Stewardship Report The Harold E. Eisenberg Foundation June 2020

As the world is in tumultuous times, we hope you are all healthy and are staying safe and well. At the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, our commitment to advancing life-changing research has never been stronger. The Harold E. Eisenberg Foundation’s dedication, advocacy, and fundraising on our behalf have enabled us to propel our Gastrointestinal (GI) Oncology Program forward. We thank you for this and for all that we have accomplished together.

Our GI oncology team continues to focus on furthering clinical studies and research, advancing clinical care, and building a pipeline of new ideas. Thanks to the Harold E. Eisenberg Foundation GI Cancer OncoSET Program, we can advance the development of novel clinical trials in GI cancers, as well as crucial translational (bench-to-bedside) research and genomic profiling activities. By coupling oncology with genomics, we aim to provide patients with personalized medicine by targeting tumors that are not responsive to current standard forms of treatment and to develop individually tailored treatments.

The Eisenberg GI Tissue Bank currently stores over 25,000 colorectal cancer tissue samples, equipping researchers with the ability to study what characterizes cancer tissues and to develop investigations aimed at improving

prevention, detection, and treatment. Our clinical research nurse Vicki Maurer continues to manage our GI oncology-specific clinical trials program.

Our most recent recipient of the Harold E. Eisenberg Research Scholar Award is Zhuoli Zhang, MD, PhD. We are pleased to offer this prestigious award each year to our scientists who are exploring new ideas aimed at discovering cures for GI cancers.

On behalf of Lurie Cancer Center and the Division of Hematology and Oncology, we thank you for your meaningful partnership. As always, and especially now, we offer our best wishes to you and your families.

With gratitude,

Leonidas C. Platanias, MD, PhD Jesse, Sara, Andrew, Abigail, Benjamin, and Elizabeth Lurie Professor of Oncology Director, Lurie Cancer Center

Al B. Benson III, MD, FACP, FASCO Professor of Medicine Associate Director, Cooperative Groups, Lurie Cancer Center

Dear Harold E. Eisenberg Foundation Board Members and Friends,

Current Use of Funds

OncoSET harnesses the power of precision medicine to identify tailored therapies for patients based on the abnormal genes specific to their tumor. To date, the Harold E. Eisenberg GI Cancer OncoSET has funded three projects, all based on precision medicine for GI cancers.

The OncoSet registry continues to enroll GI malignancy patients. This past year alone, there have been 336 patients, which include those with esophagus, pancreas, stomach, liver, small intestine, colorectal, and anal cancer.

Molecular Translational Bridge: $75,000A translational bridge award is meant to foster the translation of basic science research into clinical advancements. Dr. Elizabeth Eklund received funding from the Harold E. Eisenberg GI Cancer OncoSET Fund to explore a new research question surrounding an aspect of colon cancer in her laboratory in partnership with Dr. Ronen Sumagin and Dr. Al Benson. Studies in the Eklund laboratory demonstrated that inhibiting a specific protein target, Fap1, with a blocking peptide decreased platinum resistance in a murine xenograft model of colon cancer. This suggests development of Fap1 inhibitors may be a rational approach to targeted therapeutics in a subset of colon cancer patients.

New Immuno-Monitoring Core Support: $100,000At Lurie Cancer Center, we are working to develop approaches to make immunotherapy more effective in more cancer patients while finding approaches to diminish the toxicity of this treatment. An Immuno-Monitoring Core is a shared resource that studies immune cell phenotype and function using state-of-the-art technology. The mission of this core will be to comprehensively characterize antitumor immune responses, correlate with gene profiling, determine mechanisms of immune escape and evasion, and develop biomarkers that predict patient outcomes or possible toxicities. This will support both in vitro and in vivo gastrointestinal cancer studies.

ECOG-ACRIN Y131 Molecular Analysis for Therapy Choice (MATCH) Trial: $100,000ECOG-ACRIN is a federally-funded, national, multidisciplinary, and membership-based scientific organization that designs and conducts biomarker-driven cancer research. Northwestern is participating in a trial that affords a unique opportunity to collect information about genes associated with cancer, as well as how patients’ tumors with abnormalities respond to targeted therapy. The study hopes to address whether patients with underlying abnormalities in their tumor could achieve tumor shrinkage or prolonged time to progression with agents that target their tumor’s particular molecular abnormality.

Focus on Precision Medicine

Over the past couple of years, our technology company partner Tempus and Lurie Cancer Center have collaborated in the area of GI cancers, specifically colon cancer. Using the Harold E. Eisenberg Foundation Tissue Bank, Tempus has completed next-generation sequencing (NGS) of 500+ of our colon cancer cases. With these results, our physicians and scientists will have both pathology and genomic characterizations of 500+ colon cancer samples. In addition to the NGS, Tempus and Lurie Cancer Center have collaborated to create organoids from GI cancer over the past two years. Organoids provide a detailed view of how organs form and grow, which can also provide new insights on human development, disease, and treatment options. Drug interaction with these “mini-organs” can potentially revolutionize the field of drug discovery and open new approaches to personalized medicine. Later this year, Northwestern GI oncology investigators will meet with the Tempus genomics team to review the laboratory and clinical data that have been collected to create a comprehensive database to guide the development of future research proposals.

