2013 Annual Report. Caring for Carcinoid Foundation 20 Park Plaza, Suite 478 Boston, MA

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1 Caring for Carcinoid Foundation 20 Park Plaza, Suite 478 Boston, MA Annual Report Since its inception, the Caring for Carcinoid Foundation (CFCF) has aggressively funded research in pursuit of cures and more effective treatments for carcinoid, pancreatic, and related neuroendocrine cancers. Since 2005, we have awarded more than $7 million in large-scale, multi-year research grants to leading scientists at renowned research institutions worldwide. The Caring for Carcinoid Foundation has established itself as the leading and most efficient not-for-profit funder of carcinoid, pancreatic neuroendocrine, and related neuroendocrine cancer research. CFCF has achieved this status through guidance from its Board of Directors, whose supports allows CFCF to operate efficiently, and its Board of Scientific Advisors, whose members provide a clear vision to funding research. Each year, CFCF organizes a state-of-the-science symposium to promote discussion and collaboration between neuroendocrine cancer clinicians and researchers. Along with our focus on research, we are committed to supporting patients and their families. We conduct multiple Neuroendocrine Cancer Patient and Caregiver Educational Conferences annually; in 2013 we held educational events in Los Angeles, Palo Alto, Philadelphia, and Houston. Our award-winning and heavily trafficked website provides a searchable, neuroendocrine cancer-focused clinical trials finder, a doctor database, and a wide range of information about neuroendocrine cancers and available treatments. We publish an electronic newsletter steadily throughout the year, providing breaking news on research findings, treatments options, and other CFCF-specific updates. Houston Patient Education Event

2 Board of Directors Anne Doyle Chairman Stephen Kaufer Vice Chairman Carol Branaman Executive Committee Jonathan Soroff Clerk Nicholas Vantzelfde Treasurer Stephen Blackwood Joseph Li, MD James Panagis, MD, MPH Board of Scientific Advisors The Board of Scientific Advisors provides scientific direction to the Caring for Carcinoid Foundation. All members of the Board of Scientific Advisors are: Pioneers in medical research Published authors in the top peer-reviewed medical journals Leaders of collaborative research projects at highly-ranked universities and institutes The Board of Scientific Advisors comprises highly distinguished medical leaders who share a commitment to discovering a cure for carcinoid cancer and related neuroendocrine cancers. George Fisher, M.D., Ph.D. Co-Chairman Associate Professor of Medicine, Stanford University Comprehensive Cancer Center Ramesh Shivdasani, M.D., Ph.D. Co-Chairman Associate Professor of Medicine, Harvard Medical School Gastrointestinal Cancer Center, Dana-Farber Cancer Institute Daniel Chung, M.D. Assistant Professor of Medicine, Harvard Medical School Clinical Director, Gastrointestinal Cancer Genetics Program, Massachusetts General Hospital Andy Futreal, Ph.D. Co-Founder/Director, Cancer Genome Project, Wellcome Trust Sanger Institute Senior Investigator, Wellcome Trust Sanger Institute Todd Golub, M.D. Associate Professor of Pediatrics, Harvard Medical School Founding Member and Director of the Cancer Program, Broad Institute Charles A. Dana Investigator of Human Cancer Genetics, Dana-Farber Cancer Institute Howard Hughes Medical Institute Investigator

3 David H. Lee, Ph.D. Research Investigator Protein Analytics Abbott Bioresearch Center Andrew Leiter, M.D., Ph.D. Department of Medicine/Division of Gastroenterology, University of Massachusetts Medical School Professor of Medicine, University of Massachusetts Medical School Arnold Levine, Ph.D. Professor, The Simons Center for Systems Biology, Institute for Advanced Study Professor, Pediatrics and Biochemistry, Cancer Institute of New Jersey Thomas J. Lynch, M.D. Professor of Medicine and Director, Yale Cancer Center Physician-in-Chief, Smilow Cancer Hospital at Yale-New Haven Founding Member, Kenneth B. Schwartz Center Anil Rustgi, M.D. T. Grier Miller Professor of Medicine and Genetics, University of Pennsylvania Chief, Gastroenterology Division, University of Pennsylvania Director, Center for Molecular Studies in Digestive and Liver Disease, University of Pennsylvania Co-Director, Tumor Biology Program, Abramson Cancer Center William Sellers, M.D. VP and Global Head of Oncology, Novartis Institutes for Biomedical Research, Novartis Member, National Cancer Advisory Board Evan Vosburgh, M.D. Vice President, Verto Institute Executive Director, Raymond and Beverly Sackler Foundation Chairman, Medical Affiliates Board, Alliance for Cancer Gene Therapy

