March A Message from Molly and David Bloom. Dear Bloom Chair supporter,

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1 March 2015 A Message from Molly and David Bloom Dear Bloom Chair supporter, As many of you have heard, there has been a world-class discovery by Dr. Rodger Tiedemann, a hematologist at The Princess Margaret. Dr. Tiedemann was recruited four years ago by Dr. Donna Reece from the Mayo Clinic. I am pleased to share this three page report with you. It is an incredible feat that the discovery happened over such a short period of time. Your donation to the Bloom Chair enabled Dr. Tiedemann and his team to have the funds to unlock the mystery of why multiple myeloma returns. This research will open up the doors to new directions and new drugs to lengthen the remissions for the disease. This is revolutionary and all of you should take pride knowing that your financial support helped in making this research happen! We congratulate Dr. Donna Reece, Bloom Chair holder for her brilliant leadership of Chair activities. On behalf of the Bloom Chair and the 10,000 sufferers of multiple myeloma in Canada no words can adequately describe our appreciation. YOU MADE A DIFFERENCE! We are on a roll and want to ensure that we can continue this remarkable research by providing much needed funding. We are excited to let you know that the MM5kWalk is taking place on June 21, Our hope is to once again raise $500,000 for multiple myeloma related research. We need your continued support so that multiple myeloma patients will have an opportunity to improve survival rates with stabilizing drugs until a cure is found. That is the mission of the Bloom Chair SURVIVAL!!! The Princess Margaret is the centre of excellence in Canada for multiple myeloma research and clinical treatments. You have helped us develop this well-earned reputation with RESULTS.

2 You have saved the lives of so many multiple myeloma patients because of the new drugs coming on the market but we are only half way there as described in Dr. Tiedemann s findings. Thank you, once again for your dedication, understanding and unwavering commitment to helping us unlock the mystery of multiple myeloma. Help us complete the last half of this journey to eradicate this terrible disease. As an eight year multiple myeloma patient myself, I personally feel the agony and the excitement that dramatic progress is being made and I am still alive to witness this miracle. When Molly and I established the Molly and David Bloom Chair in Multiple Myeloma Research for a boutique cancer it was challenging to get on the radar screen versus the big cancers, but you came to our aid and provided encouragement and financial support. The goal to change the face of multiple myeloma research in Canada is being realized because of you and your loyalty and friendship. Thank you, Thank you, and Thank you! Kindest personal regards, David and Molly Bloom

3 An Important Update on the Molly and David Bloom Chair in Multiple Myeloma Research As the Chairholder of the Bloom Chair, I am delighted to announce a remarkable discovery by our multiple myeloma research team. Dr. Rodger Tiedemann, a clinician scientist with the Princess Margaret Cancer Centre and Ontario Cancer Institute has made a major discovery in his laboratory that will lead to improvements in the treatment of patients with multiple myeloma. Dr. Tiedemann s research focused on the reason that myeloma recurs after bortezomib (Velcade), one of the most effective anti-myeloma drugs available. Dr. Tiedemann identified the particular cell in the bone marrow a primitive myeloma cell with specific characteristics not previously described that hides from bortezomib (Velcade) therapy, only to grow back later. Now that the features of this cell are known, treatments can be developed to kill it to prevent cancer recurrence. This landmark research was directly funded by the Molly and David Bloom Chair in Multiple Myeloma Research. Thank you for your generosity and believing that we can conquer multiple myeloma in our lifetime! Kindest personal regards, Dr. Donna Reece Donna E. Reece, M.D. Director, Program for Multiple Myeloma and Related Diseases Division of Medical Oncology/Haematology Professor of Medicine Princess Margaret Cancer Centre, Room 5-207, 610 University Avenue, Toronto, Ontario M5G 2M9 t f donna.reece@uhn.on.ca

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5 NEWS RELEASE Cancer researchers discover root cause of multiple myeloma relapse (TORONTO, Canada Sept. 9, 2013) Clinical researchers at Princess Margaret Cancer Centre have discovered why multiple myeloma, an incurable cancer of the bone marrow, persistently escapes cure by an initially effective treatment that can keep the disease at bay for up to several years. The reason, explains research published online today in Cancer Cell, is intrinsic resistance found in immature progenitor cells that are the root cause of the disease and relapse says principal investigator Dr. Rodger Tiedemann, a hematologist specializing in multiple myeloma and lymphoma at the Princess Margaret, University Health Network (UHN). Dr. Tiedemann is also an Assistant Professor in the Faculty of Medicine, University of Toronto. The research demonstrates that the progenitor cells are untouched by mainstay therapy that uses a proteasome inhibitor drug ( Velcade ) to kill the plasma cells that make up most of the tumour. The progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission. Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time, says Dr. Tiedemann. Now that we know that progenitor cells persist and lead to relapse after Dr. Rodger Tiedemann treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist. Dr. Tiedemann talks about his findings: click here to watch. In tackling the dilemma of treatment failure, the researchers identified a cancer cell maturation hierarchy within multiple myeloma tumors and demonstrated the critical role of myeloma cell maturation in proteasome inhibitor sensitivity. The implication is clear for current drug research focused on developing new proteasome inhibitors: targeting this route alone will never cure multiple myeloma. Dr. Tiedemann says: If you think of multiple myeloma as a weed, then proteasome inhibitors such as Velcade are like a persnickety goat that eats the mature foliage above ground, producing a remission, but doesn t eat the roots, so that one day the weed returns. The research team initially analyzed high-throughput screening assays of 7,500 genes in multiple myeloma cells to identify effectors of drug response, and then studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that modulate response to the proteasome inhibitor Velcade and the mechanism underlying the drug resistance that is the barrier to cure.

6 Dr. Tiedemann is part of the latest generation of cancer researchers at UHN building on the international legacy of Drs. James Till and the late Ernest McCulloch, who pioneered a new field of science in 1961 with their discovery that some cells ( stem cells ) can self-renew repeatedly. The science has continued to advance unabated ever since, and notably with key discoveries by Dr. John Dick of cancer stem cells first in leukemia and next in colon cancer. Dr. Tiedemann s new findings underscore the clinical importance of understanding how cells are organized in the disease process. The research was funded by the Canadian Cancer Society, the Molly and David Bloom Chair in Multiple Myeloma Research, the Trustees of the Estate of Arthur Macaulay Cushing, Jeff Beedell and Jennifer Ward at McMillan LLP, and The Princess Margaret Cancer Foundation. 30 About the Princess Margaret Cancer Centre, University Health Network The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to or Media contact: Jane Finlayson, Public Affairs, (416) jane.finlayson@uhn.ca