Les Instituts Hospitalo-Universitaires, Concevoir les thérapies du futur Les instituts hospitalo-universitaires sont une création émanant du programme  « Santé et biotechnologies » des investissements d'avenir (Grand emprunt 2010). Créés autour des pôles d’excellence hospitalo-universitaires, ils ont vocation à stimuler la recherche biomédicale dans des secteurs porteurs, à assurer la promotion d’innovations et à faciliter leur exploitation dans le cadre de partenariats industriels jusqu’à leurs transferts dans la pratique de soins. Ces programmes ambitieux visent à accroître la compétitivité de la France et à permettre aux patients de bénéficier le plus tôt possible des avancées thérapeutiques.

a world class hospital for personalized Hematology … in conjunction with Denis Diderot Medical Faculty FACULTE DE MEDECINE PARIS DIDEROT a leading institute for medical research and training, at University Paris Diderot

55 Clinical Partner: The Saint-Louis Hospital (150 Beds for hematology – 110 ME/yr) First hospital in France: Hematopoietic stem cell transplantation Number of patients treated for acute leukemias lymphomas myeloma (source DPM AP-HP) 5

Research and Education Partner: The « Institut Universitaire d'Hematologie » www.univ-paris-diderot.fr/IUH/

« Institut Universitaire d'Hematologie » « First » worldwide Jean Bernard: demonstration that leukemias are cancers and first remission in leukemias Jean Dausset: the HLA system (Nobel Prize 1980) Eliane Gluckman: Cord Blood Transplantation (Honour Prize, INSERM 2011) Laurent Degos: first targeted therapy in cancer (General Motor Prize)

« Institut Universitaire d'Hematologie » Teaching and Education The PhD School ‘Biology and Biotechnology’ of Paris Diderot and Paris Descartes Universities (Pr. Sigaux) The international School for continuous education, the European School of Hematology (www.esh.org)(Pr. Gluckman)

‘Institut Universitaire d’Hématologie ’ 99 Main research areas of ‘Institut Universitaire d’Hématologie ’ Molecular and functional characterization of neoplastic blood disorders and solid tumours Focus: Multiparametric profiling of tumors Characterization of leukemic and tumour stem cells In vitro and in vivo characterization of the function of genes involved in carcinogenesis Modelling tumors in mice (transgenics and xenografts) Tumor Genetics (with the CEPH) Transplantation, cell therapy, gene therapy Focus: Histocompatibility Hemopoietic stem cell transplantation GVH Virology Focus: Interactions between virus and cells Phamacology Focus: Cell biology, molecular virology and modulation of apoptosis, differentiation and cell cycle Therapeutic manipulation of host-tumour relationships: angiogenesis, tumour stem cells, immune responses Biostatistics of therapeutic trials Focus Methodology of phase I trials Design, conduct and analysis of trials in neoplastic blood disorders 9

« Institut Universitaire d'Hematologie » First Hematology Research Center in France Budget:28 ME Number of Pi:135 , total members:430 12000 m2 for research, technology and teaching

« Institut Universitaire d'Hematologie »

‘Institut Universitaire d’Hématologie ’ International cooperations 12121212 ‘Institut Universitaire d’Hématologie ’ International cooperations 12

Le Centre Meary Complète l’offre du campus de l’Hôpital Saint-Louis, riche de ses départements académiques de recherche fondamentale translationnelle et clinique, hôpital français de référence en Hématologie et greffes de cellules hématopoïétiques. Dédié à la recherche partenariale et au développement, troisième volet du triptyque plaçant la recherche partenariale et l’innovation thérapeutique dans un continuum de développement avec la recherche académique et le soin. Réunion Meary Jeudi 5 juin 2014

Ressources biologiques Hôpital Saint-Louis AP-HP IUH Ressources biologiques Cohortes CIC 1/ L’hypothèse scientifique 3/L’essai clinique Centre Meary 2/La preuve du concept et Le développement Partenaires Industriels Bio-marqueurs Médicaments Thérapie cellulaire