4 2013 Challenge Grant The Caring for Carcinoid Foundation has received an extraordinary $1 million challenge from the Goldhirsh-Yellin Foundation. This challenge is designed to accelerate and expand a promising and exciting research portfolio, a portfolio that moves us closer to our ultimate goal of finding treatments and eventually a cure for carcinoid and other neuroendocrine tumors (NETs). This award comes at an exciting time. Despite the significant progress in treating and managing many forms of cancer, there are no cures and few standardized treatments for neuroendocrine including carcinoid and pancreatic - tumors, or NETs. That is beginning to change. Both CFCF and the Goldhirsh-Yellin Foundation believe that progress can be made by fueling research projects underway, exploring the applicability of some new forms of treatment to NETs, and by encouraging brilliant young scientists to dedicate more of their attention to these forms of cancer. In fact, CFCF is now funding its first clinical trial and seeing some really exciting breakthroughs in its research portfolio. Elizabeth Goldhirsh-Yellin is a young woman a wife and mother, recently diagnosed in much the way many NET patients are identified: by accident. A few months ago, she had an appendicitis attack. She left the hospital with an unexpected diagnosis and little in the way of standardized treatment to give her a road map for dealing with it. She had a carcinoid tumor. Thus began her journey and partnership with CFCF. Having lost both parents to cancer, Elizabeth was already practiced at identifying and supporting top researchers doing impactful work. Her own diagnosis in hand, Elizabeth is now committed to extending her philanthropy and her attention to neuroendocrine cancer research. According to Elizabeth, I am choosing to partner with the Caring for Carcinoid Foundation because they have an excellent track record of supporting great and diverse science and scientists, because they are committed to thoughtful collaboration that brings new options and information to patients like me, and because they have a disciplined peer review approach for the work they support. I am hopeful that the Goldhirsh-Yellin Foundation s support will accelerate and expand their work, and I m also hopeful that it will leverage the financial support of others in the carcinoid and NET community to do the same. The Goldhirsh-Yellin Foundation has issued a challenge to friends and supporters of the Caring for Carcinoid Foundation: each new or increased gift will be matched by the Foundation. This is an extraordinary opportunity to do everything we can to find pathways for better treatments, and to test out possible breakthrough therapies as we continue our aggressive quest for cures. We hope you will join us. The Caring for Carcinoid Foundation is enormously grateful to Elizabeth and the Goldhirsh-Yellin Foundation. Her support, and yours, hold the promise of great progress, says Ron Hollander, the Caring for Carcinoid Foundation s Executive Director. This is probably the most exciting time for CFCF s research since its founding. Recent discoveries are opening doors for possible treatments, our portfolio of clinical and basic research is expanding into new areas and we are attracting dynamic new partners, like the Goldhirsh-Yellin Foundation, to the cause. We d like nothing better than being able to say we are bringing faster progress and more hope to patients like Elizabeth. Director of Research, Lauren Erb, Elizabeth Goldhirsh-Yellin, and Executive Director, Ron Hollander

5 2013 Funded Research In 2013, the Caring for Carcinoid Foundation awarded over $1.3 million to launch high-impact research initiatives to achieve better diagnosis, better treatments, and better outcomes for neuroendocrine cancer patients. There is little federal support for rare diseases even before sequestration cuts. Private funding of carcinoid and neuroendocrine cancer research is more critical than ever and CFCF is committed to driving a robust research agenda to control and conquer neuroendocrine cancer. At first, all our research projects were discovery projects, searching for the genes, mutations, pathways associated with the disease. In 2011, a CFCF-sponsored project yielded breakthroughs in pancreatic neuroendocrine cancer that changed everything. As our BOSA Chair said: A door has been opened and we now had targets for further research. Our scientists are convinced that what we learn from these findings will enable us to rapidly accelerate the progress. In 2013, a CFCF sponsored project discovered mutations in carcinoid tumors that may open other doors. The CFCF Board is determined to do all we can to understand these results and use them to develop treatments to target these findings as rapidly as possible. This requires a significant expansion of our research portfolio to build on these breakthroughs. In 2013, CFCF envisioned a bold new wave of research funding that enabled us to move rapidly and decisively through the doors that have been opened on multiple fronts including; opportunities to fund the next wave of research to find new targets for treatments and biomarkers for diagnosis and control of the disease, attract more top labs and top investigators to the cause of controlling and conquering carcinoid and neuroendocrine cancer, and accelerate the process of identifying, refining and testing better, targeted treatments for patients and better biomarkers for diagnosing and predicting tumor behavior Rally for Medical Research, Washington, DC

