over $2.4 million to melanoma research!

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1 Since 2014, the Tara Miller Melanoma Foundation has funded over $2.4 million to melanoma research! I am on drugs that were not available a year ago. Hopefully one day we will get to see the money raised by this Foundation making a difference in someone else s fight against this terrible disease. $750,000 Funded to Melanoma Research Alliance Young Investigators / Team Science Awards: Tara Miller $225,000 to fund a study at UPenn looking at radiation and immune checkpoint blockade from mechanism to patients at University of Penn. $225,000 to fund a collaboration project between Tel-Aviv University, Dana-Farber & Hebrew University looking at novel regulators of melanoma brain metastasis. $225,000 to fund a study analyzing how chemical modifications to DNA can result in resistance to immunotherapies. to year 1 (of 3) to a Young Investigator who will be selected after the MRA Scientific Retreat. $1,684,000 Funded to melanoma research at Penn s Abramson Cancer Center 2014 $334, $400, $450, $500,000 Tara Gangadhar, MD The Wistar Institute Phase I RadVax Trial Melanoma CAR T Cell Trial Melanoma CAR T Cell Trial Ravi Amaravadi, MD DNA Vaccince Strategy Melanoma Brain Metastases Role of Estrogen in Moles Becoming Melanoma Melanoma Resistance to Targeted Therapies Novel Approach to TCell Therapy in Melanoma RadVax in Melanoma with Triple Therapy Additional Research Support Overcoming Resistance to Immunotherapy Melanoma Metastases Who Benefits from Immunotherapy Resistance to Targeted Therapies Role of Estrogen and Sensitivity to Immunotherapy PD-1 Biomarker Evaluation Anti-CTLA in Melanoma Treatment Innovative Melanoma Research Fund TOTAL $2,434,000 $134,000 $200,000 TaraMillerFoundation.org

2 Robert H. Vonderheide, MD, DPhil Director, Abramson Cancer Center John H. Glick, MD Abramson Cancer Center s Director Professor February 5, 2018 The Miller Family 2201 Atlantic Avenue Longport, NJ Dear George, Debbie, Lauren, and Kristi: The impact of the nearly $2 million that the Tara Miller Melanoma Foundation has given to Penn s Melanoma Program can be seen in the lab, in the clinic, and in scientific publications that are fundamentally changing the way we treat this disease. But Tara s lasting legacy transcends these spaces. She lives on in the work that Dr. Lynn Schuchter and her team move forward each day, and in the hearts and minds of everyone at the Abramson Cancer Center. I remember so vividly the speech Tara gave at the ACC s 40 th anniversary. She spoke with such courage and dignity in the face of the biggest challenge of her young life. What was so impactful about her speech, though, was the determination in her voice about raising funds for research. Tara spoke beautifully of the game changing therapies she received that were only possible because of philanthropy. By choosing to make that the directive for her foundation, she not only challenged all of us to do even more, but also gave us the resources to invest in a CAR-T trial in melanoma and better understand resistance to immunotherapy and targeted therapies. And this is just the beginning. While they may not have met her personally, everyone at the ACC knows Tara Miller. We all find inspiration in her story and we are all motivated by those words she chose to live by: make the best of it. That is Tara s legacy here at Penn. I speak for our entire community when I say, thank you. Sincerely, Robert H. Vonderheide, MD, DPhil Director, Abramson Cancer Center John H. Glick, MD Abramson Cancer Center s Director Professor University of Pennsylvania Perelman School of Medicine Cc: Lynn Schuchter, MD Perelman Center for Advanced Medicine Civic Center Boulevard Philadelphia, PA

3 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 M. 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. To date, the Tara Miller Melanoma Foundation has provided nearly $2 million in funding to advance the innovative research of the ACC s incredible scientists and physicians, as well as the further expansion and development of research and clinical trials. The Tara Miller Melanoma Foundation s 2017 funding supports projects in three major award categories: Team Science, Young Investigators, and Established Investigators. All three types of awards highlight the collaborative expertise that makes up the Melanoma Program at Penn. The projects selected this year each address a fundamental challenge: why treatments work for some patients, but not others. The Miller Family with Dr. Lynn Schuchter, Director of the Melanoma Program, Dr. Robert Vonderheide, Director of the Abramson Cancer Center, and funded researchers Dr. Alexander Huang and Dr. Tara Gangadhar Funding Summaries 2014 Funding Summary Tara Gangadhar, MD The Wistar Institute Phase I RadVax Trial Melanoma CAR T cell Trial $134,000 Total Funding $334, Funding Summary Melanoma CAR T cell Trial $200,000 Ravi Amaravadi, MD DNA Vaccine Strategy Total Funding $400, Funding Summary Melanoma Brain Metastases Role of Estrogen in Moles Becoming Melanoma Melanoma Resistance to Targeted Therapies Novel Approach to T cell Therapy in Melanoma RadVax in Melanoma with Triple Therapy Innovative Melanoma Research Fund Total Funding $450, Funding Summary Team Science Awards Overcoming Resistance to Melanoma Immunotherapy Understanding Melanoma Metastases Young Investigator Awards Understanding Who Benefits from Melanoma Immunotherapy Understanding Resistance to Melanoma Targeted Therapies Established Investigator Awards Role of Estrogen and Sensitivity to Melanoma Immunotherapy PD-1 Biomarker Evaluation Understanding Anti-CTLA in Melanoma Treatment Innovative Melanoma Research Fund Total Funding $500,000 Total Investment to Date $1,684,000

