Novel targets, better treatments - Investor presentation | May 2018
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Novel targets, better treatments Investor presentation | May 2018
Disclaimer
This presentation contains forward-looking statements, including (without limitation) statements concerning the progress of our clinical
pipeline, the slides captioned “GLPG: strong investment case” “GLPG: data rich 2018” “Advancing our innovation to market” “Strong R&D”
“Establishing commercial footprint” “Building the filgotinib franchise” “Inflammation market ~$65 B by 2027” “Ambition with filgotinib”
“FINCH Ph3 design for RA” “DIVERSITY & SELECTION in IBD” “Filgotinib in psoriatic arthritis” “Filgotinib in ankylosing spondylitis” “$1.9B
market with large unmet needs” “IPF: $5B market by 2025” “Building an IPF franchise” “Ph3 program ISABELA 1&2” “CF approach to
triple combo” “PELICAN” “FALCON” “’1972 for osteoarthritis” “MOR106 for atopic dermatitis” ”IGUANA Ph2 program” “2018 late-stage
clinical newsflow,” 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, and other potential indications (ii)
in the CF program, (iii) with GLPG1690, GLPG1205, and GLPG3499 in IPF, (iv) with GLPG1972 in OA, (v) with MOR106 in atopic dermatitis,
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 may
result in differences are the inherent uncertainties associated with competitive developments, clinical trial and product development
activities, regulatory approval requirements (including that data from the company's development programs may not support registration
or 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. A
further list and description of these risks, uncertainties and other risks can be found in Galapagos’ Securities and Exchange Commission
(“SEC”) filing and reports, including Galapagos’ most recent Form 20-F filing for the year ended December 31, 2017. Given these
uncertainties, 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 to update
any statement in this document to reflect any change or future development with respect thereto, any future results, or any change in
events, conditions and/or circumstances on which any such statement is based, unless specifically required by law or regulation.
Under no circumstances may any copy of this presentation, if obtained, be retained, copied or transmitted.
2
GLPG: strong investment case
Candidates for $80+B Proven platform
inflammation & fibrosis for innovation,
markets deep pipeline
Late stage data
from filgotinib Building
2018-2019 commercial
infrastructure
Strong cash position
for growth with
~$1.3 B
3
GLPG: data rich 2018
• Best-in-class JAK
Filgotinib • Topline results in 3 indications (RA, PsA, AS)
• Building commercial organization with Gilead
• ISABELA Ph3 program with ‘1690
IPF • Franchise of 3 proprietary novel assets
• Individual components validated in patients
CF • Topline 1st triple in patients Q3 ‘18
Expanding • 19 Ph2 trials in ‘18
pipeline • Additional novel drugs into clinic
4
Advancing our innovation to market
2020-2022
• Potential for multiple product launches
• New pipeline opportunities
2018-2019
• Pivotal trials
• Expansion of late stage pipeline
• Commercial preparations
2016-2017
• GILD partnership
• 2nd and 3rd PoC on novel targets
5
Strong R&D
Area Preclinical Ph1 Ph2 Ph3
10+ indications evaluated in Ph2 and Ph3,
Filgotinib pivotal trial completion as of 2018
ISABELA Ph3 to start H2 ‘18,
IPF fully proprietary
CF FALCON Ph2 to readout Q3 ‘18
Atopic dermatitis IGUANA Ph2 ongoing
OA
Ph2 to start in H1 ‘18
Inflammation >20
Fibrosis programs
6Unique target discovery engine
NOVEL TARGETS SMART DEVELOPMENT 3 PROOFS OF CONCEPT
disease-modifying rapid, multiple PoCs filgotinib (JAK1)
multiple disease areas swift moves to pivotal ‘1690 (autotaxin)
first-in-class candidates development MOR106 (IL17-C)
7Partnerships
Gilead: filgotinib
$750M upfront
$1.35B in milestone payments
profit-split, co-promote in 8 EU countries
20-30% royalties
AbbVie: CF
$600M milestones
