special focus of Biotech Finances

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France, Nord-Pas de Calais - Special Issue
BIOTECHFINANCES
Strategic information for bioindustry decision makers and investors
Eurasanté, THE BACKBONE OF LIFE SCIENCES
IN THE NORD-PAS DE CALAIS REGION
As a major player in the French life sciences industry, the Nord-Pas de Calais Region benefits from a very competitive
ecosystem. To its advantage, it possesses a well established and dynamic cluster producing quality science. Being
located just a short distance from Belgium, opportunities for partnerships and funding abound. Biotech Finances took
a closer look with Etienne Vervaecke, CEO of Eurasanté.
which enables local entrepreneurs
Biotech finances : What
to have simultaneous access to an
is the background of the Euraagency, a competitiveness cluster,
santé structure?
an incubator, and a business assoEtienne Vervaecke : Eurasanté
ciation.
was founded in 1996 by the Lille
University & Regional Hospital
BF: Four main lines of deveCenter with the aim of making its
lopment have been deliberatransfer of technology to industry
tely selected: cardiometabolic
more dynamic and organized. This
disease, cryptogenic inflaminitial mission allowed us to merge
matory bowel diseases (CIBD),
with the academic landscape of the
neurodegenerative diseases,
Nord-Pas de Calais region, as well as
and nutrition. Why were these
to support a number of partnership
chosen?
projects and start-ups. This creaE.V.: When we worked on the
tion of value, focused on the health
competitiveness cluster project, we
sector, has fueled the growth of a
wanted to specify what we offer by
true regional life sciences industry
Etienne Vervaecke
focusing on our strong points. Our regioemploying around 22,000 people in over
nal history, both in terms of academic
780 companies today. At the Eurasanté
research as well as the industrial side of things, quickly led
complex in the Lille metropolitan area in particular, this
us to the four main areas you mentioned. There is a rearepresents some 135 companies with 2,700 employees. In
son why in France the only Labex
addition to the aim of promoting
(academic cluster of excellence)
research and supporting businesses,
focused on cardiovascular diseases
animation of the ecosystem is also
Lille’s strength is
is located in Lille with companies
provided by the Nutrition, Health,
the fact that it has a
such as Genfit or Naturalpha active
Longevity (NHL) competitiveness
in the field. The same is true for
competitiveness cluster,
cluster, which is managed by an
neurodegenerative disorders, with
independent governance structure.
incubator, and business
a dedicated Labex and several
This dual responsibility of assisting
cluster all under the same companies including AlzProtect or
a cluster and an economic developGenoscreen. As for the nutrition
ment agency is a defining feature
banner.”
sector, things are a bit different. It
and great strength of the Lille region
“
Contents
Funding
Interview
Companies
Apteeus pushes back the
LFB moves forward alongside clinicians in Lille
VF Bioscience deploys
its line of probiotic nutritional supplements
Page 3
Page 4
Page 5
limits of personalized medicine
The week in brief AlzProtect, EAT-Cell
Biotech, Naturalpha, 4P Pharma, Vaxinano…
Pages 8 - 9 - 10
FUNDING Financing its biotech in Nord-Pas
de Calais: Mode of Operation
Page 11
bio TICKET
biotech companies
Lille, the strange attractor of
Page 12
Interview
BF: What scale
do you work on
for the expansion
and development
of your region?
Do you feel the
strict
regional
territorial division is something
that needs to be
overcome?
E.V.: One of the
major interests at
play in the establishment of competitiveness clusters is
the progressive “thematization” or specialization of the various health clusters
towards the areas in
which they are the
strongest. Rhône-Alpes has therefore
turned to immunology, whereas MidiPyrénées has focused on cancer, and
PACA on rare diseases. These areas
of focus should obviously exceed the
strict territorial confines of the cluster,
merging with national and/or European
players in some cases of border clusters
like ours with Belgium, for example,
which is very close to us. This dynamic
of transverse expansion is increasingly
becoming a reality, as attested by the
number of new members of the NHL
cluster outside of the Nord-Pas de
Calais region, which this year achieved
nearly 50% of the 20 subscriptions.
BF: You mention transnational
collaborations, how do you fuel
this dynamic and what impact
does this have on your funding
methods?
E.V.: Our public funders, including
the region itself, understand that their
support has served to sustain a dynamic
whose epicenter is the Nord-Pas de
Calais region but whose scope and
ambition are of international proportions. More specifically, right now we
have four European Interreg projects
underway with our partners in neigh-
boring countries. We are also in the
process of working to create research
networks with Wallonia and Flanders,
focusing on the issue of nutrition and
lifestyle diseases. At the national level,
we are working with Nantes on biomaterials, with Marseille on diagnostics,
and with Valorial on bio-markers for
large scale project. It
is important for us to
be well established among the various
French clusters - in
order to have true
international visibility. Furthermore,
we also often work
together, be it at Bio
Japan, Bio US, or
other major European trade fairs for
example.
strong industrial returns due to the high
upstream selectivity of the products.
We extensively sort the candidate files
which we submit, and the FUI ultimately finances 55% of them. At the NHL
cluster, this figure reaches 80%. This
is a strong recognition of our expertise, of which we are very proud. For
example, during the last FUI campaign
we presented 3 projects, including one
in collaboration with Lyonbiopôle, and
we got a positive response on two of
the files. In recent years we’ve noted a
real change of the type of sourcing employed in the projects that we’ve submitted. Whereas the first applications
were very “downstream” with little involvement on our end, we are currently
working on much more early-stage projects programs, cooperating intensely
with their leaders.
© Maxime Dufour Photographies
is embodied by family-owned companies such as Roquette, Lesaffre, Ingredia, or Copalis, which are all very established in and attached to the Nord-Pas
de Calais region which invests a lot in
their industrial activities and in the industry as a whole.
BF: How important is it for the
BF: Speculators entrepreneurs you work with to
announce
the use this source of funding to fischeduled
end nance their projects?
of
government E.V.: Several years ago we encountesupport for the red a lot of apprehension from entreclusters.
What preneurs towards collaborative projects
is your point of such as Bpifrance or the FUI, which
view concerning this matter?
were viewed as very complicated to
E.V.: Financial pressure is clearly organize, not fully compatible with the
mounting, and it is apparent that we Research Tax Credit (“CIR”), and the
are still in a phase of recession and payment of which often came too late
reductions in all kinds of subsidies and with respect to industrial requirements,
government
asespecially
for
sistance. In this
small businesses.
context, it is quite
This mentality has
It’s important
likely that the gochanged and we
vernment will pronow come across
to work together
vide the funding
many companies
to achieve greater
of the clusters to
which have never
local communities
had worries of this
visibility.
in 2-3 years’ time.
nature. Obtaining
To date, operaan FUI or ISI funting a center like ours costs around ding sends a strong signal to the market
€650,000 to €700,000 annually. 45% of about the reputation of a company. It’s
this figure is covered by contributions also a non-dilutive means of advancing
from private members, 35% by local one’s work, which is something very
and regional authorities, and 20% by valuable today. The partnership aspect
the government.
of this type of consortium shouldn’t be
overlooked since it can be very limiting
BF: What then would come of the to approach these things alone. In my
FUI which now funds the projects opinion, conducting group research is a
approved by the various clusters? factor of sustainable success. This helps
E.V.: The Single Interministerial Fund open innovation to move forward with
(FUI), a real linchpin of the mecha- an incrementally stronger R&D dynanisms behind the competitiveness mic. l
clusters, is not likely to be stopped or
replaced any time soon. It represents
Interview conducted by
an important aid to the sector, with
Juliette Lemaignen
2
“
”
Biotechfinances • France, Nord-Pas de Calais - Special Issue
Funding
Apteeus PUSHES BACK THE LIMITS OF
By Juliette Lemaignen
PERSONALIZED MEDICINE
H
ere is an innovative concept
which could revolutionize the
way we handle the treatment
of rare diseases. Involved in
the development of chemical
drug candidates at the INSERM U761 Laboratory (Pasteur Institute of Lille, Lille 2
University), Benoît Deprez and Terence
Beghyn have been joining forces over the
last year for the company Apteeus, incubated by Eurasanté on the campus of the
Pasteur Institute of Lille. "We realized that
the traditional concept of drug development,
which is based on the answer to a medical
question by a universal drug candidate with
a broad scope, wasn’t financially compatible
with the therapeutic niches occupied by rare
diseases,” explains Terence Beghyn, CEO
of Apteeus, who goes on to say: “The cost
of R&D, which is very great, will be very
difficult to amortize over a small population and the instances of reimbursement will
soon be unable to accommodate the overly
expensive treatments.” To work around
this problem, Apteeus decided to revert the
drug development scheme by starting with
the patient and then moving towards larger
markets while working with existing drugs.
“Our project is to automatically screen all
of the active ingredients currently sold on
the patient’s own cells while monitoring
the faulty process resulting in the disease.
Within a few days, we can thus determine which molecules could be used to
treat the pathology of the disease in question. This is the principle of personalized
medicine taken to the extreme, employing
the concept of one drug for one patient.”
Two awards in the National Competition of
the Ministry of Research
In order to specify its approach, Apteeus
initially opted to focus on inherited metabolic diseases which account for about 5%
of rare diseases and which have the advantage of being mostly monogenic and therefore easier to treat, using a single molecule
molecule to his or her patient, either as part
of an off-label prescription, as a temporary
authorization for the use of the drug for the
named patient, or lastly in the context of an
n-of-1 clinical trial.” The results of the first
use of this indication in humans should be
compiled in 2015. They will probably serve
as a go/no go for the financiers interested
in the model. Large scale deployment by
Apteeus will likely cost several million Euros
which the founders will seek to pool together
from regional and national venture capital,
with a first round secured in 2015. l
Terence Beghyn and Benoît Deprez
“We need to complete
the first round of
funding in 2015.”
that targets the cause of the disease. With the
encouragement of the two awards it received
from a national contest by the Ministry
of Research, offering a total package of
€275,000, the company is currently conducting the proof of concept of its approach in
conjunction with Dr. Dries Dobbelaere from
the Lille Regional & University Hospital
Center for two patients suffering from the
same creatine transporter defect. Leaders
of the project have already identified 15
molecules which may potentially be active
in these patients. They are furthering their
investigation by examining the potency of
these compounds on the patients’ cells and
by analyzing all available information on the
safety profile and pharmacokinetics of the
identified molecules. “The challenge is to
ensure that the drug is well active and will
not result in any uncontrolled side effects,”
explains Benoît Deprez, who has accounted
for roughly 20% of the project. “Once we’ve
obtained this information, we will be able
to convince the doctors to administer the
20 million
20 million patients currently suffer from rare diseases in
Europe, with about 5% of those affected by approximately
300 inherited metabolic diseases.
5-40
Thanks to the follow-up obtained on the first two
campaigns on patients’ cells, the founders of Apteeus
estimate that there are between 5 and 40 active molecules serving as candidates for repositioning based on
new indications from the rare diseases for each patient.
1 600+
The Apteeus library now consists of nearly 1,600 active
ingredients. And this number is constantly changing.
Partners
Pasteur Institute of Lille, Eurasanté, Lille 2
University
Opinion of Alain Gay, Head of Cardiovascular Medical Affairs and Women’s
Health at Bayer Healthcare Pharmaceuticals
In my opinion, the basic idea for the pharmaceutical industry in the coming years
is to start with the patient in order to provide him or her with better treatment.
Recent treatment developments now allow us to address major public health issues.
Now we need to improve upon this in order to provide additional service, both to
patients and practitioners. The concept of drug repositioning is, in this sense, an interesting idea. We pharmaceutical companies have molecules in our portfolio which could
meet new needs that arise and it would be interesting to identify them beyond simple
clinical observations compiled during the trials. However, one thing is certain: biotech companies must be extremely careful when it comes to the safety
and tolerance of their molecules if they wish to be of interest to us.
3
Interview
LFB MOVES FORWARD ALONGSIDE
CLINICIANS IN LILLE
A renowned company of the Lille region, the French Fractionation and Biotechnologies Laboratory (LFB) has
a presence in Nord-Pas de Calais through three sites, including a research center that is home to one of the
group’s flagship projects: a drug candidate against fetal alloimmunization. Sami Chtourou, Deputy Managing Director, Innovation and Scientific Affairs, discusses the program and more broadly the role of the LFB
within the Eurasanté structure.
employs around 550 people in Lille;
and lastly, a drug warehouse located in
Carvin where all LFB medications are
stored prior to distribution and which
has a staff of approximately 30 people.
In total, nearly 700 people work for LFB
in the Lille metropolitan area, though
the group numbers some 1,600 people
throughout France as a whole and 2,000
people worldwide. Tens of millions of
Euros in investment have been allocated
to these facilities over the last 10 years.
Sami Chtourou,
Deputy Managing Director, Innovation
and Scientific Affairs at LFB
Biotech finances : You are a
key business in the Eurasanté BioBusiness Park. In what areas are
you a major player locally and how
are your activities divided across
the region?
Sami Chtourou: We have a strong
background with Eurasanté. The establishment of our research center at this
site actually goes back some 10 years,
with an ever growing number of staff
over the years. During this period, we
have developed sound scientific excellence which is reflected throughout the
territory. We have finally been implementing an extensive network of partnerships and collaborations at the local
level. More specifically, we operate at
three different sites: a research center
with some 45 employees which I lead at
the Eurasanté campus; a production facility for drugs derived from plasma, which
BF: What drug project are your
researchers currently working on?
S. C.: Our lab innovates in the three
key areas focused on by the LFB Group:
hemostasis, immunology, and intensive
care. One of the flagship projects resulting from the technological platform
developed in Lille is a recombinant
monoclonal anti-D antibody, indicated
for preventing the risk of fetomaternal
alloimmunization. This is a condition
that can affect women pregnant with
their second child. As demonstrated by
the initial clinical results, our antibody
can destroy the Rhesus positive fetal red
blood cells causing an immune response
from the mother against her fetus, and
as such we are able to prevent the risk
of immunization. The product is undergoing a phase II clinical study in France,
and in particular at the Lille Regional &
University Hospital Center. A phase III
study is expected to start within the next
two years.
BF: What are the advantages of
being part of a business park such
as Eurasanté Bio-Business Park?
S. C.: The cluster forms a dense network
of research, educational, and care institutions with which we are able to easily
interact thanks to our geographical location. We work with the Lille Regional
& University Hospital Center and the
Lille 2 University, and particularly with
professors Jenny Goudemand, François
Fourrier, Eric Hachulla, and Pierre Desreumaux. We also appreciate the start-
4
up spirit which prevails throughout the
campus; a spirit which we share because,
though we have an industrial approach,
we maintain our responsiveness and
entrepreneurial dynamism which, in our
view, are the source of all success when it
comes to drug development.
BF: What are the areas of development in Lille?
S. C.: We have at our disposal two key
proprietary technological platforms for
antibody engineering which we use for
developing our products. The first is de-
“We also appreciate
the start-up spirit
which prevails throughout the campus,
which is the source of
all success in terms
of drug discovery.”
signed to enhance the cytotoxic activity of
the antibodies through the Fc function,
and the second increases the half-life of
the monoclonal antibodies by a factor of
3 as a result of a greater affinity of the
Fc fragment with the FcRn receptor. We
are going to provide access to these platforms to other industry players via licensing agreements on these technologies or
through co-development. Additionally,
we are continuing our efforts alongside
the cluster’s start-ups, and we try to assist
them. We have ongoing discussions with
Eurasanté and its members through our
scientific and technical partnership manager, Rémi Urbain, in order to maintain
and expand our collaboration with the
local ecosystem. l
Interview conducted by
Anne-Laure Languille
Companies
VF BIOSCIENCE DEPLOYS ITS LINE OF PROBIOTIC NUTRITIONAL SUPPLEMENTS
Maxime L. Vaeremans
and Marc Frémont
“Our flagship product
Reg’Activ reduces the blood
cholesterol level by 20%”
T
he satisfaction of having a first
dietary supplement on the market is clear on the faces of the
Franco-Belgian duo heading
VF Bioscience. Named Reg’Activ Cholestérol, the product comes in an elegant dark
red box. “The majority of our distributors
around the world have kept our design,”
says Maxime L. Vaeremans, Marketing Director for VF Bioscience. Founded in late
2011, this young and innovative company
established in the Eurasanté bio-incubator develops dietary supplements based
on patented probiotics either coming from
outside or from its own collection of 200
strains, as well as functional ingredients
such as vitamins. Released in 2013, Reg’Activ Cholestérol is designed for people with
moderate hypercholesterolemia, which affects 10-15% of the population depending
on the country. “Reg’Activ reduces the rate
of cholesterol in the blood by 20% and
improves other blood parameters related
to the risk of developing cardiovascular
disease,” explains Marc Frémont, R&D
Director of the start-up. In fact, the clinical study carried out for this product on 25
subjects demonstrated a 19% reduction in
LDL, a key marker of atherosclerosis. Lactobacillus fermentum ME-3, the probiotic
strain contained in Reg’Activ, was isolated
by a research team from the University of
Tartu in Estonia, from which VF Bioscience
obtained its license.
Fundraising underway
The company, which adheres to an almost
virtual structure composed of the two
partners, markets its product through
a network of specialist distributors in
Europe, South-East Asia, and across the
American continent. It has also been
sold in pharmacies in South France since
September. With this first scientific success,
which it hopes to turn into a commercial
success as well, VF Bioscience aims to
quickly develop its own pipeline. Financed
so far through private funds, in addition to
an equity loan of €50,000 from Bpifrance
and an interest-free loan of €40,000 from
the North Entrepreneurship Network, this
biotech company is poised to successfully
complete a €400,000 fundraiser with
Finovam in particular. This money
will allow it to develop another dietary
supplement indicated for cardiovascular
health that acts on triglycerides (reducing
triglycerides by 20-25% by the end of the
trial), as well as type 2 diabetes, which could
be taken in combination with Reg’Activ
Cholestérol. In order to boost sales of the
two products in the United States, where
15% of the population is affected by
cholesterol issues, VF Bioscience will soon
open a branch overseas. The latest flagship
product from its pipeline is a supplement
for liver function and detoxification named
Reg’Activ Vitalité, which is scheduled to be
released by the end of the year. With these
first three products, the start-up aims for
sales of €2 million in 2016. l
By Anne-Laure Languille
€1.2 billion
This sum represents the market for dietary supplements in France.
3 to 4
To accommodate its continued development, VF
Bioscience will recruit 3-4 people in the months
ahead.
4
In 2015, the company will release 4 new dietary
supplements.
Partners
Bank
CIC
Law Firm for Current Affairs
Bignon-Lebray
Law Firm for Patent Matters
Plasseraud
Consulting Firm & Incubator
Eurasanté
Opinion of Alexandre Labé, Development Director of the Nutrition, Health, Longevity Cluster
VF Bioscience has had the support of Nord Entreprendre since the end of 2013.
This is a network of business leaders who help other leaders to fortify their companies, and includes an interest-free loan between €15-90 K, in exchange for which the
company undertakes to create 5 to 10 jobs within three years. VF Bioscience boasts
several major advantages such as the experience of its leaders in the sector, a first product on the
market, and research collaborations with international institutions. But the managers have also
identified their challenges: how to achieve international deployment? How to get the company in a
sustainable research cycle? How will all of these actions be funded? These are questions
to which the two managers have found solutions.
5
Convention
BIOFIT TAKES A STEP CLOSER TO ACADEMIC
INNOVATION AND THE INDUSTRIAL WORLD
Since the first edition in 2010 in Lille, which was attended by some 330 participants, the BioFIT business
convention has taken on a whole new dimension. This year 800 researchers, biotech CEO, pharma directors,
and TTO (Technology Transfer Offices) are expected to be present in Lille on December 2 and 3 to determine
opportunities for collaboration. The program includes panel discussions and one-to-one meetings.
C
onceived and organized by
the Eurasanté Economic Development Agency and the
NHL competitiveness cluster,
BioFIT is following a rather
unique theme in the world of business
conventions: creating innovation by gathering academic and industrial players for
two days. “So it’s not a trade show,” clarifies Eurasanté. “The meeting between
public laboratory teams and industry
teams in the context of fostering development programs is BioFIT’s center of gravity, so to speak,” says Nicolas Carboni,
President of the TTO Conectus Alsace.
BioFIT: How does it work?
To conduct the meetings, academics,
industrial players, and the technology
transfer officers can schedule up to 15
individual appointments per day. With a
duration of half an hour each, they will
be held from 9:00 AM to 6:00 PM on the
sidelines of thematic discussions. From
the time the meeting platform begins
in November, it will be possible to make
contact with partners prior to the business
convention. Afterwards, each participant
will be able to flexibly manage his or her
own schedule, with the ability to set aside
time to attend the discussion panels.
With a practical overtone, these discussions
will address various topics concerning
Open Innovation. How can early-stage
innovation be financed? What are the
best practices for collaborative research?
What new trends have emerged in terms
of technology transfer and industrial
scouting? To answer these questions, high
level speakers will share their views: big
pharma open-innovation directors, TTO
directors, biotech patrons, and investors.
This will include Adrian Carter from
Boehringer Ingelheim, Jeffrey Ulmer from
Novartis Vaccines, Duncan Holmes from
GSK, and even Sanofi’s Bernd Stowasser,
just to name a few.
financed equally by local authorities, the
Nord-Pas de Calais region, and private
partners. “This allocation of resources is
necessary, as the convention cannot rely
solely on entry fees since the price has
been reduced for academics and startups”, explains Eurasanté.
Finally, BioFIT reaffirms its international
position by welcoming representatives
from 35 countries. Due to its geographical
proximity, the event will include many
players from Belgium. This is an
interesting way to promote research
collaborations between laboratories and
industrial players operating on both sides
of the border. l
By Anne-Laure Languille
Nicolas Carboni
“The triangular meeting
between academics,
biotechs, and industry
represents the most fertile
ground for developing the
innovations of tomorrow.”
TTOs are running the show
The involvement of the TTOs is one of
the attractions of the BioFIT business
convention. They will be able to fully
play their role as business facilitators
according to Nicolas Carboni of the
TTO Conectus Alsace. “The triangular
meeting between academics, biotechs,
and industry represents the most fertile
ground for developing the innovations of
tomorrow. The academic-industrial push
remains marginal, even though more
and more pharma is sourcing technology
directly with public laboratories. TTOs
are behind the creation of the meeting.”
The partnership aspect is reflected in
the sponsors of the operation, which is
6
38%
The proportion of academics and TTO who will
participate in the 2014 edition. Pharmaceutical
companies represent 34%, with investors, clusters,
and other services making up 28%.
€999
Entry fee for mature companies. €399 for startups younger than 3 years and €849 for TTOs,
clusters, and research institutes.
13
The number of panel discussions over the two
days.
SAVE
THE
DATE
June 17 & 18 , 2015
Lille, F R A NC E
The market place for innovation
in food, nutrition & health
> Qualified one-to-one meetings
> High-level conferences
nutrevent.com
7
Companies
AlzProtect is on the rise
K
nown for its research in the area of neurodegenerative diseases, AlzProtect, founded in 2007 and developed in the Eurasanté bio-incubator,
has just completed an initial fundraising campaign bringing in €2 million. “We’ve collected €1 million from a single investor, a new entrant to our
capital Pierre Besançon, €600 K from Finovam and Nord France Amorçage, as
well as €400 K from 14 other individual investors,” says Philippe Verwaerde,
head of the 10-person company. Thanks to this process, AlzProtect has advanced
to a whole new level. Its new reputation comes primarily from the fact that it
has just begun a Phase I trial for its flagship compound AZP2006. Developed
in frontotemporal dementia which, along with Alzheimer’s disease, belongs to
the group of tauopathies, AZP2006 has demonstrated encouraging preliminary
results. Once Phase I is completed, the company will again appeal to outside
Philippe Verwaerde
investors to fund the next stage, this time with the aim of raising €12 million to
go all the way to the proof of concept stage. AlzProtect is already working with Pr. Florence Pasquier from the Regional
and University Hospital Center in Lille on the design of Phase IIa which will be carried out in 2016. The molecule is
also planned to be reviewed in another Phase IIa trial looking at progressive supranuclear palsy. Priced at €6 million,
this project may be funded by a European consortium under the Horizon 2020 framework.
EAT-Cell Biotech checks your Tregs!
“Analysis of the activity of regulatory T lymphocytes should
be a statutory prerequisite for any new drug candidate under
development,” says Nadira Delhem, Head of the virus-induced cancer immunoregulatory team at the Institute of Biology in Lille. “Many developmental and treatment failures in the sector
are particularly due to an overactivity of the regulatory T lymphocytes
which inhibit the immune response. In the “best” case, a tumor will resist
a treatment, but in the “worst” case, the patient may suffer significant side
effects including autoimmune disorders.” This very important observations was validated by Dr. Delhem’s team on human cell models, as part
of a trial of a molecule whose development was halted in Phase II. “The
next step consists of marketing the product in the form of services, after
10 years of research,” adds Nadira Delhem, who will continue to serve as
Dr. Nadira Delhem
a consultant for the company EAT-Cell Biotech which operates the platform. Any biotech or pharmaceutical company, with a budget of tens or hundreds of thousands of Euros depending
on the project, can test the molecule. To test a molecule with three doses, the response time will be around 4 weeks.
Saving both time and money should prevent business developers from being skeptical for too long...
Vaxinano is developing nanoparticles for its vaccines
T
he power of nanotechnology adapted to the colossal market for vaccines is the area chosen by Prof. Didier Betbeder, head of the Nanoparticles research team of Lille 2 University. This former biotech
manager, who notably co-founded Biovector Therapeutics back in the 90s
on the concept of a nasal influenza vaccine, is resuming an entrepreneurial
stance with the launch of the Vaxinano project. The concept is to develop innovative vaccines quantitatively encapsulating specific antigens in
starch nanoparticles. It’s a bold proposition which opens this technology
up to an almost unlimited number of applications. To get started, Prof.
Betbeder set out on a project involving toxoplasmosis, co-directed by Prof.
Dimier-Poisson from the University of Tours. The team has already obtained proof of concept for their nano-vaccine in mice, and they are currently
Prof. Didier Betbeder
testing it in sheep in a controlled trial set up with the INRA and financed
by the TTO. “The first market we envision is that of animal vaccination, because it is the most accessible and
significant in terms of commercial benefits,” comments the researcher, who concludes: “However, we intend to
replicate our model in humans for other indications in the short term, such as for parasitic infections, as well as
for any illness requiring a cell-mediated vaccine such as HIV or hepatitis B, for example.”
8
Companies
Health claim: Naturalpha spreads the word to European industrials
N
aturalpha advises
ingredient producers on obtaining
health claims for their food
products, and in addition to
conducting clinical trials.
