Company: TVRD
Filing Date: 2025-01-27
Form Type: S-4/A
Source: 0001104659-25-006050
Chunk: 465

Company: Tvardi Therapeutics, Inc.
Filing Date: 2025-01-27
Form: S-4/A
Chunk 465
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 addition, approximately 50% of patients treated with SoC required dose adjustment due to adverse events. Nintedanib and pirfenidone have been shown to slow disease progression, however neither treatment reverses or prevents clinical decline in FVC lung function. Despite the significant unmet need for better treatment options and the notable side effects of both approved agents, the peak sales of nintedanib and pirfenidone were $3.8 billion and $1.1 billion, respectively, which Tvardi believes represents a significant commercial opportunity for a disease- modifying and well-tolerated treatment for patients suffering with IPF.

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Tvardi’s Solution: TTI-101 for IPF TTI-101’s differentiated mechanism of action is designed to directly inhibit STAT3 to address the unmet need in IPF without interfering with its other essential biological functions. As a central mediator across critical fibrotic signaling pathways, pY-STAT3 intrinsically increases myofibroblast proliferation and ECM deposition and extrinsically plays a major role in immune suppression, resulting in the dual cascades associated with IPF. Preclinical studies have shown that TTI-101 not only halts further development of lung fibrosis, but also has the potential to reverse established fibrosis. Through validated functional animal models of fibrosis-driven diseases, TTI-101 has been shown to inhibit STAT3 activation, both intrinsically and extrinsically. Tvardi also has demonstrated preclinically that TTI-101 impacts both key components of IPF pathology: downregulation of deposition and upregulation of degradation. In addition, clinically, Tvardi has demonstrated oral dosing with TTI-101 lowered levels of pY-STAT3 and was generally well- tolerated. In its Phase 1 clinical trial, eight patients out of ten evaluable patients had elevated baseline pY-STAT3, measured by immunohistochemistry using H-scores, defined as greater than 30 (out of a total score of 300). All eight patients demonstrated a decrease in H-score at the follow-up biopsy (approximately six weeks after initiating treatment), with a median decrease of 55%. Among the three patients who demonstrated a clinical benefit, the median decrease in the H-score was 79%. Tvardi therefore believes TTI-101 is a novel therapeutic candidate that could offer a much-needed treatment option in IPF. Unblinded results from the ongoing Phase 2 RE