I1

I2

FUEoST/EoSA

WeekGLPG1690 600 mg QD PO + SOC

Day 1GLPG1690 200 mg QD PO + SOC

Placebo QD PO + SOC

1:1:1

© Copyright 2019 Galapagos NV

Rationale, Design and Objectives of Two Phase III, Randomized, Placebo-Controlled Studies of GLPG1690,a Novel Autotaxin Inhibitor, in Idiopathic Pulmonary Fibrosis (ISABELA 1 and 2) T.M. Maher1, M. Kreuter2, D.J. Lederer3, K.K. Brown4, W. Wuyts5, N. Verbruggen6, S. Stutvoet6, A. Fieuw6, P. Ford6, W. Abi-Saab6, M. Wijsenbeek7

1NIHR Respiratory Clinical Research Facility, Royal Brompton Hospital, London, UK and Fibrosis Research Group, National Heart and Lung Institute, Imperial College London, London, UK; 2Centre for Interstitial and Rare Lung Diseases, Thoraxklinik, HeidelbergUniversity Hospital, Heidelberg, Germany and German Center for Lung Research, Giessen, Germany; 3Columbia University Irving Medical Center, New York, NY, USA; 4Department of Medicine, National Jewish Health, Denver, CO, USA; 5Unit for Interstitial LungDiseases, Department of Pulmonary Medicine, University Hospitals Leuven, Leuven, Belgium; 6Galapagos NV, Mechelen, Belgium; 7Department of Respiratory Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands

Screening

In each study, ~750 subjects will be randomized 1:1:1 across three arms; randomization will be stratified by local SOC for IPF (pirfenidone/nintedanib or no pirfenidone/nintedanib)

Treatment will be given for ≥52 weeks; studies will continue until the last subject reaches 52 weeks in the study

FU visit will occur 4 weeksafter the end-of-study visit

Study design

EoSA, end-of-study assessment; EoST, end-of-study treatment; FU, follow-up; IPF, idiopathic pulmonary fibrosis; PO, orally; QD, once daily; SOC, standard of care

Keyeligibilitycriteria

Acute IPF exacerbation

Severe pulmonary hypertension

Lung volume reduction surgery/transplant

LRTI requiring antibiotics

Interstitial lung disease associatedwith known primary diseases,

exposures or drugs

Clinically significant ECG abnormalities;QTcF >450 ms; long QT syndrome

Medications: substrates metabolized by CYP2C8; strong inducers/inhibitors of

CYP3A4; potent inducers/inhibitors of P-gp

Unstable CV, pulmonary(other than IPF) or other disease

Moderate/severe hepatic impairmentand/or abnormal liver function

Abnormal renal function

Hb level <10 g/dL

ISABELA 1EMEA Belgium Czech Republic Denmark Germany Greece Spain Turkey UKAPAC Australia TaiwanNA USALA Chile Peru

ISABELA 2EMEA France Germany Hungary Israel Italy Netherlands Poland South AfricaAPAC New Zealand South KoreaNA USA CanadaLA Argentina Brazil Mexico

6MWT, 6-Minute Walk Test; CV, cardiovascular; CYP, cytochrome P450; DLCO, diffusing capacity of the lung for carbon monoxide; ECG, electrocardiogram; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; Hb, hemoglobin;HRCT, high-resolution computed tomography; IPF, idiopathic pulmonary fibrosis; LRTI, lower respiratory tract infection; P-gp, P-glycoprotein; SOC, standard of care; SpO2, arterial oxygen saturation; QTcF, QT interval corrected for heart rate usingFridericia’s formula

6MWT, 6-Minute Walk Test; EQ-5D, EuroQoL 5-Dimensions Questionnaire; FVC, forced vital capacity; K-BILD, King’s Brief Interstitial Lung Disease; LCQ, Leicester Cough Questionnaire; PD, pharmacodynamics;PK, pharmacokinetics; QoL, quality of life; SGRQ, St. George’s Respiratory Questionnaire; VAS, Visual Analogue Scale

A wide array of robust,clinically relevantendpoints relatedto efficacy, safety,tolerability, mortality,QoL, PK/PD andbiomarkers willbe assessed

For the first time, a registrational study will assess a novel IPF treatment notonly as monotherapy, but also in combination with pirfenidone or nintedanib

Compared with previousIPF drug developmentprograms, a broader range of patients with IPF will be recruitedas eligibility criteria areless restrictive, which betterreflects clinical practice

Patients areallowed tochangebackgroundSOC treatmentthroughout thestudies, reflectingpotential real-world use

Positive findings may ultimately lead to a much-needednew treatment option for patients with IPF

