The Translational Genomics Research Institute

“RICHARD BOALS AND ROBERT BULLA HAVE A BUSINESS RELATIONSHIP. JERRY BISGROVE AND BERT GETZ HAVE A BUSINESS RELATIONSHIP. Form 990, Part VI, Line 11b The form 990 is prepared by an outside accounting firm based on information provided by the TGen Finance department. The form 990 is then reviewed by the Finance department and other members of management. The form 990 is posted on the Board website for Board review prior to filing with the IRS.”

“TGen distributes a conflict of interest questionnaire annually to all director level positions and above, in addition to any key employees designated by the Chief Operating Officer. The questionnaires are reviewed by the Chief Financial Officer and TGen's Office of Research Compliance. Those employees with conflicts are sent for further review to the Chief Operating Officer to ensure an appropriate plan is set forth. Updates to the list are handled on an as-needed basis, based on contract reviews and employee information.”

“TGen's Governance and Executive Compensation committee will act in an "advice and consent" capacity reviewing the recommendations for the President and Scientific Director regarding the compensation of disqualified persons and forwarding final recommendations to the full Board for approval. Disqualified persons (except for the President and Scientific Director) will not be present for, or participate in, Committee deliberations concerning their compensation (other than to answer questions). The President and Scientific Director will participate in the deliberations concerning the compensation of direct reports. During the decision making process, the Committee will adhere to the executive compensation philosophy. The Committee is authorized (and provided with sufficient funding) to annually engage outside independent compensation and legal advisors, when deemed necessary and advisable. The Committee will comply with the "rebuttable presumption of reasonableness" under section 4958 of the internal revenue code whenever possible. The Committee will review and understand the internal revenue code provisions dealing with "excess benefit transactions concerning disqualified persons' compensation." When developing a compensation philosophy, TGen kept in mind the following factors: The TGen Mission and Strategy The TGen Culture Trends in compensation in the external environment Trends in Recruitment of new employees Trends in organizational Employee Turnover TGEN's Life Cycle Stage”

“The Organization's governing documents, conflict of interest policy, and financial statements are provided to the general public upon request.”

“TGen has a Board of Governors that is comprised of current voting Directors and some former Directors that remain affiliated with TGen in an advisory role. The current nonvoting advisory Governors not listed as Directors in Part VII, Section A include: Betsy Bayless Susan Clark-Johnson The Honorable Diane Enos John D. Haeger, Ph.D. Ann Weaver Hart, Ph.D. Sethuraman Panchanathan, Ph.D. The Honorable Jim Slattery Victor Trastek, M.D.”

