GLPG2737 / AbbVie, Galapagos - LARVOL DELTA

CARACTERIZACIÓN CLÍNICA Y EPIDEMIOLÓGICA DE LA ENFERMEDAD RENAL POLIQUÍSTICA EN PACIENTES ATENDIDOS EN UN CENTRO DE REFERENCIA DE CUARTO NIVEL DEL CARIBE COLOMBIANO DURANTE EL PERIODO 2008-2022 (ISN-WCN 2024) - "Los pacientes que presentan una progresión rápida de esta patología se benefician del antagonista del receptor V2 de la vasopresina Tolvaptan, único aprobado hasta el momento por la FDA (34)(35). Se encuentran en investigación moléculas como lixivaptan, venglustat, bardoxolona, tesevatinib, RGLS4326 (oligonucleótido inhibidor de microARN miR-17), GLPG2737 (corrector regulador de conductancia transmembrana de fibrosis quística), los cuales han venido demostrando efectos benéficos potenciales (36)(37)(38)(39). Otros medicamentos como everolimus ha evitado la progresión del volumen renal, pero no evitó la progresión de la enfermedad (40)... La ERP es una patología sistémica de relevancia importante debido al gran impacto que puede producir al deteriorar la salud de la persona comprometida, puede cursar desde estados asintomáticos a casos donde la función renal esta severamente deteriorada y por..."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • MIR17 • PKD1 • PRKD1

Discovery of GLPG2737, a Potent Type 2 Corrector of CFTR for the Treatment of Cystic Fibrosis in Combination with a Potentiator and a Type 1 Co-corrector. (PubMed, J Med Chem) - "Investigations showed that carboxylic acid group replacement with acylsulfonamides and acylsulfonylureas improved ADMET and PK properties, leading to the discovery of the structurally novel co-corrector GLPG2737. The addition of GLPG2737 to the combination of the potentiator GLPG1837 and C1 corrector 4 led to an 8-fold increase in the F508del CFTR activity."

Combination therapy • Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (clinicaltrials.gov) - P2 | N=66 | Terminated | Sponsor: Galapagos NV | Trial completion date: Jan 2024 ➔ Apr 2023 | Active, not recruiting ➔ Terminated; The study was early terminated due to lack of efficacy.

Trial completion date • Trial termination • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

The MANGROVE Phase 2 Trial: Study Design and Baseline Characteristics of Patients With Autosomal Dominant Polycystic Kidney Disease (KIDNEY WEEK 2022) - P2 | "MANGROVE is an ongoing phase 2a, proof-of-concept trial, evaluating the efficacy and safety of the CFTR inhibitor GLPG2737 in patients with ADPKD...1. Jouret F, Devuyst O. Cell Signal 2020;73:109703."

Clinical • P2 data • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hypertension • Immunology • Nephrology • Polycystic Kidney Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • CFTR

A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (clinicaltrials.gov) - P2; N=66; Active, not recruiting; Sponsor: Galapagos NV; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • MRI

Galapagos completes patient recruitment for MANGROVE Phase 2 trial with GLPG2737 in polycystic kidney disease (GlobeNewswire) - "Galapagos NV...announces completion of recruitment in the MANGROVE Phase 2 trial with investigational CFTR inhibitor GLPG2737 in patients with autosomal dominant polycystic kidney disease (ADPKD). MANGROVE is a randomized, double-blind, placebo-controlled trial evaluating a once-daily oral dose of GLPG2737 (NCT04578548)....Galapagos expects topline results from the MANGROVE Phase 2 trial in the first half of 2023."

Enrollment closed • P2 data • Autosomal Dominant Polycystic Kidney Disease

A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Galapagos NV; Trial completion date: Nov 2022 ➔ Feb 2024

Clinical • Trial completion date • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • MRI

CFTR Rescue in Intestinal Organoids with GLPG/ABBV-2737, ABBV/GLPG-2222 and ABBV/GLPG-2451 Triple Therapy. (PubMed, Front Mol Biosci) - "The combination ABBV/GLPG-2222/ABBV-2737/ABBV/GLPG-2451 showed increased efficacy over VX-770/VX-809 for most organoids, despite considerable variation in efficacy between the different organoid cultures. These differences in CFTR restoration between organoids with comparable genotypes underline the relevance of continuing to optimize the ABBV/GLPG-Triple therapy, as well as the in vitro characterization of efficacy in clinically relevant models."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

GLPG2737: Expiry of patents related to composition-of-matter and methods of treatment outside the field of cystic fibrosis in US/ex-US, EU, Japan, China, Australia, Canada, and Taiwan in 2036 (Galapagos) - Annual Report 2020: Expiry of patents related to methods of treatment in alternative indications in 2040

Patent • Cystic Fibrosis

Galapagos announces first dosing in MANGROVE Phase 2 trial with GLPG2737 in polycystic kidney disease (GlobeNewswire) - "Galapagos...announces first dosing in the new MANGROVE Phase 2 trial with investigational CFTR inhibitor GLPG2737 in patients with autosomal dominant polycystic kidney disease (ADPKD)."

Trial status • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders

A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Galapagos NV

Clinical • New P2 trial • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

GLPG2737: Expiry of patents related to composition-of-matter and methods of treatment outside the field of cystic fibrosis in US/ex-US, Australia, Canada, Europe, and Taiwan in 2036 (Galapagos) - Annual Report 2019: Expiry of patents related to methods of treatment in alternative indications in UK in 2040

Patent

GLPG2737 in lumacaftor/ivacaftor-treated CF subjects homozygous for the F508del mutation: A randomized phase 2A trial (PELICAN). (PubMed, J Cyst Fibros) - P2a; "GLPG2737 was well tolerated and yielded significant decreases in sweat chloride concentration versus placebo in subjects homozygous for F508del receiving lumacaftor/ivacaftor, demonstrating evidence of increased CFTR activity when added to a potentiator-corrector combination."

Clinical • Journal • P2a data

Identification of GLPG/ABBV-2737, a Novel Class of Corrector, Which Exerts Functional Synergy With Other CFTR Modulators. (PubMed, Front Pharmacol) - "Here, we describe the identification of a novel F508del corrector using functional assays. We provide experimental evidence that the clinical candidate GLPG/ABBV-2737 represents a novel class of corrector exerting activity both on its own and in combination with VX809 or GLPG/ABBV-2222."

Journal

FALCON: A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis. (clinicaltrials.gov) - P1; N=10; Completed; Sponsor: Galapagos NV; Active, not recruiting ➔ Completed; Trial completion date: Apr 2020 ➔ Mar 2019; Trial primary completion date: Apr 2020 ➔ Mar 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date