taladegib (ENV 101) / Eli Lilly, Endeavor BioMed - LARVOL DELTA

Endeavor BioMedicines Receives Priority Medicines (PRIME) Designation from the European Medicines Agency for Taladegib (ENV-101) for the Treatment of Idiopathic Pulmonary Fibrosis (Businesswire) - "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."

PRIME • Idiopathic Pulmonary Fibrosis

Taladegib for the treatment of idiopathic pulmonary fibrosis (ENV-IPF-101): a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial. (PubMed, Lancet Respir Med) - P2 | "The acceptable safety profile and efficacy analyses of taladegib support further investigation in a phase 2b trial in patients with IPF (WHISTLE-PF)."

Journal • P2a data • Alopecia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pain • Pulmonary Disease • Respiratory Diseases

Endeavor BioMedicines Announces Publication of Positive Data from Phase 2a Trial in The Lancet Respiratory Medicine Evaluating taladegib (ENV-101) in Individuals with Idiopathic Pulmonary Fibrosis (Businesswire) - "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....Data also presented today in ALERT session at European Respiratory Society (ERS) Congress 2025."

P2a data • Idiopathic Pulmonary Fibrosis

…Phase 2b WHISTLE-PF trial, which is on track and expected to be completed in 2026 (Businesswire)

Trial completion date • Idiopathic Pulmonary Fibrosis

Endeavor BioMedicines to Present Results from Phase 2a Trial of Taladegib (ENV-101) in an ALERT Session at European Respiratory Society (ERS) Congress 2025 (Businesswire)

P2a data • Idiopathic Pulmonary Fibrosis

A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=94 | Terminated | Sponsor: Eli Lilly and Company | Phase classification: P1b ➔ P1 | Completed ➔ Terminated; The study was terminated due to business considerations

Phase classification • Trial termination • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Endeavor BioMedicines Receives Orphan Drug Designation from the U.S. Food and Drug Administration and European Commission for Taladegib (ENV-101) for the Treatment of Idiopathic Pulmonary Fibrosis (Businesswire) - "Endeavor BioMedicines...announced that both the European Commission (EC) and the U.S. Food and Drug Administration (FDA) have granted Orphan Drug Designation to its investigational therapy, taladegib (ENV-101), for the treatment of idiopathic pulmonary fibrosis (IPF). Endeavor is currently enrolling patients in the Phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial of taladegib in IPF, a chronic, progressive lung disease with limited treatment options. Enrollment in the WHISTLE-PF trial is on track and expected to be completed in 2026."

Enrollment status • Orphan drug • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Deep Learning-based Disease Severity Biomarkers on CT; Posthoc Analysis in a Phase 2a Placebo-controlled Study of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (ATS 2025) - P2 | "Emerging deep learning-based CT biomarkers may offer a non-invasive way to predict disease progression and assess treatment effects in antifibrotic clinical trials. The ENV-IPF-101 (NCT04968574) trial was a randomised, double-blind, placebo-controlled study of ENV-101, a novel Hedgehog (Hh) signalling pathway inhibitor, in patients with IPF... Utilizing deep learning models, patients treated with ENV-101 over 12 weeks showed significantly improved lung volume, significantly reduced pulmonary vascular volume and reduced fibrosis. These results indicate that in IPF, deep learning based quantification of lung volume and pulmonary vascular changes may provide additional insights that corroborate physiological improvement in lung function."

Biomarker • Clinical • P2a data • Retrospective data • Cognitive Disorders • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

WHISTLE-PF: Study Design of a Phase 2b, Multi-center, Randomized, Double-blind, Controlled Trial of ENV-101 (Taladegib) in Patients With Idiopathic Pulmonary Fibrosis (ATS 2025) - P2 | "WHISTLE-PF will evaluate the dose-ranging effects of the novel Hhi ENV-101 in patients with IPF. The results will increase our understanding of the potential of Hh pathway inhibition as a therapeutic approach to IPF."

