Nanobodies creating better medicines Investor presentation June 2016
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
Ablynx Powerful platform generating potentially innovative medicines CORPORATE Platform technology and late-stage clinical development company 350 staff in Ghent, Belgium TECHNOLOGY Pioneer in next generation antibody-derived drugs Nanobodies >500 patent applications and granted patents; critical know-how Validation through multiple partnerships with top tier pharma companies PRODUCTS >40 wholly-owned and partnered programmes 1 Phase III and 4 Phase II studies ongoing in-house First potential launch in 2018 PARTNERS AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck &Co., Inc., Merck KGaA, Novartis, Novo Nordisk and Taisho Pharmaceuticals > 380M cash received; > 7Bn in potential milestones; and royalties FINANCIALS 234M in cash at 31 st March 2016 350M raised in equity 100M of issued Convertible Bonds maturing in 2020 3
4 Ablynx Diversified shareholder base Ordinary shares listed on Euronext Brussels (ABLX) Sponsored Level I ADRs on the US OTC market (ABYLY) 60.9M shares outstanding 2.7M outstanding warrants (in number of shares) Breakdown of share capital % of Institutional Shareholders by Geography (representing 74% of total S/O) (June 2016) 5% 5% 4% Perceptive Advisors (US) Scandinavia 2% France 2% Other 2% 4% 3% 3% Fidelity Management Research (US) Taube Hodson Stonex Partners (UK) US 37% Boehringer Ingelheim (DE) Oppenheimer Funds (US) Benelux 32% Van Herk (NL) Other shareholders UK 26%
Unique technology
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 L V HH Ablynx s Nanobody C H 2 C H 3 C L C H 2 C H 3 small and robust easily linked together sequence homology comparable to humanised/human mabs nano- to picomolar affinities Conventional antibodies Heavy chain only antibodies able to bind and block challenging targets multiple administration routes manufacturing in microbial cells 6
7 Ablynx s drug discovery engine Rapid generation of novel biologics Immunise llamas with antigen and/or Use proprietary synthetic Nanobody phage libraries Wide range of highly diverse Nanobodies with 0.1-10nM affinities Formatted Nanobodies Cloned into microbial systems and produced through fermentation ~12-18 months
8 Ablynx s Nanobodies Platform advantages Mix and match Multiple delivery routes Multi-specific/multivalent Nanobodies that address multiple targets in a single drug molecule flexible GS linker lengths Inhalation Ocular Oral-to-topical High-yield, highconcentration, low-viscosity, microbial production Manufacturing Able to bind and block challenging targets Nanobodies against ion channels and GPCRs Customised half-life extension Hours/days/weeks Albuminbinding Nanobody Fc
Broad product pipeline
10 Hybrid business model fuels the pipeline >40 programmes, 8 Nanobodies in clinical development Product Indication Target Pre-clinical Phase I Phase II Phase III Filing caplacizumab attp vwf ALX-0061 RA IL-6R RA SLE IL-6R IL-6R + ALX-0171 RSV RSV Up to 17 programmes Immuno-Oncology Various BI 836880 Oncology VEGF/Ang2 BI 655088 Chronic kidney disease CX3CR1 ozoralizumab RA RA TNFα TNFα Greater China Japan NA Inflammation CXCR2 ALX-0141 Bone disorders RANKL Greater China ALX-0761 Psoriasis IL-17A/IL-17F ~ 15 whollyowned and partnered programmes Various
Key value drivers
Inhaled ALX-0171 (anti-rsv) For the treatment of RSV infections
13 ALX-0171 for the treatment of RSV infection Wholly-owned inhaled anti-rsv Nanobody Innovative, wholly-owned product, based on Ablynx s unique Nanobody technology Biological drug delivered by inhalation major platform advantage Most advanced product in clinical development to treat RSV infections in infants Critical pre-clinical and clinical milestones achieved Next Phase II study in infants being planned Opportunity in multi-billion dollar market
14 RSV infection in infants Leading cause of infant hospitalisation 90% of children infected by 2 years of age 1 33.8 million episodes (infants <5 years) globally p.a. 1 3.4 million hospital admissions (infants <5 years) globally p.a. 1 66,000-199,000 deaths (infants <5 years) globally p.a. 1 No approved therapeutic Evolves to distressing symptoms Symptomatic treatment Up to 20% hospitalised Long-term disease burden increased medical cost in the first year following RSV infection 2 prolonged wheezing and increased risk of asthma development 3 1 Mazur et al, Lancet 2015; 2 Shi et al, J Med Econ, 2011; 3 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014
Anti-RSV Nanobody ALX-0171 Incorporating unique Nanobody platform advantages Platform advantage Multivalent formatting Delivery via inhalation Product features 3 Nanobodies linked together that bind to the F-protein of RSV 7,000 fold increase in potency over monovalent construct 10,000 fold reduction in viral titres in vitro Neutralises 87% of a broad range of clinical RSV isolates Biological activity maintained after nebulisation Delivered directly to the site of infection Very encouraging efficacy in neonatal lamb model for infant RSV infection Safe and well-tolerated in healthy adults and adults with hyperreactive airways Phase I/IIa study in 53 infants successfuly completed Presentations available on Ablynx website: R&D portfolio 15
RANDOMISATION Inhaled ALX-0171 Phase I/IIa study in 53 hospitalised RSV-infected children Recruitment from Q4 2014 to Q1 2016 Study centres in Europe and Asia-Pacific region Adapted infant inhalation device (vibrating mesh) Inhaled ALX-0171 administered once/day, for 3 consecutive days Open-label lead-in N=5 Infants aged 5-24 months DMC* review 2:1 ALX-0171 N=20 Infants aged 3-24 months Placebo N=10 DMC* review ALX-0171 N=12 Infants aged 1-5 months Placebo N=6 Primary endpoint: Safety and tolerability of ALX-0171 * Data monitoring committee Secondary endpoints: Assessment of clinical effect (feeding, respiratory rate, O 2 saturation, wheezing, coughing, general appearance), PD, PK and immunogenicity 16
First-in-infant Phase I/IIa study Safety and tolerability Open-label group ALX-0171 (N=5) Randomised group ALX-0171 (N=30) Randomised group Placebo (N=16) Adverse events (AEs) - number (%) of subjects with an AE 4 (80.0) 9 (30.0) 4 (25.0) - number (%) of subjects with a treatment-related AE 1 (20.0) 2 (6.7) 0 (0.0) Serious adverse events (SAEs) - number (%) of subjects with an SAE 3* (60.0) 1** (3.3) 0 (0.0) - number (%) of subjects with treatment-related SAEs 0 (0.0) 0 (0.0) 0 (0.0) * 1 of whom discontinued ** subject discontinued Most common AEs were infections and respiratory disorders 3 AEs related to ALX-0171: mild cough, mild rhinorrhoea, mild fever 11 days after last dose 5 SAEs reported: hypo-responsiveness, hypotonia, pneumonia (2) and atelectasis Study primary endpoint achieved Safety and tolerability profile confirmed in the target population 17
Proportion of patients with detectable RSV 18 First-in-infant Phase I/IIa study Anti-viral effect time to undetectable virus in culture Time to undetectable virus ALX-0171 Placebo Median hours 25.3 51.9 p-value 0.014 All Placebo (N=13) All ALX-0171 (N=22) Time (hours) Cox model to compare ALX-0171 and placebo with respect to time to first undetectable virus in culture (undetectable at 2 consecutive time points) from time of start of treatment Treatment with ALX-0171 had an immediate and significant impact on viral replication in RSV-infected infants
Global Severity Score (mean + SE) 19 First-in-infant Phase I/IIa study Overall disease severity assessment Global Severity Score* All ALX-0171 (N=26) All Placebo (N=15) p-value=0.0092 based on longitudinal analysis comparing ALX-0171 and placebo with respect to the Global Severity Score, adjusting for baseline score and time * Overall disease severity assessment including feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition and fever Encouraging initial indication of therapeutic effect
Inhaled ALX-0171 Potential breakthrough for the treatment of RSV infections Direct delivery to the site of infection through inhalation µ$ µµ No treatment-related serious adverse µ events Good safety and tolerability profile confirmed Anti-drug antibodies did not have an apparent effect on PK and no apparent relation to adverse events µ µµ Demonstrated anti-viral effect and showed encouraging trends in Global Severity Score in infants (aged 1-24 months) who were hospitalised with an RSV infection Phase II dose ranging study planned to start before the end of 2016 20 20
ALX-0061 (anti-il-6r) For the treatment of inflammatory diseases
ALX-0061 for the treatment of RA and SLE Anti-IL-6R Nanobody partnered with AbbVie Best-in-class potential for the treatment of autoimmune disorders Global licensing option deal with AbbVie Completed recruitment of ~600 patients in 2 Phase IIb studies in RA top line results in Q3 2016 RA open-label extension study on-going Phase II study in SLE on-going Opportunity in multi-billion dollar markets RA: rheumatoid arthritis SLE: systemic lupus erythematosus 22
% of patients The RA landscape ALX-0061 has best-in-class potential ACR50 scores from various clinical studies 80 75 75 70 60 63 60 50 40 44 50 47 44 44 37 41 48 45 43 41 39 30 31 20 10 0 ALX-0061 1 Tocilizumab (Roche) 2 Sirukumab (J&J/GSK) 3 Sarilumab (Sanofi/Regeneron) 4 Clazakizumab (Alder) 5 Adalimumab (AbbVie) 6 1 PhIIa study (iv) (all responders): 1mg/kg Q4W; 3mg/kg Q4W; 6mg/kg Q8W; 2 Data extracted from OPTION (iv) (4 and 8 mg/kg), AMBITION (iv) (8 mg/kg) and ADACTA (iv) (8mg/kg) trials; 3 Phase II results ACR2011/EULAR 2012: 100mg Q2W; 100mg Q4W; pooled data; 4 Phase III TARGET trial (press release Nov 2015); 150 mg Q2W and 200 mg Q2W; 5 Phase IIb trial (ACR 2013), Q4W; 25 mg, 100 mg, 200 mg; 6 2003 FDA briefing document: DE19 confirmatory Phase II/III study: 20mg QW, 40mg Q2W +MTX 23
Phase IIa RA study of ALX-0061 Demonstrated best-in-class potential Highly efficacious ACR20, ACR50 and ACR70 scores of up to 100%, 75% and 63% First onset of remission as of week 2 Early signs of effect on bone oedema No disease progression as determined by MRI Convenient dosing Wide therapeutic window with potential to dose subcutaneously once a month Favourable safety profile No dose dependent increase in frequency or severity of adverse events 24
ALX-0061 Global licensing option 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 Pays a fee for each indication if they exercise the right to license ALX-0061 after completion of the Phase II studies then responsible for Phase III development, registration and commercialisation 25 25
