DRAFT – PRE-DECISIONAL & DELIBERATIVE nAb scientific summit: Thursday, August 20, 2020

12:30 Introductions and learnings from plasma by Dr. Collins and Dr. Woodcock 1:00 Topic presentation and discussion: Safety - Antibody-dependent enhancement • Discuss lessons learned on ADE based enhanced respiratory disease from previous therapeutics • Review potential implications for COVID-19 nAbs • Review ADE screening and monitoring process for COVID-19 nAb development (for neutralizing and non-neutralizing antibodies that might contribute to ADE)

1:35 Coffee break 1:45 Topic presentation and discussion: Safety – Epitope binding and viral resistance • Discuss whether epitope binding sites or combinations of site predict therapeutic efficacy • Discuss range of epitopes being targeted by nAbs and likelihood of viral resistance based on epitope conservation and use of cocktail vs. single nAb

2:20 Topic presentation and discussion: Efficacy – Effector function & antibody optimization • Review mutations being explored to increase half-life or effector function (e.g. YTE, LS) and any initial efficacy/safety data from animal studies • Discuss potential impact of mutations on Fc-mediated antibody effector functions and use of Fc region to specify and optimize immune response • Discuss optimization of antibodies to support manufacturability

2:55 Topic presentation and discussion: Efficacy – Learnings form other fields • Discuss lessons learned from nAb development and efficacy results from flu, Ebola and HIV • Discuss lessons learned and implications for prevention and vaccine development

3:20 Coffee break 3:30 Topic presentation and discussion: Assay development – assay standardization • Discuss in vitro and in vivo screening characteristics that predict efficacy and safety • Discuss process for screening for combinatorial nAb candidates and indicators of optimal nAb combinations

4:05 Closing remarks 1 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE DRAFT – PRE-DECISIONAL & DELIBERATIVE TOPIC Antibody-dependent enhancement

WHITE PAPER AUTHOR M O D E R AT O R

Barney Graham Ann M. Arvin M.D., Ph.D., Deputy Director of the Vaccine Research Center and the Chief of the M.D., Professor of Pediatrics and Microbiology & Immunology, Stanford Viral Pathogenesis Laboratory (NIAID/VRC) University and Chief of Infectious Diseases at the Packard Children's Hospital

• Dr. Graham's primary interests are vaccine development for viral diseases, viral • Research focuses on the molecular virology of varicella-zoster virus, immune responses pathogenesis, mechanisms of immunity and pandemic preparedness of children to viral infections and vaccines and herpes viruses in pregnancy • His laboratory has developed novel vaccines for RSV, influenza, Zika, and • Committee service includes National Vaccine Advisory Committee; chair, WHO coronaviruses including the first Covid-19 vaccine and monoclonal antibody products Committee on Measles Vaccine Research; NIAID and PCAST Influenza Working Groups; to enter clinical testing member, National Academy of Medicine; American Academy of Arts & Sciences

PANELISTS

Mark Esser Amanda Peppercorn Jeffrey Ravetch Takashi Komatsu Ph.D, Vice President of M.D., Medicine M.D., Ph.D., Professor at Ph.D, Senior Clinical Microbial Sciences at Development Leader, R&D Rockefeller University Virology Reviewer at FDA AstraZeneca at GlaxoSmithKline CDER

• Leads drug discovery, translational • Dr. Peppercorn has worked in all phases • Head of Leonard Wagner Lab of • Reviews nonclinical and clinical research and clinical dev't of innovative of development and infectious diseases Molecular Genetics and Immunology virology data and clinical trial medicines targeting microbiome and in strategy at GSK • Acting as scientific advisor to Vir protocols for antiviral drugs vivo expressed biologics • Leader in development of biomedical • Studies at his lab, The Ravetch Lab, • Actively involved in the • Immunologist with experience in countermeasures following dev't of IV focus on the interactions between establishment of FDA policies and clinical development for Vx, T cell zanamivir for pandemic/severe flu, antibodies and immune cells' Fc guidance on antiviral drug therapy, biomarkers and diagnostics raxibacumab for anthrax, & antibiotics receptors to better understand and development for multi-drug resistant bacteria treat disease • Significant experience in development and execution of Phase 2/3 trials 2 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE DRAFT – PRE-DECISIONAL & DELIBERATIVE TOPIC Epitope binding and viral resistance

WHITE PAPER AUTHOR M O D E R AT O R

Paul Bieniasz David Ho Ph.D., Professor and Head of the Laboratory of Retrovirology at Rockefeller M.D., Director of Aaron Diamond AIDS Research Center and Clyde and Helen University and Howard Hughes Medical Institute Investigator Wu Professor of Medicine at Columbia University