6 Funded Research Projects Implication of Heterogeneous Innate Immune Cells in Pancreatic Neuroendocrine Tumor Resistance Gabriele Bergers, PhD - University of California San Francisco $250,000 (Duration: 2 years) This grant was issued in partnership with the American Association for Cancer Research. Objective: To develop a next generation anti-angiogenic treatment strategy for neuroendocrine tumor patients by studying resistance mechanisms. All cells require an adequate blood supply to survive. Cancer cells, since they tend to replicate faster than normal cells, require an even greater blood supply. In order to achieve this, many tumors, including pancreatic neuroendocrine tumors, undergo angiogenesis, the development of new blood vessels. In 2011, sunitinib malate (an angiogenesis inhibitor) was approved by the US FDA to treat patients with pancreatic neuroendocrine tumors. This was an important advance, however; therapeutic resistance frequently emerges over time. A better understanding of why resistance emerges and strategies to overcome resistance are needed. Research Objectives: 1. Identify and investigate the composition and function of innate immune cells in human pancreatic neuroendocrine tumors. 2. Elucidate the functional significance of Gr1- and Gr1+ innate immune cell oscillation in the proangiogenic relapse and identify combinatorial treatment modalities that sustain response to sunitinib and sorafenib. Abstract: Advanced pancreatic neuroendocrine tumors (PNETs) are a lethal group of tumors for which no standard therapy exists. New therapies are desperately needed to improve the quality of life and survival of PNET patients. Inhibitors of the VEGF-signaling pathways have yielded promising results and the angiogenesis inhibitor sunitinib was recently FDA approved in PNET patients with advanced disease. Notwithstanding, the beneficial effects are transient and demonstrate the limitations of one of the so far most promising drugs for PNET patients that facilitate tumor stasis instead of shrinkage and is successful only in a subset of patients. Inevitably, the tumors begin to grow again and the disease progresses, after a fleeting period of clinical benefit that is typically measured in months. The goal of this project is to improve the anti-angiogeneic treatment strategy for pancreatic neuroendocrine tumor patients. Based on our preliminary data obtained from a transgenic model of PNET, we propose that distinct infiltrating innate immune cells oscillate in the tumor in response to therapy to override vascular growth restrictions and that the intratumoral monocyte composition and their expression pattern might be indicative of resistance to anti-angiogenic therapy. Utilizing a microfluidic single cell real time PCR platform in conjunction with 8-color FACS to isolate innate immune cells from human PNET tissues and murine PNETR during therapy, we intend to understand how the distinct innate immune cell populations endorse resistance, how they oscillate to compensate for each other and how one can more successfully inhibit innate immune cell infiltration and action to re-sensitize therapy, increase response rate and prolong survival of patients undergoing antiangiogeneic therapies. Since Sunitinib has become a FDA-approved drug, we believe that the intended studies in this proposal are timely and seminal investigating mechanisms that can be translated into new treatment modalities to hopefully guide and advance the therapeutic effort in the clinic.

