Gianfranco GROMPONE Head of Microbiota Unit … GROMPONE Head of Microbiota Unit Paris - France September 2015 CONFIDENTIAL 1 MICROBIOLOGY TECHNOLOGY INSTITUTE BIOASTER Microbiology

MICROBIOLOGY TECHNOLOGY INSTITUTE

BIOASTER – CAMPUS FRANCEGianfranco GROMPONEHead of Microbiota UnitParis - France

September 2015

1CONFIDENTIAL


BIOASTER Microbiology Technology Institute

2

Expanding Creativity, Adding Value

One collaborative culture

Onefocused approach

Onemission

For the benefit of patients

Microbiology in health and diseases

Solving technology bottlenecks

Going beyond boundaries & disciplines

Through creativity, agility, and quality

CONFIDENTIAL


The Planet BIOASTERTechnologies and fields of application

3

IMMUNOMONITORING

DATA MANAGEMENT & ANALYSIS

BIOLOGICAL SAMPLECOLLECTIONS

GENOMICS &TRANSCRIPTOMICS

METABOLOMICS & PROTEOMICS

PROTEIN &EXPRESSION

SYSTEMSENGINEERING

PRE-CLINICAL MODELS & IMAGING

TRANSLATIONALSCIENCES

VACCINES

ANTIMICROBIALS

MICROBIOTA

DIAGNOSTICS

CONFIDENTIAL


Thematic UnitsFighting pathogens, Exploiting microbiota

4

VACCINES

Enhance vaccine’s safety and efficacy

MICROBIOTA

Take full advantage of thehuman microbiota and itscontinuous cross-talk withimmune and neuronal cells

DIAGNOSTICS

Faster, scalable andcomprehensivediagnostics

ANTIMICROBIALS

Overcome hard-to-treat pathogens and multidrug-resistant bacteria

TRANSLATIONAL SCIENCES

Bridging basic discovery with clinical evaluations to support needs of the Industry through transdisciplinary projects

CONFIDENTIAL


Cross InnovationThe new age of innovation

Open innovation

Translational Medicine

Public-private collaboration

Cross innovation

Academic-driven approach

Pragmaticapproach

Industry-driven approach

Shared approach

From the 19 th century to the 1980s

Since the early 1990s

Since the mid-2000s

Today

1 2 3 4

5CONFIDENTIAL


Built on Solid FoundationsMore than a Century of Excellence

BIOASTER Founders

3Public Research Institutions

2Co-foundingleaders

3 Majors of healthcare industry

40+SMEs

6

3 FundingSupports

CONFIDENTIAL


De-risking Innovation Tailor-made Partnerships

7

INDUSTRIAL

De-

riski

ng in

nova

tion

Accelerating discovery

� Need for breakthrough innovation� High attrition rate� High financial risk

BIOASTER

RISK SHARING

INDUSTRIAL PLAYERS

ACADEMIC

CONFIDENTIAL


Laboratories & OfficesTaking research to new heights

8

New building BIOASTER 1 Lyon (Q3 2015): 2 200 m2 labs including P1, P2 and P3 labs and access to the Jean Mérieux laboratory P4. 1 600 m2 offices

Institut Pasteur, Paris600 m2 laboratories including P1 & P2 labs (250m2)

Charles Mérieux & La Doua campuses, Lyon820 m2 (390 m2) including P1 and P2 labs. Access to the Jean Mérieux laboratory P4

CONFIDENTIAL


� Time of

Collaborative R&D ProjectsKey Figures 2014

9

20Projects inexecution

22Projects*with 11 industrial partners

*from inception

� Budget of

1M

An averageper project:

3 years

CONFIDENTIAL

MICROBIOLOGY TECHNOLOGY INSTITUTE 10CONFIDENTIAL

TECHNOLOGY UNITS

MICROBIOLOGY TECHNOLOGY INSTITUTE 11

Biological Sample Collections Bridging the gap between R&D and clinic

CONFIDENTIAL

Healthcare Industrials

Academic network

BIOSPECIMENS

� Ease access to patients & healthy donor samples, microorganism strains and associated metadata (molecular, biological & clinical data)

� Fuel R&D projects with qualified retrospective and prospective samples

� Potentiate biological collection’s value

� Unique network of academic and private sector collections

� Information system� Bioinformatics� Robotics� Experienced CRA� Sample qualification &

characterization

BIOSPECIMENS™

Specimen inventorySpecimen annotationSpecimen characterization Security & compliance

A comprehensive dataexploration workflow

At a glance Strengths Keywords In-house creativity

� A 2.0 web platform, approved by collections holders, to facilitate biological resources demands and initiate new collaborations

