We take cancer personally. Basser.org

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August Holt
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1 We take cancer personally. Basser.org BRIEF BOASTS (Top Accomplishments / At a Glance) Before the Center was founded in 2012, there were no targeted therapies for BRCA-related cancers now three drugs have been approved. This research in BRCA1/2 targeted therapies has led to the FDA approvals for patients with BRCA-related ovarian cancer, breast cancer, and ovarian cancer at large. A Phase I preventative vaccine clinical trial is now completed. This vaccine was given to close to 100 patients with breast, pancreatic, ovarian and colon cancers who are in remission, but have a high-risk for recurrence. Initial analysis shows that the vaccine is safe and immunologically effective. We are planning our next trial in which we will test this vaccine in healthy individuals in with a BRCA mutation, with the long-term goal of preventing cancer altogether. Research from Penn investigators has demonstrated that many ovarian cancers actually start in the fallopian tubes, not necessarily the ovaries a finding which has refocused efforts on novel detection and study of precursor lesions in the fallopian tubes, and may bring a new option for removal of the fallopian tubes as a first-step prevention strategy for pre-menopausal women with BRCA mutations. BRCA BREAKDOWN (Facts) We all have BRCA genes, and that is a good thing! They repair damaged DNA and suppress tumors. However, men and women born with a gene mutation in BRCA1 or BRCA2 are at a heightened risk for developing certain cancers, including breast, ovarian, prostate, and pancreatic cancer, as well as melanoma. Women who carry a BRCA gene mutation have a lifetime risk of breast cancer of up to 75% along with a 50% risk of developing ovarian cancer. Men who carry the mutation have a lifetime risk of 25% of prostate cancer and are at increased risk for developing breast cancer. Both men and women who carry the mutation have an elevated risk of pancreatic cancer and melanoma. BRCA mutations are responsible for 5-10% of all breast cancers, and 10-20% of all ovarian cancers. BIG PICTURE (Overview) The Basser Center is the first comprehensive center for the research, treatment, and prevention of BRCA-related cancers. The Center was founded in 2012 by Penn alumni, Mindy and Jon Gray, with an initial $30M investment. Since then, Mindy and Jon have committed $55M to the Center.

2 Our mission is to see a world free of the devastating effects of BRCA-related cancers and, in doing so, provide a roadmap for curing genetic diseases. utreach programs at Penn and around the world. The Basser Leadership Team is comprised of: o Susan Domchek, MD, Executive Director o Ronny Drapkin, MD, PhD, Director of Gynecologic Cancer Research o Roger Greenberg, MD, PhD, Director of Basic Science o Kate Nathanson, MD, PhD, Director of Genetics o Beth Stearman, MPH, Administrative Director The Basser Center has an Internal Advisory Board that provides support, input, advice, and assistance in terms of resources, budgets, spending, and reporting for the Basser Center for BRCA. Members include: o Chair - Glen Gaulton, PhD, Vice Dean and Director, Center for Global Health o Robert Vonderheide, MD, DPhil, Director, Abramson Cancer Center o Deborah Driscoll, MD, Chair of Department of Obstetrics and Gynecology o Lynn Schuchter, MD, Chief of Division of Hematology Oncology The Basser Center also has an External Advisory Board that reviews all internal and external grant proposals and provides strategic counsel. Members of this Board include: o Alan Ashworth, PhD, Director of UCSF Helen Diller Family Comprehensive Cancer Center o Bruce Chabner, MD, Director of Clinical Research at Harvard Medical School o Judy Garber, MD, MPH, Director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute o Andrew Godwin, PhD, Deputy Director of the University of Kansas Cancer Center o Colleen McBride, PhD, Chair of the Department of Behavioral Sciences & Health Education at the Rollins School of Public Health at Emory University o John Petrini, PhD, Chair of the Molecular Biology Program at Memorial Sloan Kettering Institute o Victor Velculescu, MD, PhD, Director of Cancer Genetics and Co-Director of Cancer Biology at the Ludwig Center at Johns Hopkins Kimmel Cancer Center BY THE NUMBERS (Statistics) The Basser Center has: o Awarded grants to 26 researchers at Penn and 12 institutions worldwide. o Raised $80 million including $15 million through the two biennial Basser Jean Bash events. o Provided genetic counseling to over 1,500 people. o Registered over 1,900 BRCA1/2 carriers in our research registry. o Reached over 1.7 million people through social media (Facebook, Instagram, and Twitter). o Held over 50 outreach events. BRAGGING RIGHTS (Accomplishments) The Basser Center is making real, measurable progress: o Before the Center was founded in 2012, there were no targeted therapies for BRCA-related cancers now we have four. This research in BRCA1/2 targeted therapies has led to the FDA

