Our IPF programs


IPF is a chronic, relentlessly progressive fibrotic disorder of the lungs that typically affects adults over the age of 40. IPF affects approximately 200,000 patients in the United States and Europe and, as such, we have received orphan designation for our product candidate GLPG1690 in IPF from the European Commission and from the FDA. The clinical prognosis of patients with IPF is poor, as survival at diagnosis is two to four years. Currently, no medical therapies have been found to cure IPF. The medical treatment strategy aims to slow disease progression and improve quality of life. Lung transplantation may be an option for appropriate patients with progressive disease and minimal comorbidities.

Regulatory agencies have approved Esbriet®1 An approved drug (pirfenidone) for IPF, marketed by Roche. and Ofev®2 An approved drug (nintedanib) for IPF, marketed by Boehringer Ingelheim. for the treatment of mild to moderate IPF. Both Esbriet and Ofev have been shown to slow the rate of functional decline in IPF and are gaining ground as the standard of care worldwide. Combined sales of both drugs reached $1.1 billion in 2016, with 74% of global revenues being in the United States. These regulatory approvals represent a major breakthrough for IPF patients; yet neither drug improves lung function, and the disease in most patients on these therapies continues to progress. Moreover, the adverse effects associated with these therapies are considerable (e.g., diarrhea, liver function test abnormalities with Ofev, nausea and rash with Esbriet). Therefore, there is still a large unmet medical need as IPF remains a major cause of morbidity and mortality. We estimate global sales of approved IPF drugs will grow to nearly $5 billion in 2025.

Our IPF portfolio

Building an IPF franchise

Building an IPF franchise (graphic)

We have developed a portfolio of three candidate drugs, each with a distinct, novel mechanism of action aimed toward addressing the root causes of IPF. Having multiple mechanisms of action within our own portfolio of IPF candidates allows the possibility of exploring combinations of therapies as well. These candidates are fully proprietary to us, and we aim to commercialize successful drug candidates ourselves.


GLPG1690 is a potent and selective inhibitor of autotaxin (ATX). We identified ATX as a potential target for IPF, using an inflammation assay in our target discovery platform. Pharmacology and translational studies published by other parties since then suggest that ATX may also play a role in metabolic disease, arthritic pain, oncology, and lung disease.

We completed a Phase 2a trial (called FLORA) in IPF patients and announced topline results in August 2017. FLORA was an exploratory, randomized, double-blind, placebo-controlled trial investigating a once-daily oral dose of GLPG1690. The drug candidate was administered for 12 weeks in 23 IPF patients, 17 of whom received GLPG1690 and 6 placebo. Primary objectives of the trial were to assess safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG1690 in an IPF patient population. Secondary objectives included the evaluation of lung function, changes in disease biomarkers, FRI, and quality of life. The IPF diagnosis was confirmed by central reading.

Over the 12-week period, patients receiving GLPG1690 showed stabilization of disease, with an FVC increase of 8 mL, while patients on placebo showed an FVC reduction of 87 mL (mean from baseline). Such reductions in FVC in the placebo arm were in line with expectations based on similarly conducted third-party trials in IPF patients.

FVC: stabilization by ‘1690

FVC: stabilization by '1690 (line chart)

In addition to the demonstrated absence of lung function decline over the 12 week period, more sensitive functional respiratory imaging (FRI) confirmed disease stabilization in the GLPG1690 arm, versus disease progression in the placebo arm, reaching statistical significance on two specific parameters, despite the trial not being powered for significance.

FRI: airway volume & resistance
Significant difference between ‘1690 & placebo

FRI: airway volume & resistance (bar chart)

Patients on GLPG1690 treatment showed a clear reduction of serum LPA18:2, a biomarker for ATX inhibition, as expected based on the mechanism of action of GLPG1690. Thus, the level of target engagement observed in Phase 1 with healthy volunteers was confirmed in IPF patients in FLORA.

Steep reduction of biomarker
Plasma LPA18:2 drops in ‘1690 arm

Steep reduction of biomarker (line chart)

GLPG1690 was found to be generally well tolerated in this Phase 2 trial. Rates of discontinuation due to adverse events, as well as serious adverse event rates, were similar between patients on GLPG1690 and placebo.

Balanced safety endpoints
Between ‘1690 & placebo

Overview safety endpoints



Related TEAEs: headache (mild intensity, no change in treatment) & peripheral swelling of shin (moderate intensity, treatment temporarily stopped)

Discontinuations: 1 placebo SAE, 2 GLPG1690: withdrawal of consent and SAE

All AEs reported in subjects with ≥ 1 reported AE

Treatment emergent adverse event

67% (4)

65% (11)

Serious TE AE

33% (2)

6% (1)

Mild TE AE

0% (0)

24% (4)

Moderate TE AE

50% (3)

35% (6)

Severe TE AE

17% (1)

6% (1)

Related TE AE

0% (0)

12% (2)

Temporarily stopped treatment

0% (0)

12% (2)

Permanently stopped treatment

17% (1)

6% (1)

Following the promising results with GLPG1690 in the FLORA trial, we decided to pursue further development of the compound ourselves. We plan to progress GLPG1690 rapidly into a late stage trial and are in discussions with regulators regarding trial design.

GLPG3499 and GLPG1205

In June 2017, we nominated a new product candidate for IPF, GLPG3499. The novel mechanism of action of GLPG3499 remains undisclosed. This candidate is expected to enter Phase 1 trials in 2018. Pre-clinical data in a bleomycin mouse model for IPF show a numerical advantage with treatment with GLPG3499 over Ofev in reduction of fibrotic scores.

GLPG1205 is a GPR84 inhibitor discovered by us and we have shown favorable tolerability but no effect in UC patients in 2016. GLPG1205 will be tested in IPF patients starting in 2018. Pre-clinical data in a bleomycin mouse model for IPF show a numerical advantage with treatment with GLPG1205 over Ofev in improvement of respiratory capacity.

Additional novel mechanisms '3499 (left) and '1205 (right) in IPF

Additional novel mechanisms in IPF (graphic)

Note: both experiments are 21 day therapeutic bleomycin lung fibrosis model in mice (BLM)

1 An approved drug (pirfenidone) for IPF, marketed by Roche.
2 An approved drug (nintedanib) for IPF, marketed by Boehringer Ingelheim.