1

This is an independent study

performed by students from the

Faculté des Sciences

Pharmaceutiques de Lille

The opinions expressed are our own

and not necessarily those of Ablynx

2

Summary

Ablynx’s presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

3

Summary

Ablynx presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

4

Ablynx presentation…

•Headquartered in Ghent, Belgium, Ablynx is a spin-off of the Flanders Interuniversity Institute for Biotechnology (VIB) and the Vrije Universiteit Brussel (VUB).

•Ablynx is based on the research of Prof. Dr. R. Hamers, S. Muyldermans and was co-founded and seed-financed (€ 2M) by GIMV* and Biotech Fund Flanders in 2001.

5 GIMV*: Gewestelijke Investerings Maastschappij Vlaanderen

Ablynx story begins more than 20 years ago…

•Ablynx is a biopharmaceutical company engaged in the discovery and development of Nanobodies®, a novel class of therapeutic proteins based on single domain antibody fragments, for a range of serious life-threatening humain disease

Corporate Overview

5 nanobody products now in the clinic – 3 phase II and 2 phase I

•Strong IP position > 550 patents (The « Hamers patents ») • > 250 staff •Listed on Euronext Brussels since November 2007

Market capitalization ~ €350M Cash at 30thSeptember 2010 -€109.5M

8 potential clinical “proof-of-concepts” in the next 3 years

•4 partnerships with leading pharmaceutical companies: Novartis, Pfizer, Boehringer Ingelheim and Merck Serono

Partie I

• >25 programmes in the R&D pipeline

7

Executive Management

Experienced and international management team

Chairman and Chief Executive

Officer

Chief Financial Officer

Chief Business Officer

Chief Medical Officer

Chief Scientific

Officer

8

Summary

Ablynx presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

9

Ablynx’s Technology: Nanobodies®

Nanobodies ® are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies.

The Nanobody technology was originally developed following the discovery that camelidae (camels and llamas) possess fully functional antibodies that lack light chains.

Conventional Antibody Heavy-Chain Antibody Heavy and light chains Both chains required for antigen binding and stability

Only heavy chains Full antigen binding capacity and very stable

10

Nanobodies – beyond antibodies and small molecules

11

Nanobodies combine the advantages of conventional antibodies with some features of small-molecule drugs.

The Nanobody platform has broad applicability…

•Growth factors & receptors •Transporters •Chemokines •Cytokines & receptors •Protease •Integrins •Immunoglobulins •Micro-organisms •Ephrin receptors •Enzyme targets •Fc receptor…

•Nanobodies have been raised against >190 different targets across multiple target classes and disease indications.

•Nanobodies have been tested in 28 different in vivo disease models for proof-of-concept studies.

12

Nanobodies can recognize less accessible epitopes than conventional Antibodies…

Stijlemans et al. JBC, 2004

heavy-chain Ab’s Nanobodies

Conventional Ab’s

•recognize variable epitopes

And •recognised conserved epitopes inacessible to conventional Ab’s

•only bind to variable epitope

13

Nanobodies – beyond antibodies and small molecules

14

Powerful Nanobody formatting features…

•Formatting is the linking together of two or more Nanobodies which:

Provides flexibility in creating novel new drugs

bind to same epitopes on single target

bind to different epitopes on target

bind to different target

15

Customized Half-life...

~2 hrs

~ 1-2

days

~ 2-3

days

~ 5-6

days

~ 5-11

days

Pegylation Nanobody targeting serum protein

Peptides targeting serum albumin

For chronic indications, molecule should remain in circulation for days, ideally customized according to the needs

Nexpedite technology

Direct albumin binding

16

Ablynx’s proprietary NExpedite™ technology

Small peptide specific for Human Serum Albumin (HAS)

•< 3KDa (limited loss of benefit of Nanobodies)

•simple genetic fusion

•multiple fragments can be fused to a Nanobody if needed •depending on the fragment used, the serum circulation time

of the Nanobody it is fused to can be tailored.

