DBV TECHNOLOGIES:
THE NEXT LEADER IN THE TREATMENT
OF ALLERGY
1
Executive Summary
DBV Technologies is opening up a decisive new approach to the treatment of allergy - a major public health
problem that is constantly on the increase. Asthma, allergic respiratory diseases, atopic dermatitis and a range
of digestive disorders are all closely linked to allergy. In developed countries, food allergy develops early in life
and becomes a true burden, with a significant impact on the health and quality of life of the millions of sufferers.
At present, food allergies cannot be treated; the risk of an anaphylactic reaction during treatment
prohibits the use of standard desensitization techniques.
DBV Technologies (incorporated in 2002) has developed a unique, proprietary technology with worldwide
patent coverage. The Viaskin® process enables an allergen to be administered to healthy skin while avoiding
massive transfer into the bloodstream. The process considerably minimizes the risk of systemic allergic
reactions. This revolutionary method has undergone significant development and has yielded an
industrial-scale product. It opens up a new way of managing allergy - even in the most severe forms and the
most fragile patients.
The innovation strategy implemented by DBV Technologies from the outset has given the company all the
assets needed to become a key player in the treatment of food allergies and, more generally, allergies in the
young child. The company is now focusing its development efforts on three products:
1. Viaskin® Peanut, for the treatment of peanut allergy in adults and children, including a Phase II clinical trial
initiated in France in 2010. Safety of use has been established in a large, Phase Ib study (with 100 patients)
performed in the largest allergology centers in the USA in 2011. The clinical development program for
Viaskin® Peanut has received Fast Track designation from the US Food and Drug Administration.
2. Viaskin® Milk for the treatment of milk allergy in infants, including a Phase II clinical trial scheduled for
2013.
3. Viaskin® HDM for house dust mite allergy in infants – a condition that is hard to treat with current
desensitization methods. A Phase I clinical trial is scheduled for 2013 and will leverage some of the work
already performed on the other products.
DBV Technologies' three target allergies represent a total market of over $5 billion. The company will also
leverage other possible growth opportunities in the field of allergy (egg and sea food allergies, etc.) and the
Viaskin® technology's many applications in other therapeutic fields (vaccines, immune diseases, etc.).
2
Allergy: the world's fourth largest public health issue,
according to the WHO
According to the World Health Organization, allergies constitute the world's fourth largest public health issue
and affect about 500 million people worldwide (mainly in developed countries).
One can differentiate between:
■
food allergies (peanut, milk, egg and prawn/crustacean allergies, etc.)
■
respiratory allergies (to house dust mites and pollen)
■
allergies to venoms, contact allergies and drug allergies.
Allergies constitute a growing problem, which could
affect up to between 25% and 40% of the adult
population and more than 50% of children in
developed countries. Epidemiological studies have
already shown that over half of the US population (52%)
is sensitized to at least one allergen.
1998
2008
2015
Source: Bousquet et al. 1999.
Environmental and lifestyle changes, improved hygiene, a decrease in chronic bacterial infections, urbanization,
pollution and changing food habits are all factors that appear to have favored this rapid increase in the
prevalence of allergies.
The main food allergies
The following table lists the main food allergy rates in children (some of whom do grow out of their allergies) and
in adults: allergies to peanut, tree nuts and shellfish are among the most prevalent.
TABLE I1: Estimated food allergy rates in North America
Prevalence
Milk
Egg
Peanut
Tree nuts
Fish
Shellfish
Wheat, soy
Sesame
Overall
1
Infant/child
2.5%
1.5%
1.0%
0.5%
0.1%
0.1%
0.4%
0.1%
5.0%
Adult
0.3%
0.2%
0.6%
0.6%
0.4%
2.0%
0.3%
0.1%
3.0% to 4.0%
Source: Sicherer & Sampson, JACI 2009.
3
Peanut allergy: a life-threatening risk for millions of people
The peanut is a tropical plant from South America. It is a cheap source of proteins, lipids, vitamins and minerals.
Peanut can appear in several forms after industrial processing, the main goal of which is protein enrichment.
Peanut is a component of many foods, such as hamburgers and meat substitutes (especially in the USA), milk
(especially in India), breakfast cereals, soups and cakes. It can also be used in various non-food products, such
as plastics, adhesives and shampoos. The nut has a fat content of between 35% and 55%; peanut oil is used
for many purposes worldwide and can also cause allergic reactions1.
A nationwide survey in the USA showed that about 1.1% of the general population (i.e. over 3 million
people) are allergic to peanut2. This allergy affects both adults and children and it has been estimated
that peanut allergy affects 1.8% of young children in the United Kingdom3. The prevalence of peanut
allergy in other Western countries (e.g. Canada, France and Spain) has been studied by many researchers and
ranges from 0.9% to 1.5%4. Peanut allergy is generally considered to be a persistent allergy; in effect,
