Endeavor BioMedicines presented promising new clinical findings from a post-hoc analysis of their Phase 2a clinical trial evaluating ENV-101 (taladegib) in patients with idiopathic pulmonary fibrosis (IPF). The results, shared at the American Thoracic Society 2025 International Conference, demonstrated significant improvements across multiple lung measures for patients treated with ENV-101 compared to placebo.
The analysis revealed that IPF patients who received ENV-101 for 12 weeks experienced a significant reduction in pulmonary vessel volume, a significant increase in lung volume, and a trend toward reduced lung fibrosis compared to those receiving placebo. These findings provide further evidence supporting ENV-101's potential to reverse disease progression in IPF patients.
Novel Deep Learning Analysis Reveals Significant Benefits
The post-hoc analysis utilized Qureight's innovative deep learning-based computed tomography (CT) analytics technologies to evaluate treatment outcomes. Three specialized deep learning models were employed to quantify lung volume (Lung8), pulmonary vessel volume (Vascul8), and fibrosis extent (Fibr8) on baseline and follow-up CT scans from both ENV-101 treated (n=16) and placebo patients (n=18).
Key findings from the analysis included:
- A significant increase in lung volume for ENV-101 treated patients versus placebo (142.28 mL vs. -113.07 mL; p=0.014; effect size=0.87)
- A trend toward reduced fibrosis for ENV-101 treated patients versus placebo (-1.32pp vs. 1.32pp; p=0.063; effect size=-0.64)
- A significant reduction in normalized pulmonary vessel volume for ENV-101 treated patients versus placebo (-0.25pp vs. 0.07pp; p=0.0007; effect size=-1.28)
"These findings provide additional evidence of clinical utility of ENV-101 in patients with IPF, marking another step forward in our mission to restore hope and improve lives for those facing this otherwise devastating disease," said Lisa Lancaster, M.D., Chief Medical Officer at Endeavor BioMedicines.
Notably, ENV-101 is the first therapeutic to demonstrate a reduction in pulmonary vessel volume in IPF patients, a measure that has been correlated with improved mortality and decreased disease burden. This finding is particularly significant as lung volume, fibrotic tissue volume, and pulmonary vessel volume are all established independent predictors of mortality in IPF.
Simon Walsh, M.D., Ph.D., Chief Scientific Officer at Qureight, highlighted the advantages of their analytical approach: "Using this model, we quantified a significant treatment effect from ENV-101, with a greater effect size than forced vital capacity. Qureight's deep learning-based imaging biomarkers offer distinct advantages by capturing treatment signals from each prognostic compartment of the lung separately, optimizing for precision medicine."
Building on Previous Success
The post-hoc analysis independently validates and extends previously reported results from the Phase 2a randomized, double-blind, multi-center, placebo-controlled clinical trial of ENV-101 (NCT04968574). In that trial, ENV-101 demonstrated significant improvements in lung function and total lung volume, while also showing a reduction in key measures of lung fibrosis versus placebo with a manageable safety profile.
Deep learning-based quantification of lung volume and pulmonary vascular changes may offer valuable insights that corroborate physiological improvement in lung function. These measures potentially provide greater effect sizes than forced vital capacity (FVC), which is the current registrational endpoint in IPF clinical trials.
Moving Forward: The WHISTLE-PF Trial
Building on these promising results, Endeavor has initiated the Phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial. This global, randomized, placebo-controlled study will evaluate the therapeutic potential of ENV-101 in individuals with IPF (NCT06422884).
The WHISTLE-PF trial will assess the efficacy of various ENV-101 doses through 24 weeks of treatment, characterize the compound's safety profile, evaluate its effect on patient-reported outcomes, and measure its impact on lung capacity and lung fibrosis using chest HRCT.
Understanding IPF and ENV-101's Mechanism
IPF is a chronic, progressive lung disease affecting more than 150,000 adults in the United States. The condition involves abnormal wound-healing processes that lead to life-threatening lung scarring. With limited treatment options and a poor prognosis—average life expectancy of only three to five years after diagnosis—new therapeutic approaches are urgently needed.
ENV-101 (taladegib) works by inhibiting the Hedgehog signaling pathway. By binding to and inhibiting a key receptor in this pathway, ENV-101 stops the abnormal accumulation of myofibroblasts that cause fibrosis. This mechanism may resolve the excessive wound-healing process seen in pulmonary fibrosis, thereby improving lung volume and function.
Endeavor BioMedicines continues to advance its mission of developing medicines with the potential to deliver transformational clinical benefits to patients with life-threatening diseases. In addition to ENV-101 for fibrotic lung diseases, the company is also developing ENV-501, a HER3 antibody-drug conjugate for the treatment of HER3-positive solid tumors.
