3. ACILIMAB in vitro diagnostics 4 LYONBIOPOLE medical
technologie > > > > > > > > > > >
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> > Animal medecines Proof of Concept
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Oso............................................ Proof of Concept
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46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67
68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 Year Start: 2011 Call
for projects: FUI (FUI AAP12) Global budget: 2 820 k Public
funding: 1 447 k Duration: 36 months Stage of development at the
beginning of the project: Discovery Accredited by: Lyonbiopole
Abstract Chemotherapies can be made more efficient and better
tolerated when the active substances are concentrated and targeted
to the tumours. Through ACILIMAB a new combined therapy will be
developed which will combine active drug-substances, monoclonal
antibodies as targeting agents, and Lipidots as vectors. This
delivery strategy will be evaluated on mantle lymphoma cells which
are resistant to conventional chemotherapeutics. The aim will be to
demonstrate the therapeutic efficacy of drug-loaded
immuno-particles, so as to establish therapeutic alternatives for
currently non-curable lymphoma. Strategic business area PARTNERS
Partners > DD biotech (Company) i > YNBIOSE (Company) C >
OXCAN (Company) V > EA LETI (Research Unit) C > nticorps
anticancer (Research team) A > MMUNOLOGIE ANALYTIQUE DES I
PATHOLOGIES CHRONIQUES U823 (Research team) Public funders >
onseil gnral du Rhne C > EDER Rhne-Alpes F > onds Unique
Interministriel (FUI) F DGCIS/Oso > rand Lyon G > Rgion
Rhne-Alpes Project leader VERMOT-DESROCHES Claudine Entity: iDD
biotech Position: R&D Director Address: 27, chemin des
Peupliers 69570 Dardilly Email: [email protected]
Phone: +33 (0)4 72 52 30 88 Objectives The objectives of ACILILAB
project are: o develop a safe, easy and innovative targeted
delivery of high potent therapeutic drug T based on anti CD19 MAb
decorated Lipidots o demonstrate that MAb-targeted nanoparticles
are potentially useful as targeting T delivery systems for
chemotherapeutic agents o acquire knowledge on immuno-nanocarriers
as targeted delivery for tumour cells T o strengthen the
therapeutic arsenal for patients & clinicians T Innovative
assets Application fields Autoimmune diseases / Neurology /
Oncology Technological approaches / Keywords Biologics / Drug
delivery system / Immunotherapy / Innovative formulation/
Nanobiotechnology Through ACILIMAB new platforms were generated
dedicated to the development and characterization of drug-loaded
immunoparticles. Up to date active drug-substances were screened
and selected regarding key parameters such as activity and loading.
Futher experiments are in progress to optimize the generation, the
stability, the specific cellular binding and internalisation of
drug-loaded immuno-particles. Actual Outcomes Perspectives The main
outcomes of ACILIMAB will to combine active drug-substances,
monoclonal antibodies as targeting agents, and Lipidots as vectors
to manage the balance of beneficits and risks of chemotherapies.
Mantle lymphoma ACILIMAB > Search of partnership > Search for
technologies > Preclinical assay realization > Search for
private financing > Search for public funding > Proof of
concept LYONBIOPOLE 5 ongoing projects ongoing projects LIPOBACK
MELASCAN MIT-2M MRSA-VAC MULTICELLS MULTIMAGE MUTATION NanoEno
NANOLUPUS NIVPATH NOBLEACH ONCOFLUO OPTIMABS OREGA-17 PA-ANTIADH
PA-CONTROL PECSDELI PHOTO-SRM PILIPATH PLASMOSC PLATISSEP PLUS
POLYBIO PREDIVAC PREMAG QUINOLAC SECPATH STING 2.0 SYNFRIZZ SYNODOS
SYSCLAD TEDAC THERA8 TOLLREG TOXOCAG TULAREDRUG UROLINK VICIT
VIVABRAIN Resistance treatment and optimization of cancer treatment
by vectorisation of immune targeted active drug-substances
4. ADNA NEW Advanced Diagnostics and New therapeutic Approaches
ongoing projects Abstract The ADNA program seeks to develop a more
personalized form of medicine, focusing on infectious diseases,
cancers and rare genetic diseases by providing innovative
theranostic products and services for healthcare professionals. The
program intends to identify, validate biomarkers for providing
diagnostic and therapeutic solution to healthcare needs which are
not currently addressed efficiently. PARTNERS Partners >
INSTITUT MERIEUX (Company) > bioMrieux (Company) > CEA LETI
(Company) > Transgene SA (Company) > ST Microelectronics
(Company) > Genethon (Research unit) > enosafe (Company) G
> ospices Civils de Lyon (Healthcare H unit) > niversit
Claude Bernard Lyon 1 U (Research unit) Public funders > so /
BPI France O Design, synthesis and pharmaceutical development of
antiadhesion glycoclusters inhibitors of infection by Pseudomonas
aeruginosa Project leader GUILLEN Christine Entity: Institut Mrieux
Position: Program Director Address: 17, rue Bourgelat 69002 LYON
Email: [email protected] Phone: +33 (0)4 78 87
70 72 Objectives Based on the observation that specific genetic
factors determine how each individual patient responds to
treatment, the objective is to develop products that can be used to
better diagnose diseases or predict patient response, so that a
tailored treatment program can be devised, providing better care to
patients. Innovative assets ADNA program combines innovative assets
for each partner: Strategic business area Application fields
Genetic / Rare diseases / Infectious diseases / Inflammatory
diseases / Oncology Technological approaches / Keywords
Bioinformatics / Software / Biomanufacturing / Immunotherapy /
Innovative formulation / Vector vaccine Genethon will test on
patients the first therapy genetic treatment produced in Gn thon
bioProd, the largest bioproduction facility in Europe (this site is
not part of the ADNA program and was not granted by OSEO/BPI).
Transgene aims, with TG4010, to propose a therapeutic vaccine
associated with two companion tests, combining immunology and cell
sorting technologies. Year Start: 2012 Call for projects: FUI (FUI
AAP14) Global budget: 6 332 k Public funding: 1 980 k Duration: 36
months Stage of development at the beginning of the project:
Discovery Accredited by: Lyonbiopole Co-accredited by: Eurobiomed
Abstract The use of multivalent high affinity glycoclusters is a
promising approach for the treatment of lung infections associated
with Pseudomonas aeruginosa. These patented molecules target
bacteria key virulence factors such as lectins PA-IL and PA-IIL,
involved in adhesion to lung cell surface and biofilm formation.
ANTI-PYO activities are the evaluation and the improvement of the
anti-bacterial activity of these molecules, the industrial
manufacturing of the best molecules and the beginning of their
development in order to identify one candidate for pharmaceutical
development. Strategic business area Application fields Infectious
diseases Technological approaches / Keywords Biomanufacturing /
Functional Screening / Drug discovery / Nanobiotechnology
BioMerieux innovates in bioMarkers field, especially in sepsis and
liver cancer, associated with new technologies as Mass spectrometry
or New generation sequencing. All partners included: 49
publications, 80 posters or communications, 31 patents Transgene:
Development of therapeutic vaccine for Non-Small Cells Lung
Cancers: End of Phase IIb/III planned for 2013. Development of
therapeutic vaccine for Head & Neck cancers in collaboration
with EORTC started in 2013 Genethon: Development of genetic the6
LYONBIOPOLE rapy for Duchene Muscular Dystrophy. Begin of Clinical
trials in 2014. BioMerieux: 2 new biomarkers (for sepsis and liver
cancer) on test phases. Innovative diagnostic systems (for
immunology and molecular biology applications) under development.
