Tvardi Therapeutics Provides Update on Preliminary Data from Phase 2 REVERT Trial in Idiopathic Pulmonary Fibrosis

Tvardi Therapeutics, Inc. (“Tvardi”) (NASDAQ: TVRD), a clinical-stage biopharmaceutical company focused on the development of novel, oral, small molecule therapies targeting STAT3 to treat fibrosis-driven diseases, today provided an update on preliminary data from the Phase 2 REVERT clinical trial of TTI-101 in idiopathic pulmonary fibrosis (IPF).

The REVERT IPF Phase 2 clinical trial was a randomized, double-blind, placebo-controlled clinical trial of TTI-101 alone or in addition to nintedanib (OFEV) in patients with IPF. The study was designed to assess safety, pharmacokinetics, and exploratory outcomes related to lung function. After reviewing the preliminary safety data and exploratory efficacy results, including changes in Forced Vital Capacity (FVC), the Company concluded that the study did not meet its goals.

Overall, 88 patients were randomized to TTI-101 400mg per day (n=30), 800mg per day (n=29) or placebo (n=29), and stratified by nintedanib use, with 58% of patients receiving concomitant therapy. Preliminary data¹ demonstrated patients’ baseline characteristics were similar across treatment arms, with the exception of percent predicted FVC, which was lower in the placebo-treated patients (70.1%) compared to the TTI-101-treated arms (74.1% and 81.1%, respectively).

Discontinuation rates across treatment arms were imbalanced, with lower discontinuation rates observed in the placebo group (10.3%) compared to treated arms (400mg and 800mg; 56.7% vs 62.1%, respectively). Discontinuation rates among the TTI-101 population were primarily driven by gastrointestinal adverse events, with higher rates of events and discontinuations among patients on concurrent nintedanib.

The study was not powered to evaluate exploratory endpoints. The number of efficacy evaluable patients with at least one baseline and on-treatment FVC measurement was placebo (n=29), 400mg (n=23), and 800mg (n=27). The numbers, however, declined by the 12-week timepoint to placebo (n=24), 400mg (n=8), or 800mg (n=13). The preliminary analysis was performed on actual FVC values; values were not modeled or imputed.

Preliminary analysis of exploratory efficacy showed no statistically significant differences between placebo and treatment arms. Overall, from baseline to last visit on treatment, the proportion of patients who demonstrated FVC improvement from baseline was 41% for the placebo, and 39% and 44% for the 400mg and 800mg arms, respectively.