Corporate Highlights 2015

Transcription

EXPLORING
NEW PATHWAYS
Disease-modifying treatments for diabetic retinopathy
EXPLORING NEW PATHWAYS
Disease-modifying treatments for diabetic retinopathy
Summary
EXPLORING NEW PATHWAYS
SUMMARY
9
15
21
39
43
Chapter One - About ThromboGenics
Chapter Two - JETREA®
Chapter Three - Research and development
Chapter Four - Our organization
Chapter Five - Shareholders information
THROMBOGENICS CORPORATE HIGHLIGHTS 2015
5
Dr. Patrik De Haes Chief Executive Officer
& Dr. Staf Van Reet Chairman of the Board of Directors
Innovative diabetes pipeline heralds a promising
future. The Board of Directors and Management
Team solidly back the ThromboGenics strategy.
25
Jean Feyen Head of Preclinical Research
& Dr. Patrik De Haes Chief Executive Officer
& Dr. Andy De Deene Global Head of Development
“Our mission is simple: we want to prevent
diabetes patients from going blind.” The
ThromboGenics R&D team will advance further
this year in clinical trials on diabetic retinopathy.
4
“Our mission
is to prevent
diabetes patients
from going blind.”
— Dr. Patrik De Haes, CEO
INTERVIEW
Dr. Patrik De Haes, CEO & Dr. Staf Van Reet, Chairman of the Board of Directors
Innovative diabetes
pipeline heralds
a promising future
The Board of Directors and Management Team
solidly back the ThromboGenics strategy
ThromboGenics began 2015 with a renewed strategy: prioritizing development of innovative medicines for
back of the eye disease, with a clear focus on diabetic eye disease. This has been reinforced in the past year,
say CEO Dr. Patrik De Haes and Board Chairman Dr. Staf Van Reet.
Through substantial investments in research into innovative medicines, ThromboGenics has continued
to pursue the course it started in 2014. The company
adjusted its financial strategy and shifted certain
accents to be able to focus all its resources into
unique treatments for diabetic retinopathy. “This is
a degenerative eye disease affecting rising numbers
of patients with diabetes. Going blind is a diabetes
patient’s greatest fear. Our mission and strategy as a
company is to prevent that from happening by offering the widest possible range of innovative solutions
in which the patient’s interests always come first,”
explains CEO Patrik De Haes.
ThromboGenics aims to develop specific treatments that can stop the further progression of the
disease. Blindness is caused when blood vessels in
the retina grow into the vitreous gel of the patient’s
eye (proliferative diabetic retinopathy, PDR). There
are strong indications that ocriplasmin (THR-409)
can prevent this by separating the retina from the gel
(generating posterior vitreous detachment, PVD).
“ThromboGenics is currently the only player actively
researching possible ways to intervene at that stage
of this progressive disease.”
5
6
INTERVIEW
Clinical research has begun
Broad pipeline
Meanwhile, a clinical trial with ocriplasmin has
been launched: early this year the phase II CIRCLE
study was initiated. “We’re investigating the number of injections and the dosage necessary for the
treatment to be considered effective,” continues
Patrik De Haes. “For the first time, our product
will be administered in multiple injections, so we
developed a preclinical package to demonstrate to
the authorities that ocriplasmin is safe for repeated
injections. Both the American and European
authorities have given us the green light for this
study.”
By taking these multiple shots on goal within a
single specific disease – diabetic retinopathy –
ThromboGenics is creating a widening portfolio
of potential treatments for diabetes patients. “This
pipeline gives the company continuity and should
make ThromboGenics a prominent player in the
market,” emphasizes Staf Van Reet.
Besides the research on ocriplasmin for treatment
of PDR, other projects are in the works like treatment of diabetic macular edema. “We are investigating a number of our molecules that have the
potential to remove the edema that can occur due
to inflammation caused by diabetes,” notes Patrik
De Haes. “We are doing this using technologies
from the Flanders Institute for Biotechnology and
Bicycle Therapeutics, but we have full control over
the development. We are also evaluating other
molecules, some of which may have potential for
wider application in the various conditions related
to diabetic eye disease.”
The new focus resulted from several crucial strategic decisions in consistent cooperation between
the management and the Board of Directors. “The
management never acts without consulting the
Board and the Board members unanimously support the strategy set by the management team.”
Concretely, to begin with the marketing costs for
the commercialization of JETREA ® will be substantially scaled down. “Our organization in the
US is focusing entirely on supporting JETREA ® for
its initial indication, vitreomacular traction. We
will reinvest the US revenue in the department to
enable cost-neutral operations,” points out CEO
Patrik De Haes. “At the same time, Alcon will continue to market our product in Europe and the rest
of the world, for which ThromboGenics will receive
royalties. A part of those royalties will be used for
developing ocriplasmin for a second indication,
diabetic retinopathy.”
“Our extensive pipeline of innovative eye
medicines gives the company continuity and
should make ThromboGenics a prominent player
in the market for diabetic eye disease.”
— Dr. Staf Van Reet, Chairman of the Board of Directors
Another major step was setting up the subsidiary
Oncurious to house ThromboGenics’ research on
pediatric brain cancer. “This way, the medulloblastoma research can be pursued in a targeted way in
a separate company, in collaboration with external
partners. Our oncology company Oncurious will
be able to work more independently in the future so
ThromboGenics can concentrate on its core business,” adds Patrik De Haes.
Chairman Staf Van Reet confirms: “Making the US
organization cost-neutral, receiving a share of the
royalties via Alcon, and launching our subsidiary
Oncurious will let us focus financially on the biotech field and treatment of diabetic retinopathy.”
Investors
The renewed ThromboGenics strategy has been
well received by stakeholders and investors. Baron
Philippe Vlerick significantly increased his stake in
the company and joined the Board of Directors of
ThromboGenics in 2015 as non-executive director.
“His decision was the direct result of our strategic
focus on diabetic eye disease,” recounts Patrik De
Haes.
“The fact that someone with such broad experience
has joined the Board of Directors at a time when
the company is undergoing an important strategic
reorientation gives us a tremendous sense of
confidence,” notes Staf Van Reet. “Philippe Vlerick
is the type of investor who thinks long-term. He
immediately focuses on the essentials and is able
to advise us from that perspective.”
In fact, at ThromboGenics there is a tradition of
holding regular meetings between management
and board members. “We consult one another several times a year, and outside the official management meetings. For example, I’m in regular contact
with David Guyer and Philippe Vlerick. In terms of
business strategy they have a lot of insights I am
happy to take on board. In this way, we can ensure
a continued relationship of trust between the
Board of Directors and the management,” confirms
Patrik De Haes.
JETREA® proves its value
