Company: TVRD
Filing Date: 2025-10-07
Form Type: S-1/A
Source: 0001104659-25-097519
Chunk: 181

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-10-07
Form: S-1/A
Chunk 181
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 any change in FVC levels from baseline, or if the changes, if any, differed from participants receiving placebo. In addition, the clinical trial is ongoing, and we will not know

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whether treatment with TTI-101 will result in a change in FVC levels in a clinically meaningful manner until all clinical trials we intend to complete have been conducted. The final unblinded analysis for TTI-101 dose levels versus the matching placebo will be conducted using a mixed effect model repeated measure model with mean change from baseline as the response variable. Due to the preliminary and blinded nature of the data, this interim data set was not subject to the standard quality control measures typically associated with final clinical trial results. For example, the data that is available at the conclusion of a clinical trial would be unblinded following a data cleansing review, source verification of data using documents from the local clinical trial sites and other quality control measures to ensure the highest level of accuracy and fidelity possible. In contrast, the blinded data used for its preliminary reviews did not undergo this process and is therefore highly preliminary and not yet validated.

Hepatocellular Carcinoma

Background on HCC

HCC is the third-leading cause of cancer-related mortality globally and in the United States. Furthermore, HCC incidence and mortality rates have been increasing for decades. According to the World Health Organization, mortality in the United States was approximately 31,000 in 2022. There remains a high unmet need in HCC given a two-year survival rate less than 50% and a five-year survival rate of only 10% in the U.S. The majority of patients diagnosed with HCC present with advanced disease and have an estimated survival time of six to 20 months following diagnosis.

More than 90% of HCC cases arise in the setting of hepatic injury and inflammation, which involve production of several cytokines, notably hepatocyte growth factor and IL-6, which activate STAT3 to drive further injury, inflammation, fibrosis and proliferation. In addition, pY-STAT3 is a major contributor to immune resistance in HCC through its actions that promote the development and function of several immunosuppressive cells found within the tumor microenvironment, including myeloid-derived suppressor cells (“MDSC”). MDSCs have been demonstrated to impair the anticancer activity of immune-checkpoint inhibitor (“ICI”), therapies, and therefore, Tvardi believes that a drug inhibiting STAT3 has the potential to improve responsiveness