Taladegib

Endeavor BioMedicines is preparing to run another study with a global phase 2b idiopathic pulmonary fibrosis cohort. Endeavor BioMedicines has linked its Hedgehog inhibitor to improved lung function in a phase 2a idiopathic pulmonary fibrosis (IPF) study, sending a sonic pulse through a sector currently dominated by drugs that only slow the decline of the disease. Boehringer Ingelheim and Roche respectively turned Ofev and Esbriet into blockbusters on the back of evidence they can slow the decline in lung function. In one pivotal Ofev trial, lung function worsened (PDF) in 70% of patients who received the Boehringer drug for 52 weeks. The Esbriet label features (PDF) data from a pivotal study in which the lung function of 77% of patients taking the drug deteriorated.  While Ofev and Esbriet became blockbusters by slowing the decline of IPF patients, Endeavor wants to supplant the incumbents by reversing the disease. The phase 2a trial provides early clinical evidence that the biotech may be able to achieve that goal by targeting a type of fibroblast thought to drive IPF.  Investigators randomized 41 people with IPF to receive ENV-101 or placebo once daily. After 12 weeks, Endeavor saw a 1.9% mean improvement in a measure of lung function, namely percent predicted forced vital capacity (ppFVC) from baseline. PpFVC fell 1.3% in the placebo arm, causing the study to hit its primary endpoint with a p-value of 0.035. Endeavor shared other evidence that ENV-101 may change the course of the disease. Total lung capacity (TLC) increased 200 mL on average in the treatment group, compared to a 56-mL decline in the placebo arm. TLC increased in 80% of patients on ENV-101 and decreased in 70% of people taking placebo.  The biotech also used imaging to assess lung fibrosis. Quantitative interstitial lung disease, a measure of lung fibrosis and other attributes, fell 9.4% in the ENV-101 group while rising 1.1% in the placebo arm. Measures of quantitative lung fibrosis and ground glass also favored the study drug.   On the safety front, no patients on ENV-101 had treatment-related serious adverse events, grade 3 or 4 adverse events, or clinically meaningful safety findings on laboratory analyses and other assessments. But some mild to moderate adverse events were common, with between 43% and 57% of participants having alterations in taste, hair loss or muscle spasms while taking the study drug. Hair loss, known medically as alopecia, is mentioned in the Ofev label but only affected 0.8% of patients. Similarly, dysgeusia, the medical term for alterations in taste, features on the Esbriet label because it affected 6% of recipients of the drug. Endeavor is preparing to run another study with a global phase 2b IPF cohort and a parallel phase 2 cohort of individuals with progressive 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--(BUSINESS WIRE)-- 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 and on LinkedIn or X. View source version on businesswire.com: Contacts Media: Andrea Cohen 917-209-7163 AndreaCohen@sambrown.com Source: Endeavor BioMedicines View this news release online at: