Chantal Tasset

Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial

BACKGROUND Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohns disease. METHODS We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18-75 years with a documented history of ileal, colonic, or ileocolonic Crohns disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohns Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov, number NCT02048618. FINDINGS Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohns disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9-39], p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo. INTERPRETATION Filgotinib induced clinical remission in significantly more patients with active Crohns disease compared with placebo, and had an acceptable safety profile. FUNDING Galapagos.

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)

Objectives To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX. Methods In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response. Results Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100  or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported. Conclusions Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated. Trial registration number: NCT01888874.

Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

Objectives To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX). Methods In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12. Results Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported. Conclusions Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated. Trial registration number NCT01894516.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial

BACKGROUND The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis. METHODS The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Patients (aged ≥18 years) had active moderate-to-severe psoriatic arthritis (defined as at least five swollen joints and at least five tender joints) fulfilling Classification for psoriatic arthritis (CASPAR) criteria, active or a documented history of plaque psoriasis, and an insufficient response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Patients continued to take csDMARDs during the study if they had received this treatment for at least 12 weeks before screening and were on a stable dose for at least 4 weeks before baseline. Using an interactive web-based system, we randomly allocated patients (1:1) to filgotinib 200 mg or placebo orally once daily for 16 weeks (stratified by current use of csDMARDs and previous use of anti-tumour necrosis factor). Patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16 in the full analysis set (patients who received at least one dose of study drug), which was compared between groups with the Cochran-Mantel-Haenszel test and non-responder imputation method. This trial is registered with ClincalTrials.gov, number NCT03101670. FINDINGS Between March 9, and Sept 27, 2017, 191 patients were screened and 131 were randomly allocated to treatment (65 to filgotinib and 66 to placebo). 60 (92%) patients in the filgotinib group and 64 (97%) patients in the placebo group completed the study; five patients (8%) in the filgotinib group and two patients (3%) in the placebo group discontinued treatment. 52 (80%) of 65 patients in the filgotinib group and 22 (33%) of 66 in the placebo group achieved ACR20 at week 16 (treatment difference 47% [95% CI 30·2-59·6], p<0·0001). 37 (57%) patients who received filgotinib and 39 (59%) patients who received placebo had at least one treatment-emergent adverse event. Six participants had an event that was grade 3 or worse. The most common events were nasopharyngitis and headache, occurring at similar proportions in each group. One serious treatment-emergent adverse event was reported in each group (pneumonia and hip fracture after a fall), one of which (pneumonia) was fatal in the filgotinib group. INTERPRETATION Filgotinib is efficacious for the treatment of active psoriatic arthritis, and no new safety signals were identified. FUNDING Galapagos and Gilead Sciences.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial

BACKGROUND At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. METHODS In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270. FINDINGS Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was -1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, with a least squares mean difference between groups of -0·85 (95% CI -1·17 to -0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients in each group, the most common being nasopharyngitis (in two patients in the filgotinib group and in four patients in the placebo group). Treatment-emergent adverse events led to permanent treatment discontinuation in two patients (a case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in the placebo group). No deaths were reported during the study. INTERPRETATION Filgotinib is efficacious and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs. Further investigation of filgotinib for ankylosing spondylitis is warranted. FUNDING Galapagos and Gilead Sciences.

Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes

BackgroundThe aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies.MethodsPatients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. PROs were measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the Patient Global Assessment of Disease Activity (Patient Global), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the 36-Item Short Form Health Survey (SF-36).ResultsAt week 12, improvements in all PROs, apart from the SF-36 mental component in the add-on study, were statistically better with filgotinib than placebo; some improvements were noted as early as the first assessment time point (week 1 or week 4). Filgotinib improved HAQ-DI by 0.58–0.84 points, FACIT-Fatigue by 6.9–11.4 points, Patient Global by 25.2–35.6 mm, and Pain by 24.2–37.9 mm; scores were maintained or improved to week 24. Across all PROs, more patients achieved minimal clinically important differences and normative values with filgotinib 200 mg than placebo. Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in PROs between weeks 12 to 24.ConclusionsFilgotinib as MTX add-on therapy or as monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health-related quality of life and functional status in patients with active RA.Trial registrationMTX add-on study: ClinicalTrials.gov, NCT01888874. Registered on 28 June 2013. Monotherapy study: ClinicalTrials.gov, NCT01894516. Registered on 10 July 2013.

