Disclosed slideck at the conference : SMI Imaging Oncology in London the 12 Mach 2014

1. Imaging agents innovation challenges
adressed at a national level in France
-
The Role of AVIESAN
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SMi Imaging Oncology London - 12 March 2014
Sabin Charles CARME, PhD

2. •Context and definitions
•Adress the challenge of innovation
•Case study
•Dedicated Infrastructure of actors
•Dedicated process to unit the actors
Context Challenge Case Infrastructure Process

3. « Biomarkers » and imaging agents
Context Challenge Case Infrastructure Process

4. Biomarker
DCE MRI
FMRI
FDG PET
Volumetric CT
DWI MRI
FLT PET
Apoptosis PET
PERCIST
Tumor Growth Dynamics
Fluciclatide
K5
Flutemetamol
Florbetaben
Aposense
CK18
Context Challenge Case Infrastructure Process

5. C-Kit IHC
HER2 Gene expression
KRAS PCR
ALK FISH
BRAF V600E
PCR
Biomarker
Solanezumab
Context Challenge Case Infrastructure Process

6. IND Investigative New Drug (FDA.org)
• Manufacturing Information - Information pertaining to the composition, manufacturer,
stability, and controls used for manufacturing the drug substance and the drug product.
• Animal Pharmacology and Toxicology Studies - Preclinical data to permit an assessment as to
whether the product is reasonably safe for initial testing in humans.
• Clinical Protocols and Investigator Information - Detailed protocols for proposed clinical studies
to assess whether the initial-phase trials will expose subjects to unnecessary risks. Information
on the qualifications of clinical investigators. Commitments to obtain informed consent from
the research subjects, to obtain review of the study by an institutional review board (IRB), and
to adhere to the investigational new drug regulations.
Context Challenge Case Infrastructure Process

7. GO
NoGO
Medicinal chemistry
Synthesis
Analytical Chemistry
QC
Molecular Biology
Preclinical Imaging
Data Post-Processing
Modelling
Expertises
INDLeadValidation
Toxicology
Galenic / Formulation
Scale-Up
GMP Production
Batch validation and
release
INDDossierPreparation
Clinical Imaging
Data interpretation and
analysis
Patient recruitment and
management
CTA-FDA
Clinical trial preparation
Data statistics and
report
GO
NoGO
Discovery / Preclinical Early Clinical
Context Challenge Case Infrastructure Process

8. Imaging agent complex environment
Context Challenge Case Infrastructure Process

9. Challenge at the national level
• Need of population analysis / epidemiology to proof healthcare expenses reductions
 Patient associations / Hospital / Global Purchase Office
• Define intermediate endpoints that are consistent with a better care and response to therapy for
patients / Clarify and value the benefit risk ratio of imaging agents
 Simplify / ease regulation from regulators / access dedicated experts Trial supports
• Get appropriate funding for costly early phase trials including clinical imaging when attrition rate
is low compare to therapeutics when entering phase III
 Get dedicated funding channels and incentives, increase societal criteria for grants
Context Challenge Case Infrastructure Process

10. Neuro: Beta-Amyloid targeting agent
Medical need:
• Lack of techniques to diagnose early signs of Alzheimer disease
• Only behavioural tests at advanced stage
• Need for a quantitative reproducible technique
• Need non invasive brain measurement
Solution:
• Imaging of the beta amyloid load in brain region
Candidates:
• Florbetapir (Amyvid) – Avid Lilly (Approved MA)
• AZPET – Fluoropharma
• Florbetaben – Piramal
• Flutemetamol – GE
http://www.technologyreview.com/view/422477/fda-panel-supports-
new-diagnostic-tool-for-alzheimers/
Context Challenge Case Infrastructure Process

11. Onco: PSMA targeting agents
Medical need:
• screening of prostate cancer with a prostate-specific antigen
(PSA) blood test and or a digital rectal exam (DRE)
• Metastatic prostate cancer spread to lymph nodes and bones
• FDG PET is limited in the detection of osseous metastatic lesions
Solution:
• Imaging agent that targets the extracellular domain of prostate
specific membrane antigen (PSMA)
Candidates:
• MIP1404 – Progenics (Molecular Insigt)
• PSMA minibody- ImaginAb
• CTT-54 – Cancer Targeted Technology
[123I] MIP-1072 imaging in a patient with metastatic prostate
cancer at 4 h post-injection
http://www.sciencedirect.com/science/article/pii/S0305737212001284
Context Challenge Case Infrastructure Process