In the meantime, new studies have confirmed the
value of JETREA ® for its first indication, the treatment of vitreomacular traction. The OASIS study,
the longest-running study of patients after treatment with JETREA ®, was completed in 2015 and the
results were highly satisfactory.
“We monitored patients for two years after injection
with JETREA ®. The results undeniably demonstrate
that 1 in 2 patients with vitreomacular traction are
cured after a single injection with the product. This
“real world data” on patients who have been cured
is very important for us. It demonstrates the value
of our product, with which ThromboGenics is still
the only player on the market to offer an alternative
to surgical vitrectomy. With JETREA ® we are the
global pioneer in the new category of pharmacologic vitreolysis. This is not only something we as a
team are extremely proud of, it also forms the basis
for further research by us and other parties in the
same area. We certainly plan to continue playing
this pioneering role in the future,” concludes Patrik
De Haes.
7
8
Summary
I
CHAPTER ONE
ABOUT
THROMBOGENICS
Innovative ophthalmic medicines
ThromboGenics is a global biotechnology company focused on
delivering innovative treatments for diseases of the back of the
eye, targeting diabetic eye disease. Its first product, JETREA®
(ocriplasmin), has been approved in 54 countries worldwide.
ThromboGenics is strongly committed to R&D on treatments for diabetes-related
eye diseases like proliferative diabetic retinopathy (PDR) and diabetic macular
edema (DME). It recently launched a Phase II clinical trial with THR-409 (ocriplasmin) in diabetic retinopathy, and is preparing a scientific publication on ocriplasmin’s potential for treating retinal vein occlusion (RVO).
ThromboGenics is headquartered in Leuven, Belgium, with offices in Iselin, NJ (US)
and Dublin, Ireland. The company is listed on the NYSE Euronext Brussels exchange
under the symbol THR. More information is available at www.thrombogenics.com.
54
countries globally
gave market approval
for JETREA®
9
10
THROMBOGENICS TIMELINE 2015-2016
JAN 2015 ThromboGenics
Appoints Dominique
Vanfleteren as new Chief
Financial Officer.
JAN 2015 ThromboGenics
Appoints Emmanuèle Attout
as Independent NonExecutive Director.
JETREA®
approval in over 50
countries, in more than
20 of which patients are
being treated.
MAR 2015
MAR 2015 Positive topline results from OASIS Study
with JETREA®. Oasis Study meets primary endpoint
with 41.7% of patients treated with JETREA®
achieving VMA resolution at day 28 post injection
(p<0.001). 24 month safety data in line with JETREA®
approved label.
APR 2015 ThromboGenics
starts evaluating JETREA®
for treatment of retinal vein
occlusion (RVO). The company
is awarded a EUR 0.6 million
IWT Research Grant.
APR 2015 ThromboGenics
and VIB launch the new
oncology company
Oncurious NV to develop
TB-403 for pediatric brain
tumors (medulloblastoma).
APR 2015 EU approval
of new ready diluted
formulation of JETREA®.
11
JAN 2016 ThromboGenics initiates Phase II
CIRCLE Trial evaluating the potential of
THR-409 (ocriplasmin) to induce total
Posterior Vitreous Detachment (PVD) and
reduce the risk of disease progression from
NPDR to sight-threatening Proliferative
Diabetic Retinopathy (PDR).
JAN 2016 Oncurious NV announces FDA acceptance of its
Investigational New Drug (IND) Application for a Phase I/IIa
study with TB-403 for treatment of pediatric brain tumors.
The study is planned to start in Q1 2016.
JUN 2015 Oncurious NV appoints
Prof. Dr. Peter Carmeliet as its
Chief Scientific Strategy Advisor.
Philippe Baron Vlerick
invests in ThromboGenics and
confirms a 3.6% shareholding.
MAY 2015
NOV 2015 The FDA accepts
the Investigational New Drug
(IND) Application for a Phase
II study with JETREA® to treat
non-proliferative diabetic
retinopathy. This CIRCLE study
is a randomized, doublemasked, sham-controlled,
multi-center study to evaluate
the efficacy and safety of
multiple doses of ocriplasmin
in inducing total posterior
vitreous detachment (PVD) in
subjects with non-proliferative
diabetic retinopathy (NPDR).
NOV 2015 ThromboGenics
presents full OASIS JETREA®
trial data analysis (incl. ERG)
and further real world
Clinical Data at AAO 2015
in Las Vegas. The importance
of proper patient selection is
shown. No new safety signals
are identified and the majority
of adverse events are resolved.
12
About ThromboGenics
Corporate objectives and strategy
Our Mission
The ThromboGenics mission is to pioneer and deliver next-generation treatments
offering the potential to prevent vision loss.
We have pioneered the drug category of pharmacological vitreolysis with JETREA®,
the world’s only approved pharmacological vitreolysis treatment currently available. We will develop other solutions and expand this category.
With diabetes, a leading health challenge worldwide, we are committed to deliver
new and innovative treatments to help tackle the growing challenge of diabetesrelated eye diseases.
We want to provide solutions enabling vision preservation for all people equally. All
our work is centered on the patient: when a treatment is good for a patient, eventually it will benefit all the company’s stakeholders, internally and externally.
Broadening a global franchise in back of the eye disorders with a focus on
diabetic eye diseases
ThromboGenics will expand its work in earlier-stage projects, searching for new
pathways and compounds for developing next-generation treatments for back of
the eye disorders with a focus on diabetic eye diseases.
The company constantly seeks to broaden its franchise in ophthalmology and
beyond, through both in-house research and strategic acquisitions, joint development, and licensing deals.
Cash generation from commercializing JETREA® (in first approved
indication, sVMA/VMT) in the US and RoW via partner Alcon (Novartis)
ThromboGenics’ US organization aims to be cash-neutral from 2016 onwards and
continuous the commercialization of JETREA® in its first approved indication,
sVMA.
In Europe and the rest of the world (RoW), ThromboGenics’ partner Alcon continues to gain new marketing and reimbursement approvals and execute commercial
launches of JETREA® for treatment of VMT. It invests revenues from royalties from
Alcon and commercial activities in the US in its development activities to find nextgeneration treatments for diabetic eye diseases.
“We want to provide
solutions enabling vision
preservation for all people
equally. All our work is
centered on the patient.”
Extending clinical utility of ocriplasmin for other new indications:
diabetic retinopathy
ThromboGenics is planning clinical trials for a number of new indications.
Proliferative diabetic retinopathy (PDR) is the next target indication for ocriplasmin.
The Phase II CIRCLE study has been initiated to assess the drug’s utility for treatment of PDR. The scientific evaluation of ocriplasmin for treating retinal vein occlusion is ongoing; results should be published in 2016.
Realizing value from Oncurious NV, a new oncology company with
ThromboGenics as a major shareholder
In April 2015, the company’s oncology R&D work was incorporated in a separate
entity: Oncurious NV, a joint venture with the Flanders Institute for Biotechnology
(VIB). Oncurious is leveraging the joint expertise to develop innovative medicines
for treating pediatric brain tumors.
13
14
About ThromboGenics
II
15
CHAPTER TWO
JETREA
®
Crafting its place in a changed standard
of care for sVMA/VMT
JETREA® as treatment of symptomatic
VMA/VMT
Symptomatic VMA/VMT
With the introduction of JETREA®, for the first time retina physicians have a treatment option for symptomatic VMA (US) or VMT (outside US). If left untreated, this
progressive eye disease generally leads to significant visual distortion, deterioration in visual acuity, or even central blindness.
Symptomatic VMA/VMT is caused by traction from persistent attachment of the
vitreous (jelly-like material in the center of the eye) to the macula at the back of
the eye. The macula provides central vision needed for everyday tasks like driving,
reading and recognizing faces. Symptomatic VMA/VMT can cause symptoms like
distorted or decreased vision. When it progresses, the traction may lead to formation of a hole in the macula (called a macular hole).
A unique mechanism of action
Previously, the only treatment option for patients with symptomatic VMA/VMT
was observation, followed by surgical separation of the vitreous from the retina
called a vitrectomy. This procedure is risky. It can lead to complications like bleeding, pain, post-operative inflammation or irritation, so it is usually done only when
the patient’s vision has deteriorated significantly. The alternative is ‘observation’ or
‘watchful waiting’ until a patient is a candidate for surgical repair of the retina, but
for many this is not a suitable option as irreversible damage to the retina may have
already occurred.
JETREA® is the first pharmacological option for treating symptomatic VMA/VMT.
It is administered as an intravitreal injection, a unique procedure now routine for
retina physicians and easy to perform. JETREA® breaks down the protein fibers creating the abnormal traction between vitreous and macula that causes VMA/VMT.
By dissolving these proteins, JETREA® releases the traction and helps complete the
© University of Illinois Board of Trustees
16
JETREA®
Patient journey
Patient experiences vision changes:
metamorphopsia (blurreld vision) and/or macular
hole (central blindness)
The patient consults an ophthalmologist,
who determines the patient is suffering
from an early stage of VMA/VMT
The patient is diagnosed via optical coherence
tomography (OCT), a non-invasive imaging
detachment of the vitreous from the macula. JETREA® can
also be used when VMA/VMT has progressed and caused a
small hole in the macula (the central part of the light-sensitive layer at the back of the eye). If the treatment is successful,
the symptomatic VMA/VMT will not recur.
JETREA® allows physicians to treat patients with these symptoms at an early stage. Successful treatment can improve patients’ vision and ability to carry out normal daily activities. It
can also stop f urther progression of this disease.
technique providing instant real-time highresolution images of eye tissue.
The ophthalmologist refers the patient
to a retina specialist, who discusses the
treatment options with the patient.
Treatment options:
Observation: ‘Watchful waiting’ until the
patient’s condition deteriorates to the point of
becoming a candidate for surgical treatment and
repair of the retina. For many patients this is not
a suitable option, as irreversible damage to the
retina may have already occurred.
Injection with JETREA® : JETREA® is the first
pharmacological option for treating symptomatic
VMA/VMT. It is administered as an intravitreal
2015: New longterm clinical data: patient selection and
experience
OASIS study demonstrates effectiveness and safety
of JETREA®
In 2015, ThromboGenics reported results from OASIS, a Phase
IIIb study. OASIS is a randomized, sham-controlled, doublemasked study that followed up 220 patients for 24 months
post injection with JETREA®. It was the longest period patients have been studied post treatment with this novel medicine. The study was designed to yield long-term controlled
efficacy and safety data for JETREA® in patients being treated
for symptomatic vitreomacular adhesion (sVMA). OASIS is
the first controlled study with JETREA® of its kind since the
pivotal Phase III program’s results were announced in 2011.
injection and allows physicians to treat symptoms
at an early stage. Successful treatment can
improve patients’ vision and ability to carry out
normal daily activities. It can also stop further
progression of this disease.
Vitrectomy: Before JETREA®, the only
treatment option for patients with symptomatic
VMA/VMT was surgical separation of the vitreous
from the retina, called a vitrectomy. It is risky
and can lead to complications like bleeding,
pain, post-operative inflammation or irritation.
Because of this, it is usually only done when the
patient’s vision has deteriorated significantly. The
alternative is ‘observation’ or ‘watchful waiting’.
The key findings of the study were:
»» 41.7% of patients treated with JETREA® achieved VMA
resolution at day 28 post injection compared with only
6.2% of patients given a sham injection (p<0.001);
»» the JETREA® safety profile in this 24-month follow-up
study was consistent with the drug’s overall safety profile
as known from the approved label. No new safety events
were identified.
“JETREA® is an important
part of my toolbox when
treating patients with
symptomatic VMA. By
using careful patient selection,
a very high rate of VMA
resolution can be achieved.”
Dr. Arshad Khanani, Managing Partner of Sierra Eye Associates in Reno, Nevada
17
18
JETREA®
Mechanism
of action
Normal Separation (PVD)
Vitreous remodelling leads to progressive liquefaction with age.
The OASIS data show the importance of improved patient
selection in generating higher rates of VMA resolution with
JETREA®. Recent real-world data have confirmed that access
to more advanced diagnostic technology such as SD-OCT has
enabled retina physicians to improve patient selection. They
have thus been able to select patients with focal VMA and an
absence of epiretinal membrane (ERM), two criteria shown to
lead to better treatment outcomes with JETREA®.
Six-month interim data from ORBIT study presented
Symptomatic VMA
Incomplete separation can cause Vitreomacular
Adhesion (symptomatic VMA), that results in traction,
leading to visual disturbance.
In May 2015, six-month interim data from the “Ocriplasmin
Research to Better Inform Treatment” (ORBIT) study were
presented. This prospective, observational study is designed
to assess clinical outcomes and the safety of JETREA® administered in a real-world setting for treating symptomatic VMA/
VMT by assessing both anatomical and functional outcomes.
The study looked at a number of parameters including resolution of sVMA, full thickness macular hole (FTMH) closure,
changes in visual acuity (VA), and occurrence and time to
vitrectomy. It also monitored adverse drug reactions (ADRs)
and changes from baseline in ocular signs and symptoms
over time, such as metamorphopsia. These data will further
characterize the product’s efficacy and safety profile.
Symptomatic VMA resolved
Ocriplasmin injected intravitreally acts by weakening
and breaking the protein fibers that are causing the
adhesion and separates the vitreous body from the
retina, which relieves the traction and resolves the
symptoms.
Patients will be monitored for up to 12 months following a
single treatment with JETREA®. The ORBIT study is due to
finish in mid-2016. Six-month data showed that 58.1% of patients experienced sVMA/VMT resolution within one month
post treatment. The study also found the safety of JETREA® to
be consistent with the product’s label and the data from the
Phase III clinical trials.
US commercial organization:
custom-fit to demand
ThromboGenics has adjusted its US organization’s commercial strategy and composition to current market demand for JETREA® and to ensure it is cash-neutral
in 2016. ThromboGenics Inc. is now a lean customer-centric organization that still
supplies JETREA® via a well-established distribution network. Its US team provides
medical and scientific data-driven support to the retina community and assists
physicians’ efforts to enhance patient awareness of the options available for treating symptomatic VMA.
JETREA® in Europe and
the rest of the world
ThromboGenics’ partner Alcon continues to gain new marketing and reimbursement approvals and launch JETREA® commercially in Europe and the rest of the
world (RoW). JETREA® is now approved in 54 countries, in over 20 of which patients
are being treated and reimbursed.
19
20
JETREA®
III
CHAPTER THREE
RESEARCH AND
DEVELOPMENT
Targeting diabetic retinopathy
As a worldwide leader in ophthalmology, ThromboGenics
continuously researches drugs that address unmet medical
needs. The company’s main focus is on providing diseasemodifying treatments for disease-related conditions that
affect the back of the eye.
With diabetes today a growing problem worldwide and current treatment options
insufficient, ThromboGenics saw such an unmet need. It targets prevention and
treatment of diabetic eye diseases like diabetic retinopathy (DR) with or without
diabetic macular edema (DME), which have a very direct impact on the patient’s
quality of life.
Diabetes, a worldwide pandemic
Diabetes is a worldwide pandemic, related to a wealthy lifestyle but also to difficult economic circumstances in developing countries. The 2015 edition of the
International Diabetes Federation Atlas states:
“Some 415 million people worldwide, or 8.8% of adults aged 20-79, are estimated to
have diabetes. About 75% live in low- and middle income countries. If these trends
continue, by 2040 some 642 million people, or one adult in ten, will have diabetes.
The largest increases will take place in the regions where economies are moving
from low-income to middle-income levels.”
21
22
Research and development
Prevalence
of diabetes patients
Worldwide
2015
Worldwide
2040
Diabetic retinopathy:
a vision threatening
disease
About diabetic retinopathy
415 MIO
642 MIO
DM
222 MIO
347 MIO
DIagnosed DM
79 MIO
123 MIO
Any DR
62 MIO
98 MIO
NPDR
16 MIO
25 MIO
17 MIO
DR is a progressive disease, caused by prolonged high
blood glucose levels. Over time this causes small
blood vessel damage to the retina (the light-sensitive
layer at the back of the eye), leading to progressive loss
of vision. Of all patients with DR, 1 in 5 develops PDR,
which eventually leads to blindness. Moreover, 28% of
all DR patients develop non-proliferative diabetic retinopathy (NPDR), which also progresses from a moderate to a severe stage and causes several eye problems
before leading to PDR.
In addition to NPDR and PDR symptoms, all DR
patients have an increased risk of developing diabetic macular edema (DME); 1 in 5 actually develops
it. DME occurs when fluid leaks into the macula (the
central part of the light-sensitive layer at the back of
the eye). These leaks cause the macula to thicken and
swell, progressively distorting acute vision. In some
cases this can lead to a severe loss in central vision.
A recent report of the American Academy of
Ophthalmology projected that 6 million people will
have some form of DR in the United States in 2020, of
whom 1.34 million will have vision-threatening DR.
PDR
26 MIO
DME
DM
DR
NPDR
PDR
DME
Diabetic retinopathy (DR) is a condition occurring in
persons with diabetes, which causes damage to the
retina of the eye. It is the most common microvascular
complication of diabetes and, in its most advanced
stage – proliferative diabetic retinopathy (PDR) – also
one of the leading causes of blindness worldwide. In
the growing population of patients diagnosed with
diabetes about 35% or 1 out of 3 will develop DR.
diabetes mellitus
non-proliferative diabetic retinopathy
proliferative diabetic retinopathy
diabetic macular edema
Current treatments
Patients with early-stage DR do not usually undergo a treatment, but an ‘observation’ or ‘watchful waiting’ period during which the symptoms go untreated until they grow severe
enough to warrant treatment. Patients must therefore normally wait until they develop signs of damage to the macula
before undergoing treatment.
DR treatment options include laser therapy and anti-vascular
endothelial growth factor (VEGF) injections. But these often
require repeated injections and must be repeated several
times a year.
Some patients must continue the anti-VEGF injections for the
rest of their lives. Unfortunately, there are indications this
prolonged use might cause other complications like development of scar tissue (fibrosis) in the back of the eye, caused by
prolonged inflammation. Undesirable side effects include
partial loss of peripheral and night vision.
2040
2040
2015
2015
215.2million
328.4
35%
diabetes patients
worldwide will
develop DR
28%
of all DR patients develop
non-proliferative diabetic
retinopathy (NPDR)
199.5million
million
number of men with diabetes
Source: International Diabetes Federation - Diabetes Atlas 2015
313.3
number of women with diabetes
million
23
24
INTERVIEW
Jean Feyen, Head of Preclinical Research
Dr. Patrik De Haes, CEO
Dr. Andy De Deene, Global Head of Development
“Our mission is simple:
we want to prevent diabetes
patients from going blind”
The ThromboGenics R&D team
will advance further this year
in clinical trials on diabetic retinopathy
ThromboGenics is set to unveil its first results from reorienting and focusing on diabetic eye disease.
Internal research and validation have yielded a pipeline of four molecules with a bright future for treating
diabetic retinopathy. “Our goal is to offer treatments that improve the quality of life for patients by tackling
the root cause of the disorder.”
25
26
INTERVIEW
Diabetic retinopathy (DR) is a degenerative eye disease affecting one in three diabetes patients. “This
represents an extremely large group worldwide,
and it is growing each year with diabetes now considered a pandemic ravaging both rich and poor
countries alike,” explains CEO Patrik De Haes.
Diabetic retinopathy is a progressive disease, typically occurring when excess blood sugar causes
damage to the tiny blood vessels supplying the
retina with nutrients and oxygen. Its milder form,
non-proliferative retinopathy (NPDR), is generally accompanied by minor inflammation and
bleeding. In the more advanced and more serious
variant, proliferative diabetic retinopathy (PDR),
patients left untreated risk permanent blindness.
One in five patients with DR will eventually develop this more serious form, so early screening
and treatment are critical.
in the retina, which also tend to increase in severity
and can even cause blindness if the disease is not
treated or brought to a halt,” says Patrik De Haes.
This degenerative process is what ThromboGenics
is targeting with a range of innovative treatments.
“We actually want to alter the pathology and if
possible bring the disease to a halt, which is why
we speak of disease-modifying treatments.”
Development models
The company created a number of development
models offering a fast, efficient and consistent way
to evaluate molecules for their efficacy at different
stages and for different symptoms of DR. “In the
past year this has led to a pipeline with four projects
for which we want to move from preclinical trials
to clinical development,” says Jean Feyen, Head
of Preclinical Research at ThromboGenics. “In
addition, we are constantly researching projects
that we assess for their value in treating diabetic
“ThromboGenics is a pioneer in
pharmacologic vitreolysis. We have already
brought a validated product for this purpose
to market, so it is extremely useful to be able
to apply that experience to ocriplasmin in the
treatment of DR patients.”
— Patrik De Haes, CEO
In both the milder and more serious variants, DR
patients can also have an accumulation of fluid in
the macula or yellow spot. This fluid buildup results from local inflammation that can sometimes
further complicate or accelerate the condition.
“In other words, diabetic retinopathy is a very serious disease that causes a whole range of problems
retinopathy, from which we may later create an
official program to add to our pipeline.”
The effects of the portfolio’s four molecules are
identified using a patient group quadrant: NPDR
with DME; NPDR without DME; PDR with DME;
PDR without DME. “Depending on their functional mechanism, these molecules can be used to
treat one or more symptoms of diabetic retinopathy or may even work across the entire spectrum,”
explains Feyen.
“Different aspects can be defined in the pathology.
Diabetes causes certain proteins to be altered, negatively affecting the blood vessels in the eye. These
start to leak (hyperpermeability), causing the patient to develop irritation (inflammation). This can
lead to a buildup of fluid (diabetic macular edema)
and/or an excessive proliferation of blood vessels
(neo-angiogenesis). In the final stage, permanent
vision damage is caused by scar tissue in the eye
(fibrosis). What’s more, the disease is a vicious
circle in which the symptoms grow worse. Once an
inflammatory reaction occurs, more blood vessels
start to leak, causing new inflammation with the
resulting consequences for the patient.”
phase, total PVD can possibly protect DR patients
against further progression to the more serious
stages and potential blindness. The CIRCLE study
will also examine this aspect as the patients are
monitored.
Andy De Deene, Global Head of Development at
ThromboGenics, explains. “In a PVD, the gel-like
liquid (vitreous) is separated from the rear surface
of the eye (retina). Data show that this can prevent
uncontrolled proliferation of blood vessels in the
vitreous or on the surface of the retina in PDR. This
has also been supported by further research in
people who undergo a spontaneous PVD, showing
they do not progress to a more severe DR stage.”
ThromboGenics has already brought ocriplasmin
to market for treatment of sVMA/VMT (JETREA®),
which also involves inducing PVD through pharmacologic vitreolysis to reduce adherence of the
“Through our research, we want to
demonstrate that ocriplasmin generates a
PVD in patients with diabetic retinopathy and
is thus able to prevent them from developing
PDR and risking blindness.”
— Andy De Deene, Global Head of Development
Clinical trial with ocriplasmin
For one of the four molecules, THR-409 or ocriplasmin, the clinical phase II CIRCLE trial has already
begun. This study will investigate the safety and
efficacy of (up to) three injections with ocriplasmin to achieve a total detachment of the vitreous
from the retina in the eye (total posterior vitreous
detachment, PVD). If administered in the early
vitreous on the retina. “Through our research,
we want to demonstrate that ocriplasmin generates a PVD in patients with diabetic retinopathy
and is thus able to prevent them from developing
PDR and risking blindness. There is currently no
product on the market able to definitively stop this
disease’s progression all at once and offer lifelong
protection,” points out Andy De Deene.
27
28
INTERVIEW
“THR-687 could potentially be the follow-up to
ocriplasmin and confirm our role in this field.
Since we’ve already brought a product with
this effect to market, we’re confident we’ll be
able to claim a strong position.”
— Dr. Patrik De Haes, CEO
Double positioning of THR-317 (anti-PlGF)
For
the
molecule
THR-317
(anti-PlGF),
ThromboGenics is confident it can start clinical
trials in 2016. “There are two ways we can position
this project,” says Andy De Deene. “Preclinical
research determined that the product is highly
effective against hyperpermeability. Bringing it to
market for this purpose would put us in a highly
competitive position. But THR-317 is also effective
against other aspects of diabetic retinopathy like
inflammation and scar tissue formation. Other
treatments, such as anti-VGEF therapy, do not treat
those two problems, causing the patient’s vision to
decline in the long term.”
That is why ThromboGenics is convinced the product
can be effective as a stand-alone treatment or in
combination with, say, anti-VGEFs. “We’re investigating the possibility of administering the product
together with anti-VGEF therapy, to reinforce the
treatment by preventing inflammation and scar
tissue formation. This is yet another example of our
disease-modifying working method. Plus, it will
mean patients need fewer treatments, thus easing
their burden.”
Treatment for edema with
THR-149 (plasma kallikrein inhibitor)
A third component ThromboGenics is investigating has shown excellent results in treating the
edema formed by DR. “Our aim is to reach patients
for whom other treatments no longer work,” notes
Jean Feyen. “The greater the edema, the more leaky
blood vessels and inflammation will occur in the
eye. By removing or reducing the edema in patients
with NPDR or PDR, we can also prevent the inflammation and hyperpermeability.”
The company wants to develop this product in
sustained release form. “This would allow us to
ensure the product remains in the eye an extended
time so it can be effective longer, so the patient
requires fewer treatments.” ThromboGenics is also
exploring how this sustained release form could
be used for the future therapies the company develops. “We want to make treatment of DR patients
less of an ordeal and thus improve their quality of
life,” adds Patrik De Haes.
“We have our own diabetic eye disease
screening models, but needless to say we see
great value in collaborations with universities,
research institutes and other parties for
certain aspects.”
— Jean Feyen, Head of Preclinical Research
Product with potential:
THR-687 (integrin antagonist)
THR-687 is one of the most promising items in the
ThromboGenics pipeline for DR. “This molecule
is active in the entire spectrum of the disorder,”
explains Andy De Deene. “For example, it too
generates a PVD, like ocriplasmin, so the disease
can be stopped at an early stage. It also prevents
formation of edema, and there are indications that
in PDR it can stop the progression by preventing
formation of scar tissue and combating proliferation of blood vessels.”
“For this product as well we have pharmacologic
vitreolysis in mind, an area where we’re the global
pioneer. It could potentially be the follow-up to
ocriplasmin and confirm our role in this field.
Since we’ve already brought a product with this
effect to market, we’re confident we’ll be able to
claim a strong position,” notes Patrik De Haes.
Setting the standard in ophthalmology
The various research and development models
allow the R&D Department to very consistently
and efficiently screen molecules in-house, and
attract other parties for collaboration with
ThromboGenics. “We do no target discovery ourselves,” explains Jean Feyen. “That means we focus
on evaluating the potential of existing molecules
within new and innovative therapies for eye disease. We have our own diabetic eye disease screening models, but needless to say we see great value
in working with universities, research institutes
and other parties for certain aspects.”
CEO Patrik De Haes confirms: “ThromboGenics
also intends to share the results of its preclinical
trials with the ophthalmology community. In the
past year we have already published extensive results of that preclinical research. Of course, we’ll
continue to do this in 2016 and beyond. This will
enable us to receive peer-reviewed feedback from
the community and support the further development of our pipeline,” CEO De Haes concludes.
29
30
Disease
hallmarks
A path to disease-modifying
treatments in diabetic
retinopathy
ThromboGenics focuses on patients with NPDR or PDR, with
or without DME. Its main goal is to find novel, disease-modifying treatments that can lower the treatment burden and
stop the disease from progressing.
Inflammation
Permeability
Neuro and vascular dysfunction
Edema
Leakage, occlusion & non-perfusion
Angiogenesis
Fibrosis
Neurodegeneration
A quadrant for innovative compounds
As an expert in R&D in treatments for back of the eye diseases,
ThromboGenics developed research toolboxes for in-house
screening of novel compounds. Using these, its team can now
continuously evaluate novel molecules for treating DR in its
different stages. This yields a pipeline of 4 innovative compounds for treating DR being researched and developed in a
preclinical or clinical stage. At the same time, the company
is constantly evaluating 3 or 4 other discovery projects that
generate an inflow of novel molecules into the pipeline.
A quadrant of groups of DR patients is used to determine
which types could benefit from the novel compounds in the
pipeline.
Moreover, each compound has been evaluated for its mechanism of action in the signs and symptoms related to DR in its
different stages. Patients with diabetes have raised glucose
levels in their blood, causing changes in certain proteins and
resulting in damaged retinal microvasculature. In an early
stage, the patient suffers from leaking blood vessels (permeability), causing inflammation in the back of the eye. The
formation of inflammatory and angiogenic factors further
increases the damage and potentiate vascular leakage. This
results in hyperpermeability and edema and formation of
new blood vessels (neo-angiogenesis). The occurrence of
blood vessels along the surface of the retina or in the vitreous
eventually leads to permanent damage through the development of scar tissue (fibrosis).
Once a patient suffers from inflammation the hyperpermeability deteriorates, causing new inflammation, more edema
and more proliferation and scar tissue. The loop amplifies
itself and the disease progresses.
THR-409 (ocriplasmin): start of clinical trial (CIRCLE
study)
Research has shown that the presence of a posterior vitreous
detachment (PVD), where the vitreous is separated from the
retina, may prevent growth of new blood vessels responsible
for proliferative diabetic retinopathy (PDR). This finding is
reinforced by the fact that PDR is rare in patients with a posterior vitreous detachment.
ThromboGenics and its clinical advisors believe that using
ocriplasmin to induce a PVD in patients with NPDR can
prevent development of the new blood vessels that cause PDR,
since they can no longer use the vitreous as scaffolding to
grow along the retina’s surface or into the vitreous.
After completing preclinical research in 2015, the company
started the CIRCLE study in early 2016. CIRCLE is a Phase II,
randomized, double-masked, sham-controlled, multi-center
study to evaluate the efficacy and safety of up to 3 intravitreal injections of either 0.125mg or 0.0625mg of ocriplasmin
in subjects with moderately to very severe non-proliferative
diabetic retinopathy (NPDR). The goal is to induce total PVD
to reduce the risk of the patient developing sight-threatening
PDR.
Quadrant diabetic
retinopathy
A quadrant of diabetes patient groups in DR
is used to determine which types of patients
could benefit from the novel compounds in
the pipeline.
23.6%
4.2%
NPDR
without DME
PDR
without DME
4.5%
3.0%
NPDR
with DME
PDR
with DME
In January 2016, the first patient was enrolled in the Phase II
CIRCLE study. More than 200 subjects will be recruited into
the CIRCLE trial, about 92 in each ocriplasmin arm (0.125mg
or 0.0625mg) and 46 in the sham arm, over the next 12 months.
They will come from across the US, Canada, Europe, Middle
East and Africa.
The main endpoint of the CIRCLE study is the percentage of
patients with total PVD by the month 3 visit, confirmed by
both B-scan ultrasound and SD-OCT. The study has a number
of exploratory secondary endpoints, designed to yield further
insight into ocriplasmin’s potential in reducing risk of progression of NPDR to PDR.
For each patient recruited, the CIRCLE study will last around
24 months from the first injection. The first results are expected in the second half of 2017.
35.4%
Any DR*
*Any DR is defined as the presence of NPDR, PDR,
DME or any combination thereof.
Abbreviation(s)
DR
NPDR non-proliferative diabetic retinopathy
PDR proliferative diabetic retinopathy
DME diabetic macular edema
31
32
Ophthalmology
portfolio
summary
Neurodegeneration
Segment
Fibrosis
Angiogenesis
Edema
Hallmarks of diabetic retinopathy
Inflammation
Program
+
+
+
+
+
+
+
THR-409
OCRIPLASMIN
(1)
THR-317
+
+
+
+
+
+
+
+
+
+
+
+
+
+
ANTI-PIGF
THR-149
PLASMA
K ALLIKREIN
INHIBITOR
THR- 687
INTEGRINE
ANTAGONIST
+
+
(+)
+
+
+
(2)
(1) prevention blood vessel ingrowth in vitreous (PVD)
(2) neo-angiogenesis inhibition + prevention blood vessel ingrowth in vitreous (PVD)
+ level of therapeutic action
THR-317 (anti-PlGF): to clinical development in 2016
The compound THR-317 (anti-PlGF) can be positioned in two ways. The molecule has a mechanism of action against hyperpermeability. By reducing the leakage of blood vessels, it can
prevent inflammation in early-stage NPDR and potentially stop the disease from progressing
and generating more edema, angiogenesis and fibrosis.
Since THR-317 also tackles fibrosis and inflammation, it could also be administered to treat
PDR patients if used in combination with anti-VGEF therapy with alternating injections. AntiVEGF treatments address some symptoms of DR but the patient still has inflammation, which
if not addressed will result in scar tissue (fibrosis) leading to vision impairment and blindness.
ThromboGenics is looking at developing THR-317 as sustained release. This lowers the patient’s burden because fewer treatments are necessary and there is less chance the patient will
develop fibrosis.
Preclinical research with THR-317 is already well-advanced. ThromboGenics intends to start
the compound’s clinical development in 2016.
THR-149 (plasma kallikrein inhibitor)
Preclinical studies and clinical observations show that inhibition of the enzymatic activity of
plasma kallikrein is able to reduce the formation of bradykinins, which are key components
in the induction of edema in the back of the eye. With less edema present in the eye, the inflammation and hyperpermeability stop deteriorating. Therefore, the progression of DR can
be prevented.
ThromboGenics intends to develop THR-149 as sustained release formulation, in order to generate a long-term effect of the product in the back of the eye. Less treatments will be necessary,
again lowering the burden of the patient.
THR-687 (integrin antagonist)
The compound THR-687 (integrin antagonist) is a promising product which has the potential
to tackle the full spectrum of signs and symptoms in DR. Similar to ocriplasmin, research
shows that THR-687 can generate a PVD, preventing blood vessels to grow into the vitreous or
along the surface of the retina and reducing the risk of patients developing sight-threatening
PDR. Moreover, the molecule shows to have the potential, to reduce edema and is also to stop
inflammation.
Therefore, THR-687 could be used for early treatment of patients with NPDR with or without
DME, but at the same time for PDR patients with or without DME. ThromboGenics is currently
evaluating THR-687 in preclinical research and intends to bring the product in clinical trial in
2018. The company believes that the compound can potentially be developed as a very powerful product to offer a better and disease modifying treatment for all DR patients.
Moreover, the working mechanism of THR-687 is similar to ocriplasmin through pharmacological vitreolysis. As ThromboGenics is a pioneer in this area, developing and commercializing JETREA®, the company can use its experience to develop a product which covers the full
spectrum of DR symptoms.
33
34
Retinal vein occlusion
(RVO): scientific
publication on lysing
blood clots with
ocriplasmin
ThromboGenics is preparing a scientific publication on ocriplasmin’s potential for treating retinal
vein occlusion (RVO), the second most common
cause of blindness from retinal vascular disease
after diabetic retinopathy. RVO is thought to
negatively affect the quality of life for 16 million
patients worldwide. Patients suffering from RVO
exhibit a (full or partial) blockage of the veins that
drain the retina, caused by formation of clots.
In support of this research, ThromboGenics has
secured a €0.6 million grant from the Flemish
Agency for Innovation by Science and Technology
(IWT). It is using this grant to evaluate ocriplasmin’s ability to lyse the clots that cause RVO by
local intravenous administration of this thrombolytic agent in pre-clinical models of the disease.
For that, the company will collaborate with the
Ophthalmology Department of the University
Hospital UZ Leuven in Belgium.
The grant also supports a ThromboGenics
partnership with the Mechanical Engineering
Department of KU Leuven, which is developing a
robotic-assisted system to locally administer ocriplasmin in the retinal veins.
Oncurious nv:
TB-403 trial
In April 2015, ThromboGenics announced the
formation of its subsidiary Oncurious nv, a new
oncology company that will research and develop
treatments of brain cancers in children. This lets
ThromboGenics focus even more on meeting its
DR goals while remaining the main shareholder of
Oncurious.
The main goal of Oncurious is to speed up development of TB-403 for treatment of medulloblastoma,
a devastating cancer that affects children and
adolescents.
About medulloblastoma
Medulloblastoma is a fast-growing, malignant,
primary brain tumor. It originates in the lower
rear portion of the brain called the posterior fossa,
which controls balance, posture, and complex
motor functions like speech and balance. It is the
most common pediatric malignant brain tumor,
accounting for 20% of all brain tumors in children. In the EU and US around 400 new patients
are diagnosed annually, with boys affected twice
as much as girls. The peak age of incidence is 3-5
years, and about 80% of patients are diagnosed
before the age of 15.
Current treatment consists of surgically removing
as much tumor as possible, followed by craniospinal (brain and spine) radiation and/or chemotherapy – generally in older children (>3 years).
Although treatment improves survival, these
regimens are highly toxic to the developing brains
and are associated with significant morbidity. The
prognosis is worse if the child is less than 3 years
old, not enough tumor is removed, or there is any
spread to other regions of the brain or body.
With treatment, 60-65% of children with high-risk
medulloblastoma, and 80-90% of those with disease that has not spread, can be expected to be free
of the disease 5 years later. But treatment often
results in significant neurocognitive impairment
in children younger than 8.
The potential of TB-403 in treating
medulloblastoma
TB-403 is a humanized monoclonal antibody
against placental growth factor (PlGF). PlGF is
expressed in several types of cancer, including
medulloblastoma. High expression of the PlGF
receptor neuropilin 1 has been shown to correlate
with poor overall survival.
In a landmark paper published in Cell by Prof.
Rakesh Jain (Massachusetts General Hospital,
Harvard, Boston, US) and Peter Carmeliet (VIB/
KU Leuven, Belgium) in 2013, the authors showed
that blocking PlGF signaling in medulloblastoma
mouse models resulted in tumor regression, decreased metastasis and improved survival.
Treatment with TB-403 against PlGF in relevant
animal models for medulloblastoma has demonstrated beneficial effects on tumor growth (containment) and survival. The favorable safety profile of TB-403 has already been shown in clinical
trials in patients with other diseases. Oncurious
will initiate a Phase I/IIa program with TB-403 in
medulloblastoma, with the first patient expected
to be enrolled in 2016.
In January 2016, the FDA completed the safety
review of Oncurious’s Investigational New Drug
(IND) Application and ruled that the proposed
pediatric clinical investigation can proceed. This
was a major milestone for Oncurious. It confirms
the hope that the novel antibody TB-403 could give
pediatric oncologists a better treatment option for
children afflicted with life-threatening tumors.
ThromboGenics recently signed an agreement
with NMTRC (a neuroblastoma medulloblastoma
research foundation) for supporting the TB-403
clinical trial. The foundation has access to several
clinical centers specialized in recruiting patients
for clinical studies, which will accelerate the trial
with TB-403.
“Oncurious will
initiate a Phase
I/IIa program
with TB-403 in
medulloblastoma,
with the first patient
expected to be
enrolled in 2016.”
35
PRODUCT PIPELINE
THROMBOGENICS
EC
SE
LI
NI
AR
CA
CH
L
PRODUCT
PIPELINE
PR
RE
36
PIPELINE LEGEND
DRUG/MOLECULE
PRECLINICAL
TARGET INDICATION
CLINICAL
THR-317
sVMA/VMT
MARKET
DME
DME
NPDR & PDR
DR
MB
EXPLOR ATIVE
RESEARCH
DR
THR- 687
NPDR & PDR
THR-149
DME
LI
N
A
IC
A
L PH
SE III
AL
PH
AS
E II
C
IC
JETREA
OCRIPLASMIN
SVMA / VMT
CLINIC
M
AR
KE
T
E I
AL PHAS
C
L
N
I
THR- 409
TB - 403
MB
OCRIPLASMIN
NPDR
37
38
PRODUCT PIPELINE
IV
CHAPTER FOUR
OUR
ORGANIZATION
The people behind the ThromboGenics success
ThromboGenics employs around 85 people worldwide.
Most work at the company headquarters in Leuven
(Belgium) or from our office in New Jersey (US). The
large majority of this international team’s members hold a
Master’s or PhD degree.
ThromboGenics has tailored the size of its US organization to the market demand