> 1 Product, prototype, service > 10 Proof of concepts >
Preclinical assay > 3 Clinical trials > 31 Patents > 49
Scientific publications > 80 Communications in international
congresses > 6 PhD > 186 Sustainable Job creations at the end
of the project > 45 Job creations in Rhne-Alpes region Partners
> licityl (Company) E > anofi R&D (Company) S > entre
de recherches sur les C macromolcules vgtales (Cermav) UPR5301
(Research unit) > nstitut de Chimie et Biochimie I Molculaires
et Supramolculaires (ICBMS) - UMR5246 (UCBL-CNRS) (Research unit)
> aboratoire dIngnierie des L Systmes Macromolculaires (LISM)
UMR7255 (Research unit) > niversit de Lille II (Research unit) U
Public funders > onds Unique Interministriel (FUI) F DGCIS/Oso
> Rgion Rhne-Alpes > onseil gnral des Bouches-duC Rhne
Project leader DARBLADE Benot Entity: Elicityl Position: Healthcare
program manager Address: 746, avenue Ambroise Croizat 38920 Crolles
Email: [email protected] Phone: +33 (0)4 76 40 71 61
Objectives The objective is to develop a drug candidate to treat
lung infections related to Pseudomonas aeruginosa in patients in
intensive care and in patients with cystic fibrosis. This bacteria
is the leading cause of infection in patients in intensive care and
is responsible for 80% of mortality in patients with cystic
fibrosis. The molecules developed in ANTI-PYO will have to prevent
bacterial attachment to the lung surface, to facilitate their
elimination by the immune system and to make them much more
sensitive to standard antibiotics treatments against which the
bacteria has become resistant. Innovative assets ANTI-PYO exploits
the potential of natural carbohydrates and glycocluster technology
for the development of a new generation of molecules active against
bacterial infection. The originality of the program comes from he
use of bacterial fermentation for the T production of the
carbohydrate moieties of the glycoclusters and he versatile
architecture of the glycoT clusters to converge to the best avidity
toward bacterial molecular targets. ANTI-PYO proposes promising
anti-bacterial approach aiming at inhibiting key virulence factors
involved in bacteria adhesion and biofilm formation. Advanced
Diagnostics for New therapeutic Approaches Actual Outcomes PARTNERS
Actual Outcomes Perspectives > Job creation in Rhne-Alpes region
> Increase in turnover Pseudomonas aeruginosa lectin PA-IL A
Imberty - CNRS > Preclinical assay realization > Clinical
trial realization LYONBIOPOLE 7 ongoing projects Year Start: 2007
Call for projects: ISI Oso Global budget: 202 263 k Public funding:
89 514 k Duration: 120 months Stage of development at the beginning
of the project: Basic research / Discovery / Preclinical
development Accredited by: Lyonbiopole
www.institut-merieux.com/projetssante_adna.php ANTI-PYO
5. APIMIR ARENABUNYAL Year Start: 2011 Call for projects: ANR
(ANR2010 - BLANC) Global budget: 600 k Public funding: 600 k
Duration: 48 months Stage of development at the beginning of the
project: Basic research Accredited by: Lyonbiopole PARTNERS
Partners > Laboratory Adaptation and Pathogenicity of
Microorganisms UMR 5163 (Research unit) > Institut Pasteur
(Research unit) > Large Scale Biology (BGE) - U 1038 (Research
unit) Public funders > NR, Agence Nationale de la A Recherche
ongoing projects Abstract This proposal focuses on the basis of
host cell manipulation by Plasmodium and Toxoplasma, the agents of
malaria and toxoplasmosis, respectively. MicroRNAs are a class of
small noncoding RNAs that modulate the gene function at the
post-transcriptional level and act as a fine tuner of various
biological processes, such as development or immunity. Inspired by
the work on viruses and bacteria, we recently started to explore
whether Plasmodium and Toxoplasma co-opt, impinge on, or subvert
microRNA-directed functions as a means to alter gene expression in
host human cells. Strategic business area Project leader HAKIMI
Mohamed-Ali Entity: CNRS Position: Research Professor Address:
UMR5163, Domaine de la Merci 38700 GRENOBLE Email:
[email protected] Phone: +33 (0)6 77 43 79 54
Objectives To examin the human small microRNome patterns following
T. gondii and P. berghei infection. To select pertinent microRNAs
and experimental validation of their target (genes) pathways. For
those that have all the attributes, we will investigate more deeply
how they contri bute in host cell to promote or prevent parasite
infection by using microRNA depletion and overexpression. To
identify parasite effector molecules (small RNAs or proteins) that
hijack the RNA silencing machinery in the host cell. Innovative
assets Structural, mechanistic and inhibitor design studies of the
Bunya - and Arenavirus L-proteins Year Start: 2011 Call for
projects: ANR (ANR2011 - BLANC) Global budget: 2 204 k Public
funding: 350 k Duration: 36 months Stage of development at the
beginning of the project: Basic research Accredited by: Lyonbiopole
Abstract The ARENABUNYA-L project aims to derive a structure-based,
mechanistic model to explain how arena- and bunyavirus RNA
polymerases function in both transcription and replication of the
viral genome. Transcription in these viruses is performed by
cap-snatching but this occurs in the cytoplasm, whereas influenza
virus does this in the nucleus. Structural information on
cap-snatching will be used to optimise inhibitors as a first step
towards antiviral drug design. Strategic business area The microRNA
matured in multiple steps in the cells is taken into the
RNA-induced silencing complex (RISC) to regulate mRNA expression
and stability. Recent data point to the possibility that
apicomplexans alter the host microRNome, thereby identifying the
RNA silencing pathway as a new means by which they reshape their
cellular environment. We identified a large number of host genetic
riboregulators whose expression was tightly regulated 8 LYONBIOPOLE
by Toxoplasma infection. We also report that two immunomodulatory
microRNAs contribute to better control of parasite burden in the
brain and promoted resistance to Toxoplasma infection. >
Scientific publications 2 Partners > aboratoire Architecture et
Fonction L des Macromolcules Biologiques (AFMB) (Research unit)
> uropean Molecular Biology E Laboratory (EMBL) (Research unit)
Public funders > NR, Agence Nationale de la A Recherche Project
leader CUSACK Stephen Entity: European Molecular Biology Laboratory
Position: Head of Outstation Address: 6, rue Jules Horowitz 38042
Grenoble Email: [email protected] Phone: +33 (0)4 76 20 72 38
Objectives The overall goal of this project is to derive a
structure-based, mechanistic model to explain how segmented,
negative-strand RNA viral polymerases function in both
transcription and replication. Innovative assets We will use
recombinant arena- and bunyavirus RNA polymerases and complexes
with viral RNA to study in vitro polymerase mechanisms by
biochemical and structural biology methods. Application fields
Infectious diseases Technological approaches / Keywords Structural
Biology Toxoplasma and Plasmodium subversion of host cell miRNAs
for parasite intracellular development Application fields
Infectious diseases Technological approaches / Keywords Genetics /
Genomics Actual Outcomes PARTNERS Schematic diagram of the
architecture of cap-snatching, segmented negative strand RNA viral
polymerases. The polymerases of different genera are represented as
lines with the size in amino acid residues of the representative
species shown. The blue box at the left indicates the endonuclease
domain with the particular sequence signature of that genus written
above. The central box represents the conserved polymerase domain.
In the case of orthomyxoviruses (e.g. influenza), the three
subunits PA, PB1 and PB2 of the heterotrimeric polymerase are
represented co-linearly with the total number of residues shown.
The blue box in influenza PB2 represents the cap-binding domain,
which is possibly located in the C-terminal region of the other
L-proteins (question mark). Perspectives > Set-up of a new
R&D project > Clinical trial realization Actual Outcomes We
have determined the crystal structure of the nucleoprotein of La
Crosse orthobunyavirus in complex with single- stranded RNA and
proposed a model of how it packages the RNA genome. > Scientific
publication 1 LYONBIOPOLE 9 ongoing projects Toxoplasma and
Plasmodium subversion of host cell miRNAs for parasite
intracellular development
6. BBMUT NEW Artificial testis for fertility preservation of
children with cancer Year Start: 2013 Call for projects: Proof of
concept CLARA Global budget: 1 250 k Public funding: 355 k
Duration: 36 months Stage of development at the beginning of the
project: Preclinical development ongoing projects Abstract While
sperm cryopreservation before starting oncological treatment is
efficient for fertility preservation in adult males, in prepubertal
children only spermatogonia are available from testicular tissue,
and no system of maturation are currenty available. The company
Kallistem and academic partners (Universit Claude Bernard Lyon 1,
Hospices Civils de Lyon, INSERM, CNRS, INRA) developped a prototype
of artificial testis to perform ex vivo spermatogenesis from
immature testicular tissue. The financial support of CLARA will be
determinant to transfer this method from rat to humans. PARTNERS
Partners > Hospices Civils de Lyon (Healthcare unit) >
Kallistem (Company) > Inserm U846 (SBRI) (Research unit) >
UMR CNRS 5223 (IMP) (Research unit) Public funders > onseil
gnral de Rhne C > rand Lyon G Project leader LEJEUNE Herv
Entity: Centre Hospitalier Universitaire de Lyon Position:
Professor of Endocrinology Address: Hpital Femme Mre Enfant 59, bd
Pinel - 69500 Lyon Email: [email protected] Phone: +33 (0)4
72 12 97 92 Objectives One child out of 500 is affected by cancer.
More than 75% of them will be cured. Hence, 1/1000 young adult
(20-30 y.o.) is a cancer survivor. These therapies are known for
their gametotoxic effects that can cause sterility. The aim of the
ARTIS project is to develop a system to produce mature sperm cells
ex-vivo, from germline stem cells contained in immature testicular
tissue. This includes preclinical studies in the rat for safety
issues. The final objective is to preserve fertility of prepubertal
boys before oncological treatment known to induce sterility by
spermatogenic failure. Innovative assets Strategic business area
Application fields Oncology Technological approaches / Keywords
Cell model / Animal model / Cell therapy / Regenerative Medicine
The whole ARTIS project is innovative. To our knowledge no
artificial testis are currently available. The main steps of the
project are: Production of sperm cells in sufficient amount to
perform ICSI, Study the quality of ex-vivo produced sperm cells in
rat, tudy the quality of conceptus in the rat
(anatomo-physiological and comportmental S studies), Transfer to
human testicular tissues and study the quality of ex-vivo produced
human sperms and finally, Determine the practical and ethical
conditions for a clinical trial in prepubertal boys. Actual
Outcomes Perspectives In vitro spermatogenesis was studied in our
group from 1997 (Weiss et al. Biol Reprod. 1997;57:68-76). In 1999
we published that one application of in vitro spermatogenesis will
be to preserve fertility in prepubertal boys before oncological
treatment (Lejeune H, Durand P. Conservation de tissu testiculaire
et maturation in vitro de la ligne germinale pour prservation du
potentiel de reproduction avant traitement anticancreux chez le
garon pr-pubre. Andrologie, 1999;9:498-504.) The system is now
advanced enough to propose the development of this project for a
clinical application. > Clinical trial realization > Proof of
concept > Patents 10 LYONBIOPOLE testimony Pr. Herv Lejeune,
clinician pratician at Hpital Femme Mre Enfant The genesis of the
project goes back to the publication in 1999 of joint results with
Philippe Durand on the conservation of testicular tissue and the in
vitro maturation of the germ line. The idea of ARTIS took place
during the 2010 Industrial-Academic Meetings of CLARA, when Laurent
Davids team presented its work on the application of biopolymers in
cell culture. Experiments are conducted and the project becomes
credible when the last steps of the in vitro spermatogenesis are
conducted. The par- Broad Band ultrasound imaging using CMUT Year
Start: 2012 Call for projects: ANR (ANR2011 - TECSAN) Global
budget: 2 032 k Public funding: 782 k Duration: 42 months Stage of
development at the beginning of the project: Basic research
Accredited by: Lyonbiopole Abstract The early diagnosis of liver
diseases and/or identification of any focal lesions are key issues
to consider a favorable prognosis. These objectives require
non-invasive dedicated diagnostic tools and justify the development
of innovative techniques. The BBMUT project aims to exploit the
properties of a promising new technology of ultrasound probes,
called CMUT, to propose new techniques for imaging and
characterization of liver tissue. The CMUT probe, developped by the
company Vermon, is characterized by a large frequency band. The
harmonic imaging techniques will be especially investigated.
