A career on the science park

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1 A career on the science park Onno van de Stolpe December 2014 Copyright 2014 Galapagos NV

2 1987 MOGEN Agricultural biotech pioneer Design of transgenic plants with improved traits Close link with Prof Schilperoort Molecular Biology, LU Role: business development 2

3 1995 Molecular Probes Leader in fluorescent reagents European HQ with sales, marketing, distribution & tech assist Close link with Professor Tanke Microscopic Imaging & Technology, LU Role: managing director 3

4 1998 Introgene Gene therapy Leading Dutch biotech Close link with Alex van der Eb Molecular Carcinogenesis, LU Role: managing director genomics 4

5 1999 Galapagos From target to drug 400 people, ~ 100 million in revenues Close links with Dr. Eelco de Koning Endocrinologist LUMC Dr. Christine Mummery Developmental Biology LUMC Dr. Pieter Hiemstra Pulmunary disease LUMC 5

6 Three too s in drug development It takes too long. It is too risky. It is too expensive. 6

7 Galapagos at a glance Founded in 1999 as joint venture of Crucell and Tibotec 400 staff, research sites in 4 countries with HQ in Belgium Focus on novel mode of action medicines proprietary successful target discovery platform 4 phase II trials, 1 phase I trial, six candidates, >20 in discovery 7

8 The basis of Galapagos Novel disease targets Imbalance of target: disease Correct level of target: cure 8

9 Target identification shrna constructs clone into vector adenovirus arrayed library cellular assay 9

10 Chance of success are small. Drug discovery = attrition Drug targets Hit-to-lead Leads Candidate drugs Phase I Phase II Phase III It takes multiple targets to be successful 10

11 Value Value creation takes long.. Phase II ends Phase III begins Phase I begins Phase II begins Time Biggest value generation at clinical Proof of Concept (PoC) Keep ownership until PoC 11

12 And developing drugs is expensive 12

13 What our pipeline looked like in 2005 Targets Hit identification Hit-to-lead Rheumatoid arthritis GLPG0259 Osteoarthritis 11 GLPG Osteoporosis 19 2 Alzheimer's disease 17 Our # of programs in chemistry was limited by available cash 13

14 so we developed our alliance strategy Based on novel drug targets, discovered by Galapagos Partner has option to license program at candidate drug, Ph I or PoC Galapagos runs R&D programs through milestone payments Access to disease expertise from pharma Target to PCC Pre-clinical Phase I Phase II Phase III Launch handover to partner partner 14

15 Alliance business We received ~ 400 M cash in since 2006 (start 1 st alliance) Upfronts, success-based milestone payments + royalties 15

16 Towards a novel drug in RA Discovered target MAPKAPK5 using patient cells Identified compounds that inhibit MAPKAPK5 GLPG0259 effective in mouse RA model (reduces inflammation & bone/joint destruction) GLPG0259 reduces joint destroying enzymes in mouse RA model GLPG0259 completed Phase I clinical trials diseased 4 day treatment 16

17 GLPG0259 Phase II Interim analysis ACR20 response ACR50 response Decreased CRP Jak inhibitor (Pfizer) studies GLPG0259 study - - +/- Conclusion: discontinue trial due to limited efficacy potential in RA 17

18 April 2011 GLPG0259 failed in Phase II 18

19 And the market reacted. banking crisis 0259 failure 0634 results 19

20 Our next shot on goal: GLPG0634 A rocky road to the clinic JAK 1 target identified in 2004 by Galapagos in osteoarthritis program Molecule developed within alliance with GSK Therapeutic focus shifted from osteo- to rheumatoid arthritis GSK ended this alliance program summer 2010 Galapagos started phase I in August

21 634 efficacy Ph II POC 36 patients in 4 weak trial Changes in serum CRP (mg/l) % patients reaching ACR20 Highly efficacious with rapid onset of action, no reported side effects 21

22 22

23 Deal structure with Abbott Upfront payment $150 million Galapagos performs & funds Phase II in RA, Abbott contributes $20 million License fee $200 million after achievement Phase IIb criteria Abbott performs & funds Phase III, registration & commercialization GLPG to receive up to $1 billion in milestones + double digit royalties Phase II Phase III Marketing and sales handover after Phase IIb Benelux 23

24 And the market reacted. Abbott deal 0634 results 24

25 Where we are with 634 Running a 100 million phase II study Add-on to MTX 595 patients Monotherapy 280 patients Long term extension 25

26 Making the impossible possible 15 years balancing on the tightrope Margin between success & failure razor thin Be an optimist Follow your path to your goal It never gets easy, but it is a lot of fun 26

27 27

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