many studies indicate that fewer than 20% of children will grow out of their peanut allergy5.
Peanut allergy significantly degrades the quality of life in sufferers. In a recent study, researchers in the USA
showed that people suffering from severe peanut allergy had the same quality of life score as insulindependent diabetics6.
Peanut allergy is more severe than other common food allergies (e.g. milk and egg allergies). The clinical
picture is variable. Atopic dermatitis, asthma and digestive disorders are frequently noted but Quincke's edema
and anaphylactic signs are the most feared. The mean age at diagnosis is 3 years. Indeed, the allergy is often
revealed by cutaneous and respiratory manifestations or even anaphylactic shock. In the USA, peanut allergy
causes about 100 to 150 deaths per year. The death often results from accidental exposure to peanut: out of
seven deaths caused by ingestion of peanut-containing food, Yunginger reported four deaths due to peanut
ingestion at a restaurant or at school7. In a study of six fatal reactions to food, Sampson reported that the three
cases of peanut ingestion were related to a cupcake, a sandwich and candy8, which emphasizes this allergy's
significant impact on daily life.
1
2
3
4
5
6
7
8
Guerin et al. Rev fr Allergol 1995.
Sicherer et al., 1999a.
Hourihane et al., 2007; Du Toit et al., 2008.
Crespo et al., 1995; Kanny et al., 2001; Kagan et al., 2003.
Source: Sicherer SH, Sampson HA. Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol
2007;120:491-503.
Avery NJ, King RM, Knight S, Hourihane JO. Assessment of quality of life in children with peanut allergy. Pediatric Allergy Immunol.
2003;14: 378-82.
Yunginger KW. N Engl J Med 1992.
Sampson et al. N Engl J Med 1992.
4
Milk allergy: the first allergy to appear in the young child
Milk allergy is generally the first food allergy to appear in the child. It constitutes the most frequent food
allergy in infants and young children and is not the same as lactose intolerance, the consequences of which are
usually more benign. Milk allergy is when a person's immune system reacts abnormally to animal milk proteins;
this reaction can be fatal. Lactose intolerance relates to symptoms such as abdominal pain, flatulence and
diarrhea. In the event of doubt, an accurate diagnosis can be made by assaying for milk-specific antibodies in
the blood.
In children, there are two types of milk allergy. One occurs almost exclusively in the very young infant and
manifests itself through digestive or skin symptoms. It can be screened for with patch tests. DBV Technologies
has developed the Diallertest®, the first ready-to-use patch test for this type of milk allergy (now on sale in
France). The other type of milk allergy is more severe and includes a risk of anaphylactic shock. These forms of
milk allergy may benefit most from desensitization treatment.
The second type of milk allergy affects 2% to 3% of the general population1. The most typical symptom is acute
urticaria (hives) as soon as the infant is weaned onto formula milk. The clinical manifestations mainly affect the
gastrointestinal tract, the skin and the respiratory tract. The most severe allergic reaction is anaphylaxis. This
sudden, systemic reaction affects the whole body and, if not treated rapidly (by injection of adrenaline with an
ANAPEN- or EPIPEN-type kit), can progress to anaphylactic shock, i.e. a sharp drop in blood pressure, loss of
consciousness and, potentially, death in just a few minutes.
Milk allergy in the young child also increases the risk of developing multiple food allergy, peanut allergy and
respiratory allergies (asthma).
1
Sicherer et al. JACI, 2006
5
A major unmet medical need
Symptomatic allergy medications (antihistamines, bronchodilators, corticoids,
etc.) are used worldwide and represent a total market of $46 billion. However,
they only provide temporary symptom relief and cannot modify the underlying
allergy in the long term.
Desensitization is acknowledged by the WHO as the only disease-modifying treatment for allergy. It
consists in repeatedly administering small quantities of allergen, in order to decrease an allergic patient's
reactivity. This treatment is conventionally administered by regular, subcutaneous injections of increasing doses
of the specific allergen in hospital and under a physician's supervision. A number of more patient-friendly
administration routes (notably sublingual drops and tablets) have been developed to simplify the desensitization
treatment and enable it to be taken at home. The global immunotherapy market is worth an estimated €870
million.
For some allergies (such as food allergies), conventional desensitization products (injections, tablets
and drops) cannot be used routinely because of safety problems. In fact, some food allergens (such as
peanut and milk proteins) cannot be injected in or ingested by young children because of the risk of
anaphylactic shock. Hence, the treatment of food allergies is a major unmet medical need.
Moreover, several scientific studies have demonstrated that the early treatment of allergy helps prevent
progression to allergic diseases such as asthma or multiple food allergies. A study of children
desensitized to pollen and followed up for 5 years clearly demonstrated that early treatment of pollen allergy
reduces the likelihood of subsequently developing asthma. However, today's techniques are poorly suited
