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Galapagos 2017. De inhoudelijke discussie

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Het is niet omdat je lange tekstjes schrijft, dat het allemaal klopt wat je schrijft.
Dat is intussen bij Rekyus al verschillende malen gebleken.
Wat betreft de discussie CMO vs CSO heeft hij zich gewoon vergist en hij probeert er nu een draai aan te geven.

Maar wat zijn de feiten: een CMO is een totaal andere functie dan een CSO.
En het is helemaal niet zo uitzonderlijk dat een midstage Biotech een CMO heeft, integendeel zelfs. Dat heeft totaal niets met multinationals te maken.
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0
De tweede paragraaf van dit tekstje omschrijft heel kort maar duidelijk wat de taak is van een CMO, waarom er nu een CMO komt en niet vroeger. Heeft dus helemaal niets te maken met een CSO, ook nauwelijks overlap.

www.beursduivel.be/Beursnieuws/158948...
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1
En nog meer lectuur:

www.nature.com/nbt/journal/v24/n10/fu...

Zo zie je maar. Niet altijd klakkeloos aannemen wat hier in het kort of lang wordt neergepend.
pe26
2
@Rekyus:wederom prima uiteenzetting.
Het is voor Galapagos management een weet en voor ons een vraag, wat vanzelf duidelijk wordt.

Ben zeer benieuwd hoe je tot deze beschouwingen komt.
De gemaakte analyses zijn evenwichtig en
moleculaire/chemische kennis is van zeer hoog niveau.

Fijn dat je regelmatig post.

Viel me trouwens op dat Galapagos binnen Investor Presentation Januari GLPG1972 sterk positioneert als molecuul dat zich onderscheid van andere geneesmiddelen die in ontwikkeling zijn.
Galapagos stelt: 'GLPG1972 is most advanced disease-modifying drug in OA (Osteo-Arthritis)'.

Verwachtingen zijn hooggespannen.

In Presentatie is te zien dat in H1 2017 Galapagos start met Fase 1b in USA. De IND-aanvraag is dan ingewilligd.

Eerder was intentie starten Fase 2(a). De snellere fase 1b studie kan vergaande inzichten opleveren, zonder de hoge kosten van Fase 2a.

Galapagos heeft eerder de fase 1 MAD-studie afgerond met 3 groepen (300mg/600mg/1.050mg) met ongeveer 12-14 deelnemers per groep inclusief placebo, veronderstelt op basis van 41 deelnemers.

Fase 1b USA zal een snelle doorlooptijd hebben op basis van beperkt te openen klinieken.
Stellingname is grotere populatie en langere behandelingsduur dan uitgevoerde Fase 1 te België wat meer inzicht geeft waar Galapagos in vervolg baat bij heeft.

Weet niet of vrijwilligers kunnen worden geworven, waarbij combnaties met huidige middelen als Back-Ground Therapie, zoals corticosteroïden onderdeel zijn van de studie om safety scores te kunnen staven.
Bij kankeronderzoek gebeurt dit veel in Fase1b.

Zie: www.medelis.com/clinical-cancer-resea...

Vraag me af wat uitstekende scores Fase1b kunnen betekenen t.a.v. opschakeling naar volgende fase. FDA zal veel belang hechten aan nieuw werkingsmechanisme wat kraakbeenverlies doet verminderen.

Ook benieuwd of in EU zelfde stap genomen gaat worden en of Servier in-licentie name verricht na die mogelijke studie- uitkomsten.
NielsjeB
0
maxen
0
quote:

NielsjeB schreef op 19 jan 2017 om 21:01:


Long Term Extension Study to Assess the Safety and Efficacy of Filgotinib in Adults With Rheumatoid Arthritis

clinicaltrials.gov/ct2/show/NCT03025308

Eigenlijk dus de Darwin 3 voor phase 3.
voda
0
Galapagos creeert nieuw warrantplan

150.000 nieuwe warrants voor CMO.

(ABM FN-Dow Jones) Galapagos heeft 150.000 nieuwe warrants gecreëerd onder een nieuw warrantplan ten gunste van een werknemer van een dochtervennootschap van het bedrijf. Dit meldde het Belgisch-Nederlandse biofarmaconcern vrijdagavond.