profit-split and co-promotion in Benelux
China/Korea rights
15-20% royalties
Servier: ‘1972
$290M milestones
single digit % royalties
US rights
MorphoSys: MOR106
50/50 cost/benefit
8Establishing commercial footprint
• Experience in launch and
Further pipeline international operations
• Established global presence
expansion • Partnerships as opportunity
• Orphan, shape the market
‘1690 in IPF • Expand beyond EU
global launch • Compact medical and
patient community
• Rheumatology and IBD
Filgotinib advanced markets
• First organizations in EU
EU co-promotion
• Leverage Gilead
partnership
9Building the filgotinib franchise
Area Ph 1 Ph 2 Ph 3
RA
Crohn’s disease
Ulcerative colitis
Ankylosing spondylitis
Psoriatic arthritis
Small bowel CD
Fistulizing CD
Sjögren’s
Cutaneous lupus
Lupus nephropathy
Uveitis
Status Jan ‘18 Expected progress in 2018
10Inflammation market ~$65B by 2027
Unmet needs
• Current use of biologicsReadiness to adopt JAKs
EULAR guidelines RA Recent trends
csDMARDs (MTX, …)
2nd line • Baricitinib in Germany
1st line fastest uptake in RA
>40% bio-naive
85% high dose
• Tofacitinib in US
33d line fastest growing therapy in RA
for the last 2 years
>40% bio-naïve
UC high-dose AdComm
unanimous recommendation
Source: EULAR recommendations for the management of rheumatoid arthritis with synthetic
and biological disease-modifying antirheumatic drugs: 2016 update; Ely Lilly ; IMS; 12
KOLs interviews; Xeljanz US promotional materialAmbition with filgotinib
TOLERABILITY ACTIVITY CONVENIENCE
most selective JAK1 strong in RA once-daily oral
>2,000 PYE strong in CD in monotherapy
biologic naive
strong biomarker &
AE profile rapid onset &
sustained response
Note: potential indicated here is based on Ph2 filgotinib data, no head to
head comparison studies, filgotinib is an investigational candidate drug
13
13Filgotinib
Most JAK1 selective
JAK1 vs. JAK2 JAK1 vs. JAK3
30 30
25 25
Fold selectivity
20 20
15 15
10 10
5 05
0 00
filgotinib tofacitinib baricitinib upadacitinib filgotinib tofacitinib baricitinib upadacitinib
Source: Galapagos human whole blood assay Source: Galapagos biochemical assay
Independently confirmed at ACR 2017*
* “Ex Vivo Comparison of Baricitinib, Upadacitinib, Filgotinib, and Tofacitinib 14
for Cytokine Signaling in Human Leukocyte Subpopulations,” McInnes et al, ACR 2017Superior activity JAK class in RA
50
ACR50%
ACR50% (W12, (W12)
active delta)
placebo active active delta
40
30
28 28
20 23 23
21 20
17
10
0
100
100 mg +QD
mg Q.D. MTX 200
200 mg mg QD
Q.D. + MTX 40mg EOW
Adalimumab +
40mg EOW 2 mg2Q.D.
mg+ cDMARDS
QD 4 mg4Q.D.
mg+ QDcDMARDS 15Q.D.
15 mg mg+QD 30Q.D.
cDMARDs 30 mg mg+ cDMARDs
QD
(DARWIN-1, 2016, W12) (DARWIN-1, 2016, W12) (RA-BEAM, 2017, W12) (RA-BUILD, 2017, W12) (RA-BUILD, 2017, W12) (SELECT NEXT, 2017, (SELECT NEXT, 2017,
+ MTX + MTX cDMARDs + cDMARDs + cDMARDs + cDMARDs
W12)
+ cDMARDs
W12)
Filgotinib Baricitinib Upadacitinib
MTX IR (cDMARD IR)
Filgotinib Adalimumab Baricitinib Upadacitinib
DARWIN 1 RA-BEAM RA-BUILD SELECT-NEXT
Note: data not from head-to-head studies 15Superior activity in CD, TNF naive
Clinical remission: induction
Active delta to placebo, % responders
50
47
40
47
30
27
24 27
20
19
17
10
7
0
Filgotinib 200mg Humira 160mg W4 Xeljanz 5mg W8 Cimzia 400mg W12 Stelara 6mg/kg IV Entyvio 300mg
W10 FITZROY CLASSIC-1 Panes et al 2017 PRECISE-1 W10 W10
UNITI-2, W10 GEMINI-3
Note: data not from head-to-head studies; PRECISE-1 CIMZIA and Stelara study populations include TNF naives and TNF
responders, but TNF-IR are excluded; Humira dose is 160mg at week0 and 80mg at week 2 , Xeljanz overall study result including
TNF-IR patients did not meet primary endpoint
16Beneficial hemoglobin profile
Hb mean CFB (g/dL), W12
0.6
0.4
0.2
0
-0.2
-0.4
-0.6
pbo 100mg 200mg pbo 2mg 4mg pbo 5mg 10mg pbo 6mg 12mg 18mg
qd qd qd qd bid bid bid bid bid
filgotinib
filgotinib baricitinib
baricitinib tofacitinib
tofacitinib upadacitinib
upadacitinib
Note: data from separate RA studies not conducted by the Company.