According to the regulations of the EFSA (European
Stéphane Postic
Food Safety Authority) from
2012, manufacturers may
not include health claims on their products unless they
have been scientifically proven. Posting a turnover of
€2 million, the CRO, founded in 2001, seeks to increase
its business output. This phase will require educational
efforts directed at industry stakeholders who are reluctant to conduct clinical trials. To win them over, Naturalpha organizes training sessions on the EFSA regulations.
Compared to competitors, the 25-person company has
several assets to its advantage, including the ability to
recruit volunteers and, in particular, its access to obese
or overweight patients which is more common in NordPas de Calais than in the rest of France. One of its latest
clients also bolsters its credibility. The client in question is the Oxylane-Décathlon group, which should soon
receive its first claim for a sports nutrition product.
Recently created, 4P Pharma opens its capital to investors
F
ormed last August, the start-up 4P Pharma is the
latest creation of the Eurasanté Biotech Incubator. To fund the development of its drug candidates, it is opening its capital to investors. “A round has
just started with the aim of raising €900 K,” explains Revital Rattenbach, CEO of the start-up whose scientific leadership comes from Itschak Lamensdorf, the CEO of the
Israeli company Pharmaseed. Other fundraisers calling
for millions of Euros will follow to push the candidates
to the clinical proof of concept stage for their transfer to
a pharmaceutical company. Based at the Pasteur Institute
in Lille, 4P Pharma follows an original model. It identifies promising technologies from the TTOs and biotech companies, co-develops them with a scientific team
during maturation, and then
decides whether or not to get
a license. After sourcing from
the Southeast and North TTOs,
its portfolio contains three programs including two for which
it has posed licensing options.
The most advanced among them
is targeted at muscular dystrophy and has obtained encouraging results. The regulatory
Revital Rattenbach
pre-clinical trials will take place
in 2014/2015 before entry into clinical trials in 2016 if 4P
Pharma exercises that option.
Cousin Biotech and Lille 2 University develop innovative prosthesis
I
© Éric Flogny/Aleph
n Lille, SMEs and clinicians
work together with ease.
This has been the case with
the project bringing together Cousin Biotech, a developer of textilebased medical implants for the
last 20 years, and the team led by
Prof. François Pattou (Inserm 859,
Lille 2 University), a specialist in
non-pharmacological treatments
François Cousin
for diabetes. François Cousin,
Chairman of the Supervisory Board of the Cousin Medical Group, and Prof. François Pattou want to develop an
effective prosthesis against obesity and type 2 diabetes.
Their teams, which have been working together for several
weeks, have already co-filed two patents on the technology
in question. Their collaboration should soon be formalized
by an agreement under the orchestration of SATT Nord.
“As we move forward with confidence, this agreement will
only serve as a formality,” says François Cousin, who has
long presided over Cousin Biotech even prior to its acquisition this year by Dalle & Associates. For the SME with
€14 million in turnover and 100 employees, this program is
part of its tradition of open innovation which will enable it
to enhance its pipeline. “Such a device would complement
our range of gastric bands,” concludes François Cousin.
Diagast industrializes AboDiag technology
for the marketing planned
for 2017. Thanks to sales of
these new systems, the Lille
industrial company, which
currently boasts a turnover of €30 million, hopes to
reach €50 million within the
next 5 years, and €100 million in 10 years. Aware that
it needs to find ways to make
its ambitions into reality, it
Bruno Morino
intends to expand its production facilities and to double its workforce over the next
five years for a total investment of €15 million.
© Laurent Mayeux Photographies
D
iagast, a flagship company of the Eurasanté Park
where it was established in 1995 contributes its
Lille expertise in the area of blood transfusions
and blood-derived products along with LFB and Macopharma. Owner of the Bordeaux TPE AboDiag since last
March, Diagast launches the industrialization of its HaemTrap technology, complementing its range of Qwalys automated systems. “AboDiag technology has the advantage
of being intuitive and enabling the execution of hundreds
of tests in a very short time,” says Bruno Morino, CEO
of Diagast. The tests in question involve blood grouping,
identification of phenotypes, and the research and identification of antibodies. Diagast also needs to advance technologically and to develop support and a new subsystem
9
Entreprises
Breast cancer, and then? Kalicou innovates
T
he “Kalicou” research
project on “the experience of young women
diagnosed with breast cancer
and their partners” is about to
launch its third component.
“The impact of breast cancer
on those close to patients and
its management, in the long
term, is still not well known or
Dr. Laurence Vanlemmens
categorized,” says Dr. Laurence
Vanlemmens, oncologist at the Oscar Lambret Center. With
a pink ribbon on her chest, this passionate practitioner,
joined by Prof. Véronique Christophe, professor of health
psychology at Lille 3 University, hopes to establish a computer interface that will make it possible to assess the subjective experience of young women with this disease and
their partners in real time. This platform, which will be
developed by two IT specialists, Aquilab and Alicante, will
enable clinicians to monitor their patients in real time and
to receive specific alerts about them, or their partners,
when encountered with serious difficulties coping with the
disease in various regards, including the management of
everyday life, children, relationships, or their professional life. To complete the project, the female duo will need
€100 K.
EGID intervenes to fight diabetes
F
inding innovative answers to metabolic diseases
by focusing on non-pharmacological means is a
field of research opened up by the team of Prof.