Harold E. Eisenberg GI Cancer OncoSET

26,245specimens

in tissue bank

1,391patients

contributed

Our clinical research program has strong ties to the field of precision medicine.

Clinical Trials Update

Lurie Cancer Center has a robust clinical trials program. In fact, the strength of our program contributed to the renewal of the highly competitive Cancer Center Support Grant from the National Cancer Institute. However, the strength of a clinical trials program cannot be measured by a single institution on its own.

Lurie Cancer Center participates in many trials that end up being reviewed by the Food and Drug Administration, with the end goal of bringing new therapies to the market for all cancer patients. In the realm of GI Oncology, our program is strong, and thanks to the Harold E. Eisenberg Foundation, we have Vicki Maurer as our clinical research nurse.

As you know, Vicki serves our GI cancer patients in clinical trials. Not only does she help identify trials that might work for a specific patient, she also guides them through the consenting and enrollment process. Once a patient is enrolled, she follows him or her closely to monitor for and manage side effects and determine appropriate dose modifications.

Research Scholar Update

Charitable giving from organizations like the Harold E. Eisenberg Foundation is a catalyst in developing and sustaining new areas of medical research. Philanthropy is more critical than ever as funding from the National Institutes of Health continues to decrease.

Zhuoli Zhang, MD, PhD 2019-2020 ScholarArea of Focus: Pancreatic cancer therapy

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related mortality in the United States. Dr. Zhang proposes to optimize clinically translatable MRI approaches to amplify immune responses of combination

therapy of dendritic cell vaccine and irreversible electroporation treatment. Based on a previously developed MRI method, this proposal optimizes and validates the imaging protocol in animal models and focuses on clinical validation and translation of the MRI methods. Dr. Zhang’s initial findings demonstrate

that irreversible electroporation invokes a systemic immune response, and both primary tumor ablation and systemic antitumor immune response induced by irreversible electroporation may overcome the tumor immunosuppression associated with dendritic cell-vaccine therapy.

Sui Huang, MD, PhD2018-2019 Scholar Area of Focus: Using a molecule created in her lab to treat liver cancer

Dr. Huang is investigating a molecule her lab created, called MEAN. Dr. Huang hypothesizes that MEAN, which stands for 6-methoxyethylamino-numonafide, may be an effective way to treat liver cancer. Dr. Huang accomplished the

project, which provided preliminary data for an RO1 grant that was submitted last fall. She is now in the process of revising and resubmitting this project for consideration. Her data results are preliminary and in need of validation. Dr. Huang is actively seeking additional funding support to continue her work.

Ronen Sumagin, PhD2017-2018 ScholarArea of Focus: Investigating the connection between inflammation and cancer

In the past, Dr. Sumagin and his colleagues demonstrated a direct link between immune cell activity in the colon and the development of colorectal cancer (CRC). More recent work from the Sumagin lab has been focused on

defining the underlying mechanisms for the immune cell impact on CRC development. These studies indicate that tumor-infiltrating immune cells shift the DNA repair landscape to enhance tumor cell survival and resistance to chemotherapy. These studies also indicate that in CRC, targeting of the specific immune cell activity in combination with other approved therapies may improve disease outcomes. The group was able to publish their results in an article in DNA Cell Biology, and they are in the process of completing another paper dealing with colorectal cancer.

Bringing Breakthroughs to Patients

Investing in Top Scientists

Research Scholar Updates continued

Guang-Yu Yang, MD, PhD2016-2017 ScholarArea of Focus: Gene mutation profiling of colorectal cancer

Dr. Yang was the inaugural HaroldE. Eisenberg Scholar. The long-term objective of his research is to study the molecular mechanism of inflammation-driven cancer formation. Currently, Dr. Yang is working on three papers on

unique gene mutation profile in colorectal cancers. He also has extended his research into IBD-associated cancer, focusing on BRAF, KRAS and p53 genes, and missense oncogene mutation and chaperone proteins as therapeutic targets. He has submitted a grant proposal to the National Institutes of Health for an R01 grant that is under review.

Thank You for Your Generosity

The Harold E. Eisenberg Foundation is accelerating gastrointestinal cancer research now and into the future, bringing us closer to personalized medicine by offering truly customizable treatment solutions and improving care and outcomes for patients with cancer. Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University are deeply grateful for your continued support.

If you would like more information regarding this report or Lurie Cancer Center, please contact:

Nicole Langert Director, Major Gifts Development and Alumni Relations Northwestern University Feinberg School of Medicine Arthur J. Rubloff Building, 9th Floor 420 East Superior Street Chicago, Illinois 60611 P. 312-503-1656E. nicole.langert@northwestern.edu

Recent Publications (2020) Thanks to the Support of the Harold E. Eisenberg Foundation:

Prophylactic dendritic cell vaccination controls pancreatic cancer growth in a mouse model, Cytotherapy.

MRI radiomics for early predictionof response to vaccine therapy in a transgenicmouse model of pancreatic ductaladenocarcinoma, Journal of Translational Medicine.

Dinaciclib prolongs survival in the LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) transgenic murine models of pancreatic ductal adenocarcinoma, American Journal of Translational Research.

Charitable giving from organizations like the Harold E. Eisenberg Foundation is a catalyst in developing and sustaining new areas of medical research.