Company: TVRD
Filing Date: 2025-10-07
Form Type: S-1/A
Source: 0001104659-25-097519
Chunk: 177

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-07
Form: S-1/A
Chunk 177
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NK GP7 and Perforin) and apoptosis-inducing factors (Granzyme A and B) with increased doses of TTI-101 (p<0.05 for trend). TTI-101’s Impact on Both Extrinsic and Intrinsic STAT3 Canonical Functions Associated with IPF These findings translated into a dose-dependent relationship between TTI-101 dose and observed effects:

| ● | Pharmacokinetics — we observed TTI-101 concentration in mouse lungs accumulated in the lung four times as much as compared to its accumulation in the plasma as measured by LC/MS/MS (50mg/kg: 8868 vs 1672; 25mg/kg: 8927 vs 2348; 12.5mg/kg: 7407 vs 1995). Administration of TTI-101 in a non-disease mouse model did not accumulate in the lung. |

| ● | Pharmacodynamics — Dose-dependent decrease of pY-STAT3 observed: the higher the dose of TTI-101 administered, the lower the levels of activated STAT3. |

| ● | Biological activity — At the higher two doses of 25 mg/kg and 50 mg/kg, TTI-101 demonstrated statistically significant improvement in lung function as compared to treatment with placebo (50mg/kg: 91.3; 25mg/kg: 92.7; 12.5mg/kg: 87.9 versus 94.9) (p<0.05) or with BLM alone (86.1) (p<0.05) as measured by SO2, where mice continued to experience loss of lung function. |

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<div align='center'>TTI-101’s Demonstrated Dose-Dependent PK exposure, PD and Improved Lung Function

TTI-101 Targeted a Multitude of Key Fibrotic Mediators in Human Ex Vivo Lung Slices from IPF Patients</div>

Dr. Ivan O. Rosas is a nationally recognized expert in pulmonary and critical care medicine, currently serving as Chief of the Section of Pulmonary, Critical Care, and Sleep Medicine at BCM. In a preclinical study, published by McKenna et al, Dr. Rosas and his collaborators at BCM demonstrated that TTI-101 suppressed fibrotic markers that are not addressed with currently approved therapies (nintedanib and pirfenidone). In the study, the team used single-cell RNA sequencing on lung samples