Strategic business area Application fields Oncology Technological
approaches / Keywords Imaging (medical) / Ultrasound PARTNERS
Partners > REATIS (Research unit) C > ospices Civils de Lyon
(Healthcare H unit) > ermon (Company) V > MR930 Imagerie et
Cerveau U (INSERM) (Research unit) > aboratoire de Mcanique et L
dAcoustique (LMA) - UPR 7051 (Research unit) Public funders >
NR, Agence Nationale de la A Recherche Entity: CREATIS Position:
Professor Address: 7, av. J. Capelle 69621 Villeurbanne Email:
[email protected] Phone: +33 (0)4 72 43 85 69
Objectives esign of a CMUT probe whose specifications are adapted
to the examination of the D liver Implementation of innovative
techniques based on Chirp or composite signal emission. upply of a
native image that has improved contrast without degrading the
resolution. S evelopment of an ultrasonic method for characterizing
tissue structures adapted to D liver. uantitative measurement of
the nonlinearity parameter. Q re-clinical validation to quantify
the diagnostic relevance of the proposed approaches. P Innovative
assets The innovative aspects of the project consists in the
development of specific imaging technique for image improvement or
tissue characterisation dedicated to the large bandwidth of cmut
probe. Cmut probe and ultrasound image of a circulating contrast
agent using a harmonic imaging technique tnership with academic and
clinical actors materializes when the company Kallistem is created
in 2012. To us, CLARA promotes the synergy between partners
involved in the project. Through its selection in the CLARA Proof
of Concept program, and its financing by territorial
collectivities, the support of ARTIS corresponds to one the
2009-2013 Cancer Plan which focuses on improving access to the
preservation of fertility in cancer patients. The specificity of
the Proof of Concept programs allows us to be accompanied by CLARA
on the regulatory aspects and in our approach to Health
authorities. Project leader BASSET Olivier Actual outcomes > 3
Scientific publications > 4 Communications in international
congresses Perspectives > Preclinical assay realization
LYONBIOPOLE 11 ongoing projects ARTIS
7. BHI-PRO NEW Combining cellular and humoral immune responses
as a vaccine strategy against staphylococcus aureus Year Start:
2013 Call for projects: European funding (FP7 - Health) Global
budget: 7 000 k Public funding: 5 500 k Duration: 36 months Stage
of development at the beginning of the project: Preclinical
development Accredited by: Lyonbiopole Project supported by
Lyonbiople only PARTNERS Partners > Jenner Institute at Oxford
University (Research unit) > European Vaccine Initiative (Other)
> Preclin Biosystems (Research unit) Public funders >
European Commission ongoing projects Abstract S. aureus is one of
the most important bacterial pathogens of man. Morbidity and
mortality are associated with invasion of tissues and abscess
formation. EU costs from these infections are estimated at EUR 380
million per annum. Since there is no vaccine approved by major
regulatory agencies, and since recent clinical trials have proven
unsuccessful, prevention, like treatment, remains dependent on
antimicrobials. But resistance is increasing, so the utility of
this option will decrease in the short to medium term. Strategic
business area Project leader LE VERT Alexandre Entity: IMAXIO
Position: Directeur Gnral Address: 99, rue de Gerland 69007 LYON
Email: [email protected] Phone: +33 (0)6 79 82 92 70 Objectives
The objective of this project is to create an entirely novel
vaccine against Staphylococcus aureus infection in man. The concept
described here is to target both cellular and humoral immune
responses using a vaccine to be designed, manufactured, and
assessed in terms of safety and immunogenicity in man as part of
this grant. The novel vaccine generated will be applicable to both
beta-lactam resistant and sensitive S. aureus (MRSA & MSSA)
strains. Innovative assets The consortium will use three building
blocks to design the vaccine: A newly discovered, highly conserved
T-cell inducing antigen A commonly expressed, conserved antigen
neutralised by antibodies (Hla) An innovative, proprietary and
potent pro-immunogenic tag (IMX313) which can be fused to the
antigens. Application fields Infectious diseases Technological
approaches / Keywords Immunotherapy / Vector vaccine Bayesian
hierarchical inversion for mass spectrometry. Application to
discovery and validation of new protein biomarkers Year Start: 2011
Call for projects: ANR (ANR2010 - BLANC) Global budget: 1 824 k
Public funding: 838 k Duration: 36 months Stage of development at
the beginning of the project: Basic research, Clinical trials
Accredited by: Lyonbiopole Abstract To control the technological
variability on MS-based analytical chains for clinical proteomic
studies, we propose to introduce a relevant hierarchical modeling
of the MALDI and SRM chains within a Bayesian statistical
framework. The new Bayesian Hierarchical Inversion algorithms will
rely on the stochastic sampling inverse problem methodology. For
biostatistics, we propose to evaluate the sensitivity, specificity
of sample classification and the statistical power of biomarker
selection. Evaluation will be carried on synthetic and patient
samples within oncology and colorectal cancer studies. Strategic
business area Application fields Health & Environment /
Oncology Technological approaches / Keywords Bioinformatics /
Software / Omics Technologies / Biomolecular devices / Mass
spectrometry / Signal processing Actual Outcomes Staphylococcus
aureus Actual Outcomes The FP7 grant will be used to complete
pre-clinical tests as well as a Phase I clinical trial in humans in
2016 for the development of a vaccine indicated in Staphylococcus
aureus infections. 12 LYONBIOPOLE > Proof of concept >
Preclinical assay > Clinical trials > Scientific publications
Perspectives > Clinical trial realization Main deliverables:
Oncological data sets from synthetic and patient sample cohorts
delivered by CLIPP on MALDI platform in discovery mode, Colorectal
cancer data sets from synthetic and patient sample cohorts
delivered by bioMrieux on SRM/MRM3 platform in validation mode, A
Bayesian Hierarchical Inversion software dedicated to the MALDI
platform in discovery mode, A Bayesian Hierarchical Inversion
software dedicated to SRM/MRM3 PARTNERS Partners > CEA LETI
(Research Unit) > bioMrieux (Company) > aboratoire de
lIntgration du L Matriau au Systme (IMS) - Univ. Bordeaux, UMR 5218
(Research unit) > aboratoire Biomtrie et Biologie l Evolutive
UMR 5558 (Research unit) > entre Hospitalier - Universit de C
Dijon (Healthcare unit) Public funders > NR, Agence Nationale de
la A Recherche Project leader GRANGEAT Pierre Entity: CEA Leti
Position: Research director Address: CEA Leti, MINATEC Campus,
DTBS, 17, rue des Martyrs 38054 GRENOBLE cedex 9 Email:
[email protected] Phone: +33 (0)4 38 78 43 73 Objectives o
increase robustness of discovery and validation studies on a MALDI
platform (CLIPP) T and a SRM/ MRM3 platform (bioMrieux) by
controlling technological variability o design a Bayesian framework
combining hierarchical mixture models, probability T distributions,
and stochastic sampling inversion algorithms o evaluate the
statistical power of discrimination test T o study synthetic and
patient sample cohorts in oncology and colorectal cancer T o
combine in a single research project Bayesian inversion,
biostatistics, and proteoT mics platforms Innovative assets The
introduction of a new marker using stateof-the-art immunoassays
(ELISA) is currently expensive and time-consuming. Also the mass
spectrometry technology should shorten the delay and improve the
efficiency of protein markers discovery and validation. However,
there is a need for automatically operating a mass spectrometry
analytical chain and the associated data analysis. The proposed
Bayesian Hierarchical Inversion algorithms will improve the
measurement reliability and the sensitivity, specificity and
statistical power of biomarker discovery and associated clinical
diagnostic. platform in validation mode, A biostatistics guideline
report. > Products, prototypes, services 2 A bayesian
hierarchical inversion software for MRM in validation mode - a
bayesian hierarchical inversion software for MALDI in discovery
mode > Proof of concept 1 A bayesian hierarchical inversion
software for MRM in validation mode > 3 Clinical trials
Colorectal cancer study in MRM mode - Hepato-Cellular Carcinome
study in MALDI mode - Steatose study in MALDI mode bioMrieux
platform: liquid chromatograph (Dionex, Ultimate 3000) and SRM/MRM3
triple quadrupole mass spectrometer (ABSciex, ABI 5500QT) bioMrieux
> 0 Communications in international 1 congresses > 1 PhD
Perspectives > Search of partnership > Set-up of a new
R&D project > Preclinical assay realization > Clinical
trial realization > Search for private financing > Search for
public funding LYONBIOPOLE 13 ongoing projects BELLEROPHON
8. CELLESTIM NEW Antibiofilmogram Test PARTNERS ongoing
projects Year Start: 2013 Call for projects: FUI (FUI AAP15) Global
budget: 4 310 k Public funding: 1 285 k Duration: 36 months Stage
of development at the beginning of the project: Discovery
Accredited by: Lyonbiopole Co-accredited by: Alsace BioValley
www.antibiofilmogramme.fr Partners > BioFilm Control (Company)
> bioMrieux (Company) > Hospices Civils de Lyon (Healthcare
unit) > CHU Grenoble (Healthcare unit) > CHU Strasbourg
(Healthcare unit) > CHU Clermont-Ferrand (Healthcare unit) >
CHU Nmes (Healthcare unit) Public funders > Conseil gnral du Puy
de Dme > FEDER Auvergne > Fonds Unique Interministriel (FUI)
DGCIS/Oso > Rgion Auvergne Cellular estimation of immunity
Project leader Bernardi Thierry Entity: BioFilm Control Position:
CEO Address: Biople Clermont Limagne 63360 Saint-Beauzire Email:
