Novel targets, better treatments

Novel targets, better treatments

JP Morgan Healthcare Conference | 9-12 January 2017

2

Disclaimer

This presentation has been prepared by Galapagos and is furnished to you by Galapagos solely for your information.

This presentation contains forward-looking statements, including (without limitation) statements concerning the progress of our clinicalpipeline, the slides captioned “Strategy” “R&D ambition” “Diversified and maturing pipeline” “CF Portfolio” “High level path for CF program”two slides called “Clinical news flow” and “Outlook”, statements regarding the development of the triple combination therapy CF program,statements regarding the expected timing, design and readouts of ongoing and planned clinical trials (i) with filgotinib in RA, IBD, andother potential indications (ii) in the CF program, (iii) with GLPG1690 in IPF, (iv) with GLPG1972 in OA, (v) with MOR106 in atopicdermatitis, and expectations regarding the commercial potential of our product candidates. When used in this presentation, the words“anticipate,” “believe,” “can,” “could,” “estimate,” “expect,” “intend,” “is designed to,” “may,” “might,” “will,” “plan,” “potential,” “possible,”“predict,” “objective,” “should,” and similar expressions are intended to identify forward-looking statements.

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. Among the factors that mayresult in differences are the inherent uncertainties associated with competitive developments, clinical trial and product developmentactivities, regulatory approval requirements (including that data from the company's development programs may not support registrationor further development of its compounds due to safety, efficacy or other reasons), reliance on third parties (including Galapagos’collaboration partners AbbVie, Gilead, Servier and MorphoSys) and estimating the commercial potential of its product candidates. Afurther list and description of these risks, uncertainties and other risks can be found in Galapagos’ Securities and Exchange Commissionfiling and reports, including Galapagos’ most recent 20-F filing and subsequent reports filed by Galapagos with the SEC. Given theseuncertainties, you are advised not to place any undue reliance on such forward-looking statements.

All statements contained herein speak only as of the release date of this document. Galapagos expressly disclaims any obligation toupdate any statement in this document to reflect any change or future development with respect thereto, any future results, or anychange in events, conditions and/or circumstances on which any such statement is based, unless specifically 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 toany matter or as to the truth, accuracy, or completeness of any statement made in this presentation, made in conjunction therewith or inany accompanying materials or made at any time, orally or otherwise, in connection with the matters referred to herein and all liability inrespect of any such matter or statements is expressly excluded.

