How To Make A Profit From A Drug

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1 Nanobodies creating better medicines Corporate presentation May 2015

2 Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this presentation regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this presentation as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its parent or subsidiary undertakings or any such person s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this presentation or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this presentation. 2 2

3 Ablynx Corporate snapshot CORPORATE Drug discovery and development company in Ghent, Belgium >300 employees TECHNOLOGY Pioneer in next generation biological drugs Nanobodies >500 granted and pending patents PRODUCTS >30 programmes six at the clinical development stage Three clinical proof-of-concepts (POC) 2 wholly-owned products in later stage clinical development (Phase III & Phase II) >10 new clinical programmes anticipated over the next 3 years PARTNERS AbbVie, Boehringer Ingelheim, Eddingpharm, Merck & Co, Merck Serono and Novartis FINANCIALS 193M in cash at 31 March

4 2014 A year of great progress 1 Pipeline value creation 6 clinical trial read outs of which Phase II clinical proof-of-concept with caplacizumab in TTP 4 clinical trials initiated of which first inhaled Nanobody in patient population 2 Expanding existing collaborations Immune-onco deal with Merck & Co worth 20M upfront, 10.7M research funding and up to 1.7Bn in future milestones plus royalties 2 nd licensing agreement with Eddingpharm 3 Corporate development 1 st step in a building commercial infrastructure with appointment of Chief Commercial Officer Financial position strenghtened through oversubscribed private placement of new shares (raised 41.7M) 4 4

5 Unique technology What are Nanobodies?

6 Nanobodies Derived from heavy-chain only antibodies Camelid heavy-chain only antibodies are stable and fully functional Nanobodies represent the next generation of antibody-derived biologics C H 1 V H V HH 12-15kDa V HH V L Ablynx s Nanobody C H 2 C L C H 2 small robust C H 3 C H 3 sequence homology comparable to humanised/human mabs easily linked together nano- to picomolar affinities Conventional antibodies Heavy chain only antibodies intractable targets multiple administration routes manufacturing in microbial cells 6

7 Ablynx s platform Rapid generation of high quality biologics Immunise llamas with antigen or use synthetic library Wide range of highly diverse Nanobodies with nM affinities Formatted* Nanobodies ready for in vivo testing Cloning and production in microbial systems ~12-18 months *Glycine-serine linkers from C-terminus to N-terminus 7

8 8 Nanobody platform Competitive advantages Mix and match Targeting different pathways at once with a single Nanobody construct, e.g. multiple checkpoint inhibitors Challenging and intractable targets Nanobodies can reach conserved cryptic epitopes Nanobodies against ion channels and GPCRs Alternative delivery routes Inhalation Oral-to-topical Needle-free Ocular Cell- /tissue-homing Cell specificity Immune cell recruitment Tissue-specific targeting Customised half-life extension Fc Nanobodydrug conjugates High-yield, highconcentration, low-viscosity, microbial production Weeks/days/hours Cell killing Manufacturing Albuminbinding Nanobody Ag-1 Ag-1 Ag-2

9 Product pipeline >30 programmes in development Two wholly-owned in later stage clinical development

10 PARTNERED FULLY OWNED Proprietary and partnered programmes Multiple shots on goal Clinically validated targets First-in-class Therapeutic area Product name Target Discovery Pre-clinical Phase I Phase II Phase III Filing Haematology caplacizumab vwf Respiratory ALX-0171 RSV Oncology/ Immuno-oncology Inflammation/ Immunology Various Various Ocular Inflammation/ Immunology Various ALX-0061 IL-6R ALX-0761 IL-17F/IL-17A ozoralizumab TNFα Greater China Various Oncology/ Immuno-oncology Various Bone disorders ALX-0141 RANKL Greater China Neurology Various CXCR2 Other Various 10

11 Leading programmes in the clinic Pipeline value drivers PROPRIETARY Programme (target) Indication Key differentiating features Stage Caplacizumab (vwf) Thrombotic thrombocytopenic purpura First-in-class orphan drug Novel mode of action Inhibition of microthrombi formation Start Phase III H and MAA filing in H in EU for conditional approval ALX-0171 (RSV) Respiratory syncytial virus infection First-in-class addressing high unmet need Inhaled Nanobody delivered to infection site Highly potent trivalent construct Start first-in-infant study Q4 2014: results expected in H PARTNERED Programme (target) Indication Key differentiating features Stage Partner ALX-0061 (IL-6R) RA, SLE Best-in-class opportunity Monovalent interaction; strong affinity and preferential binding to soluble IL-6R 3 Phase II studies (RA; SLE) in 2015 RA results expected in 2016 ALX-0761 (IL-17A/F) Psoriasis Potent neutralisation of both IL-17A and IL-17F POC achieved in primate CIA* model Psoriasis Phase Ib on-going: potential clinical POC results expected in 2015 * Collagen induced arthritis model 11 11

