darwin 1 final filgotinib study results - galapagos...
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©Copyright 2015 Galapagos NV
DARWIN 1 Final filgotinib study results
30 July 2015
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This document may contain certain statements, including forward-looking statements, such as statements concerning the safety and efficacy of filgotinib following the topline 24-week results from the DARWIN 1 and/or DARWIN 2 trials and expectations regarding the commercial potential of our product candidates, which involve certain uncertainties and risks.
Forward-looking statements are often, but are not always, made through the use of words or phrases such as “believes,” “anticipates,” “expects,” “intends,” “plans,” “seeks,” “estimates,” “may,” “will,” “could,” “stands to,” “continues,” “we believe,” “we intend,” as well as similar expressions. Such forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause the actual results, performance or achievements of Galapagos, or industry results, to be materially different from any historic or future results, performance or achievements expressed or implied by such forward-looking statements.
Among the factors that may result in differences between the statements contained herein and actual future results, performance or achievements, are the inherent uncertainties associated with competitive developments, clinical trial and product development activities, regulatory approval requirements and estimating the commercial potential of our product candidates. Given these uncertainties, you are advised not to place any undue reliance on such statements.
All statements contained herein speak only as of the release date of this document and reflect the then available data, whichmight be subject to changes in light of future results, events, conditions and/or circumstances. Galapagos expressly disclaims any obligation to update any statement in this document to reflect any change or future development with respect thereto, anyfuture results, or any change in events, conditions and/or circumstances on which any such statement is based, unless required by law or regulation.
Disclaimer
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1. Filgotinib: first-in-class oral in RA
2. Transformational CF therapies
4. Platform to fill pipeline
5. Strong financials & partnerships
3. Fully-owned Ph2 programs in IBD/IPF
Galapagos at a glance5 key aspects
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• Oral administration
• Highly efficacious on patient relevant parameters (ACR50, ACR70, DAS28 remission)
• Rapid onset of action
• Safe & well tolerated
What are patients looking for in RA treatment?
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Filgotinib, a new mode of actionJAK1 discovered by us as target for bone & joint disease
Start Phase I trial
development
2005 2006 2007 2008 2009
PCC nomination
lead optimization
compound screening
JAK1 discovered using SilenceSelect®
2010 2011
Start PoC
PoC results
2012 2013 2014
Start Ph2A
Start Ph2B
2015
DARWIN final Ph2B results
Deal with AbbVie
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Selectivity mattersFilgotinib is the selective JAK1 inhibitor
0
10
20
30
baricitinib tofacitinib filgotinib
Ratio JAK1/JAK2 in human whole blood assay
(GLPG0634)
Hbrecovery¹
anemia
¹A Pardanani, et al, Leukemia (2013) 27, 1322–1327
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• High response rates
clear dose response, consistent across read-outs
fast onset of action (ACR response & subscores)
high ACR50 & ACR70 responses
• Safety (AEs): no dose effect, low AE/SAE rate
increased hemoglobin of particular interest in population
lipids: higher percentage increase in HDL than LDL
DARWIN 1 week 12 conclusions
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Competitor dataACR responses at week 24
% responders
0
10
20
30
40
50
60
70
80
90
100
ACR20 ACR50 ACR70 ACR20 ACR50 ACR70 ACR20 ACR50 ACR70
adalimumab 40 mg EOWARMADA 2003
tofacitinib 5 mg bidKremer 2012
baricitinib 4 mg qdKeystone 2014
Note: data reported in listed publications, not resulting from head-to-head studies.
