New Phase 2a Clinical Trial Results Demonstrate Endeavor BioMedicines’
ENV-101 Improved Lung Function and Reversed Key Measures of Lung Fibrosis
in Patients With Idiopathic Pulmonary Fibrosis
Data presented for the first time today during late-breaking oral session at the
American Thoracic Society 2024 International Conference
Patients who received ENV-101 experienced statistically significant improvements in lung function and total lung capacity, and reversal of multiple key quantitative measures of lung fibrosis through 12 weeks of treatment
Findings reinforce potential of ENV-101, a novel investigational Hedgehog (Hh) signaling pathway inhibitor, to be the first disease-modifying treatment for patients with idiopathic pulmonary fibrosis
SAN DIEGO – May 19, 2024 – Endeavor BioMedicines, a clinical-stage biotechnology company developing medicines with the potential to deliver transformational clinical benefits to patients with life-threatening diseases, announced results from a completed Phase 2a clinical trial that demonstrate the company’s lead investigational candidate, ENV-101, improved lung function and reversed key measures of lung fibrosis in patients with idiopathic pulmonary fibrosis (IPF) over a 12-week period. The results, which also showed that ENV-101 had an acceptable tolerability profile, were presented for the first time today in a late-breaking oral session at the American Thoracic Society 2024 (ATS 2024) International Conference.
“There is a tremendous need for IPF treatments that do more than slow the inevitable decline of lung function,” said Toby M. Maher, M.D., Ph.D., Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles, who presented the data. “These preliminary signs of clinical and antifibrotic activity suggest that ENV-101 has the potential to change the trajectory of this otherwise relentless disease.”
Current standard-of-care therapies do not address the underlying cause of IPF. They slow the decline of lung function, but do not stop or reverse it, and they have tolerability issues that limit their long-term use in most patients. ENV-101 is designed to block a cellular wound-healing pathway known as Hedgehog (Hh) that is abnormally activated in fibrotic lung diseases, such as IPF, and causes the continuous pathophysiologic buildup of scar tissue in the lungs.
Key findings from the ENV-101 Phase 2a clinical trial in IPF presented today at the ATS 2024 International Conference include:
- Patients who received ENV-101 experienced a statistically significant improvement in lung function through the 12 weeks of the trial, with a 1.9% mean improvement in percent predicted forced vital capacity (ppFVC) from baseline as compared to a mean decline in ppFVC of 1.3% for patients in the placebo group (P=0.035).
- Patients who received ENV-101 showed a statistically significant increase in total lung capacity (TLC) above baseline at 12 weeks with a 200 mL mean increase as compared to a mean decline of 56 mL for patients who received placebo (P=0.005). In ENV-101-treated patients, 80% experienced an increase in TLC while 70% of patients who received placebo showed a decrease in TLC.
- The following key measures of lung fibrosis were also evaluated by high-resolution computed tomography (HRCT):
- Treatment with ENV-101 significantly decreased the absolute percent of quantitative interstitial lung disease (QILD) from baseline by 9.4%, as compared to an increase of 1.1% for patients who received placebo (P<0.05).
- Treatment with ENV-101 decreased the absolute percent of quantitative lung fibrosis (QLF) by 2% from baseline, as compared to an increase of 0.87% in patients who received placebo (P=0.1).
- Treatment with ENV-101 decreased the absolute percent of quantitative ground glass (QGG) by 4.6% from baseline, as compared to an increase of 0.29% in patients who received placebo (P=0.07).
- There were no treatment-related serious adverse events, grade 3 or 4 adverse events, or clinically meaningful safety findings on laboratory analyses, vital signs, electrocardiograms, or physical examination reported for ENV-101-treated patients. The most common ENV-101-related adverse events were dysgeusia (alterations in taste; 57%), alopecia (52%) and muscle spasms (43%), which were all mild to moderate in severity.
“These trial results suggest ENV-101 could have transformational clinical benefits for individuals with IPF, who are in need of therapies that change treatment expectations - from slowing disease progression to potentially reversing it,” said Paul A. Frohna, M.D., Ph.D., Chief Medical Officer, Endeavor BioMedicines. “We look forward to further evaluating ENV-101’s potential in the upcoming WHISTLE-PF clinical trial.”
Based on the ENV-101 Phase 2a trial results shared today, Endeavor BioMedicines intends to initiate the Phase 2 WHISTLE-PF (Wound-remodeling Hedgehog-inhibitor ILD Study Testing Lung Function Endpoints -PF) trial. This trial is expected to include a global Phase 2b cohort in individuals with IPF and a parallel Phase 2 cohort in individuals with progressive pulmonary fibrosis (PPF). Endeavor BioMedicines recently announced the closing of a $132.5 million Series C financing that will support clinical development of ENV-101 in IPF and PPF.
About the ENV-101 Phase 2a Trial
The randomized, double-blind, placebo-controlled Phase 2a clinical trial (NCT04968574) evaluated the safety and efficacy of ENV-101 vs. placebo in 41 patients with confirmed idiopathic pulmonary fibrosis. Patients at 16 sites in five countries were randomized 1:1 to receive 200 mg of ENV-101 or placebo once daily for 12 weeks. The primary endpoint for the trial was overall safety of ENV-101. Secondary endpoints included change from baseline to week 12 on lung function, measured by forced vital capacity (FVC) mL and percent predicted FVC (ppFVC), and patient reported outcomes based on the UCSD shortness-of-breath questionnaire. Key exploratory endpoints included mean change from baseline in total lung capacity (TLC) and change from baseline for % quantitative interstitial lung disease (QILD), % quantitative lung function (QLF) and % quantitative ground glass (QGG), as measured by high-resolution computed tomography (HRCT).
About Idiopathic Pulmonary Fibrosis
IPF is a chronic, progressive lung disease that affects more than 100,000 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 ENV-101
Endeavor BioMedicines’ investigational medicine, ENV-101, is a Hedgehog signaling pathway inhibitor. By binding to and inhibiting a key receptor in the Hedgehog pathway, ENV-101 is designed to stop the abnormal accumulation of myofibroblasts that cause fibrosis. This may resolve the excessive wound-healing process seen in IPF and PPF, creating the potential to reverse fibrosis and improve lung volume and function.
About Endeavor BioMedicines
Endeavor BioMedicines is a clinical-stage biotechnology company developing medicines with the potential to deliver transformational clinical benefits to patients with life-threatening diseases. Endeavor’s lead candidate, ENV-101, is an inhibitor of the Hedgehog signaling pathway in clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). The company’s second candidate, ENV-501, is a HER3 antibody-drug conjugate (ADC) for the treatment of HER3-positive solid tumors. More information is available at www.endeavorbiomedicines.com and on LinkedIn or X.
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