Company: TVRD
Filing Date: 2025-02-14
Form Type: S-4/A
Source: 0001104659-25-013053
Chunk: 464

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: S-4/A
Chunk 464
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 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 v1.1. Tvardi’s second product candidate, TTI-109, is also an oral, small molecule STAT3 inhibitor that is structurally related to, yet chemically distinct from, TTI-101 and is designed to enhance Tvardi’s ability to target STAT3. Tvardi expects to submit an investigational new drug (IND), application for TTI-109 in the first half of 2025.

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#### Tvardi’s Pipeline
Tvardi’s current pipeline is depicted below:

The U.S. Food and Drug Administration (FDA), has granted orphan drug designation for TTI-101 in both IPF and HCC as well as Fast-Track Designation for TTI-101 in HCC.

#### TTI-101 for the Treatment of IPF
In the United States, approximately 150,000 individuals have IPF, while globally the number is estimated to be three million. Currently, approved anti-fibrotic therapies, Esbriet and Ofev, had collective peak sales of $4.9 billion, yet their use is limited as they do not reverse fibrosis or improve lung function. Based on the well-established role of pY-STAT3 in the pathogenesis of fibrosis, Tvardi believes TTI-101’s differentiated mechanism of action has the potential to address this unmet need in IPF, if approved. In preclinical models, Tvardi observed that TTI-101 led to a reduction of fibrotic tissue in the lungs and improved lung function. Tvardi also observed dose-dependent decreases in validated biomarkers associated with cell proliferation (resulting in reduced deposition) as well as increase in the modulation and activity of T cells (responsible for increased cellular and extracellular degradation). Additionally, Tvardi’s completed Phase 1 healthy volunteer drug-drug interaction clinical trial with IPF standard of care (SoC), therapies showed TTI-101 to be generally well-tolerated. No severe adverse events (SAEs), were reported. The most frequent treatment emergent adverse events (TEAEs), predominantly reported as mild in severity, resolved