Phase 2a Data Highlight Effects of Taladegib (ENV-101) on Idiopathic Pulmonary Fibrosis

In new post-hoc findings presented at the American Thoracic Society (ATS) 2025 International Conference, a phase 2a study assessing investigational taladegib (ENV-101) therapy for idiopathic pulmonary fibrosis (IPF) demonstrated the first clinical evidence of an IPF therapy leading to a pulmonary vessel volume reduction.1,2

These data, also announced by Endeavor BioMedicines, highlighted notable improvements in imaging-based markers among individuals who had been treated with taladegib over the course of 12 weeks versus those in the study’s placebo arm. Taladegib, an investigational Hedgehog signaling pathway inhibitor, was designed bind to and inhibit a key receptor in the Hedgehog pathway.

The aim of this treatment would be to resolve the excessive wound-healing process observed in pulmonary fibrosis, thereby improving lung volume as well as lung function. The findings from this post hoc analysis independently validate and build upon prior phase 2a data from the double-blind, randomized, multi-center, placebo-controlled clinical study of taladegib (NCT04968574).

That study had demonstrated significant lung function improvements as well as total lung volume improvements. The investigators of this study also demonstrated a reduction in key measures of lung fibrosis compared to those given a placebo, as well as a manageable safety profile.

The post hoc analysis implemented advanced deep learning CT quantification tools developed to evaluate volumetric changes in patients’ lung anatomy through the use of 3 proprietary algorithms: Vascul8 (pulmonary vessel volume), Lung8 (lung volume), and Fibr8 (fibrosis extent). The imaging-derived biomarkers were noted as having been independently linked with IPF progression and mortality among patients, potentially allowing for improved sensitivity over conventional physiologic endpoints such as forced vital capacity (FVC).

Among the 34 study participants highlighted in the post hoc analysis, of which there were 16 on taladegib and 18 on placebo, the following key outcomes were noted by the investigative team:

• Lung volume (Lung8) increased significantly in the taladegib cohort compared to placebo (taladegib: +142.28 mL versus placebo: −113.07 mL; P = .014; effect size = .87).
• Pulmonary vessel volume (Vascul8) demonstrated a statistically significant decrease in patients treated with taladegib compared to placebo (ENV-101: −0.25 percentage points [pp] versus placebo: +.07 pp; P = .0007; effect size = −1.28).
• Fibrosis extent (Fibr8) showed a trend toward reductions in the taladegib cohort compared to placebo (ENV-101: −1.32 pp versus placebo: +1.32 pp; P = .063; effect size = −.64).

Overall, the analysis represented the first clinical evidence of an IPF treatment leading to a reduction in patients’ pulmonary vessel volume, reinforcing the potential of taladegib to allow for a variety of therapeutic benefits and potentially modify IPF’s progression.

For any additional information on new data presented at ATS, view updates in the latest conference coverage.

References

1. Endeavor BioMedicines Presents New Clinical Findings From Post Hoc Analysis of Phase 2a Clinical Trial Evaluating ENV-101 in Patients with Idiopathic Pulmonary Fibrosis. Endeavor BioMedicines. Accessed May 20, 2025. https://endeavorbiomedicines.com/endeavor-biomedicines-presents-new-clinical-findings-from-post-hoc-analysis-of-phase-2a-clinical-trial-evaluating-env-101-in-patients-with-idiopathic-pulmonary-fibrosis/.

2. Maher TM, Molyneaux P, Gibbs J, et al. (Poster Board # P863) WHISTLE-PF: Study Design of a Phase 2b, Multi-center, Randomized, Double-blind, Controlled Trial of ENV-101 (Taladegib) in Patients With Idiopathic Pulmonary Fibrosis. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.