MICROBIOLOGY TECHNOLOGY INSTITUTE 12CONFIDENTIAL

� Identify and validate new immune biomarkers

� Immune response monitoring

� Development of tools for diagnostic applications

� State-of-the-art facilities and analyzers

� Customized tools & applications development capabilities

� Collaborations with renowned academic institutions and SMEs

� Interdisciplinary team combining immunologists, engineers, biophysicians…

� Mass / flow cytometry� Luminex, FluoroSpot� Ultrasensitive assays� Droplet-based

microfluidics� Custom assays� Robotics platform

12

ImmunomonitoringAssay development and biomarker discovery

HIGH-DIMENTIONAL SINGLE CELL ANALYSIS

� 35 parameters to simultaneously discriminate immune cell populations and to assess their functions

CYTOF® 2 35 parameters

Phenotyping Cell function-associated markers

Mass CytometryAt a glance Strengths Keywords In-house creativity


Genomics & TranscriptomicsHT technologies, HQ data analysis

CONFIDENTIAL

� Design, optimize and develop an integrated application platform dedicated to: microbial genomics, microbiome characterization and transcriptomics of microorganisms & host-pathogen interactions

� Experimental design, innovative technologies, methods and analysis tools

� Technology and biological expertises within infectiology and microbiology

� Bioinformatics� Statistics� Molecular biology� Meta-genomics� Meta-transcriptomics � HT technologies (NGS,

DNA microarray) & MT validation technologies

� Single cells

AN OPTIMIZED 16S rRNA METAGENOMIC WORKFLOW

� From sampling to data analyses, a fully automated process, in a 192 samples per run format, to reduce time and expenses

16S rRNA METAGENOMICS

DNA extractionFully automated

NGS sample prepFully automated

MISeq192 samples/run

Data management & analysis

Metagenome NGS analysis tool for 16S rRNA geneFully automated



Metabolomics & ProteomicsCross-combine approaches and technologies

CONFIDENTIAL

At a glance

� Global characterization of the cellular metabolic function and changes induced by infectious diseases, therapy intervention or microbiota modifications

Strengths

� Cross-disciplinary applications for the simultaneous study of the metabolome and the metaboproteome*

� Cross-technology approaches combining Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR)

Keywords

� 1D/2D-NMR, LC-MS/MS, LC-HRMS, CE-MS

� Targeted analyses� Metabolite & protein

profiling� Fingerprinting� Fluxomics� Chemometry� Bioinformatics

Global Metabolite Profiling

� Enhance the quality and informativeness of untargeted metabolomics studies by using in routine the technological complementary of 1H-NMR & LC-HRMS

Combining MS & NMR for metabolite profiling

+MS NMR

In-house creativity

GLOBALENHANCEDPROFILING

*subproteome involved and supporting cellular metabolic function


Protein & Expression Systems EngineeringNovel tools for biotherapeutics and diagnostics

CONFIDENTIAL

Functional vaccine

BACTERIAL VLP BASED VACCINE

� Antigen & monoclonal antibody engineering

� Virus & viral vector construction and characterization

� Work with industrial standards

INNOVATIVE SCAFFOLD DESIGN

Epitopes Capsid protein

Self-assemblyVLP

� Engineered VLP based vaccines

� Tools for RNA and protein vectorization

� Genetic engineering� Host optimization & new

host discovery� Protein design, VLPs,

oligomers � Antibody engineering� USP/DSP & analytical

technologies� Small scale bioreactor

process optimization

� Optimize expression systems through vector and host engineering

� New delivery systems � Combinatory cloning and

screening

• Safer• Highly immunogenic• Lower cost of goods



Preclinical Models and ImagingTranslational models

CONFIDENTIAL

Human hepatocyte batches

Liver Mice repopulated with human hepatocytes

� Design, refine, develop and exploit specific microbiota & infectious-based models

� Combining academic innovation & industrial application

� Dedicated team combining microbiology and animal models expertise

� Strong academic and SMEs network

� State-of-the-art equipment

� Animal models� Gnotobiology � Host-microbiota

interactions� Infectious diseases� Microbiology � Cell and molecular biology

in vivo and 3D imaging� Biosafety laboratories

(BSL-1 to 4)� Anaerobic bacterial culture

HEPATOMICS

� Improving hepatocytes batches selection through multi-omics

� Reducing costs and timelines

� Application of the 3Rs

Inter-batches variability



Data Management & Analysis Analyze, secure and share data

CONFIDENTIAL

� Advanced technology unit data management & integration

� Partnership with the CNRS/IN2P3 computing center for High Throughout data analysis