4 The Abramson Cancer Center s progress is driven by transformational philanthropy. Together we are seizing new opportunities and accelerating our position as a world leader in modern cancer research and clinical care. We already cure cancer. But with your continued help we will cure more cancer in every patient. Robert H. Vonderheide, MD, DPhil, John H. Glick, M.D. Abramson Cancer Center Director s Professor Director, Abramson Cancer Center 2014 Funding Summaries and Updates - $334,000 Tara Gangadhar, MD, Assistant Professor of Medicine researches unique, combination immunotherapy approaches to melanoma care. Dr. Gangadhar collaborated 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. She began a study treating advanced melanoma patients with pembrolizumab, a targeted immune checkpoint inhibitor or anti-pd1 drug that allows the immune system to attack cancer, prior to surgery. After a patient s tumor was surgically removed, together with Dr. Wherry, they took T cells from the resected tumor and analyzed them to learn how pembrolizumab was actually working. This research focused on: why does the drug work in some patients but not others? by seeing its response on the tumor in real time. With funding from the Tara Miller Melanoma Foundation, Dr. Gangadhar and other researchers investigated whether it was possible to predict a patient s response to Pembrolizumab and identified a relationship which could be used to predict clinical response and overall survival as early as 6 weeks post-therapy. The findings provide a framework for analyzing distinct types of treatment failures in melanoma and have implications for identifying patients for different immunotherapeutic treatment approaches. In May 2017, Dr. Gangadhar and the team published their findings in Nature, a prestigious scientific journal. The paper is the first major publication to come out of the Parker Institute for Cancer Immunotherapy research collaborative, founded by entrepreneur and philanthropist Sean Parker to foster greater collaboration between cancer centers nationally with the goal of accelerating immunotherapy research. The results of this study are having an immediate impact as clinicians are able to identify patient responses to therapy earlier and increase the chance of providing an effective treatment option. The Wistar Institute s Ashani Weeraratna, PhD, a basic scientist, used her career development award to look at the molecules identified as markers of aggression in melanoma and study how they can affect immune cells entering the tumor and their behavior once inside. The goal was 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. Dr. Weeraratna s lab submitted three papers that specifically cites her career development award funding from the Tara Miller Melanoma Foundation. The findings from this research project formed the basis for a wide array of external funding like the Women in Science team award from the Melanoma Research Alliance and L Oreal Paris that also includes Dr. Lynn Schuchter. The findings also allowed Dr. Weeraratna to apply for a Developmental Research Project that was funded, thanks, in large part, to the original assistance from the Tara Miller Melanoma Foundation. This project focuses on why tumor cells track to lymph nodes in some cases; but in others, bypass the lymph node altogether; or, leave the lymph node to go on to invade distant sites. This new project demonstrates the evolution of research driven by initial seed funding provided by the Tara Miller Melanoma Foundation. Phase I RadVax Trial 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 given in combination with radiation shrank tumors in a subset of 22 metastatic melanoma patients. It is believed that this combination of Ipi and 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. This research proved to be very promising and with additional support from the Tara Miller Melanoma Foundation in 2016, researchers expanded on the success of the Phase I RadVax Trial by adding an additional therapy to the combination. Melanoma CAR T cell Trial Tara Miller Melanoma Foundation funds helped launch a history-making phase 1 melanoma CAR T clinical trial in melanoma that takes patients T cells and transforms them to target c-met, a protein that cancer cells exhibit in overabundance on their surface. Pre-clinical laboratory work, the creation of an Institutional Review Board (IRB) protocol, and Federal Drug Administration inclusion were completed. The Tara Miller Melanoma Foundation provided funding for the contined development of this outstanding clinical trial in 2015.

