The Essential Protein Engineering Summit

JOIN 2,600 GLOBAL PARTICIPANTS REGISTER TODAY 15th Annual COVER

CONFERENCE-AT-A-GLANCE

SHORT COURSES

TRAINING SEMINARS APRIL 8-12, 2019 | SEAPORT WORLD TRADE CENTER | BOSTON, MA ENGINEERING

ONCOLOGY FINAL AGENDA

IMMUNOTHERAPY

EXPRESSION

ANALYTICAL

IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES

THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION PREMIER SPONSORS HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION The Essential REGISTER ONLINE! PEGSummit.com Protein Engineering Summit

PEGSummit.com Organized by REGISTER at PEGSummit.com | 1 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS 15th Annual REGISTER TODAY CONFERENCE AT-A-GLANCE

COVER SUNDAY MONDAY-TUESDAY WEDNESDAY-THURSDAY AM THURSDAY PM-FRIDAY 2019 PROGRAMS (APRIL 7) (APRIL 8-9) (APRIL 10-11) (APRIL 11-12) CONFERENCE-AT-A-GLANCE Engineering Bispecific ENGINEERING Display of Antibodies Engineering Antibodies SHORT COURSES Antibodies

TRAINING SEMINARS ONCOLOGY Antibodies for Advancing Bispecific Antibodies and Clinical Progress of Cancer Therapy Combination Therapy to the Clinic Antibody-Drug Conjugates

Improving Immunotherapy ENGINEERING IMMUNOTHERAPY CAR Ts, TCRs and TILs Agonist Immunotherapy Targets Efficacy and Safety

Protein Expression EXPRESSION Difficult-to-Express Proteins Optimizing Protein Expression ONCOLOGY System Engineering

ANALYTICAL Characterization of Biophysical and Analytical Support for Drug IMMUNOTHERAPY Biotherapeutics Structural Analysis Product Development

IMMUNOGENICITY Immunogenicity Case Studies COURSES DINNER SHORT TUESDAY Immunogenicity Assessment and Optimizing Bioassays PRE-CONFERENCE SHORT COURSES PRE-CONFERENCE SHORT

& BIOASSAYS COURSES DINNER SHORT THURSDAY EXPRESSION and Clinical Management Regulatory Approval of Biologics for Biologics Engineering Antibody-Drug Clinical Progress of FUSIONS & CONJUGATES Fusion Protein Therapeutics Conjugates Antibody-Drug Conjugates ANALYTICAL EMERGING THERAPEUTICS Genome Editing with CRISPR: AND TECHNOLOGIES Emerging Indications for Oncolytic Viral Therapy Towards Novel Research, Translational Therapeutic Antibodies IMMUNOENICITY and Clinical Applications & BIOASSAYS Intro to Protein Engineering Next-Generation Sequencing Intro to Immunogenicity FUSIONS & for Antibody Discovery Intro to Structure-Based Drug and Engineering CONJUGATES Design and Development Genome Editing with CRISPR: By Cambridge Healthtech Institute Intro to Immunology for Towards Novel Research, Intro to Bispecifics: History, Drug Discovery Scientists Translational and Clinical THERAPEUTICS & Engineering, and Application Applications TECHNOLOGIES Statistics 101 for Intro to Bioprocessing Assay Validation

SPONSOR/EXHIBIT INFORMATION The PEGS meeting is an outstanding conference,“ HOTEL & TRAVEL INFORMATION “ REGISTRATION INFORMATION which continues to provide a uniquely high level of technical discourse on the development of protein therapeutics, which has become harder to find at other large conferences. REGISTER ONLINE! Chief Scientific Officer, Shattuck Labs, Inc. PEGSummit.com

STAY CONNECTED @PEGSBoston #PEGS19 REGISTER at PEGSummit.com | 2 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS REGISTER TODAY PLENARY KEYNOTE SESSION COVER MONDAY, APRIL 8 | 4:00PM CONFERENCE-AT-A-GLANCE SHORT COURSES Vision for How Immunotherapy Will Shape Future of Cancer Care TRAINING SEMINARS Immunotherapy is considered by many Leena Gandhi, MD, PhD as a pillar of cancer care today, but in Vice President, Immuno-Oncology Medical Development, Lilly Oncology ENGINEERING many ways we have only scratched the surface. Our knowledge and Dr. Gandhi graduated from the NYU School of Medicine and completed her residency understanding of the complexities of at MGH, and fellowship at Dana-Farber Cancer Institute (DFCI) and MGH. She immunotherapy and its mechanisms worked as a thoracic oncologist and Phase I oncologist at DFCI and served as ONCOLOGY continue to evolve. The future of cancer Director of Clinical Trials in the thoracic oncology program from 2013- 2016. She care will be defined by our ability to joined NYU Perlmutter Cancer Center as Associate Professor of Medicine and the Director of Thoracic systematically identify and implement Medical Oncology in 2016. She has worked on Phase I, II and III trials of novel targeted therapies and IMMUNOTHERAPY opportunities for combination therapy immunotherapies in lung cancer, with a focus on evaluating potential biomarkers of response. She has to improve and standardize patient been a lead investigator in clinical trials that helped define the use of PD-L1 as a biomarker of response to response. PD-1 inhibition in non-small cell lung cancer. Dr. Gandhi most recently served as the lead investigator on EXPRESSION the KEYNOTE-189 study, establishing combination chemotherapy and immunotherapy a standard of care in initial treatment for most NSCLC. On June 25, 2018, Dr. Gandhi joined Lilly Oncology to lead immuno- oncology medical development. ANALYTICAL YOUNG SCIENTIST KEYNOTE IMMUNOENICITY & BIOASSAYS The Lassa Virus Glycoprotein: Stopping a Moving Target Lassa virus causes ~5000 deaths from Kathryn Hastie, PhD FUSIONS & viral hemorrhagic fever every year in West CONJUGATES Africa. The trimeric surface glycoprotein, Staff Scientist, Immunology and Microbiology, termed GPC, is critical for infection, is the The Scripps Research Institute target for neutralizing antibodies, and a Dr. Hastie studied Ecology and Environmental Biology, Molecular Biology and THERAPEUTICS & major component of vaccines. Structural Biochemistry at the University of Colorado, Boulder. She then joined Erica Ollmann TECHNOLOGIES analysis of Lassa GPC bound to antibodies Saphire’s group at The Scripps Research Institute and completed her graduate studies from human survivors reveals a major in October 2011. As a Staff Scientist in the Ollmann Saphire Lab, Dr. Hastie conducts an independently Achilles heel for the virus and provides NIH-funded research project aimed at expanding structural knowledge of glycoproteins of Lassa and other the needed template for development arenaviruses. In addition, she serves on international task forces to steer thought about how to better SPONSOR/EXHIBIT of immunotherapeutics and improved INFORMATION elicit and detect the right responses and to deliver a much-needed vaccine for Lassa virus, which infects vaccines. hundreds of thousands of under-served in West Africa every year. HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION THE PEGS YOUNG SCIENTIST KEYNOTE recognizes a rising star in the field of protein science who is currently in a postdoc program or who has completed a postdoc in the last five years. Nominations of candidates for this role were solicited REGISTER ONLINE! from leading industry and academic research labs in the fall of 2018, and the final selection was made on the basis of votes from a 15-person group of scientific advisors. CHI’s Young Scientist Keynotes join the company’s Student Fellowships and PEGSummit.com Featured Poster Presentations as ways of supporting the increased visibility of those new to our field. Please visit the PEGS website following the 2019 meeting for details on how you can nominate a candidate for the 2020 event.

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CONFERENCE-AT-A-GLANCE

SHORT COURSES

TRAINING SEMINARS

ENGINEERING

ONCOLOGY CORPORATE SPONSORS

IMMUNOTHERAPY

EXPRESSION

ANALYTICAL

IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES

THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION

COVER We are delighted to announce two NEW events at PEGS Boston 2019 CONFERENCE-AT-A-GLANCE to honor all women in STEM programs. SHORT COURSES Join some of the most prominent researchers TRAINING SEMINARS for interactive discussions, be inspired by their professional and personal achievements, and ENGINEERING foster a strong women-based network.

ONCOLOGY

IMMUNOTHERAPY The PEGS Summit team EXPRESSION proudly recognizes the importance of ANALYTICAL

IMMUNOENICITY & BIOASSAYS

FUSIONS & WEDNESDAY, APRIL 10 CONJUGATES 7:25 AM Women in Science Panel Discussion THERAPEUTICS & TECHNOLOGIES 10:15 AM Women in Science Speed Networking

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION REGISTRATION INFORMATION Join the conversation. REGISTER ONLINE! Be inspired. PEGSummit.com

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COVER SUNDAY, APRIL 7 AFTERNOON, 2:30 - 5:30 PM THURSDAY, APRIL 11 CONFERENCE-AT-A-GLANCE MORNING, 10:00 AM - 1:00 PM SC5: In silico Immunogenicity Predictions DINNER, 5:45 - 8:15 PM SHORT COURSES (Hands-On) Workshop SC1: Preclinical and Clinical Assessment of Vinodh B. Kurella, PhD, Principal Scientist, Protein SC12: Design Strategies and Development of TRAINING SEMINARS Immunogenicity: Multidomain Therapeutics Engineering, Merrimack Pharmaceuticals ADCs and New Modalities, Including Gene Therapy Daron Forman, PhD, Principal Scientist, Molecular Robert Lutz, PhD, Principal Consultant, Crescendo and CAR T Discovery Technologies, Bristol-Myers Squibb Biopharma Consulting ENGINEERING Darshana Jani, MSc, Associate Director, Global Lead SC13: Bioassay Quality by Design Biologics, Clinical Assay Group, Global Product SC7: Translational Biotherapeutic Thomas Little, PhD, President and CEO, Bioassay Development, Pfizer, Inc. Development Strategies Part 2: Analytical and Clinical Considerations Sciences, Thomas A. Little Consulting ONCOLOGY Magdalena Tary-Lehmann, MD, PhD, CSO, Cellular Technology Limited (CTL); Adjunct Associate Zhiqiang An, PhD, Professor, Chemistry; Director, Professor of Pathology, Case Western Reserve Texas Therapeutics Institute, University of Texas DINNER, 5:45 - 8:45 PM University (CWRU) Health Science Center at Houston IMMUNOTHERAPY Linzhi Chen, PhD, Senior Research Fellow & Scott L. Klakamp, PhD, Senior Director & Head, SC15: Transient Protein Production in Bioanalytical Group Leader, Boehringer Ingelheim Biophysics, Biologics Development Sciences, Janssen Mammalian Cells BioTherapeutics Pharmaceuticals Richard Altman, MS, Staff Scientist, Life Science Kosalaram Goteti, PhD, Director, Site Head of Liming Liu, PhD, Senior Principal Scientist, Solutions, Thermo Fisher Scientific EXPRESSION Pharmacokinetics, Pharmacodynamics and Drug Pharmacometry, EMD Serono Henry C. Chiou, PhD, Director, Cell Biology, Life Metabolism (PPDM), Merck Research Laboratories Science Solutions, Thermo Fisher Scientific SC2: Translational Biotherapeutic An Song, PhD, Senior Vice President, Development Bojiao Yin, PhD, Scientist, Protein Technologies, ANALYTICAL Development Strategies Part 1: Discovery, Sciences, Immune-Onc Therapeutics, Inc. Molecular Assessment and Early Stage Amgen Development TUESDAY, APRIL 9 * Separate Registration Required. IMMUNOENICITY Juan Carlos Almagro, PhD, Founder and Director, & BIOASSAYS GlobalBio, Inc. DINNER, 6:00 - 8:30 PM Zhiqiang An, PhD, Professor, Chemistry; Director, Texas Therapeutics Institute, University of Texas FUSIONS & Health Science Center at Houston SC9: Introduction to Biophysical Analysis for CONJUGATES Gadi Bornstein, PhD, Senior Director, Biologics Biotherapeutics: Development Applications Discovery, TESARO, Inc. Christine P. Chan, PhD, Principal Scientist, Global Manufacturing Science & Technology, Sanofi SC3: Selection, Screening and Engineering for THERAPEUTICS & SC10: CAR T-Cell Therapy for Solid Tumors TECHNOLOGIES Affinity Reagents Jonas V. Schaefer, PhD, Lab Head/Investigator II, Soldano Ferrone, MD, PhD, Division of Surgical Novartis Institutes for BioMedical Research (NIBR) Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School Jürgen Klattig, PhD, Scientist, R&D, MorphoSys AG SPONSOR/EXHIBIT Moonsoo M. Jin, PhD, Professor, Biomedical INFORMATION SC4: Understanding and Modulating Tumor Engineering, Radiology & Surgery, Molecular Imaging Microenvironment for Immunotherapy Innovations Institute, Weill Cornell Medical College HOTEL & TRAVEL INFORMATION David A. Eavarone, PhD, Associate Principal Scientist, Tara Arvedson, PhD, Director, Oncology Research, Harbour Biomed Amgen REGISTRATION INFORMATION SC11: Developability of Bispecific Antibodies: Formats and Applications REGISTER ONLINE! Nimish Gera, PhD, Director, Research and Development, Mythic Therapeutics PEGSummit.com

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COVER Cambridge Healthtech Institute Training Seminars offer real-life case studies, problems encountered and solutions applied, and extensive coverage of the basic science underlying CONFERENCE-AT-A-GLANCE each topic. Experienced Training Seminar instructors offer a mix of formal lectures, SHORT COURSES interactive discussions and activities to help attendees maximize their learning experiences. These immersive trainings will be of value to scientists from industry and academic TRAINING SEMINARS research groups who are entering new fields – and to those working in supporting roles that By Cambridge Healthtech Institute will benefit from an in-depth briefing on a specific aspect of the industry. ENGINEERING MONDAY, APRIL 8: 8:30 AM - 12:30 PM - TS11A: Introduction to Bispecifics: History, Engineering, and TUESDAY, APRIL 9: 8:30 AM - 5:25 PM Application ONCOLOGY Introduction to Bispecifics will be organized as an informative and practical TS9A: Introduction to Protein Engineering guide to get up to speed on critical aspects of bispecific antibody therapeutics. Topics will include historical successes, failures, and lessons learned. Specific CHI’s Introduction to Protein Engineering training seminar offers a comprehensive IMMUNOTHERAPY practical instruction will span mechanisms of action, engineering, developability, tutorial in the concepts, strategies and tools of protein engineering and explains regulatory considerations, and translational guidelines. Perspectives on ideal the role of this discipline in the progression of biotherapeutic research and implementation of bispecifics as targeted and immunomodulatory approaches development. Learn about the selection of functional assays to monitor changes EXPRESSION will be discussed. in desired properties, traditional and emerging display technologies and library design strategies. Also explore the engineering and enhancement of traditional Instructor: GG. Jonah Rainey, PhD, Vice President, Antibody Therapeutics, Gritstone Oncology, Inc. antibodies and discuss the roles of protein engineering in the discovery, design ANALYTICAL and development of new therapeutic modalities. The class includes briefings TS12A: Introduction to Bioprocessing on the expression platforms used for producing proteins for testing and for manufacture, and the rapidly emerging role of protein engineering in optimizing CHI’s Introduction to Bioprocessing training seminar offers a detailed survey of IMMUNOENICITY antibody and other protein therapeutics. the steps needed to produce today’s complex biopharmaceuticals, from early & BIOASSAYS Instructor: David Bramhill, PhD, Founder, Bramhill Biological Consulting, LLC development through commercial. The seminar begins with an introduction to biologic drugs and the aspects of protein science that drive the progression TS10A: Introduction to Structure-Based Drug Design and of analytical and process steps that follow. Then, step through the stages of FUSIONS & Development bioprocessing, beginning with the development of cell lines and ending at scaling CONJUGATES up for commercial production. Also explore emerging process technologies, CHI’s Introduction to Structure-Based Drug Design and Development offers an facility design considerations and the regulatory and quality standards that introduction to the concepts, strategies and tools of structure-based drug design, govern our industry throughout development. The important roles of analytical THERAPEUTICS & optimization and development. The seminar consists of presentations and live methods at all stages of development as well as formulation and stability TECHNOLOGIES demonstrations of some of the common computational tools used in the field. assessments in developing and gaining approval for a biopharmaceutical are We will cover techniques to triage therapeutics sequences, modulate affinity, also examined. create novel constructs (such as Fc-fusions, bispecifics, and protein traps) Instructors: SPONSOR/EXHIBIT along with increasing the manufacturability of a biologic. The class is directed at Sheila G. Magil, PhD, Principal Consultant, BioProcess Technology Consultants, Inc. scientists new to the industry, academic scientists and career protein engineers INFORMATION Frank J. Riske, PhD, Senior Consultant, BioProcess Technology Consultants, Inc. wanting an introduction into how structure can aid in guiding experimental HOTEL & TRAVEL INFORMATION design. Instructors: REGISTRATION INFORMATION Christopher Corbeil, PhD, Research Officer, Human Health Therapeutics, National Research Council Canada Traian Sulea, PhD, Senior Research Officer, Human Health Therapeutics, National REGISTER ONLINE! Research Council Canada PEGSummit.com

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COVER WEDNESDAY, APRIL 10: 8:30 AM - 5:45 PM - THURSDAY, APRIL 11: 1:40 - 5:20 PM - CONFERENCE-AT-A-GLANCE THURSDAY, APRIL 11: 8:30 AM - 12:30 PM FRIDAY, APRIL 12: 8:30 AM - 3:40 PM

