Company: TVRD
Filing Date: 2025-10-07
Form Type: S-1/A
Source: 0001104659-25-097519
Chunk: 175

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-07
Form: S-1/A
Chunk 175
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 BLM-induced skin fibrosis | ​ | ●Observed a reduction in BLM-induced expression of validated biomarkers for fibrosis, including Col1, TGF-β and IL-6 as measured as measured by transcripts from isolated RNA and relative RT-PCR                                                                                                                 
 ●Reduced levels of pY-STAT3 in skin tissue as measured by Western blot bands quantified by Image J analysis                                                                                                                                                                                                       
 ●Decreased skin thickness, a measure of fibrosis (p≤0.05 Tks-1 vs. TTI-101), measured by histological examination of skin sections stained with H&E and Masson’s trichome                                                                                                                                         |
| HCC                     | ​ | NASH-induced HCC                          | ​ | ●Reduced elevated hepatic enzymes and microsteatosis, or abnormal liver fat accumulation, reduced hepatic fibrosis, measured by Masson’s trichrome staining and reduced tumor growth by comparing the average tumor volume determined by MRI                                                                      |

102

| Fibrosis-driven Disease |   | Mouse Models                                    |   | Observations of TTI-101 Administration                                                                                                         |
| ​                       | ​ | Humanized mice + patient derived HCC xenografts | ​ | ●Reduced tumor size with monotherapy, as measured by tumor weight                                                                              
 ●Observed additive effect in reducing tumor size, as measured by tumor weight, with TTI-101 in combination with HCC standard of care therapies |

GEM: genetically engineered mouse Observed Reduction of Fibrotic Lung Tissue and Improved Lung Function with TTI-101 in a Bleomycin-Induced IPF Mouse Model Dr. Tweardy and his collaborators at BCM demonstrated that administration of TTI-101 resulted in downregulation of targets associated with fibrosis, attenuation of fibrosis and recovery of lung function as measured by arterial oxygen saturation levels (“SO2”). In this preclinical study, TTI-101 was dosed 14 days after induction of fibrosis with BLM. Wild-type mice exposed to BLM displayed characteristic increases in ECM deposition and subsequent administration of TTI-101 significantly decreased all established fibrotic endpoints assessed in the model, including COL1A1, α-smooth muscle actin (“α-SMA”), hypoxia-inducible factor-1α (“HIF-1α”), and plasminogen activator inhibitor-1 (“PAI-1”) (p≤0.05). Administration of TTI-101 in mice also resulted in statistically significant increases