Annual Report 2012

MissionEvery day, we strive to eliminate the world’s most devastating infectious diseases.

VisionWe envision a world where people live free from the threat of infectious disease.

About Seattle BioMedSeattle BioMed is the largest, independent, non-profit research institute in the U.S. focused solely on the world’s most devastating infectious diseases. More than 330 strong, we are dedicated to reducing human suffering and saving lives by converting knowledge into solutions.

Our research is the foundation for new vaccines, drugs and diagnostics that will benefit those who need our help most: the 14 million who will otherwise die each year from infectious diseases.

Disease FocusEmerging & Neglected Diseases African sleeping sickness Amebiasis Chagas’ disease Leishmaniasis Toxoplasmosis

MalariaTuberculosisViral Diseases HIV/AIDS Influenza

Printed on recycled paper.

© 2013 Seattle Biomedical Research Institute.

307 Westlake Avenue North, Suite 500 – Seattle, Washington 98109-5219 USAPhone: 206.256.7200 – Fax: 206.256.7229 - seattlebiomed.org

2012Freedom from Infectious Disease

ANNUAL REPORT

Seattle Biomedical Research Institute is a 501(c)3 nonprofit organization. Federal tax ID #91-0961784.

Accelerating ProgressHelp us continue to accelerate.

Letter from our President

Growing up in apartheid South Africa, I was acutely aware of the burden of disease in poor communities. It fostered in me an intense desire to help end the scourge of infectious disease, a pursuit that ultimately brought me here, to Seattle BioMed. Every day, every one of our scientists focuses his or her passion and expertise on overcoming diseases that take a staggering toll on human life and national economies. We need vaccines, new drugs and diagnostics to end the threat of HIV/AIDS, tuberculosis (TB), malaria and other infectious diseases so prevalent in resource-poor countries.

As a strong believer in the power of technology to alleviate human suffering, I have devoted my career to advancing technologies that address major health problems of the developed world. Today, I am excited to be leveraging this experience in a new direction.

As Chair of the Board of Seattle BioMed since September 2012, I work with a passionate group of trustees who share the belief that technology applied to infectious disease can transform global health. We serve on the Board because we know that, in this institution, deadly diseases—including HIV, tuberculosis and malaria—have the full attention of some of the world’s top scientists.

Seattle BioMed’s integration of systems biology, immunology and infectious disease research is spurring insights and innovations that will accelerate the development of life-saving interventions not only by us, but also by research organizations around the world.

Our recently approved five-year strategic plan aims to further accelerate this progress by focusing on three broad areas where Seattle BioMed intends to bring value: influence by creating new scientific knowledge that can be built upon, invent by partnering to develop practical and effective interventions, and educate by training future generations of scientific leaders and innovators.

We know that the development of life-saving interventions relies upon insights into the nature of disease that only come through basic research. Such insights provide launching pads for invention as Seattle BioMed scientists test out the best ways to translate these research findings into strategies that can overcome barriers to disease prevention and treatment.

As an independent research institution, Seattle BioMed has the freedom to pursue the best opportunities to advance scientific knowledge and develop solutions to infectious diseases. This means we can take risks that academic institutions or commercial enterprises often forego, but risks that are still focused on tangible outcomes, such as vaccines for HIV, TB or malaria.

Our unique independent position means we also need independent support. Translational research that bridges the gap between bench and bedside—the invent focus of our new strategic plan—unfortunately receives limited support from traditional funding sources. This funding gap must be bridged if we are to truly accelerate progress.

Through Seattle BioMed, private individuals and organizations have the opportunity to expedite scientific discovery and to advance basic research past the milestones needed to deliver new life-saving products to the field in resource-poor countries. I invite you to join us in supporting these critical efforts.

In just the past year, insights from Seattle BioMed scientists have revealed new approaches to the development of vaccines and drugs for HIV, TB, malaria and other parasitic diseases. New computational analyses have helped define when someone infected with latent TB is at risk of developing active disease. A new TB gene interaction map is beginning to reveal signaling pathways that are involved with latent TB becoming active, which will lead lead to the identification of drug targets. In the HIV field, new insights are revealing why most HIV vaccines fail to elicit broadly neutralizing antibodies, and how different vaccine designs affect the response of the innate immune system, the body’s first line of defense against infection. In malaria, researchers have discovered how the parasite commandeers liver cells, an event that is critical for their initial growth in humans. Seattle BioMed researchers have also made strides in elucidating the structures of proteins from a variety of pathogens, providing a valuable resource for future development of drugs, vaccines and diagnostic tools.

The 2012 Annual Report brings you highlights of progress made in the past year, and outlines work ahead based on our recently completed five-year strategic plan that maps out the approaches that will guide both basic research and its translation into interventions that improve and save lives.

I thank you for your support of our science this past year and invite you to continue investing in the discoveries generated at Seattle BioMed. Together, we can accelerate progress in the fight against HIV/AIDS, TB, malaria, and other infectious diseases.

New tools and new thinking are needed, and Seattle BioMed generates both. I know of no better place to be, and no better time to be here. I am honored to be the new President of this institution and to lead from the strong foundation created by Dr. Ken Stuart as we apply cutting-edge tools to infectious disease research, and partner to translate those discoveries into interventions that can save lives. While Seattle is in our name, the focus of our work is global and so are our collaborations.

One of the tools we apply is systems biology. By embracing the complexity of biology, systems approaches enable the rational design of new vaccines and drugs. Seattle BioMed has become the world’s first research institute to undertake the full integration of systems biology, infectious disease research, and immunology under one roof. In doing so, we have thrown open the doors to accelerated progress.

Letter from our Board Chair

COMING TOGETHER TO ACCELERATE PROG RESS FOR GLOBAL HEALTH

21

Alan Aderem, Ph.D. President and Director

Trevor Moody Chair, Board of Trustees

three-dimensional structures of over 560 proteins from more than 40 bacterial, protozoan and viral pathogens—significantly surpassing their contract goals and providing a valuable resource for the development of drugs, vaccine and diagnostic tools. This fall, SSGCID’s contract with the National Institute of Allergy and Infectious Diseases was renewed for another five years, and SSGCID expects

to both determine the structures of another 400 proteins and to work with collaborators to understand their particular functions in causing disease.

Scientists at Seattle BioMed have broadened the understanding of how the body responds to TB by identifying how the bacterium activates cells that suppress the immune response necessary to fight off infection. An effective vaccine will not only need to stimulate a robust immune response, but also keep these suppressor cells in check.

Seattle BioMed scientists test the best ways to apply basic research findings and partner to develop them into practical strategies for disease prevention and treatment.

Seattle BioMed researchers recently discovered how a very small number of people are able to control their HIV infection and keep the virus in check. The key lies in the balance between two different types of T-cells. Scientists are now applying systems biology to understand the underlying mechanisms, which may reveal a new drug target for AIDS prevention.

Seattle BioMed has embarked on a major project to map how TB’s 200 “control genes” (transcription factors) determine the activity of its other 3,800 genes—including those that control the bacteria’s latent state. Simultaneously, researchers have identified a signaling pathway critical to the bacteria’s exit from latency and entry into active disease. Seattle BioMed has already begun collaborations to develop drug-like molecules that inhibit this system. A drug that prevents the transition from latent to active TB would represent a giant step forward in the control of this deadly scourge, given that one third of the world’s population is latently infected with TB.

Seattle BioMed scientists, in collaboration with scientific groups at the University of Copenhagen and the University of Edinburgh, discovered how malaria parasites are able to bind to brain blood vessels and cause cerebral malaria—the most lethal form of the disease. Identifying the molecules that allow malaria parasites to ‘stick’ to the brain will accelerate the development of treatments.

Seattle BioMed fosters a continuum of training and engages with students at all levels of learning, to inspire tomorrow’s biomedical pioneers and increase the capacity of our partners in resource-poor countries.

MOVING FASTER TO IMPACT GLOBAL HEALTH

Seattle BioMed is one of a handful of research organizations around the world that are pioneering the systems biology of infectious disease research. Every day, the scientists at Seattle BioMed strive to end the threat of infectious disease by influencing how we think about those diseases, inventing new solutions, and educating the next generation of scientists and our community.

Insights into the nature of infections and the body’s response to them are the source of every new intervention against devastating diseases. In ways large and small, research findings in 2012 from Seattle BioMed are changing how we think about infectious disease.

Malaria threatens over 40 percent of the global population, sickens hundreds of millions and kills hundreds of thousands of people a year, the majority of whom are children and pregnant women in Africa. Yet, no vaccine is available, and drug resistance is a growing problem. Seattle BioMed scientists have identified how malaria parasites manipulate liver cells, where they live during the early stages of infection, to ensure their growth and survival. Strikingly, the changes caused by parasitic infection are similar to the changes that occur when cells become cancerous. This suggests that some cancer drugs could be used to prevent malaria and minimize the development of drug-resistant parasites.

Over the last five and a half years, the Seattle Structural Genomics Center for Infectious Disease (SSGCID), a large-scale collaboration led by Seattle BioMed, has solved the

Seattle BioMed initiatives supported the scientific education of over 1,100 trainees, including visiting scientists, postdoctoral scientists, graduate students, undergraduate interns, work-study students, high school students, and teachers. Of these, more than 900 students were from Washington State high schools that engaged with the on-site BioQuest program. Thirty eight percent of BioQuest Academy students this past summer were from backgrounds underrepresented in the sciences.

The Seattle-India Joint Research Training Program on Global Infectious Diseases hosted a two and a half day workshop on tuberculosis in New Delhi with 24 trainees. Discussions and lectures covered a variety of topics including drug discovery, immunology, drug resistance, and research ethics. The program also hosted two young Indian TB scientists to train at Seattle BioMed. India is estimated to have over three million cases of tuberculosis with 320,000 deaths in 2011. More than 64,000 of those cases are estimated to have multiple drug resistance.

Opposite: More than 40% of the world’s population is at risk for contracting malaria, and children are at the highest risk. A child in Africa dies from malaria every 60 seconds.

Left: BioQuest Academy students spend two weeks during the summer immersed in a real lab setting. Seventy five percent of graduates go on to earn a degree in the sciences, and about 20% have come back to work at Seattle BioMed.

Alexis Kaushansky, Ph.D., Stefan Kappe, Ph.D., and Joe Smith, Ph.D., are just three of the malaria researchers at Seattle BioMed pioneering new ways to accelerate the development of drugs and vaccines.

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INFLUENCE, INVENT AND EDUCATE TO IMPROVE LIVES

for preventative treatment long before symptoms emerge. Furthermore, being able to identify which latently infected individuals are likely to develop disease allows them to be recruited for vaccine trials, which can greatly reduce the cost of clinical trials, allowing researchers to more effectively evaluate vaccine candidates.

In 2013, scientists will conduct additional studies on samples collected from throughout Africa to confirm these results. They will also use molecular genetics to examine the role of newly identified gene candidates in controlling TB infection.

Detecting new targets for a malaria vaccine The malaria vaccine candidate most advanced in testing, RTS,S, is built on a single parasite surface protein, and has an efficacy rate of roughly 30 percent. To improve on this, Seattle BioMed scientists collaborated with the Institute for Systems Biology to discover new antigens on the surface of the malaria parasite. These antigens

Biomedical researchers around the world have been working for decades to develop vaccines that can prevent HIV/AIDS, tuberculosis (TB), and malaria. But with no simple way of measuring in the blood whether a vaccine candidate is producing the desired immune response, the process of vaccine development is painfully slow, expensive, and riddled with obstacles.

At Seattle BioMed, the integration of infectious disease research, immunology and systems biology is illuminating the path. New tools and new approaches are accelerating vaccine development against all three diseases.

Systematically learning from TB’s tricks Globally, someone falls ill from TB every four seconds, and someone dies from TB every 20 seconds. Now, new research by Seattle BioMed scientists and colleagues in South Africa has identified early indicators of whether someone latently infected with the bacteria will become sick. The breakthrough came from a study that involved 6,000 adolescents in Cape Town, South Africa. The study begins to address a particularly challenging trait of TB: its ability to remain latent within the lungs of an infected person, emerging suddenly from this dormancy to cause the active and contagious form of the disease.

Did you know?South Africa is the epicenter of

the collision between HIV and TB,

representing one third of the world’s

cases of co-infection. As many as

70% of South Africa’s TB patients

are also HIV-positive. HIV lowers the

immune response needed to fight off

infections like TB, and the exceptionally

high rates of both HIV and latent TB

in South Africa create a perfect storm

for co-infection.

NEW TOOLS AND NEW THINKING

At the outset of the study, all of the young people recruited were latently infected with TB, but none had active disease. Knowing that some small percentage of the youth were likely to progress to active TB, the researchers collected blood samples every six months for two years. By the end of that time, 35 of the adolescents had progressed to active disease.

Using a systems approach, researchers then compared the blood samples of teens that did and did not develop active disease. Analyses revealed patterns of gene expression that appeared in people who progressed to disease up to 18 months before symptoms appeared. These biological markers should enable early detection of emerging disease in people with latent TB, allowing

Above: Seattle BioMed scientists used systems approaches to generate the first predicted genome-wide regulatory network for M. tuberculosis: a blueprint for the discovery of the most influential genes in the pathogen. The size and number of lines connecting the turquoise dots represent the influence of the control genes—critical information for drug discovery.

Opposite: Collaboration is a cornerstone of research at Seattle BioMed. Systems biologists and TB researchers like (left to right) Christoph Grundner, Ph.D., Lynn Amon, Ph.D., Smitha Shankar, M.S., Dan Zak, Ph.D., and David Sherman, Ph.D., are finding creative new ways to blend their expertise and develop new tools.

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(continued on p. 7)

COLLABORATORS

could serve as additional targets for a vaccine, boosting its ability to protect against disease. Scientists are also using computational analysis to learn more about how the immune system responds to malaria and to discover more potential vaccine targets. Together, these studies could identify new vaccine candidates to improve or possibly replace RTS,S.

Re-engineering vaccines In a five-year multi-institutional collaboration led by Seattle BioMed, immunologists, virologists, structural biologists and computational designers collectively examined why so many candidate HIV/AIDS vaccines have failed to elicit neutralizing antibodies against the virus. The team discovered that previously tested vaccines fail to activate the cells that produce such antibodies. Scientists at Seattle BioMed have now designed new vaccine candidates to specifically activate those cells. The vaccine has been successfully tested in the laboratory and is ready for testing in model systems.

Meanwhile, Seattle BioMed scientists, in collaboration with scientists at the National Institutes of Health, have discovered how adding different components to a vaccine can change the character of the innate immune response that vaccine produces. Since the innate immune system then orchestrates the adaptive immune response, these insights will enable more effective vaccine design.

Much of what we study at Seattle BioMed has implications for more than one disease. Seattle BioMed scientists are now applying new knowledge about better vaccine design to both HIV/AIDS and TB. Likewise, antibody work in HIV will be important for TB and malaria. As Seattle BioMed scientists work together more closely and bring the power of systems biology to bear, the pace of discovery will further accelerate.

ConclusionSeattle BioMed research is proving the power and potential of systems approaches. Today, Seattle BioMed is one of the few places in the world that are aggressively integrating systems biology and immunology into its infectious disease research. We could neither do this, nor produce the stream of results seen in past years, without the help of our supporters. We thank them and we invite you to join our cause.

Sustained support is needed to make the most of our scientists’ discoveries. Only then can we fully maximize the potential of systems approaches and rapidly accelerate the development of life-saving interventions. Together, we strive toward breakthroughs in the treatment and prevention of infectious disease.

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United StatesAntigen Discovery, Inc.AttoDx, Inc.Baylor Research InstituteBenaroya Research Institute at Virginia MasonBeth Israel Deaconess Medical CenterCarnegie InstitutionCenters for Disease Control & PreventionCincinnati Children’s Hospital Medical CenterClemson UniversityDana-Farber Cancer InstituteDuke UniversityEmerald BioStructures, Inc. Emory UniversityFox Chase Cancer CenterFred Hutchinson Cancer Research CenterHaborview Medical Center Harvard University Howard Hughes Medical InstituteIndiana UniversityInfectious Disease Research InstituteInstitute for Systems BiologyIntellectual VenturesJ. Craig Venter Institute Johns Hopkins University Los Alamos National Laboratory Mayo ClinicNational Institutes of HealthNaval Medical Research CenterNew York University Northern Illinois UniversityNorthwestern University Oregon Health and Sciences UniversityPacific BiosciencesPacific Northwest National LaboratoryPATH PolyclinicPrinceton UniversityPublic Health - Seattle & King County Ra Pharmaceuticals, Inc.Ragon InstituteRhode Island Hospital Rockefeller UniversitySage BionetworksSeattle Children’s HospitalSequella, Inc.St. Jude Children’s Research HospitalStanford UniversityStatistics Collaborative, Inc. Texas A & M UniversityThe Scripps Research InstituteTulane UniversityU.S. Environmental Protection Agency University of California, BerkeleyUniversity of California, IrvineUniversity of California, San DiegoUniversity of California, San FranciscoUniversity of Georgia University of Iowa University of MarylandUniversity of MichiganUniversity of Missouri-Kansas CityUniversity of North Carolina University of Pennsylvania University of RochesterUniversity of San Diego University of South Florida University of Texas Health Science Center at TylerUniversity of Texas Southwestern Medical Center at DallasUniversity of Virginia University of WashingtonVanderbilt University Walter Reed Army Institute of ResearchWalter Reed Army National Military Medical CenterWashington State University Washington University in St. LouisYale UniversityYecuris Corporation

InternationalAustralian National University, Australia

Barcelona Centre for International Health Research, SpainCentro de Investigaciones Biológicas, CSIC, Spain

Charité-Universitätsmedizin Berlin, GermanyChristian de Duve Institute of Cellular Pathology, Belgium

Egerton University, KenyaETH-Zurich (Swiss Federal Institute of Technology Zurich), Switzerland

Foundation for Innovative New Diagnostics, Switzerland Griffith University, Australia

The Hospital for Sick Children, CanadaImperial College London, UK

Institut de Recherches Cliniques de Montréal, CanadaInstitut Pasteur, France Institut Pasteur, Korea

Institute of Parasitology, ASCR, Czech Republic Instituto de Parasitología y Biomedicina “López - Neyra”, CSIC, Spain

International AIDS Vaccine InitiativeInternational Centre for Diarrhoeal Disease Research, Bangladesh

International Centre for Genetic Engineering and Biotechnology, IndiaInternational Centre for Genetic Engineering and Biotechnology, Italy

Jawaharlal Nehru University, India Kagawa University, Japan

K-RITH (KwaZulu-Natal Research Institute for Tuberculosis and HIV), South Africa

Mahidol University, ThailandMcGill University, Canada

Medical College, Kolkata, IndiaNanomics Biosystems Pty Ltd, Australia

National Center for Drug Screening, ChinaNational Cheng Kung University, Taiwan

The Netherlands Cancer Institute, The NetherlandsOxford University, UK

Shanghai Institute of Materia Medica, ChinaSoutheast University, China

Sun Yat-sen University, ChinaTDR/World Health Organization

Technion, IsraelThird Military Medical University, China

TriTryp Genome Consortium Universidad de Antioquia, Colombia

Universidad del Valle, ColombiaUniversidade Federal de São Paulo, Brazil

Universidade Federal de Viçosa, BrazilUniversidade Federal do Piauí, Brazil

Université Laval, CanadaUniversity of Alberta, Canada

University of British Columbia, Canada University of Cambridge, UK

University of Cape Town, South AfricaUniversity of Copenhagen and Rigshospitalet, Denmark

University of Dundee, UKUniversity of Edinburgh, UK

University of Erlangen-Nurnberg, GermanyUniversity of Glasgow, UK

University of Lisbon, PortugalUniversity of Nairobi, Kenya

University of Queensland, Australia University of the Witwatersrand, South Africa

University of Toronto, CanadaUniversity of Waikato, New Zealand

Vrije Universiteit, The NetherlandsWalter and Eliza Hall Institute of Medical Research, Australia

Wellcome Trust Sanger Institute, UK

Systems biologist John Aitchison, Ph.D. (center) and HIV researchers Leo Stamatatos, Ph.D. (left) and Don Sodora, Ph.D., are some of the researchers making strides towards a vaccine that activates the types of immune cells best equipped to fight off HIV.

Of the 1.8 million deaths from HIV/AIDS per year worldwide, 1.2 million are in Africa. Thirty four million people globally are living with HIV.

SEATTLE BIOMED LEADERS

This is a publication of Seattle BioMed’s Communications Department. Photo credits: Kyle Minch, p. 6, Alan Aderem, p. 6 sidebar.

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National Institute of Dental and Craniofacial Research

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of General Medical SciencesPATHPaul G. Allen Family Foundation

American Lung AssociationBill & Melinda Gates FoundationBurroughs Wellcome FundFoundation for the National Institutes of HealthImplicit Bioscience Ltd.Medicines for Malaria Venture

FacultyAlan Aderem, Ph.D.

President & Director

John Aitchison, Ph.D. Professor & Director of Integrative Biology

Nick Crispe, M.D., Ph.D. Professor

Malcolm Gardner, Ph.D. Professor

Christoph Grundner, Ph.D. Assistant Professor

Helen Horton, Ph.D. Associate Professor

Stefan Kappe, Ph.D. Professor & Program Director

Peter Myler, Ph.D. Professor

Marilyn Parsons, Ph.D. Professor, Program Director & Director of Professional Development

David Sherman, Ph.D. Professor & Program Director

Joseph Smith, Ph.D. Associate Professor

Donald Sodora, Ph.D. Associate Professor

Leo Stamatatos, Ph.D. Professor & Program Director

Ken Stuart, Ph.D. Professor, Founder & President Emeritus

Kevin Urdahl, M.D., Ph.D. Assistant Professor

Ruobing Wang, M.D., Ph.D. Associate Professor

Principal ScientistsAndrew Oleinikov, Ph.D.Noah Sather, Ph.D.Daniel Zak, Ph.D.

Senior ScientistsLynn Amon, Ph.D.Peter Askovich, M.D., Ph.D. Jason Carnes, Ph.D.Amy DeRocher, Ph.D.Alan Diercks, Ph.D.Mark Gilchrist, Ph.D.Elizabeth Gold, M.D.Ihn Kyung Jang, Ph.DHeather Jaspan, M.D., Ph.D.Bryan Jensen, Ph.D.Kathleen Kennedy, Ph.D. Vladimir Litvak, Ph.D.Sebastian Mikolajczak, Ph.D.Brian Oliver, Ph.D.Stephen Ramsey, Ph.D.Tige Rustad, Ph.D.Ramsey Saleem, Ph.D.Frank Schmitz, M.D., Ph.D.Shahin Shafiani, Ph.D.Ashley Vaughan, Ph.D.

Clinical Trials Jim Kublin, M.D., Ph.D.

Medical Director

Sara Healy, M.D. Clinical Trial Investigator

Angela Talley, M.D. Lead Trials Investigator

Affiliate FacultyJerry Cangelosi, Ph.D.

Professor University of Washington

Peter Doherty, MVSc, Ph.D. Nobel Laureate University of Melbourne

Rentala Madhubala, Ph.D. Director of Advanced Instrumentation Research Facility (AIRF) Jawaharlal Nehru University, New Delhi

Rob Moritz, Ph.D Director of Proteomics Facility & Associate Professor Institute for Systems Biology

Achim Schnaufer, Ph.D. Research Group Leader & Medical Research Council (MRC) Fellow University of Edinburgh, UK

ManagementAlan Aderem, Ph.D.

President & Director

Tom Blackwell Director, Information Technology

Karen Blöchlinger, J.D., Ph.D. General Counsel

Susan Brown Vice President, Institutional Advancement

Louie Coffman Senior Vice President, Strategy & Business Development

Randy Hassler Chief Operating Officer

Drew House Senior Director, Finance

Kent Irwin Director, Operations & Facilities

Eileen Murphy Director, Program Management

Jeanine Willis Director, Human Resources

BioQuest Theresa Britschgi

Director, BioQuest

Council of Scientific AdvisorsRafi Ahmed, Ph.D.

Director, Emory Vaccine Center

Clifton E. Barry, III, Ph.D. Senior Investigator, Chief, Tuberculosis Research Section, NIAID, NIH

Samuel I. Miller Ph.D., Professor of Medicine, Microbiology, Immunology and Genome Sciences, University of Washington.

Michel C. Nussenzweig, M.D., Ph.D. Sherman Fairchild Professor, The Rockefeller University Investigator, HHMI Laboratory of Molecular Immunology

Jeffrey V. Ravetch, M.D., Ph.D. Theresa and Eugene Lang Professor, The Rockefeller University; Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology

Bennett (Ben) M. Shapiro, M.D., Chair Director of Research, Retired, Merck Research Laboratories

John W. Shiver, Ph.D. Vice President, Worldwide Basic Research Franchise Head, Vaccines, Merck Research Laboratories

Mike Tyers, Ph.D. Professor, Institute for Research in Cancer and Immunology, University of Montreal Canada Research Chair in Systems and Synthetic Biology

Thomas E. Wellems, M.D., Ph.D., Chief, Laboratory of Malaria and Vector Research NIAID, NIH

National Institutes of Health:Eunice Kennedy Shriver National Institute of Child Health and Human Development

Fogarty International CenterNational Center for Research ResourcesNational Heart, Lung, and Blood InstituteNational Institute of Allergy and Infectious Diseases

Sclavo Vaccine Association Silver Family FoundationUnited States Department of Defense – Telemedicine

& Advanced Technology Research CenterUnited States-Israel Binational Science Foundation

Alan Alhadeff

Margaret Allen, M.D.

Ellsworth Alvord, Jr., M.D.

Mark Benjamin, Sc.D.

J. Paul Blake

Carol Bryan

Vince Bryan

Robert Bunting

Alice Burgess

John Creighton, Esq.

Andrew Dale

James Davie

Nancy Duncan

Bruce Easter

Janet Lane Eaton

Marlyn Friedlander

Steve Gillis, Ph.D.

Harris Hoffman

James A. Johnson

John King

Alvin Kwiram, Ph.D

Carol Lewis

Jilan Liu, M.D., M.H.A.

Katherine M. Lombardo

Emeritus Board

Gary McGlocklin

Peter Miller, J.D.

Susan Morgensztern

Peggy Morrow

Thomas O’Rourke

Judy Pigott

Gloria Pfeif

Erick Rabins

Thomas Ranken

Chuck Robertson

Gilbert Scherer

Michael D. Stull

Ezra Teshome

Usha Varanasi, Ph.D.

Tom Waldron

Rick Weller, M.D., D.T.M. & H.

Michelle A. Williams, Sc.D.

Mary Williamson

James Woods, Ph.D.

Jeffrey Wortley

Louis Yaseen

Updated 1/2013

FUNDERS

Fiscal year ending June 30, 2012SELECT F INANCIAL DATA

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BOARD OF TRUSTEES

Dean AllenChief Executive OfficerMcKinstry

Rosemary Barker AragonExecutive DirectorPacific Hospital Preservation & Development Authority

Mark Ashida*^Vice Chair, Business Development Committee ChairChief Executive OfficerSymform

Richard BearChief Financial OfficerCRH Medical Corporation

Jane A. Biddle, Ph.D.Technology Transfer Consultant

Gregg Blodgett*^Treasurer, Finance & Audit Committee ChairDirector, Chief Financial OfficerBooyami, Inc.

Maud Daudon*Board Operations & Governance Committee Co-ChairPresident & CEOSeattle Metropolitan Chamber of Commerce

Jane Hedreen*Advancement Committee Co-ChairOwnerFlora & Henri

Darryl Johnson*^SecretaryFormer US Ambassador to Thailand & Lithuania

Kevin F. Kelly, J.D.Business Consultant, Drug and Vaccine CollaborationsRetired Partner, Cooley LLP

Alan Levy, Ph.D.Venture Partner, Medical DevicesFrazier Healthcare Ventures

Neil McDonnell, PharmDSenior Vice PresidentCardiovascular & Metabolic Diseases Therapeutic AreaTakeda Pharmaceuticals

Terrence R. MeersmanVice President, ProgramsMargaret A. Cargill Foundation

Trevor Moody*^ChairPresidentTM Strategic Advisors LLC

Todd Patrick*Immediate Past ChairPresident & CEOC3-Jian, Inc.

Christopher H. Porter, Ph.D.PresidentMedical Genesis

Alexandre PortetDeputy Director, Strategy Planning & ManagementBill & Melinda Gates Foundation

Kris Richey Curtis*Advancement Committee Co-ChairVice PresidentKinzer Real Estate Services

David R. Stewart, J.D.Executive Vice President & General CounselVulcan, Inc.

Ken Stuart, Ph.D.President Emeritus & FounderSeattle BioMed

Moya Vazquez*Board Operations & Governance Committee Co-ChairCommunity Volunteer

Bryan WhiteManaging Director & Chief Investment OfficerBlackRock Alternative Advisors

Melissa YeagerChief Operating OfficerCardeas Pharma

^ Officer

* Member of Executive Board

Updated 1/2013

*Includes one-time contribution to support scientific expansion and leadership

Audited statements available upon request. Please e-mail [email protected].

Statements of financial position

2012 2011

Cash & investments $19,867,435 $21,203,046

Pledges receivable $263,797 $3,484,055

Other assets $7,719,694 $7,683,610

Property & equipment $9,488,075 $10,170,785

Total assets $37,339,001 $42,541,496

Accounts payable & accrued expenses $6,932,498 $4,704,532

Advances & deferred obligations $8,070,453 $10,335,651

Capital project debt $1,059,932 $2,608,351

Total liabilities $16,062,883 $17,648,534

Total net assets $21,276,118 $24,892,962

Statements of activities

2012 2011

Support & revenue

Government grants $31,430,061 $27,858,893

Private grants $11,606,758 $12,599,217

Contributions $558,259 $7,621,585*

Educational program $81,405 $99,442

Investment & other income $3,037,115 $3,394,990

Total support & revenue $46,713,598 $51,574,127

Expenses

Research program $42,778,277 $38,947,458

Educational program $594,243 $869,233

Management & administrative $6,549,447 $6,080,604

Fundraising $408,474 $729,667

Total expenses $50,330,441 $46,626,962

Increase (decrease) in net assets ($3,616,843) $4,947,165

Revenue & support

2012

Contributions 1%Other income 6%

Government Grants 69%

Private Grants 24%

Budget by program area

HIV/AIDS 33%

Emerging & Neglected

Diseases 29%

Malaria 32%

Tuberculosis 6%

2012

2012 HONOR ROLL

Thank you for your support.

The 2012 donor list includes new pledges, outright gifts of cash and stock, pledge payments, and in-kind donations received from July 1, 2011, through June 30, 2012. Donors of $1,000 and above are listed on the donor wall at Seattle BioMed.

Each of our donors is important to us. Please e-mail [email protected] with any omissions or errors.

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$1,000,000+Bill & Melinda Gates FoundationJames B. Pendleton Charitable Trust

$50,000+Dean & Vicki Allen/McKinstry Co.

Charitable FoundationWashington State Department of Agriculture

$25,000+Byron & Alice Lockwood FoundationGilbert Scherer & Marlyn Friedlander

$10,000+Drs. Alan Aderem & Kathy BarkerAnonymous (2)Charles Spear Charitable TrustThe Crystal Family FoundationJames & Sarah DavieRichard & Elizabeth HedreenKeyBank FoundationTodd & Julie PatrickGloria PfeifJudy PigottBecky RobertsThe Team Trio Fund In Honor & Remembrance

of Dr. David Clemetson

$5,000+Perry, Christine, & Cooper AtkinsGregg & Jane BlodgettMaud & Marc DaudonDavid & Amy FultonGilead Sciences, Inc.Racha & Wassef HarounJane Hedreen & David ThyerMike & Liz HiltonKeyBank National AssociationKinzer Real Estate ServicesLease Crutcher Lewis

Petrizzo Bond, Inc.Gordon & Gretchen RaineLucie Robitaille & Antoine LeblondRonald & Sara SeubertDrs. Ken Stuart & Julie McElrathMike & Sandra StullVulcan Inc.Wells Fargo Insurance ServicesMelissa Yeager & Cory Van Arsdale

$2,500+Dr. John & Leslie AitchisonAlexandria Real Estate Equities Inc.Mark Ashida & Lisbet NilsonATS AutomationThe Baden FamilyDrs. Jane A. Biddle & Kenneth B. SeamonBioMed Realty Trust, Inc.Betty BottlerBristol-Myers Squibb Co.Susan P. BrownBullitt FoundationConcur Technologies, Inc.Firland FoundationGLY ConstructionGroup Health CooperativeBetsy & Eric HentzJones Lang LaSalleLeroy HoodMark Malamud & Susan HautalaTrevor J. Moody & Laura HernonMoss Adams LLPNBBJChristopher & Kathryn PorterKris Richey CurtisSabey CorporationSalal Credit UnionDaniel D. SyrdalKristin Tolle, Ph.D.Moya VazquezVLST CorporationJeanine Willis & Eric FreybergDebra Wilson

$1,000+Anonymous (4)Kevin & Patrice AuldRichard BearBonnie BerkSteve & Marijo BrantnerDavid BrennerClark Nuber P.S.Paul & Debbie CressmanEarl & Anita DaviePatrick DuffyRenee DuprelCarolynn & Hal FerrisJoAnn & Barry FormanGreg FosterM. Elizabeth HalloranRandy & Melanie HasslerLee & Ginnie HuntsmanDarryl & Kathleen JohnsonPam & Kim KaiserMargot Kenly & Bill CummingJim LaddMaureen Lee & Mark BustoLife TechnologiesDori McLennanPeter Miller & Jean JohnsonMorningside FoundationShirley Naganawa & Gary KawasakiCharles & Eleanor NolanPATHPerkins CoieAnne PfeifJudith PierceWilliam & Jennifer PollardChris & Julie PrenticeWendy & Bill RabelRegina Rabinovich & Franco PiazzaRedman Family FoundationThe Reuben B. Robertson FoundationJames & Joy RoushChristine SimonChris & Aniko Somogyi

Leo Stamatatos & Tina de JongMargaret & Hunt StockwellBob & Katie StrongSteven & Karen Van TilDoug & Stacey WaddellWaldronMariann & Kirk Zylstra