5 I am sincerely grateful to the Tara Miller Melanoma Foundation for their generosity and support of melanoma research. The Miller family and its community of supporters make a cure believable to me and inspire me to do what I do every day. Tara C. Gangadhar, MD Assistant Professor of Medicine 2015 Funding Summaries and Updates - $400,000 Melanoma CAR T cell Trial Over the past three years, funding from the Tara Miller Melanoma Foundation helped accelerate a 10 patient, Phase 1 melanoma CAR T clinical trial. Update This clinical trial is official open and enrolling patients. Dr. Tara Gangadhar serves as the principal investigator. As a Phase I study, the key goals are safety and determining whether or not the modified cells are successfully making it to the target (c-met). The trial is distinctive in that we have a highly translational element in our relationship with Dr. John Wherry s lab. We are collecting paired tissue samples before and with CAR T cells to better evaluate their effect on melanoma in order to advance our understanding and develop better treatments. Ravi Amaravadi, MD, Associate Professor of Medicine, employed therapies that inhibit autophagy, a resistance mechanism where cancer cells cannibalize in order to survive, combined with BRAF and MEK inhibitors that target melanoma from all angles to overwhelm the ability of the tumor to develop resistance. Dr. Amaravadi and his team, with support from the Tara Miller Melanoma Foundation and in collaboration with dozens of investigators in the United States and abroad, completed the first six clinical trials involving hydroxychloroquine (HCQ), an antimalarial medication that has been found to inhibit autophagy, in combination with a variety of anticancer therapeutics in diseases such as advanced melanoma. These early clinical trials showed great responses in the majority of patients and Novartis funded a randomized phase II multi-institutional study across four sites, including Penn. This trial combines HCQ with two targeted therapies: a BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib. The goal of this work is to repurpose an already existing drug to improve the efficacy of currently available standard-of-care therapies. DNA Vaccine Strategy to Melanoma Robert H. Vonderheide, MD, DPhil, Director of the Abramson Cancer Center and the John H. Glick, MD, Abramson Cancer Center s Director Professor and David Weiner, PhD, Professor of Pathology and Laboratory Medicine, have focused on research at Penn to develop a novel immune-therapeutic 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. While this important research continues, the Tara Miller Melanoma Foundation funded a different, more personalized vaccine strategy in The Miller family celebrating their investment in melanoma research with the physicians and scientists who drive the work forward.

6 Funding from the Tara Miller Melanoma Foundation is critical to our mission of discovery and providing cuttingedge treatment options for advanced melanoma. The generous funding for this project will enable our patients to receive a new T cell therapy manufactured at ACC that is customized to their tumor mutational profile. Gerald P. Linette, MD, PhD Chief Medical Officer for Cancer Immunotherapy and Clinical Director of the Sean Parker Institute 2016 Project Funding Summary - $450,000 Novel Approach to T-cell Therapy Gerald P. Linette, MD, PhD, Chief Medical Officer for Cancer Immunotherapy and Clinical Director of the Sean Parker Institute is working on a novel approach to T-cell therapy using a DNA vaccine strategy. This is a more personalized vaccine approach that utilizes the Next- Generation DNA Sequencing technique to understand how broken genes in melanoma produce neoantigens, which are proteins that presents on the surface of the cell. Dr. Linette s process collects white blood cells, characterizes the patient s melanoma, and creates a personalized vaccine using T-cell therapy. He expects neoantigen-specific T cell therapy to be more specific c and have fewer side effects compared with current forms of immunotherapy such as checkpoint inhibitors. Dr. Linette and his team, with assistance from the Tara Miller Melanoma Research Foundation, have developed a personalized melanoma vaccine to stimulate the most effective neoantigen-specific T cells that destroy the tumor. The patient s blood cells are then removed and taken back to the engineering lab to create a more potent T cell product. This critical funding has accelerated a first-in-human personalized immunotherapy trial set to open at the Abramson Cancer Center in early RADVAX in Melanoma with Triple Therapy Robert H. Vonderheide, MD, DPhil, Director of the Abramson Cancer Center and the John H. Glick, MD, Abramson Cancer Center s Director Professor and Andy J. Minn, MD, PhD, Assistant Professor of Radiation Oncology along with Amit Maity, MD, PhD, Morton M. Kligerman Professor of Radiation Oncology