Ablynx 2007 Results. Dr Edwin Moses, Chairman and CEO 28 February Nanobodies : delivering therapeutics beyond antibodies

Transcription

1 Ablynx 2007 Results Dr Edwin Moses, Chairman and CEO 28 February 2008 Nanobodies : delivering therapeutics beyond antibodies

2 Forward Looking Statements Certain statements, beliefs and opinions in this presentation are forward-looking, which reflect the Company s or, as appropriate, the Company s 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 of their 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. 1

3 Outline 2007 Key highlights Financial results The Nanobody opportunity The product pipeline Business strategy Prospects for

4 Key highlights in 2007 (1) Raised 85.2 million from its IPO on Euronext Brussels 126 million in cash at year end 150% increase in revenues to 9.9 million (2006: 4.0 million) ALX-0081, an anti-thrombotic, entered Phase I clinical trials in April and in December we reported a successful closing of the study A research and licensing deal worth up to 1.3 billion was signed with Boehringer Ingelheim in September A collaborative agreement with Boehringer Ingelheim in the area of Alzheimer s disease worth up to 206 million was announced in January 3

5 Key highlights in 2007 (2) Key Nanobody related claims of the Hamers-1 patent were maintained in opposition appeal proceedings in December Wyeth confirmed an extension of the research term with Ablynx as part of its $212 million TNF-alpha licensing agreement in December The Novartis drug discovery and development alliance was extended for another year in December 1.9 million grant was approved by the Flemish government in September to develop new therapeutic application of Nanobodies 4

6 Outline 2007 Key highlights Financial results The Nanobody opportunity The product pipeline Business strategy Prospects for

7 Profit and loss statements 000s, IFRS Revenues 9,920 3, ,090 R&D 8,785 3, Grants 1, ,067 Total operating expenses (24,232) (17,664) (10,801) (6,618) R&D expenses (18,750) (13,504) (8,041) (4,934) G&A expenses (5,482) (4,160) (2,760) (1,684) Other operating income Operating result (14,307) (13,647) (9,937) (5,517) Finance income 1, Loss before taxes (12,522) (13,233) (9,578) (5,410) Net loss for the year (12,522) (13,233) (9,580) (5,410) On 27 April 2007, Belgian parliament approved a new law that will allow Belgian companies to exempt 80% of patent income from internal IP from tax in Belgium 6

8 Cash flow statements 000s, IFRS Loss before income tax (12,522) (13,233) (9,578) (5,410) Amortization / depreciation Net movement in trade and other receivables (1,996) (802) (750) (162) Net movement in trade and other payables 15,700 7,913 1, Others Net cash used in operating activities (3,000) (4,766) (8,364) (4,323) Purchases of PPE (1,994) (1,447) (519) (714) Proceeds from sale of PPE Purchases of intangible assets (11) (25) (58) (12) Net cash used in investing activities (2,005) (1,372) (577) (726) Proceeds of issuance of ordinary shares 99,855 19,860 12,500 12,202 Proceeds from exercise of warrants - - Proceeds / repayments from borrowings (160) 332 Net cash generated from financing activities 99,695 20,192 12,500 12,202 Net (decrease) / increase 100,690 14,054 3,558 7,153 Cash and cash equivalents at end of the period 126,489 25,799 11,745 8,187 7

9 Outline 2007 Key highlights Financial results The Nanobody opportunity The product pipeline Business strategy Prospects for

10 From small molecules to monoclonal antibodies mab development has a higher success rate in the clinic versus small molecule compounds 20 FDA approved mabs, global sales of $20bn, market growing at ~15% Leading marketed monoclonal antibodies Brand name/drug Indication¹ 2006 Sales 2 Remicade /infliximab Inflammatory disease $4,253 Rituxan /MabThera /rituximab NHL $3,739 Herceptin /trastuzumab Breast cancer $3,136 Avastin /bevacizumab Colorectal cancer $2,365 Humira /adalimumab Inflammatory disease $2,044 Erbitux /cetuximab Cancer $1,100 Synagis /palivizumab Respiratory virus $1,062 Source: Novartis, Tufts Institute, Datamonitor, Monoclonal Antibodies Report Part I, June Selected approved for multiple indications 2 Global sales 9

11 Nanobodies offer a breakthrough opportunity Small protein domains (12-15 kd) derived from immunized llamas C H 1 C L V H V L V HH C H 2 C H 2 V HH C H 3 Conventional Antibody Heavy and light chains Both chains required for antigen binding and stability C H 3 Heavy-Chain Antibody Only heavy chains Full antigen binding capacity and highly stable Ablynx s Nanobody Based on the smallest functional fragment of a naturally occurring heavy-chain antibody 10

12 Nanobody advantages multi-specificity Bi-specific Nanobodies: blocking two different signalling pathways Monovalent Nanobodies each block one target and pathway only Target 1 NB1 A bi-specific Nanobody simultaneously blocks both targets and both pathways NB1 Tumor cell Signal 1 NB1 NB2 proliferation NB2 Tumor cell Target 2 Tumor cell NB2 Signal 2 survival Signal (proliferation + survival) 11