~2 hrs ~hours ~days

17

Nanobodies – beyond antibodies and small molecules

18

Potential for multiple routes of administration…

Nanobodies can be administered via injection, needle-free device (lyophilized), pulmonary,

intranasal, oral and should be administered via transdermal and ocular

Antibodies can only be administered via injection or SC

19

Nanobodies – beyond antibodies and small molecules

20

Production of Nanobodies®

To reduce the risk of immunogenicity Ablynx humanizes its Nanobodies

4. Extract mRNA, RT-PCR

5. Generate library of ~ 107

transformants

6. Select specific VHHs by panning

21

1. Immunize camel/llama with immunogenes

2. Collect blood

3. Isolate lymphocytes

Nanobody manufacturing short development timelines

Manufacturing costs are ~1/3 of typical production costs for mAb 22

Ablynx’s technology: Nanobodies®: Conclusion

The Nanobody platform

A next generation biologics To the clinic

Monoclonal antibodies Expensive to manufacture, half-life fixed

Roche/Genentech, Biogen, Amgen, Pfizer/Wyeth, Novartis, Merck, Boehringer-Ingelheim

Antibodies fragments Reducing size/cost of manufacturing, tailoring half-life & delivery

ESBAtech/Alcon, Trubion, Dyax, GSK/Domantis, Medimmune/CAT, Genmab, Wyeth/Haptogen, Affimed, Macrogenics

Alternative scaffolds Developing new platforms with Advantages over antibodies via stability, ease of manufacturing, broad target applicability

Dyax, BMS/Adnexus, Amgen/Avidia, Molecular Partners, Pieris, Anaphore

23

Ablynx presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

Ablynx’s pipeline and drug

candidate

Partie III

Ablynx’s pipeline

A

Ablynx’s cardiovascular program

B

Ablynx’s immunology

program

C

Ablynx’s pipeline and drug

candidate

Partie III

Ablynx’s pipeline

A

Ablynx’s cardiovascular program

B

Ablynx’s immunology

program

C

Pipeline

24 Molecules in development

5 nanobodies in the clinic, 3 more expected during 2011 Therapeutic targets well known

Ablynx’s pipeline and drug

candidate

Partie III

Ablynx’s pipeline

A

Ablynx’s cardiovascular program

B

Ablynx’s immunology

program

C

Acute coronary syndrome (ACS) : ALX-081

Antithrombotic Strategies in Non-ST Elevation Acute Coronary Syndromes: Acute Coronary Syndromes: Definition, Prevalence & Patients at Risk

• Includes: Unstable angina, Myocardial infarction

• 2M coronary angioplasty carried out in the 7 major pharmaceutical markets* each year

• More than 1M hospital admissions in the USA annually

• Major public health concern

Acute Coronary Syndrom

• Anti-Von Willebrand Factor

• Bivalent

• Small size : 28 kDa

• Intravenous administration

• Manufactured in E. coli

• Phase II trials : Potential PoCs in

2011

Product characteristics

*USA, Japan, Germany, France, UK, Italy and Spain

ALX-0081

• Potentialy 1st in class GpIb • Act in first mover in cascade of thrombosis • Could prevent unwanted blood clot formation

Mechanism

Clinical trials in “high risk” patients with ACS undergoing a coronary angioplasty Compare with Reo-pro : GPIIb/IIIa inhibitors

First results

• Successful ALX-0081 Phase I study

Indicating the complete inhibition of vWF

Mediated effect on platelet aggregation and clotting in coronary arteries

• Excellent efficacy and safety profile in this patient study

• Phase II : started in sept 2009 Primary goal : show superiority in safety and equivalence in efficacy compared with ReoPro® primary endpoint bleeding data expected H2 2011

ACS market opportunity

Competitive with main approved drugs : • Glycoprotein IIb/IIIa receptor antagonist (Reo-Pro) had sales of >$500M in 2009

• Inhibitor of receptor P2Y12 (Plavix) in combination with aspirin.

• Coronary angioplasty treatment (Lovenox)

Heavy intracranial bleeding and abdominal bleeding associated with high doses of these anti coagulants significant area of unmet need for a new entrant.