7 Identifying Altered Epigenetic States and Drivers in Intestinal Carcinoid and Pancreatic Neuroendocrine Tumors Bradley Bernstein, MD, PhD - Broad Institute, Massachusetts General Hospital Daniel Chung, MD - Massachusetts General Hospital Matthew Kulke, MD; Ramesh Shivdasani, MD, PhD - Dana-Farber Cancer Institute $620,000 (Duration: 2 years) Objective: To identify altered epigenetic states and drivers in carcinoid and pancreatic neuroendocrine tumors to identify new treatment strategies for patients. In parallel the team will also work to develop carcinoid and pancreatic neuroendocrine tumor models. These models will be used to assess potential new biomarkers and will also facilitate future research projects. To date, few recurrent mutations have been identified in intestinal carcinoid and pancreatic neuroendocrine tumors and of the few that have been identified the majority are in genes involved in epigenetic regulation. This suggests that epigenetic changes may be underpinning the development and maintenance of carcinoid and pancreatic neuroendocrine tumors. Therefore it is necessary to understand the epigenomes of carcinoid and pancreatic neuroendocrine tumors to identify the root causes of these cancers and to identify new therapeutic targets. With this funding, Dr. Bernstein and his collaborators will identify epigenetic alterations in carcinoid and pancreatic neuroendocrine tumors to identify new treatment strategies for patients. In the process they will build a public resource of epigenetic states, circuits and molecular dependencies for carcinoid and pancreatic neuroendocrine tumors. They will also generate new carcinoid and pancreatic neuroendocrine tumor models to assess new biomarkers and facilitate future research. Research Objectives: 1. Deep characterization of genome-wide chromatin states in primary human carcinoid tumor and pancreatic neuroendocrine tumor samples, with the goal to determine the gene regulatory circuits and aberrant epigenetic states that sustain these tumors and may thus represent therapeutic opportunities. 2. Generation of stable new carcinoid tumor and pancreatic neuroendocrine tumor models to assess new biomarkers in carcinoid tumors and their associated stroma and to determine the significance of particular histone modifications through future perturbation studies. Abstract: Considerable effort, including exome sequencing, has identified few recurrent mutations in intestinal carcinoid and pancreatic neuroendocrine (PNETs) tumors (1) (Francis et al, Nat Genet 2013, In Press). This suggests that epigenetic changes rather than mutations may disrupt normal cell behaviors to produce and sustain these unusual, often indolent cancers. Indeed, genes that regulate chromatin, such as MEN1, ATRX and DAXX, dominate the short list of recurrent mutations in these diseases (2, 3). One effect of ATRX and DAXX mutations is to lengthen telomeres through a telomerase-independent alternate pathway (4, 5) but chromatin-modifying genes mutated in NETs are also implicated in transcriptional control (6, 7) and the relative importance of these distinct effects in disease pathogenesis is unclear. The epigenomes (profiles of covalent histone modifications) in primary human carcinoid tumors and PNETs might illuminate disease mechanisms and key nodes of transcriptional dysregulation, revealing both pathogenic insights and potential therapeutic targets among the root causes of these cancers. Recent advances support this idea. First, diverse cancers carry mutations in chromatin regulator (CR) genes, including 25-75% of non-hodgkin lymphomas, 35% of pancreas adenocarcinoma, and nearly 100% of rarer entities such as papillary thyroid and NUT midline carcinoma [reviewed in (8)]. Because such mutations are common and widespread,

8 many drug companies have prioritized the development of epigenetic-based therapies. Thus, drugs with the potential to treat carcinoid and PNET tumors may be developed for other, more common indications; knowing the particular derangements in carcinoid and PNET tumors will help match the latter with appropriate drugs. Second, technical and computational advances now make it possible to determine epigenetic states across the genomes of normal and cancer tissues (9). In-depth characterization allows one to know exactly which chromatin modifications occur at individual genes and their regulatory elements; how these modifications respond to perturbation; which ones may be especially important for cancer pathogenesis; and which may present opportunities for therapy. Our overarching hypothesis is that epigenome (histone) alterations in carcinoid and PNET tumors will yield vulnerabilities that can be targeted with drugs. We propose to test this hypothesis in primary tumor samples, hence uncovering both inherent vulnerabilities and corresponding therapeutic opportunities (Specific Aim 1). Fresh-frozen tumor tissue is essential for this work and we propose in parallel to use portions of the same tissue samples to achieve another vital CFCF goal: construction of new cellular models that retain the epigenetic state of the primary tumors (Specific Aim 2). We will do this as part of a wider effort between the Broad Institute and our respective cancer centers, dividing surgical specimens into portions that are suited to each goal: epigenome analysis (Aim 1) and cell model construction (Aim 2). If we are successful, the new cell models will be invaluable tools for perturbation experiments that directly test the chromatin-related hypotheses we will generate in Aim 1.

