1st patients dosed in Phase 2 trial of oral therapy TTI-101 for IPF

The first patients have been dosed in the Phase 2 REVERTIPF trial testing Tvardi Therapeutics’ investigational therapy TTI-101 in people with idiopathic pulmonary fibrosis (IPF).

TTI-101 is an oral small molecule inhibitor of STAT3, a protein implicated in pulmonary fibrosis (PF), as well as certain types of cancer.

The REVERTIPF trial (NCT05671835) is still recruiting up to 100 adults with IPF, 40 years and older, at more than a dozen sites in the U.S.

“The REVERT_IPF trial will expand our understanding of the impact of STAT3 inhibition beyond cancer into fibrotic diseases, which severely impair and burden hundreds of thousands of people globally,” Imran Alibhai, PhD, CEO of Tvardi, said in a company press release.

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TTI-101 being tested as IPF treatment to ease fibrosis, improve lung function

IPF is a chronic lung disease characterized by inflammation and scarring (fibrosis) in the lungs due to an unknown cause, leading to progressively worsening lung function. Fibrosis is mediated by the excessive growth and activation of cells called fibroblasts.

STAT3 is an inflammatory protein that plays a role in fibroblast activation, and which has been found to accumulate in the lungs of IPF patients. By blocking it, TTI-101 is believed to ease fibrosis and improve lung function for patients.

In preclinical studies, TTI-101 was found to reverse scarring and restore lung function in animal models of IPF, according to Tvardi.

The experimental therapy received orphan drug status in the U.S. last year for IPF, a designation intended to accelerate the development of treatments for rare diseases by offering financial incentives and regulatory support.

TTI-101 also being tested for cancer in clinical trials

TTI-101 is also being evaluated in a number of clinical trials involving cancer patients.

“Interest in our IPF study continues to grow due to recently presented clinical data demonstrating TTI-101 was safe and effective in heavily pretreated cancer patients, published preclinical work highlighting TTI-101’s restorative effect in fibrosis, and the FDA’s Orphan Drug Designation for TTI-101 in IPF,” Alibhai said.

REVERTIPF is evaluating the safety and clinical activity of TTI-101, alone or in combination with the approved IPF therapy Ofev (nintedanib), against a placebo in adults with IPF.

Participants will be randomly assigned to receive oral TTI-101 tablets at one of three daily doses (400 mg, 800, or 1,200 mg), or a placebo. Tablets will be taken twice daily for 12 weeks, or about three months.

Individuals currently using Ofev must have been on a stable dose for at least three months.

The study’s main goal is to assess the safety of TTI-101 throughout the 12 weeks of treatment and the month following. Several aspects of the therapy’s pharmacokinetics, or its movement into, through, and out of the body, will also be evaluated as secondary goals.

The trial is expected to conclude in March 2025.