GLPG-1205

Michael Vi / Shutterstock Belgium-based Galapagos NV and Foster City, California-based Gilead Sciences halted the ISABELA Phase III clinical trial of ziritaxestat in idiopathic pulmonary fibrosis. Michael Vi / Shutterstock Belgium-based Galapagos NV and Foster City, California-based Gilead Sciences halted the ISABELA Phase III clinical trial of ziritaxestat in idiopathic pulmonary fibrosis. This came after the Independent Data Monitoring Committee (IDMC) conducted a regular review of unblinded data and concluded that the benefit-risk pro ’t support continuing. All trials with ziritaxestat, including a long-term extension of the Phase IIa NOVESA trial in systemic sclerosis, are being discontinued. Ziritaxestat is an investigational autotaxin inhibitor. It was discovered by Galapagos and Gilead in-licensed rights outside of Europe in July 2019 while sharing the Phase III development expenses. When Dan O’Day took over Gilead in 2019, the deal was part of his efforts to diversify Gilead’s pipeline in what he dubbed a “transformative” agreement. Gilead coughed up almost $5 billion in upfront and equity investments, which as of now, appears to be a waste of money and time. Jefferies analyst Peter Welford called the flop a “shock.” Welford once projected the drug with peak sales in IPF at $1.85 billion. He wrote in a note to clients, “We note that all clinical trials with ziritaxestat have been discontinued, including the long-term extension of the Phase IIa NOVESA trial in systemic sclerosis, suggesting a possible safety concern rather than lack of sufficient efficacy in lung fibrosis.” Galapagos shares plummeted 14% at the news. Walid Abi-Saab, chief medical officer of Galapagos, stated, “We are very disappointed not to be able to bring a novel medication to patients suffering from such a devastating disease with high unmet need. We would like to thank the patients and the medical professionals who participated in the ISABELA studies and contributed to the advancement of IPF research. We intend to learn from this data in our continued commitment to develop therapies in IPF and fibrosis.” In mid-December, Gilead and Galapagos announced they had killed a program for Jyseleca (filgotinib) for rheumatoid arthritis. In August 2020, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for the companies’ New Drug Application over safety concerns. The FDA in the CRL questioned if filgotinib had an impact on sperm parameters in male patients, as well as the overall benefit/risk pro the 200 mg dose. The two companies held a Type A meeting with the FDA and while they indicated they believe the clinical pro the 200 mg dose of Jyseleca for RA was still valid, they abandoned the program because that dose was unlikely to be approved in the U.S. without more substantial clinical trials. Jyseleca is an oral selective JAK1 inhibitor that has been the cornerstone product for the two companies’ collaboration. They were hoping Jyseleca would be able to rival other JAK inhibitors for several indications, including Pfizer’s Xeljanz, Eli Lilly’s Olumiant and AbbVie’s Rinvoq. Gilead and Galapagos also paused the development of filgotinib for other indications, including psoriatic arthritis, ankylosing spondylitis and non-infectious uveitis. They indicated plans to continue investigating the drug for Inflammatory Bowel Disease (IBD), and Gilead was keeping operational responsibility for trials in Crohn’s disease while Galapagos was assuming operational responsibility for trials in ulcerative colitis. “In this new context,” O’Day said in December, “Gilead and Galapagos believe it makes sense for Galapagos to drive commercialization in Europe. We are confident that through our strategic alliance with Galapagos, we will deliver many important new therapies for inflammatory disease in the future.” They are also continuing work on a second-line treatment for IPF, GLPG1205, despite only modest results and some concerning adverse events. Brian Skorney, an analyst at Baird, thinks investors can hold out hopes for the two companies’ inflammatory disease program, GLPG3970. In a note, he wrote, “Gilead will be looking for a change in fate when Galapagos reads out data from at least five proof-of-concept studies testing GLPG3970, their lead asset in the TOLEDO program, in various inflammatory disease over the course of the next year.” Featured Jobs on BioSpace

Galapagos NV reports first dosing in the PINTA Phase 2 trial with its GPR84 antagonist GLPG1205 in patients with idiopathic pulmonary fibrosis (IPF). Mechelen, Belgium; 31 October 2018; 22:01 CET - Galapagos NV (Euronext & NASDAQ: GLPG) reports first dosing in the PINTA Phase 2 trial with its GPR84 antagonist GLPG1205 in patients with idiopathic pulmonary fibrosis (IPF). PINTA is a randomized, double-blind, placebo-controlled Phase 2 trial investigating a 100 mg once-daily oral dose of GLPG1205 in up to 60 IPF patients. The first patient was dosed in a center opened in Slovakia. Galapagos currently has three drug candidates with distinct mechanisms of action in its fully proprietary portfolio aimed at building an IPF franchise: GLPG1690 in the ISABELA Phase 3 program, GLPG1205 in the PINTA Phase 2 trial, and GLPG3499, currently in pre-clinical development. “The first patient dosing in our PINTA Phase 2 trial shows the progress we are making in expanding our IPF franchise,” said Dr. Piet