Company: TVRD
Filing Date: 2025-02-14
Form Type: S-4/A
Source: 0001104659-25-013053
Chunk: 32

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: S-4/A
Chunk 32
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TABLE OF CONTENTS

#### Tvardi 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 SoC therapies showed TTI-101 to be generally well-tolerated. No severe adverse events were reported. The most frequent treatment emergent adverse events predominantly reported as mild in severity, resolved on study. This clinical data, including robust pharmacokinetic (PK), pharmacodynamic (PD), and tolerability data, has allowed Tvardi to rapidly progress into a Phase 2 clinical trial in IPF.

Tvardi is currently enrolling in a REVERT IPF Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial of TTI-101 to evaluate safety, tolerability and PK in patients suffering from IPF as monotherapy and in addition to nintedanib, a current SoC. Tvardi also plans to evaluate multiple efficacy measures, including the established Phase 3 efficacy endpoint of forced vital capacity (FVC). Approximately 75 patients are randomly assigned (1:1:1) to receive oral TTI-101 400 mg/day, TTI-