SHORT COURSES TS9B: Next-Generation Sequencing for Antibody Discovery and TS8C: Introduction to Immunogenicity Engineering All protein drugs generate an immunogenic response. This 1.5-day training TRAINING SEMINARS In this training seminar, participants will learn about Next-Generation Sequencing seminar provides a practical, comprehensive overview of immunogenicity – (NGS) of antibody repertoires. Part 1 will provide an introduction to the antibody the causes, how to assess, predict and prevent, and what to do if you observe repertoires, consisting of genetic background, generation of diversity, sequencing immunogenicity during preclinical, clinical and post-market approval. The ENGINEERING technologies and a hand-on session on the computational tools available for the seminar begins by detailing the science behind immunogenicity, the latest analysis antibody repertoire NGS data. Part 2 will focus on the preprocessing international guidances, followed by assay and bioanalytical assessment and analysis of data. Each step of the preprocessing will be elucidated using the strategies for traditional and emerging biologics. Other topics include predictive ONCOLOGY programming language R along with existing bioinformatics pipelines available. models and how to report immunogenicity incidents both internally and Repertoire analysis content will provide statistical quantification and visualization externally. of high-dimensional data. The course will be fully interactive with case studies, Instructors: IMMUNOTHERAPY participants will be able to download data and example scripts. Please bring your Bonnie Rup, PhD, Independent Consultant computer. Sofie Pattijn, CTO, ImmunXperts Instructors: Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH TS9C: Genome Editing with CRISPR: Towards Novel Research, EXPRESSION Zurich, Switzerland Translational and Clinical Applications Simon Friedensohn, MSc, Research Assistant, Biosystems Science and This rigorous day and a half program compiled for specialists interested in Engineering, ETH Zurich, Switzerland ANALYTICAL applying genome editing technologies for both basic and translational research TS10B: Introduction to Immunology for Drug Discovery will comprehensively review the state-of-art information on gene editing strategies and applications in various areas, such as disease modelling, drug discovery and Scientists development. Beginning from introductory level basic technology aspects, key IMMUNOENICITY This 1.5-day seminar will cover the fundamentals of human immunology for an molecular features, strengths and shortcomings of CRISPR/Cas9 systems, the & BIOASSAYS audience of scientists across different backgrounds working in pharmaceutical instructor will advance towards sharing in-depth knowledge related to virtually and biotech organizations in programs related to immunotherapy. The course all facets of present day genome editing applications, such as constructing of FUSIONS & will cover a historical perspective, basic mechanisms, fundamental concepts cell culture-based experimental platforms, engineering disease models for in vivo CONJUGATES and practical approaches to developing therapeutics and their combinations to research supporting preclinical drug development workflows, rational design and modulate the immune system. Additionally, the class will offer perspectives on functional screening of sgRNA libraries, application of CRISPR/Cas9 technology how immune responses can be monitored by assessment of biomarkers and for diagnostic and therapeutic purposes and many others. THERAPEUTICS & modulated through biopharmaceutical intervention. Through group activities, Instructor: TECHNOLOGIES attendees will actively review immunological concepts as well as design Serguei V. Kozlov, PhD, MBA, PMP, Principal Scientist/PM, Team Leader PTO, functional immunological assays and read-outs. Center for Advanced Preclinical Research, Frederick National Laboratory for Instructors: Cancer Research (NCI) Masha Fridkis-Hareli, MSc, PhD, Founder and President, ATR, LLC SPONSOR/EXHIBIT INFORMATION Tatiana Novobrantseva, PhD, Co-Founder, Head of Research and Development, Verseau Therapeutics HOTEL & TRAVEL INFORMATION TS11B: Statistics 101 for Assay Validation REGISTRATION INFORMATION This training first covers all the basic statistical concepts that are required to perform a successful assay validation, such as (non)linear models for calibration, variance component analysis, and design of experiments. We will then discuss REGISTER ONLINE! some regulatory requirements for assay validation and discuss how to ensure PEGSummit.com regulatory compliance while also guaranteeing that the assay is fit for its intended purpose. Finally, we will combine those statistical and regulatory concepts in a case study. Instructor: Perceval Sondag, Senior Manager, Statistics, PharmaLex

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CONFERENCE-AT-A-GLANCE POSTER COMPETITION Two poster awards will be given at the conference for a SHORT COURSES cash prize for best poster. Present your poster at PEGS TRAINING SEMINARS and be automatically entered to win. One winner from each poster session will be chosen based on visual appearance of poster, clarity of concepts presented, ENGINEERING audience engagement, technology advances and implications of the work presented. ONCOLOGY Reasons you should present your IMMUNOTHERAPY research poster at PEGS Boston: • Your poster will be seen by our international delegation, representing leaders from top pharmaceutical, biotech, academic and government institutions EXPRESSION • Receive $50 off your registration REGISTER AND SUBMIT • Your poster abstract will be published in our conference materials BY MARCH 1, 2019 ANALYTICAL • Automatically entered in the poster competition

IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES STUDENT FELLOWSHIPS STUDENT FELLOWSHIP DETAILS: • Receive a poster presentation slot THERAPEUTICS & PEGS SUMMIT IS PROUD TO SUPPORT AND RECOGNIZE THE SCIENTISTS OF TOMORROW! and a savings of over $900 on their TECHNOLOGIES registration fee Students are encouraged to present a research poster and qualify as a student • Present your research poster to an fellow of the event. international delegation of nearly SPONSOR/EXHIBIT 2,300 participants INFORMATION To secure a poster board and inclusion in the conference materials, • Meet face-to-face with potential HOTEL & TRAVEL INFORMATION your abstract must be submitted, approved and your registration employers and contacts to further your research and form paid in full by March 1, 2019. REGISTRATION INFORMATION collaborations • Be entered in the Poster Competition – with cash prizes! REGISTER ONLINE! Fellowships are limited to 25 students and submission deadlines must be met. Special pricing PEGSummit.com is available for students without a poster presentation. Full time graduate students and PhD candidates qualify for the student rate. See the event website for details.

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SHORT COURSES

TRAINING SEMINARS

ENGINEERING Engineering Novel First-in-Class Display of Antibodies Biologics ONCOLOGY Designing platforms to lend novel functionality and improvements in developability requires a high degree of innovation to address IMMUNOTHERAPY hard to reach and difficult targets. TheEngineering stream provides Engineering Antibodies knowledge and collaboration opportunities for scientists in this EXPRESSION highly competitive field. Display and engineering of biologics including bispecific antibodies will be highlighted for applications in ANALYTICAL oncology, immunotherapy, infectious disease, CNS, inflammation and Engineering Bispecific autoimmune disorders. Antibodies IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES

THERAPEUTICS & TECHNOLOGIES

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COVER 21ST ANNUAL

CONFERENCE-AT-A-GLANCE DISPLAY OF ANTIBODIES Engineering Novel First-in-Class Biologics SHORT COURSES

TRAINING SEMINARS April 8-9, 2019 The Twenty-first Annual Display of Antibodies is the cornerstone conference of the PEGS Summit and convenes leaders in the field year after year. This year’s meeting showcases innovation in discovery, design and engineering of biologics through molecular evolution using phage, yeast and other display methodologies. The ENGINEERING proliferation of novel constructs is possible through methods to improve library design, pharmacological and biophysical properties to create drug molecules with greater potency, modes of action, target specificity and activity than previously achievable.

ONCOLOGY SUNDAY, APRIL 7 9:10 Constructing a Synthetic Biology Toolbox 10:50 KEYNOTE PRESENTATION: Using Phage Display Parts Engineering Membrane Proteins with IMMUNOTHERAPY Recommended Short Course* C. Ronald Geyer, PhD, Professor, Pathology and Lab Phage Display Medicine, University of Saskatchewan Gregory A. Weiss, PhD, Professor, Chemistry, SC3: Selection, Screening and Engineering Antibody phage display is a powerful strategy for Molecular Biology & Biochemistry, University of for Affinity Reagents producing antibody fragments that can be used as California, Irvine EXPRESSION *Separate registration required. Click here or see parts for constructing synthetic antibody-like devices. Phage display offers a power tool for page 5 for course details. Here we describe the construction and selection remodeling proteins – their binding, catalysis, of antibody fragment libraries and the assembly solubility and other properties. However, the ANALYTICAL MONDAY, APRIL 8 of selected antibody parts into devices useful for technique has largely been confined to soluble antibody therapy, imaging, and diagnostics. proteins. My laboratory has demonstrated that 7:00 am Registration and Morning Coffee membrane proteins can also be displayed on 9:40 Development of a Complex T7 Phage IMMUNOENICITY the phage surface. In this talk, I’ll describe the Display Library for Discovery of Biomarkers of limitations of membrane protein phage display & BIOASSAYS NEW APPLICATIONS FOR PHAGE DISPLAY Lung Diseases and applying the approach to solubilize and 8:30 Chairperson’s Opening Remarks Lobelia Samavati, MD, Associate Professor of engineer membrane proteins with powerful new FUSIONS & Gregory A. Weiss, PhD, Professor, Chemistry, Molecular Medicine, Department of Medicine, Center for functions. CONJUGATES Biology & Biochemistry, University of California, Irvine Molecular Medicine and Genetics, Wayne State University School of Medicine 8:40 Protein-Directed Evolution in Genomic 11:20 Cytosolic Delivery of Proteins by Chronic respiratory diseases of unknown etiology Contexts Using Mutagenesis and CRISPR/Cas9 Bioreversible Esterification share similarities with various inflammatory THERAPEUTICS & Michael Krogh Jensen, PhD, Senior Researcher Ronald T. Raines, PhD, Firmenich Professor of and infectious diseases including tuberculosis. TECHNOLOGIES & Co-Principal Investigator, Technical University Chemistry, Department of Chemistry, Massachusetts Currently, there is no test available to discriminate of Denmark, Novo Nordisk Foundation Center for Institute of Technology Biosustainability between active TB and sarcoidosis or between active, latent TB and other respiratory diseases. The surface of mammalian cells is highly anionic. Here we describe a method for robust directed SPONSOR/EXHIBIT Using a high throughput method, we developed Accordingly, Coulombic repulsion prevents anionic INFORMATION evolution using mutagenesis in genomic contexts. two T7 phage display cDNA libraries derived from molecules from entering cells. We have tuned the The method employs error-prone PCR and Cas9- mRNA isolated from bronchoalveolar lavage (BAL) reactivity of a diazo compound to elicit the efficient mediated genome integration of mutant libraries HOTEL & TRAVEL INFORMATION cells and leukocytes of sarcoidosis patients. We O-alkylation of carboxylic acids in water. Such of 300-600 bp-sized donor variants into genomic combined these two libraries with two other libraries esterification enables proteins (including a Fab sites with efficiencies reaching 98-99% and >100K REGISTRATION INFORMATION derived from embryonic lung fibroblasts and human fragment) to traverse the plasma membrane directly, variants from a single transformation. To validate monocytes, to build a complex library. Our studies like a small-molecule prodrug. As with prodrugs, the method for directed evolution, we engineered indicate that our complex library contains diverse the nascent esters are substrates for endogenous REGISTER ONLINE! two essential enzymes in the mevalonate pathway clones that can distinguish sera from healthy controls, esterases that regenerate native proteins. of Saccharomyces cerevisiae. Taken together, our PEGSummit.com sarcoidosis, cystic fibrosis and tuberculosis. method extends on existing CRISPR technologies by facilitating efficient mutagenesis of hundreds of 10:10 Networking Coffee Break nucleotides in cognate genomic contexts.

