Novel targets, better treatments

Transcription

1 Novel targets, better treatments Investor presentation March 2018

2 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 Building an IPF franchise Ambition with filgotinib FINCH Ph3 design for RA DIVERSITY & SELECTION in IBD Filgotinib in psoriatic arthritis Filgotinib in ankylosing spondylitis CF approach to a triple combo PELICAN 1972 for osteoarthritis MOR106 for atopic dermatitis 2018 late-stage clinical newsflow Guidance 2018, 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, 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

3 GLPG: strong investment case Candidates for $80+B inflammation & fibrosis markets Proven platform for innovation, deep pipeline Late stage data from every major program in 2020 Building commercial infrastructure Strong cash position for growth with ~$1.4 B 3

4 GLPG: data rich 2018 Filgotinib Best-in-class JAK Topline results in 3 indications (RA, PsA, AS) Building commercial organization with Gilead IPF Start 1690 late stage studies in H1 18 Franchise of 3 proprietary novel assets CF Individual components validated in patients Topline 1 st triple in patients mid 18 Expanding pipeline 19 Ph2 trials in 18 Additional novel drugs into clinic 4

5 Advancing our innovation to market Potential for multiple product launches New pipeline opportunities Pivotal trials Expansion of late stage pipeline Commercial preparations GILD partnership 2nd and 3rd PoC on novel targets 5

6 Strong R&D Area Preclinical Ph1 Ph2 Ph3 Filgotinib 10+ indications evaluated in Ph2 and Ph3, pivotal trial completion as of 2018 IPF Multiple late stage trials to start in H1 18, fully proprietary CF Ph2 to start Q1 18 Atopic dermatitis OA Inflammation Fibrosis Ph2 to start H1 18 >20 programs 6

7 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 PROOF OF CONCEPTS filgotinib (JAK1) 1690 (autotaxin) MOR106 (IL17-C) 7

8 Partnerships 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 8

9 Building an IPF franchise 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 9

10 IPF: $5B market by 2025 Large unmet need remains About IPF Progressive lung scarring leading to death Median survival 2-5 years Mostly male patients, >50 years Diagnosis via HRCT or biopsy 200,000 cases in US & EU 2016 drug sales $1.2B EU 21% Japan 5% Ofev & Esbriet have limitations Only slow FVC decline ~25% annual discontinuations List price ~$95,000/yr US 74% Sources: Stifel, Global Data Note: Ofev is a drug marketed by Boehringer Ingelheim, Esbriet is a drug marketed by Roche 10

11 Positive 1690 data in patients Flora Placebo mg *= 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 11

12 FRI shows disease stabilization Flora Functional respiratory imaging tracks ahead of FVC 12

13 Strong biomarker reduction Flora Reduction of LPA18:2 in blood plasma Placebo mg Placebo 1690 BSL N=6 N=17 4 N=5 N=16 12 N=6 N=15 FU N=5 N=15 **= p<0.01 Biomarker reduction = target engagement 13

14 5 4 Ashcroft score (median) Score (median) Ashcroft score Volume (ml) Additional novel mechanisms in IPF 3499: target undisclosed BLM signs & symptoms * * 1205: targets GPR84 BLM inspiratory capacity Healthy BLM (30mg/kg bid) BLM - Ofev (60mg/kg qd) BLM - Diseased Healthy *=p>0.05 PBS + vehicle Diseased BLM + vehicle Ofev 60mg/kg qd BLM + Ninte QD, 60mpk mg/kg bid BLM+G Pressure (cm H 2 0) 3499 and 1205 reduce IPF signs & symptoms in BLM model Note: both experiments are 21 day therapeutic bleomycin lung fibrosis model in mice (BLM) 14

15 Building 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

16 Ambition with filgotinib TOLERABILITY ACTIVITY CONVENIENCE most selective JAK1 >2000 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 candidate drug 16

17 Inflammation market ~$65B by 2027 Market growth drivers ~2027 market size, $B Current use of biologics <40% Oral and monotherapy Rapid response Higher, maintained efficacy AS ~8 UC ~9 PsA ~10 CD ~10 RA ~30 Source: Goldman Sachs 2017, Leerink 2017, Stifel 2017, Global Data, Galapagos estimates 17

18 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 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

19 Superior efficacy JAK class in RA ACR50% ACR50% (W12, (W12) active delta) placebo active active delta mg QD + MTX 100 mg Q.D. + MTX (DARWIN-1, 2016, W12) 200 mg QD + MTX 200 mg Q.D. + MTX (DARWIN-1, 2016, W12) 40mg EOW + cdmards Adalimumab 40mg EOW (RA-BEAM, 2017, W12) 2 mg QD + cdmards 2 mg Q.D. + cdmards (RA-BUILD, 2017, W12) 4 mg Q.D. + cdmards (RA-BUILD, 2017, W12) 15 mg Q.D. + cdmards (SELECT NEXT, 2017, + cdmards W12) Filgotinib Baricitinib Upadacitinib Filgotinib DARWIN 1 Humira MTX IR (cdmard IR) Baricitinib 4 mg QD + cdmards 15 mg QD Upadacitinib RA-BEAM RA-BUILD SELECT-NEXT 30 mg QD 30 mg Q.D. + cdmards (SELECT NEXT, 2017, + cdmards W12) Note: data not from head-to-head studies 19

20 Superior efficacy 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 Cimzia 400mg W12 PRECISE-1 Stelara 6mg/kg IV W10 Entyvio 300mg W10 GEMINI-3 Note: data not from head-to-head studies 20

