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        <Explanation>Form 990 Part III Line 4a One of the unique qualities of BRI is the close integration of three types of medical research - laboratory research, translational research and clinical research - to improve peoples lives. Our scientists can address both the basic science issues and clinical applications, which is the best way to design studies with the highest potential for success. For BRI, discovery starts in the laboratory. A Laboratory advances in 2012 include 1 A breakthrough discovery of how allergy shots steer the immune response to prevent allergies. These findings open new horizons for understanding allergic disease and improving safety and efficacy of current allergy shots. 2 Decoding how a common change in a gene called PTPN22 may predispose children and adults to develop autoimmune diseases including Type 1 diabetes, rheumatoid arthritis and lupus. A team of researchers from BRI and Seattle Childrens are now testing how this gene may help predict the people who are at risk for autoimmune conditions and whether a therapy can be developed to compensate for this genetic change. 3 Finding a new complexity in the immune system - a mirror regulatory cell for each kind of helper T cell to tell it how to respond. 4 Discovery of a molecular pathway to regulate macrophages - cells in the immune system that are some of the first responders at sites of injury, infection and inflammation. B Translational research is the link between laboratory research and clinical research, built upon an exchange of materials and information between these two disciplines. BRI scientists and collaborators work together to study blood and serum samples along with medical and demographic data collected from people with autoimmune and immune-mediated diseases. These include multiple sclerosis, type 1 diabetes, lupus, rheumatoid arthritis, inflammatory bowel disease, allergy and asthma. BRI maintains an extensive biorepository with samples dating back to 2000, including 11 disease categories and a biorepository of healthy people for comparison purposes. Advancements in 2012 include the following 1 BRI established a new translational research core laboratory called the Human Immunophenotyping Core. Scientists use this core to identify the underlying mechanisms of disease and develop biomarkers of disease. The core is also a designated laboratory for the Immune Tolerance Network ITN. BRI Director Gerald T. Nepom, MD, PhD, serves as the director of the ITN, one of the largest government-funded clinical research networks in the nation working to accelerate new treatments for diseases of the immune system. 2 The BRI Diabetes Research Program received a 4.4 million grant from the Leona M. and Harry B. Helmsley Charitable Trust to establish the T1D Exchange Biobank Operations Center. 3 BRI scientists began new partnerships with several biopharmaceutical companies to potentially speed up translational research of diagnosis and treatment of autoimmune and immune-mediated diseases. C Clinical research studies are conducted with volunteers who participate in experimental medical approaches not available outside the clinical trial setting, and play a major role in pushing the boundaries of knowledge about their disease and new therapies. BRI conducts nearly 100 trials each year in many different diseases through a Diabetes Research Program partnership with Seattle Childrens , TrialNet and the National Institutes of Health trials with the Immune Tolerance Network and the BRI Clinical Research Program with physicians at Virginia Mason. Advancements in 2012 include 1 Multiple sclerosis research. Participation in clinical trials led to the FDA approval of a second oral agent teriflunomide for multiple sclerosis and a third anticpated in 2013. Studies in 2013 will focus on the possibility of remyelination as well as impact of treatment on brain volume measurements. Translational work also remains active with exploration of biomarkers to guide treatment decisions. 2 Rheumatology research. BRI was part of the pivotal trials for the first drug in a new class of immunotherapies called JAK inhibitors. This is the first oral medication to be approved in a number of years and the only major drug approved for rheumatoid arthritis in 2012. 3 Type 1 diabetes research. Clinical trials included the study of an artifical pancreas, new experimental drugs to modify the immune response, whether vitamin D can change how immune cells function, better ways to measure insulin secretion and how best to monitor patients at risk of developing type 1 diabetes. D Prevention is the ultimate goal of early diagnosis, before autoimmune diseases become a clinical problem. One of the important lessons learned in BRIs quest to diagnose, better treat and cure autoimmune diseases is that the earlier intervention, the better. Several pioneering advancements at BRI in 2012 focused on prevention 1 Calculating an individualss risk for the development of type 1 diabetes through the publication of a practical algorithm by BRI and collaborators at TrialNet. With this discovery, at-risk people can be closely monitoried and have opportunities to enter a prevention trial. 2 Exploring how to interrupt the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the pre-diabetic state and thereby prevent or delay the onset of type 1 diabetes. BRI is participating in an experimental drug therapy prevention trial sponsored by TrialNet offered to relatives of people with diabetes who are themselves at very high risk for developing the disease. 3 Researching how to restore balance between good and harmful cells involved in initiating disease, by regulating the immune response. BRI will lead a 2.6 million study to understand how the immune system becomes unbalanced and how it might be manipulated in people with autoimmune diseases. 4 Looking for the genetic roots of type 1 diabetes. three different research strategies are being used together to follow the precise molecular steps that are caused by susceptibility genes associated with type 1 diabetes, in a new 4.3 million grant to BRI investigators. 5 Identifying key infectious triggers and regulators of a molecule called TSLP, a key component of the early immune response in the lung airways leading to asthma and allergies. E Immunology research is driving toward individualized treatment for each person with autoimmune and immune-mediated diseases. Each persons genetics, environment and immune system mechanisms are unique, and people react to therapies differently and their responses may change over time. The optimal approach will be to individualize health care for each person and offer the right treatment at the right time. BRI is leading several worldwide efforts to personalize medicine 1 Developing a way to provide an immune system profile for individual patients. The profile will detail the expression of thousands of genes over a persons lifetime. The goal is to provide an early warning of things to come and an indication of what treatments might be needed. In 2012, the development of a low-cost genomic fingerprinting assay enabled BRI researchers to generate immune signatures of hundreds of patients with infectious and autoimmune diseases. Such an assay may on day make its way to the clinic where tools for evaluating immune health are critically needed. 2 Development of new biomarkers to allow individualized studies of responses to vaccines and food allergies.k Biomarkers were also developed to study individuals with the highest level of risk for developing type 1 diabetes. BRI serves as the inventor and international leader for the production and application of biomarkers that have contributed to a broad array of scientific advances, including the study of individual immune responses to better understand disease and how to personlize treatment.</Explanation>
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      <GeneralExplanation>
        <Explanation>Form 990 Part VI Section A Line 1a The governing body delegates to an Executive Committee comprised of four officers of the Board and the Chairs of each standing Board Committee, the authority of the Board of Directors in the management of the corporation as may be deemed by the Executive Committee to be appropriate, to be exercised in time periods between regularly scheduled meetings of the Board of Directors. The Director and the Executive Director of the corporation serve as ex officio members of the Executive Committee, without voting rights. The Executive Committee does not have the authority to amend, alter or repeal the bylaws elect, appoint or removed any member of such Executive Committee or any director or officer of the corporation amend the articles of incorporation adopt a plan of merger or adopt a plan of consolidation with another corporation authorize the sale, lease or exchange of all or substantially all the property and assets of the corporation not in the ordinary course of business authorize the voluntary dissolution of the corporation or revoke proceedings therefore adopt a plan for the distribution of the assets of the corporation or amend, alter or repeal any resolution of the Board which by its terms provides that it shall not be amended, altered or repealed by such Executive Committee. The Executive Committee also serves as the planning committee for the Board of Directors and oversees any compliance issues raised by the Board of Directors.</Explanation>
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      <GeneralExplanation>
        <Explanation>Form 990 Part VI Section A Line 6, 7 Virginia Mason Health System VMHS is the sole corporate member of Benaroya Research Institute at Virginia Mason BRI. VMHS as the sole voting member has the following approval rights 1 Election or appointment of Directors and Officers of the Board of Directors 2 Removal of Directors and Officers of the Board of Directors including any executive officer of the corporation 3 Approval of all long-range and short-range plans proposed by the Board of Directors 4 Approval of the annual capital and operating budgets proposed by the Board of Directors 5 Approval of the borrowing of funds where the amount borrowed is in excess of Five Hundred Thousand Dollars 500,000 6 Approval of the salel, lease, exchange, mortgage, pledge or disposal of all or substantially all of the property and assets 7 Approval of all amendments to or repeal of the Agreement Association or the Bylaws of the corporation 8 All other rights and powers as specified in the Washington Nonprofit Corporation Act.</Explanation>
      </GeneralExplanation>
      <GeneralExplanation>
        <Explanation>Form 990 Part VI Section B Line 11B Review of the Form 990 Process. The Virginia Mason Health System Audit and Compliance Committee ACC, a committee composed of independent community members has been delegated responsibility for oversight of the annual Form 990 preparation process including 1 selection, engagement, and review of the performance of the independent tax preparer, 2 review of the annual draft Form 990 tax return, and 3 recommendation of the final Form 990 tax return for review to the BRI Board of Directors. Annually, at the September meeting, management and the tax preparer provides the ACC with an initial draft of the Form 990 and present an overview of the Form 990 preparation process. The final draft Form 990 is reviewed and approved by the ACC in November followed by a Board review of the final Form 990 prior to filing. The final Form 990 tax return is provided to each member of the Board of Directors via electronic delivery.</Explanation>
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        <Explanation>Form 990 Part VI Section B Line 12C The Virginia Mason Health System Governance Committee has been delegated accountability for oversight of the process for disclosure, evaluation and management of conflict of interest involving any member of the Benaroya Research Institute at Virginia Mason Board of Directors, executive leadership or key employees Covered Person. Pursuant to the Conflict of Interest Policy, an annual conflict of interest questionnaire is distributed to all Covered Persons. In addition, a Covered Person has an on-going duty to disclose the existence of a conflict of interest at any time an actual or potential conflict arises. Each Covered Person is required upon appointment and annually thereafter to attest to a statement that affirms that such person has 1 received a copy of the Conflict of Interest Policy 2 has read and understands the Policy 3 has agreed to comply with the Policy and 4 understands that BRI is a charitable organization and that in order to maintain its federal tax exemption must engage in activities that accomplish its tax-exempt purposes. Written disclosures are reviewed by the Governance Committee to determine if an actual or potential conflict of interest exists and if so, how it should be managed. The Covered Person is informed in writing regarding the determination the Conflict of Interest Management Plan. No Covered Person with an actual or potential conflict of interest shall engage in an activity on BRIs behalf related to the disclosed actual or potential Conflict of Interest unless such activity is permitted by the Conflict of Interest Management Plan or until the Covered Person has undertaken all steps set forth in the Management Plan to manage, reduce or eliminate the conflict. All Covered Persons have a duty to disclose the existence of any actual or potential conflict of interest with respect to meeting agenda items. The Conflict of Interest Policy requires that copies of the Conflict of Interest Questionnaires be completed annually by each Covered Person and any Conflict of Interest Management Plan be maintained.</Explanation>
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      <GeneralExplanation>
        <Explanation>Form 990 Part VI Section B Line 15 The VMHS Compensation and Benefits Board Committee, a committee composed solely of independent directors none of whom have a conflict of interest, is accountable for setting reasonable total compensation packages for each executive, officer and key employee Executive consistent with VMHS/BRIs philosophy and principles. The Committee approves annual goals and performance criteria which are used in determining merit increases and variable compensation opportunities. The Committees assesses performance against these goals. The Committee selects and engages a qualified independent compensation consultant to review and analyze the total compensation and benefits packages of the Executives. The Committee as part of its analysis obtains from the compensation consultant appropriate comparability data including total compensation paid by similarly situated organizations for positions that are functionally comparable to each of the Executives. The Committee will consider the significant terms of the agreement with each Executive including the total compensation to be paid and the employees duties and responsibilities. Consistent with VMHS/BRIs compensation philosophy and principles, the Committee approves total compensation packages for each of the Executives based on information presented to the Committee, reasonableness and the best interest of BRI. The Committees decisions regarding compensation for each Executive are documented in written resolutions and minutes of the Committee. The Committee promptly reports its actions to the VMHS board which reports are reflected in the Boards minutes. The individuals who were reviewed in 2012 were the Board Director, Carla Greenbaum, the Executive Director and Chief Financial Officer, and Vice President and Research Executive Director.</Explanation>
      </GeneralExplanation>
      <GeneralExplanation>
        <Explanation>Form 990 Part VI Section C Line 19 The organizations Articles, Bylaws, Conflicts of Interest Policy and financial statements are made available upon request.</Explanation>
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