Through 2018, the patent expiries of Merck/GlaxoSmithKline’s Integrilin, Merck/Medicure’s Aggrastat and Sanofi-Aventis’s Lovenox/Clexane

Potential partners for Ablynx

ADP : Adenosine Diphosphate

TTP Thrombotic thrombocytopenic purpura

• Idiopathic

• Secondary : associated with pregnancy, infections, autoimmune disease, malignancies and the use of drugs such as ticlopidine and clopidogrel

Acquired TPP ~90% of total

Congenital TPP ~10% of total

• Genetic mutation and ADAMTS13 gene

• Rare disorder of the blood-coagulation system

• Causing extensive microscopic thromboses

• Inhibition of the enzyme ADAMTS13 a metalloprotease cleaving multimers of von Willebrand factor into smaller units : decreasing their activity

• Plasma exchange is the most important component of treatment for TTP : normalization of platelets • Not painful but patients require frequent and lengthly hospital stay

• Mortality remains high (8-30%)

TTP Treatment / ALX-0681

• Anti-Von Willebrand Factor

• Bivalent

• Small size : 28 kDa

• Subcutaneous administration

• Manufactured in E. coli

• Phase II trials : Potential PoCs in

2013 Study started: September 2010

• Orphan drug designation from

the FDA and EMEA

ALX-0681 TTP Treatment

TTP

• Orphan Drug Designation

• Large unmet medical need

• Could provide first drug approved for use in TTP

• May significantly reduce hospitalization frequency

• May reduce number of transfusions

• Could significantly improve quality of life by an ease administration

ALX-0681 Potential

reduce cost

Clinical trials

Significant potentiel

Phase I : Complete in 2009

Phase II : Started in september 2010, Potential PoC in 2013 Endpoint : Time to recovery of blood markers (normalization of platelets)

Conclusion : Cardiovascular Program

• 2 pathologies : rare disorder and Major public health concern

• Phase I achieved

• Unmet medical need

• ALX-0081 : Potential PoCs in 2011

• ALX-0681 : Potential PoCs in 2013

• TTP : orphan drug designation

• 2 administration forms : - IV : safety and equivalence of efficacity

- SC : easy administration

Ablynx’s pipeline and drug

candidate

Partie III

Ablynx’s pipeline

A

Ablynx’s cardiovascular program

B

Ablynx’s immunology

program

C

Immunology : Rheumatoid Arthritis

• Chronic and progressive inflammatory disorder of the joints and

surrounding tissues Life long treatment

• Frequency : 0.5 -1.0% of adults in developed countries

• 5 % in women over age 55

RA Market Opportunity

• $ 23 billion in 2015 = World market for RA biologic therapeutics expected

Global Arthritis Market Review 2008 (World Top Ten RA Drugs)

11%

29%

51%

9%COXIB

NSAID + others

anti-TNF

DMARDs

Global market Arthritis 2008 = $35Bn

Anti-TNFα “Gold standard”

=> Sales in all indications in 2009 of > $19Bn

Anti-TNFα Market

In 2009, $6.5Bn sales in the Key Geographic Markets

Main Competitor :

Market leader, followed by Remicade® and then by Humira®

Global Arthritis Market Review 2008 (World Top Ten RA Drugs)

0

2

4

6

8

10

12

14

16

18

20

$Bn

TNFalpha

market

2006 2007 2008 2009

Nanobody vs competitor

• Small Size 28 kDa • Bivalent • Subcutaneous administration Potentialy Every 4 or 8 weeks • Potentially patients would not develop anti-drug antibodies • Relatively low cost of goods

ATN-103

• Size 150 kDa

• Bivalent

• Subcutaneous administration

Twice weekly or weekly

• Nearly 30% of patients develop anti-drug antibodies

• Produced by recombinant DNA technology in a Chinese hamster ovary mammalian cell expression system

Licensing Patent expiries

in 2012

Pre-clinical => Data showed more efficacity than enbrel®

ATN-103 : First results

Phase II started in September 2009 :

=> Trials in the US and Japan were initiated and enrolment completed in September 2010

If Pfizer proceed straight to Phase III, 2014 marketing authorization feasible

=> Royalty agreement means that this could be a very important revenue stream for Ablynx

Conclusion Pipeline

• Until now: No clinical failures and attrition

• Distinction by administration (PK) and safety

• Target well known no potential risk

• Uncertainty with the immunogenicity of the Nanobodies

• 3 molecule in phase II, never phase III for the moment

• 5 molecules in clinic and 3 more in 2011

• Success of Pre-clinical/Phase I programmes

Ablynx presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

key elements

Leverage the advantages of the Nanobody technology broadly across a range of

therapeutic areas

Rapid target selection

Advance programmes internally to the optimal value creation point

Partner

Key element

Partie IV

Ablynx’s key partnerships

2007 2010 2006 2008 2009 2005

Jan

Dec

Sept Dec

Feb

Jul

Oct

May

Nov

Multi-target collaboration across several indications

options to license two of these programmes

TNFa research and licensing collaboration - $212.5 million plus royalties

selected a second Nanobody targeting TNFα that entered a Phase I clinical development.