• His research explores virus-host interactions in a variety of viral systems, but with a • HIV/AIDS researcher who has made many scientific contributions to the understanding major focus on HIV-1 replication in individual cells and animal models and treatment of HIV infection • His lab works on both innate and adaptive antiviral immunity and has discovered a • Dr. Ho's group has engineered potent antibodies that neutralize divergent strains of number of novel mechanisms by which hosts defend themselves against viruses HIV. The most promising neutralizing agent is a bispecific monoclonal antibody that • Acted as Chair of the NIH AIDS Molecular and Cellular Biology study section from 2004 entered a first-in-human clinical trial in 2019 to 2009 and served on the NCI Board of Scientific Counselors from 2010 to 2014, • Isolated and characterized a large panel of potent and diverse monoclonal antibodies Currently serves on the NIAID AIDS Research Advisory Committee that neutralize SARS-CoV-2 PANELISTS

Alina Baum Katharine J. Bar Ed Scolnick MAJ Jeff Kugelman Ph.D., Senior Staff Scientist at M.D., Assistant Professor of M.D., Core Member of Broad Ph.D, Head of the Center for Regeneron Medicine and Director of the Institute, Chief Scientist Genome Sciences at the U.S. CFAR Virus and Reservoirs Core Emeritus at Stanley Center and Army Medical Research at UPenn Professor of Biology at MIT Institute of Infectious Diseases • Leads the COVID-19 spike antibody • Research focuses on studying the • Previously served as President of • Biodefense viral geneticist and program currently in clinical trials. basic mechanisms of transmission, Merck Research Laboratories, where computational biologist • Leads a virology research group pathogenesis and persistence in HIV he helped develop 28 drugs and Vx, • Interests include outbreak response, viral developing novel Tx for viral and other chronic viral infections with 7 safe and effective Vx approved population genetics, and epitope infections including influenza and • Serves as PI, co-PI or Investigator on • Current research focus is on mental mapping hepatitis B, emerging pathogens such HIV broadly nAb clinical trials for HIV illness, e.g., bipolar disorder • Set up genomics lab at Liberian Institute as Ebola and SARS-CoV-2, as well as therapy, cure and prevention • Also holds an academic appointment for Biomedical Research to characterize the development of oncolytic viruses • Serves as co at MIT as a Professor in the Ebola viral genomes, assess for and Vx for cancer immunotherapy Department of Biology diagnostic and Tx targets and characterize sexual transmission of Ebola3 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE DRAFT – PRE-DECISIONAL & DELIBERATIVE TOPIC Antibody optimization and effector function

WHITE PAPER AUTHOR M O D E R AT O R

Galit Alter Michel Nussenzweig Ph.D., Professor of Medicine at Harvard Medical School, Group Leader at the M.D., Ph.D., Zanvil A. Cohn and Ralph M. Steinman Professor and a senior Ragon Institute of MGH, MIT and Harvard and Co-Director of the Harvard physician at the Rockefeller University. University Center for AIDS Research (CFAR)

• Dr. Alter's work focuses on the development of systems biology tools to define the • Studies molecular aspects of the immune system’s adaptive and innate responses, correlates of immunity against infectious diseases. She seeks to define the role of using a combination of biochemistry, molecular biology, and genetics innate immune recruiting antibodies in providing specificity to the innate immune • Focus of the Nussenzweig laboratory is to understand the development of effective system to kill virally infected cells antibody responses with the ultimate goal of learning how to elicit vaccine responses • Has developed a suite of antibody profiling assays, deemed Systems Serology, that against complex pathogens such as HIV-1 aims at gaining a deeper appreciation of the correlates of humoral immune activity • Member of US National Academy of Medicine and US National Academy of Sciences against HIV, tuberculosis, malaria and beyond PANELISTS

Dan Barouch Christos Kyratsous Randal Ketchem Danilo Casimiro M.D., Ph.D., Professor of Ph.D., VP of Research - Ph.D., Vice President of Ph.D., Vice President & Head Medicine and Immunology at Infectious Diseases and Viral Molecular Design at Just of Global Research and Harvard Vector Technologies at Biotherapeutics External Innovation at Sanofi Regeneron Pasteur • Also Director of the Center for • Oversees preclinical research into a • Extensive experience in Tx design with • Responsible for vaccine research and Virology and Vaccine Research at diverse portfolio of anti-pathogen particular experience in antibody search-and-evaluation function for Vx Beth Israel Deaconess Medical Center fully-human monoclonal antibodies design, analysis, and optimization for opportunities, with 20+ years of and member of the Ragon Institute and novel gene and cell therapies efficacy, half life and developability experience in R&D of Vx and biologics • Lab focuses on studying immunology • Focuses on designing drugs for viral • Has directed and completed projects in • Contributed to development and and virology of HIV-1 infection and pathogens, used to develop REGN-EB3 Tx development pipelines at Immunex, licensure of Merck’s HPV vaccine, and developing novel vaccine strategies for Ebola, and now has informed Amgen, and Just Biotherapeutics and selection of numerous Vx candidates • Group has also applied their Vx Regeneron’s efforts to develop novel Just - Evotec Biologics and monoclonal antibodies for expertise to preclinical and clinical antibodies against Covid-19 clinical development studies of other infectious diseases 4 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE DRAFT – PRE-DECISIONAL & DELIBERATIVE TOPIC Lessons from other fields

WHITE PAPER AUTHOR M O D E R AT O R

Dennis Burton Jorge Tavel Chair of the Department of Immunology and Microbiology at Scripps Research M.D., Senior Group Medical Director in Early Clinical Development at and Steering Committee Member of the Ragon Institute Genentech

