Company: TVRD
Filing Date: 2025-02-14
Form Type: 424B3
Source: 0001104659-25-014310
Chunk: 491

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: 424B3
Chunk 491
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 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 Tvardi to improve the drug product formulation with improved drug solubility.

In Tvardi’s completed in vitro preclinical studies conducted in France, China and the United States, Tvardi has 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 recent 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. To maximize the potential of TTI-109 in fibrosis-driven diseases, Tvardi is planning additional preclinical studies to be conducted in China and a first-in-human IND submission for TTI-109 in the first half of 2025.

Other Potential Development Plans for Tvardi’s STAT3 Platform

Tvardi believes its STAT3 inhibitors have broad applicability across multiple fibrosis-driven diseases including systemic sclerosis (SSc). SSc is a chronic autoimmune disease characterized by widespread progressive fibrosis of the skin and internal organs including the lung, heart and kidneys. The prevalence of SSc in the United States is approximately 100,000 and globally is 2.5 million. SSc is associated with life-threatening complications and a poor prognosis, with no FDA-approved disease modifying treatment. Similar to other fibrosis-driven diseases, pY-STAT3 plays a critical role in the intrinsic and extrinsic pro-fibrotic cascades. STAT3 inhibition in SSc has strong therapeutic rationale due to its central role in fibrosis, immune dysregulation and vascular dysfunction. In multiple SSc mouse models, Tvardi’s founder demonstrated that Tvardi’s STAT3 inhibitor, TTI-101, downregulated validated biomarkers of fibrosis, inhibited levels of pY-STAT3 in skin tissue and reduced skin fibrosis. Inhibiting STAT3 could potentially reduce fibrosis, control immune-mediated damage and improve vascular health