De Raad van Bestuur van Galapagos keurde op 20 januari het "Warrantplan 2016 (B)" goed, aldus het bedrijf. Het warrantplan is bestemd voor de kersverse chief medical officer, Dr. Walid Abi-Saab, en is goedgekeurd binnen het kader van het toegestaan kapitaal.

De warrants hebben een uitoefentermijn van 8 jaar vanaf de datum van het aanbod en een uitoefenprijs van 62,50 euro. De warrants zijn niet overdraagbaar en kunnen niet worden uitgeoefend voor de derde verjaardag van hun uitgifte. Elke warrant geeft het recht om bij uitoefening in te schrijven op één nieuw Galapagos aandeel.

Als de warrants worden uitgeoefend, zal Galapagos voor de daaruit voortvloeiende nieuwe aandelen een aanvraag indienen om ze te laten opnemen tot verhandeling op een gereglementeerde markt. De warrants op zich zullen niet worden genoteerd aan een beurs, zei het concern.

Het aandeel Galapagos sloot vrijdag vlak op 62,51 euro.

Door: ABM Financial News.

info@abmfn.nl

Redactie: +31(0)20 26 28 999

Copyright ABM Financial News. All rights reserved

(END) Dow Jones Newswires
twinkletown
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Nieuwe CMO van Galapagos krijgt 150.000 warrants
20-01-2017 22:22:43

Biotechbedrijf Galapagos geeft zijn nieuwe chief medical officer de kans om binnen drie jaar 150.000 aandelen te kopen tegen de slotkoers van donderdag.

De warrants hebben een uitoefentermijn van acht jaar en een uitoefenprijs van 62,50 euro. Dat is de slotkoers in Amsterdam en Brussel van 19 januari. Walid Abi-Saab kan ze ten vroegste binnen drie jaar uitoefenen De CMO komt op 1 maart in dienst bij Galapagos.

Het bedrijf laat nog weten dat het maatschappelijk kapitaal vandaag 250,19 miljoen bedraagt, verdeeld over 46,26 miljoen stemgerechtigde aandelen. Het aantal nog niet uitgeoefende warrants bedraagt 3,47 miljoen, dat is exclusief de 150.000 die aan Abi-Saab worden toegekend.

Galapagos eindigde vrijdag nagenoeg onveranderd op 62,51 euro.
Germanwings
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quote:

voda schreef op 20 jan 2017 om 22:27:


Galapagos creeert nieuw warrantplan

150.000 nieuwe warrants voor CMO.

(ABM FN-Dow Jones) Galapagos heeft 150.000 nieuwe warrants gecreëerd onder een nieuw warrantplan ten gunste van een werknemer van een dochtervennootschap van het bedrijf. Dit meldde het Belgisch-Nederlandse biofarmaconcern vrijdagavond.

END) Dow Jones Newswires


Is hier sprake van een nieuwe dochtervennootschap? en is Dr Ali-Saab daar dan werkzaam?

Hoe moet ik dit interpreteren?

abelheira
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harvester
0
quote:

Germanwings schreef op 21 jan 2017 om 10:44:


[...]

Is hier sprake van een nieuwe dochtervennootschap? en is Dr Ali-Saab daar dan werkzaam?

Hoe moet ik dit interpreteren?




Het lijkt inderdaad te suggereren dat het om een nieuwe dochtermatschappij gaat, maar dat hoeft ook niet zo te zijn.
De meeste werknemers zullen niet bij de beursgenoteerde holding werken.
Uiteindelijk zal de groep meer vennootschappen gaan omvatten als zij een verkoop organisatie gaan opzetten in meerdere landen en wellicht overnames gaan doen.
marcello106
2
quote:

Germanwings schreef op 21 jan 2017 om 10:44:


[...]

Is hier sprake van een nieuwe dochtervennootschap? en is Dr Ali-Saab daar dan werkzaam?

Hoe moet ik dit interpreteren?





Er is niets vreemds aan. Galapagos NV heeft diverse dochterondernemingen.

Zie pag 137.

reports.glpg.com/annual-report-2015/n...
NielsjeB
1
quote:

NielsjeB schreef op 17 jan 2017 om 23:07:


62: OP033: Reduction of tissue pSTAT3 in Crohn’s Disease patients treated with filgotinib (GLPG0634, GS-6034), a JAK1-selective inhibitor

Vermeire, S.1, De Hertogh, G.2, Chen, G.3, French, D.4, Huntzicker, E.4, Van der Aa, A.5, Van Kaem, T.5, Harrison, P.5, Tasset, C.5, Galien, R.6, Pan, Y.4, Feagan, B.7, Sandborn, W.8
1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium, 2University Hospitals Leuven, Department of Pathology, Leuven, Belgium, 3Gilead Sciences, Department of Biostatistics, Foster City, United States, 4Gilead Sciences, Biomarker Sciences, Foster City, United States, 5Galapagos NV, Mechelen, Belgium, 6Galapagos SASU, Romainville, France, 7Robarts Resaerch Institute, Ontario, Canada, 8University of California, Division of Gastroenterology, San Diego, United States

www.ecco-ibd.eu/index.php/discover-th...

OP033 Reduction of tissue pSTAT3 in Crohn's disease patients treated with filgotinib (GLPG0634, GS-6034), a JAK1-selective inhibitor
Vermeire S.*1, De Hertogh G.2, Chen G.3, French D.4, Huntzicker E.4, Van der Aa A.5, Van Kaem T.5, Harrison P.5, Tasset C.5, Galien R.6, Pan Y.4, Feagan B.7, Sandborn W.8

1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium 2University Hospitals Leuven, Department of Pathology, Leuven, Belgium 3Gilead Sciences, Department of Biostatistics, Foster City, United States 4Gilead Sciences, Biomarker Sciences, Foster City, United States 5Galapagos NV, Mechelen, Belgium 6Galapagos SASU, Romainville, France 7Robarts Resaerch Institute, Ontario, Canada 8University of California, Division of Gastroenterology, San Diego, United States

Background
Janus kinases (JAK) are a family of tyrosine kinases that play a key role in the signalling of more than 60 cytokines and growth factors. Many of these cytokines display pro-inflammatory activity in Crohn's Disease (CD). The selective JAK1 inhibitor filgotinib blocks cytokine signalling through the inhibition of STAT phosphorylation and has shown clinical efficacy in a double-blind, placebo-controlled Phase 2 study in CD (FITZROY). In order to understand the mechanism of action of filgotinib in CD patients, we measured the level of pSTAT3 in gut biopsies from this study.

Methods
CD patients were randomized 3:1 to receive 200mg filgotinib or placebo QD for the first 10 weeks. Two biopsies, one each from the most and least affected mucosa, were collected during screening and at Wk 10 from each of the 6 predefined segments of the lower gastrointestinal tract. Samples from 60 patients with complete set of paired biopsies were selected. pSTAT3 was evaluated by IHC using an antibody specific to phosphorylated Y705. H-Score was quantified using Definiens Tissue Studio software. The mixed effect ANOVA method was used for evaluating the treatment effect and difference between patients achieving clinical remission (defined as CDAI <150) and those who did not.

Results
Basal pSTAT3 level was comparable for the filgotinib and placebo groups. Following filgotinib treatment, pSTAT3 level was significantly reduced in the most affected mucosa from all segments combined: -36% (95% CI: -51%, -17%), whereas reduction in the placebo arm was not significant (although with less subjects): -24% (95% CI: -49%, +14%). In patients with clinical remission at Wk 10, pSTAT3 levels showed a significant reduction from baseline in each group: -62% (95% CI: -83%, -16%) with placebo, and -42% (95% CI: -57%,-21%) with filgotinib. In patients not achieving clinical remission, pSTAT3 from the placebo arm showed an average numerical increase of +12% (95% CI: -21%, +94%) whereas pSTAT3 was on average reduced with filgotinib: -28% (95% CI: -51%, +7%). Similar observations were made in the least affected mucosa of different segments.