12 12 Caplacizumab Wholly-owned anti-vwf Nanobody First-in-class bivalent Nanobody with Orphan Drug Status Developed for the treatment of acquired thrombotic thrombocytopenic purpura (TTP) Phase III study to start in H Filing expected in H for conditional approval in Europe based on Phase II results Peak sales potential of 300M- 400M 1 1 US, EU, Japan, other markets (Brazil, Canada, Russia, Mexico, Australia)

13 13 Caplacizumab What is the biological basis of TTP? Caplacizumab blocks the platelet ULvWF interaction Ultra-Large (UL) vwf multimers endothelium ADAMTS13 activity is impaired Platelet string formation in patients with TTP Caplacizumab binds to A1 domain of vwf and thereby inhibits platelet string formation Ex vivo assay for platelet string formation Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of TTP patients ULvWF Without treatment, fluorescently labelled platelets adhere to UL-vWF, observed as string-like structures ULvWF and anti-vwf Nanobody Caplacizumab inhibits the formation of platelet strings and potentially the associated microvascular thrombi in many organs

14 14 Acquired TTP Significant unmet medical need Severe fatigue, headache, coma, abdominal pain, weakness, nausea, bizarre behaviour, vertigo, seizures Daily PE in hospital until recovery of platelet count HEALTHY PERSON SUDDEN ONSET EMERGENCY Potentially life threatening rare disorder of the blood coagulation system incidence of 11.3 per million 1 ~10,000 acute events annually in US and Europe Extensive microscopic thrombi formed in small blood vessels throughout the body High unmet medical need no approved medicinal product for treatment available mortality remains high (10-30%) 2 and ~ 36% of patients have relapses 1 major morbidities after TTP episode such as neurocognitive impairment standard of care is plasma exchange (PE) plus immune suppressants 1 George et al, 2008; 2 Allford et al, 2003, Kremer Hovinga, 2010; Benhamou 2012

15 RANDOMISATION 15 Caplacizumab Phase II TITAN design and schedule 1:1 PE Placebo N=39 30 days 30 days 1 year follow-up Target 110 subjects Actual 75 subjects PE Caplacizumab N=36 30 days 30 days Primary endpoint: time to confirmed normalisation of platelet count Secondary endpoints: plasma exchange frequency and volume; relapse; exacerbations; mortality; major clinical events (stroke, MI, organ dysfunction); recovery from signs/symptoms; ADA 1 year follow-up Safety & efficacy endpoints Long-term endpoints: ADA; relapse; non focal neurological symptoms

16 TITAN trial summary Strong clinical proof-of-concept PRIMARY ENDPOINT Patients treated with caplacizumab achieved confirmed platelet normalisation at more than twice the rate of the group treated with placebo This effect was statistically significant (p = 0.013) SECONDARY ENDPOINT 71% fewer patients with an exacerbation No deaths in the caplacizumab arm compared to 2 deaths in the placebo arm SAFETY Increased bleeding tendency (but believed to be manageable) Overall, caplacizumab has an acceptable safety profile 16

17 Caplacizumab Current status and next steps Confirmed clinical activity and good safety profile in the clinic Intention to file for conditional approval in EU in H based on Phase II Preparations progressing to start Phase III study in H Intention to submit BLA in USA following Phase III study completion Commercialisation/partnering strategy currently under evaluation Caplacizumab could be approved for sale in Europe in

18 18 ALX-0171 Wholly-owned anti-rsv Nanobody First-in-class trivalent Nanobody for the treatment of respiratory syncytial virus (RSV) infection in infants Delivered by inhalation First-in-infant Phase IIa on-going with results expected in H Opportunity in multi-billion dollar market

19 19 RSV infection in infants High unmet medical need Leading cause of infant hospitalisation and primary viral cause of infant death ~300,000 children* (< 5 years) hospitalised per year in 7 major markets 1,2 increased medical cost in the first year following RSV infection 3 prolonged wheezing and increased risk for asthma development 4 No widely accepted drug available to treat RSV infections Synagis used as prophylaxis in high-risk pre-term infants only ($1.1Bn sales in 2013) Evolves to distressing symptoms Symptomatic treatment including inhaled corticosteroids & bronchodilator 8-20% hospitalised * Extrapolation based on estimated US prevalence 1 Hall et al, NEJM, 2009; 2 Lee et al, Human Vaccines, 2005; 3 Shi et al, J Med Econ, 2011; 4 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014

20 % of lambs with score 1 20 ALX-0171 Key milestones achieved Well tolerated in multiple Phase I clinical studies in adults In vitro and in vivo studies demonstrated potent anti-viral effect against recent clinical RSV isolates 10,000 fold reduction in viral titres and superiority over palivizumab (Synagis ) 1 daily inhalation of ALX-0171 for 3 consecutive days in neonatal lamb model for infant RSV demonstrated markedly reduced symptoms of illness ( Malaise Score ) RSV vehicle RSV ALX-0171 Vehicle RSV infection Treatment ALX-0171 or formulation buffer 1 Vaccines of the World (Oct 2013) 2 RSV Symposium (Nov 2014) presentations on