[email protected] Phone: +33 (0)4 73 33 39 80
Abstract Objectives The project is based on the assumption that the
development of an in vitro biofilm in the presence of antibiotics
is correlated with a decrease in the effectiveness of the
antibiotic treatment. This project aims to: Demonstrate the
clinical value of an early detection of the biofilm in response to
antibiotic treatment. Allow a rapid adaptation of the empiri cal
treatment administered. Choose the best antibiotic treatment for
chronic infections The Antibiofilmogramme will be a new tool to
fight against multidrug-resistant infections. The project aims to
develop a brand new antibiogram test, named Antibiofilmogramme,
that will take into account the biofilm behaviour and its medical
value to prevent therapeutic failures. The BIOFILM project offers
the possibility to the French consortium and in particular to
BioFilm Control to compete at the highest level. The recognized
experience of the consortium partners on their core activity
combined with their critical size is ideal to launch the
revolutionary test on the international market and obtain a
scientific, industrial and economic success. Strategic business
area Application fields Infectious diseases Technological
approaches / Keywords Biologics / Diagnosis Innovative assets
Development of a new automated antibiogram test (a rapid test able
to detect virulent strains within 6 hours rather than 48h to 72
hours actually) Provide guidelines and recommen dations regarding
the interpretation of in vitro antibiogram test, in the future the
biofilm behavior of germs may be taken into account when an
antibiotic treatment is prescribed The R&D studies with our
clinical partners will provide an R&D synergy to discover new
ways of treating infections multi-resistant or not. Year Start:
2012 Call for projects: ANR (ANR2011 - P2N) Global budget: 1 461 k
Public funding: 676 k Duration: 36 months Stage of development at
the beginning of the project: Basic research Accredited by:
Lyonbiopole Co-accredited by: Medicen Paris Region www.inac.cea.fr
PARTNERS Partners > tructure et Proprits S dArchitectures
Molculaires (CNRSCEA-UJF) (Research unit) > ervice de Chimie
Bioorganique et de S Marquage (SCBM) (Research unit) > oriba
Jobin Yvon (who baught H genOptics) (Company) Public funders >
NR, Agence Nationale de la A Recherche Abstract We propose a
low-cost and low-technology approach to investigate individual cell
responses, based on individual cell monitoring. This difference is
fundamental as the individual cell approach allows the
investigation of biological signals at the cellular level,
collected from a cell interacting with other cells. A second
significant advantage of our approach is the ability to access a
statistically relevant number of individual responses. We are
confident in the fact that these data should allow us to describe
different secreting-ability profiles, depending on physiological
states. Strategic business area Application fields Infectious
diseases / Inflammatory diseases Technological approaches /
Keywords Biochips Project leader ROUPIOZ Yoann Entity: CNRS
Position: Research Scientist Address: SPrAM/INAC, CEA-Grenoble
38054 Grenoble Email: [email protected] Phone: +33 (0)4 38 78 98
79 Objectives The targeted objective of our project is the
real-time monitoring on a biochip of Influenza-triggered immune
response at individual cell levels. The core of our project is the
detection of secreted proteins on surface functionalized with
specific biomolecules used as secretion-capture elements. An
optical monitoring of the interaction will be led using surface
plasmon resonance phenomenon, propagating an evanescent wave on a
gold surface. Innovative assets This project is focused on the
development of original biochips allowing the fast detection of in
vitro immune response induced by pathogens. This tool should allow
to efficiently and rapidly screen for vaccine candidates but also
to identify original pathogens inducing immune responses. Artist
view of each element to be integrated in a SPR imager (e) fully
compatible with blood cells (a) culture in a thermostatic volume
(c) supplemented with CO2 (d). The core of the technology is the
biochip sensor (b) based on a glass prism covered with a 50 nm
thick gold layer. Such technology should allow the real-time
visualization of secreting cells (f). Yoann ROUPIOZ BioFilm
Ringtest BioFilm Control Actual outcomes 60 to 70% of medical
decisions involve the result of in vitro diagnostics. The annual
global market for Microbiological Diagnosis represents 7% of the in
vitro diagnostics market, which is about 30 billion euros. It is up
to 5% per year. 90% of the market is shared equally by 14
LYONBIOPOLE three key players: bioMrieux (Machine VITEK), Siemens
(Microscan) and Becton Dickinson (Phoenix). The BIOFILM project
provides a strategic opportunity in the current context because it
can modifiy the established balance in favor of French champions
such as BioFilm Control and bioMrieux. Perspectives > Set-up of
a new R&D project > Search for private financing Actual
Outcomes We just reached the mid-project term. Most outcomes are
expected to arise during the last phase of the project. But we can
already mention the completion of the first SPR imager, dedicated
to cell culture on a chip. > 1 Prototype Prototype for cellular
culture (for 2448h) on a chip allowing SPR imaging. Perspectives
> Search of partnership Search for clinical samples. LYONBIOPOLE
15 ongoing projects BIOFILM
9. CHEMISPIKE CLARENCE Inhibition of syndecan-1 mediated cell
adhesion ongoing projects Abstract Syndecans are transmembrane
heparan sulfate proteoglycans widely expressed in developing and
adult tissues. Several studies report involvement of syndecans in
human diseases such as cancers and infectious diseases. Among
these, a syndecan-1 interaction with laminin 332 was shown to
influence epithelial cell behavior and potentially impact carcinoma
development. Through a high-throughput screening assay of a large
library of chemical agents at the Plateforme de Criblage de
Molcules Bio-Actives , we have identified promising inhibitors of
the syndecan-1 mediated cell adhesion pathway. Strategic business
area Application fields Infectious diseases / Oncology
Technological approaches / Keywords Analytical Chemistry /
Chemotherapy / Functional Screening / Drug discovery / Structural
Biology PARTNERS Partners > Institut de Biologie et Chimie des
Protines (IBCP) - UMR 5305 (CNRSUCBL1) (Research unit) >
Conception, synthse et vectorisation de biomolcules - Institut
Curie / CNRS UMR 176 (Research unit) > IBS - INSTITUT DE
BIOLOGIE STRUCTURALE - UMR 5075 (Research unit) Public funders >
ANR, Agence Nationale de la Recherche Project leader ROUSSELLE
Patricia Entity: Laboratoire de Biologie Tissulaire et Ingnierie
Thrapeutique - Institut de Biologie et Chimie des Protines - UMR
5305 CNRS UCBL Position: Research Director Address: 7, passage du
vercors 69367 Lyon Email: [email protected] Phone: +33
(0)4 72 72 26 39 Objectives The proposal CHEMISPIKE aims at:
Dissecting the molecular mechanism underlying the syndecan-1
mediated cell adhe sion cascade, Identifying, among the hits coming
from the screening, specific syndecan-1 inhibitors and determine
their intracellular target, Characterizing/optimizing the selected
molecules through medicinal chemistry and test their potential
anti-tumoral properties in vitro using colon and breast carcinoma
cells Solving the structure of the laminin 332 domain involved in
syndecan-1 interaction using X-ray crystallography. Year Start:
2012 Call for projects: ANR (ANR2011 - P2N) Global budget: 10 k
Public funding: 520 k Duration: 36 months Stage of development at
the beginning of the project: Basic research Accredited by:
Lyonbiopole Abstract As exposure to environmental carcinogens may
increase the risk of sporadic breast cancers, it is important to
decipher the role of environmental carcinogens in the chronic
carcinogenesis of human breast epithelia and their contribution in
the development of this cancer. The CLARENCE project aims to use a
tumor progression model of breast cancer that mimics progression
from the benign to the premalignant status and from the
premalignant to the malignant status to study the impact of chronic
and low-dose exposure to two environmental carcinogens. Strategic
business area Innovative assets The major innovative asset of
Chemispike relies on the fact that syndecan-1 inhibitory molecules
were tested in the context of a cell adhesion assay. Molecules were
selected upon their potential to inhibit syndecan-1 mediated
adhesion to laminin and were shown to operate at the intracellular
level most likely targeting the syndecan-1 signaling cascade. In
addition to its impact in oncology, this project could have an
impact in the treatment of infectious diseases as syndecan-1 is
known to be an important receptor/co-receptor involved in some The
chemispike project aims at identifying and developing bacterial and
viral pathogens, mediating small molecules with potential to
inhibit the interaction of the infection. cell adhesion receptor
syndecan-1 expressed at the surface of Application fields Health
& Environment / Oncology Technological approaches / Keywords
Biobank / Cell model / Animal model / Minimally Invasive
Technologies epithelial cells with proteins of the
microenvironment. Actual Outcomes The major innovative asset of
Chemispike relies on the fact that syndecan-1 inhibitory molecules
were tested in the context of a cell adhesion assay. Molecules were
selected upon their potential to inhibit syndecan-1 mediated
adhesion to laminin and were shown to operate at the intracellular
level most likely targeting the syndecan-1 signaling cascade. 16
LYONBIOPOLE In addition to its impact in oncology, this project