to the treatment of young children. Firstly, children do not like injections and the latter must be performed
under medical surveillance, which is not conceivable on a large scale. Secondly, sublingual formulations
developed for home administration are generally inappropriate for young children, who are not disciplined
enough to keep the product under the tongue long enough for effective dosing. Sublingual administration in
children sometimes induces poorly tolerated local side effects (stinging, irritation, etc.).
Desensitization would be the best possible treatment option, as long as a simple, safe, effective method
were available. However, the only current options for patients with a food allergy (and particularly the most
serious cases) are (i) strict avoidance of the foods to which they are allergic and (ii) patient education so
that the allergic reactions triggered by accidental exposure can be recognized and treated.
Hence, a widely applicable, risk-free treatment for food allergy has always been an objective for
allergists.
6
Viaskin®: the first therapeutic response to food allergies and
other allergies in young children
DBV Technologies has developed a novel method for specific epicutaneous immunotherapy (EPIT) by
using its proprietary Viaskin® technology. This innovative method consists of a skin patch that enables
desensitization by placing the allergen in contact with the immune system through the skin but avoids
passage into the blood.
The Viaskin® patch is changed daily over a relatively long period of time (as with all immunotherapy
desensitization methods).
The Viaskin® patch offers an easy-to-use treatment for food allergies in adults and young children, with
the best possible guarantees of safety.
The patch's two main features are as follows:
■
A desiccated protein extract in a controlled atmosphere, providing stability and optimal reactivity.
■
A specific design: the adhesive crown provides a tight seal and creates a "condensation chamber" between
the impermeable backing membrane and the skin. This leads to rapid hydration and solubilization of the
active substance (the allergen).
7
A revolutionary technology
Viaskin® is a proprietary technology platform protected by a solid intellectual property portfolio: the Viaskin®
technology and its applications are currently protected by fourteen granted or pending patent families.
DBV Technologies' policy of innovation and intellectual property protection constitutes a significant barrier to
market entry for potential competitors.
Development of the Viaskin® patch required the refinement of an electrospray deposition process that
uses liquid formulations to produce dry deposits of specific chemical or biological active substances.
The effect of an electrical field on the droplets
Protein deposited in the middle of the patch
A 10-micron-scale electron micrograph
of proteins electrosprayed onto the patch
A micron-scale electron micrograph of proteins
electrosprayed onto the patch
The company now has its own production equipment. The production equipment (fully developed and
patented by the company) is currently located in a pharmaceutical laboratory and is used to produce clinical trial
batches. The current production line is able to manufacture 6 million Viaskin® patches a year – enough to
satisfy demand for first two years of commercialization.
Production equipment (GEN)
A view of the 18- simultaneously operating
controlled-flow nozzles.
8
A novel and fully patented mechanism of action
A pharmaceutically industrializable technology: the Viaskin® EPIT patches developed by DBV Technologies
are unique. They store the lyophilized allergen particles (electrosprayed onto the patch) in their native, active,
antigenic state.
The main steps in the Viaskin® patch's mechanism of action as are as follows:
The central part of the patch contains a layer of
lyophilized allergen. The patch is placed on intact skin,
without any need for skin stripping or abrasion.
The condensation chamber that forms between the
skin and the central part of the patch ensures
hyperhydration of the skin and the accumulation of
water.
The accumulation of water solubilizes the previously
dry layer of allergen, which then enters into contact
with the skin. Thanks to greater hydration, the stratum
corneum becomes more permeable to the allergen.
Once the allergen has entered the epidermis, it is
captured by a population of highly specialized antigenpresenting immune cells called Langerhans cells.
These are located near to the stratum corneum in the
epidermis (this layer is made of dead cells and
constitutes the skin's outmost protective layer).
The Langerhans cells' function is to capture all the foreign bodies that manage to cross the stratum corneum
and to present them to other immune system cells in the lymph nodes. Allergen capture by these specialized
cells and the lack of passive transfer into the epidermis give rise to specific modulations of the immune
response. This novel mechanism explains why the Viaskin® products should present a very favorable
risk/benefit ratio and, as such, may constitute the only truly promising pharmaceutical approach to
safe, effective desensitization therapy.
9
Viaskin® is acknowledged by the scientific and medical
communities and the general public
Following in-depth research efforts and many scientific publications, Viaskin® technology has been
