A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis.

Inclusion Criteria:

• Female or male subject ≥18 years of age, on the day of signing the Informed ConsentForm (ICF)

• Confirmed clinical diagnosis of cystic fibrosis (CF) (documented in the subject'smedical record).

• Eligible cystic fibrosis transmembrane conductance regulator (CFTR) genotype atscreening:

• Cohort A: Homozygous for the F508del CFTR mutation

• Cohort B: Heterozygous for the F508del CFTR mutation with a potentiatornon-responsive mutation on the second allele

• Cohort C: Homozygous for the F508del CFTR mutation

• A body weight of ≥40 kg at screening.

• Stable concomitant medication for pulmonary health for CF for at least 4 weeks priorto the first study drug administration and planned continuation of the sameconcomitant medication for the duration of the dosing period of the study. Subjectswith diabetes mellitus and/or pancreatic insufficiency are eligible for the studyprovided they are on stable treatment (e.g. medication, diet, pancreatic enzymereplacement therapy) for at least 4 weeks prior to the first study drug administrationin the opinion of the investigator.

• Forced expiratory volume in 1 second (FEV1): 40% ≤ FEV1 ≤ 90% of predicted normal forage, sex, and height at screening (pre- or post bronchodilator) at screening.

• Sweat chloride concentration ≥60 mmol/L at screening.

• Non-smoker and non-user of any nicotine and or cannabis containing products. Anon-smoker is defined as an individual who has abstained from smoking for at least 1year prior to the screening. A non-user is defined as an individual who has abstainedfrom any nicotine containing products for at least 1 year prior to the screening.

Exclusion Criteria:

• History of or ongoing allergic bronchopulmonary aspergillosis.

• Medical history of cataract (or lens opacity) and/or glaucoma.

• Cataract (or lens opacity) and/or glaucoma determined by an ophthalmologist during thescreening period.

• Unstable pulmonary status or respiratory tract infection (including rhinosinusitis)requiring a change in therapy within 4 weeks prior to the first study drugadministration.

• History of clinically meaningful unstable or uncontrolled chronic disease that makesthe subject unsuitable for inclusion in the study in the opinion of the investigator.

• Need for supplemental oxygen during the day, and >2 L/minute while sleeping.

• History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms ofsplenomegaly, esophageal varices).

• History of malignancy within the past 5 years (except for basal cell carcinoma of theskin with no evidence of recurrence and/or carcinoma in situ of the cervix that hasbeen treated with no evidence of recurrence).

• Use of any moderate and strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeksprior to the first study drug administration (e.g., clarithromycin, itraconazole,ketoconazole, telithromycin, rifampin, carbamazepine).

• Use of CFTR modulator therapy (e.g., lumacaftor and/or ivacaftor) within 4 weeks priorto the first study drug administration.

• Use of any oral corticosteroid within 3 months of screening; or history of oralcorticosteroid use for ≥30 days (cumulative) within 2 years of screening.

• Abnormal liver function test at screening; defined as aspartate aminotransferase (AST)and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/orgamma-glutamyl transferase (GGT) ≥3× the upper limit of normal (ULN); and/or totalbilirubin ≥1.5× the ULN.