could have an impact in the treatment of infectious diseases as
syndecan-1 is known to be an important receptor/co-receptor
involved in some bacterial and viral pathogens, mediating
infection. > Scientific publications 8 > 8 ommunications in
international 1 C congresses > 2 PhD Perspectives PARTNERS
Partners > partement Cancer et D Environnement, Centre Lon Brard
(Research unit) > RCL, Inserm U1052-CNRS 5286 C (Research unit)
> Institut de Recherche en L Cancrologie de Montpellier (IRCM
U896) (Research unit) > aboratoire HydroSciences L Montpellier
(UMR5569 CNRS,IRD, UM1, UM2) (Research unit) > lateforme de
Recherche en P Toxicologie Environnementale et Ecotoxicologie
(Research unit) Voir le sitePROFILEXPERT (Company) Public funders
> NR, Agence Nationale de la A Recherche Project leader COHEN
Pascale Entity: Dpartement Cancer et Environnement, Centre Lon
Berard Position: Professor Address: 28, rue Lannec 69373 Lyon
Email: [email protected] Phone: +33 (0)4 78 77 28 94
Objectives o identify and establish an original in vivo or in vitro
biological model that could allow T the study of candidate
environmental molecules o investigate the cellular, molecular,
epigenetic, transcriptomic and metabolomic T impacts of chronic and
low-dose [B(a)P and/or BPA] exposure in a tumor progression model
of breast cancer o perform in vivo investigation T o identify
putative human candidate biomarkers of BPA and/or B(a)P exposure
and T putative molecular targets that could be used by agents to
overcome environmental exposure Innovative assets The overall
novelty of the research program is the strategy focused on the
combination of two environmental molecules possessing two different
mechanisms of toxicity and tested in a model of tumor progression
in breast cancer. This is in contrast with classical approaches
aimed at testing each environmental molecule individually, thus
overlooking the potential cross-talk and potentialization between
different environmental molecules. Characterization -Optimization
Establishment of exposed cell mini-bank > Preclinical assay
realization > Search for private financing > Search for
public funding Actual outcomes Perspectives > 2 Communications
in international congresses > Scientific publications
LYONBIOPOLE 17 ongoing projects Year Start: 2009 Call for projects:
ANR (ANR2008 - PCV) Global budget: 2 020 k Public funding: 625 k
Duration: 56 months Stage of development at the beginning of the
project: Basic research, Discovery, Accredited by: Lyonbiopole
Cellular, molecular and genomic investigation of chronic
environmental exposure of low doses pollutants in a tumour
progression model of breast cancer
10. COMBITOX NEW Year Start: 2012 Call for projects: ANR
(ANR2011 - ECOTECH) Global budget: 2 969 k Public funding: 999 k
Duration: 36 months Stage of development at the beginning of the
project: Prototype Accredited by: Lyonbiopole ongoing projects
Abstract The objective of this project is the conception of a
multi-parametric instrument for continuous measurement of toxic
compounds. Biosensors modules will be developed and optimized
starting from technologies developped and transferred to an in-line
measurement device. A prototype will be set up in a water pumping
station. A marketing enquiry will help us to adapt the performance
of the device according to the requirement of water-management
professionals. The device will allow the detection of bio-available
toxic compounds as well as harmful microorganisms which can impact
human health. Strategic business area Other Application fields
Health & Environment Technological approaches / Keywords
Environmental biology PARTNERS Partners > CNRS (Research unit)
> Laboratoire de bionergtique cellulaire (LBC) (Research unit)
> CEA Cadarache (Research unit) > INSA Lyon (Research unit)
> Ecole des Mines Dals (Research unit) > ap2e (Company)
Public funders > ANR, Agence Nationale de la Recherche Project
leader PIGNOL David Entity: CEA Cadarache Position: Reseach
Director Address: IBEB-LBC-CEA bat. 156 13115 St-Paul-lez-durance
Email: [email protected] Phone: +33 (0)4 42 25 30 60 Objectives
We propose an integrated and transportable device allowing for the
quick detection of numerous pollutants by non-specialists. Our
approach consists in a bio- or chemiluminescente or fluorescent
measure of a biological or biochemical interaction between a
contaminant and a biological recognising element. The objective is
to allow the control of the level of contaminants anywhere, anytime
and by anybody. The project aims at transferring the technologies
developed in our laboratories to a in-line measurement device that
will benefit from the sensitivity and specificity of the
biosensors. Innovative assets The innovative aspect of this project
is multiple since it offers systems able to provide a very fast
response and can be used by any user. It can be adapted to
different systems to be detected (chemical pollutants,
microorganisms and toxins) and aims to: Check upstream of a water
treatment plant; Monitor water quality of a wastewater treatment;
Ensure the control of sensitive river corresponding to drinking
water storage; Control of drinking water networks; Monitor the
quality of water used for raising aquatic animals; Prevent emerging
threats such as bioterrorism. Discovery and design of new antigens
for vaccines conferring broad spectrum protection against
leptospirosis Year Start: 2012 Call for projects: FUI (FUI AAP14)
Global budget: 6 116 k Public funding: 1 908 k Duration: 36 months
Stage of development at the beginning of the project: Basic
research, Discovery Accredited by: Lyonbiopole Abstract
Leptospirosis is a neglected bacterial disease affecting humans and
various mammals with a high mortality rate. Vaccination is the most
effective prevention strategy but most current vaccines do not
protect against new serovars emerged in the past few years.
COVALEPT will isolate and characterize virulent circulating strains
from the field. Protective antigens conserved amongst Leptospira
will be identified by bioinformatics, produced in native or
recombinant form and assessed in vivo in order to conceive a broad
spectrum vaccine for multi-species applications. Strategic business
area Application fields Infectious diseases Technological
approaches / Keywords Bioinformatics / Software / Biomanufacturing
/ Genetics / Genomics / Vector vaccine / Antigen discovery Actual
outcomes Our prototype for the detection of toxic compounds could
be used in the future in several environmental sites, and will be
first tested out of the lab in the following months in a water
treatment station COMBITOX Actual Outcomes The project started a
little over a year and advance in a highly satisfactory manner. The
actions implemented in recent months after the original plan and
the results match the expected 18 LYONBIOPOLE milestones. This
should allow us to obtain a functional prototype in the next 6
months. > Prototype 1 Construction of a prototype for the
biodetection of heavy metals (Cd, Hg, As, Ni, Co), toxins and
bacteria is in progress. Perspectives > Search for public
funding Funds for the miniaturization of our prototype will be
researched at the end of the project > 1 PhD > 2 Job
creations in Rhne-Alpes region > 4 Press releases >
Investissements: Thermocycler, DNA extractor, Microscope
Perspectives > Search for technologies > Clinical trial
realization PARTNERS Partners > erial (Company) M > enostar
(Company) G > ALIXAR (Company) C > XTherapeutics (Company) P
> nstitut Pasteur - Unit de Biologie I des Spirochtes (Research
unit) > etAgro Sup - Laboratoire des V Leptospires (Research
unit) Public funders > onseil gnral de lIsre C > EDER
Rhne-Alpes F > onds Unique Interministriel (FUI) F DGCIS/Oso
> rand Lyon G > renoble Alpes Mtropole G > ille de
Grenoble V Project leader Cupillard Lionel Entity: Merial Position:
R&D Leader Address: 254, rue Marcel Mrieux R&D BP 39H -
69007 Lyon Email: [email protected] Phone: +33 (0)4 72 72
55 27 ongoing projects Design of a multi-parametric instrument
continuous measurement of toxic compounds COVALEPT Objectives
Providing: leptospirosis vaccine candidate for dogs and potentially
other species, A ioinformatics, molecular and biochemical tools
that could accelerate the discovery B and development of other
bacterial antigen targets Innovative assets ew broad-spectrum
vaccines against N Leptospirosis; ollection of virulent circulating
Leptospira strains C directly isolated from infected dogs; ew
genetic tools for Leptospira, insights into N biology and virulence
mechanisms of atypical bacteria; ew software and services offers
for bacterial N protective candidates selection and antigen design;
ationally designed extraction reagents based on R chemistry of
native membrane proteins; ptimized host/vector couples for
recombinant expression of membrane proteins O > Product
marketing TESTIMONY Nathalia BOMCHIL, Merial Broad-spectrum
vaccines against Leptospirosis, a worldwide severe human and
veterinary infection, would constitute a key commercial and
sanitary advantage on the market. This scientific and technical
challenge requires the input of complementary expertise. COVALEPT
was built to achieve such synergy: the partners met regularly
during one year, from initial brainstorming to final submission. We
had the chance to be supported by Lyonbiopole who helped us define
the deliverables and organization of the project. We designed a
win-win setup, in which each partner develops innovative
technologies in its core-business while the leader benefits from
the multidisciplinary environment. The importance of the zoonosis
and the strong collaborative mindset probably led to the funding of
the project. LYONBIOPOLE 19
11. DDELPHES An innovative automated system for online
detection of microorganisms in water Year Start: 2011 Call for
projects: FUI (FUI AAP11) Global budget: 3 271 k Public funding: 1