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REGISTER TODAY 11:50 Generating Pairs of Affinity Reagents for large library and high-throughput sequencing enables reveals a major Achilles heel for the virus and Sandwich Assays through MegaSTAR routine recovery of antibodies, including functionally active provides the needed template for development Brian K. Kay, PhD, Professor & Head, Biological antibodies, against GPCRs like CXCR5. of immunotherapeutics and improved vaccines. COVER Sciences, University of Illinois, Chicago 1:50 Session Break The ‘sandwich’ assay is a robust, flexible and 5:40 Welcome Reception in the Exhibit Hall CONFERENCE-AT-A-GLANCE sensitive test that is widely employed in clinical 2:00 Synthetic DNA Technologies Sponsored by diagnostics for monitoring human health and Enable Antibody Discovery and with Poster Viewing SHORT COURSES disease. Unfortunately, identifying pairs of antibodies Optimization 7:15 End of Day takes time and luck. We have recently developed Aaron Sato, PhD, CSO, Twist Bioscience TRAINING SEMINARS a method to discover pairs of recombinant affinity Utilizing its proprietary DNA writing technology to reagents part of the phage-display process. We create oligo pools, genes, and synthetic libraries, TUESDAY, APRIL 9 will present results of applying MegaSTAR to cell Twist Pharma, a division of Twist Bioscience, provides 8:00 am Registration and Morning Coffee ENGINEERING signaling proteins and biomarkers of heart disease. the biotechnology industry with an end-to-end 12:20 pm High Quality Antibodies for antibody discovery solution. This solution includes (1) ENGINEERING SMALL PROTEINS AND a panel of high diversity synthetic antibody libraries, Therapeutic Applications (2) a proprietary human anti-GPCR antibody phage CONSTRAINED PEPTIDES ONCOLOGY Vera Molkenthin, PhD, Chief Scientist, AbCheck display library focused on this validated target class, 8:25 Chairperson’s Remarks AbCheck discovers and optimizes human antibodies and (3) a Twist Antibody Optimization (TAO) platform K. Dane Wittrup, PhD, J.R. Mares Professor, Chemical for therapeutic applications leveraging several for antibody affinity and developability optimization. Engineering & Bioengineering, Massachusetts Institute proprietary platforms including in vitro and in IMMUNOTHERAPY of Technology vivo technologies. AbCheck will present new 2:30 Problem-Solving Breakout Discussions technological developments regarding its versatile 8:30 Yeast Display of Post-Translationally 3:20 Networking Refreshment Break human antibody discovery and optimization platform Modified Polycyclic Peptides EXPRESSION with a focus on Rabbit Mass Humanization and Wilfred A. van der Donk, PhD, Richard E. Heckert AbAccelTM.. Both technologies can be combined PLENARY KEYNOTE SESSION Endowed Chair in Chemistry, Director of Graduate with AbCheck’s yeast display platform AbSieveTM Studies, Howard Hughes Medical Institute ANALYTICAL and deliver high quality leads with subnanomolar 4:00 Chairperson’s Remarks Investigator, Department of Chemistry, University of affinities and good stabilities which are compatible Rakesh Dixit, PhD, DABT, Vice President, R&D, Illinois with different antibody designs including bispecifics. Global Head, Biologics Safety Assessment, Ribosomally synthesized and post-translationally Translational Sciences, AstraZeneca modified peptides (RiPPs) constitute a large class IMMUNOENICITY 12:50 Luncheon Presentation I: Sponsored by & BIOASSAYS of natural products with vast structural diversity. Integrated Solutions for Antibody 4:10 Vision for How Immunotherapy Will Lanthionine-containing peptides (lanthipeptides) are Discovery and Beyond Shape Future of Cancer Care examples of this growing class. They contain multiple FUSIONS & Hua Tu, PhD, CEO and Founder, LakePharma Leena Gandhi, MD, PhD, Vice President, Immuno- thioether crosslinks installed post-translationally by CONJUGATES LakePharma focuses on providing complete solutions Oncology Medical Development, Lilly Oncology a single enzyme that typically forms 2-5 rings with from antibody discovery to GMP manufacturing. Immunotherapy is considered by many as a high control over regio- and chemoselectivity. This In this talk, the biotech company will share its pillar of cancer care today, but in many ways we presentation will discuss use of the biosynthetic THERAPEUTICS & experience and case studies in antibody discovery have only scratched the surface. Our knowledge machinery to display libraries of such polycyclic TECHNOLOGIES and engineering using display technology. The and understanding of the complexities of peptides. presentation provides solutions for the common immunotherapy and its mechanisms continue to problems encountered by display technology as well evolve. The future of cancer care will be defined 9:00 Integrating Computational Design with as rapid development to clinical manufacturing. by our ability to systematically identify and Screening in Mammalian Cells for Novel SPONSOR/EXHIBIT implement opportunities for combination therapy Peptide Therapeutics INFORMATION Sponsored by 1:20 Luncheon Presentation II: to improve and standardize patient response. Philip M. Kim, PhD, Associate Professor, The Donnelly Bruteforcing Hard Targets with Centre for Cellular and Biomolecular Research, HOTEL & TRAVEL INFORMATION Computationally Immuno- 4:55 The Lassa Virus Glycoprotein: Departments of Molecular Genetics and Computer Engineered SuperHuman 2.0 Stopping a Moving Target Science, University of Toronto REGISTRATION INFORMATION Jacob G. Glanville, PhD, Co-founder & CSO, Distributed Kathryn Hastie, PhD, Staff Scientist, Immunology I will present our technology platform that integrates Bio Inc. and Microbiology, The Scripps Research Institute computational library design with modern in-cell REGISTER ONLINE! Over the last decade, the iterative analysis and Lassa virus causes ~5000 deaths from viral selection strategies to uncover novel peptide computational optimization of antibody repertoires has hemorrhagic fever every year in West Africa. therapeutics. I will cover a number of different library PEGSummit.com resulted in a 1000x improvement in antibody library The trimeric surface glycoprotein, termed designs and selection methodologies, including functional sequence diversity. Here, we present a series GPC, is critical for infection, is the target for selections for phenotype or using genetic reporter of case studies against traditionally hard targets that neutralizing antibodies, and a major component systems and cell sorting, as well as methods to demonstrate the practical consequences of optimized of vaccines. Structural analysis of Lassa GPC obtain highly stable mirror image peptides. library diversity. In GPCRs, we show a combination of a bound to antibodies from human survivors REGISTER at PEGSummit.com | 12 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ENGINEERING STREAM DISPLAY OF ANTIBODIES continued PARTICIPANTS