12. Cardio: Unstable Plaque
Medical need:
• Standard angiography do not tell about the risk of
plaque rupture and clots
• Morphological imaging IVUS, OCT is still invasive
and not associated with plaque biology
Solution:
• Imaging of the biological activity of unstable
plaque: Inflammation, Fibrin, MMP, VCAM…..
Candidates:
• FDG
• TSPO GE-180 - GE
• VasoPET – Fluoropharma
• EP-2104R – EPIX (discontinued)
• P947 – Guerbet (Preclinic stage)
http://eurheartj.oxfordjournals.org/content/30/21/2566.long
http://pubs.acs.org/doi/abs/10.1021/mp300610s
Context Challenge Case Infrastructure Process

13. The purposes of Aviesan are to:
• coordinate the strategic analysis, scientific programming and operational implementation of life and health
science research;
• give a fresh boost to translational research by speeding up the transfer of fundamental knowledge to clinical
application;
• increase cross-disciplinarity by opening biology and medicine up to contributions from mathematics, physics,
chemistry, information technology, engineering sciences, human and social sciences;
• ensure that projects are consistent in thematic and infrastructure terms;
• carry out clinical, economic and social promotion of knowledge, particularly by facilitating industrial
partnerships;
• define shared standpoints in terms of European research and international cooperation;
• harmonize and cut down on red tape for laboratories so as to free up the creativity and excellence of teams.
Context Challenge Case Infrastructure Process

14. FLI is considered as a large-scale research infrastructure in France
• Missions:
• to coordinate nation-wide research activities concerned with in vivo imaging
• Matrix organization with platforms (nodes) and projects (workpackages)
• to provide scientists access to a complete range of imaging technologies and services
• 100M€ Fundings
• 40M€ for FLI nodes
 Clinical PET-MRI in Paris / 7T MRI in Marseille ….
• 60M€ for Imaging Labs (LABEX / EQUIPPEX)
 Imaging tracers IRON program / Clinical PET-MRI in Lyon / preclinical PET-MRI in Dijon
CB
A
D
E
Context Challenge Case Infrastructure Process

15. Nodes examples
Caen
Lyon
Context Challenge Case Infrastructure Process

16. FLI
• Modular targeting platform for imaging
• Probe and contrast agent development
• Nanoparticles for imaging
• Proof of concept, clinical applications, translational research
16
Context Challenge Case Infrastructure Process
IRON
WP1: Functional imaging of neurodegeneratives diseases
WP2: Phenotypic imaging in neurology and oncology
WP3: Nanomedicine and molecular radiotherapy
TRAIL
- Design of covalent and coordinative labelling strategies
- Tropism of cellular infiltration (USPIO loaded cell tracking)
- Conjugates with ligands: Aptamers, mAbs, Peptides
3 programs on « IN VIVO MOLECULAR IMAGING AGENTS »

17. Strategic Valorization Field
http://www.aviesan.fr/en/aviesan/accueil/menu-header/partenariats-industriels/les-domaines-de-valorisation-strategique-dvs
Imaging agents and theranostics
Roadmap for public-private R&D, priorities and opportunities for transferring to industry
Develop the prospective analyses, identify the new opportunities and/or markets
Bringing out innovative projects with aimed at industrial applications
• Mapping the environment and of the intellectual property / Analysis of the patent portfolio
• Mapping of the industries and analysis of the national and international industrial context
• The research landscape, its operators and its centers of excellence on a national and international leve
• Analysis of the dynamics of the targeted markets,
• Analysis of the regulatory constraints
Context Challenge Case Infrastructure Process

18. Technology transfer process
Research Preclinical dvt
Early Clinical
dvt
Late Clinical
dvt
Market
Academia
SME – PPP Consortia
Pharma/Diag industry
Patients
POC POC
TRL 4TRL 1-3 TRL 5 TRL 6 TRL 7 TRL 8-9
Translation
-Preclinical
-Manufacturing
-Clinical
-Phase1,2a
-Clinical
-Phase 2b, 3
Context Challenge Case Infrastructure Process

19. Market Aviesan
Portfolio of
imaging agents
Context Challenge Case Infrastructure Process

20. Context Challenge Case Infrastructure Process
Unite the French
actors around a
common goal
SMEs
Clusters
Academia
Clusters
Diagnostic
Industry
Pharma
Industry
Agencies
Clusters

21. Context Challenge Case Infrastructure Process
Take home message
• Industry Imaging Agent Innovation is under threat
• French AVIESAN want to address it to rise opportunity
• By matching patient needs and industry constraint with academia research
• By building dedicated infrastructure and process
• By structuring the innovation actors in dedicated clusters

22. AVIESAN
IMAGING AGENTS
VALORIZATION UNIT
sabin.carme@aviesan.fr