acknowledged by leading scientific journals in the field of allergy.
For example, the cover pages of the two leading scientific journals
in the USA (the Journal of Allergy and Clinical Immunology, JACI)
and Europe (Allergy) recently reviewed the major advances in
allergen immunotherapy over the last few decades: Viaskin® was
cited as the event in 2010 that was most likely to make a lasting
mark on the history of allergy treatment.
Another very strong acknowledgment of the Viaskin® technology was
the launch of an academia-led clinical study in the USA. In
September 2010, the Consortium for Food Allergy Research
(CoFAR) selected Viaskin® Peanut for a Phase II study funded by
the US National Institutes of Health (NIH).
Although
DBV
Technologies'
marketing activities have not targeted
the general public, the initiation of its
first clinical trial in late 2010 in the
USA had strong mass media
coverage in the USA, UK and
Australia.
Similarly, several major public and private TV channels have
broadcast some quite detailed reports on Viaskin® and the
hope of treating peanut allergy.
The reports broadcast in early 2011 by CNN, Fox News, CBS
Denver and 9news (USA) and CBC News (Canada) can be
viewed on DBV Technologies' web site.
Overall, this illustrates the strong unmet demand for a curative treatment for food allergy and the true
revolution that Viaskin® technology may represent.
10
Three high-potential products
Thanks to its adaptability, the Viaskin® patch has the potential to offer a currently unavailable treatment for not
only the main food allergies (peanut, milk, etc.) but also other allergies in young children (e.g. house dust mite
allergy).
On the basis of a detailed analysis of medical needs that are not met by today's treatments, the company has
defined two high-priority development axes:
1. Food allergies
Viaskin® Peanut is DBV Technologies' main product. It can be applied to children and adults and seeks
to steadily increase the patient's safety threshold for peanut. The total treatment duration varies according
to the allergy's history and the severity but is around two to three years, on average.
Viaskin® Milk is the second product to have been developed by the company. It enables treatment of
severe forms of milk allergy. Its high degree of safety means that use in very young infants can be envisaged.
The treatment duration is the same as for Viaskin® Peanut.
2. Allergies in the young child
Viaskin® Milk will be specifically developed for very young children so that milk allergy can be treated in
the first two years of life: the goal is to reduce the subsequent occurrence of multiple food allergies.
Viaskin® HDM is the company's desensitization product for house dust mite allergy. Currently available
immunotherapy products are not indicated in under-fives. DBV Technologies will develop Viaskin® HDM for
the treatment of house dust mite allergy in children under the age of 5.
3. Other applications of the Viaskin® technology in the field of diagnostics.
Diallertest® Milk is the first ready-to-use patch test for screening for milk
protein allergy in the young child. It was launched on the French market in
2004 and the company has sold over 150,000 units since then. It is
currently available in France under a temporary authorization of use. A pivotal
Phase III study has been requested by the authorities, with a view to completing
the standard marketing authorization application (MAA) file. Diallertest® Milk is
intended to be a "companion diagnostic" for Viaskin® Milk.
Diallertest® HDM must enable the early diagnosis of house dust mite allergy and the correspondingly early
implementation of desensitization treatment with Viaskin® HDM.
The Diallertest®/Viaskin® duo should enable the early diagnosis and early treatment of allergy in the
young child, thus preventing the development of multiple food allergies (in the case of milk allergy) and
respiratory diseases like asthma (in the case of house dust mite allergy).
The target market for DBV Technologies' first three products (Viaskin® Peanut, Viaskin® Milk and
Viaskin® HDM) is worth over $5 billion. It is important to note that for each target indication and age
group, there are (on the basis of available information) no desensitization treatments on the market or
under development.
11
Viaskin® Peanut: an ambitious development plan
DBV Technologies is undertaking an ambitious
development program for its Viaskin® technology.
clinical
Safety of use has been established in a large, Phase Ib study
(with 100 patients) performed in the largest allergology centers
in the USA. A multicenter French study of extremely allergic
patients is currently on-going and is confirming Viaskin®'s excellent
safety and very good tolerability.
The Viaskin® Peanut Efficacy and Safety (VIPES) study is a large trial that will include several hundreds of
patients with peanut allergy in 4 European countries, the USA and Canada. The protocol is being discussed
with the regulatory agencies and recruitment of the first patient is expected in the first half of 2012.
The company's MAA file could also include the results from two supporting clinical studies led by key
opinion leaders in food allergy. One (on-going) study started in France in 2010 and the other should start in
the USA in 2012:
■