Clinical • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Endeavor BioMedicines Presents New Clinical Findings From Post Hoc Analysis of Phase 2a Clinical Trial Evaluating ENV-101 in Patients with Idiopathic Pulmonary Fibrosis (Businesswire) - P2 | N=41 | NCT04968574 | Sponsor: Endeavor Biomedicines, Inc. | "Results demonstrated a significant reduction in pulmonary vessel volume, a significant increase in lung volume, and a trend towards reduced lung fibrosis for idiopathic pulmonary fibrosis (IPF) patients treated with ENV-101 for 12 weeks vs. placebo...Key Results from the Post Hoc Analysis Presented at ATS 2025: Significant increase in lung volume (Lung8) for patients in the ENV-101 treatment arm vs placebo (placebo: −113.07 mL vs ENV-101: 142.28 mL; p=0.014; effect size=0.87); Trend towards reduced fibrosis (Fibr8) for ENV-101 treated patients vs placebo (placebo: 1.32pp vs ENV-101: −1.32pp; p=0.063; effect size=−0.64); Significant reduction in normalized pulmonary vessel volume (Vascul8) for patients in the ENV-101 treatment arm vs placebo (placebo: 0.07pp vs ENV-101: -0.25pp; p=0.0007; effect size=-1.28)."

P2 data • Idiopathic Pulmonary Fibrosis

Endeavor BioMedicines Announces Upcoming Presentations at the 2025 American Thoracic Society International Conference (Businesswire) - "Endeavor BioMedicines...announced that two posters have been accepted for presentation at the American Thoracic Society 2025 (ATS 2025) International Conference. ATS 2025 will take place May 16-21, 2025, in San Francisco."

Clinical data • Idiopathic Pulmonary Fibrosis

Hedgehog signaling pathway inhibitors in the treatment of basal cell carcinoma: An Updated Review. (PubMed, J Drug Target) - "In this review, we summarize BCC's clinical presentation and histopathology and present knowledge on the most studied Hh signaling inhibitors, vismodegib and sonidegib, and other inhibitors of this signaling, such as itraconazole, patidegib, taladegib, and arsenic trioxide, in the treatment of BCC. We also present the most common Hh signaling inhibitor adverse events and their management options, which could improve patients' quality of life during treatment."

Journal • Review • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Skin Nodular Basal Cell Carcinoma

A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | Not yet recruiting ➔ Recruiting | N=320 ➔ 200

Enrollment change • Enrollment open • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

First Patient Dosed in Endeavor BioMedicines’ Phase 2b WHISTLE-PF Trial Evaluating ENV-101 for the Treatment of Idiopathic Pulmonary Fibrosis (Businesswire) - "The Phase 2b WHISTLE-PF (Wound-remodeling Hedgehog-Inhibitor ILD Study Testing Lung Function Endpoints-PF) clinical trial is a global, randomized, placebo-controlled study evaluating the therapeutic potential of ENV-101 in individuals with IPF (NCT06422884). Endeavor BioMedicines intends to conduct the trial in 14 countries globally, including Australia, where the first patient was dosed."

Trial status • Idiopathic Pulmonary Fibrosis

ENV-101, A Novel Hedgehog Inhibitor, Increases Lung Function, and Reduces Lung Fibrosis in Patients With Idiopathic Pulmonary Fibrosis: Results From a Randomized, Double-blind, Placebo-controlled Phase 2 Trial (ATS 2024) - P2 | " ENV-IPF-101 (NCT04968574) was a randomized, double-blind, placebo (PBO)-controlled trial of ENV-101, a novel Hh pathway inhibitor (Hhi), in patients with IPF conducted at 16 clinical sites in Australia, Canada, South Korea, Malaysia, and Mexico... These results suggest that ENV-101 improves IPF by reducing lung fibrosis and increasing lung volume, which translates into improved lung function in patients with IPF within 12 weeks. These results support the Phase 2b trial planned in IPF and PF-ILD."

Clinical • Late-breaking abstract • P2 data • Alopecia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial) (clinicaltrials.gov) - P2 | N=320 | Not yet recruiting | Sponsor: Endeavor Biomedicines, Inc.