THU0206 The jak1-selective inhibitor filgotinib reduces multiple markers of inflammation linked to various pathologic cell types and processes in rheumatoid arthritis patients

Background JAK1, 2, 3 and TYK2 are cytoplasmic tyrosine kinases that mediate intracellular signaling of many cytokines and growth factors. Filgotinib (GLPG0634, GS-6034) is a JAK inhibitor with high selectivity for JAK1 over other JAK family members. Filgotinib has a favorable safety and efficacy profile in two Phase 2B studies in active rheumatoid arthritis (RA) patients who were methotrexate (MTX) inadequate responders. Objectives To assess the effect of filgotinib on a background of MTX treatment on markers of inflammation in RA patients. Methods Serum samples from RA patients who were on a stable dose of MTX and received either placebo (PBO), filgotinib 100mg or 200mg once daily (QD), were collected at baseline, week 4 and week 12 and analyzed for 35 soluble serum biomarkers by validated single-plex or multiplex immunoassays. Median % changes from baseline for biomarkers are reported. Wilcoxon rank-sum test assessed the significance of difference between filgotinib treated groups and PBO. Results Filgotinib treatment induced a dose-dependent and significant decrease in a variety of biomarkers implicated in RA pathogenesis including inflammation (IL-1β, IL-6, TNFα and SAA), matrix degradation and cartilage destruction (MMP1 and MMP3), immune cell trafficking (CXCL10, ICAM-1 and VCAM-1) and angiogenesis (VEGF). Cytokines involved in TH1 (IFN-γ, IL-2, IL-12) and TH17 (IL-1β, IL-6, IL-21, IL-23) cell subset differentiation and activity were significantly decreased. Additionally, decrease in the B-cell chemoattractant CXCL13 and the myeloid growth factor GM-CSF supports the anti-inflammatory effects of filgotinib treatment.Table 1. Median percent change of biomarkers at week 12 from baseline for PBO and 200mg QD dose PBO Filgotinib PBO Filgotinib PBO (N=78) Filgotinib (N=78) 200mg QD (N=78) 200mg QD (N=78) 200mg QD (N=75) (N=75) (N=75) BAFF -2 -6NS IL-2 -7 -20** MIP-1β 0 -7* CRP -8 -78*** IL-21 0 -28** MMP-1 -6 -26*** CXCL-13 3 -40*** IL-23 -6 -25*** MMP-3 -9 -43*** EGF 0 0NS IL-4 0 0NS RESISTIN -1 -16*** GM-CSF 0 -26*** IL-5 2 -14** SAA 7 -67*** ICAM-1 0 -14*** IL-6 -20 -63*** sgp130 0 4NS IFN-γ -2 -21* IL-7 1 -17*** TNF-α 1 -15*** IL-10 -3 -17** IL-8 -2 -12NS TNF-RI 0 -15*** IL-12 0 -24*** IP-10 -2 -31** VCAM-1 0 -16*** IL-13 -1 -8** LEPTIN 6 23* VEGF -2 -26*** IL-17A 2 -18* MCP-1 4 -8NS YKL-40 -7 -33*** IL-1β -2 -26*** MIP-1α 1 -8** p-values comparing % changes between filgotinib and PBO groups: NS, p>0.05; *p<0.05; **p<0.01; ***p<0.001. Conclusions Treatment with filgotinib decreased several factors that have key roles in RA for matrix degradation, cartilage destruction, angiogenesis, leukocyte adhesion and recruitment. The changes were accompanied by decreases in cytokines that promote and activate TH1, TH17, B-cells and myeloid cells that are important in RA. These findings provide insights into filgotinib mechanism of action and are consistent with its efficacy observed in RA patients. Disclosure of Interest P. Taylor Consultant for: Galapagos NV, Pfizer, Eli Lilly, UCB, GSK, R. Westhovens: None declared, A. Van der Aa Employee of: Galapagos NV, C. Jamoul Employee of: Galapagos NV, W. Li Employee of: Gilead Sciences, L. Goyal Employee of: Gilead Sciences, Y. Pan Employee of: Gilead Sciences, P. Harrison Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV, J. Tarrant Employee of: Gilead Sciences, R. Galien Employee of: Galapagos SASU

