Tvardi Therapeutics has failed its first big test as a public company. Months after joining the Nasdaq, the biotech has reported the unappetizing mix of high dropout rates and placebolike efficacy in a phase 2 trial of its idiopathic pulmonary fibrosis (IPF) prospect.
Houston-based Tvardi secured a stock market listing through a reverse merger with Cara Therapeutics. The biotech landed on the Nasdaq with a pipeline focused on STAT3, a target implicated in cancers, fibrotic diseases and other conditions. Tvardi's big claim was that it had a way to directly inhibit the historically undruggable STAT3. The phase 2 data suggest STAT3 should perhaps stay undrugged, at least in IPF.
Investigators randomized 88 IPF patients to receive one of two doses of the STAT3 inhibitor TTI-101 or placebo. Almost 60% of patients received TTI-101 on top of Boehringer Ingelheim’s Ofev, an anti-fibrotic drug that has been long approved in IPF.
For the low and high doses of TTI-101, discontinuation rates were 56.7% and 62.1%, respectively. The discontinuation rate in the placebo arm was conversely just 10.3%. Tvardi said discontinuation rates in the TTI-101 arms were primarily driven by gastrointestinal adverse events. Discontinuation and adverse event rates were higher in patients who took TTI-101 in addition to Ofev.
Exploratory endpoints were similarly disappointing. Tvardi said FVC, a measure of lung function, improved in 41% of patients on placebo, compared to up to 44% of people on the study drug.
FVC declined by an average of 22.2 mL after 12 weeks of treatment with placebo. The declines in the two TTI-101 arms were 61.1 mL and 102.8 mL. Larger declines indicate a greater reduction in the maximum amount of air a person can forcefully exhale from their lungs. Tvardi CEO Imran Alibhai, Ph.D., outlined what the data mean for TTI-101.
“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,” Alibhai said in a statement. “We are conducting additional analyses to further understand the results and inform our next steps.”
The biotech has a shot at redeeming itself with TTI-109, another STAT3 inhibitor that is in development as a cancer drug. Tvardi is aiming to report data from a phase 2 liver cancer trial in the first half of 2026. The company has predicted it has enough cash to fund operations into the fourth quarter of 2026. Bayer, through its $1.5 billion Vividion Therapeutics buyout, is among the companies targeting STAT3 in cancer.
Shares in Tvardi fell 85% to $6.25 in premarket trading.