Company: TVRD
Filing Date: 2025-02-14
Form Type: S-4/A
Source: 0001104659-25-013053
Chunk: 34

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: S-4/A
Chunk 34
---
 versus placebo treated animals (p=0.04). Additionally, in a separate study, combination of TTI-101 with anti-PD-1 and bevacizumab demonstrated a larger reduction in tumor weight compared to anti-PD-1 and bevacizumab or saline that was statistically significant (p<0.01). Tvardi has completed a Phase 1 dose-escalation and dose-expansion clinical trial for TTI-101 in advanced tumors, enriched for patients with HCC. TTI-101 was observed to lower levels of pY-STAT3 in tumors as evidenced by biopsy sample and demonstrated a disease control rate of 53% as measured by RECIST v1.1, leading to clinical responses in HCC and other tumor types. Tvardi believes that the results to date support TTI-101’s differentiated mechanism of action to deliver therapeutic benefit as monotherapy and in combination with existing SoC agents, if approved. If approved, Tvardi does not believe that a commercial license, supply and/or collaboration agreement with the marketers of existing SoC treatments would be needed, as these commercial therapies are available in the market.

Tvardi is currently enrolling a REVERT LIVER CANCER Phase 1b/2, multicenter, open-label clinical trial designed to investigate the safety and efficacy of TTI-101 across three cohorts of patients with HCC: as monotherapy and in combination with SoC treatments pembrolizumab or atezolizumab + bevacizumab. Tvardi plans to report preliminary topline data from this clinical trial in the second half of 2025.

#### TTI-109
Tvardi’s 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 the ability to target STAT3 as a more efficient delivery vehicle for TTI-101 with the potential to improve tolerability. In Tvardi’s IND-enabling toxicology studies in rats and monkeys, TTI-109 has been observed to result in equivalent drug exposure as compared to TTI-101, with no toxicity observed. Tvardi has received pre-IND feedback from the FDA that the data package to date is sufficient to support a clinical trial of TTI-109 in oncology