and E. John Wherry, PhD, Richard and Barbara Schiffrin President s Distinguished Professor built on an existing RadVax trial and created a protocol for triple therapy. In the phase 1 clinical study, the team found that combining ipilimumab with radiation was safe and shrank tumors in 18% of metastatic melanoma patients. Taking that knowledge back to the lab shed light on a mechanism of resistance suggesting that an antibody against PD-L1, or its partner PD-1, is the ideal third treatment to improve response and immunity. Seed money from the Tara Miller Melanoma Foundation allowed for the continued exploration of a very important question about radiation enhancing the patient response to immunotherapy. As a result of the initial investment made by the Foundation, Dr. Vonderheide and the team secured a PO1 (Research Program Project) grant from the NIH. This important grant provides support for integrated, multiproject research projects involving a number of independent investigators who share knowledge and common resources. As part of the PO1, the team will open a clinical trial in spring 2018 to address the question of whether radiation can increase the patient benefit of what is currently the most active regimen for melanoma patients: ipilimumab and nivolumab. Melanoma Resistance to Targeted Therapies Arjun Raj, PhD, Assistant Professor of Bioengineering, has developed a new approach to studying single cells and implementing this new technology to better understand why cells become resistant to targeted therapy. An ongoing problem with targeted therapies is that they work for a while but then stop being effective. With support from the Tara Miller Melanoma Foundation, Dr. Raj s approach could eventually be translated either to understand the complex wiring of cells and apply multiple drugs, or to have more of a diagnostic approach to predict when resistance occurs and what the mechanism is that causes it. Dr. Raj s early successes in the first year of this project showed promise and the Tara Miller Melanoma Foundation will provide a second year of funding in 2017.

7 While I did not know her personally,tara Miller challenged all of us to work harder so that other melanoma patients would have better options. The generous support from the Tara Miller Melanoma Foundation allows us to think bigger, and to ask and answer more questions. Todd W. Ridky, MD, PhD Assistant Professor of Dermatology 2016 Project Funding Summary - $450,000 (continued) Role of Estrogen in How Moles Become Melanoma Todd Ridky, MD, PhD, Assistant Professor, Department of Dermatology, has found that estrogen plays a role in altering melanin production and skin pigmentation. Preliminary study results suggest that pregnancy-associated estrogen establishes long-term protection from melanoma, and increases the efficacy of anti-pd-1 therapy for melanoma. This study will focus on the role of estrogen in the growth of melanocytes (melanin-forming cells), allowing Dr. Ridky to better understand which moles are more likely to become melanoma. Dr. Ridky s early successes in the first year of this project showed promise and the Tara Miller Melanoma Foundation will provide a second year of funding in Melanoma Brain Metastases Qing Chen, MD, PhD, Assistant Professor, Tumor Microenvironment and Metastasis a Program, Wistar Institute, tute, with assistance from the Tara Miller Melanoma Foundation, is working to better understand how the brain s unique environment fosters metastases. Brain metastasis is the most threatening and lethal form of relapse from melanoma and carcinomas. Compared with carcinoma, melanoma has a much higher propensity to metastasize to the brain. For example, astrocytes (cells that only exist in brains) infiltrate into metastatic lesions, and this study will unravel the complex crosstalks between melanoma cancer cells and astrocytes during metastasis to reveal the mechanisms that facilitate tumor survival and growth in the brain. Dr. Chen and her team developed mouse models of melanoma brain metastasis. The melanoma related cells used had a much higher ability to form brain metastases in the experimental mice and also showed increased invasion through live brain tissue compared to the original melanoma cells. Metastatic growth in other organs requires the complex interplay between cancer cells and the connective tissue cells, a process commonly referred to as seed and soil hypothesis. The team co-cultured the brain metastatic cells with astrocytes, the most abundant support cells in the brain, and found that the addition of astrocytes increased the growth of melanoma related cells and protected them when treated with the chemotherapy drug. The team is now investigating why astrocytes are so well protected when in direct contact with brain metastatic cells. These newly identified mechanisms will provide a clearer framework for brain metastasis as a disease from which therapeutic strategies can be devised.

