Our IPF trials

Our fibrosis portfolio
CSR report


Ziritaxestat (GLPG1690) is a potent and selective inhibitor of autotaxin (ATX), for which Gilead in-licensed the ex-European rights in July 2019. ATX as a potential IPF target was identified in our target discovery platform and further evaluated with ziritaxestat in a preclinical lung fibrosis model (bleomycin-treated mice).

Over the past years, we announced positive topline results for our Phase 2a FLORA trial in IPF, and the NOVESA Phase 2a Proof of Concept trial in dcSSc with ziritaxestat. Ziritaxestat was found to be generally well-tolerated and no deaths were reported in these studies. The FLORA Phase 2a results were published in The Lancet Respiratory (Maher et al. 2018). In 2018, following the encouraging results from the FLORA trial, we announced the design of our worldwide ISABELA Phase 3 program consisting of two identically designed trials, ISABELA 1 & 2, aiming to enroll 1,500 IPF patients combined. Patients continued on their standard of care background treatment and were randomized to either 200 mg or 600 mg ziritaxestat once daily or placebo. The primary endpoint was the rate of decline of forced vital capacity (FVC) until week 52.

In February 2021, we discontinued the ISABELA Phase 3 trials in IPF. The decision was based on the recommendation of the Independent Data Monitoring Committee which, following a regular review of unblinded data, concluded that ziritaxestat’s benefit-risk profile no longer supported continuing the program. Detailed data of the ISABELA studies will be presented at future medical meetings. All clinical trials with ziritaxestat are discontinued, including the long-term extension of the Phase 2a NOVESA trial in systemic sclerosis.


GLPG1205 is a clinical candidate for IPF that showed positive topline results in the Phase 2 PINTA trial.

GLPG1205 is a small molecule selectively antagonizing GPR84. We identified the GPR84 target using our proprietary target discovery platform. The compound showed promising results in relevant preclinical models for IPF and favorable tolerability in a healthy volunteer study.

PINTA Phase 2 in IPF

The PINTA trial was a randomized, double-blind, placebo-controlled trial investigating a 100 mg once-daily oral dose of GLPG1205. The study recruited and included a total of 68 IPF patients. Participants were administered the drug candidate or placebo (2:1 randomization) for 26 weeks and could remain on their standard of care as background therapy, i.e. nintedanib, pirfenidone or neither. The primary objective of the trial was to assess the change from baseline in FVC (in mL) over 26 weeks compared to placebo. Other measures included safety, tolerability, time to major events, changes in functional exercise capacity, quality of life, pharmacokinetics, pharmacodynamics and FRI.

In November 2020 we announced the positive topline results from the PINTA trial in IPF. 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).

FVC (graphic)

Although the study was not powered to show statistical significance, the FVC trend was consistent across the three treatment strata. In addition, the change in pulmonary lobar volume, as measured by FRI, correlated with the observed FVC decline.

No relevant safety signals were observed for GLPG1205 alone or on top of pirfenidone. The most frequently reported adverse events on GLPG1205 alone were gastrointestinal disorders, especially nausea. In the treatment arm of GLPG1205 on top of nintedanib, a higher rate of early discontinuations and higher rate of treatment emergent adverse events (TEAEs) were observed. In that same arm, there was one death due to an exacerbation of IPF, which was determined to be unrelated to study treatment.


In 2020, an additional clinical product candidate was added to our fibrosis pipeline, GLPG4716, which is currently in preparation for a Phase 2 trial.

GLPG4716 is a novel, small molecule CHIT1/AMCase dual-inhibitor targeting a key pathway implicated in inflammation and tissue remodeling. We inlicensed GLPG4716 from OncoArendi in November 2020.

Increased chitinase activity is strongly induced in multiple pulmonary diseases, including IPF, SSc-ILD, sarcoidosis, as well as in other diseases with inflammatory and/or fibrotic phenotype. In humans, CHIT1 is mainly expressed by different lineages of activated blood and tissue macrophages and has been implicated in the activation and polarization cascades of macrophages, as well as the indirect activation of other immune cells. It is hypothesized that the inhibition of chitinase activity translates into a potential therapeutic benefit, as observed in a range of preclinical models. GLPG4716 has demonstrated robust anti-fibrotic activity in multiple animal models, when compared with the standard of care.

Below is the result for GLPG4716, in a preclinical IPF model, demonstrating activity comparable to one of the drugs approved for IPF:

Activity in BLM therapeutic setting

Efficacy in BLM therapeutic setting (graphic)