for JETREA®. It is now a lean customer-centric organization that still supplies
JETREA® via a well-established distribution network. The company’s US team
provides medical and scientific data-driven support to the retina community and
assists physicians’ efforts to enhance patient awareness of the options available for
treating symptomatic VMA.
These changes will make ThromboGenics’ US operations cash-flow neutral from
2016 onwards.
Executive management
Dr. Patrik De Haes – Chief Executive Officer
Dr. Patrik De Haes has over 25 years of experience in the global healthcare industry, in product development, marketing and general management. Before joining
ThromboGenics as CEO in 2008, he was head of Roche’s Global Insulin Infusion
business. Before that Patrik was President and CEO of Disetronic Medical Systems
Inc., a medical device company based in Minneapolis, USA. He also led the
global development and commercialization of the first biotech product at Sandoz
Pharma (now Novartis) in Switzerland. Patrik holds a degree in Medicine from the
University of Leuven.
39
40
Our organization
Dominique Vanfleteren – Chief Financial Officer
In January 2015, ThromboGenics appointed Dominique Vanfleteren as
its new Chief Financial Officer (CFO).
Dominique has over 25 years of experience in senior finance, operational,
control and reporting roles in quoted international biopharmaceutical
companies. Before joining ThromboGenics, Dominique spent 12 years
at UCB, a global biopharmaceutical company, where he held a number
of international managerial finance positions, the latest being CFO of
UCB’s Asia Pacific Operations, operating from Brussels and Shanghai.
Prior to joining UCB, Dominique worked for GSK for 16 years. He held a
number of senior finance positions in Brussels and London, the latest as
Finance Director of GSK’s Diversified Healthcare Services Europe.
Operations Management Team and Executive Committee
Our leadership team’s expertise and experience in research, clinical development, commercialization and financing ensure the long-term success of ThromboGenics. The Executive Committee sets the company’s
vision and strategy, while the broader Operations Management Team is
responsible for planning and overseeing this strategy’s execution.
The members of the ThromboGenics Operations Management Team
are Andy De Deene*, Claude Sander*, Dominique Vanfleteren*, Isabelle
Decoster, Jean Feyen*, Johny Van Genechten, Lene-Rose Arfelt, Lionel
Moro, Ove Pedersen, Patrik De Haes*, Paul Howes*, Rosemarie Corrigan,
and Wouter Piepers.
* Executive Committee member
Board of Directors
Appointment of Philippe baron Vlerick
Mr. Vlerick was appointed as a new Non-executive member of the Board
of ThromboGenics NV at an extraordinary shareholders’ assembly in
August.
Mr. Vlerick is owner, Chairman and CEO of several businesses in
Belgium and abroad. He currently serves as the Chairman and Chief
Executive Officer of Vlerick Group (Belgium). He also serves as the
Chairman and CEO of UCO. In addition, he is the Vice-chairman of KBC
Group, Corelio, smartphoto Group and Durabilis. Baron Vlerick is also a
member of the Board of Directors of Exmar, Hamon & Cie, Besix Group
BMT & LVD (Belgium).
Mr. Baron Vlerick holds a Degree in Philosophy and Law from the University
of Leuven, and an MBA General Management (PUB) (Ghent, Vlerick School of
Management – 1979). He also holds a Masters Degree in Business Administration
from Indiana University, Bloomington (USA – 1980).
He was elected 2006 Manager of the Year by Trends, a leading business magazine in
Belgium. He was granted the title of Baron in 2008, and became Commander of the
Order of Leopold in 2013.
Appointment of Emmanuèle Attout
Emmanuèle Attout has been an audit partner at PricewaterhouseCoopers from
1994 to 2014, in charge of audits of a range of clients including banks, insurance
companies, investment funds and asset managers. In recent years she managed
the audits of listed pharmaceutical companies and life sciences businesses, from
which she brings substantial relevant experience to the Board and to the Audit
Committee. Emmanuèle is an independent non-executive director of Atenor Group
and Schréder SA. She is also managing director of Investea sprl, a management
company aiming to render advisory services to enterprises.
From 2009 Emmanuèle was co-founder and Director of the ngo Women on Board
to promote the place of women in Board of Directors. She serves also the Board of
Toutes à l’école Belgique asbl. Emmanuèle graduated in Applied Economic Sciences
at the Catholic University of Louvain.
From left to right: Paul Howes, Emmanuèle Attout, Thomas Clay, Patrik De Haes, Luc Philips, Staf Van Reet, David Guyer, Patricia Ceysens, Philippe Vlerick (not on the picture)
41
42
Our organization
V
CHAPTER FIVE
SHAREHOLDERS
INFORMATION
Listing
ThromboGenics is listed on the Eurolist by Euronext Brussels under the symbol
THR. Since 2009 it has been listed on the NEXT 150 Index, made up of mid to large
capitalization stocks on the Euronext exchange.
Investor relations
Our investor relations policy includes:
»» Providing reliable, accurate, and valuable information in a timely manner to
help shareholders make informed decisions
»» Full transparency
»» Operating within the Company’s policies and adhering to relevant security
laws and regulations
»» Strengthening our dialogue with the investment community
»» Providing access to the senior management team
Shareholding structure
As of 31 December 2014, ThromboGenics has 36,094,349 outstanding shares and
691,000 outstanding warrants.
Thomas Clay
7.73%
Philippe Vlerick
6.44%
Norges Bank
2.95%
Public
82.88%
43
44
Shareholders information
Paying agent services
KBC Bank acts as paying agent, meaning it does not charge shareholders for dividend payments, exercise of subscription rights, and
other events concerning ThromboGenics’ shares. Shareholders should
investigate what other financial intermediaries might charge for paying
agent services.
Financial calendar
17 Mar 2016
ThromboGenics Full Year results
3 May 2016
ThromboGenics Annual Shareholders Meeting
13 May 2016
ThromboGenics Business Update Q1
25 Aug 2016
ThromboGenics Half Year Results
20 Oct 2016
ThromboGenics Business Update Q3
Registered office
ThromboGenics NV
Gaston Geenslaan 1
B-3001 Leuven
Belgium
T +32 16 75 13 10
F +32 16 75 13 11
info@thrombogenics.com
Investor relations contact
ThromboGenics NV
Gaston Geenslaan 1
B-3001 Leuven
Belgium
IR@thrombogenics.com
wouter.piepers@thrombogenics.com
www.thrombogenics.com
Contact details
ThromboGenics
Wouter Piepers, Global Head of Corporate Communications/IR
+32 16 75 13 10
wouter.piepers@thrombogenics.com
Dominique Vanfleteren, CFO
+32 16 75 13 10
dominique.vanfleteren@thrombogenics.com
45
46
Shareholders information

Corporate Highlights 2015

Transcription

Similar documents

DIABETIC RETINOPATHY

Soluble Lutein (Lutemax2020®) Prevents Retinal

Comparing Technical Failure Rates in Diabetic Retinopathy

ProArgi-9+ and the Physicians` Desk Reference

Patofisiologi dan Manajemen Up date Diabetik Neuropati

CORpORaTE HIGHlIGHTS 2014

Diabetic Care - Harvard Pilgrim Health Care

LECTURE 9 Posterior Pole retina pathology_HTN_DM retinopathy

14 artigo_ingles - AVALIAÇÃO FUNCIONAL

Empowering WOMEN through Improved Water

Inside perspective: the role of the podiatrist in diabetes

Diabetes eye health - International Diabetes Federation

Premacular Subhyaloid Haemorrhage Drainage by Frequency