Company: TVRD
Filing Date: 2025-01-27
Form Type: S-4/A
Source: 0001104659-25-006050
Chunk: 29

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-01-27
Form: S-4/A
Chunk 29
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rosis (IPF), and hepatocellular carcinoma (HCC). Tvardi expects to report unblinded data from the Phase 2 IPF clinical trial in the second half of 2025 and anticipates preliminary topline data from the Phase 1b/2 HCC clinical trial in the second half of 2025. Its second product candidate, TTI-109, is structurally related to, yet chemically distinct from, TTI-101 and is designed to enhance the ability to target STAT3. Tvardi expects to submit an investigational new drug (IND), application for TTI-109 in the first half of 2025.Tvardi’s approach is rooted in the expertise around STAT3’s functional composition and its critical role in disease pathogenesis, as well as other essential biological functions. Tvardi’s co-founder, David J. Tweardy, M.D., was one of the first to identify that STAT3, when activated by phosphorylation on tyrosine (Y) residue 705, referred to herein as pY-STAT3, acts as a central catalyst across critical fibrotic signaling pathways and is key to the cellular processes associated with fibrosis-driven diseases. Persistent pY-STAT3 drives the development and progression of the pathogenic cascade of fibrosis. By targeting pY-STAT3, Tvardi’s approach is designed to simultaneously modulate each of the 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 (SO2), to near normal levels versus animals treated with placebo where SO2levels