Taladegib

Taladegib is the first and only investigational IPF therapy to receive PRIME designation Phase 2b WHISTLE-PF trial is on track to complete enrollment in H1 2026 SAN DIEGO – November 3, 2025 – Endeavor BioMedicines (“Endeavor”), a clinical-stage biotechnology company developing medicines with the potential to deliver transformational benefits to patients with life-threatening diseases, today announced that the European Medicines Agency (EMA) has granted PRIority MEdicines (PRIME) designation for its investigational therapy, taladegib (ENV-101), for the treatment of idiopathic pulmonary fibrosis (IPF). IPF is a life-threatening lung disease characterized by progressive fibrosis of lung tissue leading to deterioration in lung function, respiratory failure, and death. IPF represents a significant unmet medical need as currently approved therapies only delay progression of the disease but are not effective in preventing deterioration in lung function. The PRIME designation was granted based on review of positive clinical results from the Phase 2a proof-of-concept trial evaluating the safety and efficacy of taladegib that indicated promising potential of this therapy to address the significant unmet need in IPF. The clinical trial demonstrated that treatment with taladegib rapidly and significantly improved lung function and total lung capacity from baseline, and reversed key measures of lung fibrosis in patients with IPF. Patients who received taladegib 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). By week 6, ppFVC exhibited an increase from baseline in the taladegib treatment group and a decrease in the placebo group that continued until the treatment was discontinued at week 12. Taladegib also demonstrated a favorable safety and tolerability profile. These results were recently published in The Lancet Respiratory Medicine. PRIME designation is granted by the EMA to drug candidates that may offer a significant therapeutic advantage over existing treatments or that benefit patients without treatment options. These medicines are considered priority medicines by the EMA, whose aim is to optimize development plans and speed up evaluations so these medicines that address significant unmet medical needs can reach patients faster. 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. Notably, only 26% of all applications for PRIME eligibility have been granted to date, highlighting the rigor of the selection process and further emphasizing the significance of taladegib’s inclusion. The PRIME designation will enable Endeavor to conduct proactive regulatory dialogue with the EMA, optimizing development and accelerating the path toward the goal of delivering an effective treatment for patients living with IPF. The PRIME designation follows Orphan Drug designations received from the EMA and U.S. Food and Drug Administration (FDA) earlier this year. “IPF has devastating effects on lung function, yet patients with this disease lack effective therapeutic options,” said John Hood, Ph.D., Co-founder, CEO and Chairman, Endeavor BioMedicines. “Our Phase 2a trial data suggest that taladegib can significantly improve lung function and lung capacity above baseline, and reverse key measures of fibrosis. Receiving EMA’s PRIME designation recognizes the potential of taladegib to transform the lives of people living with IPF. We are committed to working closely with the EMA and regulatory agencies across the world to bring this promising therapy to patients as quickly as possible.” About 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 myofibroblasts that cause fibrosis. 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 with the potential to deliver transformational clinical benefits to patients with life-threatening diseases. Endeavor’s lead candidate, taladegib (ENV-101), is an inhibitor of the Hedgehog signaling pathway in development for fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). More information is available at www.endeavorbiomedicines.com and on LinkedIn or X. Audra Friis Sam Brown Healthcare Communications 917-519-9577 audrafriis@sambrown.com