“The Translational Genomics Research Institute (TGen) is a nonprofit biomedical research institute focused on developing earlier diagnostics and smarter treatments by employing innovative advances arising from the human genome project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. FORM 990, PART III, LINE 2 IN 2013, The Translational Genomics Research Institute (TGEN) UNDERTOOK THE FOLLOWING NEW ACTIVITIES: (1) TGEN CREATED TGEN HEALTH VENTURES, LLC (TGEN HEALTH VENTURES), AN ARIZONA LIMITED LIABILITY COMPANY, FOR THE PURPOSE OF HEALTH CARE COMMERCIALIZATION OPPORTUNITIES. (2) TGEN CREATED PET CANCER DIAGNOSTICS, LLC (PET CANCER DIAGNOSTICS), AN ARIZONA LIMITED LIABILITY COMPANY, FOR THE PURPOSE OF ANIMAL DIAGNOSTICS. (3) TGEN CREATED PMED MANAGEMENT, LLC (PMED) AND PERSONALIZED MEDICINE PARTNERS, LLC (PMP), BOTH DELAWARE LIMITED LIABILITY COMPANIES, AND PERSONALIZED MEDICINE CAPITAL, LLP (PMC), A DELAWARE LIMITED LIABILITY PARTNERSHIP, TO ASSIST IN THE DEPLOYMENT OF PERSONALIZED MEDICINE FOR THE BENEFIT OF PATIENTS LOCALLY, NATIONALLY AND INTERNATIONALLY BY COMMERCIALIZING PERSONALIZED MEDICINE. (4) TGen launched the Center for Rare Childhood Disorders (C4RCD). In C4RCD, TGen's faculty will apply the latest tools of genomic medicine to provide answers for parents wanting to identify the disease or disorder affecting their child. FORM 990, PART III, LINE 3 IN 2013, The Translational Genomics Research Institute (TGEN) SOLD A MAJORITY INTEREST OF TRANSLATIONAL DRUG DEVELOPMENT, LLC (TD2, LLC), A CONTRACT RESEARCH ORGANIZATION THAT FOCUSES ON THE EARLY-STAGE DEVELOPMENT AND CONSULTATION OF CLINICAL TRIALS AND DRUG DEVELOPMENT. TGEN RETAINED A 29.4% MINORITY INTEREST OF TD2, LLC, WHICH IS RECORDED AS A PROGRAM RELATED INVESTMENT ON FORM 990, PART X, LINE 13. TGEN RECOGNIZED A $16.0 MILLION GAIN ON THE SALE OF ITS MAJORITY INTEREST. THIS GAIN IS REPORTED ON FORM 990, PART VIII, LINE 7. FORM 990, PART III, LINE 4A TGen's Integrated Cancer Genomics Division brings together bioinformatics, cutting-edge technologies and basic research to create a comprehensive attack on cancer with the ultimate goal of developing new diagnostics and treatments. Specific areas of focus include prostate cancer, melanoma, familial breast cancer, colon cancer, multiple myeloma and renal tumor research. Keeping in line with TGen's mission of developing earlier diagnostics and smarter treatments, we hope this integrated approach to cancer genome research will help to uncover important inherited and tumor derived alterations, which are associated with cancer susceptibility and important tumor characteristics such as progression and response to therapy. FORM 990, PART III, LINE 4B The Neurogenomics Division has two goals, both of which derive from the overarching mission of the Translational Genomics Research Institute (TGen). It is common knowledge that early intervention and treatment saves lives when it comes to neurological diseases. Therefore, our first goal is to improve the ability to diagnose neurological disease before it strikes. Because these diseases impact so many lives around the world either directly (by having a disease), or indirectly (by caring for a loved one with a disease), the second goal centers on the development of new 'smart-drug' therapies. There are five labs within the division, encompassing the entire breadth of neurological disease. FORM 990, PART III, LINE 4c TGen's Genotyping Technology Center analyzes bits of DNA called single nucleotide polymorphisms (SNPS) which give researchers the power to identify disease-causing genes, associations, and DNA signatures, all of which have profound implications for detection, prognosis and therapeutic intervention. The SNP Genotyping Center offers innovative solutions that address the requirements for flexibility, simplicity, throughput, economy and accuracy. and accuracy.”