9 Epigenomic Analysis of Intestinal Neuroendocrine Cells and the Epigenetic Basis of Neuroendocrine Tumors Ramesh Shivdasani, MD, PhD - Dana-Farber Cancer Institute $228,869 (Duration: 4 years) Objective: To study how epigenetic regulation controls the process by which a stem cell becomes a neuroendocrine cell and to identify how changes in epigenetic regulation can promote development of neuroendocrine tumors. With prior funding from CFCF, the Shivdasani lab has made significant progress in understanding the cell of origin for intestinal neuroendocrine tumors. Intestinal stem cells have the capacity to replicate indefinitely or to become any of many different types of intestinal cells. Dr. Shivdasani s laboratory studies how these gastrointestinal stem cells make the decision to stop behaving like a stem cell and instead to differentiate into a neuroendocrine cell that might someday become a neuroendocrine tumor cell. To build on prior progress, CFCF has awarded a second grant to Dr. Shivdasani to study how epigenetic regulation controls the process by which a stem cell becomes a neuroendocrine cell and to identify how changes in epigenetic regulation can promote development of neuroendocrine tumors. Epigenetic regulators determine which genes are turned on or off under specific conditions in a cell. While genes contain the instructions for assembling proteins, it is through epigenetic regulation that cells are able to control whether or not these proteins are actually produced. Epigenetic regulation controls the processes by which intestinal stem cells decide between remaining a stem cell and differentiating into a neuroendocrine cell. Epigenetic regulation has recently been identified as a potential cause of neuroendocrine tumor development as mutations in epigenetic regulating genes have been identified in neuroendocrine tumors. Research Objectives: 1. Elucidate key epigenetic regulatory steps in differentiation of intestinal stem cells into neuroendocrine cells. 2. Determine how epigenetic regulation controls proliferation and differentiation of neuroendocrine cells. 3. Identify new genes and pathways to target for treatment of patients with neuroendocrine tumors. Abstract: Intestinal neuroendocrine tumors arise from rare hormone secreting progenitor cells that in turn arise from selfrenewing stem cells. In current views, a key cell population in cancers, including intestinal and pancreatic neuroendocrine tumors, manifests the stem-cell properties of lifelong self-renewal, incessant replication, and immaturity. Therefore, it is very important to understand the normal basis for these properties and how individual cancers adopt them. Such understanding will inform rational approaches toward cancer prevention and therapy. Mutations in protein-coding genes drive cancer development and progression. Knowledge of such mutations in several cancers has identified prime molecular targets for therapies that are starting to extend patients lives. Mutations affect the primary DNA sequence in the single cell that eventually turns cancerous. However, the bulk of DNA in human cells does not encode proteins; much of the genome is devoted to ensuring tight control of protein-coding genes, specifically, in determining whether they will be turned on or off. This process is known as epigenetics and its vital role in normal and cancer cells is coming into sharper focus, for two reasons. First, epigenetics control cell differentiation, the process by which stem cells make the choice between indefinite replication and maturing into a committed cell type such as an intestinal or pancreatic neuroendocrine cell.

10 Second, mutations in epigenetic regulatory genes are found in many cancers, including neuroendocrine tumors, pointing to altered gene regulation as a second key driving force. In fact, the few mutations identified to date, in pancreatic neuroendocrine tumors, occur in genes that control other genes (epigenetic regulators). However, we know so little about normal epigenetic control that it is difficult to know where to begin to translate these seminal discoveries into useful treatments for patients. To narrow this gap in knowledge, here I propose timely studies to investigate the normal epigenetic control of intestinal stem and enteroendocrine progenitor differentiation and to characterize the epigenetic basis of neuroendocrine tumorigenesis.

