Company: TVRD
Filing Date: 2025-05-30
Form Type: S-1
Source: 0001104659-25-054853
Chunk: 174

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-05-30
Form: S-1
Chunk 174
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yme 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</div>

We believe our findings further support TTI-101 as a therapeutic product candidate for IPF as we were able to impact multiple mechanisms associated with the critical components of deposition and degradation in the pathogenesis of IPF.

#### Clinical Development of TTI-101 for IPF
Phase 1 TTI-101 Healthy Volunteer Drug-Drug Interaction Clinical Trial

Prior to the initiation of our ongoing Phase 2 clinical trial of TTI-101 in IPF, we completed a Phase 1 healthy volunteer clinical trial in the United States to determine the safety, tolerability and PK potential of a drug-drug interaction with IPF standard of care therapies (nintedanib and pirfenidone). The clinical trial enrolled 41 healthy volunteers,