3 approvals for patients with BRCA-related ovarian cancer, breast cancer, and ovarian cancer at large. o FDA approves olaparib for BRCA-related ovarian cancer (inherited). o FDA approves rucaparib for BRCA-related ovarian cancer (inherited and somatic). o FDA approves niraparib for ALL ovarian cancers. o OlympiAd trial- olaparib shown to be more effective than chemo in BRCA-related breast cancer. o 2018-FDA approves olaparib for BRCA-related breast cancer. o A Phase I preventative vaccine clinical trial is now completed. This vaccine was given to close to 100 patients with breast, pancreatic, ovarian and colon cancers who are in remission, but have a high-risk for recurrence. The vaccine was shown to be safe and immunologically effective. Phase II of this trial will test this vaccine in healthy individuals in with a BRCA mutation, with the long-term goal of preventing cancer altogether. o Research being conducted at the Basser Center is providing clarity to the origins of cancer and how it develops. For example, we now have strong evidence that ovarian cancer originates in the fallopian tubes and not the ovaries, which is vital information for preventative strategies and treatment. o Pre-clinical data shows the promise of a blood test for the early detection of pancreatic cancer. o Researchers and clinicians supported by the Basser Center for BRCA have been featured in more than 100 news articles. BREAKTHROUGHS AND DISCOVERIES (Research) Basser Center researchers are working on a variety of research projects to better understand BRCA mutations, including: o Understanding the mechanisms of BRCA at a basic science level; o Using mouse models to test new therapies and understand PARP inhibitor resistance; o A clinical trial testing a vaccine to ultimately prevent BRCA-related cancers and, o A telegenetics program to bring our genetic counseling to all communities. The Basser Global Prize was established by Shari Basser Potter and Len Potter to honor a visionary scientist who has conceptually advanced BRCA1/2 related research that has led to improvements in clinical care. The prize provides $100,000 in unrestricted support to the awardee's innovative BRCA1/2 related research efforts, and the awardee gives the keynote address at the annual Basser Center for BRCA Symposium. Past Global Prize awardees include: o 2013: Alan Ashworth, PhD, FRS, Institute for Cancer Research, London, England o 2014: Mary-Claire King, PhD, University of Washington, Seattle, Washington o 2015: David Livingston, MD, Dana Farber/Harvard Cancer Center, Boston, Massachusetts o 2016: Steven Narod, MD, FRCPC, PhD (hon), FRSC, tal in Toronto, Ontario, Canada o 2017: Ashok Venkitaraman, MBBS, PhD University of Cambridge The Center also supports researchers working in basic science, prevention, early detection, or targeted therapeutics relevant to the study of BRCA1/2 at institutions across the nation, including: o Lewis Cantley, PhD, Weill Cornell Medical College o Junjie Chen, PhD, MD Anderson Cancer Center