21 RANDOMISATION ALX-0171 First-in-infant inhalation study Infants aged 3 to <24 months who are hospitalised for RSV infection 24 EU centres and additional centres Southern Hemisphere (risk mitigation) Custom-developed infant inhalation device (vibrating mesh) ALX-0171 N=20 Open-label lead-in N=5 Review by DMC* 2:1 Inhaled ALX-0171 once/day or placebo 3 consecutive days Inhaled ALX-0171 once/day 3 consecutive days Placebo N=10 Primary endpoint: Safety and tolerability of ALX-0171 Started Q Results expected H Secondary endpoints: Clinical effect (feeding, respiratory rate, wheezing, coughing, general appearance) PD (viral load), PK (ALX-0171 systemic concentration) and immunogenicity * Data monitoring committee 21

22 ALX-0171 Current status and next steps Strong therapeutic effect demonstrated in a neonatal animal model for infant RSV infection Well tolerated in multiple Phase I studies in adults First-in-infant Phase IIa study initiated in Northern Hemisphere; lead-in phase successfully completed and placebo-controlled phase of the study on-going Recruitment of Phase IIa study to continue in parts of Asia-Pacific region with the goal to complete recruitment of the placebo-controlled phase by end 2015 with results anticipated in H With ALX-0171, Ablynx could potentially achieve its fifth clinical proof-ofconcept for Nanobodies, and its first for an inhaled Nanobody 22 22

23 ALX-0061 Anti-IL-6R Nanobody partnered with AbbVie Monovalent half-life extended Nanobody Best-in-class potential for the treatment of auto-immune disorders Global licensing agreement with AbbVie Phase IIb studies in RA started and Phase II study in SLE to start around mid 2015 Opportunity in multi-billion dollar markets RA: rheumatoid arthritis SLE: systemic lupus erythematosus 23

24 % of patients ALX-0061 Compelling Phase IIa results in RA patients Treatment was highly efficacious and was well tolerated No increase in adverse events upon extension of treatment No anti-drug antibodies were reported 100 ACR50 score as potential differentiating factor All unmodified ALX-0061 at week 24 (N=24) ACR20 ACR50 ACR70 DAS28 remission Boolean remission 24

25 ALX-0061 Global licensing deal with AbbVie Economics $175M upfront at signing in September 2013 $665M total potential milestones plus double-digit royalties Ablynx Perform and fund Phase I study with subcutaneous formulation (successfully completed in 2014) Perform and fund Phase II studies in RA and SLE (start 2015) AbbVie Pay a fee for each indication if they exercise the right to license ALX-0061 after completion of the Phase II studies Responsible for Phase III development and registration Commercialisation AbbVie is responsible for global commercialisation Ablynx retains option to co-promote ALX-0061 in the Benelux 25 25

26 RANDOMISATION ALX-0061 Phase IIb RA combination study with MTX* First patient dosed in March 2015 Adult subjects with moderate to severe RA despite MTX therapy Worldwide, randomised, double-blind, placebo-controlled 24 week dose finding study Eligible subjects will be invited to roll-over into open-label extension (OLE) study ALX-0061 dose 1, Q4W Primary endpoint at week 12: ACR20 response 330 subjects 1:1:1:1:1 ALX-0061 dose 2, Q4W ALX-0061 dose 2, Q2W ALX-0061 dose 3, Q2W Placebo Secondary endpoints: ACR responses over time, disease activity scores, EULAR DAS28 response, remission, effects on quality of life Other assessments: pharmacokinetics, pharmacodynamics, safety/tolerability, immunogenicity * methotrexate 26

27 RANDOMISATION 27 ALX-0061 Phase IIb RA monotherapy study First patient dosed in April 2015 Adult subjects with moderate to severe RA who are intolerant to MTX or for whom continued MTX is inappropriate Worldwide, randomised, double-blind 12 week study (Ro)Actemra arm to obtain parallel descriptive information on efficacy and safety Eligible ALX-0061 treated subjects will be invited to roll-over into an OLE study ALX-0061 dose 1, Q4W Primary endpoint at week 12: ACR20 response 1:1:1:1 ALX-0061 dose 1, Q2W ALX-0061 dose 2, Q2W Secondary endpoints: ACR responses over time, disease activity scores, EULAR DAS28 response, remission, effects on quality of life 228 subjects (Ro)Actemra 162mg Q1W (EU) or Q2W (US) Other assessments: pharmacokinetics, pharmacodynamics, safety/tolerability, immunogenicity

28 ALX-0061 Key data points in clinical development Phase I sc study Results announced 23 Oct 2014 ALX-0061 showed >80% bioavailability after sc injection Phase IIb combination and monotherapy studies in RA Top line results potentially continues development in RA Phase II RA OLE study Phase II study in SLE Top line results potentially continues development in SLE 28