New P2 trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Toby Maher, MD, PhD: Improving Lung Function with ENV-101 Treatment of Idiopathic Pulmonary Fibrosis (HCPLive) - "In a new interview during ATS 2024, the HCPLive editorial team spoke with the data's presenter Toby M. Maher, MD, PhD...Maher spoke on the findings on ENV-101 and their implications for IPF patients. 'The Hedgehog pathway is a pathway that is active during embryogenesis, so during the development of the fetus in the womb,' Maher explained. '...It appears that in people who develop pulmonary fibrosis, but also fibrosis of other organs, the Hedgehog pathway reactivates and is switched on again, for whatever reason. So within the fibrotic lung tissue, it again plays a role in proliferation and the generation of fibrotic tissue.'"

Interview • Video • Idiopathic Pulmonary Fibrosis

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 (Businesswire) - P2a | N=41 | NCT04968574 | Sponsor: Endeavor Biomedicines, Inc. | "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).....Endeavor BioMedicines intends to initiate the Phase 2 WHISTLE-PF (Wound-remodeling Hedgehog-inhibitor ILD Study Testing Lung Function Endpoints -PF) trial."

New P2 trial • P2a data • Idiopathic Pulmonary Fibrosis

Endeavor BioMedicines to Present New Data From Phase 2a Clinical Trial of ENV-101 at American Thoracic Society 2024 International Conference (Businesswire) - "Endeavor BioMedicines...announced that data from a completed Phase 2a clinical trial evaluating the company’s lead investigational candidate ENV-101 in patients with idiopathic pulmonary fibrosis (IPF) will be presented for the first time in a late-breaking oral session at the American Thoracic Society 2024 (ATS 2024) International Conference. ATS 2024 will take place May 17-22, 2024, in San Diego. The Phase 2a, randomized, double-blind, placebo-controlled clinical trial (NCT04968574) evaluated the safety and efficacy of ENV-101 vs. placebo in 41 patients with confirmed IPF who were treated for 12 weeks....Based on results from the Phase 2a trial of ENV-101, Endeavor BioMedicines intends to initiate a Phase 2 trial in patients with IPF and in a parallel cohort, patients with progressive pulmonary fibrosis (PPF), in 2024."

New P2 trial • P2a data • Idiopathic Pulmonary Fibrosis • Immunology

Activating PIK3CA mutations and hedgehog signaling may confer resistance to KRAS inhibition in colorectal cancer (AACR 2024) - "KRASG12C mutant CRC cell lines SW837 and SW1463 were treated with Sotorasib (KRASG12C inhibitor), Vismodegib and Taladegib (Hedgehog inhibitors), and cell viability was measured up to 96 hours after treatment. In the AACR Project-GENIE CRC (N = 9441) cohort, KRASG12C tumors (2.6%, 245/9441) were significantly co-mutated with PIK3CAmut (19.2%, 47/245; Odds ratio = 1.7 (95% CI: 1.2 - 2.4), Chi-Square test, p-value = 0.002). Resistance in CRC to KRASG12C inhibitors may be attributed to activated PIK3CA mutations and the Hedgehog signaling pathway. The future study will focus on detailed investigations involving comprehensive transcriptome and exome profiles in tumors and PDX models treated with anti-KRAS drugs in monotherapy and combination therapy."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • KRAS • PIK3CA

A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Endeavor Biomedicines, Inc. | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Endeavor BioMedicines Successfully Completes Phase 2a Trial of ENV-101 in Patients with Idiopathic Pulmonary Fibrosis (Businesswire) - "Endeavor expects to initiate Phase 2b study of ENV-101 for the treatment of IPF and progressive fibrosing-interstitial lung disease (PF-ILD) in 2024...Endeavor BioMedicines...announced successful completion of its Phase 2a clinical trial evaluating the company’s lead investigational compound, ENV-101, in patients with idiopathic pulmonary fibrosis (IPF). ENV-101 is an oral small molecule inhibitor of the Hedgehog (Hh) signaling pathway that offers a novel approach to treating the underlying pathologic mechanisms that cause fibrotic lung diseases."

Enrollment closed • New P2b trial • Idiopathic Pulmonary Fibrosis • Immunology

A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations (clinicaltrials.gov) - P2 | N=44 | Active, not recruiting | Sponsor: Endeavor Biomedicines, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor • PTCH1

A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Endeavor Biomedicines, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases