Nanobodies creating better medicines. Corporate presentation

Transcription

1 Nanobodies creating better medicines Corporate presentation 27 August 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 350 employees TECHNOLOGY Pioneer in next generation antibody-derived drugs Nanobodies Powerful proprietary drug discovery engine PRODUCTS >30 wholly-owned and partnered programmes across multiple indications Running 4 Phase II (RSV, RA, SLE); 1 Phase III (acquired TTP) to start in Q First potential product approval in 2018 PARTNERS AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck &Co., Merck Serono, Novartis and Taisho Pharmaceutical > 350M in cumulative cash received; > 7Bn in potential milestones plus royalties FINANCIALS 268M in cash at 30 June 2015 Quoted on Euronext (ABLX) and ADR on US OTC (ABYLY) 3

4 Unique technology Nanobodies pushing the limits of antibody technology

5 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 and robust easily linked together C H 3 C H 3 sequence homology comparable to humanised/human mabs nano- to picomolar affinities challenging and intractable targets Conventional antibodies Heavy chain only antibodies multiple administration routes manufacturing in microbial cells 5

6 6 Ablynx s drug discovery engine 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

7 7 Ablynx s Nanobodies 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

8 Multi-specific Nanobodies Key capability in the development of highly potent and selective drugs

9 Multi-valent and multi-specific Nanobodies Proven capability and performance Ease of formatting and manufacture of multi-valent and multi-specifics allows rapid development of differentiating biologics Objective Binding Target(s) Result Increase potency/ affinity Block two pathways Tri-valent RSV F protein 7,000-fold increase vs monovalent Nanobody, superior to mab benchmark Bi-valent vwf 250-fold increase in affinity vs monovalent Nanobody Bi-specific CXCR4/CD4 160-fold increase versus mixture of monovalent Nanobodies and broader HIV strain coverage Bi-specific IL-17A/F block 2 cytokines at once for more effective blocking of immune response Increase selectivity Bi-specific EGFR/CEA more potent EGFR neutralisation on double positive tumour cells versus normal cells Bi-specific CD4/IL-12R selective binding and functional activity on CD4 + T cells Multiple commercial collaborations with focus on multi-specific Nanobodies Merck & Co., Inc.: immuno-oncology Boehringer Ingelheim: oncology; ocular Merck Serono: oncology; inflammation and osteo-arthritis 9

10 Immuno-oncology (I/O) Changing the cancer treatment paradigm Huge potential Proven substantial survival impact Commercial market for I/O drugs expected to grow to >$43bn by 2020* I/O drugs expected to treat 60% of cancers* Multiple targets Multiple approaches bearing fruit Increasing number of targets Combination therapies are the next generation Nanobodies Multi-specifics potentially increase efficacy and avoid escape mechanisms Ability to manufacture and deliver a combination drug in one Nanobody molecule Nature Reviews *BofA Merrill Lynch July

11 Immuno-oncology Significant collaboration with Merck & Co., Inc. Merck & Co., Inc. viewed as front runner in the field anti-pd-1 drug, Keytruda approved in US (Sept 2014) & EU (July 2015) for the treatment of advanced melanoma; generated sales of $55M in 2014 with sales estimated to amount to $560M in 2015 and $6Bn by 2020 advancing a broad and fast-growing clinical development program for Keytruda with more than 85 clinical trials across more than 30 tumor types and more than 14,000 patients Collaboration with Merck & Co., Inc. signed Feb 14 and expanded in July 15 up to 17 programmes with focus on multi-specific combinations targeting immunecheckpoint inhibitors 33M upfront received; potentially up to 5.7bn in future milestones plus royalties *Leerink August

12 Product pipeline >30 active wholly-owned and partnered programmes

13 FULLY OWNED PARTNERED 13 Products in development Multiple shots on goal Therapeutic area Product name Target Discovery Pre-clinical Phase I Phase II Phase III Filing Clinically validated targets First-in-class Haematology Respiratory caplacizumab ALX-0171 vwf RSV Oncology/ Immuno-oncology Various Inflammation/ Immunology Various Ocular Various Other Various Inflammation/ Immunology ALX-0061 ALX-0761 ozoralizumab IL-6R IL-17F/IL-17A TNFα Greater China Japan Various Oncology/ Immuno-oncology Various Bone disorders ALX-0141 RANKL Greater China Neurology Various CXCR2 Other Various

