPF and the 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

<div align='center'>100</div>

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