Company: TVRD
Filing Date: 2025-02-14
Form Type: S-4/A
Source: 0001104659-25-013053
Chunk: 31

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: S-4/A
Chunk 31
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 key pathways of the fibrotic cascade, whereas, previous approaches only targeted single pathways. Beyond its role in fibrosis, STAT3 also has an essential role in cellular respiration in the mitochondria. Tvardi, therefore, leveraged the insights of its co-founder to design its product candidates to inhibit STAT3 activation which, it believes, will lead to disease modifying activity without impairing essential biological functions in the mitochondria.

Tvardi believes it has robust proof of concept to support the potential of STAT3 inhibitors to treat fibrosis-driven diseases. In preclinical models, TTI-101 administration resulted in statistically significant reductions in levels of well-known biomarkers of fibrosis, most notably collagen type I alpha1 chain (COL1A1) (p≤0.05). In addition, TTI-101 administration decreased the amount of fibrotic tissue in the lungs in a statistically significant manner (p≤0.05), as measured by histologic evaluation of fibrosis severity, and returned oxygen saturation (SO 2 ), to near normal levels versus animals treated with placebo where SO 2 levels continued to decline. Tvardi is currently enrolling patients in an ongoing Phase 2, randomized, double-blind, placebo-controlled clinical trial of TTI-101 as monotherapy or in addition to nintedanib, a standard of care (SoC), therapy, to evaluate its safety, tolerability and preliminary efficacy in patients suffering from IPF. It has also previously demonstrated, in a Phase 1 oncology clinical trial of TTI-101 as monotherapy enriched for patients with HCC, that TTI-101 was generally well-tolerated, targeted STAT3, lowering levels of pY-STAT3 in tumors as evidenced by biopsy sample, and demonstrated a disease control rate of 53% as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), a standard way to measure the response of a tumor to treatment. Tvardi is currently enrolling patients in its Phase 1b/2 clinical trial to investigate TTI-101 as monotherapy and in combination with SoC, in patients with HCC. The ongoing Phase 1b/2 design allows Tvardi to transition from a dose-finding and safety evaluation in the Phase 1b portion of the clinical trial, to a larger, Phase 2 portion of the clinical trial with primary efficacy endpoints, including overall response rate using RECIST v.1.1