Treatment with taladegib demonstrated improved lung function from baseline, increased total lung capacity and reversed key measures of lung fibrosis in patients with idiopathic pulmonary fibrosis Data also presented today in ALERT session at European Respiratory Society (ERS) Congress 2025 The mean change from baseline to week 12 in TLC improved significantly for the taladegib group (206.67 mL; 95% CI, 82.63 to 330.70 mL) but decreased for the placebo group (–55.58 mL; 95% CI, –170.71 to 59.55 mL) resulting in a significant between-group change from baseline to week 12 in TLC of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). An improvement from baseline to week 12 was also seen for %QILD for the taladegib group but not for the placebo group, and there was a significant between-group difference in change from baseline to week 12 (p=0.047) with mean change from baseline of -9.4% and 1.1% in the taladegib and placebo groups, respectively. The between-group difference from baseline to week 12 in percent predicted forced vital capacity (FVC) significantly favored taladegib (3.95%; 95% confidence interval [CI], 0.31% to 7.60%; p=0.035) with a mean change from baseline of 1.9% in the taladegib arm vs -1.3% for placebo. The mean change from baseline to week 12 in TLC improved significantly for the taladegib group (206.67 mL; 95% CI, 82.63 to 330.70 mL) but decreased for the placebo group (–55.58 mL; 95% CI, –170.71 to 59.55 mL) resulting in a significant between-group change from baseline to week 12 in TLC of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). An improvement from baseline to week 12 was also seen for %QILD for the taladegib group but not for the placebo group, and there was a significant between-group difference in change from baseline to week 12 (p=0.047) with mean change from baseline of -9.4% and 1.1% in the taladegib and placebo groups, respectively. The between-group difference from baseline to week 12 in percent predicted forced vital capacity (FVC) significantly favored taladegib (3.95%; 95% confidence interval [CI], 0.31% to 7.60%; p=0.035) with a mean change from baseline of 1.9% in the taladegib arm vs -1.3% for placebo. The mean change from baseline to week 12 in TLC improved significantly for the taladegib group (206.67 mL; 95% CI, 82.63 to 330.70 mL) but decreased for the placebo group (–55.58 mL; 95% CI, –170.71 to 59.55 mL) resulting in a significant between-group change from baseline to week 12 in TLC of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). SAN DIEGO – September 30, 2025 – Endeavor BioMedicines (“Endeavor”), a clinical-stage biotechnology company developing medicines with the potential to deliver transformational clinical benefits to patients with life-threatening diseases, today announced that The Lancet Respiratory Medicine has published results from a Phase 2a trial evaluating the safety and efficacy of taladegib (ENV-101) in patients with idiopathic pulmonary fibrosis (IPF). Data from the Phase 2a trial were also featured in an ALERT (Abstracts Leading to Evolution in Respiratory Medicine Trials) session at the 2025 ERS Congress in Amsterdam — a special forum highlighting high-impact, practice-changing clinical trials in respiratory medicine. The proof-of-concept clinical trial demonstrated that treatment with taladegib improved lung function from baseline, increased total lung capacity and reversed key measures of lung fibrosis in patients with idiopathic pulmonary fibrosis. Taladegib also demonstrated a favorable safety and tolerability profile. There were no treatment- related serious adverse events, treatment-related ≥grade 3 adverse events, or clinically meaningful safety findings. “Patients living with idiopathic pulmonary fibrosis face a relentless and life-altering disease that affects not only their health but every aspect of daily life,” 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. “We are encouraged by the totality of the clinical data for taladegib, as we observed not only significant improvements from baseline in FVC measured by spirometry, but also a significant increase in total lung capacity and reductions from baseline in key measures of fibrosis as measured by CT imaging. These encouraging results, published in The Lancet Respiratory Medicine and presented today during the ERS ALERT session, represent meaningful progress toward the goal of delivering an effective treatment for patients living with IPF.” The randomized, double-blind, placebo-controlled Phase 2a clinical trial evaluated the safety and efficacy of taladegib vs. placebo in 41 patients with confirmed IPF who were treated for 12 weeks. The trial was conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico and South Korea for patients with IPF older than 40 years of age who were not on background standard of care. Patients were randomized to 200 mg of taladegib or placebo administered once daily orally for 12 weeks with a 6-week follow- up. The primary endpoint was safety as assessed by the incidence and severity of clinical laboratory abnormalities, change from baseline in vital sign measurements, oxygen saturation, frequency and severity of adverse events, and number of hospitalizations during the study. Secondary endpoints included change from baseline in forced vital capacity (FVC), time to progression (defined as either an absolute decline of ≥10% in percent predicted FVC from baseline to week 12 or death) and dyspnea score on the UCSD SOBQ. Exploratory endpoints included measures of fibrosis assessed