1. STEMVAC
Breast cancer immunotherapies
Consortium Management Case
Dr. Sandra HUYGEN, PhD, MBA

2. • Breast cancer
– 1.3 million new cases worldwide (second cause of cancer death)
– + 3.2% yearly
• Early stage of disease represent the majority of cases
• In addition to surgery, 3 treatments types
– Chemotherapy
– Hormone therapy
– Selective therapies (Her2/neu)
• Treatments Limitations
– Toxicity
– Efficacy: 60 % of patients die after disease recurrence
 Clear medical need for treatments associated with
improved efficacy and safety
 Immunotherapies and targeted therapies have the
potential to address this need
Market needs

3. 3
Introduction to program
FRAMEWORK • Grant (5 partners - 3.053.260 € - 4Y)
• Developpement of innovative therapies against breast cancer
OBJECTIVES • Identify antigens specifically expressed by breast cancer stem cells.
• Followed by development into targets for cancer immunotherapies
Therapeutic vaccines: deliverable is a product ready to enter a
first-time-in-human clinical trial
Targeted therapies (monoclonal antibodies): deliverable is a
product ready to enter preclinical development
STEMVAC Kick-off

4. Consortium
Partner Expertise
UNamur
Unité de Recherches en
Physiologie Moléculaire
Academia
Stem cell culture
Cancer stem cells
UCL & De Duve Institute Academia
Gene expression
analysis
ULG & GIGA-Cancer
Metastases Research Laboratory
Academia
Innovative proteomics,
Biomarkers discovery
Targetome (TGM) Spin-off
Antibody based
targeted therapies and
in vivo imaging
GSK Vaccines Company
Vaccine R&D,
production,
commercialization
4
STEMVAC Kick-off

5. 5
Consortium & program management
STEMVAC Kick-off
Legal framework – 2 agreements
 Partner rights & obligations
 IP
 Access rights
 Publications
 Confidentiality
 Gantt chart & budget
Organization
 Steering committee
 Business development
 Valorization committee
 Executive committee
 Task forces
 Biowin
 Rw
Design control
 R&D technical review
 Marketing
 Business development
 Regulatory affairs
 Clinical affairs
 IP
 QA

6. • Academic level
– UCL: Televie, FRSM, Actions de recherches concertées
– ULg: Televie, FRSM, Actions de recherche concertées, projet
européen FP7 (ADAMANT, Marie-Curie)
– FUNDP: Televie, FNRS
• Industrial level
– Feed the pipeline with more innovative candidates
– Multiple interactions foreseen with other development projects
Synergies and multiplier effects

7. Innovation
 Stem cell primary culture from patients’ samples
 Breast cancer stem cells antigen identification
 Based on both transcriptomic and proteomic data
 Biomarker validation on large human tissue collections
 Cancer immunotherapy development
 Double translational research concept
• From the patient to the laboratory and back to the patient
STEMVAC Kick-off

8. Innovation
 Highly innovative immunotherapeutic products to target
cancer via newly discovered cancer stem cell specific
antigens.
 Most important characteristics of cancer stem cell antigens
• Identified based on their specific expression by cancer
stem cells.
• Identified at the protein level, thus taking into account
any post-translational expression regulation.
• Rigorously validated for tumor specific expression in a
series of tumoral and normal tissues.
 Identification of antigens specifically expressed by breast
cancer stem cells would be a major breakthrough.
 At this stage, there are no existing patents that would
prevent us from protecting our findings and products.
CSC SC
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9. • Very few companies engaged on cancer stem cell research
– Macrogenics (formerly Raven Biotechnology)
– Oncomed
– Focus on pancreas, colon and lung cancer.
• No clinical trial (ongoing or planned) to test immunotherapies targeting cancer
stem cell associated antigens
• No patent with broad claims that would prevent us from patenting our findings
• Patenting strategy will be designed based on earlier patent application history
• Freedom to operate has to be re-evaluated for each proposed antigen
Competitors and FTO

