Endeavor BioMedicines' WHISTLE-PF Phase 2b Trial of Taladegib Meets Primary and Key Secondary Endpoints in Patients With IPF

WHISTLE-PF trial met its primary endpoint, demonstrating a statistically significant improvement in lung function (percent predicted forced vital capacity - ppFVC) compared to placebo; data to be presented at future medical meeting

The trial demonstrated statistical significance for multiple secondary endpoints compared to placebo, including reduced lung fibrosis and increased total lung capacity (TLC) as shown by key measures on quantitative high-resolution computed tomography (HRCT) imaging

Patients treated with taladegib experienced an improvement from baseline through Week 24 in ppFVC, lung fibrosis and capacity as well as symptomatic improvement

The totality of these unprecedented results further supports taladegib’s potential to reverse the course of IPF

Endeavor to engage with global regulatory authorities regarding plans for Phase 3

SAN DIEGO--(BUSINESS WIRE)--Endeavor BioMedicines (“Endeavor”), a clinical-stage biotechnology company developing medicines for the treatment of fibrotic diseases with high unmet need, today announced that its Phase 2b WHISTLE-PF trial evaluating taladegib (ENV-101), an investigational Hedgehog signaling pathway inhibitor, met its primary endpoint and multiple key secondary endpoints in patients with idiopathic pulmonary fibrosis (IPF). Current standard-of-care therapies slow the decline of lung function but do not halt or reverse disease progression. The findings reinforce the potential of taladegib to become the first treatment to reduce lung fibrosis while increasing total lung capacity and improving FVC in patients with IPF.

The Phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial (NCT06422884) was a 24-week, randomized, double-blind, placebo-controlled, dose-ranging trial of taladegib in 213 patients with IPF. Background standard-of-care treatment was used by 73% of patients in the trial. The trial was conducted at 74 sites across 14 countries.

“The unprecedented results from WHISTLE-PF reinforce our confidence in the potential of taladegib to be the first treatment to reduce fibrosis and improve symptoms for IPF patients,” said John Hood, Ph.D., Co-founder, CEO and Chairman, Endeavor BioMedicines. “The totality of these findings, including statistically significant reductions in fibrosis and improvements in lung function, further distinguish taladegib in the IPF treatment landscape and validate our approach to targeting Hedgehog signaling. We are deeply grateful to the investigators, study coordinators, and patients worldwide whose participation enabled WHISTLE-PF to enroll ahead of expectations and achieve these important results.”

The trial met its primary endpoint with taladegib demonstrating a statistically significant improvement in ppFVC over 24 weeks relative to placebo. Treatment with taladegib resulted in an increase in ppFVC from baseline at Week 24, which reflects improvements in lung function. Notably, a pre-specified analysis of lung function while patients remained on treatment showed that continued treatment with taladegib resulted in a sustained improvement from baseline in ppFVC over 24 weeks.

Patients who received taladegib experienced significant improvement compared with placebo across several quantitative biomarkers of IPF severity on HRCT, including TLC, percent quantitative total interstitial lung disease (%QILD), and percent quantitative lung fibrosis (%QLF). For each of these HRCT measures, patients treated with taladegib showed improvements from baseline at Week 24. Taladegib also demonstrated significant improvements over placebo in FVC (mL). Although not statistically powered for this measure, a numerical improvement compared with placebo in IPF symptoms as measured by the Living with Pulmonary Fibrosis Symptoms (L-PF) questionnaire was observed.

Taladegib exhibited a tolerability profile that was consistent with previous studies. Incidence of serious adverse events was balanced between the placebo and taladegib arms.

“As an ILD physician, I’ve seen firsthand how devastating IPF is for patients and their families. Patients continue to decline despite treatment with approved standard-of-care therapies,” said Lisa Lancaster, M.D., Chief Medical Officer, Endeavor BioMedicines. “Taladegib’s potential to reverse the course of IPF provides hope for patients with this terrible disease. We look forward to presenting the data at a future medical meeting as well as engaging with regulatory authorities regarding our plans for Phase 3.”

Current standard-of-care therapies do not fully address the needs of IPF patients. They slow the decline of lung function, but do not halt or reverse it. Taladegib is designed to block the Hedgehog signaling pathway, a cellular wound-healing pathway that is abnormally activated in fibrotic lung diseases, such as IPF, and contributes to the pathophysiologic buildup of scar tissue in the lungs.

Endeavor has received Orphan Drug Designation for taladegib from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products, as well as PRIority MEdicines (PRIME) designation from the EMA. Taladegib is the first and only investigational IPF therapy to receive PRIME designation, underscoring the program’s potential to address the significant unmet need in IPF.

About the WHISTLE-PF Clinical Trial

The Phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial (NCT06422884) was a six-month, randomized, double-blind, placebo-controlled, dose-ranging trial of taladegib in 213 patients with IPF. Usage of background standard-of-care antifibrotics was permitted in the trial. The trial was conducted at 74 sites across 14 countries.

About Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease that affects more than 150,000 adults in the United States. Although the exact cause of IPF is unknown, various environmental factors can deliver repeated injuries to lung cells that trigger abnormal wound-healing processes and life-threatening lung scarring. IPF is a chronic disease with limited treatment options and a very poor prognosis. The average life expectancy is only three to five years after diagnosis.

About Taladegib

Endeavor BioMedicines’ investigational medicine taladegib (ENV-101) is a Hedgehog signaling pathway inhibitor. By binding to and inhibiting a key receptor in the Hedgehog pathway, taladegib eliminates the aberrant scarring that underlies the disease. This may resolve the excessive wound-healing process seen in pulmonary fibrosis, improving lung volume and function.

About Endeavor BioMedicines

Endeavor BioMedicines is a clinical-stage biotechnology company developing medicines for the treatment of fibrotic diseases with high unmet need. Endeavor’s lead candidate, taladegib (ENV-101), is an inhibitor of the Hedgehog signaling pathway in development for idiopathic pulmonary fibrosis. More information is available at www.endeavorbiomedicines.com and on LinkedIn or X.