Company: TVRD
Filing Date: 2025-10-20
Form Type: S-1/A
Source: 0001104659-25-100896
Chunk: 195

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-20
Form: S-1/A
Chunk 195
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 Cohort A, of 21 efficacy evaluable patients, 14 patients achieved a best response of SD. This disease control rate of 67% is comparable to the disease control rate (53%) observed in the HCC cohort of the Phase 1 trial of TTI-101 monotherapy. In Cohort B, four of eight patients achieved SD. Lastly, in Cohort C, out of 12 enrolled patients, four achieved a cPR with an overall disease control rate of 93%.

Based on our Phase 1 data and this clinical trial design, TTI-101 received Fast Track designation from the FDA. Fast Track designation may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that TTI-101 will receive marketing approval.

#### Our TTI-109 Product Candidate
Our second product candidate, TTI-109, is an oral, small-molecule, prodrug of, and mechanistically identical to, TTI-101. TTI-109 itself does not inhibit STAT3, but rapidly converts to TTI-101 in the blood. TTI-109 is designed to enhance our ability to target STAT3 as a more efficient delivery vehicle for TTI-101 with the potential to improve tolerability.

Prodrugs generated by attaching a phosphate moiety are relatively common and several have been approved by the FDA. The addition of a phosphate group improves the druggability of the active compounds, and the mechanism of action of the prodrugs remains identical to that of their parent drugs. Similarly, for TTI-109, the prodrug approach allows us to improve the drug product formulation with improved drug solubility.

In our completed in vitro preclinical studies conducted in France, China and the United States, we have observed no unexpected results compared to TTI-101. In the completed 28-day IND-enabling toxicology studies conducted in China, in rats and monkeys, TTI-109 has been observed to result in equivalent drug exposure as compared to TTI-101, with no toxicity observed.

In discussions with the FDA in a pre-IND filing, which included the preclinical data with TTI-109 and available clinical safety data with the active moiety, TTI-101, the package was sufficient to support proceeding with a clinical trial of TTI-109 in oncology. We submitted an IND application for TTI-109 in June 2025.

Other Potential Development Plans for our STAT3 Platform

We believe our STAT3 inhibitors have broad applic