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

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

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) - No abstract available

Biomarker • Clinical • P2a data • Retrospective data • Cognitive Disorders • 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) - No abstract available

Clinical • P2b data • 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=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

Metastatic Basal Cell Carcinoma: Treatment with a potentially best in class Hedgehog Inhibitor, Taladegib (EADV 2023) - "Patient was further treated by vismodegib for 12 months followed by Cemiplimab. For the first time we report here that mBCC patients who were refractory to current standard of care treatments responded to taladegib with a duration of response of around one year with fewer and manageable adverse effects."

IO biomarker • Metastases • Alopecia • Basal Cell Carcinoma • Fatigue • Non-melanoma Skin Cancer • Oncology • Pulmonary Disease • PTCH1

Endeavor BioMedicines Completes Enrollment in Phase 2a Clinical Trial of ENV-101 (Taladegib) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF) (Businesswire) - "Endeavor BioMedicines...announced that the company has completed enrollment in its Phase 2a clinical trial to evaluate the safety and efficacy of ENV-101 (taladegib) for the treatment of idiopathic pulmonary fibrosis (IPF). ENV-101 is a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway, which plays a critical role in IPF disease pathology....'This enrollment milestone is an important achievement, and we look forward to reporting topline results in Q1 of 2024.'"

Enrollment closed • P2a data • Idiopathic Pulmonary Fibrosis • Immunology

A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | N=60 ➔ 40 | Trial completion date: Aug 2023 ➔ Dec 2023 | Trial primary completion date: Aug 2023 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Drug-Drug Interaction Study of ENV-101 (Taladegib) on Nintedanib Pharmacokinetics in Healthy Subjects (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Endeavor Biomedicines, Inc. | Recruiting ➔ Completed

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

A Drug-Drug Interaction Study of ENV-101 (Taladegib) on Nintedanib Pharmacokinetics in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | Not yet recruiting ➔ Recruiting

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

A Drug-Drug Interaction Study of ENV-101 (Taladegib) on Nintedanib Pharmacokinetics in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Endeavor Biomedicines, Inc.

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

Taladegib, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Localized Esophageal or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P1b/2 | N=7 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; The sponsor sold the drug TALADEGIB to another company during the trial and thereafter no drug was available. The sponsor made a decision to stop development of this drug Taladegib.

Combination therapy • Trial termination • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Endeavor Biomedicines, Inc. | Trial completion date: Nov 2022 ➔ Aug 2023 | Trial primary completion date: Nov 2022 ➔ Aug 2023

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

A phase II study evaluating the safety and efficacy of ENV-101 (taladegib) in patients with advanced solid tumors harboring PTCH1 loss of function mutations (ESMO 2022) - P2 | "Stage 1 (phase IIa) of this protocol will enroll a total of 44 patients randomized between two dose levels. In the presence of acceptable efficacy, stage 2 (phase IIb) of this protocol will expand enrollment using a single dose level."

Clinical • P2 data • Basal Cell Carcinoma • Bladder Cancer • Brain Cancer • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Medulloblastoma • Melanoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Oral Cancer • Pancreatic Cancer • Prostate Cancer • Rhabdomyosarcoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer • PTCH1 • SMO

Endeavor BioMedicines Partners with xCures to Identify Patients with PTCH1 mutations for Phase 2 Trial of ENV-101 (taladegib) (Businesswire) - "Endeavor BioMedicines...and xCures...announced a partnership that gives patients enrolling in Endeavor's clinical trials access to the xCures platform to find the best available treatment options suited to their individual tumor profile. The partnership helps identify patients whose cancers harbor the PTCH1 mutation and may be eligible for Endeavor’s clinical trial. The xCures platform also enables patients to find more suitable treatment options if they are ineligible....Endeavor is now investigating precision therapy approaches for ENV-101 in multiple types of cancers driven by oncogenic driver mutations in PTCH1, as well as in idiopathic pulmonary fibrosis (IPF)."

Licensing / partnership • Idiopathic Pulmonary Fibrosis • Oncology • Solid Tumor