26 ALX-0061 Key data points in clinical development 2015 2016 2017 2018 Phase IIb RA combination study Phase IIb RA monotherapy study Top line results Top line results opt-in decision for RA; potentially continue development in RA Phase II RA openlabel extension study Top line results Phase II SLE study Top line results opt-in decision for SLE; potentially continue development in SLE
Caplacizumab (anti-vwf) For the treatment of acquired thrombotic thrombocytopenic purpura
28 Caplacizumab for the treatment of attp Wholly-owned anti-vwf Nanobody First-in-class bivalent Nanobody with Orphan Drug Status and patent protection up to 2035 Developed for the treatment of acquired thrombotic thrombocytopenic purpura (attp) Phase III (92 patients) on-going with results expected by end of 2017 Planned filing for conditional approval in Europe (Q1 2017) and BLA submission in USA (2018) Ablynx to lead commercialisation in Europe and USA Anticipated first launch in 2018 Peak sales potential of ~ 300M 1 1 US, EU, Japan and other major markets
29 Caplacizumab unique mode of action Rapidly stops formation of micro-clots Caplacizumab blocks the platelet ULvWF interaction ADAMTS13 activity is impaired Caplacizumab binds to A1 domain of vwf and thereby inhibits platelet string formation Ultra-Large (UL) vwf multimers endothelium Platelet string formation in patients with attp Ex vivo assay for platelet string formation Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of an attp patient 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
30 Acquired TTP (attp) Life-threatening ultra-rare acute blood clotting disorder episode diagnosis treatment attp patient Emergency Room ICU/haematology unit Sudden onset in otherwise healthy person (nausea, fever, coma,..) Initial diagnosis based on thrombocytopenia & haemolysis Plasma exchange until normalisation of platelet count + immune suppressants attp is caused by impaired activity of ADAMTS13 (<10% of that in normal plasma 1 ) extensive microclot formation in small blood vessels throughout the body leads to tissue ischemia and damage to vital organs Ultra-rare condition with incidence estimated at up to 11 per million 2 High unmet medical need with no approved therapeutic drug currently available high mortality in acute phase (10-20%) 3 and ~ 36% of patients have a recurrence 2 significant thromboembolic complications, including brain (e.g. stroke), heart and kidney damage impacts life expectancy and quality of life 1 Scully et al, BJH 2012; 2 George et al, EJH 2008; 3 Allford et al, BJH 2003, Kremer Hovinga, Blood 2010; Benhamou, Haematologica 2012
RANDOMISATION TITAN Phase II study of caplacizumab Clinical proof-of-concept achieved in attp patients 75 patients 1:1 30 days 30 days PEX Placebo N=39 30 days 30 days PEX Caplacizumab N=36 Primary endpoint: time to confirmed normalisation of platelet count Secondary endpoints: recurrences; PEX parameters; mortality; major clinical events Primary endpoint met with high statistical significance (p=0.005) - nearly 40% reduction in time to platelet normalisation = faster reversion of thrombocytopenia and reduced use of plasma exchange (PEX) 71% fewer patients with recurrences during caplacizumab treatment - potential prevention of organ damage Post-hoc analysis demonstrated that: - patients treated with caplacizumab experienced fewer major thromboembolic events as compared to placebo (nominal p=0.006) - fewer patients treated with caplacizumab were refractory to plasma exchange treatment compared to placebo Peyvandi et al,nejm 2016; EHA poster 2016 31
32 TITAN Phase II study of caplacizumab February 2016: published in world-class medical journal Three attp experts describe the impact of the TITAN trial for the attp community
RANDOMISATION 33 HERCULES Phase III study of caplacizumab Started in Q3 2015 with top line results expected in Q4 2017 Recurrence restart daily PEX and open label caplacizumab Daily PEX 30 days 1:1 Placebo* N=46 TREATMENT PERIOD** FOLLOW-UP PERIOD (4 weeks) Daily PEX 30 days 92 patients Caplacizumab* N=46 Potential extension of blinded study drug if recurrence, restart daily PEX and open label caplacizumab Primary endpoint: time to confirmed normalisation of platelet count Secondary endpoints: recurrences; mortality rate; severe morbidity; organ damage biomarkers (troponin, creatinine, LDH); PEX parameters; days in ICU/hospital; AEs; PD; PK; immunogenicity * iv bolus (10mg) followed by daily sc (10mg) ** incl. corticosteroids at start of daily PEX until underlying disease activity resolved
Caplacizumab positioning Potential new component in standard of care for attp Future standard of care could be based on three pillars Caplacizumab Daily PEX Immunosuppression Treatement duration Rapidly inhibits platelet aggregation, micro-clot formation and small blood vessel occlusion Reduces PEX duration Protects during the acute phase Prevents organ damage Reduces recurrences Removes ULvWF & auto-antibodies Replenishes ADAMTS13 Reduces activity of immune system to resolve the underlying cause of attp Reduces thromboembolic events Caplacizumab may become the first approved product for the treatment of attp 34 34
