Alexander Smolyaninov,



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«German-Russian Forum Biotechnology and Life Sciences» September, 2006 St. Petersburg Center of Cell and Gene Therapy «CRYOCENTER SAINT PETERSBURG» Stem Cell Bank «POKROVSKI» Alexander Smolyaninov, M.D.,Ph.D., General Director 1

Company Overview and Organization «CRYOCENTER SAINT PETERSBURG» is an emerging biotechnology company in Russia, focusing on the development and commercialization of gene and cell therapies to treat life-threatening diseases including genetic disorder, cancer and cardiovascular disease. Stem cells banking (including Human peripheral blood stem cells banking, Human umbilical cord hematopoietic stem/progenitor cells banking, Human Bone marrow derived stem cells banking). «CRYOCENTER SAINT PETERSBURG» is an integrated company covering all function from laboratory to the proof clinical efficacy: discovery, production, clinical development and operations, supported by quality assurance, administration and finance, and business development. 2

Goal of establishing the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» To provide effective and permanent remedies to high social impact disease by developing innovative molecular medicine therapies to improve healthcare and quality of life. To integrate a national multi-institution research and discovery program to develop treatments for serious diseases through the application of stem cells and related technologies. A core role of the Center is to attract and secure commercial partners to advance outstanding research outcomes towards clinical trials initially, and eventually into the hands of medical practitioners for the benefit of their patients. Complementary to these goals, the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» proactively works to enhance the public s awareness and understanding of stem cell and regenerative research. Involvement and collaboration with international stem cell groups and networks is a vital activity that further adds value to the Center s scientific goals. 3

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» For relevant protocols and procedures within the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» has been developed to comply with cgmp requirements. In addition to covering all stages of production, namely collection, processing, storage and release, it also addresses the following elements: equipment (purchase, use, and maintenance); materials (specifications, quarantine, and release); and quality systems (quality control, validation, and document control). 4

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» Harvesting, Aphresis Collection - fully-equipped four-room apheresis suite. 5

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» Cell Processing Center The Cell Processing Center is the most tangible aspect of a Center facility and it must conform to a variety of requirements to meet the demands of GMP. The total space of these laboratories occupies approximately 500 m2. Production is undertaken in four Class 10,000 (ISO5, Class 350) fully-equipped cleanrooms containing Class 100 (ISO7, Class 3.5) workstations. These rooms are designed to facilitate flexible, protocol-specific configurations. The rooms can operate independently under positive or negative pressure and the facility meets all physical containment level 3 (PC3) international standards. 6

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» Cryopreservation - three workspace suitable for simultaneous processing of bio-materials - two rate-controlled freezers 7

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» Storage/Banking (Vapour Phase Liquid N2) - for long-term banking, there is a vapour-phase liquid nitrogen storage facility equipped with five autofill 365-liter tanks supplied via insulated vacuum lines from a 2,000-liter supply tank. 8

Model of the Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» Support Infrastructure Patient recruitment Research Laboratories Clinical interpretation Statistical center 9

Staffing The Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» staffing is detailed in the organizational chart (see below), which conforms to cgmp requirements. Specifically, there is a production arm that includes Center of Cell and Gene Therapy «CRYOCENTER Saint Petersburg» Stem Cell Bank «POKROVSKI» staff in apheresis, cryopreservation, and the cell manipulation laboratories. To maximize flexibility, we staff the cell manipulation laboratories with hospital pharmacy technicians who have additional cell manipulation training and are employed on an as needed basis. 10

Staffing GENERAL DIRECTOR NURSE COORDINATORS DEPUTY DIRECTOR APHERESIS MANAGER PRODUCTION MANAGER Head Scientist Clinical Cell Manipulation HEAD SCIENTIST Experimental Cell manipulation QUALITY MANAGER APHERESIS NURSES DEPUTY PRODUCTION MANAGER DOCUMENTAL CONTROL OFFICERS QUALITY SYSTEMS OFFICERS SENIOR SCIENTIST - CRYOPRESERVATION FACILITY SUPERVISOR Cell Therapy Scientist PROJECT SCIENTIST Research Protocols PROJECT SCIENTIST Clinical Protocols CRYOPRESERVATION SCIENTIST CLEANROOM ASSISTANTS CELL THERAPY TECHICIANS CELL THERAPY TECHICIAN Research Protocols CELL THERAPY TECHICIAN Clinical Protocols 11

Domestic and international collaboration Institute of Experimental Cardiology, National Cardiology Research Center, Moscow, Russia, Vladimir N. Smirnov, M. D., Professor. Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch, Vladimir A. Kozlov, M. D., Professor 12

Domestic and international collaboration Research Center for Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences, Moscow, Russian, Evgeny V. Zharov, M. D., Professor Center for Regenerative Medicine, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA, David T. Scadden. Smolensk Regional Institute of Pathology, Smolensk, Russia, Alexander A. Dorosevich, M. D., Professor StemCell Technologies Inc., Canada, official distributor in Russia Chembio ltd., Irma Sakhyria 13

Domestic and international collaboration New England Cord Blood Bank, Inc., Newton, USA, John R. Rizza Sr. Massachusetts General Hospital, Center for Integration of Medicine and Innovative Technology (CIMIT), Boston, USA, Jeffrey A. Gelfand, M. D. 14

Domestic and international collaboration Department of the Public Health and Environment Sustainable Development and Healthy Environment WHO/HQ, Geneva, Switzerland, Shunichi Yamashita, M. D., Ph. D. Atomic Bomb Disease Institute of Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, Masao Tomonaga, M. D., Ph. D. 15

Research Activities Cancer Blood, bone marrow stem/progenitor cell transplantation Mesenchymal stem cell transplantation Immunotherapy Dendritic cells, natural killer cells, lymphocytes, activated macrophages Conditionally lethal suicide gene therapy Cardiovascular disorders (Infarction, heart failure, rhythm disturbances, atherosclerosis) Bone marrow stem cell transplantation Multipotent stem cells Stem cell-based gene therapy angiogenesis Orthopedic tissue repair (Joint trauma, osteogenesis imperfecta, chondrodysplasias, osteoarthritis, nonhealing fractures) Expanded chondrocytes Chondrocytes, biocompatible matrix Stem cell-derived chondrocytes Mesenchymal stem cells Diabetes Transplanted pancreatic islet cells Stem cell-derived islet cells Neurologic disorders (Parkinson's disease, Alzheimer's disease, multiple sclerosis, spinal cord injury, stroke, amyotrophic lateral sclerosis) Allogeneic or xenogeneic neural cells Stem cell-derived neural cells 16

Research Activities A. B. Smolyaninov, E. V. Zharov, K. L. Kozlov, D. A. Kirillov Base of Cell and Gene Therapy in Cardiovascular Disorders. Moscow, 2005. 17

How to contact us? Center of Cell and Gene Therapy «CRYOCENTER SAINT PETERSBURG» Stem Cell Bank «POKROVSKI» 85 Bolshoi Prospekt, Vasilievski Ostrov St Petersburg, 199106, Russia Tel +7-812-322-04-02 Fax +7-812-322-05-07 E-mail: cryocenter.spb@mail.ru www.cryocenter.spb.ru 18

We appreciate your attention! 19