R&D update - Galapagos NVfiles.glpg.com/docs/website_1/RD_update_FINAL.pdf · 2011 . 2012 . AbbVie...
Transcript of R&D update - Galapagos NVfiles.glpg.com/docs/website_1/RD_update_FINAL.pdf · 2011 . 2012 . AbbVie...
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This presentation may contain forward-looking statements, including, without limitation, statements containing the words “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continues” as well as similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which might cause the actual results, financial condition, performance or achievements of Galapagos, or industry results, to be materially different from any future results, financial conditions, performance or achievements expressed or implied by such forward-looking statements. Given these uncertainties, the audience is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as at the date of this presentation. Galapagos expressly disclaims any obligation to update any such forward-looking statements in this presentation 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, unless required by law or regulation.
Neither Galapagos nor any of its officers, employees, advisers, or agents makes any representation or warranty, express or implied, as to any matter or as to the truth, accuracy, or completeness of any statement made in this presentation, made in conjunction therewith or in any accompanying materials or made at any time, orally or otherwise, in connection with the matters referred to herein and all liability in respect of any such matter or statements is expressly excluded.
Disclaimer
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Executive team
Founded Galapagos in 1999 Previously MD Genomics at Crucell
Onno van de Stolpe CEO
Previously CFO of Wolters Kluwer Health Registered Accountant
Guillaume Jetten CFO
Previously VP Drug Discovery at Tibotec Brought 3 HIV drugs to market, including Prezista™
Piet Wigerinck CSO
Previously MD Corporate Development Europe at Invitrogen Architect of Abbott GLPG0634 deal and Galapagos’ alliances
Andre Hoekema Sr VP Corp Dev
Previously founder CSO and Board Director at Argenta > 50 publications and patents on the discovery of new drugs
Chris Newton Sr VP Services
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R&D Update
• Company strategy Onno van de Stolpe, CEO
• R&D portfolio Piet Wigerinck, CSO
• 2013 Outlook Onno van de Stolpe, CEO
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Galapagos: leading European biotech
• Two selective JAK1 molecules in Phase 2 in three indications
• Major risk sharing alliances with pharma
• Large pipeline: 4 clinical, 6 PCC, >30 discovery programs
• Leading fee-for-service provider with BioFocus & Argenta
• 800 staff, research sites in 5 countries, HQ in Belgium
• Ticker symbol
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How we built Galapagos
1999 2002 2005 2006 2009 2010
1st profitable
year
1st pharma alliance
Acquired BioFocus
IPO on Euronext
VC financing
Founded by Tibotec and Crucell
Acquired Argenta and GSK Zagreb
First novel target with clinical PoC
2011 2012
AbbVie deal
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Revenue generating business model
New mode-of-action medicine platform
Fee-for-service
Alliance business
Licensing
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Indication Partner Deal value Year
Inflammation $260 M + royalties 2006
Inflammation $1.3 B + royalties 2007
Osteoarthritis $390 M + US rights + royalties 2010
Oncology $340 M + US rights + royalties 2011
Autoimmune $1.35 B + double-digit royalties 2012
Pharma alliances
• Alliances have brought in >$440 M in cash since 2006 • Source of promising molecules and targets for GLPG
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Deal structure with AbbVie • Upfront payment $150 million
• Galapagos performs & funds Phase 2 in RA
• License fee $200 million after Phase 2b completion
• AbbVie performs & funds Phase 3, registration & commercialization
• GLPG to receive up to $1 billion in milestones + double digit royalties
• Tax benefits from Belgian Patent Income Deduction law
Phase 2
handover after
Phase 2b
Phase 3 Marketing and sales
Benelux
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Broad pipeline
Indications Company Target Lead program: stage
RA AbbVie JAK1 ‘634: Phase 2b
Lupus & Psoriasis GSK JAK1 ‘184: Phase 2
Metastasis IRA ‘187: Phase 1b
IBD GPR43 ‘974: Phase 2 start
MRSA DNA pol IIIα PCC
Inflammation JnJ novel 2 PCC’s
Osteoarthritis Servier/GLPG novel PCC
Inflammation GSK novel 2 PCC’s
Oncology Servier/GLPG novel Lead optimization
Cystic fibrosis novel Lead optimization
4 clinical programs, 6 PCC’s >30 discovery programs
Licensing
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Growth strategy
• Execute development of JAK1 program to Phase 2b results late 2014
• Build mature clinical portfolio – partnered and non-partnered
• Increase share of non-partnered programs
• Continue profitable and productive pharma alliances
• Sign new alliances and partnerships to leverage our technology
• Grow Service division revenues
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R&D Update
• Company strategy Onno van de Stolpe, CEO
• R&D portfolio Piet Wigerinck, CSO
• 2013 Outlook Onno van de Stolpe, CEO
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‘634 validates our approach 8 years from assay development to Phase 2 data
2003 2005 2006 2009 2010
PCC nomination
Hit Finding
JAK1 selected
Target Discovery
Assay Development
Start Phase 1 trial
Start PoC
2011
End PoC
2004
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‘634 in RA
• Selective JAK1 inhibitor in development for rheumatoid arthritis (RA)
• JAK1 selectivity could lead to better safety profile than current JAK
inhibitors
• ‘634 showed good efficacy & safety in POC trial in RA patients
• Good results confirmed in Phase 2a trial
• Phase 1 drug interaction study in the US ongoing
• Start Phase 2b program in June 2013
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JAKs in RA
Company RA drug JAK profile Phase
Pfizer Xeljanz® JAK3 >JAK1>JAK2 Approved in RA
Incyte/Lilly baricitinib JAK1=JAK2 Phase 3
Vertex VX-509 JAK3 Phase 2
GLPG/AbbVie ‘634 JAK1 Phase 2
Astellas/JnJ ASP015K JAK3/JAK1 Phase 2
Incyte INCB039110 JAK1/JAK2 Phase 2
‘634: opportunity to differentiate from other JAK inhibitors
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Design PoC vs Phase 2a Moderate to severe RA patients
PoC Phase 2a
# patients on stable MTX 36 91
doses Placebo vs 200 mg daily (100 mg BID, 200 mg QD)
Placebo vs 30, 75, 150, 300 mg QD
duration 28 days 28 days
study centers 1 19
countries Moldova Hungary, Moldova Russia, Ukraine
PoC: designed to give rapid evaluation Phase 2a: extended version of PoC
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Results PoC vs Phase 2a Moderate to severe RA patients
PoC Phase 2a
Efficacy
ACR √ √ DAS28 √ √ CRP √ √
HAQ-DI - √
Good efficacy & unique safety profile confirmed
Safety
Discontinuations none none
SAE none none
LDL cholesterol stable stable
Liver enzymes stable stable
Anemia absent absent
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‘634 Phase 2b program in RA Moderate to severe RA patients with inadequate MTX response
Add-on to MTX
Monotherapy
Long term extension
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Design RA Phase 2 studies
POC Add-on to MTX 12/24 w Monotherapy Long-term
Follow-up
‘634
36 + 91 pt, 4w Add-on to MTX Biologics naïve
Xeljanz® 264 pt, 6 w Monotherapy 509 pt 384 pt, 12/24 w
(vs adalimumab) Yes
Baricitinib 127 pt, 12/24 w Add-on to DMARDs 301 pt - Yes
VX-509 - 350 pt 164 pt, 12 w Yes
ASP015K - 375 pt, 12 w only 275 pt, 12 w Yes
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Add-on to MTX 7 equal cohorts
25 mg BID
50 mg BID
100 mg BID
Placebo
Week 0
200 mg QD
100 mg QD
50 mg QD
25 mg BID
50 mg BID
100 mg BID
Placebo
200 mg QD
100 mg QD
50 mg QD
Week 24 Study end
Week 12 Primary endpoint
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Add-on to MTX
25 mg BID
50 mg BID
100 mg BID
Placebo
Week 0 Week 24 Study end
Week 12 Primary endpoint
* if 20% improvement in SJC and TJC not achieved
R randomization
200 mg QD
100 mg QD
50 mg QD
25 mg BID
50 mg BID
100 mg BID
Placebo
200 mg QD
100 mg QD
50 mg QD
R
*
*
*
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50 mg QD
Placebo
50 mg QD
Week 0 Week 24 Study end
Week 12 Primary endpoint
100 mg QD
200 mg QD
100 mg QD
