taladegib (ENV 101) / Endeavor BioMed - LARVOL DELTA

Late Breaking Abstract - Treatment with taladegib results in increased lung volume and regression of markers of ILD: A Phase 2a post hoc CT analysis using Brainomix e-Lung (ERS 2026) - "e-Lung measures show that treatment with taladegib results in increased lung volumes and reduction in markers of ILD extent, confirming that taladegib is a promising future treatment for IPF."

Late-breaking abstract • P2a data • Retrospective data • Fibrosis • Immunology • Interstitial Lung Disease

Endeavor BioMedicines Presents New Quantitative Imaging Data from Analysis of Phase 2a Clinical Trial Evaluating Taladegib (ENV-101) in Patients with Idiopathic Pulmonary Fibrosis (Businesswire) - "Taladegib and placebo groups were well matched at baseline based on WRVS, a measure of peripheral fibrosis severity. Taladegib mean WRVS at baseline was 15.5% and the placebo group was 14.2%. A baseline WRVS ≥ 15 indicates increased risk of FVC decline. Patients treated with taladegib experienced a statistically significant increase in lung volume compared with placebo. Mean change in lung volume was +204 mL improvement from baseline in the taladegib group compared with −60 mL in the placebo group (p=0.003)."

P2a data • Idiopathic Pulmonary Fibrosis

Endeavor BioMedicines to Present Quantitative Image Analysis from Phase 2a Trial of Taladegib (ENV-101) at European Respiratory Society (ERS) Congress 2026 (Businesswire) - "The ERS Congress 2026 will take place from September 5 – 9 in Barcelona, Spain."

P2a data • Idiopathic Pulmonary Fibrosis • Immunology

Brainomix to Present Five New Studies at ERS Congress Demonstrating the Potential of Quantitative CT in Interstitial Lung Disease (ILD) (PRNewswire)

Clinical data • Immunology • Interstitial Lung Disease

A Study to Evaluate Pharmacokinetics and Drug-drug Interactions of ENV-101 (Taladegib) in Healthy Participants (clinicaltrials.gov) - P1 | N=57 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | Not yet recruiting ➔ Recruiting

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

Computational Mapping of Hedgehog Pathway Kinase Module Predicts Node-Specific Craniofacial Phenotypes. (PubMed, Genes (Basel)) - "This strictly in silico study identifies candidate integrated morphogenic modules whose multi-node perturbation may underlie anatomically specific craniofacial malformation patterns. Node-phenotype associations are prioritized computational hypotheses requiring experimental validation; if confirmed, the framework could inform developmental toxicity assessment, therapeutic design, and reclassification of idiopathic craniofacial anomalies."

Journal • GLI1 • GLI3 • HEY1 • HIF1A

Hedgehog Inhibitor and Paclitaxel: A Phase I Trial of the Oral Hedgehog inhibitor Taladegib in Combination with Weekly Paclitaxel in Patients with Advanced Solid Tumours. (PubMed, Invest New Drugs) - "The combination is feasible but cumulative neuropathy may limit longer term treatment. Hh signalling may be implicated in chemotherapy-induced neuropathy."

Journal • P1 data • Basal Cell Carcinoma • Brain Cancer • Medulloblastoma • Non-melanoma Skin Cancer • Oncology • Pain • Solid Tumor

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 Phase 1, Open-Label Study to Evaluate Pharmacokinetics and Drug-drug Interactions of ENV-101 (Taladegib) in Healthy Participants (clinicaltrials.gov) - P1 | N=57 | Not yet recruiting | Sponsor: Endeavor Biomedicines, Inc.

New P1 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

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=20 | Completed | Sponsor: Endeavor Biomedicines, Inc. | Active, not recruiting ➔ Completed | N=44 ➔ 20

Enrollment change • Trial completion • Oncology • Solid Tumor • PTCH1

Inhibition of Hedgehog Signaling With Taladegib Reduces Fibrogenesis in a Scar in a Jar Model of Pulmonary Fibrosis (ATS 2026) - No abstract available

Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial) (clinicaltrials.gov) - P2 | N=213 | Active, not recruiting | Sponsor: Endeavor Biomedicines, Inc. | Recruiting ➔ Active, not recruiting

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

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