novel targets, better treatments
TRANSCRIPT
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
Note: data from RA studies
14
Herpes zosterIFN-driven
Herpes zoster cases (%)
0.00
1.00
2.00
3.00
4.00
5.00
6.00
filgotinib baricitinib tofacitinib upadacitinib
Note: data from RA studies
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
filgotinib baricitinib tofacitinib upadacitinib
0.03
-0.010.00
Note: data from RA studies
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
C1 corrector ‘2851
C2 corrector ‘2737
On track to have triple in patients by mid-2017
potentiator ‘3067
C2 corrector ‘3221
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
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
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