FDA Grants Orphan Drug Designation to Taladegib, Potential Idiopathic Pulmonary Fibrosis Treatment

The FDA has granted orphan drug designation to Endeavor Biosciences’ Taladegib (ENV-101) for the treatment of idiopathic pulmonary fibrosis (IPF).1

“Receiving Orphan Drug Designation for taladegib in both the United States and European Union underscores the significant unmet medical need for patients with IPF,” Lisa Lancaster, MD, Chief Medical Officer, Endeavor BioMedicines, said in a statement.1 “We are encouraged by the potential of taladegib to reverse the course of disease across multiple measures of IPF, which is a major step forward from current standard-of-care.”

Taladegib is an investigational Hedgehog signaling pathway inhibitor designed to stop the abnormal accumulation of myofibroblasts that cause fibrosis, address the excessive wound-healing process seen in IPF, and improve lung volume and function. The therapy is currently being evaluated in the phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial.

The trial is continuing to enroll patients and should be completed in 2026. It will evaluate the efficacy of a range of taladegib doses through 24 weeks of treatment, characterize the investigational compound’s safety and tolerability, assess its effect on patient reported outcomes and its effects on lung function, lung capacity and lung fibrosis as measured by chest high-resolution computed tomography.

Endeavor recently presented data on taladegib from a post hoc analysis of a phase 2a double-blind, randomized, multi-center, placebo-controlled study at May’s American Thoracic Society (ATS) 2025 International Conference in San Francisco, California that 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.2

“We are excited to share significant findings from the post hoc analysis of the phase 2a clinical trial of ENV-101, highlighting our pulmonary vessel volume quantification model, Vascul8,” Simon Walsh, MD, PhD, Chief Scientific Officer, Qureight, said.2 “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.”

In the analysis, investigators reported promising improvements in both lung function and structural lung biomarkers, alongside a manageable safety profile. The analysis leveraged advanced deep learning CT quantification tools, including Lung8 (lung volume), Vascul8 (pulmonary vessel volume), and Fibr8 (fibrosis extent), to assess volumetric changes in lung anatomy. These imaging-based biomarkers are independently associated with disease progression and mortality in IPF, potentially offering improved sensitivity over conventional measures such as forced vital capacity (FVC).

The analysis included 34 participants, 16 receiving taladegib and 18 receiving placebo. Patients in the taladegib group showed significantly increased lung volume compared to placebo, with Lung8 data indicating a gain of +142.28 mL versus a loss of −113.07 mL in the placebo group (P = .014; effect size = 0.87). Pulmonary vessel volume also showed a statistically significant reduction in the taladegib group: Vascul8 measurements recorded a change of −0.25 percentage points (pp) versus an increase of +0.07 pp in the placebo group (P = .0007; effect size = −1.28). While not statistically significant, fibrosis extent assessed by Fibr8 trended toward improvement with taladegib (−1.32 pp vs +1.32 pp; P = .063; effect size = −0.64).2

“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,” Lancaster said in an earlier statement.2 “We are grateful to the Qureight team for partnering with us on this important analysis.”

REFERENCES

1. Willis J. Endeavor BioMedicines Receives Orphan Drug Designation from the U.S. Food and Drug Administration and European Commission for Taladegib (ENV-101) for the Treatment of Idiopathic Pulmonary Fibrosis | Endeavor BioMedicines. Endeavor BioMedicines. Published July 16, 2025. Accessed July 16, 2025. https://endeavorbiomedicines.com/endeavor-biomedicines-receives-orphan-drug-designation-from-the-u-s-food-and-drug-administration-and-european-commission-for-taladegib-env-101-for-the-treatment-of-idiopathic-pulmonary-fibrosis/

2. 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/