Novel targets, better treatments

Transcription

1 Novel targets, better treatments Investor presentation Sept 2018

2 Disclaimer This presentation contains forward-looking statements, including (without limitation) statements concerning the progress of our clinical pipeline, the slides captioned Advancing our innovation to market Strong R&D Partnerships Building the filgotinib franchise Inflammation market ~$65 B by 2027 Ambition with filgotinib FINCH Phase 3 design for RA DIVERSITY & SELECTION in IBD $1.9B market with large unmet needs Building an IPF franchise Phase 3 program ISABELA 1&2 PINTA Ph2 in IPF CF approach to triple combo FALCON 1972 for osteoarthritis ROCCELLA Phase 2 study MOR106 for atopic dermatitis IGUANA Phase 2 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 other potential indications, 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, MorphoSys, and Novartis) 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 and subsequent filings with the SEC. Given these uncertainties, you are advised not to place any undue reliance on such forward-looking statements. 2

3 Advancing our innovation to market Potential for multiple product launches New pipeline opportunities Pivotal trials Expansion of late stage pipeline Commercial preparations GILD partnership for filgotinib 2nd and 3rd PoC on novel targets 3

4 Strong R&D Area Preclinical Phase 1 Phase 2 Phase 3 Filgotinib 10+ indications evaluated in Ph2 and Ph3, pivotal trial completion as of 2018 IPF ISABELA Ph3 and PINTA Ph2 to start H2 18, fully proprietary CF FALCON Ph2 to readout Q3 18 Atopic dermatitis IGUANA Ph2 ongoing OA Inflammation Fibrosis ROCCELLA Ph2 ongoing >20 programs 4

5 Unique target discovery engine NOVEL TARGETS disease-modifying multiple disease areas first-in-class candidates SMART DEVELOPMENT rapid, multiple PoCs swift moves to pivotal development 3 PROOFS OF CONCEPT filgotinib (JAK1) 1690 (autotaxin) MOR106 (IL17-C) 5

6 Partnerships Gilead: filgotinib $725M 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 $260M milestones single digit % royalties US rights Novartis: MOR106 $111M upfront, $1B in milestones low-teens low twenties royalties all development paid MorphoSys: 50/50 cost/benefit 6 Note: all milestones are potential

7 Building the filgotinib franchise Area Phase 1 Phase 2 Phase 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

8 Inflammation market ~$65B by 2027 Unmet needs Current use of biologics <40% ~2027 market size, $B Oral and monotherapy Rapid response Higher, maintained efficacy Market growth AS ~8 UC ~9 PsA ~10 RA ~30 Differentiation vs. biologics CD ~10 Source: Goldman Sachs 2017, Leerink 2017, Stifel 2017, Global Data, Galapagos estimates 8

9 Our goal with filgotinib TOLERABILITY ACTIVITY CONVENIENCE most selective JAK1 >2,000 PYE strong biomarker & AE profile strong in RA strong in CD in biologic naive rapid onset & sustained response once-daily oral monotherapy Note: potential indicated here is based on Ph2 filgotinib data, no head to head comparison studies, filgotinib is an investigational drug candidate 9

10 Fold selectivity Filgotinib Most JAK1 selective JAK1 vs. JAK2 JAK1 vs. JAK filgotinib tofacitinib baricitinib upadacitinib 00 filgotinib tofacitinib baricitinib upadacitinib Source: Galapagos human whole blood assay Source: Galapagos biochemical assay JAK selectivity independently confirmed at ACR 2017* * Ex Vivo Comparison of Baricitinib, Upadacitinib, Filgotinib, and Tofacitinib for Cytokine Signaling in Human Leukocyte Subpopulations, McInnes et al, ACR

11 FINCH 2 ACR20%, bdmard-ir W mg Q.D mg Q.D. + cdmards cdmards (FINCH 2, 2018, (FINCH 2, 2018, W12) W12) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 5 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) Filgotinib Baricitinib Tofacitinib Upadacitinib Upadacitinib filgotinib baricitinib tofacitinib upadacitinib W12 6 mg B.I.D. + MTX (BALANCE I, Ph2, 2016, W12) 12 ( Note: data not from head-to-head studies, comparisons may be inaccurate 11 bdmard-ir

12 80 FINCH 2 ACR20%, bdmard-ir W mg Q.D. + cdmards (FINCH 2, 2018, W24) 200 mg Q.D. + cdmards (FINCH 2, 2018, W24) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W24) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W24) No PBO controlled data at W24 for ORAL STEP & SELECT BEYOND 5 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) Filgotinib Baricitinib Tofacitinib Upadacitinib filgotinib baricitinib tofacitinib upadacitinib W24 Note: data not from head-to-head studies, comparisons may be inaccurate 12