“Introduction Year-over-year, TGen adds value to Arizona's biomedical sector through scientific and medical advances, educating the next generation of scholars, and economic stimulus. A key to this success has been our State-funded support. In FY13, our 11th year of operations, we announced among other initiatives, the launch of the TGen Center for Rare Childhood Disorders (C4RCD), where our faculty will apply the latest tools of genomic medicine to provide answers for parents wanting to identify the disease or disorder affecting their child. And, thanks to Stand Up To Cancer, The Ben & Catherine Ivy Foundation, the Melanoma Research Alliance, the State's universities, multiple local health care providers and others, we initiated research projects and clinical trials in the study of melanoma and brain tumors, with the goal of delivering the latest in effective new treatments to patients as quickly as possible. In the area of Alzheimer's disease research, MindCrowd (www.mindcrowd.org) is a unique internet-based project designed to identify the genetic markers linked to learning and memory. MindCrowd harnesses the power of the Internet to study the human brain by engaging the world and seeking 1 million on-line participants. We have all met someone who can run faster or jump higher than us. When it comes to learning and remembering, the same is true. Our individual genetic blueprint - made up of billions of letters - determine, at least in part, these differences. Today, more than ever before, many patients facing cancer and other serious illnesses are hearing about TGen's patient-focused research and how it has begun to change the way we think about the practice of medicine. In a front-page New York Times article, the search for precision therapy brought San Diego-based molecular biologist Dr. Tim McDaniel to TGen when his own mother faced a rare but deadly cancer. Knowing of their patient-focused approach to research, Dr. McDaniel selected TGen scientists to help connect the best available science to his mother's treatment plan. By working together to analyze the billions of data points in her genome, they identified a unique genetic change and matched it with a therapy that improved his mother's quality of life long enough for her to celebrate her 50th wedding anniversary. TGen's patient-focused approach also enabled TGen to be selected by Stand Up To Cancer and the Melanoma Research Alliance to co-lead a national dream team of scientists and physicians in an unprecedented three-year study of the most deadly form of skin cancer. They will investigate possible new individualized approaches to patients based on the specific genomic changes in their cancers. A common thread to all of these stories is TGen's ability to sift through the billions of genetic data points generated through the sequencing of each individual genome. Advances in medicine and scientific knowledge about disease have created a ripe environment for medical advances. Nevertheless, identifying the right treatment to target cancer and other complex diseases is still difficult and cost prohibitive. The development of whole genome sequencing and advanced proteomic technologies, both occurring at TGen, addresses these challenges. TGen's application of these technologies, coupled with next-generation sequencing methods, allows our faculty to sequence an individual's entire genome more quickly and cost effectively than ever before. This has unlocked the biology of disease in entirely new ways. Sequencing pinpoints clinically actionable targets for difficult-to-treat cancers by identifying all the genetic mutations in a human genome. This creates more opportunities for clinical collaborations between TGen and its research partners and allows TGen to establish a niche for itself in clinical applications of next-generation sequencing technology. Patients benefit from access to personalized data that identifies familial genetic risks and allows them to make informed heal”

“The main focus of TGen's biomedical research has always been the patient, whether seeking a greater understanding of the biology underlying a particular disease, or using that knowledge to develop diagnostic platforms or render more precise treatment options. Driven by technology, but powered by TGen's outstanding scientific and clinical investigators, the Institute is equal to the strengths and capabilities of any of today's leading research and clinical institutes. Nowhere is this more evident than with TGen's whole genome sequencing capabilities. Whole genome sequencing allows us to dig deeper into the genome than ever before by providing more information and increasing our probability of identifying something significant. The long-term hope is that doctors will leverage this information to inform decisions about patient care. The results from these research studies appear in a number of leading scientific and medical journals and add to the growing knowledge base of molecular research and medicine. In FY13, TGen researchers published their research results in numerous scholarly peer-reviewed academic journals and through presentations at leading national and international conferences. These include publication in leading scientific journals such as Nature, Nature Genetics, Cancer, Genome Medicine, PLos One, Human Genetics, Blood, Science Translational Medicine, and a host of other disease-associated publications. FY13 Select Highlights 1. Isolation and characterization of muscle fatigue substance with anti-tumor activities. Munoz RM, Han H, Tegeler T, Petritis K, Von Hoff DD, Hoffman SA. J Cancer. 2013 May 9;4(4):343-9. Print 2013. 2. Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability. Demeure MJ, Craig DW, Sinari S, Moses TM, Christoforides A, Dinh J, Izatt T, Aldrich J, Decker A, Baker A, Cherni I, Watanabe A, Koep L, Lake D, Hostetter G, Trent JM, Von Hoff DD, Carpten JD. Genome Med. 2012 Jul 4;4(7):56. [Epub ahead of print] 3. Reciprocal Activation of Transcription Factors Underlies the Dichotomy between Proliferation and Invasion of Glioma Cells. Dhruv HD, McDonough Winslow WS, Armstrong B, Tuncali S, Eschbacher J, Kislin K, Loftus JC, Tran NL, Berens ME. PLoS One. 2013; 8(8):e72134. 4. HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, Cannon-Albright LA, Teerlink CC, Camp NJ, Johnson AM, Zuhlke KA, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Maier C, Luedeke M, Vogel W, Schleutker J, Wahlfors T, Tammela T, Schaid D, McDonnell SK, DeRycke MS, Cancel- Tassin G, Cussenot O, Wiklund F, Grnberg H, Eeles R, Easton D, Kote-Jarai Z, Whittemore AS, Hsieh CL, Giles GG, Hopper JL, Severi G, Catalona WJ, Mandal D, Ledet E, Foulkes WD, Hamel N, Mahle L, Moller P, Powell I, Bailey-Wilson JE, Carpten JD, Seminara D, Cooney KA, Isaacs WB; International Consortium for Prostate Cancer Genetics. Hum Genet. 2013 Jan; 132(1):5-14. Epub 2012 Oct 12. 5. Detection of chromosomal alterations in the circulation of cancer patients with whole- genome sequencing. Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O'Shaughnessy J, Kinzler KW, Parmigiani G, Vogelstein B, Diaz LA Jr, Velculescu VE. Sci Transl Med. 2012 Nov 28; 4(162):162ra154. 6. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, et. al. Nat Genet. 2013 Aug 28; 45(9):984-?94. Epub 2013 Aug 11. 7. An integrated map of genetic variation from 1,092 human genomes. 1000 Genomes Project Consortium,”