200 mg QD
Monotherapy 4 equal cohorts
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50 mg QD
Placebo
50 mg QD
Week 0
* 100 mg QD
200 mg QD
100 mg QD
200 mg QD
Monotherapy
* if 20% improvement in SJC and TJC not achieved
Week 24 Study end
Week 12 Primary endpoint
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ʃʃ
Darwin 2 Monotherapy QD
Darwin 3 100 mg BID
Week 0 …Week 260 Week 24 = BL for Long Term Follow Up
Darwin 1 MTX add-on BID
Darwin 1 MTX add-on QD
Darwin 3 200 mg QD
Long term extension
Option
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Design RA Phase 2 studies
POC Add-on to MTX 12/24 w Monotherapy Long-term
Follow-up
‘634
36 + 91 pt, 4w Add-on to MTX Biologics naïve
Yes
Xeljanz® 264 pt, 6 w Monotherapy 509 pt 384 pt, 12/24 w
(vs adalimumab) Yes
Baricitinib 127 pt, 12/24 w Add-on to DMARDs 301 pt - Yes
VX-509 - 350 pt 164 pt, 12 w Yes
ASP015K - 375 pt, 12 w only 275 pt, 12 w Yes
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‘634 Phase 2b program Geography
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Timelines ‘634 in RA
2013 2014
1st patient in
Trial application submissions
Last patient at 12 wk analysis
Topline 12 wk Darwin 1 & 2
Last Patient in
Presentations at major conferences
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GSK alliance History
2006 2009 2012 2013
GLPG platform quickly generates Phase 2 molecules
1st candidate
Start alliance
5th candidate
2 compounds inlicensed
(GLPG0778/0555) GSK Progresses GSK 2586184
(GLPG0778) into Phase 2
First program in the clinic
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GSK alliance Clinical studies with GSK2586184 (previously ‘778)
• GSK2586184 is an investigational selective JAK1 inhibitor in Phase 2
• GLPG performed innovative Phase 1 study
1. safety, PK study
2. inhibition inflammation pathway
• Results: dose-dependent, statistically-significant suppression of an induced inflammatory response specific inhibition of target in vivo
• Upon these results, GSK inlicensed GSK2586184 and its back-up GLPG0555 and progresses the compound into Phase 2
eligible to receive $45 M future milestones
up to double-digit royalties on global commercial sales
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Phase 2 studies with GSK2586184 GSK led studies
• Systemic lupus erythematosus
dose range 50 to 400 mg, oral BID vs placebo for up to 12 weeks
approx 150-250 patients in 66 centers in Europe, South America, Asia
primary Outcome Measures include: SELENA SEDAI score, interferon biomarkers
estimated study completion June 2014
• Chronic plaque psoriasis
oral BID for up to 12 weeks in UK and Germany
cohort A: dose range 100, 200, 400 mg vs placebo, estimated 56 patients
cohort B: open-label skin biopsy gene expression study, estimated 8 patients
estimated study completion December 2013
Source: ClinicalTrials.gov
Galapagos milestone payment upon successful POC
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‘974 Inhibits novel target for inflammatory diseases
• GPR43 (FFA2) is a GPCR
ligand: Short Chain Fatty Acids (SCFA)
SCFAs induce human neutrophil chemotaxis GPR43 plays key role in neutrophil biology
mainly expressed on immune cells, GI epithelium, and adipocytes
• GPR43 is upregulated in gut tissue of IBD patients
• GLPG0974 is a potent & selective antagonist of human GPR43
reduces migration of neutrophils
first inhibitor of GPR43 to be evaluated clinically
no animal models available
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‘974 mode of action SCFA induced neutrophil migration
• Inflammation
• Loose interactions between endothelial cells & neutrophils
• Neutrophil rolling
• Interaction CD11b with ICAM1
• Neutrophil adherence
• Neutrophil migration to site of inflammation by interaction with chemokines
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‘974 Results multiple ascending dose (MAD) study
Pharmacokinetics (Day 13) Pharmacodynamics (Day 13) Acetate-induced CD11b up regulation
Dose-proportional increase in exposure, 24 h inhibition at 200 mg BID
32 healthy volunteers, 4 cohorts, per cohort 6 active & 2 placebo
1
10
100
1000
10000
0 4 8 12 16 20 24
GLP
G09
74 (
ng/m
L)
Hours post dose
-60
-40
-20
0
20
40
60
80
100
0 4 8 12 16 20 24%
