Novel targets, better treatments

Transcription

1 Novel targets, better treatments Investor presentation November 2016 Copyright 2016 Galapagos NV

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 clinical pipeline, the slides captioned Clinical pipeline R&D ambition High level path for CF program Clinical news flow 2016 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 and IBD, (ii) in the CF program, (iii) with GLPG1690 in IPF, (iv) with GLPG1972 in OA, (v) with MOR106 in inflammation, 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 forwardlooking 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 partner for cystic fibrosis, AbbVie, and its collaboration partner for filgotinib, Gilead) 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 filing and reports, including Galapagos most recent 20-F filing and subsequent reports filed by Galapagos with the SEC. 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. Neither Galapagos nor any of its officers, employees, advisers, or agents makes any representation or warranty, express or implied, as to any matter or as to the truth, accuracy, or completeness of any statement made in this presentation, made in conjunction therewith or in any accompanying materials or made at any time, orally or otherwise, in connection with the matters referred to herein and all liability in respect of any such matter or statements is expressly excluded. 2

3 Listed on Euronext & NASDAQ: GLPG Novel mode of action drugs Proof of platform: filgotinib in Ph 3 Partners: GILD, ABBV, Servier, MOR Q3 cash ~$1B, market cap ~$3B 480 employees at 4 EU sites 3

4 Our strategy Identify novel drug targets in human cells Design & develop first-in-class drugs Deliver on our key product partnerships Build a commercial EU organization Take selected programs to market ourselves 4

5 Our R&D focus areas Galapagos Inflammation Fibrosis Metabolic Anti-infectives Rheumatoid arthritis Cystic fibrosis Type 2 diabetes Hepatitis B Crohn s disease Ulcerative colitis Idiopathic pulmonary fibrosis Osteoarthritis NASH Ankylosing spondylitis Psoriatic arthritis Lupus Atopic dermatitis 5

6 R&D ambition: 1 Ph3 start every 2 years 3 Proofs of Concept / year Development 3 Pre-clinical candidates / year 8 new targets / year Research 6

7 Diversified and maturing pipeline Area Pre-clinical Phase 1 Phase 2 Phase 3 Partner RA JAK1 filgotinib CD JAK1 filgotinib Gilead UC JAK1 filgotinib CF Potentiator CF C AbbVie CF C IPF Autotaxin 1690 OA 1972 Servier Atop. D MOR106 MorphoSys IPF 2938 Atop. D 2534 partnered 7

8 Two key partnerships GLPG retains significant rights in both deals Filgotinib JAK1 in autoimmune Gilead GLPG co-develops, contributes 20% of cost Upfront $725M, milestones $1.35B profit split in co-promote territory: EU big 5 + Benelux Royalties 20%+ CF Triple combo for 90% of patients AbbVie 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 mid-teens to 20% 8

9 Filgotinib Rheumatoid arthritis Inflammatory bowel disease JAK1 selective inhibitor >1,300 patient years experience in large Ph2 studies Ph3 RA (FINCH) 3,200 patients in 3 global studies Ph3 IBD (DIVERSITY/SELECTION) 2,620 patients in 2 global studies Once daily, oral dosing Best-in-class activity, favorable safety in RA & Crohn s studies Low risk for drug-drug interaction Ph3 Crohn s (DIVERSITY), Ph2/3 UC (SELECTION) first dosing Q4 16 9

10 Selectivity matters Filgotinib is the selective JAK1 inhibitor Hb recovery¹ 30 Ratio JAK1/JAK2 in human whole blood assay anemia 0 baricitinib Xeljanz ABT-494 filgotinib (upadacitinib) ¹A Pardanani, et al, Leukemia (2013) 27,

11 Filgotinib in RA and Crohn s >1,300 patient years experience Shown high activity in Ph2 studies Once daily oral Best lipid profile Full rebound of hemoglobin No impact on NK cells Filgotinib to be broadly explored in inflammation Based on data from Phase 2 studies 11

12 FINCH Ph3 for RA 100 and 200 mg FINCH 1: MTX - IR FINCH 2: biologic - IR 1, weeks ACR20 at W12 MTX add-on adulimumab control radiographic assessment weeks ACR20 at W12 cdmard add-on FINCH 3: MTX naive 1, weeks ACR20 at W24 monotherapy, +MTX arms radiographic assessment 12

