STEMVAC Breast cancer immunotherapiesConsortium Management Case

Dr. Sandra HUYGEN, PhD, MBA

• 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 withimproved efficacy and safety

Immunotherapies and targeted therapies have thepotential to address this need

Market needs

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 afirst-time-in-human clinical trial

Targeted therapies (monoclonal antibodies): deliverable is aproduct ready to enter preclinical development

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Consortium

Partner Expertise

UNamurUnité de Recherches en Physiologie Moléculaire

AcademiaStem cell cultureCancer stem cells

UCL & De Duve Institute AcademiaGene expression

analysis

ULG & GIGA-CancerMetastases Research Laboratory

AcademiaInnovative proteomics, Biomarkers discovery

Targetome (TGM) Spin-offAntibody based

targeted therapies and in vivo imaging

GSK Vaccines CompanyVaccine R&D, production,

commercialization

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Consortium & program management

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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

• 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

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

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Innovation

Highly innovative immunotherapeutic products to targetcancer via newly discovered cancer stem cell specificantigens.

Most important characteristics of cancer stem cell antigens

• Identified based on their specific expression by cancerstem cells.

• Identified at the protein level, thus taking into accountany post-translational expression regulation.

• Rigorously validated for tumor specific expression in aseries of tumoral and normal tissues.

Identification of antigens specifically expressed by breastcancer stem cells would be a major breakthrough.

At this stage, there are no existing patents that wouldprevent us from protecting our findings and products.

CSC SC

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• 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

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Gantt chart & budget

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Program flow details

Breast Cancer Cell lines Human Breast Tissue Primary Culturescancer

normalCSC

Proteomics

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

mAbDevelop

ment

1

ULg

-FU

ND

P

• 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

ULg

UC

LG

SK

TGM

Target Validation

4

ULg

-FU

ND

P-

UC

L-G

SK

• Functional assays using siRNA and xenografts

Breast Cancer Stem Cells (CSC)

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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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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

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Valorization & marketing

The results of the research phase of the project, i.e. newtargets for cancer immunotherapy, will be patented. Based onthese results, GSK and Targetome will develop new therapiesfor breast cancer

Targetome is granted an exclusive option on the IP generatedduring the project in the field of monoclonal antibodies

Targetome will develop monoclonal antibodies forimmunotargeted therapies

GSK is granted an exclusive option on the IP generated duringthe project in the field of cancer vaccines / active cancerimmunotherapies

The proposed products will be commercialized within theexisting worldwide GSK commercial structure

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Social economic impact

• We estimate that the performance of this project (2013-2017)will require the creation of about 10 qualified and highlyqualified stable positions in Wallonia, mostly in Targetome andGSK.

• If successful, after 2017 the project will create and maintain

Worldwide early clinical trials: several hundreds ofpositions, 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, severalhundreds of positions in Wallonia

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Summary

Integrated research and development project to createinnovative 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

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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!

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For more information

Dr. Sandra HUYGEN, PhD, MBA

Consortium management & synergies expert

sandra.huygen@allianses.bewww.allianses.be

0032/486.467.191