inhi
biti
on v
s pr
edos
e D
1 Time after last dosing (h)
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‘974 MAD study Conclusion
• Well tolerated and safe
no relevant treatment-emergent AEs
no relevant effects on lab safety parameters, ECGs and vital signs
• Excellent pharmacokinetics
good and dose-proportional exposure
terminal half life of 5.5 h
• Good pharmacodynamics
dose-dependent response
inhibition during 24 h, sustained over 14 days
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About ulcerative colitis
• Disease of the colon characterized by ulcers
• Intermittent disease with periods of exacerbated
symptoms, and relatively symptom-free periods
• Main symptom of active disease is constant diarrhea mixed with blood
• Peak incidence between 15 and 25 years
• Prevalence 200-250 per 100.000 individuals per year
• Total market value by 2021¹: $3.7 B
1 Source: Decision Resources
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‘974 PoC in ulcerative colitis
• 45 patients with mild to moderate ulcerative colitis
• 4 week dosing, 200 mg BID vs placebo
• Four countries: Belgium, Slovakia, Czech Republic, Latvia
• Evaluate safety & tolerability, characterize PK
• Explore efficacy & effects on selected biomarkers
mayo score, Partial Mayo score & histopathological Geboes index
faecal calprotectin, serum CRP, MPO in biopsies
Phase 2 PoC results expected Q1 2014
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‘187 vs Cilengitide
GLPG0187 Cilengitide
Small molecule Peptide
Highly potent in vitro cell assays Moderately potent in vitro cell assays Improvement in survival in animal model No effect on survival in animal model
Clinical i.v. dosing (continuous infusion) Clinical i.v. dosing (1h infusion 2x/wk)
Good clinical safety profile Good clinical safety profile
Comparative integrin receptor inhibition spectrum
Integrin binding affinity IC50 (nM) <10nM; 10-100nM; >100nM
αvβ1 αvβ3 αvβ5 αvβ6 αvβ8 α5β1
Cilengitide 11 6 5 122 436 30.5
GLPG0187 1 4 2 1 1 8
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‘187 status • Cilengitide (Merck-Serono)
missed primary endpoint Phase 3 study in GBM study
most advanced compound in class of RGD-integrin antagonists
GBM patients, MGMT-positive patients, on top of SOC
further analysis pending
• GLPG0187
enrollment completed for Phase 1b safety study
end-stage solid tumor patients
no treatment related adverse events
additional patients included following request of investigators
confirm early sign of clinical response in GBM patients
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About Cystic Fibrosis
• Fatal inherited disease of the lungs & digestive
system
• Debilitating disease, impairs quality of life
• Life expectancy: 37 years
• 70,000 patients worldwide, 30,000 in the US
• Patients carry a defective gene/protein (CFTR)
CFTR channel transports chloride across cell membrane
5 different classes of mutations
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Surface liquid allows cilia to efficiently clear mucus, particles and pathogens to maintain airway health
1. Dehydration of airway surface liquid
2. Mucus builds up on cilia, particles and pathogens become trapped
3. Lung infection
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Most CF patients are Class II (ΔF508) We target the main mutation
Representative genotype
W1282X ΔF508 G551D R117H D1152H
3849+10kb C→T
Allele frequency ~6% ~70% ~3% <2% <1%
Drugs in development PTC124 VX809+Kalydeco®
VX661+Kalydeco® Kalydeco® N/A N/A
Potentiator Potentiator + corrector
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Bring superior treatment to the patient
• Objective: superior combination of potentiator & corrector
• Testing cascade in place with state-of-the-art & gold standard technologies
• Learning from Vertex: Ussing chamber predicts clinical outcome
• 3 programs in hit-to-lead, new potentiator in lead optimization
• Programs proprietary to GLPG
CF programs on track to deliver PCC in 2013
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Galapagos CF potentiators Ussing chamber data
ΔF508-CFTR homozygous primary cells were grown for 21 days and corrected with 3 µM VX-809 for 48h Kalydeco®
GLPG 1 1 GLPG 2
Compound EC50 (nM)
Kalydeco® 133