AB0494 Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, Shows Similar PK and PD Profiles in Japanese and Caucasian Healthy Volunteers

Background Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor combining a favorable safety profile and clinical efficacy in patients after 4 weeks of dosing with rheumatoid arthritis (RA) with a rapid onset of action. Its once-daily oral administration is supported by the long half-life of an active metabolite with the same JAK1 selectivity profile as the parent compound. Given ethnicity may cause for differences in drug metabolism and pharmacokinetics (PK), and pharmacodynamics (PD) resulting in variability in clinical response, filgotinib was studied in Japanese healthy volunteers to evaluate the potential for different dosing requirements compared to Caucasians. Objectives Compare the PK, PD and safety of filgotinib in Japanese to Caucasian healthy volunteers at 200 mg filgotinib. Methods In a single-center Phase 1 study, 2 panels of 10 Japanese (1st and 2nd generation residing outside Japan for less than 5 years) and 10 Caucasian healthy volunteers received once daily 200 mg filgotinib or placebo for 10 days. The PK of filgotinib and its active metabolite were evaluated, and the overall PD of the two moieties was assessed in whole blood using ex vivo IL-6 induced phosphorylation of STAT1 (pSTAT1) as biomarker for JAK1 activity and GM-CSF induced phosphorylation of STAT5 (pSTAT5) for JAK2 activity. Standard safety assessments were performed throughout the study duration. Results Steady state in filgotinib plasma concentrations was reached in 2 days in both Japanese and Caucasian volunteers with half-lives of 6 and 11 hours, respectively. In both ethnic groups, the active metabolite showed plasma concentrations well exceeding those of filgotinib with half-life values ranging of 17-20 hours and overall exposures for filgotinib and its metabolite being the same between the populations. In both ethnic groups, IL-6 induced pSTAT1 was inhibited over the entire 24 hour post-dosing period, with maximum inhibition observed between 1 and 5 hours post dose. No relevant inhibition of JAK2 activity was observed in Japanese and Caucasian healthy volunteers confirming the JAK1 over JAK2 selectivity of filgotinib. In Japanese healthy volunteers, filgotinib was generally safe and well tolerated with no relevant differences in safety profile as compared to Caucasian healthy volunteers. Conclusions Filgotinib showed comparable PK, PD and safety profiles in Japanese and Caucasian healthy volunteers. The similarity in the PK and PD response suggests that there are no relevant differences among the groups in drug metabolism or sensitivity to selective inhibition of JAK1. Thus, these data support that filgotinib could be safely administered without dose adjustment to Japanese RA patients. Disclosure of Interest F. Namour Shareholder of: GALAPAGOS, Employee of: GALAPAGOS, B. Vayssière Employee of: GALAPAGOS, R. Galien Shareholder of: GALAPAGOS, Employee of: GALAPAGOS, L. Fagard Employee of: GALAPAGOS, A. Van der Aa Shareholder of: GALAPAGOS, Employee of: GALAPAGOS, P. Harrison Shareholder of: GALAPAGOS, Employee of: GALAPAGOS, C. Tasset Shareholder of: GALAPAGOS, Employee of: GALAPAGOS

Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, a selective JAK1 inhibitor

Filgotinib (GS‐6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohns disease. The aim of the present study was to investigate the impact of age and renal impairment (RI) on the pharmacokinetics (PK) of filgotinib and its main metabolite.