REGISTER TODAY 9:30 Platforms for the Generation and 11:50 A Novel Strategy for the Generation of we will share recent data demonstrating isolation of Screening of Cyclic Peptide Libraries Yeast Surface Display Antibody Fab Libraries VHHs to membrane proteins. Ali Tavassoli, PhD, Professor, Chemical Biology, Stefan Zielonka, PhD, Group Leader & Principal 1:20 Ice Cream Break in the Exhibit Hall with University of Southampton Scientist, Protein Engineering & Antibody COVER Poster Viewing Cyclic peptide libraries have demonstrated significant Technologies, Discovery Technologies, Global Research and Development, Merck KGaA CONFERENCE-AT-A-GLANCE potential when employed against challenging targets NGS IN NATURAL AND ARTIFICIAL Yeast surface display emerged as a promising such as protein-protein interactions. SICLOPPS is ANTIBODY REPERTOIRES SHORT COURSES a genetically encoded method for the intracellular platform technology for antibody engineering. Still, generation of cyclic peptide libraries of over a hundred generation of libraries comprising heavy chain as well 2:00 Chairperson’s Remarks TRAINING SEMINARS million members. SICLOPPS libraries can be interfaced as light chain diversities is a cumbersome process Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc. with a variety of cell-based assays. Here, we will involving multiple steps. We recently implemented report the use of this approach for the identification of a focused approach for the construction of Fab 2:05 Using Structural Information to Aid ENGINEERING inhibitors of a variety of challenging targets. antibody libraries using type IIs restriction enzymes. in silico Therapeutic Design from Next- This method seems to be valid for the generation of Generation Sequencing Repertoires of 10:00 Coffee Break in the Exhibit Hall with YSD diversities with adequate qualities. Antibodies Poster Viewing Sponsored by Charlotte Deane, PhD, Professor of Structural ONCOLOGY 12:20 pm Luncheon Presentation I: Bioinformatics & Head of Department, Department NOVEL TECHNOLOGIES Highly Specific Claudin6 Antibodies of Statistics University of Oxford; Head of the Oxford for Targeting Solid Tumors 10:45 Chairperson’s Remarks Protein Informatics Group, University of Oxford Benjamin Doranz, PhD, MBA, President and CEO, IMMUNOTHERAPY Jennifer R. Cochran, PhD, Shriram Chair of We have built the freely available Observed Antibody Integral Molecular Bioengineering; Professor of Bioengineering, and (by Space database of over half-a-billion antibody courtesy) Chemical Engineering, Stanford University Claudin6 is upregulated in tumors, but unlike other sequences. Using this data, I will show how claudins, is not expressed in normal tissue. Using our predicted structural information can enrich data EXPRESSION 10:50 Specificity and Polyreactivity: Designing MPS Antibody Discovery platform, we have discovered from next-generation sequencing experiments. In Antibodies Against Receptor Families for lead candidate antibodies that bind unique residues particular, ABOSS, our novel method for filtering Desired Reactivity on Claudin6 (creating novel IP) and do not bind any Ig-seq data, which considers the structural viability ANALYTICAL Christilyn Graff, PhD, Director, Antibody Discovery and other membrane protein in the human proteome. of each sequence and TAP, our novel therapeutic Engineering, Biogen antibody profiler that provides five computational Specificity Profiling and High-Resolution developability guidelines. Targeting receptor families can present a challenge Epitope Mapping of mAbs Targeting depending on the level of sequence and structural IMMUNOENICITY Membrane Proteins 2:35 Analysis of Human Antibody Repertoires & BIOASSAYS homology. From highly conserved to more divergent families, in vitro display libraries can be used to focus Duncan Huston-Paterson, DPhil, Product Manager, Eline T. Luning Prak, MD, PhD, Associate Professor, Integral Molecular Department of Pathology and Laboratory Medicine, the antibody response to the desired specificity. Perelman School of Medicine, University of Antigen optimization, in concert with knowledge of Specificity testing across the proteome de-risks FUSIONS & Pennsylvania CONJUGATES ligand/receptor interactions across the family, can lead selection and has been applied to hundreds also be used to direct the response. This talk will of mAbs using our Membrane Proteome Array of This talk will focus on different methods for the highlight our efforts to isolate antibodies that are 5,300 membrane proteins. Conformational epitopes analysis of antibody repertoires including RNA- and THERAPEUTICS & either highly specific or polyreactive, in order to better generate novel IP and mechanistic insights, and DNA-based methods in bulk populations as well as TECHNOLOGIES understand the implication of targeting one or more we have mapped >1,000 such epitopes with >95% single cell analysis. I will describe the strengths and members of the receptor family. success rate using our Shotgun Mutagenesis limitations of each method and which methods are platform. most useful for different types of research questions. 11:20 A Platform Enabling High-Throughput Sponsored by Sponsored by SPONSOR/EXHIBIT Functional Screening of Antibody Libraries 12:50 Luncheon Presentation II: 3:05 Rational Library Design for INFORMATION Ryan Kelly, PhD, Research Scientist, xCella Efficient Membrane Protein the Affinity Maturation of Biosciences Targeting Antibodies Discovery Antibodies HOTEL & TRAVEL INFORMATION We present a novel platform for rapid antibody Using Synthetic Antibody Libraries and CIS Richard Buick, PhD, CTO, Fusion Antibodies plc discovery based on cell binding and functional Display A case study will be shown for the affinity maturation REGISTRATION INFORMATION activity readouts. Our microcapillary array technology Guy Hermans, PhD, CSO, Isogenica Ltd. of an anti-Cathepsin S antibody by rational library allows us to screen antibody libraries, displayed on or Isogenica’s llamdA™ library is a highly diverse, fully design followed by molecular docking of variants in a REGISTER ONLINE! secreted by yeast and mammalian cells, using a wide synthetic VHH library. It can be used to discover step-wise combinatorial fashion. variety of assay formats. This proprietary hardware VHHs in phage display format, as well as through our PEGSummit.com and software platform combined with xEmplar™, proprietary CIS display selection process. In this talk, our human-inspired synthetic antibody library, have we will briefly discuss the benefits this library design enabled the isolation of antibodies against multiple brings and illustrate some of the unique benefits of clinically relevant targets. VHH technology over conventional antibodies. Also,

REGISTER at PEGSummit.com | 13 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ENGINEERING STREAM DISPLAY OF ANTIBODIES continued PARTICIPANTS Sponsored by REGISTER TODAY 3:20 Use of Mammalian Virus be regulatable. Large sequence freedom coupled Display to Select Antibodies with strong selection for each diversification process Specific for Complex Membrane Antigens provides flexibility for demand-driven regulation to COVER Ernest Smith, PhD, CSO, Senior VP, Research, Vaccinex, dynamically balance antigen recognition capacities Inc and associated autoimmune risks according to host needs. We use single B cell culture, antibody specificity CONFERENCE-AT-A-GLANCE We have developed a technology to enable direct testing, and deep Ig sequencing analysis to investigate incorporation of multipass membrane proteins such Ig tolerance filter porosity. SHORT COURSES as GPCRs and ion channels into the membrane of a mammalian virus. Antigen expressing virus can be 4:55 Going Directly from Sequence to Clone: TRAINING SEMINARS readily purified and used for antibody selection using Isolation of Antibodies after Identifying Them either vaccinia, phage or yeast display methods. This by NGS method is rapid, does not require any detergents or Fortunato Ferrara, PhD, Vice President, Specifica, Inc. ENGINEERING refolding, and can be applied to multiple cell types in order to maximize protein expression and to provide Going easily from sequence to clones presently properly folded protein that is necessary for antibody represents the primary bottleneck in the full selection. exploitation of next-generation sequencing (NGS) ONCOLOGY applied to in vitro antibody selection. We have 3:35 Refreshment Break in the Exhibit Hall with devised and tested a number of different methods Poster Viewing to generate antibody clones identified by NGS. This IMMUNOTHERAPY talk will describe the success we obtained with 4:25 Shaping of Primary Ig Repertoires the different methods, how effective they were to Duane R. Wesemann, MD, PhD, Principal Investigator, reach into the abundance rank, and the affinities and Assistant Professor of Medicine, Harvard Medical binding properties of antibodies derived at different EXPRESSION School; Associate Physician, Brigham and Women’s abundance depths. Hospital B cell immunoglobulin (Ig) repertoire composition 5:25 End of Display of Antibodies shapes immune responses. The generation of Ig 5:30 Registration for Dinner Short Courses ANALYTICAL diversity begins with Ig variable region exon assembly from gene segments, random inter-segment junction sequence diversity, and combinations of Ig heavy and Recommended Dinner Short Course* IMMUNOENICITY light chain. This generates vast preemptive sequence & BIOASSAYS freedom in early developing B lineage cell Ig genes SC11: Developability of Bispecific that can anticipate a great diversity of threats. This Antibodies: Formats and Applications freedom is met with large restrictions that ultimately *Separate registration required. Click here or see FUSIONS & define the naïve (i.e. preimmune) Ig repertoire. page 5 for course details. CONJUGATES Activation-induced somatic hypermutation (SHM), which further diversifies Ig V regions, is also met with strong selection that shapes Ig affinity maturation. THERAPEUTICS & While individual repertoire features, such as affinity for TECHNOLOGIES self and competition for foreign antigen, are known to drive selection, the selection filters themselves may

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REGISTER TODAY 20TH ANNUAL ENGINEERING ANTIBODIES COVER New Science and Technologies for the Discovery and Engineering of Next-Generation Biotherapeutics