21 Beneficial hemoglobin profile EPO-JAK2 selectivity 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. 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 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. filgotinib Westhovens et al, and Kavanaugh et al, ARD 2016; baricitinib Dougados et al, Annrheumdis 2016, RA-BUILD and Tanaka EULAR 2016 abstract RA-BEAM; tofacitinib Van Vollenhoven abstract 2013, 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: 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 DVT and infections Event Per 100 PYE filgotinib (50-)200mg daily DARWIN 3 Wk 84 upadacitinib 6 and 12mg BID baricitinib 2 and 4mg QD tofacitinib 5mg bid tocilizumab 4 and 8 mg/kg adalimumab Genovese, ACR2017 Genovese et al., ACR2017 Genovese et al, ACR 2017 Wollenhaupt et al, ACR 2017 Genovese et al, ACR 2012 Burmester et al, 2011 Patient year exposure 1, ,637 5,891 14,994 23,943 Serious infection Herpes Zoster NR NR DVT/PEs N cases/100py 2/1, / /6, /1,849* * DVT/PE data on tofacitinib from Mease et al, ACR2017, 5mg bid 24

25 FINCH Ph3 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 FINCH 2 topline expected H2 18; recruitment completion expected FINCH 1 (Q2) & FINCH 3 (Q3)

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 Ph2/3 1,300 pts 58 weeks Mayo score components Induction & maintenance SELECTION 2 Long term extension study Interim decision SELECTION expected H1 18; recruitment completion DIVERSITY expected H2 19

27 Filgotinib in psoriatic arthritis EQUATOR trial fully recruited 16 weeks Screening filgotinib, 200mg once daily (n=62) Placebo (n=62) Follow-up Patients with moderate to severe psoriatic arthritis Recruitment in 8 European countries Primary objective: ACR20 at week 16 Expected completion Q

28 Filgotinib in ankylosing spondylitis TORTUGA trial fully recruited 12 weeks Screening filgotinib, 200mg once daily (n=50) Placebo (n=50) Follow-up Patients with moderate to severe ankylosing spondylitis Recruitment in 8 European countries Primary objective: ASDAS at week 12 Expected completion H

29 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 Multiple triples in patient studies Triple studies in US & Europe >130 patients, 10 countries, >60 sites in studies to date Interim results of 1 st triple therapy in patients expected mid 18 2 nd triple therapy completed dosing in healthy volunteers 29

30 PELICAN up to 4 wks 4 wks up to 3 wks Screening 2737, oral (n=12) Placebo (n=6) Follow-up 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 Q

31 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 US planned in H

32 Strong reduction of ARGS 1972 Ph1b 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 32

33 MOR106 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 start in H

34 % change from baseline MOR106 Ph1b EASI, % change from baseline, pooled data, median Weeks after start of treatment Infusion Placebo MOR106 34

35 2018 late-stage clinical newsflow TRIAL INITIATIONS Late stage 1690 in IPF Ph in IPF CF 1 st triple (FALCON) Ph2 2 nd CF triple combo Ph in OA in US Ph2 MOR106 in AtD POC DATA Filgotinib in PsoA (EQUATOR) Filgotinib in AS (TORTUGA) CF PELICAN CF FALCON PIVOTAL DATA Filgotinib in RA (FINCH 2) Filgotinib interim UC (SELECTION, go/no go) Recruitment completed for FINCH 1, FINCH 3 35

36 glpg.com

37 Cash, cash equivalents & restricted cash Cash Burn: 154.1M M ,152.4 Dec-16 Cash proceeds from capital increases (non cash) currency translation effect Cash income from milestones Cash expense Dec-17 Cash burn of 154M, cash of 1.15B end of Dec Notes: includes restricted cash of 7.7 M in Dec 16 and 1.2 M in Dec 17 excluding tax receivable from Belgian & French governments of 75.8 M in Dec 17 37

38 Update on Belgian tax regime Application Old: Patent Income Deduction (PID) New: Innovation Income Deduction (IID) Tax base reduction on patent related income (upfront, milestones, (embedded) royalties); e.g. filgotinib, CF Deduction 80% of gross revenues 85% of net revenues Carry-forward No Yes Belgian corporate tax rate 2016: 34% 2020: 25% Effective tax rate 6.8% 3.75% 38

39 Guidance 2018 Operating cash burn between million cash-flow from operations and investing includes cash income and R&D investments reflects an increase in spending in filgotinib, GLPG1690, CF and other proprietary programs 39

40 ALBATROSS 4 wks up to 2 wks 2222, oral, 300 mg once daily (n=14) Screening 2222, oral, 150 mg once daily (n=14) Placebo (n=7) Ivacaftor 150 mg twice daily Follow-up Adult CF patients Class III/Class II, on stable ivacaftor treatment 37 patients enrolled in Europe and Australia 40

41 Clear activity profile D29 vs. baseline Sweat chloride Absolute ppfev 1 changes mmol/l %ppfev Placebo 150 mg 300 mg 0 Placebo 150 mg mg * * -5 * (p<0.05) 41

42 Cohort B Cohort A FLAMINGO 2222 in homozygous F508del patients 4 wks up to 2 wks 2222, oral, dose 1 or 2 once daily (n=20) Screening Placebo (n=5) 2222, oral, dose 3 or 4 once daily (n=20) Followup Placebo (n=5) Comparable to study of VX-661 In F508del homozygous Donaldson 2017 Adult CF patients homozygous F508del mutation 59 patients enrolled in two sequential cohorts (A & B) 4 doses GLPG2222 QD 24 sites: US, UK, Belgium, Netherlands, Serbia, Spain 42

43 On target activity Mean changes D29 vs. baseline Sweat chloride Absolute ppfev 1 changes mmol/l %ppfev 1 Pbo Dose 1 Dose 2 Dose 3 Dose 4 Pbo Dose 1 Dose 2 Dose 3 Dose * (p<0.05) * LOCF values Mean ±SE Dose dependent decrease in SwCl, demonstrating CFTR on target activity