13 FINCH 2 ACR50%, bdmard-ir 50 W mg Q.D mg Q.D. + cdmards cdmards (FINCH 2, 2018, (FINCH 2, 2018, W12) W12) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 5 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) filgotinib baricitinib tofacitinib upadacitinib Filgotinib Baricitinib Tofacitinib Upadacitinib Upadacitinib W12 bdmard-ir 6 mg B.I.D. + MTX (BALANCE I, Ph2, 2016, W12) 12 m (B P Note: data not from head-to-head studies, comparisons may be inaccurate 13

14 50 45 FINCH 2 ACR50%, bdmard-ir W mg Q.D. + cdmards (FINCH 2, 2018, W24) 200 mg Q.D. + cdmards (FINCH 2, 2018, W24) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W24) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W24) No PBO controlled data at W24 for ORAL STEP & SELECT BEYOND 5 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) Filgotinib Baricitinib Tofacitinib Upadacitinib filgotinib baricitinib tofacitinib upadacitinib W24 Note: data not from head-to-head studies, comparisons may be inaccurate 14

15 FINCH 2 ACR70%, bdmard-ir W mg Q.D mg Q.D. + cdmards cdmards (FINCH 2, 2018, (FINCH 2, 2018, W12) W12) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W12) 5 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W12) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W12) filgotinib baricitinib tofacitinib upadacitinib Filgotinib Baricitinib Tofacitinib upadacitinib Upadacitinib W12 6 mg B.I.D. + MTX (BALANCE I, Ph2, 2016, W12) 12 mg B MT (BALAN Ph2, 2 W1 Note: data not from head-to-head studies, comparisons may be inaccurate 15 bdmard-ir

16 35 FINCH 2 ACR70%, bdmard-ir W mg Q.D. + cdmards (FINCH 2, 2018, W24) 200 mg Q.D. + cdmards (FINCH 2, 2018, W24) 2 mg Q.D. + cdmards (RA-BEACON, 2016, W24) 4 mg Q.D. + cdmards (RA-BEACON, 2016, W24) No PBO controlled data at W24 for ORAL STEP & SELECT BEYOND 5 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 10 mg B.I.D. + MTX (ORAL STEP, 2013, W24) 15 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) 30 mg Q.D. + cdmards (SELECT BEYOND, 2017, W24) Filgotinib Baricitinib Tofacitinib Upadacitinib filgotinib baricitinib tofacitinib upadacitinib W24 Note: data not from head-to-head studies, comparisons may be inaccurate 16

17 Activity in CD, TNF naive Clinical remission: induction Active delta to placebo, % responders Filgotinib 200mg W10 FITZROY Humira 160mg W4 CLASSIC-1 Xeljanz 5mg W8 Panes et al 2017 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 17 7 Cimzia 400mg W12 PRECISE-1 Stelara 6mg/kg IV UNITI-2, W10 W10 Entyvio 300mg W10 GEMINI-3

18 Activity in psoriatic arthritis ACR20, mixed population, W12 placebo active treatment difference active treatment vs placebo EQUATOR (W16) Pooled OPAL (W12) ADEPT (W12) RAPID-PSA (W12) FUTURE 2 (W12) CR (W16) M (W16) Filgotinib Xeljanz Humira Cimzia Cosentyx Guselkumab Risankizumab W12/16 Mixed population REFERENCES/ Xeljanz (tofacitinib) 5 mg b.i.d. Pooled OPAL (Ph3) Nash at ACR 2017 Humira (adalimumab) 40 mg QC EOW ADEPT (Ph3) Mease 2005 (! Only TNF-naïves) Cimzia (certolizumab pegol) 400 mg Q4W RAPID-PSA (Ph3) Mease 2014 Cosentyx (secukinumab) 150 mg QW W0,4 + Q4W thereafter FUTURE 2 (Ph3) EPAR & McInnes 2015 Guselkumab 100 mg W0,4 + Q8W thereafter CR (Ph2) Deodhar at ACR2017 Risankizumab 150 mg Q4W M (Ph2) Mease at ACR

19 Activity in psoriatic arthritis ACR50, mixed population, W12/ placebo active treatment difference active treatment vs placebo EQUATOR (W16) Pooled OPAL (W12) ADEPT (W12) RAPID-PSA (W12) FUTURE 5 (W16) M (W16) Pooled SPIRIT (W12) PSUMMIT 2 (W12) P Filgotinib Xeljanz Humira Cimzia Cosentyx Risankizumab Taltz Stelara W12/16 Mixed population NOTE: data not from head to head studies, comparisons may be inaccurate REFERENCES/ Xeljanz (tofacitinib) 5 mg b.i.d. Pooled OPAL (Ph3) Nash at ACR 2017 Humira (adalimumab) 40 mg QC EOW ADEPT (Ph3) Mease 2005 (! Only TNF-naïves) Cimzia (certolizumab pegol) 400 mg Q4W RAPID-PSA (Ph3) Mease 2014 Cosentyx (secukinumab) 150 mg QW W0,4 + Q4W thereafter FUTURE 5 (Ph3) Mease 2018 Risankizumab 150 mg Q4W M (Ph2) Mease at ACR