“1. In August 2012, a Phase I/II, multi-center trial designed to test the safety and preliminary efficacy of a first-in-class cancer treatment opened worldwide at the Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare. PR610 is designed to activate in tissues with low levels of oxygen, which is characteristic of many cancers. This "targeted" approach should deliver more active drug to cancer tissue and less active drug to normal tissue. The two-part trial, would first determine acceptable dose levels of PR610 in patients with various types of advanced cancer. After determining acceptable dose levels, the study would then evaluate the safety and efficacy of PR610 when given to patients with non-small cell lung cancer whose tumors contain a certain genetic mutation. 2. In November 2012, a new cancer drug combination demonstrated significant improvement in overall survival of late-stage pancreatic cancer patients compared to those receiving standard treatment, according to results of a Phase III clinical trial. SHC/TGen Physicians were first to design a clinical trial to determine the safety, tolerability and effectiveness of nab-paclitaxel (Abraxane) in combination with the standard drug gemcitabine in patients with advanced pancreatic cancer. Results of that multicenter study chaired by Dr. Daniel Von Hoff were encouraging enough that it led to one of the largest international studies ever done in pancreatic cancer, with 861 patients. 3. In March 2013, The FDA has approved a thyroid cancer drug successfully tested at Virginia G. Piper Cancer Center Clinical Trials, a partnership of Scottsdale Healthcare and the Translational Genomics Research Institute (TGen). The U.S. Food and Drug Administration approved Cabozantinib for the treatment of progressive, metastatic medullary thyroid cancer (MTC), a rare endocrine gland cancer affecting the thyroid. Previously, MTC patients had limited treatment options. 4. In April 2013, TGen and SHC reported the safety and preliminary efficacy of a new class of tumor fighting drugs. Early results from the phase I, first in-human study of an RNA interference (RNAi) drug were announced during the American Association for Cancer Research (AACR) Annual Meeting 2013, April 6-10, in Washington, D.C. Tekmira Pharmaceuticals developed TKM-080301 (also known as TKM-PLK1). The study was conducted at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership with TGen. It found that the RNAi drug acts by silencing the PLK1 gene involved in tumor growth and can be safely administered in humans. Most patients tolerated the drug well; some showed therapeutic benefit. Grant Support In addition to philanthropic donations and research contracts, grant funding is an important funding source for research. In FY2013, TGen investigators submitted 117 grants totaling $98M. TGen was awarded 12 grants, totaling $10.5M, with an additional 26 grants pending and in reviews totaling $14M. Additionally, TGen received $5.4M from 2010 and 2011 pending grants, bringing the awarded total for 2012 to $15.9. TGen's success rate currently rests at 22 percent of total grants submitted, placing the Institute nearly 4 percent higher than the national average (NIH overall success rate). FY13 Highlights 1. Three-year grant from the National Institutes of Health (NIH) totaling $1,207,367 to Dr. Nhan Tran to develop small molecule chemical probes against the TWEAK-Fn14 signaling pathway to treat glioma invasion. 2. Five-year grant from the National Institutes of Health (NIH) totaling $1,515,154 to Drs. Haiyong Han and Daniel Von Hoff to study targeted stromal collagen in pancreatic cancer. 3. Four-year grant from the National Institutes of Health (NIH) totaling $1,800,094 to Dr. Lance Price to study the rapid emergence of Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) ST398. 4. Five-year subcontracted grant to MRIGlobal from the Virginia Contracting Agency totalin”