17 RA-BUILD;
filgotinib – Westhovens et al, and Kavanaugh et al, ARD 2016; baricitinib – Dougados et al, Annrheumdis 2016,
tofacitinib – FDA AdComm briefing document May 2012; upadacitinib – Genovese et al A&R 2016 BALANCE 2.No reduction of NK cells
NK cells, mean CFB (%), W12
10
No impact
0
-10
-20
-30
-40
-50
pbo 100mg 200mg pbo 2mg 4mg pbo 5mg 15mg pbo 6mg 12mg 18mg
qd qd qd qd bid bid bid bid bid
filgotinib
filgotinib baricitinib
baricitinib* tofacitinib
tofacitinib** upadacitinib
upadacitinib
Note: data from separate RA studies not conducted by the Company.
filgotinib – Westhovens et al, and Kavanaugh et al, ARD 2016; baricitinib – FDA briefing documents bariciitinib AdComm 23 April 2018; tofacitinib – Van Vollenhoven abstract
2013, median CFB at W6; upadacitinib – Genovese et al A&R 2016 BALANCE 2. 18Reduction of platelets
platelets, mean CFB (giga/L), W12
30
20
Change from baseline (109/L)
10
0
-10
-20
-30
-40
pbo 100mg 200mg pbo 2mg qd 4mg qd pbo 5mg 10mg pbo 6mg 12mg 18mg
qd qd bid bid bid bid bid
filgotinib
filgotinib baricitinib
baricitinib tofacitinib
tofacitinib upadacitinib
upadacitinib
Note: filgotinib – DARWIN 1 W12 results; baricitinib – Dougados et al, Annrheumdis 2016;
tofacitinib – FDA AdComm briefing document May 2012, upadacitinib – Genovese et al ACR 2017 19Low incidence DVT and infections
Event filgotinib upadacitinib baricitinib tofacitinib tocilizumab adalimumab
Per 100 PYE
(50-)200mg daily 6 and 12mg BID 2 and 4mg QD 5mg bid 4 and 8 mg/kg
DARWIN 3 Wk 84
Genovese, Genovese et al., Genovese et al, Wollenhaupt et al, Genovese et al, Burmester et al,
ACR2017 ACR2017 ACR 2017 ACR 2017 ACR 2012 2011
Patient year
1,708 725 6,637 5,891 14,994 23,943
exposure
Serious
1.5 2.3 2.9 2.2 4.5 4.6
infection
Herpes
1.2 3.7 3.2 3.6 NR NR
Zoster
DVT/PEs 2/1,708 5/725 31/6,754 3/1,849*
- -
N cases/100PY 0.1 0.7 0.5 0.2
* DVT/PE data on tofacitinib from Mease et al, ACR2017, 5mg bid 20FINCH Ph3 design for RA
100 and 200 mg
FINCH 1: MTX - IR 1,650 52 weeks ACR20 at W12
MTX add-on
adalimumab control
radiographic assessment
FINCH 2: biologic - IR 423 24 weeks ACR20 at W12
cDMARD add-on
FINCH 3: MTX naive 1,200 52 weeks ACR20 at W24
monotherapy, +MTX arms
radiographic assessment
FINCH 2 topline expected H2 ’18;
FINCH 1 & 3 fully recruitedDIVERSITY & SELECTION in IBD
100 and 200 mg
DIVERSITY 1 Crohn’s Ph3 58 weeks PRO2, endoscopic response
1,320 pts Induction & maintenance
DIVERSITY 2 Long term extension study
SELECTION 1 UC Ph2/3 58 weeks Mayo score components
1,300 pts Induction & maintenance
SELECTION 2 Long term extension study
Interim decision SELECTION expected H1 ’18;
recruitment completion DIVERSITY expected H2 ’19Filgotinib in psoriatic arthritis
EQUATOR trial fully recruited
16 weeks
filgotinib, 200mg once daily (n=62)
Screening Follow-up
placebo (n=62)
• Patients with moderate to severe psoriatic arthritis
• Recruitment in 8 European countries
• Primary objective: ACR20 at week 16
• Expected completion Q2 ‘18
23Filgotinib in ankylosing spondylitis
TORTUGA trial fully recruited
12 weeks
filgotinib, 200mg once daily (n=50)
Screening Follow-up
placebo (n=50)
• Patients with moderate to severe ankylosing spondylitis
• Recruitment in 8 European countries
• Primary objective: ASDAS at week 12
• Expected completion H2 ’18
24There is no cure yet for IPF
About IPF
• Progressive lung fibrosis leading to
death
• 200,000 prevalent cases in US & EU
• ~75,000 new cases annually
• Median survival 2-5 years
• > 50% of patients misdiagnosed