Research and licensing collaboration on Alzheimer’s disease target - €206 million in milestones plus royalties

Strategic alliance worth up to €1.3 billion: 10 programmes with potential milestone payments up to €1.25 billion, plus royalties and co-promotion options in certain EU countries. In addition, up to €75 million including research-based payments, research milestones,

2 target 50/50 co discovery/ co-development collaboration (oncology & immunology). €10 million upfront fee and profit share on any products

BI selected a Nanobody lead candidate for further development for the treatment of Alzheimer’s disease.

agreed to collaborate to co-discover and co-develop Nanobodies against an inflammatory disease target.

POTENTIAL DEAL VALUE €2.2 billion in milestones and royalties

Ablynx’s platform is validated by partnerships with leading pharma compagnies

WHY Ablynx's balanced business model of internally

funded programs and partner supported programs allows the company to manage the

risks associated with such programs.

More than €117M in cash already received

Ablynx’s goal build a unique proprietary pipeline

Partnerships, fair’s fair…

•Upfront payments •Milestone payments •Royalties And •Annual licence payment

•Licenses rights •Provides scientific support, ressources and expertise

key elements

Leverage the advantages of the Nanobody technology broadly across a range of

therapeutic areas

Rapidly demonstrate proof-of-concept in the clinic

Advance programmes internally to the optimal value creation point

Partner

Key element

Partie IV

Balanced value creation

Ablynx Partners

70% R&D staff

dedicated to ablynx’s in-house programme

Only 30% of Ablynx’s

R&D staff dedicated to partnerships

98% of accessible

targets available for in-house pipeline

< 2% of accessible

targets partnered to date

Significant value creation

for the Ablynx pipeline

Potential value increased through partnered programmes

Ablynx presentation

Partie I

Ablynx’s Technology:

Nanobodies®

Partie II

Ablynx’s business strategy

Partie IV

Ablynx’s pipeline and drug

candidate

Partie III

Financial analysis

Partie V

Financial analysis

Partie V

Ablynx on the stock exchange

A

Ablynx’s revenues and expenses

B

How long will it last ?

C

Financial analysis

Partie V

Summary

Ablynx on the stock exchange

A

Ablynx’s revenues and expenses

B

How long will it last ?

C

Ablynx at the begining

From 2002 to 2006

Sofinnova Partners SAS (Fr) Gilde (Pays-Bas)

Alta (USA) Abingworth (RU)

Existant Shareholder

KBC et SR One (USA) Existant Shareholder

From 2007

IPO

Jan 2002

Ap 2004

Au 2006

€ 3M

€ 25M

€ 40M

TOTAL =

€ 68 M

Nov 2007

€ 86M

Shareholder at the end of 2009

18,77%

16,07%

11,12%

8,50%

Majority Shareholder

= 54,46%

Stock exchange prices

IPO Fund raising €85.2 million

Shares issued ≈ 10.7 M Aggregate number ≈ 34.7 M

€ 7.3 /share

Decrease and increase of the share value with the BEL20 Loss per share at the end of 2010 of € 0.58

€ 8.1 /share

SPO Fund raising €50 M

Shares issued ≈ 6.7 M Aggregate number ≈ 43.6 M

Financial analysis

Partie V

Summary

Ablynx on the stock exchange

A

Ablynx’s revenues and expenses

B

How long will it last ?

C

0

5

10

15

20

25

30

35

Mil

lion

s €

Grants

R & D

Revenues

R & D revenues from partnerships Upfront payment Milestones payment

29.683

1.09

16.755

9.920

3.969

0.844

31.432

0

10

20

30

40

50

60

Mil

lio

ns

€

General and administrative

R & D

Expenses

R & D expenses : ↗ €5.7 million in 2010 Personnel costs (224 employees in 2010 vs. 195 in 2009) External development (↗ €3.8 million due to clinical trials)