13 Potential for multiple routes of administration Delivery routes for conventional antibodies Potential delivery routes for Nanobodies Injection Oral Pulmonary Needle free Transdermal Intranasal 12

14 The power of Nanobodies EPHRIN/ EPHRIN RECEPTORS T CELL CO-ACTIVATOR LIGANDS/ RECEPTORS SERINE PROTEASES PROTEASES CYTOKINES AND RECEPTORS INTEGRINS CHEMOKINES GROWTH FACTORS AND RECEPTORS ADAMOLYSINS Fc Fc RECEPTORS INTERLEUKINS ENZYME AND RECEPTORS TARGETS ANGIO- POETINS TRANS- VIRAL PORTERS COAT PROTEINS 13

15 The Nanobody platform allows rapid discovery Target 3-6 years for conventional antibodies IND Target 26 months for ALX-0081 IND > 1 year Platform engine allows Ablynx to initiate 6-8 new discovery programmes every year Ablynx aims to advance at least 5 Ablynx proprietary compounds into clinical development over the next 5 years 14

16 Outline 2007 Key highlights Financial results The Nanobody opportunity The Product pipeline Business strategy Prospects for

17 Ablynx s internal programmes Target Selection Lead Identification Lead Optimization Pre-clinical Phase I Phase II Phase III Registration IND Launch ALX-0081: Acute thrombosis ALX0681: Thrombosis/TTP IND End-08 Phase II End-08 Bone diseases Inflammation Inflammation Inflammation Inflammation Infectious diseases Neurology Respiratory diseases Infectious diseases 16

18 ALX a novel anti-thrombotic Anti-vWF Nanobody Bivalent Nanobody 28kDa Two identical anti-vwf A1 domains Inhibits platelet adhesion to collagen at high shear rate Potential clinical benefits ALX-0081 Anti-vWF Nanobody Improved efficacy and safety profile over ReoPro Improved efficacy in addition to multi-drug standard regimen Blockbuster opportunity Breakthrough in management of acute thrombotic events New mode of action, first mover in cascade of thrombosis Cost of goods benefits Manufactured in microbial system (to >g/l) Scalable process, stable liquid formulation 17

19 ALX positive pre-clinical data Higher potency and superior safety compared to ReoPro Superior efficacy and safety compared to Plavix ALX-0081 more effective than aspirin/heparin/plavix combination ALX-0081 in combination with aspirin/heparin/plavix leads to improved efficacy without compromising safety Efficacy [%] ALX-0081 efficacy ALX-0081 bleeding Reopro efficacy Reopro bleeding Plavix efficacy Plavix bleeding ,000 10, ,000 Dose [ug/kg] Surgical bleeding 18

20 ALX Phase I study design and objectives Study design A Phase I, double blind, randomized, placebo-controlled, parallel group study in 40 healthy male volunteers Primary objective Determine the safety and tolerability of single ascending intravenous doses of ALX-0081 Secondary objectives Investigate the pharmacokinetic profile of ALX-0081 Investigate possible immunogenic effects of ALX-0081 Investigate the effect of ALX-0081 on bleeding 19

21 ALX successful Phase I clinical trial Safe and well tolerated No serious adverse effects or dose limiting toxicity No signs of clinically significant bleeding No immunogenic response Pharmacodynamic effects Biomarker allows easy monitoring of efficacy Predicted potency of ALX-0081 was confirmed 20

22 Multiple dose study ALX-0081 A Phase Ib, double-blind, randomized, placebo-controlled study of ALX-0081 multiple dose administration in stable angina patients undergoing percutaneous coronary intervention (PCI) Treatment Patients Single dose followed by multiple dosing Dose escalation guided by safety and efficacy marker Up to 64 patients with stable angina undergoing elective PCI procedure Primary Secondary Objectives Determine biologically effective dose and Phase II recommended dose Determine safety and tolerance in patients undergoing PCI Document biological and clinical response to therapy Endpoints Evaluate dose limiting toxicities Evaluate adverse events, immunogenicity and pharmacological profile Evaluate biomarker Evaluate marker for early clinical responses 21

23 ALX-0081 line extension ALX-0081 ALX-0681 Formulation Intravenous Sub-Cutaneous Regimen Acute treatment Acute treatment Prevention of early recurrence Duration 1-3 days 1-3 weeks Medical Need Competitor Key driver PCI procedures TTP acute event Vascular surgery ReoPro, GPIIb/IIIa inhibitors, combination of aspirin, heparin and Plavix ~4 million PCIs / year in major markets Acute TTP patients Recurrent ACS TTP (familial form) Stroke (combination therapy) Plavix, GPIIb/IIIa inhibitors, antithrombin ~2.5 million new and recurrent ACS patients (US) per year All TTP patients Source: American Heart Association and American Stroke Association: Heart Disease and Stroke Statistics 2008 Update At-A-Glance NHS (Northern Network of Cardiac Care): Primary Angioplasty Strategic Report December 2006 European Society of cardiology: Euro Heart Survey Programme ACS and ACSII 22