29 29 Additional clinical assets Licensed to partners ALX-0761 anti-il-17a/f Merck Serono (global) ALX-0141 anti-rankl Eddingpharm (Greater China) Ozoralizumab anti-tnfα Eddingpharm (Greater China)

30 Partnerships Broad platform exploitation and cash generation

31 31 Current partnerships Broad platform exploitation and value creation Global licensing deal for ALX-0061 (anti-il-6r) in RA and SLE Strategic discovery alliance (focus on bi-specifics) multiple programmes on-going 2 licensing deals in Greater China for ALX-0141 and ozoralizumab 2 discovery deals: ion channel deal; immune-onco deal with focus on multi-specifics 4 agreements: multiple programmes on-going (lead project in Phase Ib) Target-based discovery deal >20 active programmes; > 340M in non-dilutive cash received ~ 3Bn in potential future milestones plus royalties

32 Outlook Potential value enhancing events

33 2015 Potential value drivers Developing the pipeline Programme read outs Commercial Caplacizumab (vwf): i) confirm regulatory pathway ii) start Ph III in acquired TTP ALX-0061 (IL-6R): dose first patient in: i) Ph IIb RA combination therapy ii) Ph IIb RA monotherapy iii) Ph II in SLE ALX-0171 (RSV): complete recruitment of Phase IIa Partnered programmes: potential start of 3 Phase I s ALX-0761 (IL-17A/F) (Merck Serono): expect POC Phase Ib results in psoriasis patients in H Potential in vivo pre-clinical POC results from initial programmes as part of IO collaboration with Merck & Co Caplacizumab (vwf): determine partnering and commercialisation strategy Potential milestone payments from on-going partnerships Continuing partnering discussions Extend existing collaborations/ enter into new collaborations An important year ahead! 33 33

34 34 Long term value creation Some potential clinical and regulatory key events Clinical study results Key regulatory events 2015 ALX-0761 Phase Ib POC (psoriasis) Licensed to Merck Serono (worldwide) 2016 ALX-0171 Infant Phase IIa (RSV) Wholly-owned ALX-0061 Phase IIb combination therapy (RA) AbbVie have option to license worldwide ALX-0061 Phase IIb monotherapy (RA) AbbVie have option to license worldwide 2017 Caplacizumab MAA filing EU Phase III results (TTP) Wholly-owned ALX-0171 Infant Phase IIb (RSV) Wholly-owned ALX-0141 and ozoralizumab Phase I/II in China Licensed to Eddingpharm (China) ALX-0761 Phase IIa (psoriasis) Licensed to Merck Serono (worldwide) 2018 Caplacizumab conditional approval EU and BLA filing in US Wholly-owned ALX-0061 Phase II (SLE) AbbVie have option to license worldwide Results from various patient studies with partners

35 Questions CONTACT DETAILS Investor Relations investors@ ablynx.com

36 Addendum

37 Shareholders Diversified shareholder base Ordinary shares listed on Euronext Brussels (ABLX) Sponsored level I ADRs on the US OTC market (ABYLY) 54.3M shares outstanding 2.7M outstanding warrants Free float is ~90% Total shares outstanding by type % of Institutional and Private Bank Owners by Geography (representing 65% of total S/O) Abingworth (UK); 9,03% Boehringer Ingelheim (DE); 3,94% France; 2,86% Other; 5,23% Aviva Investors (UK); 5,00% Perceptive Advisors (US); 3,82% Scandinavia; 4,49% US; 33,87% Other institutional and retail investors; 72,15% Polar Capital Funds Plc (UK); 3,05% FMR LLC (US); 3,01% Benelux; 32,59% UK; 20,97% 37

38 38 Financial summary Full year results 2014 M Revenue Operating result (29.8) (17.7) (16.2) Cash position Anticipated net cash burn for 2015 of approx M 1 Cash, cash equivalents, restricted cash and short-term investments at the end of the period

39 39 Ablynx shares Three-year performance

40 Nanobodies Pushing the limits of antibody technology scfv lgg Diabody Bi-specific, tetra-valent DVD-lg Nanobodies 1 st generation 150 kda bi-valent fixed half-life mono-specific 2 nd generation kda mono- or bi-valent short or long half-life bi-specific 3 rd generation kda valency of choice short or long half-life multi-specific 40

41 Nanobodies Compared to other platforms and mabs Features Nanobodies DARTS (MacroGenics) Darpins (Molecular Partners) mabs Speed of discovery ++/ /+++ Formatting flexibility Bi-specific formats ++/ Manufacturability High concentration formulation ++/+++ ND ND +/- Tailored in vivo half-life Alternative routes of administration Broad target applicability incl. GPCRs and ion channels +++ ND +/ ND ND +/- Clinical validation Ph II Ph I Ph II Multiple marketed ND: not demonstrated 41 41

