Galapagos Advances GLPG4617 Into Phase 2 Trial

In a move that refocuses its clinical pipeline, Galapagos is discontinuing the development of GLPG1205, its experimental therapy for idiopathic pulmonary fibrosis (IPF), and advancing its most recent IPF candidate, GLPG4617, into a Phase 2 clinical trial.

These and other decisions toward a “more risk-balanced pipeline” are expected to generate savings of €150 million (about $182 million) over one year.

This IPF pipeline trimming comes nearly three months after the company announced discontinuation of the clinical program of ziritaxestat (GLPG1690), an experimental oral therapy for IPF that was already being tested in Phase 3 trials.

The prior decision was based on a recommendation from the independent data monitoring committee overseeing the Phase 3 ISABELA 1 (NCT03711162) and ISABELA 2 (NCT03733444) trials, which considered that the therapy had a non-favorable benefit-risk profile.

Now, Galapagos decided to prioritize treatment candidates with the most significant clinical success in its core therapeutic areas, namely inflammation, fibrosis (scarring), and kidney diseases. In turn, early research in metabolic diseases and osteoarthritis was stopped.

“We are working towards a right-sized, refocused version of Galapagos, setting us on a path towards success with our first commercial product, new R&D opportunities, substantial clinical news flow, and a lengthened cash runway for validation of our early pipeline assets,” Bart Filius, Galapagos’ president and chief operating officer, said in a press release.

In September, Jyseleca (filgotinib), an oral treatment developed by Galapagos in collaboration with Gilead, was approved in the European Union (EU) for the treatment of rheumatoid arthritis. The company now stated it remains fully committed to supports the therapy’s launch in the EU.

“Within our fibrosis portfolio, we expect to progress early clinical compounds with novel mechanisms of action, with the aim to develop novel treatments to help patients suffering from this debilitating condition,” the company stated.

GLPG1205 is a small molecule that suppresses GPR84, a protein known to promote chronic inflammation in IPF. As such, the therapy was expected to lower inflammation and lung damage, thereby improving lung function in people with IPF.

Notably, GLPG1205 showed early promising results in the Phase 2 PINTA study (NCT03725852), which assessed and compared its safety and efficacy to those of a placebo in 68 adults with IPF.

Top-line, six-month data from PINTA demonstrated the therapy was generally well-tolerated and able to slow patients’ lung function decline, regardless of being given alone or alongside other background IPF therapies, such as Esbriet (pirfenidone) or Ofev (nintedanib).

While this early study lacked power to reach statistical significance, its findings prompted Galapagos to outline plans for further evaluating GLPG1205 in a future dose-finding Phase 2b trial.

As it refocused its pipeline, the biotech also decided to drop GLPG1205, while concentrating on its most recent IPF candidate, GLPG4617.

Formerly known as OATD-01, GLPG4617  originally was developed by OncoArendi Therapeutics, which sold the therapy’s global research, development and commercialization rights to Galapagos back in November 2020.

The investigational therapy works by blocking the activity of chitinases — enzymes involved in multiple fibrosis-associated processes, including tissue remodeling and inflammation, and that are overly active in IPF.

Preclinical research in animal models of pulmonary fibrosis suggested that GLPG4617 promotes anti-fibrotic effects comparable to Ofev. In Phase 1 clinical studies involving healthy volunteers, the therapy was found to be well-tolerated and to effectively suppress chitinase activity, supporting its proposed mechanisms of action.

Now, Galapagos plans to launch a Phase 2 trial to evaluate GLPG4617’s safety and effectiveness in IPF patients.

“We believe that our strong cash position, expert teams, and solid scientific foundation position us well for future growth,” said Onno van de Stolpe, Galapagos’ CEO.