149 k Duration: 36 months Stage of development at the beginning of
the project: Basic research Accredited by: Lyonbiopole
Co-accredited by: Axelera, Risques Partners > Bertin
Technologies (Company) > Cylergie, Centre de recherche de Cofely
(Company) > CEA LETI (Research Unit) > Ademtech (Company)
> Amoba (Company) > Suez environnement (Company) Public
funders > Fonds Unique Interministriel (FUI) DGCIS/Oso >
Grand Lyon > FEDER PACA Project leader TROUCHET Daniel Entity:
Bertin Technologies Position: Senior Expert Address: 10, bis Avenue
Ampre 78180 Montigny-le-Bretonneux Email: [email protected] Phone:
+33 (0)1 39 30 60 34 ongoing projects Abstract Objectives Three
decrees respectively in 2004 and 2010, impose a follow-up of
Legionella in wet cooling towers and sanitary water network. The
classic strategy which consists in increase organic and inorganic
substance amounts cannot be an answer to the microbiological
treatment. Then, DDELPHES proposes to develop a full automated
system, enabling analysis of the micro-organisms present in water
(bacteria and amoeba). This system will make possible to carry out
an uninterrupted follow-up of the microbiological quality of water
and, by consequence, better control the treatment application. The
objectives are the development of standalone subsystems for
Sampling and concentration of the water, DNA preparation and
automated qPCR on a chip, and then the development of a standalone
integrated device (demonstrator) allowing rapid and insitu analysis
of micro- organisms in water systems. The Microbial targets are
Legionella spp and pneumophila, Amoebae (Naegleria fowleri,
Willaertia). The device will allow for automated water sampling,
on-line analysis and results sending within a few hours. It will be
tested on field with a view to industrialization and marketing of a
product. Localized delivery of chemotherapy induced by ultrasound
Year Start: 2013 Call for projects: Proof of concept CLARA Global
budget: 1 061 k Public funding: 435 k Duration: 24 months Stage of
development at the beginning of the project: Preclinical
development The DDELPHES project aims to develop a standalone, in
situ and fast analysis system based on qPCR. Up to now, such
devices do not exist. The project will be based on a combination of
advanced technologies involving biology, automation and
miniaturization in order to obtain a compact, sensitive and robust
equipment. Amoeba real time monitoring could allow for green
treatment using them as biological agents. Partners > SERM U1032
(LabTAU) (Research IN unit) > aviskills (Company) C > entre
Lon Brard (Healthcare unit) C Public funders > onseil gnral de
Rhne C > rand Lyon G Abstract Acoustic cavitation can be defined
as the dynamic of bubbles of vapor under an ultrasonic field. It is
clearly established in the literature that cavitation favors
transmembrane penetration of molecules and increases the ratio
efficacy / toxicity of chemotherapies. The project would allow
testing on preclinical models a therapeutic prototype combined with
conventional drugs and performing clinical pilot study on selected
targets. Strategic business area Innovative assets PARTNERS
Application fields Oncology (Breast, Sarcoma) Technological
approaches / Keywords Chemotherapy / Ultrasound Project leader
LAFON Cyril Entity: INSERM U1032 (LabTAU) Position: Senior
investigator - Team leader Address: 151, cours Albert Thomas 69424
Lyon CEDEX 03 Email: [email protected] Phone: +33 (0)4 72 68 19
20 Objectives The present project aims at developing an ultrasonic
medical device that could potentialize chemotherapy for the
treatment of various cancers. Negative hormone receptors breast
cancer (207 000 cases/year) and soft-tissue sarcoma (4000
cases/year) have been identified as potential targets. Both cancers
do not respond well to available treatments. The conventional
chemotherapies demonstrated their relative efficacy but remain
associated to a significant systemic toxicity. The non specific
distribution of the cytotoxic drugs results in reduced therapeutic
efficacy and side effects. Innovative assets INSERM filed a patent
on a method for stabilizing ultrasonic cavitation. The company
CAVISKILLS SAS licensed this patent and aims at exploiting this
idea by developing a clinical device for delivering
chemotherapeutic drugs locally. The goal is to enhance the efficacy
the treatment and reduce associated side effects. The treatment is
completely non invasive and performed under ultrasound imaging
guidance. Strategic business area Health & Environment
Application fields Health & Environment Technological
approaches / Keywords Biochips Functional decomposition DDELPHES
tasks Actual Outcomes Up to now a standalone concentration device,
a sample preparation module and a qPCR module have been developed
at the prototype stage. Uptake and extraction protocols and kits
have been developed and tested. The limits of detection obtained
are better than required for amoeba. For legionella, they are good
when bacteria are in clean water but not with cooling tower water,
which is an important issue to solve. > Product, prototype,
service 1 1 concentration module 1 sample prep module+ 1 qPCR
module 20 LYONBIOPOLE > Sustainable Job creations at the 2 end
of the project Perspectives > Product marketing Automated
concentration module TESTIMONY Daniel TROUCHET, Bertin Technologies
The DDELPHES project addresses a major public health concern (water
microbial contamination) and the consortium balance between
research, industry and end-users, ensures to have at project
disposal the available key technologies necessary to reach its
goals, which were the key points for the funding of the project.
The partnership has been built mainly through networking and it was
already partially set via former projects collaborations when
Bertin joined it. Lyonbiople participated in the consortium final
elaboration, and in particular they helped to find a key partner
(Ademtech) and to define the work program. They also contributed to
keep the development with a view of industrialization and marketing
of a product and facilitated scientific exchanges between experts
during the project progress. Schematic of the Caviskills clinical
device for treating soft tissues sarcomas Actual outcomes TESTIMONY
> Products, prototypes, services > Clinical trials > Press
release Cyril Lafon, senior researcher at LabTAU INSERM Unit For
the past few years, LabTAU laboratory has worked in close
relationship with the CLB (Lon Brard Cancer Center), particularly
on the clinical application of ultrasounds, and with the CRCL
(Cancer Research Center of Lyon) on the transfection theme. In
2011, CLARA allowed its collaborations to catalyze by putting in
contact the founders of Caviskills. When CLARA financed CLUB, an
emerging Perspectives > Set-up of a new R&D project >
Clinical trial realization > Product marketing > Search for
private financing > Search for public funding project, partners
were able to carry out a preliminary market study, thus allowing us
to validate the interest for the technology and to select clinical
targets. The interest of the collaboration proposed via the CLARA
Proof of Concept program is to be able to bring together
complementary regional actors essential to the implementation of
such a pluridisciplinary project (academics for engineering
sciences and biology with clinicians and industrials). LYONBIOPOLE
21 ongoing projects PARTNERS DELICHIUS NEW
12. DIVRESCUE Doc Calipso Development of a pronostic biomarker
for immuno-depressed cancer patients and of the associated
immuno-reconstitution treatment PARTNERS Partners > Cytheris
(Company) > Centre Lon Brard (Healthcare unit) > ImmunID
Technologies (Company) Public funders > FEDER Rhne-Alpes >
Fonds Unique Interministriel (FUI) DGCIS/Oso > Rgion Rhne-Alpes
> Rgion Ile-de-France ongoing projects Abstract Studies in
metastatic breast cancer patients have demonstrated that reduced T
cell receptor diversity (divpenia) combined with lymphopenia was
associated with a poor overall survival. The project will evaluate
the immune status of each patient through the measure of
combinatorial diversity (ImmunTraCkeR test) and ALC (absolute
lymphocyte count) in order to detect immunodeficient
lympho-divpenic patients. Eligible lympho-divpenic patients will
benefit of an immunotherapy allowing the regeneration of an
immunocompetent immune system through administration of
glycosylated cytokine IL-7. Project leader MANUEL Manuarii Entity:
ImmunID Position: Chief Scientific Officer Assistant Address: 17,
rue des Martyrs 38000 grenoble Email: [email protected] Phone:
+33 (0)4 38 78 57 70 Objectives Utilizing an innovative diagnostic
and therapeutic approach, DivRescue will develop a new way to treat
cancer patients, enabling assessment of their immune deficit
characterized by lymphopenia and divpenia and correcting it with
interleukin-7. We expect this approach to ultimately lead to an
increase in patient survival. Innovative assets The partners will
combine their cellular, molecular and bio-computing technologies
with their immunological and clinical skills in order to treat
patient immune deficits and demonstrate the impact of immune
response on clinical response. Targeting an increase in patient
survival, this theragnostic approach is the first of its kind in
the world. Strategic business area Year Start: 2010 Call for
projects: Proof of concept CLARA Global budget: 1 256 k Public
funding: 627 k Duration: 36 months Stage of development at the
beginning of the project: Discovery Today, the early diagnosis of
small tumors is possible through the use of screening biological
tests and medical imaging. In most cases, surgical resection of
tumors is the primary means of therapy. Given the poor tolerability
of standard surgical treatment, new techniques have been developed.