General and administrative : stabilised at €8.9 million

17.664

24.232

37.336

51.844

Preclinical

Phase I

Phase II

2006

ALX-0081

2007

ALX-0681 ATN-103

ALX-0081

2008

ALX-0061 ALX-0141

ALX-0081 ALX-0681 ATN-103

2009

ALX-0061 ALX-0171 ALX-0651

ALX-0681 ALX-0141

ATN-103 ALX-0081

2010

ALX-0651 ALX-0171 + 1

ALX-0141 ALX-0061 PF-

05230905

ALX-0081/ALX-0681 (TTP) ATN-

103

57.394

Loss for the year

Loss for the year balanced with the € 50 million from SPO

0

20

40

60

80

100

120

140

3,3 18,2 11,7

25,8

126,5113,6

92,3

115,9

Mill

ions

€

Cash

Cash

Cash

IPO € 85.2 million

In 2010 : € 85.500 in short term investments

SPO € 50 million

Financial analysis

Partie V

Summary

Ablynx on the stock exchange

A

Ablynx’s revenues and expenses

B

How long will it last ?

C

Ablynx at the end of 2010

Low non-current liabilities (€ 1.134 million in 2010 vs. € 0 in 2009)

Considerable cash (€ 115.9 million in 2010 vs. € 92.3 million in 2009)

Revenues €31.4 million

3 more deals in 2010

Reasonable loss for the year (excluding the SPO)

5 nanobody-based products in clinical trials (3 in phase II, 2 in phase I)

With €115.9 million in cash and with expenses growing from €50 million / year to €70 million, Ablynx could continue its activities

during approximately 2 years

63

SWOT Strengths

Opportunities

Weaknesses

Threats

Strengths

•Diverse and broad pipeline with 5 drugs in clinical trials •Potent technology platform that combines benefits of conventional monoclonal antibodies and small molecule drugs •Strong IP position > 550 patents •Partnerships with several major pharmaceutical companies to provide specialist expertise and finance for drug development and reduce risks •Lower cost manufacturing •Strong management with broad experience

Weaknesses

•Dependency on milestone payments to fund research activities •No track record in large clinical trial

64

SWOT Strengths

Opportunities

Weaknesses

Threats

Opportunities •Nanobodies can be administered through alternative delivery route •Nanobodies can recognize less accessible epitopes than conventional Antibodies •Innovative product •Strong growth in antibodies-based therapeutics market

Threats •Market for some therapeutic programmes highly competitive •Immunogenicity

65

ANY QUESTIONS? 66

67

Back-up

68

Competitors

Aug 2005 The Opposition Division of the European Patent Office upheld the key composition of matter claims for Nanobodies contained within EP 0 656 946, one of the Hamers Patents, following opposition proceedings initiated by Domantis.

Founded in 2000 Buy by GSK in 2006 treat many diseases including rheumatoid arthritis Anti-TNF

Oct 2009 Ablynx reached a settlement with Domantis

Feb 2010 Ablynx successfully opposed a half-life extension patent which had been granted to Domantis and that this patent had been revoked in full.

In 2006 : 13 proprietary therapeutic programs 9 partnered therapeutic programs (Bristol Myers Squibb,Abbott)

69

contract manufacturer for protein, antibody and immunodiagnostic solutions

Competitors

designed to support research and development

utilizes a multi-tiered protein expression platform which consists of bacterial, yeast and mammalian expression systems v

antibody production

Shark Antibody

70

Needle-Free

•It works by forcing liquid medication at high speed through a tiny orifice that is held against the skin.

•This creates an ultra-fine stream of high-pressure fluid that penetrates the skin without using a needle.

•Injections can be IM, SC or ID

IM SC ID How does it works

Device advantages

•Better patient compliance – no needle-phobia •Superior safety by removing the potential of a needlestick injury •Speed of Injection •Easy transport…

71

Nanobodies – beyond antibodies and small molecules

Nanobodies may have the potential to be given to patients as an inhaled drug, as a skin patch or as a pill.

Nanobodies have been raised against >190 different targets.

Nanobodies can be made quickly and cost effectively, because they are simple and stable molecules.

Nanobodies are small, 1/10 of the size of a conventional antibody, and so can penetrate tumours and other diseased tissue better.

Nanobodies can be linked together to generate tailor-made therapeutics for acute and chronic diseases..

72

Production of Nanobodies®

To reduce the risk of immunogenicity Ablynx humanizes its Nanobodies

4. Extract mRNA, RT-PCR

5. Generate library of ~ 107

transformants

6. Select specific VHHs by panning

73

1. Immunize camel/llama with immunogenes

2. Collect blood

3. Isolate lymphocytes