8 Our work is at a critical juncture now where federal dollars are simply not enough to meet our goal of developing new drugs for melanoma. Philanthropic funding from the Tara Miller Melanoma Foundation allows us to make a major advances towards new melanoma therapies and now we are poised to see how new drugs intersect with immunotherapy. Ravi K. Amaravadi, MD Associate Professor of Medicine and Co-Leader of the Cancer Therapeutics Program 2017 Project Funding Summary - $500,000 Overcoming Resistance to Melanoma Immunotherapy Ravi Amaravadi, MD, and his team will use funding from the Tara Miller Melanoma Foundation, to build on an exciting recent finding regarding resistance to melanoma immunotherapy. The team targeted an enzyme, mtor, that is crucial to tumor growth while also blocking autophagy - the mechanism that has made past attempts to target that enzyme resistant to treatment because cells cannibalize in order to survive. They were able to use this finding to develop a drug that successfully inhibits tumor growth of melanoma. Numerous drugs are FDA approved to target mtor, but in doing that they also turn on autophagy and make the tumor resistant. Dr. Amaravadi and his team have found a compound that targets an different enzyme in the lysosome called PPT1 and inhibits both mtor and autophagy. With this new funding, the team will work to develop these compounds into drugs that are suitable for human patients. Understanding Melanoma Metastases A team led by Ashani Weeraratna, PhD of the Wistar Institute and Giorgos Karakousis, MD of Penn Medicine is working to better understand melanoma metastases. The team s focus is to better disrupt angiogenesis, the process of developing a new blood supply that facilitates cancer growth. A constant new blood supply potentially provides a route for primary melanomas to bypass the lymph nodes and travel to distant sites where they metastasize. Funding from the Tara Miller Melanoma Foundation will allow researchers to study whether tumors largely bypass lymphatics due to increased angiogenesis. Understanding Who Benefits from Melanoma Immunotherapy A completely new observation that the immune effects of anti-pd1 therapy can be identified in the peripheral blood as early as three weeks into therapy or after one dose was recently publicked in Nature. This publication suggests that the activity of anti-pd1 therapy may occur very early, as opposed to the previous understanding that it was slow acting. This discovery opened the door for further research and with support from the Tara Miller Melanoma Foundation, Alexander Huang, MD and John Wherry, PhD will actively pursue two questions: 1) Can early imaging or biopsy predict responders and non-responders and 2) Is the early addition of a second therapy benefical for those without an initial response? Understanding Resistance to Targeted Therapies By focusing on drug resistance on a single cell level, Dr. Arjun Raj found evidence for a non-genetic origin to the initial stages of acquired resistance. He and his team recently had a paper accepted by Nature that focuses on this very idea as it relates to resistance to vemurafenib in melanoma treatment. Dr. Raj and his team s next step is to explore the clinical ramifications of this work, particularly deciphering the molecular pathways associated with the appearance of these rare cells affecting resistance to targeted therapies. Role of Estrogen and Sensitivity to Melanoma Immunotherapy Through mouse models, Dr. Todd Ridky and his team established that in melanoma specifically, an estrogen-related protein activates cancer cell differentiation. The cancer cells divide less frequently, make more pigment, and become more visible and vulnerable to the natural immune system making it harder for the cancer to become resistant to immunotherapies. These experiments provide much of the pre-clinical data necessary to support a clinical trial to determine whether this estrogen-related protein improves efficacy of a-pd- 1 therapy in people with melanoma. If successful, adding the estrogen-related protein to immune checkpoint blockade therapy would significantly improve outcomes for melanoma patients. PD-1 Biomarker Evaluation Cancer cells evade the immune system by expressing PD-L1 on their surface. Wei Guo, PhD and his team discovered that melanoma cells secrete high levels of exosomes that carry surface PD-L1. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 is closely associated with anti-pd-1 therapy response. The results indicate that melanoma cells effectively combat the immune system through exosomal PD-L1, and suggest the potential in applying circulating exosomal PD-L1 to predict patients response to anti-pd-1 therapies. The team is continuing their work on the immunosuppression function of exosomes from melanoma patients with acquired resistance to combined anti-braf and antimek therapy. Understanding Anti-CTLA in Melanoma Treatment Anti-CTLA4 therapies have been in the clinic for a number of years. Despite this we still know little about the mechanisms of resistance to anti-ctla4 therapies. Erica Stone, PhD s lab is trying to understand potential new mechanisms of resistance to anti-ctla4 by exploring which cell types anti-ctla4 binds to in vivo and investigating if expression of surface CTLA4 on T cells within the tumor is associated with response to Ipilimumab. We hope that our research will lead to the development of a biomarker to identify the patients who will benefit most from anti-ctla4 therapy.

