GLPG1205 / Galapagos, Gilead - LARVOL DELTA

Revealing the suppressors: A new PET imaging approach for detecting MDSCs before and after immunotherapy in a model of brain metastases (SNMMI 2025) - "A subset of vehicle mice was blocked with GPR84 antagonist GLPG1205 (2 mg/kg; n=11) to assess tracer specificity. Organs of interest were analyzed via gamma counting and autoradiography, and quantitative polymerase chain reaction (qPCR) was used to assess Gpr84 and Tspo expression in whole brains of vehicle (n=5), treated (n=5), and sham (n=5) mice... PET imaging and autoradiography revealed localization of immunosuppressive MDSCs in both brain and extracranial tumors of vehicle-treated mice (Fig. 1B-C, Fig. S1A)."

IO biomarker • Melanoma • Oncology • Solid Tumor

Targeting GPR84 to alleviate acute immune-mediated liver injury. (PubMed, Mol Med) - "Our findings suggest that GPR84 plays a pivotal role in immune-mediated liver injury, primarily through its expression on hematopoietic cells. Targeting GPR84, particularly with the antagonist GLPG1205, offers a promising therapeutic strategy for treating immune-related liver diseases."

Journal • Hepatology • Inflammation • Liver Failure • ITGAM • STAT3 • TNFA

Targeting Medium Chain Fatty Acid Metabolism to Control Chronic Gvhd (TCT-ASTCT-CIBMTR 2025) - P2 | "GPR84 is a valid target for the prevention and treatment of cGVHD. Because GLPG1205 has been found safe in a phase 2 trial (NCT03725852) for idiopathic pulmonary fibrosis (IPF), testing this GPR84 antagonist and a diet low in MCFAs for cGVHD treatment is possible in clinical settings."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • CD8

Development and comparison of two novel PET tracers for imaging pro-inflammatory receptor GPR84 in human cells and tissues (SNMMI 2024) - "Co-incubation with GPR84 antagonist (GLPG1205, 1000x by mass) reduced tracer binding in hGPR84-HEK293 cells by >90% (Fig 1D, p<0... Both tracers enable specific detection of GPR84 and innate immune activation in cells and UC tissue. [18F]MGX-110S shows high potential for translation given its favorable half-life, in vivo distribution, and specificity for GPR84."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Septic Shock • Ulcerative Colitis

The GPR84 Antagonist GLPG1205 Reduces Features of Disease in Experimental Severe Asthma. (PubMed, Am J Respir Cell Mol Biol) - No abstract available

Journal • Asthma • CNS Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

PET Imaging of Innate Immune Activation Using C Radiotracers Targeting GPR84. (PubMed, JACS Au) - "Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro...When compared with C-DPA-713-an existing radiotracer used to image innate immune activation in clinical research studies-C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology."

Journal • CNS Disorders • Inflammation

Human IPF lung tissue implanted on the chick chorioallantoic membrane as a novel in vivo model for antifibrotic drug testing (ICLAF 2022) - "Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

GLPG1205 for idiopathic pulmonary fibrosis: a Phase 2 randomised placebo-controlled trial. (PubMed, Eur Respir J) - P2 | "Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo."

Journal • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

GLPG1205 shows reduction in lung volume decline over 26 weeks vs placebo when measured with novel volumetric CT analysis in IPF patients (ERS 2022) - P2 | "The PINTA trial (NCT03725852) was a double-blind placebo (PBO)-controlled study of GLPG1205 in 68 IPF patients...Novel imaging quantification software may provide alternative trial endpoints allowing for smaller trial sizes. These will require standardised imaging protocols and power calculations."

Clinical • Idiopathic Pulmonary Fibrosis

Human Lung Tissue Implanted on the Chick Chorioallantoic Membrane as a Novel In Vivo Model of IPF. (PubMed, Am J Respir Cell Mol Biol) - "Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Results of a phase 2 study of GLPG1205 for idiopathic pulmonary fibrosis (PINTA) (ERS 2021) - P2 | "IPF patients received oral GLPG1205 100mg or PBO once daily, on top of standard of care (nintedanib/pirfenidone/neither) for 26 weeks. This along with the observed safety profile for GLPG1205 alone supports further development. Funding Galapagos"

P2 data • Fibrosis • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] SESSION 134: The future of idiopathic pulmonary fibrosis (ERS 2021) - "The live session is scheduled from September 5-7 and each presenter will have a 5-minutes live, slide show presentation followed at the end of the session by 30-minutes general discussion. This session includes the Best Abstract for Assembly 12 - Interstitial Lung Diseases, entitled "Results of a phase 2 study of GLPG1205 for idiopathic pulmonary fibrosis (PINTA)”"

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

GLPG1205, a GPR84 Modulator: Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "GPR84 receptor occupancy with GLPG1205 vs placebo confirmed target engagement. These results support further clinical development of GLPG1205."

Clinical • Journal • PK/PD data

Effect of GLPG1205, a GPR84 Modulator, on CYP2C9, CYP2C19, and CYP1A2 Enzymes: In Vitro and Phase 1 Studies. (PubMed, Clin Pharmacol Drug Dev) - P1 | "GLPG1205 may be concomitantly administered with pirfenidone in future clinical development; therefore, the potential for GLPG1205 to interact with enzymes involved in the metabolism of pirfenidone (cytochrome P450 [CYP] 1A2, CYP2C9, 2C19) was evaluated...GLPG1205 had no effect on the exposure of CYP2C9 and CYP1A2 substrates or metabolites; however, a trend toward increased omeprazole (CYP2C19 substrate) exposure was observed...GLPG1205 had a favorable safety and tolerability profile. In conclusion, GLPG1205 100 mg once daily does not interact with CYP2C9, CYP2C19, or CYP1A2 to a clinically relevant extent and may be administered concomitantly with drugs metabolized by these enzymes."

Clinical • Journal • P1 data • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CYP1A2 • CYP2C19 • CYP2C9

GLPG1205: Expiry of patents related to composition-of-matter and method of treatment in US/ex-US, EU, Australia, China, Canada and Japan in 2032 (Galapagos) - Annual Report 2020: Expiry of patents related to method of treatment using GLPG1205 in further indications in 2038; Expiry of patents related to improved methods for treating lung disorders using GLPG1205 in EU in 2041

Patent • Idiopathic Pulmonary Fibrosis

Evaluation of Mass Balance and Absolute Bioavailability of GLPG1205 (clinicaltrials.gov) - P1; N=12; Completed; Sponsor: Galapagos NV; Recruiting ➔ Completed

Clinical • Trial completion

Evaluation of Mass Balance and Absolute Bioavailability of GLPG1205 (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Galapagos NV; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Evaluation of Mass Balance and Absolute Bioavailability of GLPG1205 (clinicaltrials.gov) - P1; N=12; Not yet recruiting; Sponsor: Galapagos NV

Clinical • New P1 trial

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GLPG1205 in Healthy Japanese and Caucasian Male Subjects (clinicaltrials.gov) - P1; N=32; Completed; Sponsor: Galapagos NV; Active, not recruiting ➔ Completed

Clinical • Trial completion

Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists. (PubMed, J Med Chem) - "Three GPR84 antagonists (S)-2-((1,4-dioxan-2-yl)methoxy)-9-(cyclopropylethynyl)-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one (GLPG1205), sodium 2-(3-pentylphenyl)acetate (PBI-4050), and sodium 2-(3,5-dipentylphenyl)acetate (PBI-4547) have displayed therapeutic effects in animal models of several inflammatory and fibrotic diseases and are being evaluated in clinical studies. Although GLPG1205 has failed in a clinical trial for ulcerative colitis, it is undergoing another phase II clinical study for idiopathic pulmonary fibrosis. Further studies are needed to resolve the GPR84 structure, identify more endogenous ligands, elucidate their physiological and pathological roles, and fulfill the therapeutic potential of GPR84 antagonists and agonists."

Journal • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Bowel Disease • Respiratory Diseases • Ulcerative Colitis

Galapagos reports positive topline results with GLPG1205 in IPF patients in PINTA Proof-of-Concept trial (GlobeNewswire) - P2a, N=68; PINTA (NCT03725852); Sponsor: Galapagos NV; "Galapagos NV...announces positive topline results with its investigational GPR84 antagonist GLPG1205 in Proof-of-Concept Phase 2 trial in idiopathic pulmonary fibrosis (IPF) patients....At week 26, patients receiving GLPG1205 on top of standard of care showed a smaller FVC decline, with a difference of 42mL versus placebo on top of standard of care (-76mL on placebo; -34mL on treatment)....No relevant safety signals were observed for GLPG1205 alone and on top of pirfenidone....Based on the results of this trial, Galapagos plans to progress GLPG1205 in a dose finding Phase 2b trial. The full results of the PINTA trial will be submitted to a future medical conference and peer-reviewed medical journals."

P2a data • Idiopathic Pulmonary Fibrosis

Galapagos reports positive topline results with GLPG1205 in IPF patients in PINTA Proof-of-Concept trial - P2, N=26; PINTA (NCT03725852); Sponsor: Galapagos NV; "'Keeping in mind the limitations of this early clinical study, the PINTA study with GLPG1205 is a positive trial. The consistent changes observed across treatment strata, using different analytical methods, including FRI, are very encouraging. While we need to understand more about long-term tolerability of the drug, the PINTA results warrant further investigation,' said Prof. Dr. Toby Maher."

Media quote • P2 data • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GLPG1205 in Healthy Japanese and Caucasian Male Subjects (clinicaltrials.gov) - P1; N=32; Active, not recruiting; Sponsor: Galapagos NV; Recruiting ➔ Active, not recruiting; N=56 ➔ 32

Clinical • Enrollment change • Enrollment closed

GLPG1205: Data from P2 PINTA trial (NCT03725852) for idiopathic pulmonary fibrosis in Q4 2020 (Galapagos) - Q3 2020 Results

P2 data • Idiopathic Pulmonary Fibrosis

PINTA: A Clinical Study to Test How Effective and Safe GLPG1205 is for Patients With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2; N=69; Completed; Sponsor: Galapagos NV; Active, not recruiting ➔ Completed

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