Caplacizumab for the treatment of attp Potentially Ablynx s first marketed product Strategic opportunity to self-commercialise in EU5 and USA Concentrated patient presentation Established KOL network and reference centres Modest commercial infrastructure requirements Contract sales, distributors and/or commercial partners in other territories Market opportunity No direct competition in attp Potential key component in future standard of care Orphan Drug status with patent protection to 2035 Peak sales potential in attp of ~ 300M Potential launch in 2018 35 35
Immuno-oncology Major collaboration with Merck & Co, Inc. and wholly-owned programmes
Immuno-oncology Changing the cancer treatment paradigm Huge market potential Market expected to grow to >$43bn by 2020* I/O drugs expected to treat 60% of cancers* Proven substantial survival impact Multiple targets Increasing number of targets Combination therapies are the future Multi-specific Nanobodies - the next wave! Bind multiple targets (2, 3, 4 or 5) with one Nanobody molecule Potential to increase efficacy and avoid escape mechanisms Technology allows rapid exploration of combinations Manufacturing simplicity and cost-effectiveness *BofA Merrill Lynch July 2015 Nature Reviews - 2012 37
38 Immuno-oncology Multi-specific Nanobodies versus combination mabs One tri-specific Nanobody is 4x smaller than a mab More difficult for mabs to bind to different targets simultaneously mab 2 Tri-specific Nanobody mab 3 mab 1 mab Target 1 Target 2 Target 3 Multi-specific Nanobodies may block multiple targets simultaneously Target 3 Target 2 Target 1
Multi-specific Nanobodies Major immuno-oncology collaboration with Merck & Co., Inc. Merck & Co., Inc. leader in the field Heavily investing in I/O R&D pipeline (~80% of total R&D budget*) Keytruda approved in advanced melanoma (first line) and metastatic NSCLC Sales of Keytruda estimated to reach $6Bn by 2020** >160 clinical studies for Keytruda in >30 tumor types Merck & Co., Inc. and Ablynx in collaboration Initially signed in Feb 14; significantly expanded in July 15 Targeting multiple immune-checkpoint modulators Up to 17 fully-funded Nanobody programmes; focus on multi-specific combinations 33M upfront; up to 5.7Bn in potential future milestones plus royalties First in vivo pre-clinical milestone ( 3.5M) achieved in October 2015 with a bi-specific Nanobody *Bryan Garnier Oct 2015 **Leerink August 2015 39
Outlook
41 Potential news flow 2016-2017 Focus on sustainable value creation 2016 2017 Q1 2016 - Phase I start with VEGF/Ang2 (BI) - 8M - publication of data from TITAN study in the NEJM Q2 2016 - Phase I start with CX3CR1 (BI) - 8M - Phase I start with CXCR2 (Novartis) - Phase I/IIa results with ALX-0171 (53 infants) - Successfully raised 74M in a Private Placement Q3 2016 - ALX-0061 results from Phase IIb monotherapy study - ALX-0061 results from Phase IIb combination study - start follow-up study with HERCULES patients Q4 2016 - opt-in decision by AbbVie for ALX-0061 in RA - start Phase II efficacy study of ALX-0171 PLUS Start 1 additional Phase I study with partner Pre-clinical milestones Caplacizumab (attp) wholly-owned - filing for conditional approval in Europe (H1) - HERCULES Phase III study results (H2) ALX-0061 (RA) AbbVie have an option - potential start of Phase III RA study (H2) ALX-0171 (RSV) wholly-owned - complete recruitment of Phase II efficacy study (H2) Immuno-oncology with Merck & Co., Inc. - start of multiple IND enabling studies - pre-clinical milestones PLUS BI starts Phase II with anti-vegf/ang2 (BI) Up to 6 additional Phase I/II starts (internal + partnered)
42 Ablynx Investment thesis Unique and powerful validated technology platform which has been used to generate potential medicines in a wide range of therapeutic areas Very well funded hybrid business model which supports >40 programmes, some together with pharmaceutical partners, offering a balanced range of risk and reward A number of short and medium term pre-clinical, clinical and commercial catalysts
Questions CONTACT DETAILS Investor Relations +32 9 262 00 00 investors@ ablynx.com www.ablynx.com
Addendum
45 Ablynx s funding history Ensuring a solid cash position to execute corporate strategy 800,000,000 700,000,000 600,000,000 Market cap Capital raised CB 100M ABB 74M 500,000,000 ABB 41M 400,000,000 300,000,000 IPO 85M SPO 50M ABB 31M 200,000,000 100,000,000 0 2001 2002 2004 2006 2007 2010 2011 2012 2013 2014 2015 2016 Private company 70M raised venture capital Public company 381M raised Bond-, institutional-, retail investors
Convertible bond transaction Key terms Issuer Ablynx NV Securities offered Senior Unsecured Convertible Bonds Denomination 100,000 per bond Issue size Maturity Issue/redemption price Issuer call 100 million 27 May 2020 (5 years) 100% Upon conversion, issuer has the flexibility to repay the bonds in cash or in shares or a mixture Mechanism that gives Ablynx the opportunity to redeem the bonds at par plus accrued interest from year 3 during a period the shares trade at a price >130% of the conversion price Coupon 3.25%, payable semi-annually Reference Price Conversion price and Ratio Use of proceeds 10.2219 12.93 7,733.952 Ordinary Shares per 100,000 principal amount of Bonds Accelerate the development of proprietary clinical pipeline, initiate pre-commercial activities and advance earlier stage wholly-owned product candidates into the clinic Joint bookrunners J.P. Morgan Securities Ltd and BofA Merrill Lynch 46 46