9 2015 MELANOMA RESEARCH ALLIANCE TEAM SCIENCE AWARD University of Pennsylvania Radiation and Immune Checkpoint Blockade from Mechanism to Patients $225,000 Robert Vonderheide, M.D., University of Pennsylvania E. John Wherry, Ph.D., University of Pennsylvania Andy Minn, M.D., Ph.D., University of Pennsylvania Young Investigator: Tara Gangadhar, M.D., University of Pennsylvania Young Investigator: Christina Twyman-Saint Victor, M.D., University of Pennsylvania Young Investigator generously funded by the Tara Miller Melanoma Foundation Project: This team of investigators aims to explore new combinations of radiation and immunotherapy treatments to fight drug resistance and ultimately improve care for melanoma patients. Update: The investigators discovered that blocking a protein expressed on the surface of T cells allows these cells to better recognize melanoma and launch a tumor-killing immune response. The researchers also uncovered a key pathway melanoma uses to ward off attack by the immune system, and devised a clinical trial to test a combination therapy that targets this resistance pathway. In addition, the research team discovered certain features in patients tumor or blood samples that can predict the effectiveness of immunotherapy. The researchers published their findings in the prestigious scientific journals Nature and Cell, and presented them at nearly 40 scientific meetings. The team also expects that radiation therapy given with immunotherapy will improve efficacy and they plan to assess this in two clinical studies for which they have already started patient recruitment. One study will test the effects of radiation therapy combined with pembrolizumab in patients with various types of metastatic cancers, while the other study will assess the effects of radiation therapy combined with a different cancer immunotherapy (tremelimumab) for patients with metastatic melanoma, lung, breast or pancreatic cancers MELANOMA RESEARCH ALLIANCE TEAM SCIENCE AWARD Tel-Aviv University, Dana-Farber, and Hebrew University Identification of Novel Regulators of Melanoma Brain Metastasis $225,000 Carmit Levy, Ph.D, Tel-Aviv University Michael Goldberg, Ph.D., Dana-Farber Cancer Institute Young Investigator: Yuval Tabach, Ph.D., Hebrew University Young Investigator generously funded by the Tara Miller Melanoma Foundation

10 Project: The Levy team, which includes Dr. Tabach, is interested in better understanding the underlying molecular drivers that cause melanoma to spread to the brain, with the hope of eventually developing therapies to target these pathways to block melanoma spreading to the brain. They will perform a computational analysis to determine patterns of DNA modifications and gene expression that are associated with melanoma brain metastasis. These findings will then help the team identify candidate genes that can suppress the spread of melanoma to the brain. Finally, the team will study gene expression in brain metastases samples derived from melanoma patients. Update: The team has: Identified additional melanoma brain metastasis datasets to include in their computational analysis; Initiated their genetic screen in mice using the cutting-edge CRISPR-Cas9 technology of gene editing; Identified several candidate genes that normally block the spread of melanoma cells to the brain; and Started dissecting melanoma brain metastasis tissue samples from patients for DNA sequencing TARA MILLER MELANOMA FOUNDATION - MRA YOUNG INVESTIGATOR AWARD University of Texas M.D. Anderson Cancer Center Epigenetic Effectors of Responses to Immune Checkpoint Blockade Agents $225,000 Young Investigator: Kunal Rai, Ph.D., University of Texas M.D. Anderson Cancer Center Mentor: Jennifer Wargo, M.D., University of Texas M.D. Anderson Cancer Center Project: Define genetic basis of resistance to immunotherapy with innovative high-throughput genomic analysis of tumor samples from patients being treated with anti-pd1 and combination anti-pd1/anti-ctla4 agents. The study will provide comprehensive knowledge on relationships between the chemical modifications to the tumor genome and the tumor s response its microenvironment, with the aim of testing anti-pd1 or anti-pd1/anti-ctla4 combinations with epigenetic inhibitors. Update: The first progress report for this project is due 6/15/ TARA MILLER MELANOMA FOUNDATION - MRA YOUNG INVESTIGATOR AWARD $225,000 ( of 3 year commitment paid in 2018) Research grant to be selected April 2018