antibodies as drugs: translating molecules into treatments

Scientific Organizers: Paul W. H. I. Parren, Genmab B.V., Netherlands Erica Ollmann Saphire, The Scripps Research Institute, USA

Antibodies carry an enormous potential in prophylaxis and treatment of human disease. Antibody therapies may be divided into two distinct but highly related disciplines. First, antibodies can be elicited de novo using vaccines. Our understanding of what constitutes an effective antibody response at the molecular level and the science of eliciting such antibodies in vivo is progressing rapidly. Second, isolated antibodies represent powerful drugs when developed as biopharmaceuticals, as demonstrated by the ever-expanding list of approved molecules as well as by the large number of antibody products in development in a wide range of therapeutic areas. The antibody landscape is changing as the field has moved from empirical to knowledge-based, designer approaches for which understanding of mechanisms of action at the molecular level is critical. Translating such basic knowledge into novel products and applications requires scientists from many disciplines including structural and cellular immunology, biology, engineering, chemistry and medicine to interact closely. Consequently, the field of antibody-based vaccines and therapeutics has become an interface area where experts meet and work together. The 2018 Keystone Symposia antibodies conference aims to provide a platform for knowledge-sharing from the molecular to the systems level to navigate the newest developments and insights to prevent, treat and cure major human diseases.

Session Topics:• Protective Antibody Responses • Workshop 1: Vaccines• From Molecules to Vaccines • Antibodies as Biopharmaceuticals • Antibody Fc-Mediated Mechanisms I & II• Workshop 2: Therapeutic Antibodies • Exploiting Effector Cell Responses • Novel Ways to Deliver Antibody Therapy• From Molecules to the Clinic

Scholarship Application & Discounted Abstract Deadline: October 24, 2017Abstract Deadline: November 21, 2017Discounted Registration Deadline: December 19, 2017

February 25–March 1, 2018 | Whistler Conference Centre | Whistler, British Columbia | Canada

Antibodies as Drugs: Translating Molecules into Treatments

www.keystonesymposia.org/meetings | 1.800.253.0685 | 1.970.262.1230

a 501(c)(3) nonprofit educational organization

Note: Scholarships are available for graduate students and postdoctoral fellows and are awarded based on the abstract submitted. Submitting an abstract is an excellent opportunity to gain exposure for your work. Abstracts submitted by the abstract deadline will also be considered for short talks on the program.Upper image of B12 antibody bound to HIV courtesy of the National Institute of Allergy and Infectious Diseases, NIH

Meeting Hashtag: #KSantibodies www.keystonesymposia.org/18C1

SUNDAY, FEBRUARY 25Arrival and Registration

MONDAY, FEBRUARY 26Welcome and Keynote Address *Paul W. H. I. Parren, Leiden University Medical Center, Netherlands*Erica Ollmann Saphire, La Jolla Institute for Immunology, USA*David I. Watkins, University of Miami, USADennis R. Burton, The Scripps Research Institute, USAMolecular Vaccine Design Guided by Human Anti-Viral Antibodies

Protective Antibody Responses *David I. Watkins, University of Miami, USAGeorge Georgiou, University of Texas at Austin, USAThe Human Serological and BCR Antibody Repertoires in Cancer,Autoimmunity or following VaccinationErica Ollmann Saphire, La Jolla Institute for Immunology, USASystematic Analysis of Monoclonal Antibodies Against Ebola VirusGP Defines Features that Contribute to ProtectionAntonio Lanzavecchia, Vir Biotechnology, Inc., USALessons from the Analysis of the Immune Response to P. falciparumArthur S. Kim, Washington University School of Medicine, USAShort Talk: Identification of Protective Antibody Epitopes on theEastern Equine Encephalitis Virus Envelope ProteinSarah Elliott, Wistar Institute, USAShort Talk: DNA-Encoded Monoclonal Antibody (DMAb) for AcuteProphylaxis Against Influenza

Workshop 1: Antibodies and Protection *Ann J. Hessell, Oregon Health & Science University, USATongqing Zhou, NIAID, National Institutes of Health, USAStructural Basis of Zika-Neutralizing Monoclonal Antibodies Elicited inImmunized Macaque MonkeysBrett W. Jagger, Washington University, USAEfficacy of Zika Virus Vaccines Against Zika Infection in Mice DuringPregnancyLaura A. Powell, Vanderbilt University, USACross-Reactive and Potently Neutralizing Antibody Response in aDonor Naturally Infected with Ross River VirusNatasha D. Durham, Tufts University, USANeutralizing Antibodies Remodel the Conformational Landscape ofEbola GPHideki Hasegawa, National Institute of Infectious Diseases, JapanEnhancement of Anti-Viral Effects of an Intranasal InactivatedInfluenza Vaccine-Derived Broadly Neutralizing Antibody by IgAPolymerizationBryan Briney, The Scripps Research Institute, USAExceptionally Deep Antibody Repertoire Sequencing to Guide mAbDiscovery and DevelopmentRon Diskin, Weizmann Institute of Science, IsraelTargeting TfR1-Tropic Arenaviruses at their Achilles Heel:Structure-Based Rational Design of Universal Immunotherapy

Matthijs M. Jore, Radboud University Medical Center, NetherlandsEngineered Antibodies Against Plasmodium Transmission from Manto Mosquito

From Molecules to Vaccines *Erica Ollmann Saphire, La Jolla Institute for Immunology, USANancy L. Haigwood, Oregon Health & Science University, USAAntibody-Based HIV Therapeutics: "Hit Early, Hit Hard"James E. Crowe, Jr., Vanderbilt University Medical Center, USAGenetic and Structural Basis for Virus Neutralization by HumanAntibodiesRobert F. Garry, Tulane University Health Sciences Center, USAAntibody Treatment of Lassa Virus: From the Field to the Lab and BackRuoke Wang, Tsinghua University, ChinaShort Talk: Delineating Antibody Recognition Against EnvelopeProtein of Zika Virus during Natural Infection

Poster Session 1

TUESDAY, FEBRUARY 27Antibodies as Biopharmaceuticals Janine Schuurman, Genmab B.V., NetherlandsTherapeutic Antibody Panorama: Highways, Scenic Routes andDead-Ends Karl Dane Wittrup, Massachusetts Institute of Technology, USAPrinciples of Effective Antibody TherapeuticsMarie H. Kosco-Vilbois, AC Immune, SwitzerlandCreating Molecules that Succeed in the ClinicEmma M. Lees, Bristol Myers Squibb, USAJTX-2011: Mechanism of Action of an Agonist Antibody TargetingICOS*Ira Mellman, Genentech, Inc., USAAntibodies in Cancer ImmunotherapyCory Brooks, California State University, Fresno, USAShort Talk: Glycosylation of MUC1 Influences the Binding of aTherapeutic Antibody by Altering the Conformational Equilibrium of theAntigenAlexander W. Koch, Novartis Institutes for BioMedical Research, USAShort Talk: Targeting Coagulation Factor XI (FXI) for ThrombosisPrevention

Antibody Fc-Mediated Mechanisms I *Pierre Bruhns, Institut Pasteur, FrancePamela J. Bjorkman, California Institute of Technology, USAStructural Studies of Antibody and Receptor Binding to HIV-1 EnvJan Terje Andersen, Oslo University Hospital, NorwayHERA: A Human Endothelial Cell-Based Recycling Assay forScreening of FcRn Targeted Molecules Jeffrey S. Miller, University of Minnesota, USAStrategies to Use Trispecific Killer Engagers to Make NK CellsAntigen Specific

* Session Chair † Invited but not yet accepted Program current as of December 11, 2021. Meal formats are based on meeting venue. For the most up-to-date details, visit https://www.keystonesymposia.org.

KEYSTONE SYMPOSIAon Molecular and Cellular Biology

Antibodies as Drugs: Translating Molecules into Treatments (C1)February 25-March 1, 2018 • Whistler Conference Centre • Whistler, BC, Canada

Scientific Organizers: Paul W. H. I. Parren and Erica Ollmann SaphireSponsored by Bioverativ Therapeutics, Genentech, Inc., ImmunoGen, Inc., Merck & Co., Inc., OncoMed Pharmaceuticals, Inc., Pfizer Inc. and

Regeneron Pharmaceuticals, Inc.Discounted Abstract & Scholarship Deadline: October 24, 2017 / Abstract Deadline: November 21, 2017 / Discounted Registration Deadline: December 19, 2017

Julie M. Fox, Washington University, USAShort Talk: Antibody Therapy Reduces Chikungunya Virus Diseasethrough an FcgR-Dependent MechanismJames A. Ernst, Genentech, Inc., USAShort Talk: Optimizing Antibodies for Targeting the Tau Protein forAlzheimer's Disease and Other Tauopathies

