Company: TVRD
Filing Date: 2025-02-14
Form Type: S-4/A
Source: 0001104659-25-013053
Chunk: 475

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-02-14
Form: S-4/A
Chunk 475
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patitis (NASH), models demonstrated that treatment with TTI-101 reduced (1) elevated hepatic enzymes and microsteatosis, or abnormal liver fat accumulation, (2) hepatic fibrosis, measured by Masson’s trichrome staining and (3) tumor growth as evidenced by reduction in average tumor volume determined by MRI. In SSc preclinical models, TTI-101 demonstrated an observed reduction in dermal fibrosis, measured by histological examination of skin sections stained with H&E and Masson’s trichome.

In a broad range of cancer models, TTI-101 demonstrated the capability to intrinsically induce apoptosis, or cell death, of tumor cells as evidenced by reduction in tumor weight or tumor volume and extrinsically overcome immune suppression in the tumor microenvironment as monotherapy and in combination with immune checkpoint inhibitors, as measured by immunohistochemical staining. Tvardi believes this preclinical data supports the development of TTI-101 across fibrosis-driven diseases. Tvardi also completed Phase 1 clinical trials of TTI-101 in advanced cancers and in healthy volunteers and are currently conducting two Phase 2 clinical trials of TTI-101 in IPF and HCC, respectively.

#### Tvardi’s TTI-109 Product Candidate
Tvardi’s second product candidate, TTI-109, is an oral, small-molecule, prodrug of, and mechanistically identical to, TTI-101. TTI-109 itself does not inhibit STAT3, but rapidly converts to TTI-101 in the blood. TTI-109 is designed to enhance its ability to target STAT3 as a more efficient delivery vehicle for TTI-101 with

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the potential to improve tolerability. In Tvardi’s IND-enabling toxicology studies in rats and monkeys, TTI-109 has been observed to result in equivalent drug exposure as compared to TTI-101, with no toxicity observed. Tvardi has received pre-IND feedback from the FDA that its data package to date is sufficient to support a clinical trial of TTI-109 in oncology. To maximize the potential of TTI-109 in fibrosis-driven diseases, Tvardi is planning additional preclinical studies and a first-in-human IND submission for TTI-109 in the first half of 2025.

#### Idiopathic Pulmonary Fibrosis
Background on Idiopathic Pulmonary Fibrosis

IPF is