ARACHILD is a French, Phase II pilot study sponsored by the Paris Public Hospitals Group (APHP). The last patient was included in March 2011. The data for the initial 6-month study period should be
released shortly, followed by the full data during the first half of 2013. At present, the Viaskin®'s safety has
been confirmed.
■
The CoFAR study (funded by the US National Institutes of Health and led by Professor Hugh Sampson in
New York), should start in 2012 and is scheduled to run for four years. The preliminary data from the first
12-month period is scheduled for release in Q1 2014. This study will significantly reinforce the Viaskin®
technology's profile within the scientific community.
■
The company expects to file a registration application with the FDA for Viaskin® Peanut by 2016.
The whole Viaskin® Peanut development program has been granted "Fast Track" designation by
the FDA, thus securing the coming development phases.
12
Viaskin® Milk: Fast Track development
Viaskin® Milk is the second desensitization product developed by DBV Technologies.
Since milk allergy is often the first allergy to occur in sometimes very young children,
desensitization with Viaskin® Milk seeks to enable allergic children to reintroduce milk into
their everyday diet and prevent the development of new food allergies.
Given the sale and use (since 2004) of over 150,000 Diallertest® Milk patches with an excellent safety
profile and the prior performance of a pilot desensitization study in the clinic, DBV Technologies should
be able to launch a Phase II clinical trial in 2013 without needing to perform a Phase I study beforehand.
Grant of marketing authorization will be considered after the performance of a confirmatory, Phase III study with
the optimal dose defined in the Phase II study.
The results of this Phase II clinical study should be available in the second half of 2014.
The company has already performed a pilot study, the results of which were published in JACI1. It was a
double-blind, placebo-controlled study in children aged between 3 months and 15 years and who were unable
to drink more than 10 ml of milk. The treatment did not generate any serious adverse events, premature study
withdrawals or adverse events requiring treatment.
The results of the pilot study showed that after 3 months of treatment, the dose of milk tolerated by the
patients had increased 12-fold.
Groupe Lait- Evolution du challenge oral
Volume de lait toléré avant apparition de symptômes (ml)
100
Enfants capables
de boire un biberon
après 3 mois
67,1
64,6
47,1
25,5
10
10
9,1
9,1
3,6
27,1
20
4,1
1,6
1,6
1,3
0,6
0,6
9,1
4,1
1
Démarrage
de l’étude
0,1
0,1
OC 1 - T0
OC 2 - 3 mths
OC 3 - 6 mths
OC 4 - 9 mths
Some patients who could not even tolerate the equivalent of a drop of milk without having severe reactions
were able to ingest significant quantities after 3 to 6 months of treatment (left-hand graph, shown above).
In the graph on the right (relating to control patients treated for the first 3 months with a placebo, i.e. a patch
lacking any active substance), no improvement was observed. The same patients were then treated with
Viaskin® Milk between month 3 and month 6; 80% witnessed an increase in their milk tolerance. This pilot study
is the first to have evidenced the clinical efficacy of this epicutaneous method.
1
Dupont C, JACI 2010
13
Diallertest®: a confirmatory Phase III study
Diallertest® Milk has been developed by DBV Technologies as the first diagnostic test for milk protein allergy in
children. It is currently available on the French market, under a temporary authorization of use granted
by the regulatory authorities. To date, over 150,000 tests have been sold.
The Diallertest® Milk kit includes two ready-to-use devices
(applicators) and patch tests to apply to the skin. The first patch
contains 500 µg of dried milk. The second device does not
contain any protein and is designed to test the skin's reactivity; it
serves as a negative control and is used to interpret the result of
the main test.
Diallertest® Milk is positioned as a companion diagnostic for Viaskin®
Milk; this could accelerate uptake of the Viaskin® Milk treatment by
increasing the diagnosis rate.
Given the device's history of use, marketing authorization in Europe just
requires the performance of a Phase III study, the protocol of which has
been discussed with and approved by the European Medicines Agency.
14
An intensive clinical development program
The diagram below summarizes the company's on-going and future development plans.
A large clinical program: in 2012 and 2013, no fewer than 6 clinical trials on children and adults will be
performed in the largest allergology centers in Europe and the USA, including four performed by DBV
Technologies itself on Viaskin® Peanut (a potentially pivotal Phase IIb study), Viaskin® Milk (Phase IIb),
Viaskin® HDM (Phase I) and Diallertest® (a pivotal Phase III study) and two above-mentioned studies
coordinated by prestigious organizations in France (AP-HP) and the USA (NIH and CoFAR).
The company will release specific details of each step in the program.
15
DBV Technologies in brief
DBV Technologies has the organizational and human resources needed to pursue its research and
development programs.
Management team:
■
Pierre-Henri Benhamou, co-founder, President and CEO
■
Bertrand Dupont, co-founder and Chief Technical Officer
■
David Schilansky, Chief Financial Officer
■
Laurent Martin, Regulatory Affairs Director