Financial summary Full-year results Q1 2016 million Q1 2016 Q1 2015 Change Total revenue and grant income 27.4 14.1 94% R&D income 27.2 13.9 96% Grants 0.2 0.2 - Operating expenses (28.1) (19.1) 47% R&D (24.9) (16.7) 49% G&A (3.2) (2.5) 28% Operating result (0.7) (5.0) 86% Net financial result 17.5 1.1 >100% Net result 16.8 (4.0) >100% Net cash flow (2.5) (12.9) 81% Cash at 31 March (3) 233.7 (1) 193.3 (2) 21% (1) Including 1.3 million in restricted cash (2) Including 2.0 million in restricted cash (3) Cash, cash equivalents, restricted cash and short-term investments at the end of the period 47
48 Ablynx shares Four-year performance
Nanobodies Expanding 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 30-210 kda mono- or bi-valent short or long half-life bi-specific 3 rd generation 12-75 kda valency of choice short or long half-life multi-specific 49
Excellent biophysical properties Exceptional CMC profile Chemical uniformity & stability no N-glycosylation no C-terminal Lys residues prone to chemical instability are engineered out Physical stability Hydrophilic by nature Intrinsic low aggregation propensity Easy to manufacture mammalian cells bacteria yeast High yield and high concentrations Batch-to-batch consistency Excellent storage stability Alternative administration routes Inherent Nanobody properties and Ablynx expertise results in exceptional CMC profile 50
51 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 VEGF/Ang2 block 2 proteins at once; superior anti-tumour effect vs reference mab drugs 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; immunology Merck KGaA: oncology; inflammation and osteo-arthritis Novo Nordisk: undisclosed disease area
Multi-specific Nanobodies Strategic Alliance with Boehringer Ingelheim Signed September 2007 Therapeutic indications Scope Exclusivity Economics Boehringer Ingelheim Oncology, immunology 6 Nanobody programmes still progressing Worldwide exclusivity 15M equity investment Up to 60M in funding during research term Up to 125M in milestone payments per programme Plus tiered royalties (to mid-teens) Responsible for development, manufacturing and commercialisation > 75M in cash received to date First bi-specific Nanobody in Phase Ib study in patients with solid tumours - 8M milestone 52 52
Anti-VEGF/Ang2 Nanobody Highly potent in pre-clinical cancer models Anti-VEGF/Ang2 Nanobody demonstrated strong in vivo proof-of-mechanism data in various cancer models: selective and potent inhibition of VEGF-A and Ang2 in vitro superior efficacy as compared to reference monoclonal antibody drugs Superior anti-tumour efficacy Pancreas cancer model (PAXF 546) Phase Ib in patients with solid tumours ongoing Days Poster presentation available on Ablynx website: http://www.ablynx.com/technology-innovation/nanobodies-competitive-features/ Avastin : anti-vegf mab, marketed by Roche; AMG386: anti-ang1/2 peptibody developed by Amgen (Phase III halted in April 2015 in patients with ovarian cancer) 53
Multi-specific Nanobodies Drug discovery collaboration with Novo Nordisk Signed November 2015 Therapeutic indication Scope Exclusivity Research funding Economics Novo Nordisk Undisclosed 1 programme with option to second programme Worldwide exclusivity 4M during 3 years 5M upfront payment 4M option fee for second programme Up to 182M in milestone payments per programme Plus tiered royalties Responsible for development, manufacturing and commercialisation 54 54
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 55
OD450-520 nm 56 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 1.0 0.8 0.6 0.4 0.2 7,000-fold 0.0 10-11 10-10 10-9 10-8 10-7 10-6 10-5 10-4 Concentration (M) palivizumab A-strain B-strain Total n 32 29 61 palivizumab 0 (0%) 11 (38%) 11 (18%) ALX-0171 30 (94%) 23 (79%) 53 (87%) p value <0.0001 <0.0001 <0.0001 Number of strains neutralised below lower limit of detection Improved potency over mab Increased strain coverage
Proprietary tetravalent anti-gitr Nanobody Efficacy as monotherapy or in combination with anti-pd1 mab Tumor efficacy in a syngeneic mouse model Vehicle Irrelevant Nb + PD-1 mab GITR Nb GITR Nb + PD-1 mab p < 0.0001 p < 0.0001 GITR Nb PD1 mab CT26 colon carcinoma tumours were grown to 90 mm 3 in size prior to start of treatment (Day 0) Tetravalent anti-gitr Nb-IgG1 57
Proprietary tetravalent anti-gitr Nanobody Efficacy as monotherapy or in combination with anti-pd1 mab Individual tumor efficacy plots Vehicle 0/10 Reg Irr Nb + PD-1 mab 0/10 Reg GITR Nb 1/10 Reg GITR Nb + PD-1 mab 5/10 Reg CT26 colon carcinoma tumours were grown to 90 mm 3 in size prior to start of treatment (Day 0) Reg = regressed below baseline volume 58
59 Inhaled ALX-0171 Successfully completed 3 Phase I inhalation studies in adults Number of subjects Dose SAD and MAD Outcome First-in-human study 60 2x/day for 5 days Well-tolerated, no clinically relevant adverse events or effects on lung function Safety study in adults with hyper-reactive airways PK study 41 daily for 5 days and single iv dose 24 daily for 5 days Some cases of mild bronchoconstriction which could be immediately reversed Local half-life of ALX-0171 is ~20 hours confirming potential for once-daily dosing Inhaled ALX-0171 administered safely to >100 adults
