EMBARGOED UNTIL MARCH 26, 2014 AT 9:00 A.M. EST

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1 EMBARGOED UNTIL MARCH 26, 2014 AT 9:00 A.M. EST 2014 CANADA GAIRDNER AWARDS HONOUR TOP MEDICAL DISCOVERIES TORONTO, ON (March 26, 2014) - The Gairdner Foundation is pleased to announce the winners of the 2014 Canada Gairdner Awards, recognizing some of the most significant medical discoveries from around the world. This year s winners showcase a broad range of new medical discoveries related to cardiovascular disease, cancer, immunotherapy and human parasitic diseases. Among the world s most esteemed medical research prizes, the awards distinguish Canada as a leader in science and provide a $100,000 CDN prize to each scientist for their work. The Canada Gairdner Awards promote a stronger culture of research and innovation across the country, inspiring a new generation of researchers. The selections for the Canada Gairdner International Awards, recognizing individuals from various fields for seminal discoveries or contributions to medical science, are: James P. Allison, Ph.D., Professor and Chair, Department of Immunology, The University of Texas, MD Anderson Cancer Center, Houston Awarded for his discovery of immune checkpoint blockade and its successful application to immune therapy of cancer. The work: Allison s research has focused on T cell biology. T cells are white blood cells that scan our bodies for cellular abnormalities and infections. Allison s work discovered the receptor these cells use to recognize and bind to antigens for attack. Immunologists have long wondered why the immune system doesn t fight off cancer cells itself and Allison discovered the first blocker that blocks the immune system from doing so. This discovery was the immune checkpoint molecule called CTLA-4, which turns off T cells before they can respond to tumors they ve been set to destroy. Allison developed an antibody to block CTLA-4, freeing T cells to attack tumors, and leading to the development of the drug ipilimumab. The U.S. Food and Drug Administration (FDA) approved ipilimumab (Yervoy ) for treatment of metastatic melanoma in The impact: Allison s concept has opened a new field of cancer therapy, immune checkpoint blockade, and many cancer patients are alive today because of his vision. Immune checkpoint blockade treats the immune system instead of the tumor which provides the option to work across other cancers. In addition to melanoma, ipilimumab has been effective in clinical trials against prostate, kidney, lung and ovarian cancers. Titia de Lange, Ph.D., Leon Hess Professor; American Cancer Society Professor; Head, Laboratory of Cell Biology and Genetics; Director, Anderson Center for Cancer Research; Rockefeller University, New York Awarded for her discovery of the mechanisms by which mammalian telomeres are protected from deleterious DNA repair and damage responses. 1

2 The work: The problem de Lange has focused on for the past two decades is a basic problem in cell biology. Chromosomes are made of protein and a single molecule of deoxyribonucleic acid (DNA) and have two ends. Our body has a vigilant surveillance system which is always looking for damage to our DNA, including breaks which can lead to various diseases, such as cancer. The ends of chromosomes are called telomeres and Dr. de Lange discovered that they are bound by a complex of proteins she named shelterin. De Lange s work addressed the mechanism by which telomeres protect chromosome ends, an issue she refers to as the telomere end-protection problem. De Lange revealed that telomeres need to repress six distinct DNA damage response (DDR) pathways that threaten genome integrity. She identified the shelterin protein complex that protects telomeres and established how distinct shelterin subunits repress different DDR pathways. The impact: Her work has solved a long-standing riddle in biology, one that has profound implications for our understanding of effective cell proliferation, chromosome integrity and a diverse array of human disorders including cancer and aging. The work on the telomere endprotection problem and the types of genome instability that result from lack of telomere function has informed scientists about the events involved in early tumorigenesis when telomeres shorten due to the lack of telomerase. De Lange s findings argue that the genome instability in human cancer is in part due to loss of telomere function. Furthermore, understanding how telomeres solve the end-protection problem is directly relevant to the telomeropathies, which are diseases caused by compromised telomere function. Professor Sir Marc Feldmann, FRS, FAA, Head, Kennedy Institute of Rheumatology; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford Sir Ravinder Nath Maini, FRS, FMedSci, FRCP, Visiting Professor Kennedy Institute of Rheumatology, University of Oxford, Oxford Awarded for the discovery of anti-tnf therapy for the treatment of rheumatoid arthritis and other inflammatory diseases. The work: Rheumatoid arthritis (RA) is a common, chronic, painful and disabling autoimmune disease. Prior to the work of Drs. Feldmann and Maini, the treatment of RA was not based on understanding of which molecules were produced in excess. In the mid-1980 s, the team began work on unravelling which molecules might be the culprit of this disease in hopes of determining which targets would be ideal for treatment. Experiments in the laboratory on cells from joints of patients and in an animal model of RA demonstrated that tumor necrosis factor (TNF), a molecule belonging to the cytokine family, was a major driver of inflammation and joint damage. They discovered a monoclonal antibody-based treatment that blocked the action of TNF and was safe and effective for treating in RA. Anti-TNF therapy works in most patients rapidly to reduce pain, improve mobility, reduce work disability, improve social functioning, and, when compared with patients on conventional synthetic drug treatments, reduces the risk of heart attacks, strokes and increases life expectancy. It has a major role in protecting joints from degeneration, thus maintaining good physical function and reducing the need for joint surgery. The impact: They discovered the first treatment for RA, using monoclonal antibodies which are genetically engineered natural defense molecules. Not only was this a novel treatment, but it was the first demonstration of the efficacy of a biological therapy for a chronic autoimmune disease and led to the recognition by the pharmaceutical industry that biological drugs are a viable class of therapeutic agents that can compete with traditional chemical drugs. The 2