■
Wence Agbotounou, Chief Clinical Trials Officer
26 staff members federated around an experienced management team; the company has a team of
professionals from a wide range of backgrounds and with fully intermeshing skills for developing its business.
Blue-chip investors like Sofinnova have supported the company from the outset. They have recently been
joined by leading industrial businesses (ALK Abelló and Shire Laboratories) and specialist investors (Innobio
and Lundbeckfond Ventures). In all, as of end December 2011, these investors had provided about €39 million
in equity via several rounds of fundraising. The company aims at becoming a leading specialty pharmaceutical
company in the field of allergy and the first in the world to offer treatment to the most allergic patients. It intends
to sell to the European market directly through its own sales operation and will rely on strategic alliances in
North America and in Asian countries.
An internationally renowned Scientific Advisory Board: the company's SAB comprises eight international
experts, including several key opinion leaders in the field of food allergy and pediatrics.
16
Appendix I – Management
Pierre-Henri Benhamou, co-founder, President and CEO: a pediatric physician specializing in gastroenterology.
Pierre-Henri Benhamou MD has held a number of senior clinical positions (including that of Senior Consultant) at
Saint-Vincent-de-Paul Hospital in Paris. As DBV Technologies' current CEO, he received the Prize for Innovation
from the Altran Foundation in 2003 for his work on the development of patch tests for the diagnosis of cow’s milk
protein allergy. He also serves as the company's Chief Scientific Officer. Pierre-Henri Benhamou has authored many
scientific publications and has forged many collaborative links in France and worldwide.
Bertrand Dupont, co-founder and Chief Technical Officer: a graduate in Engineering from the Ecole Nationale
Supérieure des Arts et Métiers in Paris.
Prior to co-founding DBV Technologies, Bertrand Dupont pursued a career in teaching and consultancy. In 1996, he
began applying his knowledge and experience of mechanical engineering to biomedical research. From 2000
onwards, he has played a key role in the development of the Viaskin® patch technology and its applications. As CTO,
Bertrand is responsible for all the technical processes and the industrial manufacturing facilities developed for
Viaskin®.
David Schilansky, Chief Financial Officer: a graduate of Paris Dauphine University and Imperial College London.
David supervises all the group's financial activities, collaborations and business development activities. He is a
former Deputy CFO at Ipsen, a company he joined in 2006. David held senior management positions within the
Finance & Administration Department and was involved several corporate acquisitions and the creation of an Investor
Relations department. In 2011, David also served as interim CFO and as a member of the Executive Committee.
Prior to joining Ipsen, David spent three years at UBS Warburg's M&A division and three years at Thomson as an
Investor Relations Officer.
Laurent Martin, Regulatory Affairs Director: holds a PharmD from René Descartes University of Paris, MBA from
Paris Sorbonne and a Masters in Public Health Law from Paris-Sud University.
Laurent joined DBV Technologies after over 15 years in the pharmaceutical industry. He has extensive experience in
managing international pharmaceutical development projects (in Europe and the USA) and in the registration of
pharmaceutical products (particularly via the centralized procedure at the EMA). He acquired regulatory affairs skills
in various pharma companies, such as Galderma, Guerbet and, most recently, Orphan Europe, where his last
position was Interim Head Pharmacist, Pharmaceutical and Preclinical Developments Director and Quality Director.
Laurent is coordinating the international development, registration and clinical trial authorizations for DBV
Technologies' pharmaceutical products.
Wence Agbotounou, Chief Clinical Trials Officer: holds a PhD in Pharmacology from Pierre & Marie Curie
University, Paris, and an Executive MBA from ESCP Paris management school.
Wence has occupied management positions in many leading CROs, such as Quintiles and PRA International. As a
Global Project Manager and then Project Director, he launched and successfully managed global Phase II and Phase
III clinical trials (including several pivotal immunotherapy trials) for large and mid-sized pharma companies.
17
Appendix II – Funding
Blue-chip investors like Sofinnova have supported the company from the outset. They have recently been
joined by leading industrial businesses (ALK Abelló and Shire Laboratories) and specialist investors (Innobio
and Lundbeckfond Ventures). In all, as of end December 2011, these investors had provided about €39 million
in equity via several rounds of fundraising.
January 2011:
Series C - InnoBio, Lundbeckfond Ventures, Shire plc, ALTO Invest, Sofinnova and ALK
Abello €19.4 million
2009:
Series B fundraising -Sofinnova Partners and ALK Abello
2006:
Series A fundraising - Sofinnova Partners and Apax Partners
2003:
Seed funding - Cap Decisif and Creagro
2002:
Starting equity from DBV Technologies' founders
Annexe III – Principaux Investisseurs
Annexe IV – Principales collaborations scientifiques
18
Annexe V – Bibliography