François Pattou, Director of the U 859 diabetes cell therapy unit of the European Genomic Institute for Diabetes
(EGID), responds to a growing health need. In just a few
years diabetes has become a true epidemic, affecting
more than 382 million people worldwide in 2013. A gogetter by nature, Pr. Pattou has connected a serious of collaborative projects in order to arrive at sufficient means
to develop an ambitious R&D policy. The academic team
works towards this goal with several industry players,
including Macopharma to develop a program in the area
of islet transplantation for type 1 diabetes, which has
already successfully treated
45 patients, as well as Cousin
Biotech, for project to develop medical devices capable of
reproducing proven surgical
operations but with a much
less invasive nature. EGID also
takes part in the ISI IT-Diab
Consortium, as well as the IMI
Direct project, both geared towards characterizing markers
of response in patients.
Prof. François Pattou
Biostatistics: Orgamétrie boosts its growth
D
oubling its turnover
in five years’ time is
the goal that has been
set by the CRO Orgamétrie,
which specializes in biostatistical studies and clinical trials
both before and after marketing
authorization. To achieve this,
the Roubaix company which
currently generates €3 million
Dr. Pierre Clerson
in turnover is mapping out its
future development. First, it will restructure its human
resources with the installation of middle management for
better division of labor. The second operation will include
bolstering its data management ability organized around
an eCRF solution for data collection, a shift which it began
a few years ago. Finally, a diversification of its activities is
also part of its strategy. Orgamétrie also invested €100 K
in another kind of Lille CRO, Oncovet Clinical Research,
which aims to offer pharmaceutical companies models of
dogs and cats which are naturally sick. “This three-stage
rocket is in combination with our daily efforts to sustain
our collaborations with industry players and to remain a
choice partner,” says Pierre Clerson, doctor and CEO of
Orgamétrie, who also publishes seven to eight scientific
papers per year.
Lunginnov: from diagnosis to treatment for respiratory infections
A
llowing practitioners to predict respiratory aggravation in a patient using a specific biomarker
is the mission set forth by Philippe Lassalle, CEO
of the Lille company Lunginnov. After the discovery of
the molecule Endocan and its properties of expression
at the level of respiratory endothelium, this researcher
at the Pasteur Institute in Lille has developed a kit capable of predicting two main types of diseases: sepsis
and lung inflammation. An application is also under development in the field of oncology, with the possibility
of using Endocan as a marker of angiogenic response. So
far self-funded through revenue from product sales and
10
services (€170,000 in 2013), as well
a grant provided by Bpifrance and
by individual investors, Lunginnov
is seeking industrial and financial
partners to accelerate its activities
and advance its program of therapeutic development linked to the
Endocan marker. This product
could enter the clinical stage by
2017/2018, which in the meantime
will require a fundraiser for several
million Euros.
Philippe Lassalle
Funding
Financing its biotech company in NordPas de Calais: Mode of Operation
I
n order to support the development of its economic network, the Nord-Pas de Calais region has implemented a range of financial tools available at different stages and for all amounts, both for start-ups
as well as more “late-stage” companies. Biotech finances has prepared an overview of these devices
and how they work.
FINANCE
Funding contributors
Finovam, IRD, Nord France Amorçage, the Nord-Pas de Calais Region, the Business Angels of North
France, Invest Innovate, the North
Entrepreneurship Network, LMI INNOVATION, Clubster Santé, Bpifrance.
•
The Nord-Pas de Calais region invests in
a development contract intended for SMEs
with fewer than 250 employees through grants
which can reach up to 10% of the investment
amounts anticipated by the companies.
In order to make the funding and support
of technology start-ups in the Nord-Pas de
Calais region more dynamic, the venture
capital branches of Finorpa (Finorpa SCR) and
IRD (Inovam) merged in February 2014 to
create Finovam, a regional prime-pumping
company allocated €15 million. Finovam aims
to strengthen the development and financing
of innovative seed projects, primarily
technological, by providing additional
resources to support long-term projects with
great potential. In particular, Finovam
invested €2 million in the latest round for
AlzProtect, set up in the Eurasanté bioincubator. In the eyes of Hélène Cannard, a
Finovam Board Member, it is important for
biotech companies “to structure enough
equity funds to enable them to finance preclinical phases and then to grant access to
venture capital.”
The proximity to Belgium is favorable
for investment coming from that country: IRD
has historically held a partnership with
Louvain Vives II, a cross-border fund based in
Leuven, which has the ability to intervene in
Nord-Pas de Calais.
The Nord France Amorçage regional
pump-priming fund was launched in late
2012. It supports small and medium-sized
companies in the priming and post-priming
stage, as well as the innovative projects of
existing companies. Acting only as a coinvestor, Nord France Amorçage may invest
up to €800 K in companies.
The “Business Angles of North France”
association aims to serve as an intermediary
between companies seeking funding and the
business angels in the region. It also seeks to
educate and inform project leaders on the
importance of opening the capital of their
•
•
•
•
business, and it lets business angels know
about potential investments.
Along these same lines, the Clubster
Santé business network has launched the
“Invest Innovate” platform with Eurasanté,
which is responsible for linking project
leaders/entrepreneurs with a group of about
one hundred investors consisting of private
individuals who are able to inject between
€150 K to €500 K, whether or not they want to
be involved in management. Over 3 to 4
meetings per year, the different members
attend presentation pitches. “The North is an
important contributor to the ISF,” says Etienne
Vervaecke, Director of Eurasanté. “It would be
a shame not to allocate these funds, using the
TEPA device, to innovative companies, and
that’s exactly what we try to do with Invest
Innovate.” Since 2009, Invest Innovate has
made it possible to raise approximately €40
million for the 48 projects presented.