by high-resolution computed tomography (HRCT). Key published findings from the taladegib Phase 2a clinical trial include: There were no serious adverse events or ≥grade 3 adverse events considered related to taladegib, and no deaths occurred during the trial. The most common taladegib-related adverse events were Grade 1 or Grade 2 and included alterations in taste, hair loss/thinning and muscle spasms. Patients who received taladegib experienced a statistically significant improvement in lung function assessed via spirometry through the 12 weeks of treatment. The between-group difference from baseline to week 12 in percent predicted forced vital capacity (FVC) significantly favored taladegib (3.95%; 95% confidence interval [CI], 0.31% to 7.60%; p=0.035) with a mean change from baseline of 1.9% in the taladegib arm vs -1.3% for placebo. By week 6, both percent predicted FVC and mean FVC (mL) exhibited an increase from baseline in the taladegib treatment group and a decrease in the placebo group that continued until the study drug was discontinued at week 12. Patients who received taladegib experienced improvement across several measures assessed by quantitative analysis of lung fibrosis on High Resolution Computed Tomography (HRCT) including in total lung capacity (TLC), percent quantitative total interstitial lung disease (%QILD), percent quantitative lung fibrosis (%QLF), and percent quantitative ground glass (%QGG). Improvements were seen in TLC, %QILD, %QLF and %QGG for the taladegib treatment group, while these measures of disease remained stable or worsened for the placebo group. The mean change from baseline to week 12 in TLC improved significantly for the taladegib group (206.67 mL; 95% CI, 82.63 to 330.70 mL) but decreased for the placebo group (–55.58 mL; 95% CI, –170.71 to 59.55 mL) resulting in a significant between-group change from baseline to week 12 in TLC of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). An improvement from baseline to week 12 was also seen for %QILD for the taladegib group but not for the placebo group, and there was a significant between-group difference in change from baseline to week 12 (p=0.047) with mean change from baseline of -9.4% and 1.1% in the taladegib and placebo groups, respectively. The between-group difference from baseline to week 12 in percent predicted forced vital capacity (FVC) significantly favored taladegib (3.95%; 95% confidence interval [CI], 0.31% to 7.60%; p=0.035) with a mean change from baseline of 1.9% in the taladegib arm vs -1.3% for placebo. By week 6, both percent predicted FVC and mean FVC (mL) exhibited an increase from baseline in the taladegib treatment group and a decrease in the placebo group that continued until the study drug was discontinued at week 12. Improvements were seen in TLC, %QILD, %QLF and %QGG for the taladegib treatment group, while these measures of disease remained stable or worsened for the placebo group. The mean change from baseline to week 12 in TLC improved significantly for the taladegib group (206.67 mL; 95% CI, 82.63 to 330.70 mL) but decreased for the placebo group (–55.58 mL; 95% CI, –170.71 to 59.55 mL) resulting in a significant between-group change from baseline to week 12 in TLC of 257.0 mL (95% CI, 86.8 to 427.2 mL; p=0.004). An improvement from baseline to week 12 was also seen for %QILD for the taladegib group but not for the placebo group, and there was a significant between-group difference in change from baseline to week 12 (p=0.047) with mean change from baseline of -9.4% and 1.1% in the taladegib and placebo groups, respectively. “We are honored that the results of our Phase 2a trial have been published in The Lancet Respiratory Medicine, one of the world’s most respected and top-tier medical journals, and also selected as an ALERT presentation at ERS. This recognition is a testament to the dedication of our scientific and clinical teams, the investigators, and most importantly, the patients who participated in the trial,” said John Hood, Ph.D., Co- Founder, CEO and Chairman, Endeavor BioMedicines. “Our team remains committed to advancing taladegib with our current Phase 2b WHISTLE-PF trial, which is on track and expected to be completed in 2026.” About 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 myofibroblasts that cause fibrosis. 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 with the potential to deliver transformational clinical benefits to patients with life-threatening diseases. Endeavor’s lead candidate, taladegib (ENV-101), is an inhibitor of the Hedgehog signaling pathway in development for fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). More information is available at www.endeavorbiomedicines.com and on LinkedIn or X. Audra Friis Sam Brown Healthcare Communications 917-519-9577 audrafriis@sambrown.com