Of these, laparoscopic surgery limits the morbidity of the incision
and percutaneous treatment avoids dissection of tissues. However,
laparoscopic technique remains limited in terms of accuracy and
percutaneous treatment requires constant radiation monitoring and
protection. Strategic business area Actual Outcomes Perspectives
> Products, prototypes, services > Clinical trials > Press
release > Set-up of a new R&D project > Clinical trial
realization > Product marketing > Search for private
financing 22 LYONBIOPOLE > Search for public funding Project
leader COLOMBEL Marc Entity: Centre Hospitalier Universitaire de
Lyon Position: Urologist Surgeon Address: Hpital Edouard Herriot 5,
place dArsonval - 69003 Lyon Email: [email protected]
Phone: +33 (0)8 99 96 06 56 Objectives Our project is to introduce
a new concept of robots that will automatically locate a treatment
probe close to the tumor using an innovative three-dimensional
navigation robot that is guided by a tracking sensor implanted in
the body and/or that uses image analysis to process. Innovative
assets The latest innovations in ablative technologies such as
cryotherapy or high intensity focused ultrasounds have been
successfully adapted to treat solid tumors. These techniques aimed
at focally destroy prostate, kidney, brain, liver are guided by
ultrasound, CT or MRI which are unsatisfactory given a lack of
precision and the risk of radiation exposure. The innovative asset
of this project is the design a three-dimensional navigation robot
capable of targeting a solid tumor with a treatment device taking
into account body motion (i.e. breathing) in real-time with an
accuracy below 1 mm. DocCalipso three-dimensional navigation robot
1996-2013 Adept Technology, Inc. ImmunID Forecast Station IFS for
the detection of Divpenia Actual outcomes Partners > dept
(Company) A > ospices Civils de Lyon (Healthcare H unit) Public
funders > EDER Rhne-Alpes F > Rgion Rhne-Alpes Abstract
Application fields Oncology Technological approaches / Keywords
Drug delivery system / Imaging (medical) Application fields
Oncology Technological approaches / Keywords Genetics / Genomics /
Immunotherapy (PCR and NGS) PARTNERS If successful, this generation
of surgical tools will mark a new step in medical engineering for
its remarkable precision, and the possibility to adapt the system
to many applications in cancer treatment (ablation, injection,
tracking..). This projects was made realizable by the merging of
our two clinical and robotic engineering and very motivated teams.
We seized this unique opportunity to realize our dreams that
robotic assisted tracking will represent the next breakthrough in
cancer treatments. Perspectives > Preclinical assay realization
Starting by the end of 2013 > Proof of concept 1
Three-dimensional navigation robot LYONBIOPOLE 23 ongoing projects
Year Start: 2011 Call for projects: FUI (FUI AAP11) Global budget:
4 395 k Public funding: 2 572 k Duration: 42 months Stage of
development at the beginning of the project: Clinical trials
Accredited by: Lyonbiopole Co-accredited by: Medicen Paris Region
Robot navigation for tumor focal therapy
13. DORGAN EMER-FAB Year Start: 2012 Call for projects: ANR
(ANR2011 - TECSAN) Global budget: 1988 k Public funding: 875 k
Duration: 36 months Stage of development at the beginning of the
project: Preclinical development Accredited by: Lyonbiopole ongoing
projects Abstract In external beam radiotherapy and brachytherapy,
verification of the delivered dose at the target volume during each
radiotherapy session and for the whole treatment is a key issue for
quality assurance. To be reliable, this dosimetric monitoring must
be independent of the dose delivering system and obtained in
real-time. In interventional radiology, the skin entrance dose must
be determined in real-time. Also emerging radiotherapy modalities
require reliable dosimetry. The DoRGaN project proposes to develop
a multi-channel dosimetry system based on the use of GaN
radioluminescent transducers. Strategic business area Application
fields Oncology / Medical physics Technological approaches /
Keywords Minimally Invasive Technologies / Radiotherapy / Dosimetry
Actual Outcomes Real-time dosimetry system prototypes for
independent in vivo dose assessment and efficient quality assurance
have been developed for brachytherapy and small field radiotherapy.
This is an important step towards dose guided procedures for best
clinical outcome with the lowest toxicity level. The new developed
quality assurance instrument is relevant for patient safety in
current procedure and becomes of key importance when new technology
and practice are introduced at the same time. 24 LYONBIOPOLE
PARTNERS Partners > Institut des Nanotechnologies de Lyon,
UMR5270 (Research unit) > Hospices Civils de Lyon (HCL) -
Service de Radiophysique et Radiovigilance (Healthcare unit) >
CHU de Grenoble - Service de Radiothrapie (Healthcare unit) >
DOSILAB (Company) Public funders > ANR, Agence Nationale de la
Recherche Project leader PITTET Patrick Entity: Institut des
Nanotechnologies de Lyon Position: Research Engineer Address: Bt.
Brillouin, 43, Bd du 11 novembre 1918 - 69622 Villeurbanne Email:
[email protected] Phone: +33 (0)4 72 44 62 82 Objectives
Support ongoing work on real-time in situ dosimetry for demanding
applications such as IMRT with small irradiation fields and high
dose gradients Iinvestigate GaN dosimetry potential for emerging
therapies such as hadrontherapy Develop real-time in vivo dosimetry
for PDR and HDR brachytherapy esign GaN dosimeter arrays to detect
the maximum skin dose area during D interventional radiology
procedures in real-time rovide an user-friendly system for QA of
dose delivery systems and giving clear and P real-time patient dose
exposure data to the medical staff at an attractive cost. >
Products, prototypes 2 Brachytherapy instrumented phantom
(currently setup at the HCL) - Small field radiotherapy
instrumented phantom (in manufacturing) > Scientific
publications 2 > Communications in international 5 congresses
> 1 PhD > 1 License Agreement An exclusive licence agreement
on the SECURIDOSE technology has been signed between DOSILAB on one
side and Universit Lyon 1, Universit Joseph Fourier, CHU de
Grenoble, CPE Lyon on the other side Year Start: 2011 Call for
projects: FUI (FUI AAP10) Global budget: 2 486 k Public funding: 1
357 k Duration: 36 months Stage of development at the beginning of
the project: Preclinical development Accredited by: Lyonbiopole
Abstract The project is dedicated to the development and the
regulatory validation of an original and complete model for the
development and production of immunotherapeutic solutions against
the CCHF virus (Crimean Congo Hemorrhagic Fever). The virus causes
severe hemorrhagic fever. It occurs in Africa, Eastern Europe and
Turkey, where it represents, in the absence of any satisfactory
therapeutic solution, a public health issue for those who are
directly exposed, in particular healthcare workers. Strategic
business area Innovative assets The DoRGaN project develops real
time dosimetric systems based on the patented Securidose
technology. The GaN radioluminescent transducer yields a high real
time signal from a small detecting volume and is suitable for use
in small fields and for high dose gradients. New instrumented
phantom prototypes have been designed and characterized for quality
assurance during brachytherapy and small field radiotherapy for
independent real time treatment verification. Development,
regulatory validation and production of new specific polyclonal
immunoglobulin against the Crimean Congo Hemorrhagic Fever Virus
(CCHFV) Application fields Infectious diseases Technological
approaches / Keywords Immunotherapy / Vector vaccine PARTNERS
Partners > ABENTECH (Company) F > anofi Pasteur (Company) S
> aboratoire Jean Mrieux P4 Inserm L (Research unit) > entre
international de recherche C en infectiologie (CIRI) Inserm
U1111CNRS UMR5308 (Research unit) Public funders > onds Unique
Interministriel (FUI) F DGCIS/Oso > rand Lyon G Project leader
LEPINE Bertrand Entity: Fabentech Position: CEO Address: 321,
avenue Jean-Jaures 69007 LYON Email: [email protected]
Phone: +33 (0)4 37 70 69 67 Objectives dentify and select the
appropriate CCHF viral strain among various circulating I species.
evelop CCHF antigens to be used for horse hyperimmunisation
(VLP...) D alidate a Proof of concept both in vitro (development of
specific in vitro assays) and in V vivo (development of an animal
model for CCHF infection by the BSL-4 laboratory). evelop a GMP
assay to quantify the activity of specific anti-CCHF antibodies for
the D release of clinical and commercial batches. roduction of
specific polyclonal immunoglobulin against the CCHF virus. P
Innovative assets Development of Virus-Like-Particule CCHF DNA
vectorization of VLP Production and purification of specific
anti-CCHFV immunoglobulins Development of in vitro and in vivo
tools for CHCF laboratory-studies Instrumented phantom prototype
for brachytherapy quality assurance Pierrick Guiral > 1 Job
creation in Rhne-Alpes region Perspectives > Set-up of a new
R&D project > Preclinical assay realization > Clinical
trial realization > Product marketing Actual outcomes Validate
the initial proof-of-concept on anti-CCHFV F(ab)2 by in vitro
seroneutralization assays and in vivo assays on IFNAR-/- mice.