Mondoulet L., Dioszeghy V., Dhelft V., Ligouis M.,
Larcher T., Cherel Y., Dupont C., Benhamou PH.
Epicutaneous immunotherapy (EPIT) blocks the allergic
esophago-gatro-enteropathy induced by sustained oral
exposure to peanuts in sensitized mice. 2012 PloS One in
press

Dioszeghy V., Mondoulet L., Dhelft V., Ligouis M.,
Puteaux E., Benhamou PH, Dupont C. Epicutaneous
immunotherapy results in rapid allergen uptake by
dendritic cells through intact skin and downregulates the
allergen-specific response in sensitized mice. J Immunol.,
2011,186: 5629-37.





Posters

Mondoulet L. Dioszeghy V., Ligouis M., Vanoirbeek J.,
Nemery B., Dupont C., Benhamou PH. Epicutaneous
Immunotherapy Using a New Epicutaneous Delivery
System in Mice Sensitized to Peanuts. Int. Arch. Allergy
Immunol., 2011; 154:299-309.
Epicutaneous (EPIT) vs Sublingual (SLIT) and
Subcutaneous (SCIT) Immunotherapy in a Model of
Peanut Sensitized Mice :a dose-effect study.
Mondoulet L., Dioszeghy V., Ligouis M., Dhelft V.,
Puteaux E., Dupont C., Benhamou PH.
EAACI, june 2011, Istanbul, Turkey

Dupont C, Kalach N, Soulaines P, Legoué-Morillon S,
Piloquet H, Benhamou PH. Cow's milk epicutaneous
immunotherapy in children: a pilot trial of safety,
acceptability, and impact on allergic reactivity. J Allergy
Clin Immunol. 2010 May;125(5):1165-7.
Efficacy of Epicutaneous Immunotherapy (EPIT) in a
model of Mice Sensitized to Milk.
Mondoulet L., Dioszeghy V., Puteaux E., Ligouis M.,
Dhelft V., Dupont C., Benhamou PH.
EAACI, june 2011, Istanbul, Turkey

CD25+CD4+Tregs mediate the protection from oral
peanut-induced esophageal lesions of sensitized mice
treated by epicutaneous immunotherapy.
Dioszeghy V., Mondoulet L., Dheft V., Ligouis M.,
Puteaux E., Dupont C., Benhamou PH.
EAACI, june 2011, Istanbul, Turkey.