Wigerinck, Chief Scientific Officer at Galapagos. “We are strongly committed to the rapid development of our fully proprietary IPF portfolio to address this important unmet medical need.” About GLPG1205 GLPG1205, fully proprietary to Galapagos, is a small molecule selectively antagonizing GPR84. Galapagos identified the GPR84 target using its proprietary target discovery platform and developed GLPG1205 as an antagonist of this target. GLPG1205 showed promising results in relevant pre-clinical models for IPF, and there is growing evidence in scientific literature and in clinical research that GPR84 plays a role in this disease. GLPG1205 successfully completed several Phase 1 trials, showing favorable findings relating to tolerability, and target engagement in healthy volunteers. GLPG1205 showed good tolerability but no activity in ulcerative colitis patients in 2016. GLPG1205 is an investigational drug and its efficacy and safety have not yet been established. For information about the studies with GLPG1205: (NCT03725852) For more information about GLPG1205: About IPF IPF is a chronic, relentlessly progressive fibrotic disorder of the lungs that typically affects adults over the age of 40. There are approximately 200,000 patients with IPF in the U.S. and Europe. As such, IPF is considered a rare disease. The clinical prognosis of patients with IPF is poor as the median survival at diagnosis is 2 to 4 years. Currently, no medical therapies have been found to cure IPF. The medical treatment strategy aims to slow the disease progression and improve the quality of life. About the PINTA trial PINTA is a randomized, double-blind, placebo-controlled Phase 2 trial investigating a 100 mg once-daily oral dose of GLPG1205. The drug candidate or placebo will be administered for 26 weeks in up to 60 IPF patients. Patients may remain on their local standard of care as background therapy, whether or not they were previously or currently are treated with Esbriet ® [1] (pirfenidone) and Ofev ® [2] (nintedanib). The primary objective of the trial is to assess the change from baseline in Forced Vital Capacity (FVC in mL) over 26 weeks compared to placebo. Secondary measures include safety, tolerability, pharmacokinetics and pharmacodynamics, time to major events, changes in functional exercise capacity, and quality of life. Recruitment for PINTA is planned in 10 countries in Europe, North Africa, and the Middle East. About Galapagos Galapagos (Euronext & NASDAQ: GLPG) is a clinical-stage biotechnology company specialized in the discovery and development of small molecule medicines with novel modes of action. Galapagos’ pipeline comprises Phase 3 through to discovery programs in inflammation, fibrosis, osteoarthritis and other indications. Our target discovery platform has delivered three novel mechanisms showing promising patient results in, respectively, inflammatory diseases, idiopathic pulmonary fibrosis and atopic dermatitis. Galapagos is focused on the development and commercialization of novel medicines that will improve people’s lives. The Galapagos group, including fee-for-service subsidiary Fidelta, has approximately 700 employees, operating from its Mechelen, Belgium headquarters and facilities in the Netherlands, France, Switzerland, the US and Croatia. More information at . Contact Investors: Elizabeth Goodwin VP IR & Corporate Communications +1 781 460 1784 Sofie Van Gijsel Director IR +32 485191415 ir@glpg.com Media: Evelyn Fox Director Communications +31 6 53 591 999 communications@glpg.com Forward-looking statements This release may contain forward-looking statements, including statements regarding Galapagos’ strategic ambitions, the mode of action and/or potential activity of GLPG1205, the anticipated timing of future clinical studies with GLPG1205, the progression and results of such studies and the unmet medical need for IPF treatments. Galapagos cautions the reader that forward-looking statements are not guarantees of future performance. Forward-looking statements involve known and unknown risks, uncertainties and other factors which might cause the actual results, financial condition and liquidity, performance or achievements of Galapagos, or industry results, to be materially different from any historic or future results, financial conditions and liquidity, performance or achievements expressed or implied by such forward-looking statements. In addition, even if Galapagos’ results, performance, financial condition and liquidity, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. Among the factors that may result in differences are the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements (including that data from the ongoing and planned clinical research programs may not support registration or further development of GLPG1205 due to safety, efficacy or other reasons), and estimating the commercial potential of Galapagos’ product candidates. A further list and description of these risks, uncertainties and other risks can be found in Galapagos’ Securities and Exchange Commission (SEC) filings and reports, including in Galapagos’ most recent annual report on Form 20-F filed with the SEC and subsequent filings and reports filed by Galapagos with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. Galapagos expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements, unless specifically required by law or regulation.