Additional Phase 2 REVERT IPF Data Shows Greater Fibrosis Reduction With TTI-101

Tvardi Therapeutics reported additional phase 2 data from its REVERT IPF trial on January 8, 2026, showing that patients with idiopathic pulmonary fibrosis (IFP) treated with the STAT3 inhibitor TTI-101 experienced greater reductions in lung fibrosis at 12 weeks compared with placebo.1

“Our subsequent analyses of the REVERT IPF clinical trial data set revealed deeper insights into the impact of TTI-101 on the inhibition of STAT3 in fibrosis and inflammation,” said Tvardi Chief Executive Officer Imran Alibhai, PhD, in a statement.1 “Notably, treatment with TTI-101 was associated with improvement in blinded fibrosis scores vs placebo and reductions in IL-6 levels consistent with STAT3 pathway inhibition. Further interrogation into FVC after 12 weeks of TTI-101 was encouraging despite the placebo-treated patients’ FVC decline being lower than expected compared to historical controls.”

This update follows the October 13, 2025, announcement of preliminary results, in which the company reported that the study did not meet its primary objectives.2 In the initial analysis, 88 patients were randomized to TTI-101 400mg per day (n=30), 800mg per day (n=29) or placebo (n=29). The study was not powered to assess exploratory endpoints, with only 8 patients on 400 mg, 13 on 800 mg, and 24 on placebo who had efficacy data at 12 weeks.

The preliminary analysis of exploratory efficacy showed statistically significant differences between placebo and treatment arms.2 The study found 39% on 400 mg, 44% on 88 mg, and 41% on placebo demonstrated FVC improvement.

“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,” Alibhai said in an October 2025 statement.2

Due to the lack of significant data, investigators conducted a secondary analysis of REVERT IPF, a phase 2, randomized, double-blind, placebo-controlled trial assessing TT-1010 alone or in addition to nintedanib (OFEV) in patients with IPF.1 The team sought to assess the safety, pharmacokinetics, and exploratory outcomes of TT-101 related to lung function.

The study only included patients exposed to TT-101 for 12 weeks; the trial excluded patients with < 60% of the expected dosing (n = 1) no measurable TT-101 in the blood (n = 2), and no reported adverse events (n = 2). One participant was excluded after initially showing improvement in pulmonary function on TTI-101 but later experiencing a decline due to acute bronchitis deemed unrelated to the study drug.1

REVERT IPF included 40 patients, with 16 randomized to TTI-1010 and 24 randomized to placebo. The study observed a greater fibrosis decline from baseline to week 12 on the high-resolution CT lung fibrosis score in patients treated with TTI-101 compared to placebo (-9.4% vs -2.4%). Patients on TTI-101 vs placebo also experienced a greater IL-6 decline, especially among patients in the TT1-101 arm who had greater baseline IL-6.1

Furthermore, 63% of patients treated with TTI-1010 demonstrated an increase in forced vital capacity (FVC) at 12 weeks, compared with 46% on placebo. The mean FVC change in patients treated with TTI-101 was -15 mL, which was less of a decline compared to patients on placebo (-22 mL).1

“With these data in-hand, we eagerly await results from the ongoing healthy volunteer study of our next-generation STAT3 inhibitor, TTI-109,” Alibhai continued. “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. If successful, we will move quickly to identify next steps for this promising, potentially disease modifying therapy across a range of fibrosis-driven diseases where STAT3 activation is implicated.”1

References

1. Tvardi Therapeutics Announces Further Phase 2 REVERT IPF Data, Expanding Clinical Insights. GlobeNewsWire. Published on January 8, 2026. Accessed January 12, 2026. https://www.globenewswire.com/news-release/2026/01/08/3215337/0/en/Tvardi-Therapeutics-Announces-Further-Phase-2-REVERT-IPF-Data-Expanding-Clinical-Insights.html

2. Tvardi Therapeutics Provides Update on Preliminary Data from Phase 2 REVERT Trial in Idiopathic Pulmonary Fibrosis. Tvardi Therapeutics. Published on October 13, 2025. Accessed January 12, 2026. https://ir.tvarditherapeutics.com/news-releases/news-release-details/tvardi-therapeutics-provides-update-preliminary-data-phase-2