3 effective results have not only transformed the treatment for patients, but have led to other successful anti-tnf treatments, and encouraged much further work using antibodies for treatment. Harold Fisher Dvorak, M.D., Mallinckrodt Distinguished Professor of Pathology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston Napoleone Ferrara, M.D., Distinguished Professor of Pathology; Distinguished Adjunct Professor of Opthalmology; Senior Deputy Director for Basic Sciences, UC San Diego Moores Cancer Center, La Jolla Awarded for discovering Vascular Endothelial Growth Factor (VEGF), a key molecular mediator of new blood vessel formation and the development of effective anti-vegf therapy for cancer and wet macular degeneration. The work: Blood vessels are the part of the circulatory system that transports blood throughout the body and also play a vital role in virtually every medical condition. In 1983, Dr. Dvorak reported a tumour-derived protein that caused the cells lining tumor blood vessels to become leaky (hyperpermeable) to circulating molecules. He called the protein vascular permeability factor (VPF). Subsequently, he demonstrated that VPF was also secreted by many normal cells and plays a key role in wound healing and chronic inflammatory diseases. At the same time, Dr. Ferrara noted that cells released a factor that caused cells to divide. This factor stimulated the production of new blood vessels from pre-existing vessels (angiogenesis). In 1989, Dr. Ferrara reported for the first time the isolation and sequencing of vascular endothelial growth factor (VEGF) which, after testing, ended up being the exact same molecule as VPF, and VEGF became its new name. The impact: Dr. Dvorak s research demonstrated that most malignant tumors make VEGF, which assists the tumors to grow beyond minimal size by forming new blood vessels and connective tissue support as in wound healing. Dr. Ferrara s cloning and characterization of VEGF enabled progress in this field. In addition, Dr. Ferrara and his team made key advances in understanding how VEGF was made, how it acted and its role. Importantly, Dr. Ferrara and his colleagues pioneered the clinical development of an inhibiting antibody against VEGF which opened up a new era of cancer therapy because this new approach focused on choking off the blood supply that tumours need in order to grow and spread. These findings also spearheaded the development of an anti-vegf antibody fragment (ranibizumab) which has shown dramatic efficacy in maintaining and improving vision in wet age-related macular degeneration (AMD) patients. The Canada Gairdner Global Health Award, recognizing someone who is responsible for a scientific advancement that has made a significant impact on health in the developing world, goes to: Satoshi Omura, Ph.D., Distinguished Emeritus Professor; Special Coordinator, Department of Drug Discovery Sciences, Kitasato University, Tokyo Awarded for the discovery of the microorganism Streptomyces avermitilis and its extraordinary biologic activity that in partnership with Merck led to the identification of avermectin and development of ivermectin, a highly successful treatment for many parasitic diseases, and the global consortium directed at eliminating river blindness. 3

