Company: TVRD
Filing Date: 2025-01-27
Form Type: S-4/A
Source: 0001104659-25-006050
Chunk: 31

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-01-27
Form: S-4/A
Chunk 31
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 in the lungs and improved lung function. Tvardi 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, Tvardi’s 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 were reported. The most frequent treatment emergent adverse events predominantly reported as mild in severity, resolved on study. This clinical data, including robust pharmacokinetic (PK), pharmacodynamic (PD), and tolerability data, has allowed Tvardi to rapidly progress into a Phase 2 clinical trial in IPF.

Tvardi is currently enrolling in a REVERTPhase 2, multicenter, randomized, double-blind, placebo- controlled clinical trial of TTI-101 to evaluate safety, tolerability and PK in patients suffering from IPF as monotherapy and in addition to nintedanib, a current SoC. Tvardi also plans to evaluate multiple efficacy measures, including the established Phase 3 efficacy endpoint of forced vital capacity (FVC). Approximately 75 patients are randomly assigned (1:1:1) to receive oral TTI-101 400 mg/day, TTI-101 800 mg/day or placebo for 12 weeks as monotherapy or in addition to SoC, nintedanib. The natural course of disease for patients suffering from IPF even when treated with SoC, is a decline in lung function as measured by FVC. Preliminary blinded data from the two dose levels of TTI-101 and placebo in 38 patients to date have reported approximately 50% of patients’ FVC values near or above baseline. Tvardi expects to report unblinded data from this clinical trial in the second half of 2025.

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#### TTI-101 for the Treatment of HCCHCC, 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