active treatment
placebo
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• Inclusion:
diagnosis of RA since at least 6 months (2010 ACR/EULAR criteria of RA & ACR functional class I-III)
≥6 SJC (66 joint count) and ≥8 TJC (68 joint count)
screening serum CRP ≥0.7 x ULN*
MTX for ≥6 months on stable dose (15 – 25 mg/week)
• Exclusion:
current therapy with any DMARD other than MTX
current or previous RA treatment with a biologic DMARD
Key eligibility criteria
* ULN = 9 mg/L
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Patient dispositionScreenedN=1276
RandomizedN=599
PlaceboN=86
Randomized & exposed
N=594
Not exposedN=5
Not eligible at screeningN=677
50 mgN=82
100 mgN=85
200 mgN=86
2x25 mgN=86
2x50 mgN=85
2x100 mgN=84
PlaceboN=53
100 mgN=15
2x50 mgN=15
50 mgN=57
100 mgN=19
100 mgN=78
200 mgN=80
2x25 mgN=60
2x50 mgN=17
2x50 mgN=80
2x100 mgN=83
W13-24
W0-12
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Baseline characteristicsDemographics & disease
qd groups bid groups
Placebo 50 mg 100 mg 200 mg2 x
25 mg2 x
50 mg2 x
100 mg
Age, mean, years 52 53 52 55 52 55 54
Female 81% 84% 76% 86% 79% 76% 83%
Duration of RA, mean, years 8 7 8 9 9 8 10
DAS28(CRP), mean 6.0 6.1 6.1 6.2 6.1 6.1 6.1
CRP, mean, mg/L 16 28 25 27 26 25 27
TJC68, mean 25 25 25 29 25 27 26
SJC66, mean 16 17 16 17 16 18 16
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Early discontinuationsWeek 0-24
Categories are not mutually exclusive
Low discontinuation rate, equally distributed across groups
placebo only(N=56)
filgotinib exposed (N=538)
Safety 3.6% 3.9%
Efficacy 0.0% 0.6%
Other 7.1% 6.1%
Total 10.7% 10.2%
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ACR20ITT-NRI
Placebo
50 mg
100 mg
200 mg
2x25 mg
2x50 mg
2x100 mg
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
45
56
62
70
57 59
80
42
5560
73
5660
80**
***
***
***
0
10
20
30
40
50
60
70
80
90
100
W12 W24
*: p<0.05; **: p<0.01; ***: p<0.001
% responders
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ACR50ITT-NRI
% responders
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
Placebo
50 mg
100 mg
200 mg
2x25 mg
2x50 mg
2x100 mg15
32
39
43
28
34
55
17
35
46
50
35 35
55
*
*
* * * *
**
***
***
***
***
***
0
10
20
30
40
50
60
70
W12 W24
*: p<0.05; **: p<0.01; ***: p<0.001
15
ACR70ITT-NRI
% responders
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
Placebo
50 mg
100 mg
200 mg
2x25 mg
2x50 mg
2x100 mg
8
16
20
24
14
19
31
9
22
33
29
21
24
39
** *
*
****
**
***
0
5
10
15
20
25
30
35
40
45
50
W12 W24
*: p<0.05; **: p<0.01; ***: p<0.001
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ACR70 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)
0
5
10
15
20
25
30
35
40
45
50
tofacitinib 5 mg bid(n= 71)
Kremer 2012
sarilumab 200mg E2W(n=399)
Genovese 2015
adalimumab 40 mg EOW(n=67)
Weinblatt 2003
baricitinib 4 mg qd(n=52)
Keystone 2014
filgotinib 100 mg bid(n=84)
DARWIN1 2015
active treatment
placebo
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ACR responsesITT-NRI, at week 24
% responders
Placebo
50 mg
100 mg
200 mg
2x25 mg
2x50 mg
2x100 mg
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
42
55
60
73
5660
80
17
35
4650
35 35
55
9
22
3329
2124
39* * *
* **
****
***
***
******
***
***
0
10
20
30
40
50
60
70
80
90
100
ACR20 ACR50 ACR70*: p<0.05; **: p<0.01; ***: p<0.001
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-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0 4 8 12 16 20 24Week
bid vs placebo
Placebo 2x25 mg 2x50 mg 2x100 mg
DAS28(CRP)ITT-LOCF
*: p<0.05; **: p<0.01; ***: p<0.001
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
mean CFB
**
***
***
***
***
***
***
***
*
**
***
**
***
***
**
***
*** ***
***
***
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DAS28(CRP) Non-responders at week 12 switching to 100 mg/day
-3
-2.5
-2
-1.5
-1
-0.5
0
0.5
0 4 8 12 16 20 24
Week
Placebo to 100 mg Placebo to 2x50 mg 50 mg to 100 mg 2x25 mg to 2x50 mg
switch
mean CFB
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DAS28(CRP)ITT-LOCF, at week 24: remission rate & low disease activity
Subjects who switch treatment at week 12 are handled as if they discontinued at week 12.