Table 1. Percent reduction of pSTAT3 at Week 10 from most affected area in all segments in CD patients


Conclusion
Significant reduction of pSTAT3 by filgotinib on inflamed gut of CD patients provides direct evidence of its anti-inflammatory effect. Clinical remission status is associated with a decrease in pSTAT3. In non-remitters, the observed pSTAT3 reduction with filgotinib illustrates its pharmacodynamic effect through JAK1 inhibition. A large phase 3 program in CD and UC is ongoing.


www.ecco-ibd.eu/index.php/publication...
NielsjeB
0
DOP075 Efficacy of filgotinib, a selective JAK1 inhibitor, is independent of prior anti-TNF exposure: subgroup analysis of the phase 2 FITZROY study in moderate-to-severe Crohn's disease

D'Haens G.1, Schreiber S.2, Petryka R.3, Kuehbacher T.4, Hebuterne X.5, Roblin X.6, Klopocka M.7, Goldis A.8, Wisniewska-Jarosinska M.9, Baranovsky A.10, Sike R.11, Stoyanova K.12, Meuleners L.13, Tasset C.13, Van der Aa A.13, Harrison P.13, Vermeire S.*14

1Academic Medical Center (AMC), Department of Gastroenterology, Amsterdam, Netherlands 2University Medical Center Schleswig-Holstein Kiel, Department of Internal Medicine I, Kiel, Germany 3Vivamed, Warsaw, Poland 4Asklepios Hospital West Hamburg, Department of Gastroenterology, Hamburg, Germany 5CHU Nice Hopital l'Archet, Department of Gastroenterology and Nutrition, Nice Cedex 3, France 6North Hospital, Department of Gastroenterology, Saint Priez en Jarez, France 7NC University in Torun, Collegium Medicum, Bydgoszcz, Poland 8Dr. Goldis Center for Gastroenterology, Ltd., Timisoara, Romania 9Santa LLC, Santa Familia Research, Prevention and Treatment Centre, Lodz, Poland 10City Clinical Hospital #31, St. Petersburg, Russian Federation 11Szent Margit Hospital, Budapest, Hungary 12PSI Pharma Support EOOD, Sofia, Bulgaria 13Galapagos NV, Mechelen, Belgium 14University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium

Background
Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor. This 20-week Phase 2 study evaluated efficacy and safety of filgotinib in patients with active Crohn's disease (CD). The primary endpoint (CDAI remission at Week 10) was met with an acceptable safety profile. Here, an exploratory subgroup analysis of the first 10 weeks, based upon prior exposure to anti-TNF therapy, is presented.

Methods
174 patients with moderate-to-severely active CD (CDAI: 220 to 450) and ulcerations confirmed by centrally read endoscopy were randomized 3:1 to receive 200mg filgotinib (FIL) or placebo (PBO) QD for 10 weeks. Immunosuppressants were to be discontinued prior to treatment initiation but corticosteroid-treated patients remained on stable doses until Week 10. Patients naïve to anti-TNF therapy as well as patients who were previously exposed to anti-TNF with no response or loss-of-response were included. Endpoints include clinical outcome (CDAI), patient-reported outcomes (PRO: CDAI and IBDQ), histopathology (D'Haens score) and combined clinical-biological response (CDAI and biomarkers).

Results
Baseline characteristics were similar in FIL and PBO groups, including mean disease duration (8.3 years), mean CDAI score (293), mean CRP (15.6mg/L, 41%>10mg/L), oral corticosteroids (51%, mean daily dose 20.8 mg/day). 42% of the patients were anti-TNF naïve, 58% were anti-TNF non-responder. Clinical remission (CDAI<150) was induced at Week 10 in 47% of FIL patients versus 23% on PBO (p=0.0077).

CDAI remission and response were higher in the FIL group versus PBO irrespective of prior anti-TNF therapy. PRO measured by changes from baseline in PRO2 score and general well-being (CDAI component), as well as quality of life assessed by IBDQ improved more in both FIL subgroups compared to PBO. A combined clinical-biological response endpoint confirmed these findings in the subgroup with elevated CRP or faecal calprotectin at baseline. Histopathology at Week 10 showed numerically greater effects after FIL treatment versus PBO for both subgroups (Table 1).

FIL was safe and well tolerated. Similar incidences in SAEs, TEAEs leading to discontinuation and infections were observed in both anti-TNF subgroups, with a somewhat higher incidence of TEAEs in anti-TNF non-responders.