14 Clinical pipeline Key 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 micro-clot formation Start Phase III Q 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 First-in-infant study on-going: 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) on-going; RA results expected in H

15 15 Caplacizumab Wholly-owned anti-vwf Nanobody First-in-class bivalent Nanobody with Orphan Drug Status Developed to treat acquired thrombotic thrombocytopenic purpura (TTP) Filing expected in H for conditional approval in Europe based on Phase II results Phase III study to start in Q to support BLA submission in USA Ablynx committed to lead commercialisation in Europe and USA Peak sales potential of 300M- 400M 1 1 US, EU, Japan, other markets (Brazil, Canada, Russia, Mexico, Australia)

16 16 Thrombotic thrombocytopenic purpura (TTP) Life-threatening acute blood clotting disorder episode diagnosis treatment TTP patient Emergency Room ICU/haematology unit Acute onset in otherwise healthy person Initial diagnosis based on thrombocytopenia & haemolysis Plasma exchange initiation Haematologist Key decision maker Extensive microscopic clots formed in small blood vessels throughout the body Ultra-rare disease incidence of ~11/million 1 (acquired TTP - 90%; congenital TTP - 10%) ~10,000 acute events annually in US and Europe High unmet medical need no therapeutic drug approved for this indication mortality remains high (10-30%) 2 and ~ 36% of patients relapse 1 major morbidities after TTP episode such as neurocognitive impairment current standard of care: plasma exchange (PE) plus immune suppressants 1 George et al, 2008; 2 Allford et al, 2003, Kremer Hovinga, 2010; Benhamou 2012

17 17 Caplacizumab mode of action Stops formation of micro-clots 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

18 RANDOMISATION 18 Caplacizumab proven clinical benefit Strong clinical proof-of-concept in TITAN Phase II study Study design Study results PE Placebo N=39 30 days 30 days Time to platelet normalisation Median days (95% CI) No prior PE Caplacizumab 3.0 (2.7, 3.9) N = 34 Placebo 4.9 (3.2, 6.6) N = 35 1:1 Median days (95% CI) One prior PE 2.4 (1.9, 3.0) N = (2.9, 5.7) N = 4 PE 30 days 30 days Number of subjects Caplacizumab Placebo 75 subjects Caplacizumab N=36 Subjects with exacerbation within 30 days after stopping PE 3 (8%) 11 (28%) Primary endpoint: time to confirmed normalisation of platelet count Secondary endpoints: exacerbations; relapses; PE parameters; mortality; major clinical events Deaths 0 2 Primary endpoint met (p=0.005) 40% reduction in time to platelet normalisation 71% fewer patients with exacerbations Filing for conditional approval in Europe in 2017 based on TITAN results

19 RANDOMISATION 19 Caplacizumab Phase III study Double-blind placebo controlled study (Q to Q4 2017) Primary endpoint: time to confirmed normalisation of platelet count Exacerbation restart daily PE and open label caplacizumab 1:1 30 days Daily PE Placebo* N=46 TREATMENT PERIOD** * iv bolus (10mg) followed by daily sc (10mg) ** incl. corticosteroids at start of daily PE until underlying disease activity resolved FOLLOW-UP PERIOD (4 weeks) Daily PE 30 days 92 subjects Caplacizumab* N=46 Potential extension of blinded study drug if relapse, restart daily PE and open label caplacizumab Secondary endpoints: exacerbations/relapses; mortality rate; severe morbidity; organ damage biomarkers (troponin, creatinine, LDH); PE parameters; days in ICU/hospital; AEs; PD; PK; immunogenicity

20 Caplacizumab commercial strategy Ablynx to retain 100% ownership in Europe and USA Strategic opportunity to develop into a commercial stage company targets an ultra rare indication with high unmet medical need clear benefit demonstrated in the clinic strong support from medical community established KOL network modest commercial infrastructure requirements Filing for conditional approval in Europe in H Phase III on track to start in Q to support BLA submission in USA in 2018 Development of patient registries underway Caplacizumab could be approved for sale in Europe in

21 21 ALX-0171 Wholly-owned anti-rsv Nanobody First-in-class trivalent Nanobody Developed 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