9
21
36
2623 24
40
9
12
1426
16 14
24
*
***
******
***
0
10
20
30
40
50
60
70
Placebo 50 mg 100mg 200 mg 2x25 mg 2x50 mg 2x100 mg
*: p<0.05; **: p<0.01; ***: p<0.001
Remission <2.6 (%) Low disease activity [2.6,3.2] (%)% responders
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DAS28(CRP)ITT-LOCF, at week 24: remission rate & low disease activity
% responders
Note: data reported in listed publications, not resulting from head-to-head studies.Ph3 dose (competitors) vs best Ph2 dose (filgotinib)
0
10
20
30
40
50
60
70
baricitinib 4 mg qd (n=52)Keystone 2014
sarilumab 200mg E2W (n=399)Genovese 2015
filgotinib 100 mg bid (n=84)DARWIN1 2015
Remission <2.6 (%) Low disease activity [2.6,3.2] (%)
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Overview safety endpointsWeek 0-24
Subjects with:placebo only
(N=56)filgotinib exposed
(N=538)
TE AE 57.1% 52.6%
Serious TE AE 7.1% 2.0%
Serious TE infection 1.8% 0.9%
SAE leading to death 0.0% 0.2%
TE AE leading to stop 3.6% 3.3%
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TEAEs of special interestWeek 0-24
* non fatal and not considered drug related
Subjects with:placebo only
(N=56)filgotinib exposed
(N=538)
All infections 17.9% 25.5%
All serious infections 1.8% 0.9%
Herpes zoster 1.8% 0.7%
Urinary tract infections 1.8% 3.7%
Upper RTI 1.8% 3.7%
Pneumonia 0.0% 0.4%
MACE* 0.0% 0.4%
No cases of opportunistic infections, tuberculosis, malignancies or lymphoma
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SafetyWeek 0-24, change versus baseline
Parameter Measure
Hemoglobin increase up to 4%
Platelets decrease towards mid normal value
Lymphocytes no effect
Neutrophils decrease towards mid normal value
Creatinine increase up to 11%
ALT no CTCAE gr 3-4
Lipids increase of HDL (up to 23%) > LDL (up to 13%)
Male reproductive hormonesno clinically meaningful changes; no discontinuations
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Hemoglobin Data up to W24
Responder: at least 20% drop in TJC68 and SJC66 versus baseline
-6
-4
-2
0
2
4
6
8
0 4 8 12 16 20 24
Week
Continued groups (qd vs placebo)
Placebo in resp. 50 mg in resp. 100 mg 200 mg
mean % CFB
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• Fast onset of action
• Clear dose response
• No difference between bid and qd regimens
• Sustained high level of ACR20 and ACR50 response
• Further increase in efficacy over 24 weeks
ACR70 response
DAS28 CRP remission
DAS28 CRP low disease activity
Conclusions – efficacyWeek 0-24
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• Low drop out rate
• Similar incidence in TEAEs, SAEs and serious infections between filgotiniband placebo
• No dose dependent increase of infections
• Stabilization of decrease in neutrophils, increase in creatinine
• Safety profile consistent with data at week 12
• Confirmation of differentiated safety profile versus other JAKs in RA:
increase in Hb, HDL>LDL, no effect on lymphocytes
Conclusions – safetyWeek 0-24
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• Patients
• Investigators
• Team
• AbbVie
Thank you
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Filgotinib: DARWIN 2, license decision, FITZROY
Triple combo CF program on track to deliver
Strong balance sheet to support R&D
Fully owned programs in IBD/IPF
Proprietary target discovery to feed pipeline