Galapagos at a glance

Listed on Euronext & NASDAQ: GLPG

Proof of platform: filgotinib in Ph3

480 employees at 4 EU sites

Novel mode of action drugs

Partners: GILD, ABBV, Servier, MOR

Q3 cash ~$1B, market cap ~$3B

Our strategy

Take selectedprograms to

market ourselves

Deliver on ourkey product partnerships

Design & developfirst-in-classdrugs

Identifynovel drug targets

in human cells

Build a commercial EU

organization

R&D focus areas

Galapagos

Fibrosis

Cystic fibrosis

Idiopathic pulmonary fibrosis

NASH

Inflammation

Rheumatoid arthritis

Crohn’s disease

Ulcerative colitis

Osteoarthritis

Ankylosing spondylitis

Psoriatic arthritis

Lupus

Atopic dermatitis

Anti-infectives

Hepatitis B

Metabolic

Type 2 diabetes

R&D ambition

8 NEWTARGETS

3 PRECLINICALCANDIDATES

3 PROOFS OF CONCEPT

1 PHASE 3START

every year

every year

every year

every 2 years

7

Diversified and maturing pipeline

partnered

Area Pre-clinical Phase 1 Phase 2 Phase 3

RA

CD

UC

CF

CF

CF

IPF

OA

Atop. D

IPF

Atop. D

‘1972

JAK1 filgotinib

Autotaxin ‘1690

MOR106

Potentiator ‘2451

JAK1 filgotinib

C1 ‘2222

C2 ‘2737

‘1837

JAK1 filgotinib

‘2938

‘2534

CF

Triple combo for 90% of patients

GLPG responsible to end Ph2, contributes to Ph3

Milestones $600M,incl. $250M increase for Ph1 & 2

Profit split in co-promote territory: Benelux, GLPG retains China/S.Korea

Royalties mid-teens to 20%

Filgotinib

JAK1 in autoimmune

GLPG co-develops, contributes 20% of cost

Upfront $725M, milestones $1.35B

Profit split in co-promote territory: EU big 5 + Benelux

Royalties 20%+

Two key partnershipsGLPG retains significant rights in both deals

Filgotinib

High activity in Ph2 studies

Favorable lipid profile

Once daily oral

Full rebound of hemoglobin

No impact on NK cells

>1,300 patient years’ exposure

Ph3 in RA, Crohn’s, and UC

10

Selectivity mattersFilgotinib is the selective JAK1 inhibitor

0

10

20

30

baricitinib Xeljanz™ ABT-494 filgotinib

Ratio JAK1/JAK2 in human whole blood assayHb

recovery¹

anemia

(upadacitinib)

1: A Pardanani, et al, Leukemia (2013) 27, 1322–1327

11

17

35

46

50

0

10

20

30

40

50

% responders

High efficacy rates in DARWIN ACR50, QD groups, ITT-NRI, at week 24

0

32

40

45

0

10

20

30

40

50

DARWIN 1(+ MTX)

DARWIN 2

(monotherapy)

100 mg & 200 mg being tested in FINCH Phase 3 program

39

33

47

16

Placebo

50 mg

100 mg

200 mg

Westhovens et al, Ann. Rheum. Dis., 2016Kavanaugh et al, Ann. Rheum. Dis, 2016

12

HemoglobinEPO-JAK2 selectivity

Hb mean CFB (g/dL), W12

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

pbo 100mgqd

200mgqd

pbo 2mgqd

4mgqd

pbo 5mgbid

10mgbid

pbo 6mgbid

12mgbid

18mgbid

filgotinib baricitinib tofacitinib upadacitinib

Monitoring required

Note: data from RA studies

13

NK cellsIL15 - JAK3 selectivity

NK cells mean CFB (%), W12

-50

-40

-30

-20

-10

0

10

pbo 100mgqd

200mgqd

pbo 2mgqd

4mgqd

pbo 5mgbid

15mgbid

pbo 6mgbid

12mgbid

18mgbid

filgotinib baricitinib* tofacitinib** upadacitinib

* Calculated from RA-BEAM (Tanaka) and RA-BUILD data (Dougados)** median CFB at W6

Monitoring totallymphocytes required


14

Herpes zosterIFN-driven

Herpes zoster cases (%)

0.00

1.00

2.00

3.00

4.00

5.00

6.00



15

Lipid improvementJAK1-selectivity

LDL/HDL mean CFB, W12, inversed

-0.05-0.03

-0.27

-0.02 -0.02

0.020.05

0.14

0.06

-0.3

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

pbo 100mgqd

200mgqd

pbo 2mgqd

4mgqd

pbo 5mgbid

10mgbid

pbo 6mgbid

12mgbid

18mgbid


0.03

-0.010.00


FINCH Ph3 for RA100 and 200 mg

FINCH 1: MTX - IR ACR20 at W12MTX add-onadulimumab controlradiographic assessment

1,650 52 weeks

FINCH 2: biologic - IR 423 24 weeks ACR20 at W12cDMARD add-on

FINCH 3: MTX naive 1,200 52 weeks ACR20 at W24monotherapy, +MTX armsradiographic assessment

17

FITZROY: SES-CD endoscopyImprovement by at least 50%, ITT-NRI, Week 10

% s

ub

jects

14%

(6/44)

23%

(10/44)

25%

(32/128)

39%

(50/128)

0

10

20

30

40

50

Central Reading ♯ Local Reading ♯

Placebo

200 mg

+

♯: Only using segments explored at both baseline and week 10 (matching segments)

+: p<0.10

∆=11%

∆=16%

Vermeire et al., The Lancet, 2016

DIVERSITY & SELECTION in IBD100 and 200 mg

DIVERSITY 1 PRO2, endoscopic response Induction & maintenance

Crohn’s Ph31,320 pts

58 weeks

DIVERSITY 2 Long term extension study

SELECTION 1 Mayo score components Induction & maintenance

UC Ph2/31,300 pts

58 weeks

SELECTION 2 Long term extension study

19

RA & IBD: $28B market todayAnalyst anticipated peak sales filgotinib $2-6B

RA Market size ~ $20B

~1.5M patients (US+EU)

