Human Stem Cells Institute

Human Stem Cells Institute OJSC (HSCI) (Институт Стволовых Клеток Человека or «ИСКЧ») is a Russian public biotech company founded in 2003. HSCI engages in R&D as well as commercialization and marketing of innovative proprietary products and services in the areas of cell-based, gene and post-genome technologies. HSCI aims to foster a new culture of medical care – developing new health care opportunities in such areas as personalized and preventive medicine.

Today, HSCI’s projects encompass the five main focus areas of modern biomedical technologies: regenerative medicine, bio-insurance, medical genetics, gene therapy, biopharmaceuticals (within the international project SynBio).

HSCI owns the largest family cord blood stem cell bank in Russia – Gemabank®, as well as the reproductive cell and tissue bank Reprobank® (personal storage, donation).

The Company launched Neovasculgen®, the first-in-class gene-therapy drug for treating Peripheral Arterial Disease, including Critical Limb Ischemia, and also introduced the innovative cell technology SPRS-therapy, which entails the use of autologous dermal fibroblasts to repair skin damage due to aging and other structural changes.

HSCI is implementing a socially significant project to create its own Russia-wide network of Genetico medical genetics centers to provide genetic diagnostics and consulting services for monogenic inherited diseases as well as multifactorial disorders (Ethnogene, PGD and other services).

The Company actively promotes its products on the Russian market and intends to open new markets throughout the world.

HSCI is listed on the Innovation & Investment Market (iIM) of the Moscow Exchange (ticker ISKJ). The Company conducted its IPO in December 2009, becoming the first Russian biotech company to go public.

History
In 2003, the Human Stem Cells Institute and Gemabank were established. Over the next few years, the Company increased its client base while expanding its technological abilities. In 2008, HSCI gained a blocking stake in the German biotech company, SymbioTec GmbH, which owns international patents for a new generation of drugs to treat cancer and infectious diseases. In 2009, HSCI successfully raised RUB 142.5 million in an IPO on MICEX and became the first publicly traded biotech company in Russia. The Company continued to expand in 2010, when it gained a 50% stake in Hemafund, Ukraine’s largest family cord blood bank. In 2011, HSCI initiated the SynBio Project, as a long-term partnership with RUSNANO (a state-owned fund for supporting nanotechnologies) and some major R&D companies from Russia and Europe including Pharmsynthez, Xenetic Biosciences and SymbioTec (which was acquired by Xenetic Biosciences pursuant to the SynBio project agreement ). The project is founded on strong principles of international scientific cooperation, as participating research centers are found in England, Germany, and Russia.

Research and Development
HSCI is engaged in scientific studies and research in the main fields of biomedical technology with the aim of creating innovative products (drugs, medical devices, technologies, services, etc.) which are capable of solving urgent and complex challenges faced by clinical medicine today and which could be incorporated into contemporary healthcare practices. Within of each of the main fields of biomedical technology – cell (regenerative medicine), gene (genetic medicine) and post-genome (biopharmaceuticals) technologies – the Company is currently undertaking several scientific research projects.

Regenerative medicine

 * Gemacell and Cryocell – prototypes of drugs based on cells from umbilical cord blood for the treatment of chronic cirrhosis of the liver (clinical trial protocol Gemacell-cirrhosis within the SynBio project) and ischemic heart disease (clinical trial protocols Gemacell-IHD and Cryocell-IHD); these drugs are currently undergoing clinical trials.
 * SPRB+SPRG-therapy – a set of personalized diagnostics and treatment procedures for restoration of periodontium soft and hard tissues by applying biocomposite osteoplastic material and autologous gingival fibroblasts. SPRB-therapy (Service for Personal Regeneration of Bone) is a cell-based technology for treating patients with pathologies affecting periodontal hard tissues (i.e. bone tissues lost due to infection or other pathological processes). This is a medical service which includes isolation of the patient’s gingival cells, cell processing and placement of cell cultures in bioresorptive media to grow personal tissue-engineered product for transplantation into the same person during surgical treatment of periodontal pathologies. This service is a logical continuation of SPRG-therapy (Service for Personal Regeneration of Gum) – a cell-based technology designed to correct and restore periodontal soft tissues by applying autologous gingival fibroblasts. HSCI received an authorization to use this technology in December 2010. Together, these two services, based on the same technology platform for tissue engineering, provide an effective instrument for treating patients with destructive forms of periodontal diseases (for the comprehensive restoration of various periodontal tissues).
 * Nucleostim – a medical innovation that delivers gene-therapy osteoplastic material composed of a carrier and active component – vascular endothelial growth factor (VEGF) embedded in a plasmid vector. The nucleic acids provide the main action mechanism and hence effectiveness of the product in osteoplastic surgery (traumatology, orthopedics and oral surgery). This is the only project of its kind in Russia.