Unsecured loans: the Northern
Entrepreneurship Network and LMI
Innovation grant unsecured loans without
interest or collateral to individuals only. The
project leader can also receive up to €90 K in
the form of a loan from each of these
organizations.
Bpifrance is a key player in the funding
of biotechnology companies in the Nord-Pas
de Calais region. Included in the assistance it
offers for innovation, Bpifrance funds biotech
companies both in the process of being created
(feasibility studies, etc.), as well as those in the
development phase (equity loans, etc.). The
assistance to the development of a drug
candidate is part of Bpifrance’s scope.
•
•
•
SUPPORT
Sources of Support
Eurasanté, J’innove en Nord-Pas
de Calais, Regional Chamber of
Commerce and Industry, the “Nutrition, Health, Longevity” Cluster,
and the Pasteur Institute of Lille.
An important partner for biotechs in the NordPas de Calais region, the Eurasanté economic
development agency supports the health/
biotech industry through a team of forty
individuals specializing in different areas:
support for development and the creation of
innovative businesses, research development,
15
15 projects approved by Eurasanté have had access
to the FUI.
€142 million
14 projects supported by the NHL Cluster are winners of Future Investments, and have thus received
a total funding of more than €142 million.
€163 million
Since 2006, Eurasanté has backed 72 projects
funded with a total R&D budget of €163 million and
nearly €70 million of public aid awarded.
the incubation of innovative projects, and
guiding the “Nutrition, Health,, Longevity”
competitiveness cluster. Addressing both food
health and therapeutic & biotechnological
innovation, this cluster has helped to
approve numerous FUI projects focused on
three themes: neurodegenerative diseases,
chronic inflammatory bowel disease, and
cardiometabolic & nutrition related diseases.
Lille is also known of its expertise and skills
pertaining to blood related products, with the
presence of companies such as Macopharma
and Diagast. For Etienne Vervaecke, CEO
of Eurasanté, the role of the development
agency extends far beyond regional borders:
“We are very active in the promotion of the
area in order to attract businesses to the
Nord-Pas de Calais region”, a region where
“there is a flurry of activity related to the
health industry, which is hardly known and
recognized!” Eurasanté organizes professional
events, such as BioFIT and NutrEvent, and
aims to accelerate financial and scientific
partnerships. Eurasanté is also a privileged
contact when it comes to raising funds: “We
have a network in capital investment, venture
capital, and the business angels in France and
Belgium.” l
11
BIO Ticket
By H. Ella
Lille, the strange attractor of biotech companies
I
s it the proximity to Brussels, the distance
from Paris, or perhaps the vitality of
its research centers which makes Lille
a major attractive center in the field of life
sciences? Perhaps it’s all the above and then
some. With companies operating in sectors
as diverse as
genomics and diagnostic
kits, the latest generation of antibodies or
innovative treatments for metabolic diseases,
the whole spectrum of life sciences seem to
be represented. As such, with nearly 2,200
researchers and no less than 780 companies
in the health industry, the Nord-Pas de Calais
region ranks third place. With all of this
diversity, the Lille region has been attracting
biotech companies for many years, and it’s the
sort of place that makes full use of all creative
will. Particularly sensitive to initial conditions,
the development and creation of businesses
requires a truly innovative ecosystem from the
get-go. A special partner of research centers
and excellent universities, the Lille bio-cluster
Eurasanté has been able to mobilize many
different energies, including local investors:
Finorpa and Inovam. These investors, in the
final phase of integration, merged their primepumping activities under the name Finovam,
preferring a single fund of €15 million to
crumbling abilities as can often be seen in
our beautiful regions. Such an operation is
uncommon since it involved the combination
of two actors, one public and the other private,
each having distinct purposes beforehand.
The goal now is to move to the next level
more quickly with an interregional seed fund
coving the Picardie, Champagne-Ardenne,
and Lorraine regions, which will benefit from
the support of the National Priming Fund.
Today, with the presence of a few champions,
including the most iconic, Genfit, which has
one of the largest market capitalizations, the
Lille region can look at how far it’s come with
peace of mind. l
u Strategic Overview
The main deals in Nord-Pas de Calais during the year 2014
Genfit
Capital increase
€49.7 M
Multiples
MTDCapital increase
€5,4 MNord Capital Partners
AlzProtectCapital increase
€2 M
Pierre Besançon, Finovam, Nord France Amorçage, business angels
MDoloris
Capital increase
€1,1 M
Historical shareholders including Finovam and Siparex
AlzProtect
Obtaining a grant
€1 M
Bpifrance
OCR
Capital increase
€700 k
Nord France Amorçage, A&S (Autonomie et Solidarité) and business angels
Lipofabrik
Capital increase
€200 k
Business angels
Cousin Biotech
Transfer
ND
Dalle & Associates
Agro-Levures et Dérivés SASTransferND
Lesaffre
AgrauxineTransferND
Lesaffre
This special issue received support from
Cette action est cofinancée par l’Union européenne
BIO
BIOTEC
HFINAN TECHFIN
BIOTECHFINANCES
CES
AN
Hebdomadaire • Lundi 13
L’INFORMAT
octobre 2014 • N° 653
ION STRA
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Hebdomadaire
• Lundi
L’INFOR
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22 septemb
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MATION
STRATé
N° 650
Hebdomad
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Lundi 6
octobre
2014
• N° 652
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