1st line 2nd 3rd

IBDMarket size ~ $8B

~0.5M patients (US+EU)

TNF

non-TNF

JAK

100%

0%

40%

80%

60%

20%

Sources: IMS Health Autoimmune Data Platform, IPSOS Healthcare,IMS Health Analytics, GlobalData 2016, Nature Drug Discovery Review May 2016

1st line 2nd 3rd

20

Cystic fibrosis

Develop triple combination therapy

Portfolio strategy combined with innovative clinical design

Competitive patient data for potentiator ‘1837

Thijs Timmers18 years old, CF patient

21

CF portfolio

Preclinical Ph1 Ph2 Status

Ph2 results:

Ph1 results: H1 ’17

Ph1 start: H1 ’17

Ph2 start:

Ph1 start: H2 ‘17

Ph1 results: H1 ’17

Ph1 start: H2 ‘17

potentiator ‘1837

C1 corrector ‘2222

potentiator ‘2451



On track to have triple in patients by mid-2017

potentiator ‘3067


22

SAPHIRA 1‘1837 Ph2a open label trial

26 patients harboring a G551D mutation

• 25 Kalydeco treated & 1 naive patient

• recruited at 16 centers in 6 EU countries & Australia

• study executed within 1 year

• primary endpoints: safety & tolerability

• secondary endpoints: sweat chloride, FEV1, plasma levels

Washout

7 days

Screen onKalydeco / naïve

14 days 4 days

500 mg b.i.d.

125 mg b.i.d.

7 days

250 mg b.i.d.

7 days

Washout

23

Sweat chloride vs exposureSAPHIRA 1

*** p<0.001

125mg 250mg 500mg

24

Sweat chloride‘1837 exposure on Day 29 in SAPHIRA 1

125mg 250mg 500mg 125mg 250mg 500mg

25

Effect on FEV1 in SAPHIRA 1

26

• Generally well-tolerated

• Three serious adverse events in 2 patients

1 with non-cardiac CPK increase

1 with distal intestinal obstruction syndrome (screening) & pulmonary exacerbation (D28) of CF, resulting in hospitalization

• All other adverse events mild/moderate

• Most common adverse events: headaches, fatigue

• Some respiratory adverse events in 1st week

low incidence in weeks 2-4

Safety & tolerabilityAdverse events in SAPHIRA 1

27

SAPHIRA 1 toplineConclusions on ‘1837

• First potentiator after Kalydeco to show positive results in G551D

• Appears safe & well tolerated

• Statistically significant decreases in sweat chloride

• Full restoration of FEV1 % loss from Kalydeco washout

• Supports our predictive in vitro assays

• Strengthening of our dosing modelling for triple combination

28

‘2451 + ‘2222 ‘2451 +‘2222+‘2737

% of dual comboCFTR restoration

Dual and triple combinationsF508del/F508del primary cells

GLPG triple combo achieves greater CFTR vs Orkambi in vitro

100%

400%

300%

ORKAMBI®

200%

29

Triple combination in heterozygotesG542X/F508del organoids

GLPGtriple combo

Lumen area after stimulation, % increase vs untreated

25

50

75

100

ORKAMBI®

30

High level path for CF program

FiH studies Combinations in healthy volunteers Patient evaluations

‘2451

‘2222

‘2737

DUALP + C1

TRIPLE

TRIPLE

SAPHIRA ‘1837

‘2222

Potentiators

Correctors

Combinations

1Q 2Q 3Q 4Q

20171Q 2Q 3Q 4Q

2016

31

CF marketF market growing

Drug sales, $M Patients servedby therapy, K

Source: Vertex pharmaceuticals, Bloomberg* consensus peak sales for VRTX

0

200

400

600

800

1,000

2012 2013 2014 2015 2016

20169

202475

KALYDECO®

ORKAMBI®

32

IPF: scarring and stiffening of lung tissue~75,000 patients in US & Europe

Growing literature evidence of autotaxin role in IPF

Phase 1: target engagement, favorable safety & PKFLORA: Ph2A biomarker study in IPF patients

