Company: TVRD
Filing Date: 2025-10-20
Form Type: S-1/A
Source: 0001104659-25-100896
Chunk: 183

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-20
Form: S-1/A
Chunk 183
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ing STAT3, TTI-101 Demonstrated to Downregulate Genes of the “IPF Therapeutic Gap” in Ex Vivo Human Lung Slices**</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, all of whom received 1,200 mg/day of TTI-101 in addition to nintedanib or pirfenidone.

No severe adverse events (“SAEs”), were reported in this clinical trial. The most frequent treatment-emergent adverse events (“TEAEs”), were predominantly mild in severity and resolved on study with no change in therapy. One subject withdrew early due to a severe non-serious adverse event of pneumonia, which was deemed by the clinical trial investigator to be possibly related to TTI-101.

When comparing the drug-drug interactions between the two evaluated standard of care therapies when concurrently administered with TTI-101, optimal exposures were observed with nintedanib. Based on the findings of this healthy volunteer DDI clinical trial, we chose nintedanib as the standard of care in our ongoing Phase 2 clinical trial.

REVERT IPF Phase 2 Clinical Trial of TTI-101 in Patients suffering from IPF

Unblinded Data from Phase 2 Clinical Trial

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

The trial was a Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial of TTI-101 to evaluate safety, tolerability and PK in patients suffering from IPF. In addition to safety and