SAT0231 Effects of the jak1-selective inhibitor filgotinib on gene expression profile in blood of patients with active rheumatoid arthritis

Background: Filgotinib (FIL), an oral selective JAK1 inhibitor, has shown good safety and efficacy in two phase 2b studies (background methotrexate (MTX, DARWIN 1) and as monotherapy (DARWIN 2)) in active rheumatoid arthritis (RA) patients with inadequate response to MTX1,2. We conducted a large-scale RNA sequencing study of genes expressed in blood samples from these studies. Objectives: Identify RA-associated gene transcripts that are altered in response to FIL treatment. Methods: PAXgene blood samples from 242 RA patients receiving either a stable dose of MTX and placebo (PBO) or FIL 200 mg once daily (QD, DARWIN 1); or PBO, FIL 100 mg, or 200 mg monotherapy QD (DARWIN 2), were collected and analyzed at baseline, week 1 and/or week 12. RNA in whole blood was sequenced (Illumina HiSeq 2500) after globin depletion. Differential gene expression analysis was performed on all time-paired data after subtracting gene expression changes in the PBO group. Spearman’s rank correlation of gene expression to time, dose, and disease activity score (DAS28) were calculated on samples without missing values. A false-discovery rate (FDR) of 10% was applied for all analyses Results: Top-ranked gene sets positively associated with DAS28 disease activity at baseline over both studies included interferon alpha (IFN-α) and IFN gamma (IFN-γ) response, IL6/JAK/STAT3 signaling, and toll-like receptor signaling pathways (FDR<10%). Of 197 genes that positively correlated with disease score (increased gene expression with increased DAS28, FDR<10%), 117 (59%) trended toward reduced expression at 12 weeks with FIL in both studies. These genes were enriched in pathways which included granulocyte and macrophage activation. Conversely, of 256 genes negatively correlated with disease score (FDR<10%), 169 (66%) trended toward increased expression post-FIL (figure 1). Of 14724 genes expressed at >1CPM in at least 5% of the samples, 607 were differentially expressed following FIL treatment in either DARWIN1 or DARWIN2 with 48 genes significant in both studies (FDR<10%). Genes reaching significance in at least one study showed consistent magnitude and direction of change in both studies and were enriched in JAK/STAT, innate and adaptive immunity, and autoimmune associated pathways. CISH, SOCS2, SOCS3, VWA5a, APCDD1, DNASE1L3, and PIM3 correlated with both duration of treatment and FIL dose (FDR<10%). CISH and SOCS confirm JAK pathway modulation. Figure 1 Heatmap of 453 DAS28-correlated genes and the corresponding change in gene expression with 12 wk FIL in Phase2b RA studies Conclusions: RA patients treated with FIL show reproducible changes in gene expression consistent with modulation of JAK/STAT signaling and innate and adaptive immunity. FIL was shown to partially reverse the dysregulated gene expression profile associated with baseline DAS28 score, consistent with the efficacy observed in RA patients. References [1]Kavanaugh A, et al. Ann Rheum Dis2017;76:1009–19. [2]Westhovens R, et al. Ann Rheum Dis2017;76:998–1008. Disclosure of Interest: P. Taylor Consultant for: AbbVie, Biogen, BMS, Galapagos, GSK, Janssen, Lilly, MSD, Novartis, Sandoz, UCB;, J. Tarrant Employee of: GSI Employee, L. Zhao Employee of: GSI Employee, Y. Gindin Employee of: GSI Employee, A. Mirza Employee of: GSI Employee, P. Harrison Employee of: GLPG Employee, C. Tasset Employee of: GLPG Employee, R. Galien Employee of: GLPG Employee, A. Van der Aa Employee of: GLPG Employee, B. Downie Employee of: GSI Employee