Novel mode of actionOnce or twice daily oralOrphan status in EU, requested in US

Topline exploratory Ph2A H2 ‘17

‘1690: fully owned autotaxin inhibitor

33

‘1690 in vivo activity 21-day prophylactic mouse bleomycin model

‘1690 at 30 mg/kg bid significantly superior to Esbriet

Ashcroft fibrotic score Collagen content

vehicle

BLM + vehicle

BLM + pirfenidone 50 mg/kg bid

BLM + ‘1690 10 mg/kg bid

BLM + ‘1690 30 mg/kg bid

BLM + Esbriet 50 mg/kg bid

34

FLORA: topline H2’17GLPG1690 exploratory Ph2A trial in IPF

Flora

GLPG1690, oral, 600 mg once daily (n=18)

4 weeks

Screening

12 weeks 2 weeks

Follow-upPlacebo (n=6)

• IPF patients diagnosed by HRCT/biopsy, centrally confirmed

• No pirfenidone/nintedanib 4wks prior to screening

• 17 sites in UK, Italy & Ukraine

• Primary endpoints: safety, tolerability, PK/PD

• Secondary endpoints: FVC, QoL, FRI, serum & BALF biomarkers

35

US74%

EU21%

Japan5%

IPF: $2.4B market by 2022 Diagnosed prevalent cases 109K in US/EU

Source: Global Data

Drug sales, region

0.0

0.5

1.0

1.5

2.0

2.5

2015 2016 2017 2018 2019 2020 2021 2022

Esbriet Ofev Other

Sales of approved IPF drugs, $B

36

OA: breakdown of joint cartilage118 M patients in US & EuropeNo disease-modifying drugs approved today

Undisclosed mechanism of action

Phase 1: target engagement, favorable safety and PKHalf-life ~10 hours, steady state after 2 days

Inhibits cartilage breakdown in healthy volunteers

Collaboration with Servier includes full US rights for GLPGGLPG intends to file IND for Ph1B patient study H1 '17

‘1972 for osteoarthritis

37

Marked reduction of cartilage breakdown biomarker at D14 with ‘1972

0

20

40

60

80

100

120

cohort C-300mg cohort D-600mg cohort E-1050mg

se

rum

bio

ma

rke

r (

%)

DAY1 mean placebo

DAY1 mean '1972

DAY14 mean placebo

DAY14 mean '1972

‘1972 Ph1 toplinePharmacodynamics: cartilage breakdown biomarker in MAD

DAY1 placebo

DAY1 ‘1972

DAY14 ‘1972

DAY14 placebo

38

Osteoarthritis: unmet need is large’1972 most advanced disease-modifying drug in OA

Source: Global Data

117

121

125

128

131

110

115

120

125

130

135

2016 2018 20120 2022 2024

Prevalence US & EU, M casesLocalization

1HAND 3

HIP

2KNEE

2020

39

AD: inflammatory disease causing very dry skin, severe itching 66M patients in US & EuropeNo disease-modifying drugs approved today

First-in-class human MAbNovel mechanism: IL-17C target discovered by Galapagos

Ph1 (SAD): favorable safety & PK in healthy volunteers Ph1 (MAD): dosing of 24 moderate to severe AD patients