4 The work: In 1973, the Kitasato Institute in Japan, led by Professor Satoshi Omura, formed a collaborative research partnership with Merck to discover new animal health products. Within this partnership, Professor Omura and his research team based at the Kitasato Institute in Tokyo isolated and screened microorganisms and sent the promising ones to the Merck laboratories in the United States. Of particular interest was a microorganism, Streptomyces avermitilis, isolated from soil near an oceanside golf course in Japan which had potent bioactivity. Researchers at Merck s lab conducted further testing on the microorganism and then the compound responsible for the activity was named avermectin. Scientists at Merck refined avermectin under the name ivermectin, which was the safest and most potent derivative. Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found. The impact: Ivermectin, commercialized in 1981 as a highly successful veterinary drug active against both internal and external parasites, was later found to be safe and effective for treating several human parasitic diseases such as Onchocerciasis (river blindness) and Lymphatic filariasis (elephantiasis). Merck joined forces with the World Health Organization (WHO), the Special Programme for Research and Training in Tropical Diseases (TDR) and the Onchocerciasis Control Programme in West Africa (OCP) to test the drug in humans. Ivermectin was registered for human use by French regulators in With the Kitasato Institute agreeing to forego royalties, Dr. Roy Vagelos, the then Chief Executive of Merck, announced that ivermectin would be provided free of charge for the treatment of river blindness for as long as it is needed, a pledge that is still being honoured. Utilizing a truly international partnership involving the public and private sectors, governments of disease-endemic countries and affected communities, mass drug administration commenced in 1988 and the donation has allowed the goal of eliminating both diseases to become achievable in the near future. Ivermectin has also become the drug of choice to treat strongyloidiasis, scabies and head lice and research is being conducted into its effectiveness against other neglected tropical diseases. The Canada Gairdner Wightman Award, given to a Canadian who has demonstrated outstanding leadership in medicine and medical science throughout his/her career, is awarded to: Salim Yusuf, MBBS, DPHIL, FRCP(UK), FRCPC, FACC, FRSC, OC, Professor of Medicine, McMaster University; Director, Population Health Research Institute, VP of Research, Hamilton Health Sciences, Hamilton General Hospital, David Braley Research Institute, Hamilton Awarded for his exceptional leadership in global clinical trials and population studies of cardiovascular disease that shaped best guidelines for prevention and treatment. The work: Dr. Yusuf s epidemiological work in over 60 countries in all the inhabited continents of the world shows the majority of risks of both cardiovascular and cerebrovascular disease are attributable to the same few risk factors. He currently leads the largest ever study revealing the role of societal changes in cardiovascular disease (CVD) among 155,000 people from 700 communities in 22 high, middle and low income countries. Dr. Yusuf led the HOPE Trial that demonstrated that Ramipril (an ACE inhibitor) saved lives, prevented heart attacks and strokes among patients with stable heart disease. The impact: Dr. Yusuf s trials (such as SOLVD, HOPE, OASIS, CHARM, ON-TARGET, TRANSCEND, etc.) on the prevention and treatment of CVD and related conditions (such as 4

5 hypertension and diabetes) have improved the care of patients. His research and insights have produced substantial changes in guidelines for the prevention and treatment of disease. His large trials have led to more effective treatments for acute heart attacks, congestive heart failure, heart rhythm abnormalities and chronic heart disorders. These studies have led to better understanding of the role of societal changes on behaviours and risk factors, and how they lead to CVD. Over the last three decades he has built capacity for clinical and population research across Canada and the world by establishing networks at over 1,500 sites in 85 countries. The Canada Gairdner Awards will be presented at a dinner in Toronto on October 30 th, 2014 as part of the Gairdner National Program, a two week lecture series given by Canada Gairdner Award winners at 24 universities from St John's to Vancouver. The National Program reaches students across the country, making the superstars of science accessible and inspiring the next generation of researchers. The Canada Gairdner Awards distinguish Canada as a leader in biomedical research, raising the profile of science both nationally and on the world stage, said Dr. John Dirks, President and Scientific Director, Gairdner Foundation. This year s winners are an exceptional example of highly effective outcomes from translational research. The Gairdner Foundation: Making Science Matter The Canada Gairdner Awards were created in 1959 to recognize and reward the achievements of medical researchers whose work contributes significantly to improving the quality of human life. They are Canada s only globally known and respected international science awards, and Gairdner is the only national organization that consistently brings the world s best biomedical researchers to Canada to share their ideas and work with scientists across the country. In so doing, it enlarges networks and enhances Canada s international reputation, while providing a realistic and unbiased benchmark for Canada s leading scientists. All winners are chosen by an adjudication committee and all choices are deemed final. For further information: Sommer Ellis Director of Communications, Gairdner Foundation sommer@gairdner.org Main: ext.202 Cell:

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