Table 1

Variable/unit/population Anti-TNF naive Anti-TNF non-responder
PBO=16 FIL=57 PBO=28 FIL=71
Clinical remission (CDAI<150), %, ITT-NRI 13 60 29 37
100-points clinical response (CDAI improvement with =100 points), %, ITT-NRI 44 67 39 54
PRO2 score, mean change from baseline, ITT-LOCF (7×(mean daily number of liquid or very soft stools + 7×(mean daily abdominal pain score)) -19.8 -24.8 -13.2 -19.5
PRO2 remission (PRO2 =28), %, ITT-NRI 31 61 29 41
CDAI general well-being score, mean change from baseline, ITT-LOCF -0.78 -1.08 -0.58 -0.90
Total IBDQ score, mean change from baseline, ITT-LOCF 19.7 40.8 16.3 28.2
Overall total histopathology score, mean change from baseline, ITT-LOCF -0.3 -3.9 -0.7 -3.2
Anti-TNF naive Anti-TNF non-responder
PBO=9 FIL=39 PBO=18 FIL=54
Combined clinical-biological response, %, ITT-NRI (CDAI score <150 points and CRP decrease >50% and/or fecal calprotectin decraese >50% from baseline) 36 6 20
CDAI: Crohn's Disease Activity Index; ITT: Intent-to-treat; NRI: Non-responder imputation; LOCF: Last observation carried forward; IBDQ: Inflammatory Bowel Disease Questionnaire; ITT population = 172 patients (2 pts without post-baseline assessments).

Conclusion
Efficacy of filgotinib was shown in CD patients independently of their prior anti-TNF exposure, and was consistent across all endpoints. The safety profile was also similar. These data suggest a favourable risk/benefit profile, in both anti-TNF naives and anti-TNF non-responders.

www.ecco-ibd.eu/index.php/publication...
NielsjeB
0
OP023 Maintenance of clinical effect in patients with moderate-to-severe Crohn's disease treated with filgotinib, a selective JAK1 inhibitor: exploratory 20-week data analysis of the phase 2 FITZROY study

Vermeire S.*1, Schreiber S.2, Petryka R.3, Kuehbacher T.4, Hebuterne X.5, Roblin X.6, Klopocka M.7, Goldis A.8, Wisniewska-Jarosinska M.9, Baranovsky A.10, Sike R.11, Stoyanova K.12, Meuleners L.13, Tasset C.13, Van der Aa A.13, Harrison P.13

1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium 2University Medical Center Schleswig-Holstein Kiel, Department of Internal Medicine I, Kiel, Germany 3Vivamed, Warsaw, Poland 4Asklepios Hospital West Hamburg, Department of Gastroenterology, Hamburg, Germany 5CHU Nice Hopital l'Archet, Department of Gastroenterology and Nutrition, Nice Cedex 3, France 6North Hospital, Department of Gastroenterology, Saint Priez en Jarez, France 7NC University in Torun, Collegium Medicum, Bydgoszcz, Poland 8Dr. Goldis Center for Gastroenterology, Ltd., Timisoara, Romania 9Santa LLC, Santa Familia Research, Prevention and Treatment Centre, Lodz, Poland 10City Clinical Hospital #31, St. Petersburg, Russian Federation 11Szent Margit Hospital, Budapest, Hungary 12PSI Pharma Support EOOD, Sofia, Bulgaria 13Galapagos NV, Mechelen, Belgium

Background
Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor, which demonstrated efficacy in patients with rheumatoid arthritis. This 20-week Phase 2 study evaluated the efficacy and safety of filgotinib in patients with moderate-to-severely active Crohn's disease (CD). The primary endpoint (CDAI remission at Week 10) was met with an acceptable safety profile. Here, efficacy data from the exploratory Week 10–20 period as well as overall safety data are presented.

Methods
174 patients with moderate-to-severely active CD (CDAI: 220 to 450) and ulcerations confirmed by centrally read endoscopy were randomized 3:1 to receive 200mg filgotinib (FIL) or placebo (PBO) QD for 10 weeks. Immunosuppressants were to be discontinued prior to treatment initiation but corticosteroid-treated patients remained on stable doses until Week 10. Based on clinical response at Week 10 (CDAI decrease from baseline =100, as calculated by the investigator), patients were assigned to FIL (200mg or 100mg QD) or PBO for an additional 10 weeks. Patients assessed as clinical responders underwent mandatory corticosteroid tapering after Week 10. The second part of the study was exploratory.