11 Theragnostics of Neuroendocrine Tumors with Somatostatin Antagonists Wolfgang Weber, MD, PhD; Diane Reidy-Lagunes, MD - Memorial Sloan Kettering Cancer Center $250,000 (Duration: 2 years) Objective: To conduct a clinical trial for patients with carcinoid cancer for both treatment with the radionuclide, Lutetium-177 and imaging with the radionuclide, Gallium-68. This trial may provide proof of concept data to assess the potential for peptide receptor radionuclide therapy with somatostatin antagonists as a new treatment strategy for neuroendocrine tumor patients. This could pave the way for development of a new treatment and diagnostic imaging strategy for patients with neuroendocrine tumors in the US. Peptide Receptor Radionuclide Therapy (PRRT) is a technique widely used in Europe for the management of patients with metastatic neuroendocrine tumors. There are currently clinical trials in the United States for PRRT with somatostatin agonists as described below. PRRT delivers targeted radiation therapy by exploiting the physiology of neuroendocrine tumors. Most neuroendocrine tumors, including carcinoid, have specialized cellular receptors that bind to somatostatin, a hormone that exists naturally in the human body. Scientists have developed artificial analogs of somatostatin to attach to these receptors. These are called somatostatin agonists and they include agents like octreotide. Somatostatin agonists are able to target neuroendocrine tumors by binding to the somatostatin receptors present on tumor cells. The PRRT currently in use typically combines a somatostatin agonist with a radioactive substance called a radionuclide to form highly specialized molecules called radiopeptides. These radiopeptides can bind receptors on tumor cells where they emit radiation that can either 1) be read for diagnostic imaging or 2) kill tumor cells. Studies have suggested that PRRT with somatostatin agonists can lead to a decrease in tumor size and alleviation of symptoms in some patients. However, not all patients respond and there can be serious side effects including kidney failure. To date, randomized prospective clinical trials, of the nature typically required by the FDA for regulatory approval have not yet been completed. However, there is currently a prospective randomized clinical trial of PRRT with somatostatin agonists in the United States enrolling patients at multiple centers. The Memorial Sloan-Kettering Clinical Trial To improve effectiveness while reducing side effects, Dr. Weber and his collaborators have developed a technique for next generation PRRT. Instead of somatostatin agonists, this next generation PRRT will employ somatostatin antagonists. Based on preclinical data, Dr. Weber believes that somatostatin receptor antagonists can be more effective and generate fewer side effects than the substances that are currently being used to treat patients. Specifically, this trial will assess the potential viability of 68 Ga-DOTA-JR11 and 177 Lu-DOTA-JR11 as a pair of diagnostic and therapeutic radiopeptides for neuroendocrine tumor patients. Gallium 68 is a radionuclide that can be used in diagnostic PET scans. Lutetium 177 is a radionuclide often used with somatostatin analogs to form therapeutic radiopeptides. This study will assess the sensitivity of gallium 68 and the safety of lutetium 177 when combined with the somatostatin antagonist, DOTA-JR11 developed by the researchers. Eight patients with progressive, metastatic and inoperable tumors will participate in a clinical trial of peptide receptor radionuclide therapy with the somatostatin antagonist DOTA-JR11. Thanks to funding from another large Foundation these eight patients will enroll alongside an additional 12 patients for a total of 20 patients enrolled. This trial may provide proof of concept data to assess the potential for peptide receptor radionuclide therapy with somatostatin antagonists as a new treatment for patients in the United States. Furthermore, strong data from this trial could enhance the commercial potential of these specific compounds. This could pave the way for development of a new treatment and diagnostic imaging strategy for patients with neuroendocrine tumors in the United States.

12 Research Objectives: 1. Assess biodistribution and tumor uptake of 68Ga-DOTA-JR11 and compare the sensitivity of 68Ga-DOTA-JR11 PET with conventional imaging 2. Determine tumor and normal organ doses after administration of 177Lu-DOTA-JR11; and 3. Obtain preliminary data on tumor response to 177LU-DOTA-JR11. Abstract: Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs has been developed in the 1990s, and is now frequently used in Europe for treatment of metastatic neuroendocrine tumors. However, not all patients respond well to PRRT; there are serious side effects, most notably chronic renal failure due to the renal excretion of the radiopeptides. Thus, there is a clear need to develop new ligands with higher tumor uptake and a more favorable tumorto-kidney dose ratio. To address this need, members of our group have developed radiolabeled somatostatin receptor type 2 antagonists. These are the first radiolabeled somatostain receptor antagonists. In this project we will study the second generation somatostatin receptor antagonists, 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11, as a pair of diagnostic/therapeutic radiopharmaceuticals (theragnostics) in patients with neuroendocrine tumors. Specifically, we will (i) assess biodistribution and tumor uptake of 68Ga-DOTA-JR11 and to compare the sensitivity of 68Ga-DOTA-JR11 PET with conventional staging procedures; (ii) determine tumor and normal organ doses after administration of 177Lu-DOTA- JR11; and (iii) obtain preliminary data on tumor response to 177Lu-DOTA-JR11. We will conduct a clinical trial including 8 patients with well to moderately differentiated, progressive and inoperable midgut carcinoids. Patients will first undergo a PET/CT with 68Ga-DOTA-JR11. Patients with sufficient tumor uptake of 68Ga-DOTA-JR11 will be offered therapy with 177Lu-DOTA-JR11. Therapy will be preceded by a dosimetric study to determine the amount of radioactivity that can be safely administered.