Poster Session 2

WEDNESDAY, FEBRUARY 28Antibody Fc-Mediated Mechanisms II *Marjolein van Egmond, VU University Medical Center, NetherlandsPaul W. H. I. Parren, Leiden University Medical Center, NetherlandsComplement Activation at the Molecular LevelSuzan Huberdina Maria Rooijakkers, University Medical CenterUtrecht, NetherlandsEMBO Young Investigator Lecture: Antibody-Mediated Killing ofBacteria by ComplementGalit Alter, MIT and Harvard University, USACorrelate Guided Approaches to Develop Antibodies Against EbolaVirus InfectionPierre Bruhns, Institut Pasteur, FranceAnalyses of Single Ab-Secreting Cells using Droplet MicrofluidicsDavid P. Humphreys, UCB Pharma, UKShort Talk: On Target Hexamerisation of IgG1 Driven by a Mutantform of IgM Tail-Piece C-Terminal FusionDieke J. van Rees, Sanquin Research and Landsteiner Laboratory,NetherlandsShort Talk: Sodium Stibogluconate in Conjunction with CD47-SIRPCheckpoint Blockade Enables Rituximab-Mediated Killing of BLymphoma Cells by Neutrophils

Workshop 2: Therapeutic Antibodies *Ida Hiemstra, Genmab, Netherlands*Devin Sok, International AIDS Vaccine Initiative, USANon-Human Primate Pharmacokinetics of HIV Broadly NeutralizingAntibodies Isolated from Cow ImmunizationsAmarendra Pegu, NIAID, National Institutes of Health, USATrispecific Antibodies Mediate Highly Potent and Broad Neutralizationof HIV and Confer Expanded Protection Against SHIV Infection inMacaquesSanjay Ram, University of Massachusetts, USAPotentiation of Efficacy of a Candidate ImmunotherapeuticAnti-Neisseria Gonorrhoeae Antibody by Enhancing IgG Fc HexamerFormationNina G. Caculitan, Genentech, Inc., USADiscovery of the Determinants of Antibody-Drug Conjugate Efficacyand a Novel Resistance Mechanism to Anti-HER2 TherapeuticsJordana Griffiths, University of Southampton, UKTargeting OX40 in Cancer Immunotherapy John Engelhardt, Bristol-Myers Squibb Company, USANext Generation Anti-CTLA-4 Antibodies

Ezio Bonvini, MacroGenics, Inc, USATailoring Cytolytic Activity, Proliferation and Cytokine Release viaCD3 Engineering of DART® Molecules for Redirected T-cell KillingMichael Johnston, Queen's University Belfast, UKDevelopment of AMG 655 Conjugated Polymeric NanoparticlesTargeting Death Receptor 5 for the Treatment of Pancreatic Cancer

Exploiting Effector Cell Responses *Pamela J. Bjorkman, California Institute of Technology, USASergio A. Quezada, University College London, UKRegulatory T Cells, Polymorphisms and Response to CheckpointBlockade: From Mechanisms to Potential BiomarkersBertrand Routy, Centre hospitalier de l’Université de Montréal,CanadaThe Gut Microbiota as a Novel Predictor of Immune CheckpointInhibitors Response? Marjolein van Egmond, VU University Medical Center, NetherlandsTranslating Antibody–Effector Cell Cross-Talk to ImmunotherapyMaria Mar Naranjo, Centre National de la Recherche Scientifique,FranceShort Talk: Key Immunomodulatory Role of Neutrophils in theInduction of Protective Immunity by Antiviral Monoclonal Antibodies

THURSDAY, MARCH 1Novel Ways to Deliver Antibody Therapy *Janine Schuurman, Genmab B.V., NetherlandsUgur Sahin, BioNTech AG, GermanyAntibody and mRNA-Based TherapeuticsMark Cobbold, AstraZeneca, USARetargeting T Cells for Tumor TherapyMarkus Schmid, University of Zurich, SwitzerlandParacrine Delivery of Therapeutic ProteinsJohannes Lutz, Curevac AG, GermanymRNA-Encoded Antibodies for Passive ImmunizationKalie Mix, Sanofi, USAShort Talk: Cytosolic Delivery of AntibodiesJeffrey J. Bunker, University of Chicago, USAShort Talk: Natural Polyreactive IgA Antibodies Coat the IntestinalMicrobiota

From Molecules to the Clinic *Paul W. H. I. Parren, Leiden University Medical Center, NetherlandsDavid E. Szymkowski, Szymkowski David, USAExploring Novel Mechanisms of Action and Clinical Outcomes ofTherapeutic Antibodies Fc-Engineered to Optimally Engage FcGamma RIIbJohn M. Lambert, , USAAntibody-Drug Conjugates (ADCs): The Magic Bullet Revisited

Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

FRIDAY, MARCH 2






Departure






antibodies as drugs: translating molecules into treatments

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