Tvardi Therapeutics Said Preliminary Data From Phase 2 REVERT Trial of TTI-101 In Idiopathic Pulmonary Fibrosis Show That The Study Did Not Meet Its Goals

Author: Benzinga Newsdesk | October 13, 2025 06:32am

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.

FVC change from baseline overlapped between treatment arms, with large variability within each cohort. Notably, the placebo-treated patients' FVC decline was lower than expected compared to historical controls.

Preliminary Summary of Change from Baseline in FVC (mL) at 12 Weeks While on Treatment

	Placebo	TTI-101 – 400mg	TTI-101 – 800mg
n	24	8	13
Mean in mL (SD2)	-22.2 (126.0)	-61.1 (190.7)	-102.8 (238.3)

Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi, stated, "In the aggregate, we did not observe a benefit of TTI-101 treatment in this IPF study. The limited data set, high variability within treatment arms, and unexpected performance of the placebo arm make it difficult to provide more definitive conclusions at this time. We are conducting additional analyses to further understand the results and inform our next steps. I want to sincerely thank the patients, their families, investigators, and site staff for their commitment to this study."

"Importantly, we remain on track to report preliminary topline data in the first half of 2026 from a healthy volunteer study on our next-generation STAT3 inhibitor, TTI-109, and from the Phase 2 trial of TTI-101 in hepatocellular carcinoma. TTI-109 is designed to enhance TTI-101's ability to target STAT3 as a more efficient delivery vehicle with the potential to improve tolerability. Once the healthy volunteer TTI-109 study is completed, we will assess the opportunity to expand into other STAT3-driven indications."

As of June 30, 2025, the Company reported $41.0 million in cash, cash equivalents, and short-term investments, which is expected to fund operations into the fourth quarter of 2026.

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