42 Nanobodies Most versatile and clinically validated platform Technology Ablynx Nanobodies Affimed Macrogenics Pieris Molecular partners F-Star Genmab TandAb DART Anticalins DARPINs mab2-fcab Duo-bodies Clinical programmes* Amgen Abbvie Chugai GSK Genentech Roche Sanofi J&J BMS Technology BiTE DvD-Ig Bispecific mab Domain Ab 2-in-1 CrossMab Bispecific mab Fyno Mab Centyrins Adnectins Clinical programmes* * No. of molecules binding to more than one target or epitope in clinical development 42

43 Bi-specific Nanobodies Synergistically improve potency All HIV strains need the primary receptor CD4 and a chemokine co-receptor to enter and infect host CD4+ T cells X4 type viruses use CXCR4; R5 type viruses use CCR5 Synergistic improvement in HIV-1 blockade of CXCR4-CD4 bi-specific Nanobody over monovalent Nanobodies up to 320-fold enhancement with bi-specific Nanobody over mono-specific only 2-fold enhancement with combination of monovalents in solution (1:1) over monospecific linking of the Nanobodies is essential for strong enhancement Blockade of HIV infection in vitro* CD4 + anti-cxcr4/cd4 anti-cxcr4 anti-cd4 anti-cxcr4 + anti-cd4 CXCR4 * Infection of HIV1 X4 NL4.3 in human MT-4 T cells Collaboration with Dr. Dominique Schols, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium 43

44 OD nm 44 Nanobodies Multi-valent formatting to improve potency Tri-valent anti-rsv (ALX-0171) improve activity and strain coverage by multi-valency superior virus neutralisation as compared to palivizumab 5-fold more clinical isolates neutralised below LLOD with ALX-0171 compared with palivizumab ,000-fold Concentration (M) palivizumab A-strain B-strain Total n palivizumab 0 (0%) 11 (38%) 11 (18%) ALX (94%) 23 (79%) 53 (87%) p value < < < Number of strains neutralised below lower limit of detection Improved potency over mab Increased strain coverage

45 Nanobody formatting Biparatopic format yields the required potency and efficacy Potent but not efficacious Lower potency but efficacious Biparatopic is both potent and efficacious 45

46 Caplacizumab Phase II study Primary endpoint Median days to confirmed platelet response subjects with no prior plasma exchange (95% CI) Caplacizumab 3.00 (2.74, 3.88) N = 34 Placebo 4.92 (3.21, 6.59) N = 35 25th & 75th percentile 2.72 & & Median days to confirmed platelet response subjects with one prior plasma exchange (95% CI) 2.44 (1.92, 2.97) N = (2.91, 5.68) N = 4 25th & 75th percentile 1.92 & & 5.23 N = 36 N = 39 Overall Hazard Rate Ratio for caplacizumab vs. placebo (95% CI), N = (1.278, 3.778) Stratified log-rank test p-value The group of patients treated with caplacizumab in conjunction with the standard of care achieved confirmed platelet normalisation at more than twice the rate of the group receiving the standard of care plus placebo Time to confirmed platelet normalisation 46

47 Caplacizumab Phase II study Secondary endpoints Caplacizumab N* = 36 Placebo N* = 39 Subjects with an exacerbation within 30 days after stopping daily PEX Subjects in complete remission within 30 days after stopping daily PEX as measured by confirmed platelet response and absence of exacerbations Subjects with an exacerbation and/or relapse at 1 month follow-up after study drug treatment was completed 3 (8%) 11 (28%) 29 (81%) 18 (46%) 13 (36.1%) 13 (33.3%) Deaths 0 2 These top line secondary endpoints illustrate the potential protective effect of caplacizumab treatment in the acute phase of TTP * Intention-to-Treat (ITT) population: 75 subjects, all randomised to caplacizumab (36) or placebo (39) 47

48 48 Caplacizumab Safety profile in TITAN Phase II trials Proportion of subjects Caplacizumab N = 35 Placebo N = 37 Subjects with any TEAE 97% 100% - with bleeding event 54% 38% Subjects with any TE Serious AEs 57% 51% - with serious bleeding event 6% 5% Subjects discontinued due to TEAE 8% 0% Number of events Caplacizumab N = 35 Placebo N= 37 Number of TEAEs Number of TE Serious AEs Increased bleeding tendency in caplacizumab arm 80% of reported events were mild only 3 subjects required drug treatment (tranexamic acid, methylergonovine) no requirement for vwf/fviii substitution

49 Caplacizumab Commercial opportunity TITAN investigators, other KOLs and payers overwhelmingly positive about caplacizumab product profile and value proposition Orphan Drug addressing a high unmet medical need innovative MOA providing specific platelet protective effect, thereby having the potential to reduce morbidity due to organ damage potential for shorter duration of acute and life-threatening episodes potential for less exacerbations and relapses potential cost savings (reduction in volume and days of plasma exchange; shorter time in intensive care) Ablynx estimates peak sales for caplacizumab to be in the range of 300M- 400M* If the manufacturer can achieve these data at launch, this is a winning product US payer * US, EU5, Japan, other mkts / Jefferies estimates: $400 million peak sales (14 Oct 2014) 49