% of lambs with score 1 Mean % lung tissue with viral lesions Inhaled ALX-0171 Strong therapeutic effect demonstrated in vivo Strong therapeutic effect* following daily inhalation for 3 consecutive days in neonatal lamb model for infant RSV 100 Malaise score** - Lambs 60 Lung viral lesions - Lambs (day 6 post infection) 80 60 40 20 0 0 1 2 3 4 5 6 Control ALX-0171 50 40 30 20 10 0 Control ALX-0171 RSV infection Treatment ALX-0171 or formulation buffer * RSV Symposium November 2014 ** Composite assessment of disease related parameters such as weakness, depression, lethargy, drooping of ears and not eating 60
First-in-infant Phase I/IIa study Baseline characteristics balanced within randomised groups Open-label group ALX-0171 Randomised group ALX-0171 Randomised group Placebo Number of subjects randomised 5 32 16 Number (%) of subjects in the safety population (who received at least one dose) 5 (100) 30* 16 Mean age (months) 7.1 7.9 8.2 Males (%) 4 (80.0) 22 (73.3) 10 (62.5) Mean weight (kg) 8.0 7.4 7.7 Mean number of days between onset of symptoms and screening Mean Global Severity Score** (day 1, predose) 3.4 3.9 3.8 10.0 7.3 7.3 * 2 subjects discontinued between randomisation and dosing (1 SAE due to severity of infection and 1 due to protocol deviation) ** a composite score reflecting an assessment of feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition and fever 61
First-in-infant Phase I/IIa study Well-tolerated and favourable safety profile Open-label group ALX-0171 (N=5) Randomised group ALX-0171 (N=30) Randomised group Placebo (N=16) Adverse events (AEs) - number (%) of subjects with an AE 4 (80.0) 9 (30.0) 4 (25.0) - number (%) of subjects with a treatment-related AE 1 (20.0) 2 (6.7) 0 (0.0) Serious adverse events (SAEs) - number (%) of subjects with an SAE 3* (60.0) 1** (3.3) 0 (0.0) - number (%) of subjects with treatment-related SAEs 0 (0.0) 0 (0.0) 0 (0.0) Treatment-related adverse events: Mild cough upon first SD inhalation which did not reoccur after the 2 nd and 3 rd administrations Mild rhinorrhoea upon SD inhalation Mild fever 11 days after last dose * 1 of whom discontinued ** subject discontinued 62
63 First-in-infant Phase I/IIa study PK and immunogenicity Pharmacokinetics (PK) ALX-0171 detected in serum samples 6 hours after the last dose consistent with lung exposure At follow-up visit, treatment-emergent anti-drug antibodies were detected in 23% of patients, consistent with general immune activation in the lungs due to the RSV infection no relation seen with adverse events no apparent effect on PK
First-in-infant Phase I/IIa study Anti-viral effect explored using nasal swabs 2 methods used to measure anti-viral effect qrt-pcr: measuring all viral RNA plaque assay: measuring infectious virus 2 outcomes per method viral load over time (nasal swabs taken prior to dosing and 6 hours after) time to undetectable virus: measures the time from start of treatment until the time of the first undetectable viral titre in 2 consecutive nasal swabs Study population (open-label, lead-in group and double-blind, randomised treatment group) ALX-0171: N=30 (excludes 4 subjects* with unconfirmed RSV infection; and 1 with no result) placebo: N=15 (excludes 1 subject* with unconfirmed RSV infection) * No evidence for RSV infection by plaque or qrt-pcr assay at any time during the study; presumed false positives from rapid diagnostic strip test 64
65 First-in-infant Phase I/IIa study Anti-viral effect viral load over time plaque assay qrt-pcr All ALX-0171 (N=30) All Placebo (N=15) All ALX-0171 (N=30) All Placebo (N=15) Treatment with ALX-0171 had an immediate impact on viral replication in RSV-infected infants
First-in-infant Phase I/IIa study Clinical effect Post-hoc assessment of clinical effect based on the Global Severity Score* clinical score (up to 20 points) that allows categorisation of infants with respiratory infections on 7 different parameters: feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition and fever Study population: double-blind, randomised treatment group ALX-0171: N=26 (excludes 4 subjects** with unconfirmed RSV infection) Placebo: N=15 (excludes 1 subject** with unconfirmed RSV infection) * Poster presentation, Justicia et al: Development and validation of a new clinical scale for infants suffering from acute respiratory infection ** No evidence for RSV infection by plaque or qrt-pcr assay at any time during the study; presumed false positives with diagnostic test 66
67 First-in-infant Phase I/IIa study Effect on Global Severity Score longitudinal analysis Type 3 Tests of Fixed Effects Effect Numerator DF Denominator DF F Value P-value Treatment 1 36 7.59 0.0092 Time 4 147 6.25 0.0001 Baseline score 1 36 71.34 <.0001 Interpretation of P-values Significant effect of all covariates Severity scores decrease over time, differ between ALX and Placebo, and are positively correlated with baseline score
RSV pipeline Therapeutics and vaccines currently in clinical development Name Population Mode of Action Company ALS-008176 Infant, Children, Adults cytidine nucleoside analogue Alios Biopharma Inc. BTA-C585 Healthy Adults Only fusion protein inhibitor Arivagen Therapeutics. GS-5806/Presatovir Adult fusion protein inhibitor Gilead Sciences AK0529 Infant Children fusion protein inhibitor Ark Biosciences Inc. MEDI8897 Infant Children Adult Human IgG- anti Fusion protein MedImmune LLC RI-002 Children Adult IGIV ADMA Biologics, Inc. ALX-0171 Infant Children Nanobody Ablynx Polyclonal AB Adults Polyclonal AB NIAID/IMPAACT MVABNRSV Adult Vaccine Bavarian Nordic D46cpΔM2-2 Infant Children Adult vaccine NIAID DPX-RSV(A) Adult vaccine Dalhousie University GSK3003895A Adult vaccine GlaxoSmithKline GSK3389245A Adult vaccine GlaxoSmithKline JNJ-61187191 Adult vaccine Janssen Sciences/Crucell MEDI7510 Elderly vaccine MedImmune LLC PanAd3-RSV Adult vaccine ReiThera Srl REGN2222 Infant Children Vaccine Regeneron Pharmaceuticals RSVcps2 Infant Children vaccine NIAID/IMPAACT RSV-F Infant Children Adults vaccine Novavax RSVLIDΔM2-2 Infant Children vaccine NIAID/IMPAACT RSVΔNS2Δ1313I1314L Infant Children vaccine NIAID * Other Medimmune vaccine candidates for infants in NIAID sponsored studies 68
69 ALX-0061 Best-in-class potential in an expanding market Features Small (26kD) Potential benefits Penetrates faster and more effectively into tissues anti-il-6r anti-hsa Targets human serum albumin 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 Results from Phase IIa RA study have demonstrated that ALX-0061 has a compelling efficacy and safety profile and allows convenient dosing (every 2 to 4 weeks)
RANDOMISATION (N=37) 70 ALX-0061 Phase IIa study design Week 0-12 Week 12-24 ALX-0061 1mg/kg Q4W N=9 N=8 ALX-0061 1mg/kg Q4W unmodified N=1 ALX-0061 3mg/kg Q4W modified ALX-0061 3mg/kg Q4W N=10 N=8 ALX-0061 3mg/kg Q4W unmodified N=2 ALX-0061 6mg/kg Q4W modified ALX-0061 6mg/kg Q8W N=9 N=8 ALX-0061 6mg/kg Q8W unmodified N=1 ALX-0061 6mg/kg Q4W modified Placebo N=6 N=3 Placebo placebo N=3 ALX-0061 3mg/kg Q4W switched Dose modification based on EULAR response at week10 24/28 patients completed the study at their ALX-0061 starting dose
% of patients ALX-0061 Compelling Phase IIa efficacy results in RA patients 100 ACR50 score as potential differentiating factor 80 60 83 71 58 63 40 29 20 0 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 71
72 ALX-0061 Well tolerated safety profile demonstrated in Phase IIa RA study Treatment Emergent Adverse Events (AE) Patient counts All ALX-0061 week 0-12 N=31 All ALX-0061 week 12-24 N=31 Any AE 17 (57 events) 16 (56 events) Serious Adverse Events 1* 1* Rash** 3 1 ALT and AST elevations (>2.5x ULN, <5x ULN) 1 1 Lipid level changes 0 0 Neutropenia 0 0 Serious infections 0 0 * Unlikely to be associated with ALX-0061 treatment ** One patient with pre-existing condition. Rash disappeared in the other 2 patients. No worsening or increase of adverse events upon extension of treatment Treatment was well tolerated at all doses
ALX-0061 Preferential binding to soluble IL-6R It has been hypothesised that classic IL-6 signalling via membrane-bound IL-6R (mil-6r) does not contribute to chronic inflammation However, IL-6 trans-signalling through soluble IL-6R (sil-6r) is believed to be associated with chronic inflammatory conditions Hence, preferential binding to sil-6r is believed to be associated with less side effects as compared to binding to mil-6r (higher risk to interfere with normal physiology which may lead to unwanted neutropenia and infection) *Gottschalk et al, Frontiers in Immunology, Oct 2015 73 73
RANDOMISATION ALX-0061 Phase IIb RA combination study with MTX* results Q3 2016 First patient dosed in March 2015; recruitment of 345 patients completed in December 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 345 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 74
RANDOMISATION 75 ALX-0061 Phase IIb RA monotherapy study results Q3 2016 First patient dosed in April 2015; recruitment of 251 patients completed in February 2016 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 251 subjects (Ro)Actemra 162mg Q1W (EU) or Q2W (US) Other assessments: pharmacokinetics, pharmacodynamics, safety/tolerability, immunogenicity
RANDOMISATION 76 ALX-0061 Phase II study in SLE results in 2018 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
DAS28 CRP Response of ALX-0061 vs. filgotinib Pooled data vs. highest reported responses 100% ALX-0061, Pooled 100% DARWIN1, highest reported responses 80% 21% 80% 60% 60% 4% 24% 40% 40% 14% 20% 0% 50% 63% Week 12 Week 24 20% 0% 7% 7% Week 12 - Pbo 36% Week 12-100 mg BID 9% 9% Week 24 - Pbo 40% Week 24-100 mg BID Remission Low disease activity Low disease activity Remission ALX-0061 as presented on 4 October 2012 and 13 February 2013 DARWIN1 as presented by Galapagos on 30 July 2015 77
Therapeutics targeting IL-6(R) Drugs currently in development (inflammatory) Drug Target Company Disease Dosing Stage SAR153191 REGN88 IL-6R CNTO 136 IL-6 J&J/ GSK Sanofi/ Regeneron CDP6038 IL-6 R-Pharm/ UCB RA, uveitis ALD518 IL-6 Alder / Vitaeris RA, NSCLC, GVHD* 150 or 200 mg Q2W RA 50 mg Q4W, 100 mg Q2W RA PF-04236921 IL-6 Pfizer SLE, CD, RA RYI-008 ARGX-109 SA237 Actemra follow-on Tocilizumab biosimilar Tocilizumab biosimilar Tocilizumab biosimilar IL-6 Bird Rock Bio/ argenx 60-120-240 mg Q2W 25-100-200 mg Q4W RA Q4W SLE, CD Q8W RA Q4W / Q8W PhI IL-6R Chugai/ Roche RA, NMO** Q4W or less frequent BLA submitted, MAA planned 2016; projected RA launch 2017 PhIII, submissions planned 2016; projected launch end-2017 (US)/2018 (EU5/Japan) PhIII started April 2016 PhII, Vitaeris aims to name a new lead indication in 3Q16 RA PhI SLE, CD PhII IL-6R BioXpress Research IL-6R Pan- Pharmaceuticals RA PhI NMO/NMOSD PhIII Research IL-6R Epirus Research * Graft versus host disease; ** Neuromyelitis optica 78 78
79 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 574 545 Number of TE Serious AEs 44 36 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
Proportion of patients without confirmed platelet response 80 Caplacizumab Phase II TITAN trial Primary endpoint time to platelet normalisation Time to platelet normalisation Caplacizumab Placebo Median days (95% CI), NO prior PEX Median days (95% CI), one prior PEX 3.0 (2.7, 3.9) N = 34 2.4 (1.9, 3.0) N = 2 4.9 (3.2, 6.6) N = 35 4.3 (2.9, 5.7) N = 4 N = 36 N = 39 Overall hazard rate ratio (95% CI) caplacizumab vs. placebo 2.2 (1.3, 3.8) N = 75 Stratified log-rank test p-value* 0.005 * log-rank test p-value = 0.005 evaluated time to confirmed platelet response between the 4 groups presented above The group of patients treated with caplacizumab achieved confirmed platelet normalisation at more than twice the rate of the group receiving placebo
81 Caplacizumab Phase II TITAN trial Key secondary outcomes and safety profile of caplacizumab In the caplacizumab group, fewer patients had recurrences of attp, but a higher number of recurrences was observed during the follow-up period Proportion (number) of subjects (ITT population) Caplacizumab N = 36 Placebo N = 39 Complete remission 81% (29) 46% (18) Recurrence during caplacizumab treatment 8% (3) 28% (11) Recurrence up to 1 month follow-up 28% (10) 28% (11) Deaths, n 0 2 Acceptable safety profile (manageable mild bleeding tendency) Proportion of subjects (safety population) 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%
Caplacizumab Phase II TITAN trial Underlying disease activity based on ADAMTS13 activity Data plotted: ADAMTS13 activity data available closest to treatment stop or data close to the day of exacerbation 7 patients relapsed within 10 days after stopping caplacizumab all had continuous low ADAMTS13 activity (<10%) during and near treatment stop continue caplacizumab treatment in case underlying disease activity is not resolved 82
83 Caplacizumab Phase II TITAN data Post-hoc analysis of TTP related clinically relevant AE Post-hoc analysis of data from the TITAN study TTP related clinically relevant adverse events during study drug treatment Component Caplacizumab Placebo N=35 N=37 Death 0 2 TTP recurrence 3 11 Acute myocardial infarction 0 2 Cardiac failure 0 1 Deep venous thrombosis 0 2 Ischaemic stroke 0 1 Pulmonary embolism 1 1 TOTAL 4* (11%) 16* (43%) * A subject may have experienced more than one event Had the composite endpoint been prospectively defined, the difference between both groups would have been statistically significant (post-hoc nominal p-value of 0.006).
Caplacizumab Phase II TITAN data Post-hoc analysis on refractoriness to treatment Data published in a letter to the editor in the NEJM, issue 23 June 2016 Refractoriness to treatment, n (%) Caplacizumab N=35 Placebo N=37 Failure of platelet response after 7 days despite 2 (5.7) 8 (21.6)* daily PEX treatment (1) Absence of platelet count doubling after 4 days of standard treatment, and LDH>ULN (2) 0 (0) 4 (10.8) * 2 patients in the placebo group who discontinued the study prematurely (before 7 days) without reaching the platelet count criteria (i.e. platelet count <150x10 9 /l) were counted as refractory to treatment (1) Sayani, F.A. and C.S. Abrams, How I treat refractory thrombotic thrombocytopenic purpura. Blood, 2015. 125(25): p. 3860-7 (2) Soucemarianadin, M., et al., Twice-daily therapeutical plasma exchange-based salvage therapy in severe autoimmune thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. European journal of haematology, 2015 84
Arthritis score ALX-0761 Bi-specific Nanobody in psoriasis ALX-0761 blocks both IL-17A and IL-17F (involved in inflammation); binds HSA 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 KGaA completed Phase I SAD study in healthy volunteers Phase Ib study completed in 40 patients with psoriasis Secukinumab (Novartis) (anti-il-17a) approved in 2015 and has estimated peak sales of ~$500M* anti-il17f anti-hsa anti-il17a Proof-of-concept achieved in primate collagen induced arthritis model 1 80 60 40 20 0 4 6 16 26 36 46 56 Days Vehicle ALX-0761 (2.8mg/kg) ALX-0761 (10mg/kg) * Analysts estimates 2014 1 Poster available on Ablynx website: R&D>pipeline 85
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) the first anti-il-17a therapeutic on the market (approved in 2015) 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 2015 86 86
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 Psoriatic arthritis; ankylosing spondylitis; RA in patients IR to TNF Approved (Jan 2015) PhII and PhIII RG4934 IL-17A Roche Psoriatic arthritis PhI but no update since 2010 UCB-4940 IL17A/F UCB Psoriatic arthritis PhII CNTO 6785 IL-17A Janssen RA PhII ABT-122 COVA-322 IL-17A/ TNFα IL-17A/ TNFα AbbVie Janssen/ Covagen AG RA Psoriatic arthritis Psoriasis PhIII PhIII PhII PhII PhI/II Sales potential of $500M - $1Bn for anti-il-17 drugs in psoriasis 1 1 Trinity Partners, Nature Reviews, Drug Discovery, Jan 2015 87 87