$884,000 to Melanoma Research

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1 $884,000 to Melanoma Research EVERY DOLLAR IN GOES OUT! The Miller family funds all event and foundation costs so that every dollar raised goes directly to research and is 100% tax deductible. $734,000 $150,000 to Dr. Schuchter s Melanoma Research at The University of Pennsylvania to fund a Young Investigator as part of a Melanoma Research Alliance (MRA) Team Science Award at Penn It is very important to The Tara Miller Melanoma Foundation to make sure all money goes to research that is truly making an impact. Tara s mission was to change the odds for melanoma patients. To accomplish this goal, we need to not only raise money for research but also ensure we are selecting ground breaking and game changing research to fund. We have worked closely with Dr. Schuchter (Tara s doctor at Penn) to identify and fund projects that we believe will truly help get us one step closer to Tara s mission of never having another 28 year old girl walk in her path. Learn more about the research in the following pages.

2 Tara had a profound impact on my life, both as a person and a physician. Her lesson to make the best of any situation inspires me every day and will stay with me always. I am eternally grateful for the Miller family who took the tragic and untimely death of a loved one, as a catalyst for action and hope. THE TARA MILLER MELANOMA FOUNDATION IMPACT REPORT Lynn Schuchter, MD, Chief, Division of Hematology/Oncology Program Leader, Melanoma Research Program Abramson Cancer Center Building On a History of Trailblazing, Personalized Care: The Melanoma Research Program at Penn Medicine s Abramson Cancer Center (ACC) has set a standard in excellence for treating melanoma patients: but they have not done it alone. Just as research discoveries require scientific collaboration, so, too, do they depend on strong philanthropic partners. With your support, and that of the Tara Miller Melanoma Foundation, Penn s Melanoma Program continues to write the next chapter in the story of cancer treatment one that is exploding with discoveries of new genes and therapeutic targets. Robert Vonderheide, MD, DPhil Giorgos C. Karakousis, MD Lynn M. Schuchter, MD Katherine L. Nathanson, MD Emily Y. Chu, MD, PhD T R A N S L AT I O N A L S C I E N C E PAT H O L O G Y D E R M AT O L O G Y S U R G E R Y / C L I N. R E S E A R C H I N. R E S E A R C H T R A N S. S C I E N C E B A S I C S C I E N C E Ravi K. Amaravadi, MD Carl H. June, MD David E. Elder, MD, ChB O N C O L O G Y / C L O N C O L O G Y / C L I N. R E S E A R C H O N C O L O G Y / C L I N. R E S E A R C H Strength Through Philanthropic Support: The Tara Miller Melanoma Foundation has supported the innovative research of the Abramson Cancer Center s incredible scientists and physicians as well as the further expansion and development of research and trials. D E R M AT O L O G Y Tara C. Gandaghar, MD Christopher J. Miller, MD 2014 Funding Summary Tara Gangadhar, MD The Wistar Institute $50,000 Phase I RadVax Trial $100,000 Melanoma CAR T cell Trial $134,000 Total Funding $334, Funding Summary Melanoma CAR T cell Trial $200,000 Ravi Amaravadi, MD $100,000 DNA Vaccine Strategy $100,000 Total Funding $400,000 Total Investment to Date $734,000 $50,000 (in addition to $75,000 grant from the Melanoma Research Alliance) Recent Accomplishments: Since 2011, four new drugs and one combination therapy have been approved to treat melanoma by the FDA, marking the first time in 25 years that new drugs for melanoma patients are available. In 2014, the Melanoma Research Program, in partnership with the Wistar Institute, successfully competed for a new SPORE grant in melanoma. This prestigious NIH grant will be a game changer for melanoma research over the next five years.