Results
Baseline characteristics were similar in both initial treatment groups, including mean disease duration (8.3 y), mean CDAI score (293), mean CRP (15.6 mg/L, 41%>10mg/L), oral corticosteroids (51%, mean daily dose 20.8 mg/day).

At Week 20, 50–71% of initial FIL 200mg responders showed clinical remission and 67–79% showed clinical response, depending on their assignment to FIL 200mg QD, FIL 100mg QD or PBO. The FIL initial responders also maintained their gains in quality of life, as revealed by an IBDQ score at Week 20 that was at least 38.1 points higher than baseline. 59% (13/22) of patients not responding to PBO after 10 weeks showed clinical response at Week 20 upon being switched to FIL 100mg QD, and 32% (7/22) showed clinical remission.

The proportion of patients experiencing at least one TEAE was 75% with FIL (all periods of FIL exposure) and 67% with PBO (all periods of PBO exposure). Serious TEAEs occurred in 9% of FIL patients and 4% of PBO patients. TEAEs leading to discontinuation occurred in 18% for FIL and 9% for PBO. Serious infections were reported in 3% of FIL patients, and none in the PBO group.

Conclusion
Clinical efficacy, induced with filgotinib after 10 weeks of treatment, as well as IBDQ improvements were sustained through Week 20 despite mandatory steroid tapering. 100mg filgotinib also showed efficacy, however this needs to be further evaluated. The efficacy and safety data of filgotinib suggest a favourable risk/benefit profile.

www.ecco-ibd.eu/index.php/publication...
NielsjeB
0
P047 Therapeutic dosing of filgotinib (GS-6034, GLPG0634) is efficacious in the mouse DSS model of colitis

Kim S., Zheng J., Lu B., Alonzo D., Kanwar B., Smith V.

Gilead Sciences, Inc, Foster City, United States

Background
Janus kinase (JAK) family proteins, JAK1, JAK2, JAK3, and TYK2, are key non-receptor tyrosine kinases, activated by common gamma chain cytokines, interferons, and other growth factors. Filgotinib (GS-6034) is a selective JAK1 inhibitor. Recently completed clinical phase 2 trials in RA and Crohn's disease demonstrated clinical benefits in patients with an acceptable safety profile relative to pan-JAK inhibitors. Previously, preclinical benefits of GS-6034 were demonstrated in a preventive mode in a murine model of dextran sulfate sodium (DSS)-induced colitis. Here, we evaluated preclinical benefits of therapeutic dosing of GS-6034 in the DSS-induced colitis model.

Methods
Colitis was induced in female C57BL/6 mice (n=15/group) by 4% DSS in drinking water for 7 days. GS-6034 (30, 10, and 3 mg/kg) was orally administered once daily beginning on Day 5, once disease had been established, until Day 14 at study completion. Efficacy was assessed via disease activity index (DAI: stool consistency, hemoccults, and body weight change) and histopathological measures (inflammation, gland loss, erosion, and hyperplasia), both accepted metrics of colitis.

Results
All animals were included in the evaluation. 30 mg/kg of GS-6034 demonstrated efficacy in all measures including body weight change, stool consistency, hemoccults, colon length and weight, and histopathological assessment. 10 mg/kg of GS-6034 demonstrated efficacy in some measures including body weight change and colon length and weight. Disease-induced body weight loss was improved in 30 and 10 mg/kg of GS-6034 groups (37% and 28%, respectively; vehicle as 0%; sham as 100%; p<0.05 to vehicle). DAI score was lower in 30 mg/kg of GS-6034 group (67% to vehicle as 100%, p<0.05 to vehicle) and showed a trend of reduction in 10 mg/kg of GS-6034 group. Normal stool consistency was well maintained in 30 mg/kg GS-6034 group throughout the study period (185% to vehicle as 100%, p<0.05 to vehicle). None of animals in 30 mg/kg GS-6034 group showed diarrhea throughout the study period. The median ratio of colon weight/ length (mg/ cm) was 34 in 30 and 10 mg/kg of GS-6034 groups vs. 45 in vehicle group (p<0.05 to vehicle; 22 in sham group). The sum of histopathology measures was 3.9 in 30 mg/kg of GS-6034 group vs. 6.8 in vehicle group (p<0.05 to vehicle).

