European Network for the Advancement of Clinical Gene Transfer and - PDF document

E DITION NOV 2009 Sixth Framework programme EC-DG research LSHB-CT-2006-018933 European Network for the Advancement of Clinical Gene Transfer and Therapy Adenovirus platform Non viral AAV methods platform platform CLINIGENE Retrovirus Cell therapy platform platform Lentivector platform Coordinator: Odile Cohen-Haguenauer: clinigene.noe@lbpa.ens-cachan.fr Tel: +33 1 47 40 76 80 - Fax: +33 1 47 40 76 81 Management Team: clinigene.admi@ens-cachan.fr Tel: +33 1 47 40 76 58 - Fax: +33 1 47 40 68 83 École Normale Supérieure de Cachan - 61, avenue du Président Wilson - 94235 Cachan Cedex - France

Adenovirus platform Non viral AAV methods platform platform CLINIGENE The general objectives of CLINIGENE Retrovirus Cell therapy platform platform are the following: Lentivector ◗ Foster interaction between all stakeholders: regulators, pre-clinical & clin- platform ical investigators, scientists, companies (otherwise competitors), patients’ groups, in order to streamline integration of multidisciplinary expertise. General Organisation ◗ Establish quality, safety, efficacy and morally acceptable standards for clinical gene transfer products. ◗ Identify the “critical path” to accelerate the transit phase from preclinical to clinical phase by integrating expertise and generating new knowledge. ◗ Improve competitiveness by spreading of excellence and disseminating STANDARDS knowledge. ◗ Obtain clinically significant improvement in the treatment of some human dis- eases by gene therapy. CLINIGENE INTEGRATION & ETHICS New Tools / Critical path Core of Clinical case studies Academic (not funded by NoE) Partners Vector Integration:“Hands-on” knowledge Systems Task Forces ROTATE ROTATION ◗ Sharing Facilities; Exchange & high level training and Emerging Technologies ◗ General Biosafety & immunotoxicology POTENTIAL 20% of funds to be assigned (novel projects) ◗ Accelerate the transit phase from bench to bed-side: “critical path” for R&D INDUSTRY (new partners) ◗ Sustained action with Regulatory authority PARTNERS SPREADING EXCELLENCE ◗ Integration knowledge within the Network - Public Web-site: www.clinigene.eu Club of Interest - Scientific & strategic software: Clinisoft - Clininews: bimonthly newsletter Potential impact on R&D ◗ A new entity towards sustainability: translating into a new EU-Institute science policy & society Confronting & evaluating orientations & output at the International level: the NoE-Governance ◗ Scientific Advisory Board: Lucio Luzzato (chair) ◗ Scientific International Board: Inder Verma (chair) ◗ Ethical Review Board: Alastair Kent (chair) Nancy King (vice chair) * Name of the experts available on www.clinigene.eu Emerging Technologies Overcoming bottlenecks & limitations of current Gene system capable of escaping its subsequent integration, even at background level, into Therapy technologies the host cell genome? How can the risk of insertional mutagenesis be evaluated? Are there technologies and methods to prevent this major side-effect? Bottlenecks to be adressed, current limitations, solutions to be tested and if possible exemplified by the CliniGene-NoE. Flexibility funds For the technological platforms: AAV, Adenovirus, Retro- ◗ The goal of these flexibility funds is to improve the integration and virus, Lentivirus, Genetically modified cells, Non viral technol- the synergy within Clinigene. Calls for flexibility funds are unique ogy (i) General, (ii) Naked DNA, (iii) Physical vectorisation-elec- opportunities to promote (i) novelty, in identifying emerging troporation, (iv) Chemical vectorisation, novel viral vectors… techologies and benefit from quick initial funding of related Two main orientations for emerging tech- programmes, (ii) priviledged contacts between labs, (iii) dis- nologies: semination & outreach, including international contacts. ◗ Direct in vivo gene transfer: can the gene transfer prod- ◗ Over 20% of the total budget is dedicated to these ”flexi ucts be directly administered in vivo, whatever the route funds”. Specific internal call for tender are open twice a year. of choice and reach its target without reaching unwant- A strong and positive dynamics is generated: programmes must ed others? (“off-the-shelf” Gene therapy) . involve collaborative work between two CliniGene partners at least. ◗ It’s all about transgene integration: Is there a gene transfer vector