50/50 collaboration with MORTopline results expected H2 ‘17

MOR106 for atopic dermatitis

Intravenous infusion

40

Cash & cash equivalents

• €938 M on 30 Sept ‘16

• €78 M cash burn YTD 30 Sept ‘16

• $70 M in milestones achieved in Q4 ‘16

41

Clinical news flow

Disease area Program H1 ’17 H2 ’17

Rheumatoid arthritis filgotinibDARWIN 3 interimEULAR

ACR

Crohn’s filgotinib ECCO/DDW UEGW

Ulcerative colitis filgotinib ECCO/DDWUEGWPh2 interim/start Ph3

Additional indications filgotinib Start multiple POCs Start multiple POCs

Cystic fibrosis multiple

‘2451 Ph 1 results‘2737 Ph 1 results‘3067 Ph 1 startECFS‘2222 Ph2A startUS IND

Start triple in patientsNACFC‘2851 Ph 1 start‘3221 Ph 1 start

42

Disease area Program H1 ’17 H2 ’17

IPF GLPG1690 Ph2A recruited Topline Ph2A

IPF GLPG2938 Submit Ph1

Osteoarthritis GLPG1972GLPG files US INDStart Ph1B in US

Atopic dermatitis MOR106 Topline Ph1B

Atopic dermatitis GLPG2534 Start Ph1

Clinical news flow

Outlook

Filgotinib in Ph3

Further discovery programsreach clinic

CF triple combo on track

Platform to fill pipeline

Solid balance sheet

Patient data in IPF and AD

44

Appendix slides

45

Comparison JAK inhibitors profile

Hb NK cells Platelets Lipids ALT H. zoster

filgotinib

ABT-494

baricitinib

tofacitinib

Best profile

Not/less favorable profile

Unknown

46

0

20

40

60

80

100

tofacitinib 5 mgbid

(n= 71)Kremer 2012

sarilumab200mg E2W

(n=399)Genovese 2015

adalimumab 40mg EOW(n=67)

Weinblatt 2003

baricitinib 4 mgqd

(n=52)Keystone 2014

filgotinib 200mg QD(n=84)

DARWIN1 2015

ACR50 at week 24

% responders

Note: data reported in listed publications, not resulting from head-to-head studies.Ph3/marketed dose (competitors) vs best Ph2 dose (filgotinib)

active treatment

placebo

47

23

47

41

60

*

**

0

20

40

60

80

100

100-points clinical responseClinical remission

Crohn’s: primary endpoint achievedFITZROY study CDAI responses, ITT-NRI, Week 10

% r

esp

onders

*: p<0.05; **: p<0.01

Placebo (n=44)

200 mg (n=130)

48

Competition TNF naivesClinical remission: induction

% responders

21 2018

16

12

23

13

37

17 19 24

18

48

0

10

20

30

40

50

60

70

80

Xeljanz5mg W4

Cimzia400mg W12PRECISE-1

Stelara6mg/kg IV W8

Entyvio300mg W10GEMINI-3

Humira160mg W4CLASSIC-1

Eldelumab20mg/kg W11

Phase 2A

Filgotinib200mg W10

FITZROY

Active Delta Placebo

Note: data not from head-to-head studies

49

Cystic fibrosis Use of potentiators and correctors

CLASS II CLASS IIINORMAL

F508del G551DCF mutation

~90% 4%Allele frequency

Orkambi® Kalydeco®Approved/filed drugs

Potentiator+C1+C2 PotentiatorGalapagos

CellNucleus

Cl-

Cl-

CellNucleus

CellNucleus

CellNucleus

50

Autotaxin biology

• ATX is main source of LPA in blood

• LPA controls activities like migration, contraction & survival

• Conditional genetic deletion of ATX in bronchial epithelial cells or macrophages attenuates disease severity in IPF models

‘1690At the heart of fibrotic pathways

51

FLORA: topline Q2’17GLPG1690 exploratory phase 2a trial in IPF

• IPF patients diagnosed by HRCT/biopsy, centrally confirmed

• No pirfenidone/nintedanib 4wks prior to screening

• 15 sites in UK, Italy & Ukraine

• Primary endpoints: safety, tolerability, PK/PD

• Secondary endpoints: FVC, QoL, FRI, serum & BALF biomarkers

target engagement shown by LPA

disease biomarkers: KL-6/Muc1, CCL18, MMP1/7, surfactant protein A/D,extracellular matrix turnover

12-wk 2-wk4-wk

Screening

GLPG1690, oral, 600 mg once daily (n=18)

Placebo (n=6)Follow-up

52

MOR106 in atopic dermatitis

• IL-17C target of MOR106

• Dual mode of action

• First-in-class

• Topline results from Ph1 study H2 ‘17

IL-17A

Haines and Cua, Immunity (2011)

Documents

Novel targets, better treatments