Company: TVRD
Filing Date: 2025-10-20
Form Type: S-1/A
Source: 0001104659-25-100896
Chunk: 166

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-20
Form: S-1/A
Chunk 166
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,000 individuals have IPF, while globally the number is estimated to be three million. Currently, approved anti-fibrotic therapies, Esbriet and Ofev, had collective peak sales of $4.9 billion, yet their use is limited as they do not reverse fibrosis or improve lung function. Based on the well-established role of pY-STAT3 in the pathogenesis of fibrosis, we believe TTI-101’s differentiated mechanism of action has the potential to address this unmet need in IPF, if approved. In preclinical models, we observed that TTI-101 led to a reduction of fibrotic tissue in the lungs and improved lung function. We also observed dose-dependent decreases in validated biomarkers associated with cell proliferation (resulting in reduced deposition) as well as increase in the modulation and activity of T cells (responsible for increased cellular and extracellular degradation). Additionally, our completed Phase 1 healthy volunteer drug-drug interaction clinical trial with IPF SoC, therapies showed TTI-101 to be generally well-tolerated. No severe adverse events (“SAEs”), were reported. The most frequent treatment emergent adverse events (“TEAEs”), predominantly reported as mild in severity, resolved on study. Our clinical data, including robust pharmacokinetic (“PK”), pharmacodynamic (“PD”), and tolerability data, has allowed us to rapidly progress into a Phase 2 clinical trial in IPF.

We reported preliminary data from our REVERT IPF Phase 2 clinical trial of TTI-101 in IPF in October 2025 and concluded that the study did not meet its goals. We are conducting additional analyses to further understand these results and inform next steps.

#### TTI-101 for the Treatment of HCC
HCC, a fibrosis-driven cancer, is the third-leading cause of cancer-related mortality in the United States and globally, with an estimated survival of six to 20 months following diagnosis. Treatment with the current SoC in first line remains suboptimal with an overall response rate (“ORR”), of 10% to 27%. Following progression on first-line therapies, response rates are further reduced (ORR of ≤5%) for patients who go on to receive second-line therapies. Overall response rate is defined as the proportion of patients who have achieved a partial response (≥30% decrease in the sum of the diameters of target lesions, as compared with the baseline sum of diameters) or a complete response (disappearance of all target lesions).