50 RSV therapeutics Studies currently on-going in infants Administration Entity Dosing ALS8176 (Alios/J&J) oral suspension NCE nucleoside analogue 2/day 5 mg/kg* ALX-0171 (Ablynx) pulmonary nebulisation biologic 1/day MOA polymerase inhibitor fusion inhibitor In vitro potency serotype A 200 nm** IC nm Development status PhII infant study started July 2014 (SAD/MAD; N=168) Results: Nov 2015 PhIIa infant study to start Q (MD; N=35) Results: Q * Based on 375 mg dosing schedule in adult challenge trial (see press release Jul 2014) ** Assuming abstract from 8th RSV conference Oct 2012 refers to ALS-8176 but not explicitly mentioned (Deval et al.) 50

51 RSV pipeline Therapeutics and vaccines currently in development Product Company Class Target population Phase RI-002 ADMA Biologics Anti-RSV antibody prophylaxis Immune-compromised patients RSV vaccine Novavax RSV F-vaccine Infants (maternal immunisation) Phase III ongoing GSK GSK RSV vaccine Infants and children Phase I in adults MEDI-7510* MEDI-8897 MedImmune/ AstraZeneca MedImmune/ AstraZeneca Phase II in pregnant women initiated Q3 14 RSV vaccine Older adults Phase I in older adults Anti-RSV antibody prophylaxis Infants and children RSV-001 Okairos/GSK RSV vaccine Infants and immunecompromised adults ALS-8176 Alios/J&J Nucleoside analogue Infants GS-5806 Gilead RSV fusion inhibitor (Older) adults and bone marrow transplant patients (BMT) Phase I in adults Phase I completed Phase II in infants First-in-infant study withdrawn Phase IIb in (older) adults and BMT ongoing ALX-0171 Ablynx Anti-RSV Nanobody Infants and children 3 Phase I s in adults completed; Phase IIa in infants ongoing ALN-RSV01 MDT-637 Alnylam/Hyowa Hakko Kirin Microdose /Teva Nucleocapsid gene sirna Immune-compromised adults Phase II in lung transplant patients but no longer mentioned as part of pipeline RSV fusion inhibitor Infants and children Healthy adult volunteer challenge study ongoing * Other Medimmune vaccine candidates for infants in NIAID sponsored studies 51

52 Log10 FFU/mL BAL Mean % Involvement 52 ALX-0171 In vivo proof-of-concept achieved Mean viral titers in BALF (day 6 post infection) Lung viral lesions (day 6 post infection) Vehicle RSV Vehicle RSV ALX Vehicle RSV Vehicle RSV ALX-0171 Suitability of neonatal lamb model compared with human challenge model Lambs develop lower respiratory tract infection which is associated with general malaise and specific lung pathology (comparable to infants) Treatment at peak of viral load on day 3 post infection (symptoms and lung pathology are already clearly present) Lambs develop clinical symptoms such as wheezing (comparable to infants)

53 % of lambs with score 1 ALX-0171 Highly effective in RSV infected lambs Malaise Score RSV vehicle RSV ALX-0171 Vehicle Subjective scoring (0 to 4*) of parameters that measure general health Malaise score: weakness, depression, lethargy, drooping of ears, and not eating RSV infection Treatment ALX-0171 or formulation buffer Daily inhalation of ALX-0171 markedly reduced symptoms of illness Daily inhalation of ALX-0171 markedly reduced symptoms of illness in RSV infected neonatal lambs * 0 = no clinical signs; 4 = animals down 53

54 ALX-0171 Successful Phase I inhalation studies in adults September 2012 Phase I first-in-human study 60 healthy volunteers single-ascending dose and multiple dose up to 210 mg inhaled twice daily for 5 days well tolerated, with no clinically relevant adverse events or effects on lung function May 2014 Phase I safety study in adults with hyper-reactive airways 24 subjects single-ascending dose and multiple dose part up to 200 mg inhaled daily for five days some cases of mild bronchoconstriction which could be immediately reversed May 2014 Phase I PK study 41 healthy volunteers single and multiple dose of 200 mg inhaled daily for 5 days and single dose of 0.3 mg/kg iv local half-life of ALX-0171 is approximately 20 hours, confirming potential for once-daily dosing 54 54

55 ALX-0171 Commercial opportunity First-in-class potential addressing a disease with a high unmet medical need no adequate therapeutic treatment for RSV infections in infants Most infants are infected with RSV during their first year of life Nearly all children will have had an RSV infection by the age of 2 Opportunity to treat RSV infection in infants hospitalised setting (~300,000 infants per year in the 7 major markets) out-patient setting (~2 million infants <1 year of age per year in 7 major markets) Current prophylaxis with a mab is expensive and only partially protective. Any new treatment strategy for RSV bronchiolitis is very welcome BE KOL 55