20 Activity in AS ASDAS CFB, W12 Note: data not from head to head studies, comparisons may be inaccurate ASDAS CFB: Ankylosing Spondylitis Disease Activity Score, change from baseline ASDAS is a composite score of 5 domains: (1) Total back pain on 0-10 scale (based on BASDAI question 2); (2) Patient s global assessment of disease activity on 0-10 scale; (3) Peripheral joint pain and/or swelling on 0-10 scale (based on BASDAI question 3); (4) Duration of morning stiffness on 0-10 scale (based on BASDAI question 6); (5) CRP in mg/l. 20

21 Beneficial hemoglobin profile Hb mean CFB (g/dl), W pbo 100mg200mg qd qd pbo 2mg qd 4mg qd pbo 5mg bid 10mg bid pbo 6mg bid 12mg bid 18mg bid filgotinib baricitinib tofacitinib upadacitinib Note: data from separate RA studies not conducted by the Company, comparisons may be inaccurate filgotinib Westhovens et al, and Kavanaugh et al, ARD 2016; baricitinib Dougados et al, Annrheumdis 2016, 21 RA-BUILD; tofacitinib FDA AdComm briefing document May 2012; upadacitinib Genovese et al A&R 2016 BALANCE 2.

22 No reduction of NK cells NK cells, mean CFB (%), W No impact pbo 100mg200mg qd qd pbo 2mg qd 4mg qd pbo 5mg bid 15mg bid pbo 6mg bid 12mg bid 18mg bid filgotinib baricitinib* tofacitinib** upadacitinib Note: data from separate RA studies not conducted by the Company, comparisons may be inaccurate filgotinib Westhovens et al, and Kavanaugh et al, ARD 2016; baricitinib FDA briefing documents bariciitinib AdComm 23 April 2018; tofacitinib Van Vollenhoven abstract 2014, median CFB at W6; upadacitinib Genovese et al A&R 2016 BALANCE 2. 22

23 Change from baseline (10 9 /L) Reduction of platelets platelets, mean CFB (giga/l), W pbo 100mg qd 200mg qd pbo 2mg qd 4mg qd pbo 5mg bid 10mg bid pbo 6mg bid 12mg bid 18mg bid filgotinib baricitinib tofacitinib upadacitinib Note: data from separate RA studies not conducted by the Company, comparisons may not be accurate filgotinib DARWIN 1 W12 results; baricitinib Dougados et al, Annrheumdis 2016; tofacitinib FDA AdComm briefing document May 2012, upadacitinib Genovese et al ACR

24 Low incidence of DVT and infections Event per 100 PYE filgotinib upadacitinib baricitinib tofacitinib tocilizumab adalimumab mg 6 and 12 mg bid 2 and 4 mg QD 5 mg bid 4 and 8 mg/kg DARWIN3 wk108 & FINCH2 Genovese ACR2017 Genovese et al ACR2017 Wollenhaupt ACR 2017 Genovese ACR 2012 Burmester 2011 Patient year exp. 2, ,637 5,278 14,994 23,943 Serious infection Herpes Zoster DVT/PE 2/2, ND ND 5/ /6, /1, Deaths ND ND Note: data not from head-to-head studies, comparisons may not be accurate Tofacitinib DVT/PE data from Mease, ACR2017 (5mg bd), and death data from 2012 FDA Medical review Baricitinib: DVT/PE Weinblatt ACR

25 FINCH Phase 3 design for RA 100 and 200 mg FINCH 1: MTX-IR 1, weeks ACR20 at W12 MTX add-on adalimumab control radiographic assessment FINCH 2: biologic-ir weeks ACR20 at W12 cdmard add-on FINCH 3: MTX naive 1, weeks ACR20 at W24 monotherapy, +MTX arms radiographic assessment

26 DIVERSITY & SELECTION in IBD 100 and 200 mg DIVERSITY 1 Crohn s Ph3 1,320 pts 58 weeks PRO2, endoscopic response Induction & maintenance DIVERSITY 2 Long term extension study SELECTION 1 UC Ph3 1,300 pts 58 weeks Mayo score components Induction & maintenance SELECTION 2 Long term extension study

27 $1.9B market with large unmet needs 2017 drug sales $1.9B Ofev & Esbriet have limitations only slow FVC decline ~25% annual discontinuations Ofev Esbriet Sources: Global Data, Maher et al. BMC Pulmonary Medicine (2017) 17:124, sales figures from Roche and Boehringer Ingelheim Note: Ofev is a drug marketed by Boehringer Ingelheim, Esbriet is a drug marketed by Roche 27