Source: IPF: a disease with similarities and links to cancer biology. C Vancheri et al, Eur Respir J 2010
25$1.9B market with large unmet needs
2017 drug sales $1.9B
Ofev® & Esbriet® have limitations
• only slow FVC decline
• ~25% annual discontinuations
• list price in US ~$95,000/yr
Ofev Esbriet
Sources: Stifel, Global Data, Maher et al. BMC Pulmonary Medicine (2017) 17:124
Note: Ofev is a drug marketed by Boehringer Ingelheim, Esbriet is a drug marketed by Roche 26IPF: $5B market by 2025
Improve outcomes
• shorten diagnosis time
• improve efficacy
Improve treatment • combination therapies
• more diagnosed • long term treatment
patients treated compliance
Current unmet • patients longer on
needs treatment
• lengthy diagnosis • awareness and
education
• low treatment rate and
duration
• low survival
Galapagos aspiration
Sources: Stifel, Global Data, Galapagos assessment
27Building an IPF franchise
ets
Drug (MoA) Pre-clinical Ph 1 Ph 2 Ph 3
'1690 (Autotaxin)
'1205 (GPR84)
'3499
Status Jan ‘18 Expected progress in 2018
• Fully proprietary, oral therapies
• Three novel modes of action to address unmet need
• Opportunity to investigate combinations
• ‘1690 has orphan drug designation in EU & US
GLPG to commercialize IPF assets
28Positive ‘1690 data in patients Flora
Placebo ‘1690 600mg QD
*= pFlora
FRI indicates disease stabilization
Functional respiratory imaging tracks ahead of FVC
30Strong biomarker reduction Flora
Reduction of LPA18:2 in blood plasma
Placebo ‘1690 600mg QD
BSL 4 12 FU
Placebo N=6 N=5 N=6 N=5
‘1690 N=17 N=16 N=15 N=15
**= pPh3 program ISABELA 1&2
52 weeks
‘1690 dose A
Follow
Screening ‘1690 dose B OLE
-up
Topline Part 1 expected Q3 ‘18
Placebo
• 1500 IPF patients total, remain on standard of care throughout
• Global study with substantial US and EU component
• Primary endpoint: forced vital capacity (FVC) at 52 weeks
• Secondary: hospitalizations, mortality, quality of life, safety/tolerability
Robust Ph3 program expected to begin in H2 ‘18
32Additional novel mechanisms in IPF
‘3499: target undisclosed ‘1205: targets GPR84
BLM – signs & symptoms BLM – inspiratory capacity
Ashcroft score (median)
Healthy
5 BLM - ‘1205 (30mg/kg bid)
BLM - Ofev (60mg/kg qd)
* * BLM - Diseased
4
Volume (mL)
Ashcroft
Score (median)
score
3
2
1
Ofev ‘3499
cle
pk
5
Healthy Diseased 60mg/kg
e
9-
icl
0m
hi
99
10mg/kg
h
ve
ve
,6
39
Pressure (cm H20)
+
QD
2
+
qd
G1
*=p>0.05
M
bid
S
BL
PB
e
+
nt
M
Ni
BL
+
M
BL
‘3499 and ‘1205 reduce IPF signs & symptoms in BLM model
Note: both experiments are 21 day therapeutic bleomycin lung fibrosis model in mice (BLM) 33CF approach to triple combo
2005 - today 2018 -
Discover novel correctors Validate triple combo
& potentiators in patients
Validate individual components in Comprehensive clinical network
patients: Multiple triples in patient studies
Potentiator: SAPHIRA Triple studies in US & Europe
C1: ALBATROSS, FLAMINGO
C2: PELICAN
• >130 patients, 10 countries, >60 sites in studies to date
• Interim results of 1st triple therapy in patients (FALCON) expected Q3 ‘18
• 2nd triple therapy completed dosing in healthy volunteers
34PELICAN
up to 4 wks 4 wks up to 3 wks
‘2737, oral (n=12)
Screening Follow-up
placebo (n=6)
orkambi (400 mg lumacaftor, 250 mg ivacaftor twice daily)
• Adult CF patients homozygous for F508del mutation
• Patients remain on stable dose of Orkambi
• 10 sites in Germany
• Primary endpoints: safety & tolerability
• Secondary endpoints: sweat chloride, FEV1, CFQ-R
Fully recruited; topline expected Q2 ‘18