• Also acts as Director of the NIH Consortium for HIV Vaccine Development (CHAVD) and • Has led the development and execution of first in human and proof of concept clinical Scientific Director of the IAVI Neutralizing Antibody Center (NAZ) trials for multiple antimicrobial programs • Pioneered the discovery and characterization of human neutralizing antibodies to • Prior to joining Genentech, served as Deputy Director, Division of Clinical Research at the viruses, particularly broadly neutralizing antibodies to HIV and HCV, but also to RSV National Institutes of Health and Ebola virus, and the use of such antibodies to facilitate rational HIV vaccine • Previously responsible for strategy and protocol designs for studies in patient populations design who failed standard-of-care HCV therapy and for HIV/HCV co-infected patient

PANELISTS

Shelly Krebs James Crowe Jonathan Abraham Yunda Huang Chief of B cell Biology, Military Director of Vanderbilt Vaccine M.D., Ph.D., Assistant Ph.D., Principal Staff Scientist HIV Research Program, WRAIR Center and Professor of Professor, Department of at Fred Hutchinson and Pediatrics and Pathology Microbiology at Harvard Affiliate Associate Professor, Medical School University of Washington • Antibody research focuses on learning • His laboratory has a broad portfolio • Work focuses on developing ab-based • Research focuses on: how HIV-positive individuals develop of work in the area of viral Tx to treat emerging viral infections • Statistical design and analysis of Vx potent antibody responses, using those immunology and antibody sciences, • Co-leads the Therapeutics Working and mAb clinical trials related to the insights to inform HIV Vx strategies with the goal to discover mechanisms Group of the Massachusetts Consortium prevention and/or treatment of HIV • Recently has focused on effects of Zika of immunity important to developing on Pathogen Readiness which conducts and other infectious diseases Vx in flavivirus-endemic populations to new therapeutics and vaccines research that involves isolating abs • Development of statistical methods elicit cross-reactive ab responses • Founder of IDBiologics, an early stage from convalescing individuals to for analyses of Vx-induced immune • Lab section has pivoted to developing biotech company, developing human determine how these abs work against responses, and HIV mAb PK/PD ab products for SARS-Cov-2 virus to help mAbs for infectious diseases SARS-CoV-2's spike protein • Design and analysis of assay detect, prevent and treat coronavirus qualification/validation 5 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE DRAFT – PRE-DECISIONAL & DELIBERATIVE TOPIC Assay standardization

WHITE PAPER AUTHOR M O D E R AT O R

Erica Ollmann Saphire John Dye Ph.D., Professor of the La Jolla Institute for Immunology Ph.D., Chief of Viral Immunology at U.S. Army Medical Research Institute of Infectious Diseases

• Research focuses on explaining at the molecular level, how and why viruses are • Oversees the execution of research programs to develop medical countermeasures pathogenic and providing the 3D roadmap for medical defense against highly pathogenic viruses of military importance that are studied in Biosafety • Dr. Saphire’s team has conducted extensive research and solved the structures of the Level 3 and Level 4 containment laboratories Ebola, Sudan, Marburg, Bundibugyo and Lassa virus glycoproteins, explaining where • Research focuses on filovirus vaccines and therapeutics, with the ultimate aim of human abs can defeat these viruses, and what ab features correlate with protection counteracting the Ebola virus and other related viruses • Currently leads a Bill & Melinda Gates Foundation- and NIAID-supported consortium to • Has led teams to track immune response in hundreds of survivors of high-risk evaluate antibody therapeutics against SARS-CoV-2 to prevent and treat COVID-19 pathogens, determining an "immune profile" to drive Vx and Tx development PANELISTS

Holly Soares Bette Korber Steven Kozlowski Hendrik Neubert Ph.D., Vice President and Ph.d., Laboratory Fellow and M.D., Director of Office of Ph.D, Senior Director of Head of Precision Medicine Scientist Level 6 at the Los Biotechnology Products (OBP) Biomedicine Design at Pfizer at Pfizer Alamos National Laboratory in OBQ at CDER/FDA

• Her group supports biomarker • Heads the HIV sequence and • His office is responsible for the quality • Leads a translational biomeasures and strategies for proof of mechanism, immunology database project review of monoclonal antibodies and most protein biomarkers group across early signs of efficacy and patient (www.hiv.lanl.gov) and the new therapeutic proteins at CDER several disease areas stratification Covid-19 analysis pipeline project • Has been involved in all phases of the • Has developed biomarker assays • Previously has led translational (www.cov.lanl.gov) regulatory process from pre-IND product based on mass spectrometry and flow medicine groups at Pfizer, BMS and • Leads an interdisciplinary team that development though licensing and post- cytometry to enable mechanistic Abbvie provides bioinformatics, theoretical, approval supplements PK/PD and PBPK modeling • Has chaired fNIH public private and statistical support, focusing on • Has a background in immunology and has scientific boards and has authored viral diversity and the human immune been involved in manufacturing initiatives 100+ publications response to infection to advance quality 6 FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE