RESEARCH Background

Research is a core component of Dana-Farber’s activities. Research generates the tools that allow DFCI to advance its mission to reduce and eventually eliminate the suffering caused by cancer. High-impact cancer research benefits from a close association between research and clinical care. Dana-Farber scientists have played central roles in the development of targeted therapies that produce substantial clinical responses with minimal side effects. DFCI’s researchers have also been pioneers in the design of novel therapies that harness the power of the immune system to fight and reject cancer.

Research at DFCI generally falls into one of four categories: investigator-directed laboratory research, clinical research, research in business units known as Integrative Research Centers and Programs, and enterprise-level overarching research projects. Each of these can be supported by technology platforms (commonly referred to as

“cores”) that can be accessed by all researchers at DFCI. These activities and entities are described below.

Investigator-Directed Laboratory Research

The fundamental type of research performed at DFCI is research designed and directed by a faculty member in his or her own laboratory. Approximately 160 faculty members are designated as Independent Investigators who have the authority to direct their own research. They include scientists who work in “wet labs” – biology, biochemistry, chemistry – and “dry labs” – statistics, computational biology, population sciences, and behavioral studies. All DFCI faculty must be faculty members in good standing at one of the Harvard University schools, usually Harvard Medical School and/or The Harvard T.H. Chan School of Public Health. Faculty are members of academic departments at Harvard as well as members of one of seven internal research departments within DFCI:

• Medical Oncology is responsible for providing cancer care to adult patients and for performing research relevant to that purpose. Therefore, research in this department tends to be focused on work that will impact patients either through clinical trials or explicitly translational research.

However, some members of this department also perform basic research. Medical Oncology also houses the Division of Population Sciences which conducts research on outcomes and dissemination of cancer treatments, healthcare policy, disparities in cancer treatment, and behavior modification.

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• Pediatric Oncology is responsible for providing cancer care to children. Research includes clinical trials, translational research, and fundamental biological discovery.

• Radiation Oncology is responsible for providing radiation-based care to adults and children with cancer and also performs clinical research. Radiation Oncology also houses a laboratory-based group that performs discovery research in the area of DNA damage and repair.

• Psychosocial Oncology and Palliative Care is responsible for providing psychological and social work support for cancer patients as well as palliative care. Research is designed to understand optimal strategies for delivering this care and improving the quality of life for cancer patients.

• Cancer Biology faculty perform basic discovery research in a variety of cancer related areas.

They include leaders in cancer genetics, signal transduction, systems biology, metabolism, and chemical and structural biology.

• Cancer Immunology and Virology focuses on basic discovery research in immunology and HIV pathobiology.

• Biostatistics and Computational Biology faculty perform basic research in the methodology of statistics but also provide collaborative support in the design and analysis of clinical trials.

Clinical Research

Clinical research is performed through the DF/HCC, the largest NCI-designated Comprehensive Cancer Center in the country based on total NCI funding. The Center grant, now in its 43rd year, originally supported DFCI alone but now includes a consortium of five hospitals (Dana-Farber, BWH, BIDMC, BCH, and MGH) and two schools (Harvard Medical School and the Harvard T.H. Chan School of Public Health). Dana-Farber is the lead member of the consortium, and the DFCI President and CEO is the overall director of DF/HCC. This clinical research enterprise has been responsible for generating recent advances in cancer therapeutics. For example, DFCI clinical researchers helped define molecularly targeted therapeutics for lung cancer and have generated groundbreaking results in modifying the immune system to fight cancer.

Integrative Research Centers and Programs

While investigator-driven research programs have produced scientific results that eventually impacted the lives of cancer patients, DFCI leadership believes that this process can be accelerated. Integrative Research Centers (each a

“Center”) were created around specific targeted areas of science. The mission of each Center is to provide a technology platform and collaborative home in which investigators from any department in the institute could pursue ideas related to the purpose of that Center.

Some Centers, like the Belfer Center for Applied Cancer Science (“Belfer”), have attracted significant partnerships with industry. For example, through Belfer, DFCI entered into a collaboration agreement with Merck and with Sanofi/Aventis over multi-year periods. Each agreement included milestone and royalty payments to DFCI for pharmaceuticals developed through these collaborations. The Belfer Center now occupies approximately 12,000 square feet of the space on the fourth floor of the Longwood Center.

The Program in Cancer Chemical Biology focuses on advances in chemical biology, a key area for DFCI.

Pharmaceutical companies have traditionally been DFCI’s partners in drug development. However, risk aversion and the changing landscape of cancer have led to a strategic refusal of most companies to develop drugs against

“difficult” targets or against targets that drive a relatively small number of cancers. Nonetheless, in order for DFCI to meet its mission, the Institute is dedicated to finding ways to develop drugs that will help patients whose cancers are driven by abnormalities that fall into these categories. Accomplishing this goal requires DFCI scientists to develop candidate drugs themselves. If DFCI can “de-risk” these candidates sufficiently by demonstrating their efficacy against their targets and their likely safety in humans, DFCI may be able to license these compounds to drug companies that could then complete their clinical development and make new drugs available to patients.

DFCI’s Program in Cancer Chemical Biology recruits chemists who can screen for and design compounds that block some of the most important molecular targets in cancer. The Chemical Biology Program now occupies most

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of the second and third floors of Longwood Center and their proximity to the Belfer Center on the fourth floor provides the means to accelerate the development of candidate drugs.