35FALCON 2 weeks 2 weeks
Part 1, dose A
Screening Dual Triple Follow-up
homozygous
Part 2, dose B
Dual Triple
Screening heterozygous min Follow-up
ToplineDual
Part 1 expected Q3 ‘18Triple
homozygous
• F508del patients, n=8 in each cohort
• Recruitment in Europe, incl. UK
• Primary endpoints: safety, tolerability, PK
• Secondary endpoints: sweat chloride, ppFEV%, CFQ-R
36‘1972 for osteoarthritis
OA: breakdown of joint cartilage
118 M patients in US, Europe & Japan
No disease-modifying drugs approved today
Targets ADAMTS-5
Inhibits cartilage breakdown biomarker in healthy volunteers
Phase 1: clear target engagement, favorable safety & PK
GLPG Ph1b 30-patient study in US: positive data
Ph2 start in H1 ‘18
37‘1972 targets ADAMTS-5 in OA
• ‘1972 is a potent and selective
chondroprotective ADAMTS-5 inhibitor
• ADAMTS-5 plays a key role in aggrecan
degradation in OA
• Strong literature evidence for ADAMTS-5:
validated in animal models²,³
validated in human samples¹
ARGS levels increased in human knee
synovial fluid in OA 4
Source: ¹ Song, 2007; ² Glasson, 2005 & Malfait, 2010; ³ Miller, 2016; 4 Larsson, 2009
38‘1972 protects cartilage
Histopathology in mouse model
cartilage
vehicle ‘1972 ‘1972 ‘1972
low dose medium dose high dose
39Strong reduction of ARGS
‘1972 Ph1b study in OA patients
-20
vs baseline
vs baseline
0
% reduction
% reduction
Placebo
placebo
20
Low dose
‘1972 dose 1
ARGS ARGS
Med dose
‘1972 dose 2
‘1972
High dose 3
40
Blood serum
60
1 8 15 22 29 36 43 50
Days post-dosing
Dose-dependent reduction of ARGS, well-tolerated in OA patients
40MOR106 for atopic dermatitis
AtopicD: disease causing very dry skin, severe itching
35M patients in US, Europe & Japan
First-in-class human MAb
Novel MOA: IL-17C target discovered by Galapagos
Ph1 (SAD): favorable safety & PK in healthy volunteers
Ph1b (MAD): 83% patients at EASI50 within 4 weeks at highest dose
Ph2 IGUANA study started in Q2 ‘18
41Dual mode of action
• IL-17C target of MOR106
• Dual action described
• Local amplifier of inflammation
• First-in-class
IL-17A
Source: Haines & Cua, Immunity 2011
42MOR106 Ph1b
EASI, % change from baseline, pooled data, median
0
-10
% change from baseline
-20
-30
-40
-50
Placebo
-60
MOR106
-70
-80
-90
-100
0 2 4 6 8 10 12 14
Weeks after start of treatment
Infusion
Source: Thaci et al, AAD 2018
43IGUANA Ph2 program
12 weeks
MOR106, 1mg/kg
MOR106, 3 mg/kg 16 wk
Screening
Follow-up
MOR106,
Topline Part 1 10mg/kg
expected Q3 ‘18
Placebo
• 180 patients with moderate-to-severe AtD
• IV infusion at 2 or 4 week intervals for 1 & 3 mg/kg
• IV infusion at 2 week interval for 10 mg/kg
• Recruitment in Europe
• Primary endpoint: % change in EASI score at week 12
442018 late-stage clinical newsflow
TRIAL INITIATIONS POC DATA PIVOTAL DATA
Ph3 ‘1690 in IPF Filgotinib in PsoA Filgotinib in RA
Ph2 ‘1205 in IPF (EQUATOR) (FINCH 2)
Ѵ Ph2 1st CF triple (FALCON) Filgotinib in AS Filgotinib interim UC
(TORTUGA) (SELECTION, go/no go)
Ph2 2nd CF triple combo
CF PELICAN
Ph2 ‘1972 in OA in US
CF FALCON Ѵ Recruitment completed
Ѵ Ph2 MOR106 in AtD for FINCH 1, FINCH 3
45
45glpg.com
Cash & cash equivalents
Cash Burn: €41.3M €M
1,151.2 17.0
3.9 -5.6
-58.3
1,108.2
Dec-17 Cash Currency Cash income Cash expense Mar-18
proceeds translation from
from capital effects milestones
increases
Q1 ‘18 cash burn of €41M, cash of ≈€1.1B end of March
Notes:
• excluding tax incentive receivable from Belgian & French governments of €80.9 M in March ‘18
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