CONFERENCE-AT-A-GLANCE April 10-11, 2019 SHORT COURSES The field of protein engineering is at an exciting point in its development, with new generations of therapeutic antibodies now progressing through development and TRAINING SEMINARS into the market, great advances in protein science and discovery technology and a body of clinical evidence that can be used to inform the development of safe, highly effective therapies for unmet medical needs. The PEGS Engineering Antibodies conference explores case examples of the most significant emerging technologies used by protein engineers working at the discovery and design stages to quickly and efficiently craft biotherapeutics directed at the most elusive targets and biological functions. ENGINEERING TUESDAY, APRIL 9 polyreactivity, affinity and repertoires on a single cell 10:15 Women in Science Speed Networking in level. We circumvented this issue by using single- the Exhibit Hall ONCOLOGY cell compartmentalization in droplet microfluidics Recommended Short Course* and characterized plasmablasts and plasma cells SC11: Developability of Bispecific following immunization or autoimmune antibody ARTIFICIAL INTELLIGENCE AND MACHINE LEARNING IN ANTIBODY IMMUNOTHERAPY Antibodies: Formats and Applications responses in mice and humans. *Separate registration required. Click here or see DISCOVERY page 5 for course details. 9:10 Microfluidic Technology to Identify and Isolate Antigen-Specific T Cells 10:55 Antibody Discovery and Engineering EXPRESSION Julie Brouchon, PhD, Postdoctoral Associate, Weitz Using Deep Learning WEDNESDAY, APRIL 10 Lab, Harvard University Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich, Switzerland Isolation of antigen-specific T cells is fundamental 7:15 am Registration and Morning Coffee Deep learning, as a part of a family of tools related ANALYTICAL to study autoimmune diseases and to develop immunotherapies. Unfortunately, these cells are to artificial intelligence, is an emerging field of information and computer science that uses large 7:25 - 8:25 PANEL DISCUSSION: Women in rare and cannot be easily identified by surface markers. We overcome these challenges by data sets to extract features and representations. IMMUNOENICITY Science – Inspired Professional and Personal Antibody discovery and engineering is reliant Stories compartmentalizing cells into microfluidic droplets & BIOASSAYS and performing a functional assay relying on T cell- on experimental platforms of high-throughput Moderator: Women in Bio, Boston Chapter target cell interaction and subsequent fluorescent expression and screening of libraries. Here, I will Panelists: detection of cytokine secretion. In one day, we can describe how we are applying deep learning to FUSIONS & Susan Richards, PhD, Presidential Scientific Fellow, augment the discovery and engineering of antibodies CONJUGATES screen several million cells to isolate live, antigen- Translational Medicine Early Development, Sanofi R&D specific T cells. by moving beyond experimental screening. Joanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune 9:40 High Throughput Antibody Discovery in 11:25 KEYNOTE PRESENTATION: THERAPEUTICS & Additional Panelists to be Announced the Digital Age TECHNOLOGIES Implementing Artificial Intelligence Jane Seagal, PhD, Principal Research Scientist, Global in Biotherapeutic Discovery and Biologics, AbbVie Development The constantly growing demand for novel therapeutic DEEP SEQUENCING AND B-CELL Philip Tagari, PhD, Vice President, Research, SPONSOR/EXHIBIT biologics drives technology innovation enabling Amgen INFORMATION CLONING IN ANTIBODY DISCOVERY efficient antibody discovery. Optimization and The very rapid “democratization” of machine 8:30 Chairperson’s Opening Remarks ‘digitalization’ of antibody discovery workflows is learning provides a broad range of opportunities HOTEL & TRAVEL INFORMATION Jane Seagal, PhD, Principal Research Scientist, Global essential for successful identification of antibodies in the complete lifecycle of therapeutics Biologics, AbbVie against challenging targets and the sampling diverse discovery and development. Strategies and REGISTRATION INFORMATION antibody repertoires. In this talk, automated platform examples will be discussed in molecule design 8:40 Antibody Affinity and Repertoires from technologies enabling both hybridoma and single and selection, manufacturability assessment, Single Antibody-Producing Cells B cell workflows are presented highlighting the REGISTER ONLINE! novel prognostic biomarkers, clinical trial design Pierre Bruhns, PhD, Professor, Antibodies in Therapy & integration of sequence information, screening data, and “beyond the medicine”. PEGSummit.com Pathology, Pasteur Institute, France and informatics for large panels of antibodies. The antibody response represents the circulating fraction of antibodies produced by plasma blasts 10:10 Coffee Break in the Exhibit Hall with and plasma cells. Weak to lack of expression of Poster Viewing membrane-bound antibody prevents conventional technologies to assess their antibody specificity/ REGISTER at PEGSummit.com | 15 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ENGINEERING STREAM ENGINEERING ANTIBODIES continued PARTICIPANTS

REGISTER TODAY 11:55 Machine Learning in Computational FAST AND NIMBLE ANTIBODY DISCOVERY 5:45 Networking Reception in the Exhibit Hall Biology to Accelerate Heterologous Protein AND DEVELOPMENT with Poster Viewing Production 2:10 Chairperson’s Remarks 7:00 End of Day COVER Elizabeth Brunk, PhD, Postdoctoral Research Fellow, Gregory C. Ippolito, PhD, Research Assistant Systems Biology Research Group, University of Professor, Molecular Biosciences, LIVESTRONG CONFERENCE-AT-A-GLANCE California, San Diego Cancer Institute, The University of Texas at Austin THURSDAY, APRIL 11 Standardized, multi-omics datasets are becoming SHORT COURSES increasingly available, but major impediments prevent 2:15 Lessons Learned on Rapid Discovery from 8:00 am Registration and Morning Coffee the realization of impact of big data resources. the DARPA Pandemic Prevention Platform (P3) TRAINING SEMINARS Modern machine learning methods bring the promise Gregory C. Ippolito, PhD, Research Assistant EMERGING TECHNOLOGIES IN ANTIBODY of leveraging large-scale omics data to make Professor, Molecular Biosciences, LIVESTRONG ENGINEERING accurate predictions. Here, I present recent efforts Cancer Institute, The University of Texas at Austin 8:30 Chairperson’s Remarks ENGINEERING on the development of appropriate in silico tools The DARPA P3 program is focused on the rapid and cross-disciplinary training resources, which are discovery, production, and delivery of antibody Christoph Spiess, PhD, Senior Scientist, Antibody paramount for further progress in big data science. countermeasures to halt infectious disease outbreaks Engineering, Genentech in 60 days or less. Four P3 performer teams were 12:25 pm Biologics by Design: Sponsored by 8:35 A Paradigm Shift: Moving from Traditional ONCOLOGY chosen to deploy distinct technologies for antibody Screening towards Data Driven Antibody Design Incorporating Physics-based discovery related to this effort. Lessons learned shall Methods into Prediction Models Kristin Brown, Director, Protein Design and be discussed. Informatics, GlaxoSmithKline for Protein Stability and Binding Affinity IMMUNOTHERAPY Machine learning, artificial intelligence, andin silico Eliud Oloo, PhD, Senior Principal Scientist, Schrödinger 2:45 Case Study of Antibody Discovery and Development from a Small and Nimble Biotech design are phrases that have had high visibility in the Combining experiment with physics-based news and scientific papers over the last few years. computational approaches and Machine Learning Abhishek Datta, PhD, Director, Antibody Discovery & EXPRESSION Engineering, Scholar Rock Effectively incorporating these techniques within is emerging as a promising strategy for advancing antibody discovery has the potential to transform how Since its inception 6 years ago, Scholar Rock has the discovery of biologic treatments, including we design antibodies. This transformation requires successfully executed multiple antibody drug monoclonal antibodies, vaccines, and enzyme a shift in how we design experiments to generate discovery campaigns, including one for its lead ANALYTICAL replacement therapies. To develop effective relevant data. I will be discussing different strategies antibody, SRK-015 that is currently in the clinic. In this statistical correlations and learned predictive models that enable this change in paradigm. applicable to the design and optimization of biologics, presentation, Scholar Rock discusses a case study IMMUNOENICITY it is important to take into account structure-based wherein the combination of an accelerated naïve 9:05 New High-Throughput Technologies to & BIOASSAYS features. Structural properties are however often discovery and optimization campaign, coupled with Design and Optimize Non-Antibody Scaffolds difficult and expensive to obtain by experiment. We development/availability of an in vivo model that Gabriel Rocklin, PhD, Assistant Professor, Department describe physics-based computational methods that enabled rapid pharmacodynamic read-out, led to the of Pharmacology & Center for Synthetic Biology, FUSIONS & narrow this gap by calculating properties derived successful identification of an antibody candidate. Northwestern University CONJUGATES from structure and simulation, thus complementing 3:15 Fast and Deep: Rapid High-Throughput Optimizing the therapeutic suitability of protein experimental measurements. Antibody Discovery from Deep Mining of scaffolds remains an unsolved challenge. We have developed a multiplexed mass spectrometry Sponsored by Natural Immune Repertoires THERAPEUTICS & 12:55 Luncheon Presentation I: approach to assay thousands of de novo designed TECHNOLOGIES Build Better Biologics with Kevin Heyries, PhD, Co-Founder, Business Development and Strategy Lead, AbCellera scaffolds for properties that are inaccessible to other Machine Learning and Synbio high-throughput techniques, including stability against AbCellera’s antibody discovery platform can Claes Gustafsson, PhD, CCO, Co-Founder, ATUM protein degradation and aggregation, the extent of screen millions of single antibody secreting cells SPONSOR/EXHIBIT conformational fluctuations, and the efficiency of This presentation will showcase how ATUM combines in less than a day using multistep and multiplexed INFORMATION intracellular delivery. Data from these large-scale recent developments in genome engineering, secretion assays and high-throughput imaging. assays enables us to optimize these properties in de automation, big data and product analytics to We will demonstrate how this technology is being novo scaffold design. HOTEL & TRAVEL INFORMATION increase efficiency of engineering and developability applied to rapid identification of antibodies from of biologics and cell lines. Cell lines generated using humans exposed to viral pathogens under the DARPA 9:35 Merck’s BRAIN – “Biologics Research REGISTRATION INFORMATION the LeapIn® transposase combined with optimized Pandemic Prevention Platform (P3) project and vector constructs, proprietary codon optimization All-in-One”: Building a Request System for how these capabilities can be applied to difficult Quality Control of Purified Proteins and QSAR-based protein engineering allow for an membrane protein targets. REGISTER ONLINE! information rich and efficient optimization of mAbs, Erin Williams, Associate Lab, Head, Quality Control, Protein Sciences - Quality Control, EMD Serono PEGSummit.com bispecifics, CAR-T molecules, and the increasingly 3:45 Refreshment Break in the Exhibit Hall with complex biologics approaching the market place. Poster Viewing We have established a global data and workflow platform at Merck for increasing the efficiency of our 1:55 Session Break 4:45 Problem-Solving Breakout Discussions antibody discovery, protein production, and quality