13 % subjects FITZROY: SES-CD endoscopy Improvement by at least 50%, ITT-NRI, Week 10 + =16% =11% Central reading # Local reading # +: p<0.10 : Only using segments explored at both baseline and week 10 (matching segments) 13

14 FITZROY: histopathology ITT-LOCF, W10 mean CFB *: p<0.05 * * Total score = sum of all 7 histological variables (architectural changes + mononuclear cells in lamina propria + epithelial damage + polymorphonuclear cells in lamina propria + neutrophils in epithelium + erosion or ulceration + granuloma) 14

15 DIVERSITY & SELECTION in IBD 100 and 200 mg DIVERSITY 1 Crohn s Ph3 1,320 pts 58 weeks Remission: PRO2, endoscopic W10 & W58 Induction & maintenance DIVERSITY 2 Long term extension/maintenance study SELECTION 1 UC Ph2/3 1,300 pts 58 weeks Remission: Mayo score W10 & W58 Induction & maintenance SELECTION 2 Long term extension/maintenance study 15

16 Cystic fibrosis Use of potentiators and correctors NORMAL CLASS II CLASS III Cl- Cl- Cell Nucleus Cell Nucleus Cell Nucleus CF mutation F508del G551D Allele frequency ~90% 4% Approved/filed drugs Orkambi Kalydeco Galapagos Potentiator +C1 +C2 Potentiator 16

17 CF portfolio Preclinical Ph1 Ph2 Status Potentiator 1837 Potentiator 2451 Potentiator 3067 C1 corrector 2222 C1 corrector 2851 C2 corrector 2737 Ph2 results: H2 16 Ph1 results: H1 17 Ph1 start: 2017 Ph2 start: Q4 16 Ph1 start: 2017 Ph1 start: Q4 16 On track to have triple combo in patients by mid

18 1837: superior potentiator G551D/F508del primary cells CFTR function = 10.5% FEV1 in Ph3 studies Kalydeco

19 SAPHIRA on track 1837 Ph2 trial Dose escalation with 1837 Follow-up 4-wk SAPHIRA 1: G551D (26 pts) - enrollment completed SAPHIRA 2: S1251N (7 pts) - data published Recruitment in 6 EU countries & Australia Includes Kalydeco naive & treated (after 7d washout period) Primary endpoints: safety & tolerability Secondary endpoints: sweat chloride, FEV1, plasma levels 19

20 SAPHIRA 2 Impact of ivacaftor washout, treated vs naïve Short (7 days) washout for ivacaftor pretreated subjects (n=3): Substantial increase of sweat chloride levels, confirming its value as biomarker Slight FEV 1 decline (-3%) 20

21 SAPHIRA 2 Changes in FEV 1 in S1251N Confirmation of in vitro assays 21

22 SAPHIRA 2 Changes in sweat chloride in S1251N Day 15 (2 wks on 62.5 mg b.i.d.) Day 29 (2 wks on 125 mg b.i.d.) SwCl > 15 mmol/l > 50 mmol/l > 15 mmol/l > 50 mmol/l # Subjects 2/5 0/5 4/5 1/5 Confirmation of in vitro assays 22

23 Dual and triple combinations F508del/F508del primary cells % of dual combo CFTR restoration 400% 300% 200% 100% Orkambi GLPG triple combo achieves greater CFTR vs Orkambi in vitro 23

24 Triple combination in heterozygotes G542X/F508del organoids Lumen area after stimulation, % increase vs untreated Orkambi GLPG triple combo 24

25 High level path for CF program Q 2Q 3Q 4Q Q 2Q 3Q 4Q Potentiators SAPHIRA Correctors Combinations DUAL P + C1 TRIPLE TRIPLE FiH studies Combinations in healthy volunteers Patient evaluations 25

26 1690: fully owned Autotaxin inhibitor 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 and PK Phase 2: Ph2A biomarker study in IPF patients Novel mode of action Once or twice daily oral Orphan status in EU, requested in US Topline exploratory Ph2A in Q

27 1690 in vivo activity 21-day prophylactic mouse bleomycin model Ashcroft fibrotic score Collagen content vehicle BLM + vehicle BLM + pirfenidone 50 mg/kg bid BLM mg/kg bid BLM mg/kg bid 1690 at 30 mg/kg bid significantly superior to pirfenidone 27