Le Centre Meary CENTRE DE FORMATION ET DE RECHERCHES TRANSLATIONNELLES EN HEMATO-ONCOLOGIE Objectif : mettre en place les infrastructures et plateformes nécessaires à une recherche capable de se positionner au meilleur niveau mondial, pour accéder rapidement à une médecine plus personnalisée Réunion Meary Jeudi 5 juin 2014

Le Centre Meary Un projet stratégique (plan stratégique 2010-2014 de l’AP-HP), dispositif majeur du projet SLI Un jalon supplémentaire pour renforcer la spécialisation historique en hémato-oncologie de l’hôpital Saint-Louis Un centre dédié à l’innovation et à l’interface publique-privée : étroitement associé à la recherche fondamentale, translationnelle ou clinique et aux soins dispensés à l’hôpital, il permettra aux entreprises privées consacrées à la recherche médicale de trouver l’environnement optimal pour mener à bien leurs travaux. Saint-Louis constituera ainsi un des trois ou quatre centres de niveau mondial en recherche clinique et pour le soin en hémato-oncologie. Réunion Meary Jeudi 5 juin 2014

Meary, le concept Idée Public Médecins Ingénieurs Privé Chercheurs Onco-Hémato Focus biomarqueurs Médecine de précision Public Privé Médecins Ingénieurs Chercheurs Médicament et dispositifs médicaux FORMATION Réunion Meary Jeudi 5 juin 2014

Laboratoires Formation Plateformes Meary, 3 dimensions Réunion Meary Jeudi 5 juin 2014

Meary, 4 piliers Ressources bio OMICS Thérapie cellulaire Info/bioinfo Réunion Meary Jeudi 5 juin 2014

Le bâtiment Meary en résumé Construit sur la dalle Méary de l’Hôpital Saint-Louis. Rénovation complète de l’entresol (850 m² environ) de la « dalle MEARY » ainsi que la construction de deux niveaux supplémentaires de 1 000m² chacun, Surface totale de 2 850 m², recouvert d’une toiture terrasse végétalisée destinée à créer une continuité avec le jardin mitoyen. Le bâtiment abritera notamment : Un auditorium de 120 places et son environnement d’espaces de convivialité Un ensemble de plateformes à très haut débit de grade industriel Un centre de ressources biologiques annotées adapté aux grandes cohortes Un centre serveur Des laboratoires d’interface public-privé notamment pour le co-développement de nouveaux dispositifs médicaux et médicaments ciblés Une salle de formation pour « l’Ecole de l’Innovation » Une plateforme production de Médicaments Thérapie Innovante Réunion Meary Jeudi 5 juin 2014

recherche fondamentale Institut Universitaire d’Hématologie Paris-Diderot recherche fondamentale Institut Universitaire d’Hématologie Fondation partenariale Saint-Louis recherche translationnelle Centre Meary recherche clinique Pole d’hématologie Immunologie, Cancerologie Hôpital Saint-Louis AP-HP

Cancer Research Institutes Paris Alliance of Cancer Research Institutes 23

Oncology in the „Grand Paris“ Strengths 3600 scientists (including post-docs, PhD students) Research budget (excluding trials) ~230 Meuros/yr cancer health care for ~17 million people 600 medical oncologists, 1800 other physicians A comprehensive set of scientific and medical ressources Strong involvement in medical innovation more than 60% of French high-impact factor publications Excellence in basic, translational and clinical research more than 40% of French clinical trials in oncology Good Ecosystem large number of SMEs in biotechnology and several Pharmas. good Universities and « Grandes Ecoles »

Oncology in the „Grand Paris“ Weaknesses Scattering of ressources and geographical dispersion of clinical and research centers Competing Institutions Suboptimal translational perspectives and low level of industrial collaborations Suboptimal integration of cancer research facilities and biological resources

Oncology in the „Grand Paris“ Opportunities 2011: new strategic programs for regional networks in research and innovation the “Canceropôle Ile de France” the “Medicen Cluster” 2011: the Grand Emprunt (the Big Loan) a special action of the French Government designed to reinvigorate the National research system none of the six “IHU” laureates dealt with cancer, but both Gustave Roussy Institute and St. Louis Institute were classified in positions 7 and 8 of the Nation-wide competition : merging of both projects was suggested by the International Committee The Government decided to launch a new call for proposals dedicated to Oncology

The PACRI Project Governmental Constraints No overlap with existing programs financed by the Big Loan or INCa a lot of successful applications: LabeX, EquipeX “promising IHU”, SIRIC etc… Low Budget (seeding money) but requirement of a major leverage effect

The PACRI Project Method: setting an ad-hoc program committee Directors (Presidents) and scientific directors of the three major cancer institutes and of AP-HP (Paris Public Hospitals) To decide :Go /no Go To define/nominate: the objectives “federating, strengthening and increasing the efficiency and visibility of Cancer research in the Paris area” breakthrough questions, for which PACRI claims a number of internationally recognized experts the partners of the project the Director of the program

of Cancer research in the Paris area” The PACRI Project PACRI objectives “federating, strengthening and increasing the efficiency and visibility of Cancer research in the Paris area” to promote trans-institutional research networks particularly in the fields of molecular genetics, cell biology (integrated Omics: genomics/proteomics/metabolomics/systems biology), mouse models relevant to human cancers, preclinical studies, as well as immune exploration, focusing on practical, therapy-relevant aspects. to organize a series of shared technological platforms including bioinformatics, screening through cell biology imaging or immune cellular interactions… and “mouse clinics” dedicated to production of xenograft or genetically defined models of tumors and efficient exploration of therapeutic interventions, notably with approved drugs or those under development. to create an integrated educational system for recruiting, training and tutoring the next generation of cancer researchers and clinical oncologists

The PACRI Project breakthrough questions Can we approach the genetic and epigenetic heterogeneity of cancers and their evolution after treatment by novel technologies and mathematical models? Could tumors constitute a metabolic micro-ecosystem - notably in the interactions between cancer and stromal cells - that explains therapy resistance? Could conventional (or targeted) therapies induce an anticancer immune response and is this implicated in their clinical efficacy? Can we design efficient strategies combining immunotherapies with conventional or targeted therapies in preclinical models? Can we construct in vitro or animal models that more accurately reflect the growth of human cancers in patients? How can these be conveniently used to assess anticancer drugs?

PACRI program stimulate the exploration of selected breakthrough concepts designed to treat cancer create a “mouse cancer clinics” designed to monitor drug effects on both xenotransplanted primary human cancers and genetically defined, oncogene-driven murine cancers offer a dual service to industrial partners: * a framework for the preclinical evaluation of drugs * an improved technology for monitoring innovative clinical trials under the guidance of the PACRI faculty streamline and unify the education of graduate and postgraduate students, the formation of clinical oncologists, organize foreign exchanges at the highest international standards and boost clinical and societal integration.

PACRI breakthrough questions Science & technology Clinical and industrial impact Technology platforms Breakthrough questions Excellence Preclinical & clinical drug development Education & training 32

Architecture of the PACRI Project I. Innovation II. Platforms III. Integration IV. Education WP1: Heterogeneity WP2: Function WP3: Immunology WP4: Models WP5: Platforms WP6: Integration WP7: Education 33

Research Institutes & Hospitals « CLCC » Saint Louis Cochin HEGP Beaujon Research budget ~230 Meuros/yr

PACRI Partners National Research/ Education Institutions National Associations Local/regional Institutions National Research/ Education Institutions Private Partners Universities

PACRI strategy: elitism The PACRI Faculty: 25 top scientists and clinicians-scientists working in its founding institutions The PACRI Director: Guido Kroemer

PACRI Public Private Partnerships and Medicen concerted actions Biotech. and Pharma. Companies PP platforms and labs. IP managment Carnot Institute IGR&D SPC SATT Villejuif building Paris Meary building Research and development Resources sharing Annotated Bioressources Patient cohorts Cellular and animal models Advanced proof of concept Maturation processes