What is CliniGene? CliniGene academic partners: A. Aiuti (FCSR-TIGET, Milan), R. Ali (University College The role of the European Network for the Advancement of Clinical Gene T rans- London), A. Auricchio fer and Therapy (CLINIGENE) is to mobilise efficiently all interested parties, most- (TIGEM, Napoli), S. Aymé ly involving academic research and production centers together with companies, (INSERM, Paris), patients’ groups and regulatory bodies. Our goal is to integrate multidisciplinary C. Baum (Hannover Medical School), F. Bosch research in order to decipher the key elements which can lead to improved safe- (Universitat Autonoma ty and clinical efficacy of gene transfer/therapy medicinal products, i.e. for clin- de Barcelona), ical applications. Control and test methods will be established that may be ap- J. Bubenik (IMG-CAS, plied as platforms for particular gene transfer products. Besides quality control, Prague), M. Carrondo & safety is of germane concern since in the event where the treatment would be P. Cruz (IBET, Oeiras), proven safe, it could be administered early enough in the course of the disease N. Cartier (INSERM, to achieve genuine cure, so that clinical gene transfer may be called therapy. Paris), K. Cichutek (Paul-Ehrlich-Institute, Integration of research activities Langen), O. Cohen- Haguenauer (ENS-Cachan & APHP, Paris), N. Deglon Clinical development process (CEA, Saclay), G. Dickson Manufacturing Pharmaco- Preclinical Clinical trials Standardisation (Royal Holloway, London), toxicology models M. Federspiel (Mayo AAV R platform Clinic, Rochester), E G. Gahrton (Karolinska Retrovirus European platform Network Institutet, Stockholm), S for the B. Gänsbacher Advancement Cell therapy Feasibility of E platform of Clinical (Technische Universitaet vector system Gene Transfer standard A Muenchen), H. Hauser and Therapy Adenovirus profile (CLINIGENE) platform (Helmholtz center, R and Emerging Braunschweig), A. Jacobs Lentivector Technologies C platform (University of Cologne), H C. von Kalle (DKFZ, Non viral methods platform Heidelberg), D. Klatzmann (APHP, Paris), S. Kochanek devices (University of Ulm), Efficient and safe disease cure for assessing safety N. Mermod (University of in a faster way and Tools at lower costs for predicting benefit and effectiveness Lausanne), L. Mir (CNRS, if possible Villejuif), P. Moullier for accelerating advanced knowledge integration (CHU Nantes), P. Moullier (GENETHON, Club of Interest (CoI) Evry) The Club of Interest is the opportunity for external organisations Lentigen, Vical, Cellgenesys, AGTC, Targeted Genetics. A. Panet (Hebrew to get involved with CliniGene; organisations such as industries, CLUB OF SOCIAL INTEREST including public authorities, regu- University, Jerusalem), patients organisations, regulatory agencies, national ethics com- latory bodies: EU centralised, national and international, Learned M. Peschanski (INSERM, mittees. The CoI main goal is to create a long-term framework Societies and patients associations such as: Genetic Interest Group: Evry), D. Scherman in which basic research and technology transfer are closely linked www.gig.org.uk (A. Kent), Europa Donna: www.europadonna.fr (N. with the following objectives: to i) disseminate advanced fun- (INSERM, Paris), Zernik), Eurordis: www.eurordis.org (F. Bignami & M Lipucci). damental scientific information and standards, ii) create aca- S. Yla-Herttuala EXPERT EXTERNAL SCIENTISTS besides the three governance demic/industry synergies, iii) establish new research partner- bodies (SAB, IB & ERB – see p3): Academic scientists & doc- (University of Kuopio) ships in emerging topics, iv) accelerate technology transfer, v) tors joining the CoI have the status of Associate partner: E. Al- CliniGene industry orient the project towards market needs and finally vi) assess ton (ICL, GB); Y. Bigot (CNRS, FR); P. Bosma (GI, NL); H. Bueler partners: BioAlliance technological and scientific options. The Club of Interest is made (Univ. Zurich, CH); B. Blits (AMT, NL); M. Collins (UCL, GB); F.L. Pharma, BioReliance, up of distinct groups of interest: Cosset (INSERM, FR); J.L. Darlix (INSERM, FR); J. Farrar (Uni. CellGenix, Clean Cells, INDUSTRY COL: EU: Ark Ther., AMT, GeneIBET, ECBio, Alan Boyd Col. Cork, IE); S. Fruehauf (Univ. Heidelberg, DE); Z. Izsvak, (Del- Epixis, Genosafe, Oxford Consult., EUFETS, Cellectis, Austrianova, Artelis, Henogen, bruck, DE); Mauro Giacca (ICGEB, IT); J. Kleinschmidt (DKFZ, DE); Biomedica, Plasmid MolMed, Procure, Miltenyi, CEVEC, EuropaBio, EBE, Crucell, N. Maitland (UY, GB); B. Massie (Univ. Montreal, CA); A. Nathwani Factory, Transgene. Crusade, Huntingdon, IGEA, Microsafe, Cobra, Poly+ Trans., (UCL, GB); T. O’Brien, (REMEDI, IRL); M. Sitbon (IGMM, FR); R. Sny- Quintiles, Selexis, Schering AG, TexCell, Arthrogen, OZ Bio- der (UFL, US); M. Themis (ICL, GB); T. Vandendriessche (VIB, BE): sciences, Fovea, Genomining. USA: Florida Biologix, Ceregene, NB: FhG and Klinikum Braunschweig are partners linked to HZI.