Endeavor BioMedicines said Thursday that its Phase 2b WHISTLE-PF trial of taladegib (ENV-101), an investigational Hedgehog signaling pathway inhibitor, met its primary endpoint and multiple key secondary endpoints in patients with idiopathic pulmonary fibrosis. The 24-week, randomized, double-blind, placebo-controlled, dose-ranging trial enrolled 213 patients with IPF across 74 sites in 14 countries, with 73 percent of patients on background standard-of-care treatment.
The primary endpoint was a statistically significant improvement in percent predicted forced vital capacity, a measure of how much air a person can forcefully exhale, at 24 weeks versus placebo. A pre-specified analysis showed a sustained improvement from baseline in lung function over the 24 weeks on taladegib. The trial also hit multiple secondary endpoints: reduced lung fibrosis and increased total lung capacity as shown by quantitative high-resolution computed tomography imaging, with the company citing statistically significant reductions in fibrosis measures and symptomatic improvement.
The mechanism is what sets the program apart. Taladegib inhibits the Hedgehog signaling pathway, which the company says eliminates the myofibroblasts that drive fibrosis and addresses the abnormal wound-healing process behind the disease. Current standard-of-care therapies, Boehringer Ingelheim’s Ofev and Roche’s Esbriet, slow the decline of lung function but do not halt or reverse progression. A Phase 2a study reported in 2024 had already suggested taladegib could put the disease into reverse, and the imaging analysis presented at the European Respiratory Society Congress showed taladegib-treated patients gaining an average of 204 mL in lung volume while placebo patients lost 60 mL.
Endeavor is holding back detailed data for a future medical meeting, so the topline figures are company-reported pending peer scrutiny. On safety, the rate of serious adverse events was balanced between the taladegib and placebo arms. The company plans to engage with global regulatory authorities on a Phase 3 strategy. For the IPF market, where the two incumbents sell against each other as decline-slowing therapies, a drug that can show reversal would redraw the competitive map; the Phase 3 design and the full dataset will determine whether the claim survives.