evelop a specific validated ELISA and D establish a correlation
between ELISA values and F(ab)2 efficacy evelop VLP CCHF based
tools such as D ELISA, or cellular entry tests Vectorization of
CCHF VLP for DNA immunization in horses > Products, prototypes,
services > Proof of concept Perspectives > Search of
partnership > Search for technologies > Preclinical assay
realization > Search for private financing LYONBIOPOLE 25
ongoing projects Dosimetry by Radioluminescence of GaN for in vivo
real-time patient dose assessment for radiotherapy, brachytherapy
and interventional radiology
14. ETICS NEW Accelerated development program of immunotherapy
solutions against emerging diseases Year Start: 2012 Call for
projects: ISI Oso Global budget: 26 620 k Public funding: 9 507 k
Duration: 63 months Stage of development at the beginning of the
project: Discovery Accredited by: Lyonbiopole ongoing projects
Abstract The EMER-IT program proposes to build a complete value
chain for developing, producing and commercializing innovative
specific polyclonal immunoglobulins against at least four emerging
pathogens (such as Encephalitis of Nipah, Ebola hemorrhagic fever
or Lassa, SARS). These specific polyclonal immunoglobulins will be
produced with an ambitious immunization approach that will be
implemented by using synthetic nanovectorization of antigens in DNA
form. The proof of concept of efficacy of each specific polyclonal
immunoglobulin product will then be established. PARTNERS Partners
> ABENTECH (Company) F > n-Cell-Art (Company) I > IRI -
equipe Enveloppes virales et C ingniere des rtrovirus (Research
team) > Laboratoire Jean Mrieux P4 - Inserm (Research unit) >
Institut du thorax (Inserm U915) (Research unit) Public funders
> Oso / BPI France Project leader VACHER Laurent Entity:
Fabentech Position: R&D programs leader Address: Immeuble
Domilyon, 321, Avenue Jean Jaures - 69007 Lyon Email:
[email protected] Phone: +33 (0)4 37 70 67 67 Objectives
Identify and select the appropriate strains of highly pathogenic
viruses according to epidemic needs and health risks Develop,
manufacture and commercialize specific polyclonal immunoglobulins
against emerging infectious diseases Develop an innovative antigen
approach using synthetic DNA nano-vectorization of VLP to be used
for horse hyperimmunization against any emerging pathogens targeted
Implement a pilot plant for the GMP production of specific
polyclonal immunoglobulin products Develop a new DNA-based
veterinary vaccine for horses by In-Cell-Art Innovative assets
Strategic business area Application fields Infectious disease
Technological approaches / Keywords Immunotherapy DNA-based antigen
nano-vectorization Virus-Like Particles (VLP) nano-vectorization
Innovative platform for the develoment and flexible production of
specific polyclonal immunoglobulins Single-use based pilot plant
for GMP production of immunoglobulins Evolved Tissue Inspired Cell
Systems Year Start: 2011 Call for projects: ISI Oso Global budget:
14 400 k Public funding: 7 600 k Duration: 60 months Stage of
development at the beginning of the project: Preclinical
development Accredited by: Lyonbiopole PARTNERS Partners > YTOO
Cell Architects (Company) C > ellectis (Company) C > EA iRTSV
France (Research unit) C Public funders > so / BPI France O
Entity: CYTOO SA Position: CEO Address: MINATEC -BHT-B52 - 7 Parvis
Louis Nel - BP50 - 38040 Grenoble Email: [email protected] Phone:
+33 (0)4 38 88 47 05 Abstract The use of more relevant cells during
pharma-tox screening would help the search for new drugs and pick
up toxicity issues earlier. Conversion however to 3D cell culture
represents a huge challenge as it is badly adapted to the
constraints of automated screening and high content imaging and
analysis. The ETICS program aims at providing an alternative
option: combine the potential of adhesive micropatterns, soft
substrates and standardized fluorescent cell lines enabling more
physiological cellular models and reliable high content imaging and
analysis optimized for pharma-tox drug screening. Project leader
LEBOZEC Marc Objectives The ETICS program aims to provide cell
models that are more physiologically relevant as well as better
suited for high content imaging and analysis (HCA) than
conventional methods. This will be obtained by cultivating cells on
micropatterned surfaces with softness properties similar to the
original tissue. Specific fluorescent cells lines expressing
standardized levels of fluorescent proteins will be used to
demonstrate that more meaningful and reproducible experimental
results are obtained under these conditions. Strategic business
area Application fields All pathologies area Technological
approaches / Keywords Cell model / Genetics / Genomics A model
illustrating the combination of soft surfaces, adhesive
micropatterns and fluorescent cells Human epidemics recorded for 6
emerging diseases Actual Outcomes > Products, prototypes,
services > Clinical trials > Product on the market > Job
creation in Rhne-Alpes region 26 LYONBIOPOLE Perspectives >
Search of competences > Product marketing LYONBIOPOLE 27 ongoing
projects EMER-IT
15. FEMTOKINE FLUMA Year Start: 2010 Call for projects: FUI
(FUI AAP10) Global budget: 2 170 k Public funding: 1 267 k
Duration: 48 months Stage of development at the beginning of the
project: Clinical trials Accredited by: Lyonbiopole Co-accredited
by: Eurobiomed ongoing projects Abstract PARTNERS Partners >
DICIA BIOTECHNOLOGY (Company) IN > ospices Civils de Lyon
(Healthcare H unit) > xCell (Company) T > INGULEX (Company) S
Public funders > FEDER Rhne-Alpes > Fonds Unique
Interministriel (FUI) DGCIS/Oso > Grand Lyon > Rgion
Rhne-Alpes Project leader LEGASTELOIS Stphane Entity: Indicia
Biotechnology Position: CEO Address: 33, avenue de la Californie
69600 Oullins Email: [email protected] Phone: +33 (0)4 72 39
14 92 Different conformations of the Influenza virus matrix protein
M1 and their role during entry and budding Year Start: 2011 Call
for projects: ANR (ANR2010 - BLANC) Global budget: 314 k Public
funding: 212 k Duration: 36 months Stage of development at the
beginning of the project: Basic research Accredited by: Lyonbiopole
Biobanking: patients in clinical remission induced by surgical or
drug therapeutic management and patients under cellular therapy
Immunoassay validation following FDA guidelines New immuno-assay
development Kits adaptation for intestinal biopsy diagnostic
Samples analysis to validate immunological biomarkers as predictors
of clinical recurrence of CD: - T cell analysis in blood and in
biopsies - Determination of immunological markers in plasma and
biopsies - Measurement of inflammation markers in serum and stools
Influenza viruses contain three major subviral components: the
envelope, matrix protein 1 (M1) and the core harboring the RNA
genome. M1 forms a shell beneath the viral envelope that sustains
the virion architecture. Upon acidification of the virion within
the endosomes, M1 undergoes a conformational change resulting in
disassembly of the M1 matrix, virus uncoating and the release of
the vRNP into the host cell. The project aims to elucidate the
structural basis of M1 activation of Influenza virus assembly and
budding and establish the exact roles of M1 during these processes.
Strategic business area Innovative assets Strategic business area
Application fields Autoimmune diseases Technological approaches /
Keywords Biobank / Immunomonitoring High sensitive immunoassays for
the prediction of relapses of Crohns disease and therapeutic follow
up. Clinical validation of biomarkers Technical development and
clinical validation of immunoassays. Application fields Infectious
diseases Technological approaches / Keywords Structural Biology The
accuracy of immunologic biomarkers to predict the relapse of CD
might be superior to that of inflammatory markers and requires
ultrasensitive methods for immunomonitoring immune responses.
Actual Outcomes testominy > 1 Product, prototype, service >
Communication in international 1 congress > License Agreement 1
> Sustainable Job creations at the 2 end of the project > 1
Job creation in Rhne-Alpes region > 1 Start-up Creation Creation
of Singulex Europe subsidiary in 2010 > Increase in turnover
Stphane LEGASTELOIS, Indicia Singulex and Indicia signed a
partnering agreement by which Indicia acquired the rights to use
the new Singulexs Erenna Immunoassay platform. The technology is
dedicated to the measurement of cytokines and other biomarkers at
the femtogramme level. This level of performance makes possible the
monitoring of immunological disorders in human inflammatory
diseases such as Crohn disease 28 LYONBIOPOLE Femtokine was built
around partners having access to human patients suffering from
Crohn disease. Hospices Civils de Lyon and TxCell were both
conducting clinical trials on this pathology. Singulex R&D
Europe provides the technology while Indicia offers the Immunoassay
plateform and sample analysis. Lyonbiopole gave significant support
to identify partners, prepare the project submission file and give
assistance in the follow-up of the project Partners > nit of
Virus Host Cell Interactions U UMI 3265 (Research unit) Public
funders > NR, Agence Nationale de la A Recherche Project leader
WEISSENHORN Winfried Entity: Unit of Viral Host Cell Interaction
(UVHCI) Position: Professor, team leader Address: 6, rue Jules
Horowitz, BP181 F-38042 Cedex 9 Grenoble Email: [email protected]
Phone: +33 (0)4 76 20 72 81 Abstract Femtokine aims to develop
tools dedicated to the identification and validation of
immunological biomarkers that are specifically involved in Crohn
Disease (CD), a chronic inflammatory pathology of the digestive
tract. The disease suffers from a lack of non invasive biomarkers
that are needed to assess the severity of the pathology, together
with the efficacy and toxicity of therapeutic treatments. The
project consists of generating a bank of samples from CD patients,
measuring and validating a panel of biomarkers based on an unique
and ultra-sensitive proteomic plate-form. Objectives PARTNERS
Objectives stablish the cloning, expression and purification of
full-length M1 protein derived from E different Influenza strains.
creen for crystallization conditions for full-length M1 protein at
neutral and low pH. To S facilitate crystallization of M1 in
different conformations we will generate conformation specific
llama VHH nanobodies and try co-crystallization with known complex
partners. Determination of high resolution structures of
full-length M1protein. stablish conditions that allow us to study
protein coat formation by M1 in vitro. E Innovative assets The
project concentrates on the structural biology of the complete
viral matrix protein M1. We hypothesize that the crystal structure
of a complete M1 protein will provide important insight into its
function during uncoating and during assembly and budding. Our work
might provide novel insight into the ESCRT-independent budding of
influenza virus and the structural details of M1 at neutral and low
pH will hel