28 Building an IPF franchise Drug (MoA) Pre-clinical Preclinical 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 expects to commercialize IPF assets, if approved 28

29 1690 data in patients Flora Placebo mg QD *= p<0.05 Placebo 1690 BSL N=6 N=17 4 N=3 N=16 8 N=4 N=15 12 N=4 N=13 FU N=4 N=15 FVC stabilization over 12-week period 29

30 FRI indicates disease stabilization Flora Functional respiratory imaging tracks ahead of FVC Source: Mignot et al, ATS

31 Phase 3 program ISABELA 1&2 ISABELA 1&2 at least 52 weeks 1690 dose A Screening 1690 dose B Topline Part 1 expected Q3 18 Placebo Follow-up 1500 IPF patients total, remain on standard of care throughout Global study with US and EU component Primary endpoint: forced vital capacity (FVC) at 52 weeks Secondary: hospitalizations, mortality, quality of life, safety/tolerability Robust Phase 3 program expected to begin in H

32 PINTA Phase 2 in IPF 26 weeks Screening GLPG1205, 100mg once daily (n=40) placebo (n=20) Follow-up 60 IPF patients on local standard of care Primary endpoint: forced vital capacity (FVC) at 26 weeks Secondary: safety, tolerability, PK and PD, time to major events, changes in functional exercise capacity, and quality of life Recruitment in 10 countries in Europe, North Africa, and the Middle East 32

33 CF approach to triple combo today Discover novel correctors & potentiators Validate triple combo in patients Validate individual components in patients: Potentiator: SAPHIRA C1: ALBATROSS, FLAMINGO C2: PELICAN Comprehensive clinical network Triple study in patients >130 patients, 10 countries, >60 sites in studies to date Part 1 results of 1 st triple therapy in patients (FALCON) expected Q3 18 Galapagos reviewing its collaboration with AbbVie 33

34 FALCON 2 weeks 2 weeks Part 1, dose A Screening Dual Triple Follow-up homozygous Part 2, dose B Dual Triple Screening Topline Part 1 expected Q3 18 Dual heterozygous min homozygous Triple Follow-up F508del patients, n=8 in each cohort Recruitment in Europe, including UK Primary endpoints: safety, tolerability, PK Secondary endpoints: sweat chloride, ppfev%, CFQ-R 34

35 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, generally well-tolerated GLPG Phase 1b 30-patient trial completed in US ROCCELLA global Phase 2 trial underway 35

36 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,

37 1972 protects cartilage Histopathology in mouse model cartilage vehicle 1972 low dose 1972 medium dose 1972 high dose Source: Amantini et al OARSI

38 Reduction of ARGS 1972 Phase 1b study in OA patients -20 ARGS % reduction vs baseline Blood serum ARGS % reduction vs baseline placebo Placebo 1972 Low dose Med dose High dose Days post-dosing Dose-dependent reduction of ARGS, well-tolerated in OA patients 38

39 ROCCELLA Phase 2 study 52 weeks 1972 dose A Screening 1972 dose B Topline Part 1 expected 1972 dose Q3 C 18 Follow-up Placebo 850 patients with knee osteoarthritis, recruited globally Primary endpoint: reduction in cartilage loss at 52 weeks Secondary: change in structural and clinical parameters, safety/tolerability Robust Phase 2 program, GLPG runs US component 39

40 MOR106 for atopic dermatitis AtopicD: disease causing very dry skin, severe itching First-in-class human MAb Novel MOA: IL-17C target discovered by Galapagos Partnered with Novartis and MorphoSys Phase 1 (SAD): favorable tolerability & PK in healthy volunteers Phase 1b (MAD): 83% patients at EASI50 in 4 weeks at highest dose IGUANA Phase 2 study started in Q2 18 Additional studies planned 40

41 Dual mode of action IL-17C target of MOR106 Dual action described Local amplifier of inflammation First-in-class IL-17A Source: Haines & Cua, Immunity

42 % change from baseline MOR106 Phase 1b EASI, % change from baseline, pooled data, median Weeks after start of treatment Infusion Placebo MOR106 Source: Thaci et al, AAD

43 IGUANA Phase 2 program 12 weeks MOR106, 1mg/kg Screening MOR106, 3 mg/kg Topline Part 1 MOR106, expected 10mg/kg Q3 18 Placebo 16 wk Follow-up 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 43

44 Q4 18 expected newsflow TRIAL INITIATIONS 1 st dosing ISABELA (IPF Ph3) 1 st dosing PINTA (IPF Ph2) Ph1 starts PH2 DATA CF FALCON PIVOTAL DATA EQUATOR ACR Filgotinib late breaker R&D Update 25 the Yale Club 44

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