13 Patient Education Events The Caring for Carcinoid Foundation (CFCF) is dedicated to empowering patients and equipping them with a comprehensive understanding of treatment options so they can make the best informed decisions when deciding their care. In this spirit, CFCF is pleased to bring together our extensive community of patients, loved ones, medical professionals, and supporters for our annual series of free education events. Los Angeles Neuroendocrine Tumor Patient Education Conference CFCF returned to Southern California for its annual patient education event with Cedars-Sinai Medical Center. Date and Location: April 12 at Cedars-Sinai Medical Center, Los Angeles, CA Presenters Include: Edward Wolin, MD, Co-Director, Carcinoid & Neuroendocrine Tumor Program, Cedars-Sinai Medical Center Arash Asher, MD, Director, Cancer Survivorship & Rehabilitation, Cedars-Sinai Medical Center Focus on Neuroendocrine Tumors: Patient and Caregiver Conference This is CFCF s third collaboration with the University of Pennsylvania Abramson Cancer Center. Those unable to attend in person will be able join a live discussion with conference presenters over the internet. Date and Location: Presenters Include: September 27 at the Hilton Hotel, Philadelphia, PA David Metz, MD, Associate Chief for Clinical Affairs, Gastroenterology, University of Pennsylvania James Yao, MD, Associate Prof. of Medicine, University of Texas MD Anderson Cancer Center Stanford Neuroendocrine Tumor Patient Education Conference CFCF will return to Northern California for its fourth event in conjunction with Stanford Cancer Center. Date and Location: Presenters Include: October 12 at the Stanford University Arrillaga Alumni Center, Stanford, CA George Fisher, MD, PhD, Physician Leader & Cancer Clinical Trials Director, Stanford University Pamela Kunz, MD, Medical Oncologist, Stanford University Greta Macaire, RD, CSO, Certified Specialist in Oncology Nutrition, University of California, San Francisco Cancer Center Jeffrey Norton, MD, Professor of Surgery, Stanford University Houston Neuroendocrine Tumor Patient Education Conference CFCF will welcome Worldwide NET Cancer Day with its third event in Texas. This seminar will be co-sponsored with the Methodist Cancer Center in participation with the MD Anderson Cancer Center. Date and Location: Presenters Include: November 8 at the Methodist Cancer Center, Houston, TX Eric Liu, MD, Surgical Oncologist, Vanderbilt University Medical Center Diane Reidy Lagunes, MD, Medical Oncologist, Memorial Sloan-Kettering Cancer Center Alexandria Phan, MD, Hematologist/Oncologist, Houston Methodist James Yao, MD, Associate Prof. of Medicine, University of Texas MD Anderson Cancer Center

14 Community Events The Caring for Carcinoid Foundation brings the neuroendocrine cancer community together through a series of highly visible athletic events and grassroots fundraising events across the nation. Team members and fundraisers include patients, caregivers, physicians and friends, run, bike, walk, and swim to a cure. The events benefit patients by empowering them to go out into their communities and advocate and fight for increased awareness of their disease. Cycle for Survival February 2013 Indoor cycling teams in New York and Boston Ride to raise funds for Dr. Diane Reidy Lagunes at Memorial Sloan Kettering Cancer Center Walk with Chuck May 2013 Walking event organized and sponsored by Prospect Transportation/Eichholz Family Contact is Neary King and Melissa Eichholz Company event in Carstadt, New Jersey Held in honor of Charles Eichholz Annual Event Donation made on Firstgiving fundraising page and by mail Maple Point Middle School Dodgeball Tournament June 2013 Organized and sponsored by Maple Point Middle School in Middletown, Pennsylvania Event in honor of Dennis Howie, organized by wife Jennifer Howie, a teacher for gifted students Pan Mass Challenge August 2013 Long distance bike riding challenge across the state of Massachusetts Annual event for CFCF 50+ Participants each year Remembering OC, Pay it Forward August 2013 Organized by Kristin O Connor, has organized the event several times before Event in memory of Christian O Connor (husband of Kristin) Friends and family gather for a Mets game and barbeque Dana Farber Jimmy Fund Walk September 2013 Annual event with a team that continues to grow in numbers 2013 Jimmy Fund Walk 2013 Pan Mass Challenge