3 2014 FUNDING SUMMARY Inspiration is felt throughout the Abramson Cancer Center: it empowers all of us to move beyond current expectations and challenge cancer on every level. We are in a transformative time in melanoma research, because of the collaborations across institutions as well as our tremendous philanthropic partners. The projects supported by the Tara Miller Melanoma Foundation are revolutionizing immunotherapy and targeted therapies for melanoma, bringing options and hope where there were previously none. Chi V. Dang, MD, PhD, John H. Glick, M.D. Abramson Cancer Center Director s Professor Director, Abramson Cancer Center Tara Gangadhar, MD, Assistant Professor of Medicine is developing unique, combination immunotherapy approaches to melanoma care. She has begun a study giving Pembrolizumab, a targeted immune checkpoint inhibitor or anti-pd1 drug that allows the immune system to attack cancer, to advanced melanoma patients prior to surgery. After a patient s tumor has been surgically removed, Dr. Gangadhar then collaborates with E. John Wherry, PhD, Director of the Institute for Immunology, who is an international leader in the field of immunotherapies and the development of anti-pd1 drugs. Together they take T cells from the resected tumor and analyze them to learn how Pembrolizumab is actually working. They are addressing the question: why does the drug work in some patients but not others? by seeing its response on the tumor in real time. They are also figuring out mechanisms of resistance to treatment and, subsequently, improving upon treatment options for melanoma patients. The study is also asking if providing early administration of anti-pd1 drugs, before the onset of advanced metastatic melanoma, is helpful in preventing widespread metastasis. The Wistar Institute s Ashani Weeraratna, PhD, a basic scientist, is using her support to look at the molecules identified as markers of aggression in melanoma and how they can affect immune cells entering the tumor and their behavior once inside. The goal is to target those molecules and make the immune system within the tumor more efficient, with the hope that therapies like checkpoint inhibitors will be more effective as well. Phase I RadVax Trial The combination of ipilimumab an FDA-approved anti-ctla4 antibody that lifts the breaks on the immune system and allows T cells to infiltrate and attack tumor cells with radiation shrank tumors in a subset of 22 metastatic melanoma patients. It is believed that adding radiation results in a synergistic attack, turning the destroyed tumor cells into a vaccine against the cancer. The treatment has earned the name RadVax because of its vaccine-like qualities. Melanoma CAR T cell Trial Tara Miller Melanoma Foundation funds will help launch a history-making phase 1 melanoma CAR T clinical trial in melanoma that will take patients T cells and transform them to target c-met, a protein that cancer cells exhibit in overabundance on their surface. Pre-clinical laboratory work, creating an Institutional Review Board (IRB) protocol, and Federal Drug Administration inclusion has all been completed FUNDING SUMMARY Melanoma CAR T cell Trial Over the course of the next two years, the Tara Miller Melanoma Foundation funds will accelerate a 10 patient, Phase 1 melanoma CAR T clinical trial. Ravi Amaravadi, MD, Associate Professor of Medicine, will employ combination therapies of autophagy, a resistance mechanism where cancer cells cannibalize in order to survive, with BRAF and MEK inhibitors that target melanoma from all angles to overwhelm the ability of the tumor to develop resistance. DNA Vaccine Strategy to Melanoma Bob Vonderheide, MD, DPhil, Hanna Wise Professor in Cancer Research and Associate Director of Translational Research and David Weiner, PhD, Professor of Pathology and Laboratory Medicine, have focused on research at Penn to develop a novel immunetherapeutic vaccine to treat many types of cancer. They identified a target known as htert that is expressed in more than 90% of all human cancers, but rarely in normal cells. Dr. Weiner has developed a TERT DNA vaccine that is currently being used in a phase I clinical trial to test its safety, given in conjunction with IL-12 DNA adjuvant to further boost immunity, and delivered by electroporation. Based on these initial findings, expanding this DNA vaccine strategy to treat melanoma patients is a very exciting new research opportunity and funding from the Tara Miller Melanoma Foundation will help to fund this expansion.

4 Letter from Lynn Schuchter, MD C. Willard Robinson Professor of Hematology-Oncology Chief, Division of Hematology-Oncology Program Leader, Melanoma Research Program, Abramson Cancer Center February 2016 The Tara Miller Melanoma Foundation Post Office Box 3154 Margate City, NJ Dear Debbie, George, Kristi, and Lauren: It is a pleasure to provide you with the enclosed progress report for the Tara Miller Melanoma Foundation. Tara s generosity of spirit continues to inspire and motivate me, and the entire Abramson Cancer Center community. Every day we work to live up to her tremendous expectations and charge to find a cure for melanoma. I am pleased to thank you for your tremendous support and update you on how the Tara Miller Melanoma Foundation has advanced melanoma research and patient care at Penn Medicine s Abramson Cancer Center. Scientific advancements are only possible because of the dedicated support of our philanthropic partners. You have galvanized an incredibly dedicated community of supporters and advocates through the Tara Miller Melanoma Foundation- a community championing revolutions in immunotherapy and targeted therapies for melanoma. Your support provides a strong foundation and crucial seed funding that allows our dedicated team to translate scientific discoveries into clinical therapies, conduct history-making trials, and better provide exemplary and compassionate care to our patients. When it comes to transforming the health of our nation, there is no better return on investment than training the next generation of physician-scientists. As you will see within the enclosed report, the Tara Miller Melanoma Foundation is supporting two young innovators: Tara Gangadhar, MD, and Ashani Weeraratna, PhD, who are changing the way we think about, and treat, melanoma. For instance, your support allows Dr. Weeraratna to take early research and develop it into projects that can qualify for NIH grants and other funding. The chance to get the preliminary data needed to prove the hypotheses being discussed is critical. A big goal of her research is to identify drugs to put into phase one clinical trials. An exciting recent development is the identification of a FDA approved drug used to treat diabetes that will be very important to the disruption of cancer growth. Additionally, the Abramson Cancer Center s Melanoma Research Program continues to unlock the full capacity of immunotherapy, using insights gained from CAR T cells clinical trials in leukemia and lymphoma to develop strategies targeting melanoma. Treating solid tumor cancers with CAR T cells is the next big step, and a portion of the Tara Miller Melanoma Foundation s funds will launch Penn Medicine s history making work in immunotherapy for melanoma. Inspiration is felt throughout the Abramson Cancer Center: it empowers all of us to move beyond current expectations and challenge cancer on every level. We are in a transformative time in melanoma research, not only because of collaborations across institutions, but also because of you and your dedicated Jersey Shore community. You are fueling the development and advancement of innovative therapies and treatments. Together we are carrying on Tara s mission to keep pushing for a melanoma cure. Her life is a heartening reminder of how far we have come, but how much more work we have to do. We will not stop until we have reached our goal. Thank you, again. All my best, Lynn Schuchter, MD Penn Medicine Development and Alumni Relations 3535 Market Street, Suite 750 Philadelphia, PA