“In FY13, TGen launched 2 initiatives to leverage internal discoveries and developments in genomics research and informatics tools. These are: 1. TGen Animal Health: A research and development project with a local Arizona firm to evaluate the portability of human diagnostic tools in the treatment of canine cancer. TGen is one of the early adopters of the canine model as a vehicle to accelerate human research. 2. Translational Systems, LLC: Translational Systems, LLC was created to facilitate the commercialization of a suite of informatics tools used in the creation, analysis and interaction of data from a variety of sources including patient samples and genomic data. Invention Disclosures TGen filed 28 invention disclosures in FY13 based on discoveries stemming from TGen-led research, and 26 provisional patent applications. Contracts and Collaborations TGen signed a total of 440 contracts in FY13, broken down as follows: a. 113 CDAs b. 70 MTAs c. 40 Research Collaborations d. 38 Consulting Agreements e. 79 Professional Service Agreements f. 4 Commercialization Licenses g. 96 agreements covering miscellaneous activities A sample of the universities, institutes, medical centers and corporations that TGen worked with include: Veterinary Neurological Center; Texas Engineering Experiment Station (TEES); Hills Pet Nutrition; Mayo Clinic; Illumina; Pathogene; Phoenix Children's Hospital; Spectrum Health Hospitals; Geisinger Clinic; Michigan State University; AztraZeneca Pharmaceuticals; Onyx Pharmaceuticals; Novartis Horsham Research Centre; Dignity Health; MMRC; Hoffmann- LaRoche; FDA/AZ Dept of Health Services; and Ventana Medical Systems. Job Creation Sixteen new full-time equivalent positions were created in 2013 with salaries and benefits totaling $1,213,836. Salaries for temporary positions (those positions created for a finite period of time) totaled $93,600 and student salaries were just over $340,000, bringing the overall total to $1,647,436. Eighty-eight percent of full-time TGen staff holds a college degree and fifty percent holds an advanced degree. FY13 full-time positions filled (new and replacements) included: - Accountant II - Assistant Professor - Bioinformatician, Associate - Business Analyst - Chief Financial Officer - Clinical Research Coordinator - Sr. Engineer, High-Performance Computing - Histotechnologist - IT Administrator - Manager, Physician In Chief's Office - Post-Doc Fellow - Research Associate - Research Associate II - Research Associate III - SharePoint Developer - Education and Outreach Specialist - Sr. Data Base Administrator - Staff Scientist - Vice President, Corporate Development Education and Public Outreach TGen gears its science education and community outreach toward the development of a talented bioscience workforce in Arizona and increased public fluency in genomic science and translational medicine. Education FY13 saw 45 Arizona students - selected from nearly 500 Arizona applicants - participate in TGen's flagship, paid summer internship program, Helios Scholars at TGen. Nearly every TGen division hosted interns for hands-on experiences: grants and research administration, environmental health and safety, cancer, neurological disease, diabetes and infectious disease. Cohort demographics: 73 percent attended public colleges or universities in Arizona; 24 percent self-identified as races/ethnicities underrepresented in the biosciences; 22 percent were in high school, 69 percent in college and 9 percent in graduate or medical school. TGen re-engaged the nearly 250 Helios Scholars alumni for the second annual alumni networking reception in July. Intern alumni from every Helios Scholars' class (2007-2013) attended the reception to expand their Arizona bioscience networks. Alumni also provide guidance to each new summer intern class, sit on the selection committee and act as ambassadors for the biosciences within their social and professional networks. The Ben and Catherine Ivy Foundation awarded”

“Description:consortium/contractual total fees:5182007”

“Description:outside research services total fees:1437179”

“Description:consulting total fees:659265”

“Description:temporary services total fees:116645”