Tvardi Therapeutics' STAT3 Inhibitor Fails Phase 2 IPF Trial

Tvardi Therapeutics, a recently public biotech company, has encountered a significant setback in its clinical development program. The company's STAT3 inhibitor, TTI-101, failed to demonstrate efficacy in a phase 2 trial for idiopathic pulmonary fibrosis (IPF), while also exhibiting high dropout rates due to adverse events.

Trial Results and Safety Concerns

The phase 2 trial, which enrolled 88 IPF patients, evaluated two doses of TTI-101 against a placebo. Nearly 60% of participants received TTI-101 in combination with Boehringer Ingelheim's approved anti-fibrotic drug, Ofev. The study revealed concerning discontinuation rates of 56.7% and 62.1% for the low and high doses of TTI-101, respectively, compared to just 10.3% in the placebo arm.

Tvardi attributed the high discontinuation rates primarily to gastrointestinal adverse events, with patients receiving TTI-101 in addition to Ofev experiencing even higher rates of discontinuation and adverse events.

Efficacy Outcomes

Exploratory endpoints failed to demonstrate a clear benefit of TTI-101 treatment. Forced vital capacity (FVC), a key measure of lung function, improved in 41% of placebo patients compared to up to 44% of those receiving the study drug. Moreover, FVC declines were more pronounced in the TTI-101 arms, with average reductions of 61.1 mL and 102.8 mL after 12 weeks, versus 22.2 mL in the placebo group.

Tvardi CEO Imran Alibhai, Ph.D., acknowledged the disappointing results, stating, "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."

Market Impact and Future Prospects

The news had an immediate and severe impact on Tvardi's stock price, which plummeted 85% to $6.25 in premarket trading. Despite this setback, the company is not abandoning its STAT3 inhibitor program entirely. Tvardi is currently developing another STAT3 inhibitor, TTI-109, as a potential cancer treatment. The company anticipates reporting data from a phase 2 liver cancer trial in the first half of 2026.

Tvardi projects that its current cash reserves will fund operations into the fourth quarter of 2026, providing some runway to pursue alternative development strategies. The company joins other pharmaceutical firms, including Bayer's Vividion Therapeutics, in the pursuit of effective STAT3-targeting therapies, particularly in oncology.