1. EU bladder cancer research: challenges and opportunities Maria Vidal, MD, PhD Head of Unit Directorate E – Health Research DG Research and Innovation European Commission

2. Opportunities Stratified medicine to deliver: Stratified populations Translation to the clinic Cost savings Innovation, jobs Implementation in daily health care Evidence-based health care policies Incidence NCDs is increasing: ageing, risk factors Prevention: behaviour, early detection Patient biology: diagnostics, progression, toxicity, quality of life Expenditures: costs versus health gains Inequalities: EU28 and beyond Coordination (MS), collaboration (public- public, public-private, global,…) Challenges Cancer in Europe Year 2013  incidence: 2.7 million  mortality: 1.2 million  prevalence: 13 million Cancer deaths per 100,000 inhabitants (Eurostat, 2012)

3. Relevant Commission cancer policies Directorate General SubjectObjectives EMPLOccupational cancerCarcinogens/mutagens at workplace SANTE Tobacco Products DirectiveRegulate tobacco sales, labeling SANTE Expert Group Cancer control (MS) Prevention, benchmarking, guidelines, common priorities JRCCancer registration (MS) European Cancer Information System (ECIS) SANTECancer prevention (MS) ECAC (risk factors), EU breast, colorectal, cervical cancer screening guidelines ECHAREACHToxicity of chemicals

4. translational research  metastasis  tumour microenvironment  biomarkers, drugs, MoAbs  imaging  models  resistance  technology  prevention  early detection investigator-driven trials palliative & end-of-life care EU cancer research – what’s being funded (FP7) € 1,5 billion (2007-2013) Increased focus on clinical research

5. Achievements Best markers of bladder cancer outcome is studied in a prospective multi- center validation study Pre-validation of markers in the world's largest bladder cancer biobank Risk-based recommendations for patient management Less cystoscopies: € 40 million cost savings increased survival, better quality-of-life Prediction of bladder cancer disease course using risk scores that combine molecular and clinical risk factors

6. 6 Achievements robust/standardized protocol for urinary proteomics characterization of 1936 urine proteins 111 candidate biomarkers assessed based on patient versus controls cohorts Good biomarker pipeline for validation and commercialisation Together with UROMOL it provided the basis for: Led to clinical validation of two urothelial biomarker panels in 2016 It has spurred urine biomarker research in kidney, pancreatic, prostate cancer Novel MS-based strategies to Discover and Evaluate Cancer Biomarkers in urine - Application to Diagnosis of Bladder Cancer Translation of novel Biomarkers for Bladder Cancer for clinical outcome prediction (FP7)

7. Linking 29 national/regional funding organisations in 20 countries on translational cancer research  1st joint call on 'Validation of biomarkers for personalised cancer medicine'  2 nd joint call on 'Primary and secondary prevention'  3rd joint call on 'Tertiary prevention'  Portfolio analysis of national cancer funding initiatives  Three cancer charities joined  Overall contributions by national funders: € ~33 million Coordinating national cancer research efforts TRANSCAN-2 started 1 January 2015  1 st joint call on 'Tumour heterogeneity' (€ 16 million)  2 nd joint call on 'Immunotherapy' (€ 10 million) Eg CTC-SCAN (prostate cancer)

8. RISK FACTORS. Genetic prostate cancer variants as biomarkers of disease progression Collected prostate cancer biological samples and clinical data (5500 samples + 7000 controls) from different European countries Identified new prostate cancer risk variants and PSA variants Elucidated the role of biomarker HNF1 in cancer progression

9. Horizon 2020: Three priorities Excellent science Industrial leadership Societal challenges €24 billion European Research Council Future & Emerging technologies (FET) Marie Curie Research infrastr. €29 billion SC1 Health (€7.4b) SC2 Food & bio eco SC3 Energy SC4 Transport SC5 Environment SC6 EU in the world SC7 Security €17 billion Leadership in Enabling and Industrial Technologies (LEIT) Risk finance Innovation in SMEs IMI Stronger focus on end-users Broad topics Challenge-driven

10. 10 Horizon 2020 3 main pillars, including Societal Challenges Health: €7.5 Bn Pillar 2 Pillar 1 Pillar 3

11. 11 Challenge Health, Demographic Change and Wellbeing

12. Infectious Diseases (2014-2017) Human biomonitoring (2016-2017) Maternal and child health (2016-2017) Health ICT (2014-2017) Healthy ageing (2014-2017) Personalised medicine 2014-15: EUR 1.3 B 2016-17: EUR 1.4 B

13. Implemented through various instruments

14. translational research  metastasis  tumour microenvironment  biomarkers, drugs, MoAbs  imaging  models  resistance  technology  prevention  early detection investigator-driven trials palliative & end-of-life care EU cancer research – what’s being funded HORIZON2020 € 420 million (2014-2015*) € 103 million on cancer prevention and early diagnosis  Increased focus on innovation and research to patients, to market