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REGISTER TODAY control processes. We share examples of how is a challenge for the successful and safe targeting the use of this platform has transformed our daily of T-cell dependent bispecific (TDB) antibodies. By research work, e.g., in organizing and performing fine-tuning the avidity driven binding to HER2, we COVER QC of produced proteins, including standard and engineered an anti-HER2/CD3 TDB that selectively bispecific antibodies, and how it supports discovery binds and kills HER2 overexpressing tumor cells CONFERENCE-AT-A-GLANCE and engineering groups using B-cell cloning workflows with high potency, while sparing cells with normal and engineering of (SEED) bispecific antibodies. expression levels. The underlying concept may SHORT COURSES expand to other targets and applications that require 10:05 Coffee Break in the Exhibit Hall with an improved therapeutic index. Poster Viewing TRAINING SEMINARS 12:05 pm Intratumoral Delivery and Retention OPTIMIZING ANTIBODY TARGETING AND of Cytokines and Agonist Antibodies SPECIFICITY K. Dane Wittrup, PhD, C.P. Dubbs Professor, Chemical ENGINEERING 11:05 Using Deep Sequencing Datasets to Engineering and Biological Engineering; Associate Director, Koch Institute for Integrative Cancer Tailor Specificity Research, Massachusetts Institute of Technology Tim Whitehead, Associate Professor, Department Despite broad efforts, delivery of immune agonistic ONCOLOGY Chemical and Biological Engineering, University of Colorado, Boulder payloads via systemic administration is plagued by poor therapeutic indices, due to extensive off- Next-generation sequencing has presented target exposure. We are examining the fundamental protein scientists with the ability to observe entire IMMUNOTHERAPY micropharmacokinetic issues involved in intratumoral populations of molecules before, during, and after a administration and find that bispecific constructs that high-throughput screen or selection for function. My are retained in particular subdomains of the tumor, as talk will present an overview of how we can leverage defined by extracellular matrix composition, can exert EXPRESSION this large amount of sequence-function information profound therapeutic effects while largely sparing to program antibody specificity in typical antibody from systemic exposure or toxicity. discovery workflows. I will also present on how ANALYTICAL we use NGS to mimic evolutionary landscapes of 12:35 End of Engineering Antibodies neutralizing, specific anti-Influenza antibodies. 11:35 Engineering of a T-Cell Dependent Recommended Short Course* IMMUNOENICITY Bispecific Antibody to Broaden the Therapeutic SC12: Design Strategies and Development & BIOASSAYS Index for Solid Tumors of ADCs Christoph Spiess, PhD, Senior Scientist, Antibody *Separate registration required. Click here or see page 5 for course details. FUSIONS & Engineering, Genentech CONJUGATES The lack of tumor-specific targets for solid tumors

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REGISTER TODAY 10TH ANNUAL ENGINEERING BISPECIFIC ANTIBODIES COVER Improving Therapeutic Properties for Oncology and Beyond

CONFERENCE-AT-A-GLANCE April 11-12, 2019 SHORT COURSES The world of bispecific strategies, formats and clinical results has been gearing up over the past several years. Now in its tenth year, the Engineering Bispecific Antibodies TRAINING SEMINARS conference was the first one in the community to address the vast challenges and exciting new engineering and manufacturing advances that are enabling the next generation of improved bispecific antibodies. Come see for yourself why this field is leading a transformation beyond oncology to many other areas of medicine.

ENGINEERING THURSDAY, APRIL 11 2:50 BBB Transport Vehicle (TV): A Novel 4:50 Tissue-Specific Delivery of Antibodies: Brain Delivery Platform Improving Efficacy by Putting Antibodies at the 12:00 pm Registration Mark Dennis, PhD, Fellow, Denali Therapeutics Site of Action ONCOLOGY 12:35 Luncheon in the Exhibit Hall with Poster The BBB Transport Vehicle (TV) enables the delivery Martin Jack Borrok, PhD, Scientist II, AstraZeneca Viewing of large molecule therapeutics to the brain for the Upon vascular administration, bio-therapeutics become treatment of neurological diseases. The TV platform broadly distributed throughout the body with only a IMMUNOTHERAPY BISPECIFICS FOR CNS AND contains an engineered Fc domain that binds the fraction of dosed drugs reaching the intended organ or COMPARTMENTAL DELIVERY transferrin receptor and utilizes receptor-mediated tissue target. By targeting existing transport systems transcytosis to cross the BBB. This platform can be in the lungs (and other organs), we can improve both 1:40 Chairperson’s Opening Remarks formatted for efficient delivery of both antibodies the delivery and efficacy of therapeutics that act within EXPRESSION Mahiuddin Ahmed, PhD, CSO, Y-mAbs Therapeutics (ATV) and enzymes (ETV) across the BBB. these tissues while concurrently reducing unintended interactions in tissues not being targeted. 1:50 Emerging Technologies for Delivery of 3:20 The Journey to ‘the’ Antibody: Sponsored by ANALYTICAL Biotherapeutics and Gene Therapy across the Accessing a Versatile Toolbox 5:20 End of Day Blood–Brain Barrier María González Pajuelo, CSO, 5:20 Registration for Dinner Short Courses Danica Stanimirovic, PhD, Research Director, FairJourney Biologics Translational Bioscience, National Research Council IMMUNOENICITY To maximize the possibility to select “the” antibody, Recommended Dinner Short Course* & BIOASSAYS Canada at FJB we have taken antibody discovery to an SC12: Design Strategies and Development 2:20 Co-Targeting Ephrin Receptor Tyrosine unprecedent level by creating a versatile toolbox that allows the selection by phage display of antibody of ADCs Kinases A2 and A3 in Cancer Stem Cells *Separate registration required. Click here or see FUSIONS & Reduces Growth of Recurrent Glioblastoma fragments of different species from large naïve and immune repertoires. Ultimately these fragments can page 5 for course details. CONJUGATES Sheila K. Singh, MD, PhD FRCS(C), Pediatric be engineered and converted to mono- and bi-specific Neurosurgeon, McMaster Children’s Hospital, Interim formats that are produced in CHO cells Division Head, Neurosurgery, Hamilton Health THERAPEUTICS & Sciences; Director, McMaster Surgeon Scientist FRIDAY, APRIL 12 TECHNOLOGIES 3:50 Networking Refreshment Break Program, Professor of Surgery, McMaster University; 8:00 am Morning Coffee Principal Investigator, Stem Cell and Cancer Research 4:20 T Cell Engineering to Overcome Tumor Institute, McMaster University; Senior Canada Heterogeneity and Microenvironment Research Chair in Human Cancer Stem Cell Biology, BISPECIFIC ANTIBODIES FOR SPONSOR/EXHIBIT Inhibition in Brain Tumors IMMUNOTHERAPY: SEEING CLINICAL INFORMATION Michael DeGroote Centre for Learning and Discovery Sujith K. Joseph, PhD, Scientist, Pediatrics Recurrent glioblastoma (rGBM) remains vastly Hematology-Oncology, Center for Cell and Gene RESULTS HOTEL & TRAVEL INFORMATION understudied with few biological targets for Therapy, Baylor College of Medicine 8:30 Chairperson’s Remarks therapeutic development. In our present study, we Successful T cell immunotherapy depends Ertan Eryilmaz, PhD, Senior Scientist, Takeda REGISTRATION INFORMATION identify that co-expression of EphA2 and EphA3 on overcoming tumor heterogeneity and functionally marks a potent glioblastoma stem cells microenvironment inhibition. Use of multivalent CAR 8:35 Blockade of Multiple Checkpoint (GSC) population in rGBM. We developed a EphA2/ T-cells demonstrate advantage when targeting highly Receptors with Bispecific DART® Molecules REGISTER ONLINE! EphA3 bispecific-antibody (BsAb) and demonstrate heterogeneous brain tumors. Additionally, grafting an Gundo Diedrich, PhD, Director, Antibody Engineering, PEGSummit.com that treatment with the BsAb reduces rGBM tumor intrinsic checkpoint reversal receptor (CPR) to CAR MacroGenics burden. Therefore, we present the development of T-cells can help them overcome the inhibitory effects Therapeutic blockade of immune checkpoint pathways rational therapeutic approaches against biologically of brain tumor microenvironment. with monoclonal antibodies has provided remarkable relevant targets in rGBM. anti-tumor activity, translating to a significant improvement in overall survival in subsets of cancer REGISTER at PEGSummit.com | 18 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ENGINEERING STREAM ENGINEERING BISPECIFIC ANTIBODIES continued PARTICIPANTS REGISTER TODAY patients. Dual blockade of checkpoint pathways with INFECTIOUS DISEASE APPLICATIONS ENGINEERED FCs IN BISPECIFICS: bispecific antibodies may further enhance clinical DRIVING DESIRED PK, ACUTE ACTIVITY benefits. The development of two bispecific DART 10:30 Chairperson’s Remarks molecules targeting PD-1 and LAG-3 (MGD013) or Ertan Eryilmaz, PhD, Senior Scientist, Takeda AND LONG-TERM BIOLOGICAL COVER CONSEQUENCES PD-1 and CTLA-4 (MGD019) will be presented. 10:35 Rational Design of a Trispecific Antibody CONFERENCE-AT-A-GLANCE 9:05 Tumor-Localized Activation of the Targeting the HIV-1 Env with Elevated Anti- 1:25 Chairperson’s Remarks Immune System Using Antibody-Anticalin® Viral Activity G. Jonah Rainey, PhD, Vice President, Antibody SHORT COURSES Fusion Proteins Zhi-Yong Yang, PhD, Director, Synthetic & Immune Therapeutics, Gritstone Oncology, Inc. Biology, Sanofi Marina Pavlidou, PhD, Project Leader, Discovery, Pieris 1:40 The Astonishing Diversity of Fc Domain TRAINING SEMINARS Pharmaceuticals We engineered trispecific antibodies that allow a single molecule to interact with three independent Functions and the Development of Novel Fc 4-1BB (CD137), a key costimulatory immunoreceptor, is Engineered IgG Variants a highly promising therapeutic target for the treatment HIV-1 envelope determinants. These trispecific Stylianos Bournazos, PhD, Research Assistant ENGINEERING of cancer. We utilized the Anticalin technology to antibodies exhibited higher potency and breadth than any single anti-HIV-1 antibody and showed protective Professor, Laboratory of Molecular Genetics and develop 4-1BB-bispecific fusion proteins for tumor- Immunology, Rockefeller University localized activation of the immune system to overcome efficacy in an animal model of HIV-1 infection. Trispecific antibodies thus constitute a platform to ONCOLOGY toxicity and efficacy limitations of current 4-1BB- 2:10 Engineering Fc of BiSAbs to Restore and targeting antibodies. We describe the characterization engage multiple therapeutic targets through a single Extend Half-Life of PRS-343, a 4-1BB/HER2-targeting bispecific, and protein and could be applicable for diverse diseases Clifford William Sachs, PhD, Director, Research and the in vitro and in vivo preclinical data supporting the including infections, cancer and autoimmunity. Development, Toxicology, AstraZeneca IMMUNOTHERAPY ongoing first-in-patient trial of this drug candidate. 11:05 Beyond Blinatumomab: Antiviral Activity A systematic evaluation of pharmacokinetics (PK) Beyond PRS-343, the versatility of the Anticalin of BiTE® Antibody Constructs Targeting HIV of Bispecific IgG scaffolds and parental monoclonal platform allows for the generation of a wide range of Johannes Brozy, PhD, Senior Associate Scientist, antibodies (mAbs) in cynomolgus monkeys identified bispecifics for localized T-cell activation, including a EXPRESSION BiTE® Technology, Amgen Research (Munich) GmbH sites of ScFv attachment and immunogenicity of high level of flexibility in molecular geometry and target parental mAbs as key determinants of PK. Across HIV is a chronic infection well controlled with the valency to optimize good drug-like properties and scaffolds, introduction of half-life extension mutations current cART. However, a cure for HIV is still lacking. superior efficacy of drug candidates generated within in the Fc portion of the BiS increased half-life by 2 to ANALYTICAL Here, we show in vitro and ex vivo data that a BiTE this therapeutic protein class. 5-fold. Collectively, these data identified structural antibody construct targeting HIV gp120 resulted in considerations and engineering approaches to 9:35 XPAT-T cell Engagers – A Sponsored by substantially reduced HIV replication. In addition, facilitate development of Bispecific IgG scaffolds. IMMUNOENICITY Novel Format to Mitigate the these BiTE antibody constructs display efficient killing & BIOASSAYS On-Target, Off-Tumor Problem of gp120-expressing cells and inhibited replication in 2:40 Modulating Functionality in Bispecifics – Volker Schellenberger, PhD, President and Chief ex vivo HIV-infected PBMCs or macrophages. Towards Better Therapeutics Technology Officer, Research & Discovery, Amunix 11:35 Human and Bispecific Antibodies as Martin Steegmaier, PhD, Head of Discovery, Large FUSIONS & Pharmaceuticals, Inc. Immunotherapies for Chikungunya Virus Molecule Research, Roche Pharma Research and Early CONJUGATES Amunix developed a novel format of highly-selective Development (pRED), Roche Innovation Center Munich Jonathan R. Lai, PhD, Professor, Department of bispecific T cell engagers based on our proprietary Biochemistry, Albert Einstein College of Medicine Therapeutic performance of recombinant antibodies XPAT platform (XTENylated Protease Activatable in relies on two independent mechanisms: antigen Chikungunya virus (CHIKV) is a widespread mosquito- THERAPEUTICS & Tumor). XTENylation provides long in vivo half-life recognition and Fc-mediated antibody effector borne alphavirus that causes a severe and persistent TECHNOLOGIES and universal masking applicable to any antibody. functions. Interaction of Fc-fragment with different arthralgia. We describe the use of single B-cell T cell activation is >10,000 fold reduced prior to FcR triggers antibody-dependent cellular cytotoxicity sorting to identify protective monoclonal antibodies local proteolysis in the tumor microenvironment. In and complement-dependent cytotoxicity and that target the two envelope glycoproteins, E1 and SPONSOR/EXHIBIT vivo studies in xenografts and non-human primates determines pharmacokinetic half-life. Engineered E2, from convalescent CHIKV patients. Viral escape INFORMATION demonstrate >100x improved therapeutic window hIgG Fc domains with completely abolished FcγR studies revealed the sites of susceptibility on both E1 relative to conventional T cell engagers such as BiTEs. and C1q interactions, and with unaffected FcRn and E2. This information was then used to engineer HOTEL & TRAVEL INFORMATION interactions and Fc stability have been previously novel bispecific antibodies that enable simultaneous 10:05 Networking Coffee Break described by us. The impact of antibody Fc targeting of multiple epitopes in a single agent. REGISTRATION INFORMATION engineering, however, goes beyond the modulation These antibodies have strong potential for use as of the affinity or functionally of the interaction with immunotherapies to prevent or treat CHIKV infection. various FcRs or the neonatal Fc receptor (FcRn). REGISTER ONLINE! 12:05 pm Presentation to be Announced Specifically in the context of bispecific antibody PEGSummit.com engineering, the Fc functionality needs to be matched 12:35 Luncheon Presentation (Sponsorship with the often-unique mode of action of the bispecific Opportunity Available) or Enjoy Lunch on Your Own therapeutic to provide a unique PK profile or to match 1:05 Networking Refreshment Break the requirement for effector function according