Conclusion
Therapeutic dosing of GS-6034 dose dependently slowed disease progression and demonstrated efficacy in all measures of disease activity.

www.ecco-ibd.eu/index.php/publication...
NielsjeB
0
P610 Efficacy and safety of GLPG1205, a GPR84 antagonist, in ulcerative colitis: multi-centre proof-of-concept study

Vermeire S.*1, Reinisch W.2,3, Wasko-Czopnik D.4, Van Kaem T.5, Desrivot J.6, Vanhoutte F.5, Beetens J.5

1University Hospital Leuven, Gastroenterology, Leuven, Belgium 2McMaster University, Gastroenterology, Hamilton, Canada 3Medical University Vienna, Gastroenterology & Hepatology, Vienna, Austria 4Medical University of Wroclaw, Gastroenterology & Hepatology, Wroclaw, Poland 5Galapagos NV, Development, Mechelen, Belgium 6Galapagos SASU, Development, Romainville, France

Background
GPR84, a GPCR activated by medium-chain free fatty acids, is primarily expressed on white blood cells (polymorphonuclear, monocyte/macrophage). GLPG1205 is a potent and selective antagonist of GPR84, inhibiting GPR84-induced neutrophil migration in vitro. In a mouse IBD model (DSS), GLPG1205 dose-dependently decreased disease activity, histological activity, neutrophil influx as well as colonic MPO content.

Methods
The efficacy and safety of GLPG1205 in moderate-to-severe UC (Mayo score 6–12 with an endoscopic subcore of =2) was evaluated in an exploratory, double-blind study, in 63 patients (aged 18–75) treated for 12 weeks with 100 mg q.d. GLPG1205 or placebo (pbo) in a 2:1 randomization (NCT02337608). A stable background of 5-aminosalicylates, immunosuppressants or steroids was allowed. Mayo scores and biopsies for Geboes scores and myeloperoxidase (MPO) positive cells (immunohistochemistry) were collected at baseline (BL) and week 8. Fecal calprotectin (FC), subscores for partial Mayo and PK were evaluated at BL and week 4, 8 and 12.

Results
Baseline characteristics, including duration of disease (6.9 y), prior and concomitant medication, Mayo score, FC, MPO positive cells were similar in both groups. At primary endpoint (W8), there was no statistically significant difference in Mayo score, Mayo clinical response, clinical remission, mucosal healing, Geboes Index, and histological response (MPO) between GLPG1205 and placebo (see table). Over the total 12-week treatment period, no treatment difference was observed in the partial Mayo score, the Mayo sub-scores or FC changes. GLPG1205 was well tolerated. Worsening of colitis, leading to study discontinuation, was reported by 4 patients (3 GLPG1205, 1 placebo). Patients showed a good drug exposure with average plasma concentrations within the range of exposures observed in healthy subjects.


Outcome parameter Time Placebo GLPG1205 (100 mg QD) p-value
(N=21) (N=40)
Mayo score (mean) BL 8.7 8.7
Week 8 6.3 6.3 0.5005
Mayo response (%)1 Week 8 48% 40% 0.6143
Mayo remission (%)2 Week 8 5% 5% 0.9084
Mucosal healing (%)3 Week 8 10% 5% 0.6261
MPO positive cells (median) BL 5% 7%
Week 8 5% %
Fecal calprotectin (median) (mg/kg) BL 325 335
Week 8 189 264
1Decrease in Mayo score =3 points and =30% and a decrease in rectal bleeding =1 or an absolute score 0/1. 2Mayo score =2 and no individual subscore >1. 3Endoscopy subscore 0 or 1. BL = baseline.

Conclusion
In this 12-week first-in-patient study with a GPR84 antagonist in patients with moderate to severe UC, GLPG1205 was well-tolerated. Compared to placebo, GLPG1205 had no effect on the clinical parameters or on the biomarkers related to the mode of action (FC or MPO). Therefore, our data suggest that inhibition of GPR84-mediated processes on inflammatory cells may not be relevant in the pathophysiology of active UC.

www.ecco-ibd.eu/index.php/publication...
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