$500+The Aitchison LabAnonymous (3)Rosemary Barker Aragon & Luis AragonNitin Baliga, Ph.D. & Janet CebbalosJohn & Tricia BencichKaren BlöchlingerSissy Bouchard, Ed.D. & Tom Bouchard, Ph.D.Hal BreierRobert & Theresa BritschgiTom & Claudia CampanileJohn W. Creighton IIIDr. and Mr. DiracJennifer DodsonBeth & Marc DroppertRobert & Deborah FlemingKerry Fowler & Jan GrayRachel & Paul FreedMalcolm J. Gardner & Ruobing WangTed and Barbara GauldRobyn & Philip GradHamilton Hazlehurst & Pam BekinsHelen Horton & Donald CarterDrew & Alison HouseKent & Louise IrwinJ & C Voyageurs Ltd.Allegra JohnsonR. Hans & Kelly KempMaryann Jordan & Joe McDonnellChristopher KarpChiEun KimMichael Kreis & Cathryn VandenbrinkLaird Norton Company LLCPeter & Melba LancasterDon & Carla LewisTerry Meersman & Carmen de la HozMichael & Julie MetzgerSusan & Isaac MorgenszternPeter Myler & Alexa AllenRobert & Carol OdemGeoff & Kathy OslerMarilyn ParsonsLindsey & Justin PatrickPatricia PfeifPrairie FoundationAudi Purnaveja

Erick & Marta Rabins & FamilyRobert L. & Virginia R. RauschChris RiveraScott & Kerry RosenkranzSABArchitects, Inc.Will & Lee SchoentrupSellen ConstructionDrs. David Sherman & Jeanette FarrellHaeryung Shin & Andrew von NordenflychtKristin Stred & Terry PretherSandhya Subramanian, Steve SeitzKate TuneTad WhitesideAnn P. WyckoffJane Zalutsky & Mark Kantor

$250+Lynn Amon and Ed KromerAnonymousMatt ArentzCameron BaysKristin & Steven BeaulieuJeanne BrovoldLarry T. & Maggie S. BurkeClete & Bronwen CasperBetty ChandlerNick Crispe, Ph.D.Joshua CurtisMark & Deb DavisBarclay DeanKen DuncanBarbara FieldenChristoph GrundnerSierra Hansen & Barbara WilsonKitty HarmonJoe & Denise HarrisRichard HarrisHerd Freed HartzToni HatzakisLeslie Helm & Marie AnchordoguyRafael HernandezGordon HofmanArthur E. HoltzKaty Horan & Dan Filonowich in honor

of Heath Fox & Julie RichmanDavid C. HowlandElizabeth JamesGail JamesIrene & Timothy KilgallonJoseph King & Whitney McClearyAlvin & Verla Kwiram

Alan & Sharon LevyKim Loveall PriceLoveall Price & Associates LLCThe Madden FamilyGeorge & Beverly MartinMcGraw-HillTracy MitchellBob & Nicole MooneyJoanne & Bruce Montgomery, M.D.Peggy MorrowEileen & Barry MurphyAlex NachmanDavid & Julie ParkDavid PostonSally QuyMaria K. ReyesDr. Mack & Susan RicheySteve & Charlotte RobertsMike RuhlRussell Investments Matching Gifts ProgramPaul & Robin SchachterSidiya SchoppertGenie ShethBarbara A. ShickichJeff Shober & Deb Nalty, M.D.Joseph & Leia SmithDon SodoraJay SorensenDavid & Lucinda StewartErik StromMichael SwiftJasna H. TrnkaJames TuckerDavid TuttDr. Maria VasilakisWashington Biotechnology &

Biomedical AssociationPeter I. WayBrandon WeberKatherine WeybrightRon Wilkowski & Kyla Fairchild

You hold the key to our acceleration.The people with the most influence on global health are people like you. You have invested your time and money, and you have joined us on our journey to end the threat of infectious disease. Individuals, foundations and corporations that imagine a world free from this burden play a significant role in enabling Seattle BioMed to expand research programs, recruit innovative scientists and form powerful collaborations that will ultimately lead to a healthier world.

MissionEvery day, we strive to eliminate the world’s most devastating infectious diseases.

VisionWe envision a world where people live free from the threat of infectious disease.

About Seattle BioMedSeattle BioMed is the largest, independent, non-profit research institute in the U.S. focused solely on the world’s most devastating infectious diseases. More than 330 strong, we are dedicated to reducing human suffering and saving lives by converting knowledge into solutions.

Our research is the foundation for new vaccines, drugs and diagnostics that will benefit those who need our help most: the 14 million who will otherwise die each year from infectious diseases.

Disease FocusEmerging & Neglected Diseases African sleeping sickness Amebiasis Chagas’ disease Leishmaniasis Toxoplasmosis

MalariaTuberculosisViral Diseases HIV/AIDS Influenza

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© 2013 Seattle Biomedical Research Institute.

307 Westlake Avenue North, Suite 500 – Seattle, Washington 98109-5219 USAPhone: 206.256.7200 – Fax: 206.256.7229 - seattlebiomed.org

2012Freedom from Infectious Disease

ANNUAL REPORT

Seattle Biomedical Research Institute is a 501(c)3 nonprofit organization. Federal tax ID #91-0961784.

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