Company: TVRD
Filing Date: 2025-01-27
Form Type: S-4/A
Source: 0001104659-25-006050
Chunk: 466

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-01-27
Form: S-4/A
Chunk 466
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-1 α), and plasminogen activator inhibitor-1 (PAI-1) (p≤0.05). Administration of TTI-101 in mice also resulted in statistically significant increases in SO 2levels (p≤0.05), which returned to near normal levels, as compared to vehicle, where SO 2levels continued to decline in untreated mice. p = “p-value,” the conventional method for determining the statistical significance of a result, which represents the probability that random chance caused the result (e.g., a p-value = 0.01 means that there is a 1% probability that the difference between the control group and the treatment group is purely due to random chance). Generally, a p-value less than 0.05 is considered statistically significant. Reduction of Lung Fibrosis and Statistically Significant Improvement of Oxygen Saturation Observed with TTI-101 TTI-101 Targeted Multiple Pathogenic Steps of IPF in a BLM-Induced IPF Mouse Model Tvardi conducted a dose-range-finding, PK and PD preclinical study of TTI-101 in the BLM-induced IPF model to understand the therapeutic impact on reducing the severity of fibrosis and inflammation in relationship to TTI-101’s PK and PD profile in the United States. TTI-101 was administered nine days after induction of BLM-induced fibrosis, in human equivalent doses (HED), of 200, 400 and 800 mg/day. Biomarkers to identify the mechanism of action, drug exposure, pY-STAT3 levels and clinical outcomes (fibrosis and SO 2) were evaluated.

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Tvardi observed dose-dependent decreases in validated biomarkers associated with myofibroblast proliferation and ECM deposition downstream of intrinsic STAT3 signaling, as measured in florescence units of gene expression by RT-PCR, BLM + placebo vs BLM + either 12.5, 25 or 50mg/kg TTI-101. Specifically, Tvardi demonstrated significant decreases in biomarkers associated with clotting and coagulation (PAI1 and Ptafr), myeloid infiltration and macrophage activation (Ccl2 and IL-6), fibroblast activation and proliferation (Ccl2 and IL-6) and ECM deposition (Ccl2 and IL-6) with increased doses of TTI-101 (p<0.05 for trend). In addition, Tvardi demonstrated dose-dependent increases in validated biomarkers