22 22 RSV infection in infants High unmet medical need Leading cause of infant hospitalisation and primary viral cause of infant death ~65% of infants are infected in their first year of life ~300,000 children* (< 5 years) hospitalised per year in 7 major markets 1,2 ~2.1 million outpatient visits annually in the USA among children <5 years of age increased medical cost in the first year following RSV infection 3 prolonged wheezing and increased risk of asthma development 4 No current treatment options available Synagis used as prophylaxis in high-risk pre-term infants only ($900M sales in 2014) 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

23 % of lambs with score 1 Mean % lung tissue with viral lesions 23 ALX-0171 Key milestones achieved Well tolerated in multiple Phase I clinical studies in adults Strong in vitro and in vivo study results potent anti-viral effect against recent clinical RSV isolates 10,000 fold reduction in viral titres and superiority in vitro compared with palivizumab (Synagis ) 1 daily inhalation of ALX-0171 for 3 consecutive days in neonatal lamb model for infant RSV demonstrated markedly reduced signs and symptoms of illness ( Malaise Score ) 2 and viral lesions 100 Malaise score 60 Lung viral lesions (day 6 post infection) 80 Control ALX Control ALX-0171 RSV infection Treatment ALX-0171 or formulation buffer 1 Vaccines of the World (Oct 2013) 2 RSV Symposium (Nov 2014) presentations on

24 RANDOMISATION ALX-0171 First-in-infant inhalation study on-going Infants aged 3 to <24 months who are hospitalised for RSV infection Study centres in Europe and Asia-Pacific region 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 24

25 ALX-0171 Significant progress today and next steps Strong therapeutic effect demonstrated in a relevant neonatal animal model for infant RSV infection Well tolerated in multiple Phase I studies in adults First-in-infant Phase IIa study on-going with results expected in H Worldwide Phase IIb infant study planned to start in 2016 Potential POC for an inhaled Nanobody 25 25

26 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 2 Phase IIb studies in RA and Phase II study in SLE on-going Opportunity in multi-billion dollar markets RA: rheumatoid arthritis SLE: systemic lupus erythematosus 26

27 % of patients ALX-0061 Compelling Phase IIa results in RA patients 100 ACR50 score as potential differentiating factor All unmodified ALX-0061 at week 24 (N=24) ACR20 ACR50 ACR70 DAS28 remission Boolean remission Data published 13 February 2013: press release available on Ablynx s website 27

28 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 (on-going) 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 28 28

29 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 29

30 RANDOMISATION 30 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

31 RANDOMISATION 31 ALX-0061 Phase II study in SLE First patient dosed in August 2015 Adult subjects with moderate to severe active, seropositive SLE despite standard of care Worldwide, randomised, double-blind, placebo-controlled 48 week dose-range finding study ALX-0061 dose 1, Q4W Primary endpoint at week 24: mbicla 1 response ~300 subjects 1:1:1:1:1 ALX-0061 dose 2, Q4W ALX-0061 dose 2, Q2W ALX-0061 dose 3, Q2W Placebo Secondary endpoints: (m)bicla, (m)sri 2, (m)sledai 3-2K and BILAG over time; patient s and physician s global assessment; flare rate; corticosteroid reduction Other assessments: pharmacokinetics, pharmacodynamics, safety/tolerability, immunogenicity 1 modified BILAG-based Combined Lupus Assessment 2 modified SLE responder index 3 modified SLE disease activity index 2000

32 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 32

33 33 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) Ozoralizumab anti-tnfα Taisho Pharmaceutical (Japan)

34 Partnerships Broad platform exploitation and cash generation

35 35 Current partnerships Broad platform exploitation and value creation Global licensing deal for ALX-0061 (anti-il-6r) in RA and SLE Immuno-onco deal (up to 17 programmes) with focus on multi-specifics; Ion channel deal Strategic discovery alliance (focus on bi-specifics) 8 programmes on-going 6 programmes on-going (lead project in Phase Ib) Two licensing deals in Greater China (ALX-0141 and ozoralizumab) Licensing deal in Japan for ozoralizumab in RA Target-based discovery deal Research collaboration in multiple sclerosis >25 active programmes; > 350M in non-dilutive cash received ~ 7Bn in potential future milestones plus royalties

36 Outlook Potential value enhancing events

37 2015 objectives Maximising stakeholder value 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 advancing ALX-0761 (IL-17A/F) (Merck Serono): study completion by end 2015 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 37 37

38 38 Long term value creation 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

39 Questions CONTACT DETAILS Investor Relations investors@ ablynx.com