28 FLORA: topline Q2 17 GLPG1690 exploratory Ph2A trial in IPF Flora Screening 4-wk GLPG1690, oral, 600 mg once daily (n=18) Placebo (n=6) 12-wk Follow-up 2-wk 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 28

29 1972 for osteoarthritis OA: breakdown of joint cartilage 118 M patients in US & Europe No disease-modifying drugs approved today Undisclosed mechanism of action Phase 1: target engagement, favorable safety and PK Half-life ~10 hours, steady state after 3 days Inhibits cartilage breakdown in healthy volunteers Collaboration with Servier includes full US rights for GLPG GLPG to file IND for patient study by end

30 serum biomarker (%) 1972 Ph1 topline Pharmacodynamics: cartilage breakdown biomarker in MAD DAY1 mean placebo DAY1 mean '1972 DAY14 mean placebo DAY14 mean ' cohort C-300mg cohort D-600mg cohort E-1050mg Marked reduction of cartilage breakdown at D14 with

31 MOR106 for atopic dermatitis AD: inflammatory disease causing very dry skin, severe itching 66M patients in US & Europe No disease-modifying drugs approved today First-in-class human MAb based on MOR s Ylanthia platform Novel 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 Intravenous infusion 50/50 collaboration with MOR Topline results from Ph1B expected H

32 Cash, cash equivalents & restricted cash M Dec-15 Gilead transaction Cash proceeds from warrant exercises Currency translation (non-cash) 32 Operational cash burn Cash burn of 78 M in line with guidance Notes: includes restricted cash of 7.9 M in Dec 15 and 8.0 M in Sep-16 excludes tax receivable from Belgian & French governments of 67.3 M in Sep-16 Sep-16

33 Clinical news flow Disease area Program Partner H2 16 FY 17 Rheumatoid arthritis filgotinib Start Ph3 Crohn s filgotinib First dosing Ph 3 in Q4 Ulcerative colitis filgotinib First dosing Ph 2/3 in Q4 Additional indications filgotinib Start multiple POCs with filgotinib Cystic fibrosis multiple 1837 Ph 2 results 2737 Ph 1 start 2451 Ph 1 results 2737 Ph 1 results Additional Ph 1 starts Triple selection Start triple in patients 33

34 Clinical news flow Disease area Program Partner H2 16 FY 17 IPF GLPG1690 Ph 2 recruited Topline Ph2A IPF GLPG2938 Start Ph1 Osteoarthritis GLPG1972 GLPG files US IND Start Ph2 in US Atopic dermatitis MOR106 First patient dosing Topline Ph1B Atopic dermatitis GLPG2534 Start Ph1 34

35 Outlook Filgotinib in Ph3 CF triple combo on track Further discovery programs to reach the clinic Platform to fill pipeline Solid balance sheet 35

36 Appendix slides 36

37 Comparison JAK inhibitors profile filgotinib ABT-494 baricitinib tofacitinib Hb NK cells Platelets Atherogenic index Dosing adjustment* Best profile Not/less favorable profile Unknown * Based on drug drug interaction and special populations 37

38 High efficacy rates in DARWIN ACR50, QD groups, ITT-NRI, at week 24 % responders 70 DARWIN 1 (+ MTX) 70 DARWIN 2 (monotherapy) Placebo mg 100 mg 200 mg mg & 200 mg to be tested in FINCH Phase 3 program 0 0 Subjects who switch treatment at week 12 are handled as if they discontinued at week 12 38

39 Crohn s: primary endpoint achieved FITZROY study CDAI responses, ITT-NRI, Week 10 % responders * 60 Placebo (n=44) ** mg (n=130) Clinical remission 100-points clinical response *: p<0.05; **: p<

40 Competition TNF naives Clinical remission: induction % responders Active Delta Placebo Xeljanz 5mg W4 Cimzia 400mg W12 PRECISE-1 Stelara 6mg/kg IV W8 Entyvio 300mg W10 GEMINI-3 Humira 160mg W4 CLASSIC-1 Eldelumab 20mg/kg W11 Phase 2A Filgotinib 200mg W10 FITZROY Note: data not from head-to-head studies 40

41 1690 At the heart of fibrotic pathways 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 41

42 Medical conferences Dates Topics ACR Nov 11 16, Washington DC DARWIN PROs & biomarkers, modelling AIBD Dec 8-10, Orlando FITZROY patient reported outcomes 42