Epicutaneous immunotherapy requires intact skin and not
stripped skin to properly activate and mature dendritic
cells toward induction of desensitisation.
Dioszeghy V., Mondoulet L., Dheft V., Ligouis M.,
Puteaux E., Dupont C., Benhamou PH.
EAACI, june 2011, Istanbul, Turkey.

Epicutaneous Immunotherapy down-regulates the skin
local production in response to skin application of peanut
of peanut protein extract in mice sensitized to peanut.
Dioszeghy V., Mondoulet L., Dheft V., Ligouis M.,
Puteaux E., Dupont C., Benhamou PH. FOCIS, June
2010 , Boston, USA

Epicutaneous immunotherapy inhibits peanut-induced
anaphylaxis in a Guinea pig model.
Mondoulet L., Dioszeghy V., Ligouis M., Dhelft V.,
Dupont C., Benhamou PH.
EAACI, june 2010, London, England
Model of Eosinophilic Esophagitis (EE) and Villus
Atrophy (VA) after Challenge in Mice Sensitized to
Peanuts: Improvement by Epicutaneous Immunotherapy
(EPIT).
Mondoulet L., Dioszeghy V., Ligouis M., Dhelft V.
Larcher T., Cherel Y. Dupont C., Benhamou PH. AAAAI,
March 2010, New Orleans, USA.
Dupont C, Soulaines P, Lapillonne A, Donne N, Kalach N,
Benhamou P. Atopy patch test for early diagnosis of cow's
milk allergy in preterm infants. J Pediatr Gastroenterol
Nutr. 2010 Apr;50(4):463-4.

Mondoulet L., Dioszeghy V., Ligouis M., Dhelft V.,
Dupont C., Benhamou PH. Epicutaneous immunotherapy
on intact skin using a new delivery system in a murine
model of allergy Clin Exp Allergy, 2010; 40, 659-667.

Benhamou PH, Kalach N, Soulaines P, Donne N, Dupont
C. Ready-to-use house dust mites atopy patch test (HDMDiallertest), a new screening tool for detection of house
dust mites allergy in children. Eur Ann Allergy Clin
Immunol. 2009 Oct;41(5):146-51.

Kalach N, Soulaines P, de Boissieu D, Dupont C. A pilot
study of the usefulness and safety of a ready-to-use atopy
patch test (Diallertest) versus a comparator (Finn
Chamber) during cow's milk allergy in children. J Allergy
Clin Immunol. 2005 Dec;116(6):1321-6.
Congress

Oral Communications

Efficacy of epicutaneous immunotherapy (EPIT) in a large
cohort of sensitized mice.
Mondoulet L., Dioszeghy V., Ligouis M., Dupont C.,
Benhamou PH.
GA2LEN-EAACI, february 2009, Davos, Switzerland and
EEACI, June 2009, Warsaw – Poland.
The crucial role of the stratum corneum superficial layers
during epicutaneous immunotherapy (EPIT).
Mondoulet L., Dioszeghy V., Ligouis M., Puteaux E.,
Dhekft V., Dupont C., Benhamou PH.
AAAAI, March 2011, San Francisco, USA

A model of eosinophilic esophagitis (EE) and villus
atrophy (VA) after challenge in mice sensitized to peanuts:
improvement by epicutaneous immunotherapy (EPIT).
Mondoulet L. Dioszeghy V., Dupont C., Benhamou PH.
ESPGHAN, june 2010, Istanbul, Turkey.

New delivery system across intact skin inducing specific
antigen uptake by Langherans cells in sensitized mice.
Dioszeghy V., Mondoulet L., Dhelft V., Ligouis M.,
Dupont C., Benhamou PH.
EAACI, june 2010, London, England.

In epicutaneous immunotherapy, application of allergen on
intact skin result on rapid uptake by the dendritic cells in
sensitized mice.
Dioszeghy V., Mondoulet L., Dheft V., Dupont C.,
Benhamou PH.
EAACI, june 2009, Warsaw, Poland.

Epicutaneous Immunotherapy (EPIT) for House Dust Mite
(HDM) Allergy using Viakin® Technology
Mondoulet L., Ligouis M., Chariglione S., Dupont C.,
Benhamou PH.
AAAAI,
March
2009,
Washington,
US
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