� Software developers� Data managers

� Data management & integration

� Multi-parametric analysis

� Data intensive computing

TRANSMART

� Clinical and gene expression data visualization

� Workflow management� Lab information

management system

MULTIOMICS DATA INTEGRATION & VISUALIZATION

DATA ANALYSIS

Lab equipment

Biobank

+

PHENOTYPIC DATA

Medical record

EXPERIMENTALDATA



THEMATIC UNITS

CONFIDENTIAL


Thematic UnitsFighting pathogens, Exploiting microbiota

19

VACCINES

Enhance vaccine’s safety and efficacy

MICROBIOTA

Take full advantage of thehuman microbiota and itscontinuous cross-talk withimmune and neuronal cells

DIAGNOSTICS

Faster, scalable and comprehensive

diagnostics

ANTIMICROBIALS

Overcome hard-to-treat pathogens and multidrug-resistant bacteria

TRANSLATIONAL SCIENCES

Bridging basic discovery with clinical evaluations to support needs of the industry through transdisciplinary projects.

CONFIDENTIAL


VaccinesEnhancing vaccine’s efficacy and safety

CONFIDENTIAL

� Personalized prediction of vaccine efficacy & safety� Immunogenicity & reactogenicity in specific populations� Antigen design & expression� Antigen production optimization

IN VITRO ENABLING TECHNOLOGIES � Alternative expression systems (yeast, insects, mammalian)� Epitope prediction� Omics� Immunomonitoring

IN VIVO ENABLING TECHNOLOGIES � Predicting immunogenicity, efficacy & safety in animal models

of human diseases

Main target areas


AntimicrobialsOvercome hard-to-treat pathogens & MDR bacteria

CONFIDENTIAL

ENABLING TECHNOLOGIES� Screening (virtual, phenotypic, target-based, function-based,

competitive-based and in vivo mimicking)� Pre clinical models & imaging� Immuno-profiling� Omics� Data management & analysis

� Identification & characterization of new antimicrobials� Drug combo & synergies� Host-pathogens interactions� Microbiota protection� Bacteriophage/Bacteriocin approaches

*In partnership

Main target areas


MicrobiotaTaking full advantage of microbiota

CONFIDENTIAL

GUT MICROBIOTA MODULATION: prebiotics, probiotics, symbiotics, commensals, nutraceuticals, phytotherapeutics, drugs, antimicrobials

GUT MICROBIOTA DYSBIOSIS & DISEASES: antibiotic associated diarrhea, IBD/IBS, MICI, colorectal cancer, malnutrition, autism, obesity, etc…

OTHERS MICROBIOTA: lung & airways, skin (cosmetics), vagina (women health), oral cavity and nasal cavity (MRSA)

GUT MICROBIOTA CHARACTERIZATION� Omics (structure, composition, ecological approach)� Predictive models

Main target areas


DiagnosticsFaster, scalable and comprehensive diagnostics

CONFIDENTIAL

Main target areas

SMART TECHNOLOGY & DEVICES APPLICATION* :� Preanalytics / clinical sample preparation / non invasive sampling� Culture-free detection� Point-of-care / field testing� Imaging methods

*In partnership

BIOMARKER DISCOVERY & CONFIRMATON :� Pathogen identification / Antimicrobial resistance� Virulence factors / Diseases severity� Host (immune) response� Microbiota analysis� Drug response prognosis / Therapeutic monitoring & compliance

INFORMATION TECHNOLOGIES: � (De)centralized computing� Expert systems / software� Multi-parametric data analysis & integration� Clinical Information databases


Translational SciencesTransdisciplinary research projects

Main target areas

TRANSLATIONAL RESEARCH:� Mechanistic understanding of natural infections� Identification of pre-clinical tools for the rapid screening of

new therapeutic strategies� Identification of molecular signatures and biomarkers to

evaluate health status and infectious diseases progression

MULTI-THEMATIC PROJECTS :

� Role of microbiota on vaccine/antibiotic efficacy� Predictive biomarkers of drug and vaccine efficacy� Personalized medicine against infectious diseases

ENABLING TECHNOLOGIES:

� Multi-omics analysis (clinical, genomics, transcriptomics, proteomics and metabolomics)

� Multi parametric data analysis� Multi system data integration

CONFIDENTIAL


More information at www.bioaster.org

25

Contacts:[email protected]

CONFIDENTIAL

Documents

Gianfranco GROMPONE Head of Microbiota Unit … GROMPONE Head of Microbiota Unit Paris - France September 2015 CONFIDENTIAL 1 MICROBIOLOGY TECHNOLOGY INSTITUTE BIOASTER Microbiology