Conclusions

References Acknowledgments

TMM has received personal fees from AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Galapagos, GlaxoSmithKline, Indalo Therapeutics, Pliant Therapeutics, ProMetic, Roche, Samumed and UCB; and stock options from Apellis outside the submitted work. His institution received grants or research fees from AstraZeneca, GlaxoSmithKline and UCB outside the submitted work. MK reportsgrants and personal fees from Galapagos during the conduct of the study; and grants and personal fees from Boehringer Ingelheim and Roche outside the submitted work. DJL reports personal fees from Galapagosduring the conduct of the study; personal fees from Philips Respironics, Roche, Sanofi Genzyme and Veracyte; grants and personal fees from Boehringer Ingelheim, Fibrogen, and Global Blood Therapeutics; unpaidSteering Committee membership for Galecto; and institutional fees for consultancy work from the Pulmonary Fibrosis Foundation outside the submitted work. KKB reports personal fees from Galapagos during theconduct of the study; conversation under CDA with Genoa Pharmaceuticals; grants from National Heart, Lung, and Blood Institute; and personal fees from Aeolus, AstraZeneca, aTyr Pharma, Biogen, Boehringer Ingelheim, Galapagos, Galecto BioTech, MedImmune, Novartis, Roche/Genentech, ProMetic, Patara and Third Pole outside the submitted work. WW reports no personal fees; the University Hospitals Leuven received consultancy fees from Galapagos during the conduct of the study and grants from Boehringer Ingelheim and Roche outside the submitted work. NV, SS, PF and WA-S are employees of, and have received warrants from, Galapagos. AF is an employee of Galapagos. MW reports no personal fees; the Erasmus MC received an advisory board fee from Galapagos, and speaker and advisory board fees from Boehringer Ingelheim andHoffmann-La Roche outside the submitted work.

1. Fisher M, Nathan SD, Hill C, et al. J Manag Care Spec Pharm 2017, 23(3-b Suppl):S17–S24; 2. Sharif R. Am J Manag Care 2017, 23(11 Suppl):S176–S182; 3. Vancheri C, Failla M, Crimi N, et al. Eur Respir J 2010, 35;157–169; 4. Raghu G. Eur Respir Rev 2017, 26(145) pii:170071; 5. Maher TM, van der Aar EM, Van de Steen O, et al. Lancet Respir Med 2018, 6(8):627–635

Editorial support was provided by Debbie Sherwood, BSc, Aspire Scientific(Bollington, UK), and funded by Galapagos NV (Mechelen, Belgium)

Disclosures

Endpoints

Inclusion Exclusion

Rate of decline in FVC over 52 weeks

Minimum treatment period is 52 weekswith a proportion ofsubjects to remain onstudy drug for longer,allowing longer-termefficacy and safety data to be collected

The study design is innovative and ambitious

Disease progression; time to first respiratory-relatedhospitalization; SGRQ change from baseline

Additional efficacy measures (e.g. 6MWT); cough (VAS cough, urge to coughLCQ); mortality; biomarkers; PK and PD; QoL (EQ-5D, K-BILD); safety

IPF is a rare disease with an estimated prevalence in Europe and North America of3–9 cases per 100,0001

Unmet need for novel, well-tolerated agents that reduce lung function decline, improve quality of life, and prolong life expectancy

Median survival without therapy is 2–3 years2,3

IPF is associated with progressive loss of lung function2

Introduction and rationale

IPF, idiopathic pulmonary fibrosis; SOC, standard of care

IPF, idiopathic pulmonary fibrosis; PD, pharmacodynamics; PK, pharmacokinetics; QoL, quality of life; SOC, standard of care

Participating countries as of April 02 2019APAC, Asia-Pacific; EMEA, Europe, the Middle East and Africa; LA, Latin America; NA, North America

■ ISABELA 1 ■ ISABELA 2 ■ Both ISABELA 1 & 2

Keymilestones

Participating countries

ISABELA 2recruitmentinitiated

ISABELA 1recruitmentinitiated

Phase IIaFLORA studycompleted

Other secondary

Key secondary

Primary

ISABELA 1 and 2 (NCT03711162 and NCT03733444) are two identicallydesigned, phase III studies with the primary objective of evaluating the

efficacy of GLPG1690 compared with placebo, each given on top oflocal SOC (i.e. pirfenidone, nintedanib or neither), in subjects with IPF

The first-in-class autotaxin inhibitor GLPG1690 has demonstrated encouraging resultsin early clinical trials, including the phase IIa FLORA study, warranting further evaluation

as a once-daily oral therapy for IPF5

Current SOC with the antifibrotic agents pirfenidoneor nintedanib slows disease progression,but prognosis remains poor4

IPF diagnosis (last 5 years)

IPF diagnosis by central review based on HRCT +/- lung biopsy

Extent of fibrotic changes> extent of emphysema

Receiving local SOC (pirfenidone or nintedanib;

neither pirfenidone nor nintedanib)

Males or females aged ≥40 years

FEV1/FVC ≥0.7

FVC ≥45% predicted of normal

Visit 1: able to walk ≥150 m during 6MWT

Visit 2: resting SpO2 ≥88% with max6 L O2/min; during walk SpO2 ≥83% with6 L O2/min or 88% with 0, 2 or 4 L O2/min

DLCO corrected for Hb ≥30%predicted of normal

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