GLPG 1 81
GLPG 2 129
ΔF508 patient cells G551D assay
Superior opening CFTR confirmed with GLPG series in Ussing chamber
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CF strategy
• Successful collaboration with CF Foundation
• First disease in which Galapagos will discover, develop and launch its own
medicines
• Bring best in class potentiator to G551D population
• Progress correctors in discovery to address the ∆F508 population
• Galapagos in strong position with own potentiator
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Our scientific achievements in 2012 Pre-clinical programs (1)
• Alliance with GSK: delivered fifth PCC
• Alliance with J&J: delivered second PCC
• Alliance with Servier:
delivered first PCC in osteoarthritis (OA) alliance
achieved milestones in OA & oncology alliance
• Alliance with MorphoSys: on track to deliver PCC in 2013
• Cystic Fibrosis: on track to deliver PCC in 2013
• Anti-infectives:
delivered first candidate antibiotic against MRSA strains
on track to enter the clinic in 2014
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Our scientific achievements in 2012 Clinical programs (2)
• GLPG0634 selective JAK1 inhibitor
Phase 2a data in RA patients
• GLPG0974: novel GPR43 antagonist
excellent results second Phase I trial
• GLPG0187: Integrin Receptor Antagonist for cancer metastasis
study extended to confirm early sign of activity
• GLPG0778/GSK2586184:
start Phase 2 studies in SLE and Psoriasis
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Therapeutic scope
Target finding Discovery Early development Phase 2
Lupus
Inflammation
Osteoarthritis
Infectious disease
Oncology
Inflammatory bowel disease
RA Psoriasis
Cystic fibrosis
Metabolic
Fibrosis
GLPG0187
= Clinical development by partner
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Achieving excellence in R&D • Our strengths
novel modes of action discovered in relevant human primary cells
expertise in inflammation, orphan, metabolic, anti-infectives
synergies with service division
speed of execution
• Our challenges
aim for therapeutic value
select the right diseases
progress the best targets
kill projects early
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First into humans in next 18 months
Project Partner 2013 2014 (preliminary)
GLPG1179 GSK
GLPG1205 Janssen
GLPG1332 Servier - OA
CAM-1 (GLPG1492) unpartnered
GLPG1577 GSK
GLPG1690 Janssen
Healthy volunteers Preclinical
Undisclosed
Undisclosed
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Clinical progress in 2013
Disease area Phase 1 Phase 2a
Rheumatoid arthritis
Inflammation
Metastasis
SLE
Psoriasis
GLPG0974
= Expected progress in 2013
GSK2586184*
= Inlicensed at Phase 1 by GSK
* GLPG code = GLPG0778
GSK2586184*
Phase 2b
GLPG0187
PoC GLPG0974
GLPG0634
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News flow 2013
• Start 2 Phase 2 studies
‘634 in RA
‘974 in ulcerative colitis
• Start 2 Phase 1 First-in-Human with new modes-of-action
• Delivery of PCC with potentiator in cystic fibrosis
• Delivery of more PCCs in the alliances and internal programs
• Presence at scientific conferences
‘634: EULAR, ACR
‘974: ASPET meeting
Three Phase 2 and multiple Phase 1 programs by end 2013
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R&D Update
• Company strategy Onno van de Stolpe, CEO
• R&D portfolio Piet Wigerinck, CSO
• 2013 Outlook Onno van de Stolpe, CEO
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Bright outlook for Galapagos
• Leadership in JAK1 space: two compounds in Phase 2 in three indications
• AbbVie deal & inlicensing by GSK highlight success of our approach
• Broad pipeline provides further opportunities for clinical success
both in internal and alliance programs
• Business model supports investment in promising proprietary programs
Galapagos in excellent position to build on its R&D strengths
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2015 and beyond
• Expected licensing of ‘634 by AbbVie brings in $200 M
• Multiple clinical programs being progressed by our partners
• Maturing proprietary pipeline with multiple clinical programs
• Shift model from early out-licensing to late stage internal development
Galapagos on track to be successful beyond GLPG0634