5 2015 Melanoma Research Alliance Team Science Award University of Pennsylvania: Radiation and immune checkpoint blockade from mechanism to patients Young Investigator funded by The Tara Miller Melanoma Foundation $225,000 Total Investment ($75,000 per year in ) Robert Vonderheide, Associate Professor of Medicine, University of Pennsylvania Andy Minn, Assistant Professor, Department of Radiation Oncology, University of Pennsylvania John Wherry, Associate Professor, Department of Microbiology, University of Pennsylvania Young Investigator: Tara Gangadhar, Assistant Professor of Medicine, University of Pennsylvania Young Investigator: Christina Twyman- Saint, Instructor of Medicine, University of Pennsylvania Summary: Melanoma can suppress the immune system through receptors that act as brakes for T cell activation. Immune checkpoint blockade (ICB) can reverse this process and has resulted in unprecedented improvement in survival. Unfortunately, the majority of patients still relapse, making the elucidation of resistance mechanisms and combination therapies high priority. We have assembled a multi- disciplinary melanoma research team dedicated to rapid discovery and clinical impact. Members include experts in cancer immunology, immune checkpoint biology, discovery of resistance mechanisms and melanoma clinical trials. Our goal is to simultaneously use mouse models and clinical trials to discover resistance mechanisms and ways to improve ICB that are readily deployable in the clinic. We are investigating if radiation (RT) and other therapies can diversify T cells with potential to attack melanoma and then unleash this potential with ICB combinations that minimizes resistance. As a first step, we initiated a clinical trial of ICB combined with RT for stage IV melanoma, which was led by Young Investigators supported by MRA, and used mouse models to mimic the clinical trial. Remarkable responses occurred; however, improvement was still needed. Using mice and patients, we discovered resistance mechanisms, insight into how RT cooperates with ICB and biomarkers consistent with the translational potential of our findings. We used this information to design second- generation clinical trials, which will soon start. This proposal will iterate this bench- to- bedside approach by 1) testing ways to enhance RT and further improve ICB, 2) discover additional resistance mechanisms and how to reverse them, and 3) use biospecimens from our second- generation clinical trials to examine biomarkers and mechanisms revealed by mouse studies. We anticipate these efforts will have rapid clinical impact, allowing us to design third- generation clinical trials to reduce the mortality of melanoma. Research Impact: This team of investigators aims to explore novel combinations of radiation and immune checkpoint blockade to combat drug resistance and ultimately improve therapeutic approaches for melanoma patients. About the Young Investigators: Tara Gangadhar, M.D. (Funded by the Tara Miller Melanoma Foundation s investment of $75,000 per year for 3 years) Dr. Gangadhar is an Assistant Professor of Medicine in the Department of Hematology/Oncology at the Abramson Cancer Center at University of Pennsylvania. She received her M.D. degree at New York University and completed her residency in Internal Medicine at Indiana University. Following her residency, she was a postdoctoral fellow at the University of Chicago. As part of this Team Science Award, Dr. Gangadhar will be involved in studies to examine treatment related biomarkers from the clinical trial. She will be mentored by the lead Principal Investigator, Dr. Robert Vonderheide. Christina Twyman- Saint Victor, M.D. Dr. Twyman- Saint Victor is an Instructor of Medicine at the University of Pennsylvania. She received her M.D. degree and completed her residency in Internal Medicine at Johns Hopkins University. She also completed a fellowship in gastroenterology at the University of Pennsylvania. As part of this team, Dr. Twyman- Saint Victor will be involved in pre- clinical work of anti PD- 1 resistance. Her mentor for the project will be team Principal Investigator Dr. Andy Minn, Assistant Professor of Radiation Oncology at the University of Pennsylvania.