WHAT ARE NANOBODIES?

Nanobodies® are a novel class of proprietary therapeutic proteins based on single-domain antibody
fragments that contain the unique structural and functional properties of naturally-occurring heavy chain only
antibodies.

Ablynx’s proprietary Nanobody platform allows for the rapid generation and large-scale production of novel
biological therapeutics that have potential in a wide range of human diseases.

The Nanobody technology was originally developed following the discovery and identification that camelidae (e.g.
camels and llamas) possess fully functional antibodies that consist of heavy chains only and therefore lack light
chains. These heavy-chain only antibodies contain a single variable domain(VHH) and two constant domains (CH2,
CH3).

The cloned and isolated single variable domains have full antigen binding capacity and are very stable. These
single variable domains, with their unique structural and functional properties, form the basis of a new generation
of therapeutic molecules which Ablynx has named “Nanobodies”.

Due to their small size and unique structure, Nanobodies are ideal building blocks for the generation of novel
biological drugs with multiple competitive advantages over other therapeutic molecules.
Ability to bind multiple targets with one therapeutic Nanobody molecule. These therapeutic molecules may
contain Nanobody building blocks combined with each other (up to 7), or be combined with other protein
domains or with other molecules or drugs.

Multi-specific (binding different targets; currently 2 bi-specific Nanobodies in the clinic), multivalent (binding
identical targets; currently 2 Nanobodies in the clinic) and bi-paratopic (binding different epitopes on the same
target) Nanobody molecules have been successfully produced and their potential therapeutic effect
demonstrated. The different Nanobody building blocks are linked together with Glycine-Serine linkers with
flexible lengths.

Nanobodies can interact with epitopes on targets which are hidden or shielded from the much larger conventional
antibodies.Functional selective Nanobodies have been generated against GPCRs as well as ion-gated, ligand-gate
and voltage-gated ion channels (multiple programmes on-going, both internally and with partners including
Merck & Co., Novartis, and Genzyme).

The robustness and stability of Nanobodies allows administration through multiple delivery routes, including
intravenous and subcutaneous injection (currently 5 Nanobodies in the clinic)and nebulisation directly into the
respiratory tract (currently 1 Nanobody in the clinic), as well as potentially through the ocular route and orally for
local treatment in the gut.
Ability to tailor the in vivo half-life of a Nanobody from a few hours to >3 weeksto achieve the desired properties,
such as the use in chronic versus acute indications. Ablynx’s proprietary half-life extension technology is based on
a Nanobody that binds to human serum albumin, thereby increasing the in vivo serum half-life of the therapeutic
molecule.

Two clinical proof-of-concepts have been achieved in patients with rheumatoid arthritis with two Nanobodies
that incorporate this proprietary half-life extension technology.

As a result of their formatting flexibility, specific Nanobody formats can be developed to increase cell
specificity. For example, Nanobodies with low activity on normal cells can be linked to an anti-“anchor”-
Nanobody resulting in avid binding on tumour cells, dramatically improving the potency of the Nanobody on
tumour cells. The same principle can also be applied for localised treatment in certain tissues like the joints
and the eye, using a tissue-specific anchor to ensure high local concentrations while minimising systemic
exposure. Lastly, taking advantage of the ability of Nanobodies to be readily formatted into multi-specifics,
we can design Nanobody drugs that result in improved tumour cell killing by recruiting immune cells to
tumours.

Nanobodies can be applied in the field of antibody-drug conjugate technologies (ADC), which uses antibodies or
antibody-derived molecules to deliver highly potent anticancer agents to cancer cells.

An ADC consists of a cell-killing agent which is covalently attached to a Nanobody that binds to a target antigen
on cancer cells. In this case, the Nanobody serves to deliver the cell-killing agent specifically into the cancer cells
where the cytotoxic is internalised and released to specifically kill the cancer cells.
Because of their simple structure and stability, Nanobodies can be easily coupled to cytotoxic compounds without
losing any binding affinity, and yielding a uniform conjugate, whereas for antibodies the result can often be a
mixture of antibodies with a varying number of warheads linked to it. In addition, the formatting flexibility of
Nanobodies can be leveraged to combine different binding specificities into one drug to minimize killing of
normal cells, or to target different receptors to enhance efficiency of uptake of the cytotoxic payload into tumour
cells.

Nanobodies (including multi-specific, multivalent and bi-paratopic constructs) are encoded by single genes and
are efficiently produced in various prokaryotic and eukaryotic hosts, including bacteria, yeast, and mammalian
cells. They can be formulated at high concentrations and maintain low viscosity, enabling multiple routes of
administration, including low volume injectables.
Ablynx’s strategy is to use the Company’s unique Nanobody technology to develop therapeutics in areas of high
unmet medical need where Nanobodies offer a clear promotable advantage over existing products and
technologies.

The Company employs a hybrid business model where it invests directly in its own development programmes as
well as collaborating with pharmaceutical partners at all stages of discovery and development. Where there are
appropriate opportunities, Ablynx will retain some or all rights to commercialise its products.

Ablynx’s ambition is to develop differentiated and innovative medicines which have the potential to make a real
difference to society, as well as creating sustainable value for all its stakeholders.

Intellectual Property
 Ablynx
 >Technology & innovation
 >Intellectual Property

Ablynx, a Sanofi company, has a strong and broad patent portfolio of more than 500 pending and granted patents
in about 100 families which covers various aspects of the discovery, generation, optimisation, formatting,
manufacture, administration, formulation and clinical use of Nanobodies, as well as covering its clinical
development programmes and product candidates.

This patent portfolio, combined with the extensive experience and expertise that Ablynx has established as the
first company to discover and develop Nanobodies and to achieve clinical proof-of-concept for multiple clinical
programmes, puts Ablynx in a unique position to exploit the Nanobody platform in the field of therapy and
diagnosis.

Ablynx is also the holder worldwide of the trademarks Ablynx®, Nanobody® and Nanoclone®.
Current Partnerships
 Ablynx
 >Partnerships
 >Current Partnerships

Boehringer Ingelheim

In September 2007, Ablynx entered into a global strategic alliance with Boehringer Ingelheim (BI), with a potential
deal value of €1.3 billion plus royalties, to discover, develop and commercialise up to ten different Nanobody
therapeutics. Ablynx will receive milestone payments of up to €125 million for each Nanobody that is developed,
as well as royalties. Ablynx and BI are collaborating in the discovery of Nanobodies against agreed targets across
multiple therapeutic areas including immunology, oncology and respiratory disease. BI will be exclusively
responsible for the development, manufacture and commercialisation of any products resulting from the
collaboration.

On 4 November 2015, Boehringer Ingelheim presented positive pre-clinical results with the bi-specific anti-
VEGF/Ang2 Nanobody in relevant cancer models, demonstrating that this bi-specific Nanobody strongly impairs
proliferation and survival of human endothelial cells. In addition, it has superior efficacy as compared to inhibition
of the individual pathways by the reference monoclonal antibody drugs and was found to be well tolerated in
cynomolgus monkeys. These strong in vivo proof-of-mechanism results support the evaluation of this Nanobody
in Phase I clinical studies, which will trigger a milestone payment to Ablynx at study start.
Click here to view the presented poster.
Eddingpharm

First collaboration

In October 2013, Ablynx granted an exclusive, royalty-bearing license to Eddingpharm, a leading Chinese
pharmaceutical company, to develop and commercialise its anti-RANKL Nanobody, ALX-0141, in the mainland of
the People’s Republic of China, the Hong Kong and Macao Special Administrative Regions, and Taiwan, for all
indications, including osteoporosis and bone metastases.

Under the terms of the agreement, Eddingpharm will be responsible for the clinical development, registration and
commercialisation in Greater China of anti-RANKL Nanobody therapeutics. Ablynx will have access to the data
generated by Eddingpharm to support potential licensing discussions in other geographic regions.

Ablynx has received a €2 million upfront payment from Eddingpharm and is entitled to receive commercial
milestone payments plus tiered, double-digit royalties of up to 20%, based on annual net sales of ALX-0141
generated by Eddingpharm in Greater China.

Second collaboration

On 1 September 2014, Ablynx expanded its relationship with Eddingpharm by granting Eddingpharm an
exclusive, royalty-bearing license to develop and commercialise Ablynx’s anti-TNFα Nanobody, ozoralizumab
(ATN-103), in the mainland of the People’s Republic of China, the Hong Kong and Macao Special Administrative
Regions, and Taiwan, for all indications, including rheumatoid arthritis (RA).

Under the terms of the agreement, Eddingpharm will be responsible for the clinical development, registration and
commercialisation in Greater China of anti-TNFα Nanobody therapeutics. Ablynx will have access to the clinical
data generated by Eddingpharm to support potential licensing discussions in other geographic regions.

Ablynx has received an upfront payment of €2 million and is entitled to receive development and commercial
milestone payments plus tiered, double-digit royalties of up to 20%, based on annual net sales of ozoralizumab
generated by Eddingpharm in Greater China.
Merck & Co.

First collaboration

In October 2012, Ablynx entered into a collaboration with a subsidiary of Merck & Co. (known outside the US and
Canada as MSD.) to develop and commercialise Nanobody candidates directed towards a voltage gated ion
channel with the option to develop and commercialise a Nanobody to a second target.

Under the terms of the agreement, Merck gained exclusive global rights to Nanobodies against the selected
target, with an option for similar rights to a second target. Upon signing, Merck has paid Ablynx a €6.5 million
upfront payment and a €2 million fee for research funding. In addition, Ablynx will be eligible to receive up to €448
million in research, regulatory and commercial milestone payments associated with the progress of multiple
candidates as well as tiered royalties on any products derived from the collaboration. Ablynx is responsible for the
discovery of Nanobody candidates and Merck will be responsible for the research, development, manufacturing
and commercialisation of any Nanobody product resulting from the collaboration.

Second collaboration

In February 2014, Ablynx entered into a second research collaboration and licensing agreement with a subsidiary
of Merck & Co. This new exclusive collaboration and licensing agreement is focused on the discovery and
development of several predefined Nanobody candidates (including bi- and tri-specifics) directed toward so called
“immune checkpoint modulators”, proteins believed to provide potential targets for the development of cancer
immunotherapies, a rapidly emerging approach to the treatment of a wide range of cancer types. Under the
terms of the agreement, Ablynx received an upfront payment of €20 million and up to €10.7 million in research
funding during the initial three year research term of the collaboration. In addition, Ablynx is eligible to receive
development, regulatory and commercial milestone payments on achieved sales thresholds for a number of
products with ultimate potential to accrue as much as €1.7 billion plus tiered royalties. Merck will be responsible
for the development, manufacturing and commercialisation of any products resulting from the collaboration.

In July 2015, Ablynx and Merck & Co., Inc. significantly expanded the size and scope of the deal to include up to 12
additional Nanobody programmes against individual protein targets and target combinations (mono-specific and
multi-specific Nanobodies) through to the in vivo pre-clinical proof-of-concept stage, after which Merck will have
the option to advance specified lead candidates. Under the terms of this four year expansion, Ablynx will receive a
€13 million upfront payment comprising exclusivity fees and FTE payments as well as further research funding
over the term of the collaboration. In addition, Ablynx will be eligible to receive additional exclusivity fees,
depending on the number of programmes for which Merck decides to exercise its licensing option, plus
development, regulatory and commercial milestone payments of up to €340 million per programme, as well as
tiered royalties on annual net sales upon commercialisation of any Nanobody products. Merck will be responsible
for clinical development, manufacturing and commercialisation of any products resulting from the collaboration.

Merck KGaA

First collaboration

In September 2008, Ablynx entered into a collaboration with Merck KGaA (previously called Merck Serono) under
which Merck KGaA and Ablynx co-discover and co-develop Nanobodies against two targets in immunology and
oncology. The agreement included an upfront cash payment to Ablynx of €10 million and both companies will
share equally all research and development costs and the resulting profits. Ablynx has options to opt-out during
the research and development programmes, in which case Ablynx is eligible to receive milestones and royalties.
Total development and commercial milestones, depending on the point of opt-out by Ablynx, could reach up to
€325 million should a product be approved in multiple indications in all major markets.

Second collaboration

In October 2010, Ablynx and Merck KGaA entered into a second collaboration to co-discover and co-develop
Nanobodies against one inflammatory disease target, more specifically in rheumatology. This agreement
included an upfront payment of €10 million for one target and Ablynx is responsible for all activities and costs up
to the delivery of a preclinical package (except manufacturing) that will form the basis for the filing of an IND or
IND equivalent. Once Ablynx reaches IND stage, Merck Serono has the option to accept Ablynx’s IND package
and if they do, Ablynx will receive a €15 million milestone payment and still own 50% of this programme. Ablynx
has the option to continue to co-develop together with Merck KGaA on a 50:50 co-development basis until the
products reach the market. Ablynx and Merck KGaA will then also share the resulting profits. Ablynx also has the
flexibility to convert this collaboration into an exclusive, worldwide licensing deal with milestone payments and
significant royalties which are scaled against sales of the products.

Third collaboration
In November 2011, Ablynx further expanded its relationship with Merck KGaA, and entered into a third agreement
to co-discover and co-develop Nanobodies against two targets in osteoarthritis. The companies will exploit the
unique Nanobody features and will develop multi-specific products, which have extended half-lives.

Under the terms of the agreement, Ablynx has received an upfront payment of €20 million and is fully responsible
for all activities and costs for each programme, excluding manufacturing costs and costs relating to certain in vivo
models, up to the delivery of the pre-clinical package that will form the basis of an Investigational New Drug (IND)
filing or IND equivalent filing. Ablynx is entitled to receive a further €15 million for each programme if the pre-
clinical packages are accepted by Merck KGaA. At that point, Ablynx has the option to continue with Merck KGaA
on a 50:50 co-development basis and share the resulting profits, or to convert this collaboration into an exclusive,
worldwide licensing deal with milestone payments and tiered royalties.

Fourth collaboration

In September 2013, Ablynx and Merck KGaA further expanded their relationship through a multi-year research
alliance that could lead to at least four co-discovery and co-development collaborations.

Beginning 2015, both parties mutually agreed to amend this Strategic Collaboration Agreement to focus on two
particular bi-specific Nanobody programmes going forward. Ablynx will, at no cost, regain full ownership of three
other promising pre-clinical programmes which have been generated under this Strategic Collaboration
Agreement in various therapeutic areas, including immuno-oncology. Merck KGaA has provided full financial
support for this Strategic Collaboration Agreement, with €11.5 million in non-refundable cash paid to Ablynx so
far and approximately €1.0 million to be paid before the end of this year. In addition, Ablynx is eligible to receive
future milestone payments and royalties related to the two specific programmes being pursued in this
partnership.
Novo Nordisk

On 25 November 2015, Ablynx announced that it had entered into a global exclusive collaboration and licensing
agreement with Novo Nordisk to discover and develop novel multi-specific Nanobody drug candidates for use in
an undisclosed disease area, with an option to expand the agreement to include a second Nanobody programme.

Under the terms of the agreement, Ablynx will receive an upfront license fee of €5 million and up to €4 million in
research funding during the initial three year research term of the collaboration. If Novo Nordisk decides to
exercise the option to the second programme, the Company will pay Ablynx an exercise fee of €4 million. In
addition, Ablynx is eligible to receive potential development, regulatory and commercial milestone payments of
up to €182 million per programme plus tiered royalties on the annual net sales on any products resulting from the
collaboration. Novo Nordisk will be responsible for the development, manufacturing and commercialisation of
any products resulting from this agreement.

Taisho Pharmaceutical Co., Ltd.

In June 2015, Ablynx announced that it had entered into an exclusive license agreement with Taisho
Pharmaceutical Co., Ltd., (“Taisho”) for the development and commercialisation of Ablynx’s anti-TNFα
Nanobody, ozoralizumab, in Japan,for the treatment of RA.

Under the terms of the agreement, Taisho will be responsible for development, registration and
commercialisation of anti-TNFα Nanobody therapeutics in Japan. Ablynx will receive an upfront payment of US$3
million and is entitled to receive development and commercial milestone payments plus royalties based on annual
net sales of anti-TNFα Nanobody therapeutics generated in Japan.
Vobarilizumab (ALX-0061) – anti-IL-6R Nanobody to treat auto-immune disorders

o Vobarilizumab is being developed for the treatment of rheumatoid arthritis (RA) and systemic lupus
erythematosus (SLE)

o Phase IIb monotherapy study (head-to-head versus tocilizumab) in 251 RA patients completed in July
2016; demonstrating that vobarilizumab induced clinical remission based on the disease activity score
(DAS28 CRP < 2.6) in up to 41% of patients, as compared to 27% of patients treated with toclizumab

o Phase IIb combination therapy (+MTX) study in 345 RA completed in August 2016 with up to 51% of
treated patients achieving clinical remission at week 24 (DAS28 ERP < 2.6)

o The results of the two Phase II studies in RA also confirmed the favourable safety profile of vobarilizumab
and the potential monthly adminisatration

o 94% of eligible patients from both Phase IIb RA studies rolled-over into the 2 year open-label extension
study of vobarilizumab; results expected in 2018

o Phase II study in 312 SLE patients completed in March 2018; primary endpoint of dose response based on
the modified BILAG-based combined lupus assessment at week 24 not met; safety findings through
week 58 were favourable for vobarilizumab
Rheumatoid arthritis (RA)

RA is characterised by chronic and progressive joint inflammation that typically results in permanent, debilitating
tissue damage, which is further compounded by joint deformation. The condition is associated with lower quality
of life, premature death, disability, and unemployment. It is estimated that up to 1 percent of the adult population
worldwide suffer from RA.

Systemic lupus erythematosus (SLE)

SLE is a complex, multi-organ, autoimmune disorder characterised by the production of pathogenic

autoantibodies and tissue deposition of immune complexes, which result in widespread tissue damage. Although
the aetiology of SLE is not fully understood, multiple genetic, environmental, and hormonal factors have been
implicated in its development. The disease displays a broad variety of symptoms and highly variable clinical
features, including systemic, cutaneous, renal, musculoskeletal, and haematological manifestations.
Approximately 5 million people worldwide suffer from a form of lupus and 90 percent of people diagnosed are
women.
Vobarilizumab mode of action

Vobarilizumab targets the interleukin 6 pathway via its IL-6 receptor (IL-6R). IL-6 is a pro-inflammatory cytokine
that plays a role in T-cell activation, production of acute phase proteins in response to inflammation, induction of
immunoglobulin production, and stimulation of osteoclast differentiation and activation. Vobarilizumab (26kD)
has a very strong affinity for the soluble IL-6R and contains an anti-IL-6R Nanobody linked to an anti-human
serum albumin (HSA) Nanobody, thereby increasing the in vivo serum half-life.

Ozoralizumab – anti-TNFα Nanobody to treat auto-immune disorders

o Ozoralizumab is being developed for the treatment of auto-immune disorders with initial focus on
rheumatoid arthritis (RA)

o Ozoralizumab achieved clinical proof-of-concept in a Phase IIa RA study

o Exclusive license agreement signed with Eddingpharm in 2014 to develop and commercialise
ozoralizumab in Mainland China, Hong Kong, Macao and Taiwan

o Exclusive license agreement signed with Taisho Pharmaceutical 2015 to develop and commercialise
ozoralizumab in Japan
Rheumatoid arthritis (RA)

RA is characterised by chronic and progressive joint inflammation that typically results in permanent, debilitating
tissue damage, which is further compounded by joint deformation. The condition is associated with lower quality
of life, premature death, disability, and unemployment. It is estimated that up to 1 percent of the adult population
worldwide suffer from RA.

Ozoralizumab mode of action

Ozoralizumab (38kD) is a trivalent Nanobody that potently neutralises TNFα and binds to serum albumin to
increase its in vivo half-life. TNFα promotes the inflammatory response which in turn causes many of the clinical
problems associated with auto-immune disorders such as rheumatoid arthritis, ankylosing spondylitis,
inflammatory bowel disease and psoriasis.

Partnering opportunity

Ablynx is currently looking for partners to develop and commercialise ozoralizumab outside of Greater China and
Japan. For further information, please contact Gosia Ciesiolka, Director Business Development.
Caplacizumab – wholly-owned anti-vWF Nanobody to treat acquired Thrombotic Thrombocytopenic Purpura
(aTTP)

o Caplacizumab has the potential to become an important new component in the standard of care for
acquired thrombotic thrombocytopenic purpura (aTTP)

o Early October 2017, Ablynx announced positive topline results from the Phase III HERCULES study with
caplacizumab:

 Caplacizumab meets primary endpoint and key secondary endpoints

 Statistically significant reduction in time to platelet count response, with at any given
time patients treated with caplacizumab 50% more likely to achieve platelet count
response

 74% relative reduction in the percentage of patients with aTTP-related death, a

recurrence of aTTP, or at least one major thromboembolic event during the study drug
treatment period

 67% relative reduction in the percentage of patients with aTTP recurrence during the
overall study period
 No caplacizumab-treated patients had refractory disease

 Trend to faster normalisation of organ damage markers

 Safety profile consistent with Phase II TITAN results and mechanism of action

 Data will be used to drive the registration process for caplacizumab in Europe and the USA.

 If approved by regulatory authorities, caplacizumab will be the first therapeutic specifically

indicated for the treatment of aTTP
o At 59th Annual Meeting of the American Society of Hematology (ASH) in Atlanta, GA, USA, additional
results from the Phase III HERCULES study were presented showing that treatment with caplacizumab
resulted in:

 38% relative reduction in the number of days of plasma exchange (PEX)

 41% relative reduction in the volume of plasma used

 65% relative reduction in the number of days in the intensive care unit (ICU)

 31% relative reduction in the number of days in hospital

o Caplacizumab is expected to be launched in 2018
Unmet medical need in aTTP
Acquired TTP is an ultra-rare, acute, life-threatening blood clotting disorder that leads to extensive micro-clot
formation in the small blood vessels throughout the body and tissue ischaemia and damage to vital organs,
including the heart, brain and kidneys. Mortality is high at 10-20%[2], with vast majority within 2 weeks post
diagnosis, and about 36% of patients suffer from recurrences [1] after initial treatment with the current standard-
of-care, which consists of plasma exchange (PE) plus immune-suppressive treatment. In addition, the organ
damage caused by a TTP episode may result in poor longer term outcomes.
There remains a high unmet medical need to immediately inhibit the formation of microvascular thrombi, thereby
reducing the risk of further organ damage. Maintenance of this platelet-protective effect is required until the
underlying auto-immune activity has been resolved. Caplacizumab is being developed to address this unmet need
and its clinical effect has been demonstrated in the Phase II TITAN study.

von Willebrand factor

von Willebrand factor (vWF) is a blood glycoprotein involved in haemostasis, a complex process that controls
bleeding, and its primary function is to bind to other proteins, including glycoprotein Ib in the initiation of platelet
adhesion.

What is the biological basis of TTP?

TTP exists in two forms: a congenital and an acquired form, with the latter accounting for >90% of the patients.
The condition is characterised by severe thrombocytopenia (low blood platelet count), haemolytic anaemia
(abnormal break down of red blood cells) and signs and symptoms of tissue ischemia (insufficient blood supply to
organs), including stroke or myocardial infarctions. The ischemic damage may result in both acute complications
as well as poor longer term outcomes. In the majority of patients, it is an autoimmune condition where auto-
antibodies are generated to the enzyme ADAMTS13, which is responsible for ultra large vWF (ULvWF) cleavage.
As a result of impaired ADAMTS13 activity (typically <10% of that in normal plasma), these ULvWF molecules
spontaneously bind to platelets, resulting in ULvWF mediated platelet string formation in the small blood vessels.

Caplacizumab mode of action

Caplacizumab is a highly potent and selective bivalent anti-vWF Nanobody that received Orphan Drug
Designation in the US and EU in 2009. It could be the first drug specifically approved for the treatment of acquired
TTP.

Caplacizumab inhibits the interaction between vWF and platelets by targeting the A1 domain of vWF and thus has
the potential to immediately block the ULvWF mediated platelet interactions and the formation of the string-like
clots in the blood of patients with acquired TTP.
ALX-0141 – anti-RANKL Nanobody to treat bone-loss related disorders

o ALX-0141 is being developed for the treatment of bone-loss related disorders including osteoporosis and
bone metastasis

o ALX-0141 successfully completed a Phase I study in post-menopausal women

o Exclusive license agreement signed with Eddingpharm in October 2013 to develop and commercialise
ALX-0141 in Mainland China, Hong Kong, Macao and Taiwan

o Ablynx is not pursuing this programme internally and is looking for licensing opportunities outside
Greater China
Osteoporosis and Bone Metastasis

Osteoporosis is a progressive bone disease characterised by a decrease in bone mass and density which can lead
to an increased risk for fractures. Bone metastasis, or metastatic bone disease, is a class of cancer metastases that
results from primary tumor invasion to bone. Unlike haematological malignanciesthat originate in the blood and
form non-solid tumours, bone metastasis generally arise from epithelial tumors and form a solid mass inside the
bone.

ALX-0141 mode of action

ALX-0141 (41kD) specifically targets RANKL, a key mediator of bone resorption and an essential regulator of
osteoclasts, the cells involved in the breakdown of bone. ALX-0141 is a trivalent Nanobody targeting RANKL and
that binds to serum albumin to increase its in vivo half-life.

Partnering opportunity

Ablynx is currently looking for partners to develop and commercialise ALX-0141 outside of Greater China. For
further information, please contact Gosia Ciesiolka, Director Business Development.
ALX-0761/M1095 – anti-IL-17A/F to treat auto-immune disorders

o ALX-0761/M1095 is being developed for the treatment of auto-immune disorders

o ALX-0761/M1095 achieved pre-clinical proof-of-concept in an animal model for rheumatoid arthritis

o ALX-0761/M1095 was exclusively licensed to Merck KGaA in June 2013

o In January 2017, Merck KGaA reported encouraging results from a Phase Ib study in psoriasis patients
with ALX-0761/M1095, via a clinical trials website (https://clinicaltrials.gov/NCT02156466).

o In March 2017, Merck KGaA presented strong additional results from the Phase Ib study of M1095/ALX-
0761 in psoriasis patients: PASI 90 achieved in 100% of patients in highest dose group; rapid and
sustained clinical effect demonstrated
Psoriasis

Psoriasis is a common, chronic, relapsing, immune-mediated systemic disease characterised by skin lesions
including red, scaly patches, papules and plaques, which usually itch. The skin lesions seen in psoriasis may vary in
severity from minor localised patches to complete body coverage. About 50% of patients with severe and
moderate psoriasis receive only topical or no treatment at all and more than half of the patients are dissatified
with current treatments. Recent research suggests that IL-17 blockers could be more efficaceous than TNFa
blockers for the treatment of psoriasis (source: Nature Biotechnology, Vol 33, Jan 2015; Nature Reviews Drug
Disovery, Hilary Bartlett & Ryan Million, Jan 2015).

ALX-0761/M1095 mode of action

ALX-0761/M1095 (40kD) is a trivalent, bi-specific Nanobody that blocks both IL-17A and IL-17F and that binds to
human serum albumin for in vivo serum half-life extension. Th17 cells and IL-17 are associated with the pathology
of many human inflammatory and autoimmune disorders like psoriasis, rheumatoid arthritis (RA) and multiple
sclerosis.
ALX-0171 – wholly-owned anti-RSV Nanobody to treat Respiratory Syncytial Virus (RSV) infection in infants

o RSV therapeutic administered via inhalation - major Nanobody platform advantage

o Most advanced product in clinical development to treat RSV infections in infants

o Critical pre-clinical (neonatal lamb model) and clinical (adult study and study in infants hospitalised with
RSV infection) milestones achieved

o Phase IIb dose ranging efficacy study in infants started in Q1 2017

Unmet need in RSV infection

RSV is the leading cause of infant hospitalisation[1] (> 3 milion per year, infants < 5 years of age) and the primary
viral cause of infant death[1] (66,000-199,000 deaths, infants <5 years of age). RSV infection has also been
associated with prolonged wheezing and an increased risk for asthma development later in life [2]. However, there
are no drugs specifically approved for the treatment of RSV infections. Hence, there is a high need for a specific
and effective treatment for RSV infection in infants.

ALX-0171 unique route of administration

The physical robustness and stability of Nanobodies allows them to survive the extreme conditions needed for
drug nebulisation. ALX-0171 is the first Nanobody treatment developed for delivery directly into the lungs by
nebulisation, i.e. the site of RSV infection.

ALX-0171 mode of action

ALX-0171 (42kD) has first-in-class potential for the treatment of RSV infection. It is a trivalent, Nanobody that
inhibits RSV replication by binding the F-protein on the virus’ surface and thereby neutralises RSV by blocking
virus uptake into cells, allowing the host’s immune system to clear the virus.