10. 10
Gantt chart & budget
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11. 11
Program flow details
Breast Cancer Cell lines Human Breast Tissue Primary Cultures
cancer
normal
CSC
Proteo
mics
Total proteome Membranome (after cell surface biotinylation)
Mass spectrometry identification of a repertoire of biomarker specific for breast CSC
Data
analysis
• PCR and IHC on human normal tissues
• PCR and IHC on collections of human breast cancer
Vaccine
Develop
ment
mAb
Develop
ment
1
ULg-FUNDP
• Transcriptomic analysis (microarrays)
• Bioinformatic treatment of data for antigen selection
CSC
SC (stem cells)
2
3
5 6 • Selection of the most promising antigens
• Preclinical PoC and validation
• Production of a clinical grade product
• Selection of accessible biomarkers
• Antibody generation
• Preclinical evaluation
ULgUCLGSK
TGM
Target
Validation
4
ULg-
FUNDP-
UCL-GSK
• Functional assays using siRNA and xenografts
Breast
Cancer
Stem
Cells
(CSC)
STEMVAC Kick-off

12. Risk & mitigation
 Cell culture steps could introduce biological biases
• Analysis based on short term cultured primary cells
 Need to enrich the culture in cancer stem cells
• Use of short-term culture, in normoxic vs hypoxic conditions
• Sampling of cells after chemotherapy whenever possible
 False positives in specifically expressed genes
• Integration of transcriptomic and proteomic data
• Rigorous validation on tumor tissue banks
 Cancer therapeutic vaccine development is a high risk activity
• First cancer vaccine approved in 2010 in the US
• GSK’s approach is supported by two ongoing phase III clinical trials
• Rigorous project management which includes regulatory experts
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13. Risk & mitigation
 Choice of antigens to be used for development is critical
 Go/No Go decision point is proposed after the research phase
 Decision will involve all partners and take into account 5 pre-
specified criteria
– Commercial
– Competition
– IP– Expression
– Biology
STEMVAC Kick-off

14. Valorization & marketing
 The results of the research phase of the project, i.e. new
targets for cancer immunotherapy, will be patented. Based on
these results, GSK and Targetome will develop new therapies
for breast cancer
 Targetome is granted an exclusive option on the IP generated
during the project in the field of monoclonal antibodies
 Targetome will develop monoclonal antibodies for
immunotargeted therapies
 GSK is granted an exclusive option on the IP generated during
the project in the field of cancer vaccines / active cancer
immunotherapies
 The proposed products will be commercialized within the
existing worldwide GSK commercial structure
STEMVAC Kick-off

15. Social economic impact
• We estimate that the performance of this project (2013-2017)
will require the creation of about 10 qualified and highly
qualified stable positions in Wallonia, mostly in Targetome and
GSK.
• If successful, after 2017 the project will create and maintain
 Worldwide early clinical trials: several hundreds of
positions, out of which around 40 in Wallonia
 Worldwide late clinical trials: several hundreds of positions,
out of which around 150 in Wallonia
 For vaccine production and commercialization, several
hundreds of positions in Wallonia
STEMVAC Kick-off

16. Summary
 Integrated research and development project to create
innovative new therapies against cancer
 Breast cancer: a worldwide unmet medical need
 Synergy between the partners’ expertise
 Innovation lies in the nature of the proposed therapies
• Immunotherapies
• Targeting novel antigens
• Targeting Stem Cells
STEMVAC Kick-off

17. Opportunity for the Walloon region
 Strengtening wallonia expertise (genomics, proteomics, bioinformatics, cancer stem
cells)
 Cutting-edge cancer stem cell research
 With a input from Biotech and Pharma from the research phase onwards
 For a successful technology transfer and to create value
Thank you for your attention!
STEMVAC Kick-off

18. For more
information
Dr. Sandra HUYGEN, PhD, MBA
Consortium management & synergies expert
sandra.huygen@allianses.be
www.allianses.be
0032/486.467.191