Genetic medicine

 * Gemascreen services using DNA array – a set of genetic diagnostics and consulting services to identify carrier status of inherited diseases and predisposition to them as well as subsequent consultation regarding prevention or early treatment measures in the case that susceptibility is discovered. These services are offered based on a DNA array developed specially by HSCI which allows for diagnosis of more than 80 inherited diseases for which the population of the Russian Federation is most susceptible.
 * Preventative treatment program for primary immunodeficiency diseases– a medical service based on Preimplantation Genetic Diagnosis (PGD) which helps ensure the birth of a healthy child through application of genetic controls during the use of assisted reproductive technologies.
 * Reprogramming technologies which make it possible to derive from differentiate (non-pluripotent) cells induced Pluripotent Stem сells (iPS cells). The Company is pursuing research into two different areas in relation to such reprogramming technologies. The first is related to the development of a testing system for trials of new drugs intended for the treatment of inheritable nervous system disorders. The second area is the development of technologies for obtaining large quantities of neural stem cells from iPS cells for the purpose of restorative cell therapy.
 * Human artificial chromosome (HAC) – a microchromosome created via chromosome engineering technology carrying one or more therapeutic genes. The main advantage represented by HAC is the possibility of achieving stable, long-term expression without impacting the cell’s genome, which presents substantial opportunities to develop products for treating patients with genetically determined diseases.

Biopharmaceuticals (SynBio project)

 * Development of drugs using histone proteins as vectors for genetic constructs as well as research on the clinical efficacy of using histone H1.3 taking into account its selective anticancer activity.
 * Development of drugs using a novel technology employing polysialic acid conjugates as the active ingredient to provide the sustained action and effect of the medications.

Subsidiaries and Affiliates

 * RGMC LLC (Regenerative and Genetic Medical Center of the Human Stem Cells Institute, Russia) was specially created in October 2012 for providing HSCI’s medical services (with the aim to use tax allowance).
 * Cell Technology Laboratory LLC (Russia) is a research subdivision of HSCI in Russia created for developing innovative cell- and gene-based technologies with promising medical application including such as ESC and iPS.
 * Vitacel LLC (Russia) is focused on developing innovative cell-based and tissue engineering technologies; has developed and patented SPRS-therapy – a set of personalized diagnostics and treatment procedures for individual skin regeneration based on the use of autologous dermal fibroblasts to repair skin damage due to aging or other structural changes. The company is currently developing the technology of restoring periodontium soft and hard tissues by application of autologous gingival fibroblasts and biocomposite osteoplastic material.
 * Cryonix CJSC (Russia) is developing cell-based medications as well as introducing new therapeutics based on Histone H1. The Company also represents Gemabank’s services in Saint Petersburg and the region.
 * NextGen Company Limited (Russia) the company focuses on R&D in the area of cell and gene therapy, on the development of new ways to treat inherited diseases using Assisted Reproductive Technologies and on the creation of DNA arrays for the diagnosis of inherited diseases and predisposition to them.
 * Hemafund Medical Centre LLC (Ukraine) is a family cord blood bank and the market leader in Ukraine. The specialists of Hemafund are actively implementing partnership programs with colleagues from Western European countries.
 * Hemafund Medical Biotech Company LLC (Ukraine) works to advance R&D projects in cell technology, develop new methods of treatment and implement them into clinical practice.
 *  IceGen LLC (Russia) - IceGen LLC was created in August 2011 for the consolidation of the shares of participants of the SynBio project (except RUSNANO OJSC) as an asset holding company.
 * SynBio LLC (Russia) is a special project company established to develop innovative medicines, first-in-class and those known as BioBetters.