DFCI also has a collaborative relationship with The Broad Institute (the “Broad”), a nonprofit biomedical, bioinformatics and genomic research organization pursuant to which the Broad’s cancer program, which focuses on cancer genomics, is directed by a Farber physician scientist and includes collaborations with several Dana-Farber scientists. In addition, the Broad provides Dana-Dana-Farber-based initiatives with genomic support and software under separate research services and/or software license agreements.

Enterprise-Level Research

An enormous amount of information can be gained by the analysis of large numbers of individuals who have cancer.

Dana-Farber, its satellites, and its partner institutions (BWH and BCH) see approximately 21,000 new patients every year who have cancer. By collecting data on the patients who consent (currently about 70%), DFCI can create a resource that can be used by faculty to answer questions about cancer behavior and treatment.

There are two broad categories of data that are required from cancer specimens: clinical data and molecular data. A specific example of applying this resource is the PROFILE project in which researchers perform genomic analysis on the cancer materials from consented patients. DFCI currently has over 40,000 consented patients in the database with more than 16,000 molecular profiles completed. A web-based query tool allows investigators to mine these data for the presence of specific cancer-related mutations and, then, for consented patients, to link those molecular data to the data on clinical behavior.

The power of this database is manifested in three ways. First, investigators can perform analyses to test the effect of specific mutations on cancer behaviors. Second, molecular results that have treatment implications are returned to the treating clinician who can prescribe the appropriate drug for the appropriate molecular abnormality. And, third, the Institute can accelerate the process of clinical drug development by using the database to recruit participants to clinical trials of drugs targeted against specific mutations.

Core Services

Modern cancer research relies heavily on expensive technologies and resources that no single laboratory can support. To answer this need, the Institute has made capital investments in Core Services (“Cores”) which provide these centralized services in an efficient manner in return for a fee from the investigator. Examples of Cores range from the Biospecimen Repository which provides centralized long term freezer storage, to the Microarray Core, which provides genome analysis. One of the most highly used and expensive Cores is the Animal Resource Facility.

Nearly 50% of DFCI investigators use mice in models of disease or treatment. For example, genetically modified mice are essential for demonstrating that a gene or pathway discovered in cells in a laboratory are truly responsible for driving the development of cancer. Mice are also essential for testing whether a candidate drug or a change in the immune system can lead to shrinkage of cancer. For these reasons and many more the utilization of mice in cancer research continues to grow.

Mice are kept in a central vivarium in which they are housed and cared for. Humane treatment of mice requires an extensive infrastructure to assure that they are kept in germ-free conditions at the proper temperature and humidity.

The new vivarium to be constructed as part of the Project is expected to provide enhanced support of cancer research being performed throughout the Institute. For more information about the vivarium, see “THE PROJECT” herein.

Another important Core is the Cell Manipulation Lab. This facility has both clinical and research purposes.

Clinically, it manufactures all of the cellular material that the Institute’s affiliated hospitals use for bone marrow transplantation. On the research side, it manufactures cell-based materials that are used in a variety of cutting edge trials in cancer immunology and gene therapy. The relocation and expansion of the Cell Manipulation Lab as part of the Project is expected to provide the Institute with opportunities to co-localize research faculty who work in areas that the Cell Manipulation Lab materials will support.

NIH Funding

The Institute competes for NIH funding with cancer centers, research facilities, and hospitals across the county, and has ranked third or higher among independent cancer centers in NIH funding every year since 2000. The following

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information reflects NIH awards made in 2013 through 2015 to the top five independent cancer centers ranked in order of NIH funding for cancer research.

NIH Funding to Cancer Centers (in millions)

Institutions: 2013 2014 2015

Fred Hutchinson Cancer Research Center $199,132 $222,447 $232,617

Dana-Farber Cancer Institute 115,845 122,814 125,296

Univ. of Texas MD Anderson Cancer Center 130,803 120,877 119,591

Sloan-Kettering Institute for Cancer Research 111,289 113,568 117,253

St. Jude Children’s Research Hospital 64,635 62,482 66,612

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Source: NIH RePORTER data updated through April 2016.

Research Revenues

The following chart sets forth total research revenue from all sources for each of the three years from 2013 through 2015 and for the six months ended March 31, 2015 and March 31, 2016. The information reflects research revenues as opposed to awards, and also includes proceeds from gifts.

DFCI Research Revenues

Federal Grants $126,820 $113,898 $117,975 $55,108 $61,022

Federal Contracts 6,069 7,938 9,739 5,082 3,079

Clinical Trials 21,799 24,704 29,505 12,833 17,577

Non - Government Grants 31,208 32,635 36,232 18,740 16,826

Commercial Agreements 22,651 22,572 24,871 12,574 13,454

Billing Accounts (subcontracts) 39,827 39,398 37,435 18,497 19,770

Other 883 687 606 (643) 307

Direct and Indirect Grants & Contract

Revenues 249,257 241,832 256,363 122,191 132,035

Gift Statement of Operations (“SOP”)

Revenue¹ 65,957 68,269 91,815 39,269 42,828

Royalty SOP Revenue² 3,601 12,000 9,447 4,054 4,862

Research Revenue $318,815 $322,101 $357,625 $165,514 $179,725 __________________________________________

1 Gift SOP Revenue is comprised of Net Assets Released from Restrictions & Contribution Revenue

2 Royalty SOP Revenue is comprised of Net Assets Released from Agency Revenue