15. TREATMENT. Professional cross-priming for prostate and ovarian cancer ProdigyTM instrumentation Objectives: Fully automated magnetic selection system to select patient dendritic cells (DCs) Optimised DC product that recognises patient prostate tumour material Standardisation of markers and treatment protocol in clinical setting Phase I/II clinical trial Contribute to survival of prostate cancer patients Marketing of patented, clinical grade cell product 6 academic partners, 1 SME (Miltenyi) 5 years € 6 million Started 9/2015 6 academic partners, 1 SME (Miltenyi) 5 years € 6 million Started 9/2015

16. DIAGNOSTICS: opportunities for SMEs Cancer indication ProjectBeneficiaryEU funding What it will deliver Bladder cancerLAUREN CYTOSYSTEMS LTD € 3.1 million a commercial non-invasive in vitro diagnostic based on MCM2+ Bladder cancerBLACANDI Genomic Expression Aps € 50,000 Filtration Device using biomarkers to substitute cystoscopy prostate cancerPCSP CANVAX € 50,000 Olfactory-receptor and volatile organic compounds in urine based diagnostic Prostate cancerProCanEx PT THERAGNOSTIC BV € 50,000 Diagnostic kit based on protein kinase activity profiling in exosomes prostate cancerOcProDX Otturos € 50,000 multiplexed protein diagnostic blood test for Organ-Confined Prostate cancer: OCProDx prostate cancerBioGuidePcA€ 50,000 diagnostic test prostate cancer surveillance *http://cordis.europa.eu/projects/home_en.html

17. Prevention Aetiology Diagnosis / Prognosis Therapy Model Systems Survivorship / QoL Screening Stratification high-risk groups Molecular understanding of disease Molecular classification of cancer sub-types Risk factors Biomarker identification for: Diagnosis Prognosis Prediction Monitoring E.g: blood, urine, saliva, tissue, tumour, imaging Targeted drugs via biology-driven hypothesis bio-informatics to guide treatments Novel clinical trial design Wide range of animal models In silico models In vitro & ex-vivo models ('xenopatients') Solutions for side effects Quality-of-life: Debilitation Infertility Fatigue Early death Second cancers Prostate cancer cohorts, screening Risk factors prostate cancer Modelling prognosis in prostate cancer Image-guided radio and immunotherapy for prostate cancer Identify radiosensi- tive breast, prostate, lung cancer patients Biomarkers prostate cancer Towards precision medicine in cancer

18. MIB: Multi-modal, endoscopic biophotonic imaging of bladder cancer for point-of-care diagnosis BlaC E-assay: Portable electrochemical assay system for on-chip quantitative estimation of bladder cancer biomarkers in real samples URO-BEST: Urothelial carcinoma biomarkers based diagnostic tEST BLACANDI: BLACANDI can improve life quality and cut costs of diagnosing and managing bladder cancer in half LAUREN: Bladder cancer urine cell analysis PLATINDX: A test predicting the efficacy of common platinum drugs enabling personalized chemotherapy for bladder cancer patients

19. Risk factors Molecular pathogenesis Biomarkers Targeted therapies Medical devices: o Molecular diagnostics chips o Biomarkers o Endoscope o imaging EU bladder cancer research 16 projects € 25 million

20. Innovative Medicines Initiative Public-private partnership between the EU and pharmaceutical industry Strategic Research Agenda 2014-2020 Cancer research is one of the priorities Public-private partnership between the EU and pharmaceutical industry Strategic Research Agenda 2014-2020 Cancer research is one of the priorities Imaging biomarkers -omics; xenopatients In vitro models Circulating tumour cell based biomarkers Prostate cancer models Blood-based biomarkersOmics-based models and biomarkers Imaging biomarkers

21. Funding opportunities for bladder cancer Understanding health, well-being and diseases SC1-PM-02-2017: New concepts in patient stratification SC1-PM-04-2016: Networking and optimising the use of population and patient cohorts at EU level Treating and managing diseases SC1-PM-09–2016: New therapies for chronic diseases SC1-PM-10–2017: Comparing the effectiveness of existing healthcare interventions in the adult population Treating and managing diseases SC1-PM-09–2016: New therapies for chronic diseases SC1-PM-10–2017: Comparing the effectiveness of existing healthcare interventions in the adult population SME instrument SMEInst-05-2016-2017: Supporting innovative SMEs in the healthcare biotechnology sector SC1 Work Programme 2016-17 € 935 million

22. Collaborative projects Public-private partnership with big pharma Public-public partnerships with EU Member States & beyond Blue sky research Grants for small businesses Loans for small and big R&I companies Knowledge triangle: Higher education, business, R&I Bladder cancer research and Horizon 2020 Societal Challenge 1: Health HORIZON 2020

23. Thank you! Malvezzi et al. (2015) European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Annals of Oncology 26: 779–786, 2015