Endeavor BioMedicines Reports Positive Phase 2a Results for Taladegib in Idiopathic Pulmonary Fibrosis, Published in The Lancet Respiratory Medicine
Endeavor BioMedicines (“Endeavor”), a clinical-stage biotechnology company focused on developing transformative therapies for life-threatening diseases, has announced the publication of Phase 2a clinical trial results for taladegib (ENV-101) in The Lancet Respiratory Medicine. The trial investigated the safety and efficacy of taladegib in patients diagnosed with idiopathic pulmonary fibrosis (IPF), a progressive and debilitating lung disease with high unmet medical need. In addition to publication, the trial data were featured at the 2025 European Respiratory Society (ERS) Congress in Amsterdam during an ALERT (Abstracts Leading to Evolution in Respiratory Medicine Trials) session, which spotlights practice-changing and high-impact clinical trials in the respiratory medicine field.
The Phase 2a proof-of-concept study demonstrated that taladegib significantly improved lung function in IPF patients, increased total lung capacity, and reversed key measures of lung fibrosis. Furthermore, the therapy exhibited a favorable safety and tolerability profile, with no treatment-related serious adverse events, no ≥grade 3 adverse events linked to the drug, and no clinically meaningful safety concerns observed.
“Patients living with idiopathic pulmonary fibrosis endure a relentless disease that profoundly impacts their health and daily life,” said Toby M. Maher, M.D., Ph.D., Professor of Medicine and Director of Interstitial Lung Disease at the Keck School of Medicine, University of Southern California, Los Angeles. “The results with taladegib are very encouraging. We observed not only meaningful improvements from baseline in forced vital capacity (FVC) measured via spirometry but also an increase in total lung capacity and reductions in fibrosis as measured by high-resolution CT imaging. These findings, now published in The Lancet Respiratory Medicine and highlighted at the ERS ALERT session, represent an important step toward delivering a potential effective therapy for patients living with IPF.”
Study Design and Patient Population
The Phase 2a trial was a randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of taladegib compared with placebo in 41 patients with confirmed idiopathic pulmonary fibrosis. Conducted across 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea, the study enrolled patients aged over 40 who were not receiving any standard-of-care treatment for IPF at the time of enrollment.
Patients were randomized to receive either 200 mg of taladegib or placebo, administered orally once daily for a 12-week treatment period, followed by a six-week follow-up phase. The primary endpoint of the study was safety, assessed through clinical laboratory evaluations, vital sign monitoring, oxygen saturation measurements, adverse event frequency and severity, and the number of hospitalizations. Secondary endpoints included change from baseline in forced vital capacity (FVC), time to disease progression—defined as either an absolute decline of ≥10% in percent predicted FVC or death—and dyspnea assessment using the UCSD Shortness of Breath Questionnaire (SOBQ). Exploratory endpoints focused on fibrosis evaluation using high-resolution computed tomography (HRCT) metrics.
Key Efficacy Findings
The taladegib Phase 2a trial demonstrated compelling improvements in lung function and measures of fibrosis. Notably, patients treated with taladegib showed a statistically significant improvement in FVC over the 12-week treatment period. The between-group difference in percent predicted FVC from baseline to week 12 favored taladegib, with a 3.95% difference (95% confidence interval [CI], 0.31% to 7.60%; p=0.035). The taladegib arm achieved a mean FVC change of 1.9% from baseline, compared with a decline of –1.3% in the placebo group.
Improvements in FVC were observed as early as week 6, with the taladegib group showing increased FVC while the placebo group continued to experience declines through week 12. These findings suggest that taladegib may provide early and sustained benefit in lung function for IPF patients.
HRCT-Based Assessments of Fibrosis
In addition to functional improvements, quantitative HRCT analyses indicated reductions in fibrosis for patients receiving taladegib. Key measures included total lung capacity (TLC), percent quantitative total interstitial lung disease (%QILD), percent quantitative lung fibrosis (%QLF), and percent quantitative ground-glass opacity (%QGG). Patients treated with taladegib experienced improvements across these endpoints, whereas the placebo group exhibited stability or worsening of disease measures.
Specifically, mean TLC increased by 206.67 mL in the taladegib arm (95% CI, 82.63 to 330.70 mL), compared with a decrease of –55.58 mL in the placebo group (95% CI, –170.71 to 59.55 mL), resulting in a significant between-group difference of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). Likewise, %QILD improved in the taladegib group with a mean change of –9.4%, while the placebo group experienced a slight increase of 1.1%, yielding a statistically significant between-group difference (p=0.047). Similar trends were observed for %QLF and %QGG, demonstrating the potential of taladegib to modify the underlying fibrotic process in IPF.
Safety and Tolerability
Taladegib was well-tolerated throughout the 12-week study. There were no treatment-related serious adverse events or deaths, and no ≥grade 3 adverse events were considered related to the drug. The most common treatment-related adverse events were mild to moderate (Grade 1 or 2) and included alterations in taste, hair thinning or loss, and muscle spasms. These findings indicate that taladegib has a favorable safety profile suitable for continued clinical development.
Significance and Next Steps
The publication of these results in The Lancet Respiratory Medicine and the presentation at the ERS ALERT session highlight the clinical significance of taladegib as a potential new therapy for IPF. The data provide strong evidence that taladegib not only improves lung function and reduces fibrosis but also maintains a positive safety profile, supporting its further investigation in larger, longer-term studies.
John Hood, Ph.D., Co-Founder, CEO, and Chairman of Endeavor BioMedicines, commented, “We are honored that the results of our Phase 2a trial have been recognized by The Lancet Respiratory Medicine, one of the world’s leading medical journals, and also selected for an ALERT presentation at ERS. This acknowledgment reflects the dedication of our scientific and clinical teams, the investigators, and most importantly, the patients who participated in the trial. The positive findings from this study validate the promise of taladegib and encourage us to continue advancing its development.”
Endeavor is currently conducting the Phase 2b WHISTLE-PF trial to further evaluate taladegib’s efficacy and safety in a broader IPF patient population. The Phase 2b study is on track for completion in 2026 and will provide critical data to support potential future regulatory submissions.
About Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis is a chronic, progressive lung disease characterized by scarring of lung tissue, leading to a decline in lung function and, ultimately, respiratory failure. The disease typically affects adults over the age of 50 and is associated with significant morbidity and mortality. Current treatment options are limited, and there remains a critical need for therapies that can slow or reverse the fibrotic process, improve lung function, and enhance patients’ quality of life.
Taladegib, an investigational oral therapy developed by Endeavor, targets molecular pathways involved in fibrosis, offering the potential for disease modification rather than solely symptomatic relief. The Phase 2a trial results suggest that taladegib could represent a meaningful advancement in IPF treatment, with both functional and radiographic improvements observed in a relatively short 12-week period.
The Phase 2a clinical trial of taladegib in IPF patients represents a significant milestone for Endeavor BioMedicines and the broader respiratory medicine community. The combination of improved lung function, reductions in fibrosis as measured by HRCT, and a strong safety profile underscores the potential of taladegib as a transformative therapy for patients living with idiopathic pulmonary fibrosis. The ongoing Phase 2b WHISTLE-PF study will further define the clinical profile of taladegib and its potential role in changing the treatment landscape for this challenging disease.
By advancing taladegib through carefully designed clinical trials and sharing data in top-tier publications and forums such as The Lancet Respiratory Medicine and ERS, Endeavor continues to demonstrate its commitment to developing innovative therapies that address critical unmet medical needs and improve patient outcomes.