56 56 ALX-0061 Potentially best-in-class anti-il-6r Features Potential benefits Small (26kD) anti-il-6r anti-hsa Penetrates faster and more effectively into tissues Targets human serum albumin (HSA) Monovalent binding Preferential binding of soluble vs. membrane bound IL-6R Strong affinity to soluble IL-6R Low immunogenic potential Tailored PK Prolongs half-life Improved trafficking to inflamed tissue Avoids target cross-linking Superior benefit/risk profile Fast target engagement resulting in fast onset of action Improved safety profile Extended therapeutic window Convenient dosing and scheduling

57 % of patients 57 IL-6(R) and JAK inhibitors ACR50 scores from different clinical studies Week 12 Week ALX Tocilizumab (Roche) 2 Sirukumab (J&J) 3 Sarilumab (Sanofi) 4 Clazakizumab (BMS) 5 Tofacitinib (Pfizer) 6 Filgotinib (Galapagos) 7 1 All pooled/unmodified ALX-0061 treated patients (pooled) at week 12 and week 24; 2 Data extracted from LITHE (4 and 8 mg/kg), OPTION (4 and 8 mg/kg), TOWARD (8 mg/kg) trials; 3 Smolen JS, et al. Ann Rheum Dis 2014 (100 mg Q2W); 4 Phase III MOBILITY trial; 150 mg Q2W and 200 mg Q2W; 5 Phase IIb trial (ACR 2013), Q4W; 25 mg, 100 mg, 200 mg; 6 Data extracted from Phase III Scan, Sync and Standard trials; 5 mg BID and 10 mg BID; 7 Data presented by Galapagos (100 mg BID) on 14 th -15 th April 2015

58 DAS28 CRP Response of ALX-0061 vs. filgotinib Pooled data vs. highest reported responses 100% ALX-0061, 12w Data 100% DARWIN1, 12w Data 80% 80% 60% 4% 60% 40% 40% 14% 20% 50% 20% 36% 7% 0% 0% Pbo Pooled 0% 7% Pbo 100mg BID Remission Low disease activity Remission Low disease activity ALX-0061 as presented on October 4, 2012 DARWIN1 as presented by Galapagos on April 14/15,

59 ALX-0061 Commercial opportunity Potential to treat moderate to severe RA first line biologic monotherapy or in combination with methotrexate (MTX) patients refractory or intolerant to anti-tnfα (Ro)Actemra (the only marketed IL-6R blocker) generated sales of $840M in 2013 and sales are expected to grow to ~$1.5B in and ~$4.8B by ALX-0061 as a novel option for the treatment of severe SLE high unmet medical need among moderate and severe SLE populations ~5 million people worldwide suffer from a form of lupus SLE market expected to grow to $4B in I would definitely consider it as a first line biologic RA treatment. IT KOL 1 Decision Resources SG Cross Asset Research Decision Resources

60 Global RA market Opportunity for anti-il6(r) drugs Global RA market market share and CAGR for the different drug classes* Class Sales ($m) CAGR ( ) (%) Market share (%) In 2013, Humira (AbbVie) for the treatment of auto-immune disorders, was the world s largest selling drug with ~$11B in sales (approved in 7 indications) (Ro)Actemra (Roche/Genentech/Chugai) is currently the only IL-6R inhibitor on the market (used as 2nd and 1st line biologic) (Ro)Actemra generated sales of $840M in 2013 and sales are expected to grow to ~$1.5B in and ~$4.8B by Sales ($m) CAGR ( ) (%) Market share (%) TNF inhibitor % 84% 16,076 4% 69% B-cell depletion 1, % 7.5% 1,285 1% 6% T-cell modulator % 5.6% 2,010 17% 9% IL-6 inhibitor % 4.2% 2,034 24% 9% JAK inhibitor 0 0% 0% 1,566 0% 7% Syk inhibitor 0 0% 0% 313 0% 1.3% IL-17 inhibitor 0 0% 0% 90 0% 0.4% Source: First Word Pharma Decision Resources 2014; 2 SG Cross Asset Research

61 Therapeutics targeting IL-6(R) Drugs currently in development Drug Target Company Disease Dosing Stage SAR REGN88 IL-6R CNTO 136 IL-6 J&J/ GSK Sanofi/ Regeneron RA, uveitis ALD518 IL-6 Alder RA, NSCLC, GVHD* CDP6038 IL-6 R-Pharm/ UCB 150 or 200 mg q2w RA 50 mg q4w, 100 mg q2w RA PF IL-6 Pfizer SLE, CD, RA SA237 Actemra follow-on mg q4w mg q2w RA q4w SLE, CD q8w IL-6R Chugai RA, NMO Q4w or less frequent PhIII/Phii Launch RA mid-2017 PhIII Launch end 2017 PhII dose finding Launch >2018 (following BMS returning the asset) PhII RA PhI SLE, CD PhII RA PhI NMO/NMOSD PhIII FE IL-6 Ferring Various Phase II (Crohn s) Tocilizumab biosimilar Tocilizumab biosimilar IL-6R BioXpress Research IL-6R Panpharmaceuticals Research * Graft versus host disease; ** Neuromyelitis optica 61 61