24 Outline 2007 Key highlights Financial results The Nanobody opportunity The Product pipeline Business strategy Prospects for

25 Ablynx business strategy Ideally retain projects in-house until at least Phase IIa Collaborate selectively to access expertise, targets, technologies or financial resources Retain strategic flexibility by providing exclusivity on targets rather than indications or therapeutic areas Maintain ~70% of R&D resources dedicated to building Ablynx s own portfolio 24

26 Ablynx s Portfolio of Funded Projects Target Selection Lead Identification Lead Optimization Pre-clinical Phase I Phase II Phase III Registration IND Launch Rheumatoid arthritis Alzheimer's disease Musculoskeletal Bone diseases Various Various 25

27 The Nanobody target universe ~ 2000 targets unpartnered Ablynx has partnered < 2% of the targets amenable to Nanobody technology partnered targets 26

28 A product generator Nanobody Platform 2008 In-house Partners Value creation new discovery programmes per year 5 IND s by 2012 Ablynx accesses skills, technologies, targets or financial resources potential value created: $0.5 billion* *Nov 2006 In Vivo article: an IND is worth $100M 27

29 Outline 2007 Key highlights Financial results The Nanobody opportunity The product pipeline Business strategy Prospects for

30 Prospects for 2008 (1) ALX-0081: multi-dose Phase Ib study carried out accelerate the programme by carrying out the multiple-dose study directly in the target patient population rather than healthy volunteers ALX-0081: Phase II development started aim to initiate Phase II study before the end of 2008 ALX-0681: subcutaneous delivery progressing towards the clinic aim to file an IND-equivalent by the end of

31 Prospects for 2008 (2) Further develop our own product pipeline: advance and expand pre-clinical studies initiate 6-8 new Nanobody programmes Further develop Ablynx s technology platform and explore the key Nanobody advantages in areas such as alternative routes of administration Partners advancing their programmes & Ablynx receiving milestone payments from our collaborations New commercial deals with shared risk and return 30

32 Achievements since IPO 7 November 2007 Raised a total of 85.2 million from its IPO on Euronext Brussels 126 million in cash at year end 150% increase in revenues to 9.9 million (2006: 4.0 million) Positive final results for ALX-0081 were reported in December Key Nanobody related claims of the Hamers-1 patent were maintained in opposition appeal proceedings Wyeth confirmed extension of the research term with us as part of its $212 million TNF-alpha licensing agreement Extension of the drug discovery and development alliance with Novartis for another year 31

33 Ablynx Annual Results 2007 Dr Edwin Moses, Chairman and CEO 28 February 2008 Nanobodies : delivering therapeutics beyond antibodies

34 Flexibility through formatting Extend half-life from few hours to three weeks Avid binding/cross-linking to increase potency or gain function Acquire an effector mechanism Combine multiple specificities Nanobodies are flexible and can be formatted for a specific activity or half life 33

35 ALX market overview Market size Growth potential Acute Coronary Syndrome 2.8 million ACS per year in the seven major markets 1 Sales of GPIIb/IIIa inhibitors > $600mm in Angioplasty (stenting) very likely to become standard of care for heart attack patients Restricted use of GPIIb/IIIa inhibitors in those patients 3 TTP Four cases of TTP per year per one million inhabitants in the US and EU 1 Market exclusivity Medical need ALX-0081 potential Full control of thrombotic events still lacking with current multi-drug treatment regimen (e.g. Aspirin, Heparin, Plavix and ReoPro ) Aspirin resistance (5-57%) and Plavix resistance (4-63%) Need for immediate and effective treatment in the ambulance/emergency room Immediate onset of treatment effect Biomarker for monitoring of safety and efficacy already implemented in Phase I Favorable safety profile allowing for early intervention treatment strategies Patients suffer from small thrombi Plasma substitutions (every 1-3 weeks) Episodes repeated and may prove fatal Immediate onset of activity Easy monitoring of treatment effects (safety and efficacy) Favorable safety profile Potential to change course of the disease and improve quality of life Source: 1 Datamonitor s Pipeline Insight: Antithrombotics, Reaching the untreated prophylaxis market report, DMHC2284 March ThomsonPharma Database 3 Cardiovascular diseases in Europe. Euro Heart Survey and National Registries of Cardiovascular diseases and patient management 2004, performed by the European Society of Cardiology 34

36 ALX Clinical development strategy - ACS Multiple dose Phase Ib in stable angina (ACS) Well controlled target population Establish safety and pharmacological profile with repeat dosing Establish proof of pharmacological concept (biomarker) Evaluate clinical endpoints Phase IIa study Widen patient population: unstable angina, acute MI (STEMI, Non-STEMI) Endpoint improved efficacy (early clinical marker, validate biomarker) Endpoint reduced bleeding events 35

37 ALX Clinical development strategy - TTP Phase I study in healthy volunteers Single dose and multiple dose Safety, tolerance, PK and PD Phase II study in TTP Safety Efficacy (prolongation of interval to subsequent plasma transfusions) Can become pivotal registration study for TTP 36