4 o Katherine Crew, MD, Columbia University Medical Center o Sonia Franco, MD, PhD, Johns Hopkins Medicine o Tony Huang, PhD, New York University School of Medicine o Neil Johnson, PhD, Fox Chase Cancer Center o Noah Kauff, MD, Duke Cancer Center o Alexander Mazin, PhD, Drexel University College of Medicine o Jeffrey Parvin, MD, PhD, Ohio State University School of Medicine o Richard T. Pomerantz, PhD, Temple University Lewis Katz School of Medicine o Mark Robson, MD, Memorial Sloan Kettering Cancer Center o Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute o David Solit, MD, Memorial Sloan Kettering Cancer Center o Patrick Sung, DPhil, Yale School of Medicine o Vered Stearns, MD, Johns Hopkins Medicine o Zoltan Szallasi, MD, o David Yu, MD, PhD, Emory University School of Medicine BUILDING BUZZ (Awareness and Social Media) Education is one of the best tools for prevention. Awareness saves lives! It is estimated that there may be one million individuals in the U.S. with a BRCA mutation. It is estimated that only 10% of these individuals are aware that they have a mutation. Our goal is to educate the other 90% so individuals and families are empowered with knowledge and options. We are building a worldwide community focused on BRCA-related cancers: o Through live events, webinars, social media, and awareness campaigns, the Basser Center continuously reaches out to high-risk communities around the globe to help individuals become aware, get tested, and understand all their available options. Our #InvisibleGenes social media campaign is spreading awareness of hereditary cancers through a video created by senior management at Facebook that seeks to unearth the invisible traits we inherit. o The traits we inherit from our family define and connect us in countless ways. Sometimes these traits are obvious, like curly hair or dimples. However, sometimes what we inherit remains hidden, like BRCA gene mutations, which can increase risk for developing certain type of cancers. o Basser can be followed on social media through Facebook, Twitter, and Instagram (@BasserBRCA). o Our social media campaign video has been viewed by close to 1 million people. BUILDING OUR NETWORK (Philanthropy) The Basser Center has raised $80 million since its inception. Our research advancements and outreach efforts are in large part due to our generous philanthropic partners and dedicated volunteers. Every gift strengthens our collective impact on improving options and creating a better future for those affected by BRCA1/2 gene mutations. Given the continued downward trends in federal funding for cancer research, finding the resources to support high impact and high reward science is increasingly difficult. Private philanthropy plays a vital role in moving BRCA research forward at a quicker pace.

5 The Basser Center Leadership Council tirelessly advocates, informs, and engages on behalf of the Basser Center. The c and provides hope to patients and families by securing the resources needed to accelerate BRCA-related research, care, and education. Members include: o Mindy Gray, Chair o Tamsen Brown o Cindy Price Gavin o Susan Getz o Michael J. Haas o Lisa Jacobs o Michele Konner o Trace McCreary o Shari Potter o Jessica Queller o Heidi Rieger o Stacey Sager o Helene Silverman Sorin o Jill Steinberg o Dana Zucker o Anonymous members The Young Leadership Council (YLC) serves as a forum for young adults to become more engaged with the mission of the Basser Center, stay informed about the latest advances in BRCArelated cancer research, and advocate and raise awareness of the Center. Through personal philanthropy and fundraising events, this committed group supports innovative BRCA-related cancer research, patient care, and educational priorities. The YLC co-chairs are Rachel Presser and Erika Stallings. Since its founding in 2016, the group has expanded to over 65 members in 17 states. A list of members can be found at basser.org/ylc. BASSER AND BEYOND (A Look to the Future) In May 2017, Mindy and Jon Gray made an additional $21M gift to the Basser Center for BRCA, bringing their total commitment to $55M. Through our dedicated support of our leadership, scientific community, and philanthropic partners, some of our research goals for the next 5 years include: o Uncovering biomarkers for early detection of ovarian cancer. Recent research from Penn investigators has demonstrated that many ovarian cancers actually start in the fallopian tubes, not necessarily the ovaries a finding which has refocused efforts on novel detection and study of precursor lesions in the fallopian tubes, and may bring a new option for removal of the fallopian tubes as a first-step prevention strategy for pre-menopausal women with BRCA mutations. o Testing strategies that use personalized cellular therapies such as chimeric antigen receptors (CAR) T cell therapy or tumor vaccines to re-program the immune system to recognize and attack or, in the case of vaccines, prevent BRCA1/2-associated cancers of all types. o Studying PARP inhibitors in combination with other drugs, including immune checkpoint inhibitors or targeted therapies, for the treatment of BRCA1/2-associated cancer while carefully analyzing predictors of response and resistance. o Extending the reach of preventive care and educational programs through new avenues for testing and telegenetics. Experts from leading institutions and organizations across the country have joined forces and launched a pilot study of patients with an increased risk for BRCA mutations, aimed at making the testing process more accessible to the public, and expanding the number of individuals who can be tested.

Progress Update June 2017 Lay Summary Funding: $6,000,000 Grant Funded: July 2015 Dream Team Members Dream Team Leader:

Progress Update June 2017 Lay Summary Funding: $6,000,000 Grant Funded: July 2015 Dream Team Members Dream Team Leader: SU2C -Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant: DNA Repair Therapies for Ovarian Cancer AND SU2C Catalyst Merck-Supported Supplemental