62 Rheumatoid arthritis Current and emerging therapies 1% JAK inhibitors Total RA market 2013: $14bn Expected to grow to $18bn by % 6% 6% 9% 7% IL-6R inhibitors B-Cell therapies Selective costimulation modulators Conventional DMARDs TNFα inhibitors TNFα inhibitors dominate the RA market; but for >30% of patients, alternative treatment approaches are needed (patients may not respond or may not tolerate the drug, or become refractory) Anti-IL-6R treatment is clinically validated with (Ro)Actemra ; ALX-0061 falls within the anti-il-6r drug class AbbVie is committed to various drugs with differents MOAs (transcript Q conf call): Behind HUMIRA we have a rich pipeline of mid- and late-stage immunology assets in clinical development. We're also working to advance several other mid-stage immunology programs, including ABT-122 (our anti-il-17 TNF combination) and an anti-il-6 antibody, among others. All of our R&D efforts are focused on advancing the standard of care in each of our areas of immunology leadership. Source: AbbVie; Decision Resources 2014 Source: AbbVie; Decision Resources

63 Arthritis score ALX-0761 Bi-specific Nanobody in psoriasis ALX-0761 blocks both IL-17A and IL-17F (involved in inflammation); binds HAS for improved PK Targeting both IL-17A and IL-17F could be more effective in blocking the inflammatory response IL-17F forms homodimer and heterodimers with IL-17A IL-17F exerts similar in vitro biological activity as IL-17A but is secreted by different cell types Developed by Merck Serono completed Phase I SAD study in healthy volunteers ongoing Phase Ib study in patients with psoriasis (results expected in 2015) Secukinumab (Novartis) most advanced anti-il-17a in development (registration phase) with estimated peak sales of ~$500M* anti-il17f anti-hsa anti-il17a Proof-of-concept achieved in primate collagen induced arthritis model Days Vehicle ALX-0761 (2.8mg/kg) ALX-0761 (10mg/kg) * Analysts estimates Poster available on Ablynx website: R&D>pipeline 63

64 Unmet need in psoriasis Rationale for targeting IL-17-T h 17 IL-17A and TNFα are pro-inflammatory cytokines, produced by lineages of T H 1 and T H 17 cells, which are found in blood and skin lesions of people with psoriasis ~50% of patients with moderate to severe psoriasis receive only topical or no treatment at all and >50% of patients dissatisfied with current treatments Novartis Cosentyx (secukinumab) will be the first anti-il-17a therapeutic on the market (2015 expected) Research suggests that IL-17A(F) blockers maybe more efficacious than anti-tnfα drugs for the treatment of psoriasis Source: Nature Biotechnology, Jan 2015; Hilary Bartlett & Ryan Million, Nature Reviews, Drug Discovery, Jan

65 Therapeutics targeting IL-17A/F Drugs in development Drug Target Company Disease Stage secukinumab IL-17A Novartis Psoriasis ixekizumab Il-17A Eli Lilly Psoriasis Psoriatic arthritis brodalumab IL-17RA Amgen/Astra Zeneca Psoriatic arthritis; ankylosing spondylitis; RA in patients IR to TNF Psoriasis Psoriatic arthritis Asthma Filed PhII and PhIII PhIII completed PhIII RG4934 IL-17A Roche Psoriatic arthritis PhI but no update since 2010 RG7624 IL-17A/F Roche Autoimmune (no specific indication) PhIII PhIII PhII PhII to start early 2015 UCB-4940 IL17A/F UCB Psoriasis PhIb MAD in patients CNTO 6785 IL-17A Janssen RA PhII ABT-122 COVA-322 IL-17A/ TNFα IL-17A/ TNFα AbbVie Janssen/ Covagen AG RA in patients with an inadequate response to methotrexate Psoriasis PhII PhI/II Sales potential of $500M - $1Bn for anti-il-17 drugs in psoriasis 1 1 Trinity Partners, Nature Reviews, Drug Discovery, Jan

66 Clinical stage products licensed in China Chinese Pharma market to grow to $163B by Anti-TNFα ozoralizumab inflammation Phase II proof-of-concept achieved in patients with RA (Pfizer) Ablynx regained worldwide rights to anti-tnfα Nanobodies from Pfizer exclusively licensed to Eddingpharm in Greater China in Aug M upfront; development and commercial milestones; up to 20% royalties pre-clinical study in China on-going anti-tnf anti-hsa anti-tnf Ablynx will have access to the clinical data generated by Eddingpharm Anti-RANKL ALX-0141 bone disorders Phase I study successfully completed (Ablynx) exclusively licensed to Eddingpharm in Greater China in Oct M upfront; commercial milestones; up to 20% royalties pre-clinical study in China currently on-going anti-rankl anti-hsa anti-rankl Ablynx will have access to the clinical data generated by Eddingpharm 1 Espicom 66