REGISTER at PEGSummit.com | 19 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ENGINEERING STREAM ENGINEERING BISPECIFIC ANTIBODIES continued PARTICIPANTS REGISTER TODAY to biological needs and safety requirements. Antagonistic antibodies can also be turned into agonists by switching the format and functionality of the Fc moiety. Examples of tailoring Fc functionality COVER will be given for bispecific molecules currently being developed for immunological, ophthalmological and CONFERENCE-AT-A-GLANCE neuroscience indications. SHORT COURSES 3:10 EAGLE, A Novel Bispecific-Like Platform and Immunomodulatory Strategy TRAINING SEMINARS James Broderick, MD, CEO and Founder, Palleon Pharmaceuticals Inc. Glyco-immune checkpoints have emerged as a ENGINEERING novel mechanism of immune regulation of both innate and adaptive immunity and cancer immune escape. We have developed a novel bispecific-like platform named EAGLE (Enzyme-Antibody Glyco- ONCOLOGY Ligand Editing) with robust anti-tumor efficacy (~50% complete regression) in syngeneic EMT6 tumor models as a monotherapy. Here we reported IMMUNOTHERAPY how different bispecific-like configurations impact biological activity, pharmacokinetics, and toxicity of EAGLEs preclinically. EXPRESSION 3:40 End of Conference

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TRAINING SEMINARS

ENGINEERING Antibodies for Advancing Antibody Therapeutics to the Clinic ONCOLOGY Cancer Therapy Antibody therapies are advancing to clinical development for cancer and results to date are extremely encouraging. The oncology stream IMMUNOTHERAPY will focus on identifying emerging targets, investigating novel Advancing Bispecific constructs including ADCs and bispecific antibodies, and highlighting EXPRESSION approaches for combination therapies. The Oncology stream will Antibodies and Combination explore the latest trends and comparing strategies and recent Therapy to the Clinic ANALYTICAL successes from discovery to preclinical and clinical development.

IMMUNOENICITY & BIOASSAYS Clinical Progress FUSIONS & CONJUGATES of Antibody-Drug Conjugates THERAPEUTICS & TECHNOLOGIES

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COVER 9TH ANNUAL

CONFERENCE-AT-A-GLANCE ANTIBODIES FOR CANCER THERAPY Driving Breakthrough Therapies SHORT COURSES April 8-9, 2019 TRAINING SEMINARS Antibodies have great specificity and potency to be directed against cancer. The latest wave of novel antibody designs leverages our current knowledge of the tumor microenvironment and immune cell populations and our understanding of biology for selective targeting. Don’t miss the Ninth Annual Antibodies for Cancer Therapy ENGINEERING conference for a meeting of the great thought leaders in the field to share creative ideas and advance clinical progress.

SUNDAY, APRIL 7 the tumor to be an in situ vaccine. In mice with two singular target has largely been explored. However, ONCOLOGY tumors of the same type, immunosuppression from advancements in our understanding of cancer, Recommended Short Course(s)* the distant tumor can be overcome by inhibition of immune biology, and protein/cellular engineering Treg cells. Clinical translation is being pursued. approaches begin to define what seemed like science SC2: Translational Biotherapeutic IMMUNOTHERAPY fiction only a few years ago. The spatial temporal Development Strategies Part 1: Discovery, 9:10 Role of HLA Antigen Presentation in coordination of modulating different biologies and Molecular Assessment and Early Stage Resistance to Immune Checkpoint Blockade cell types within emerging cancer immunotherapy will Development F. Stephen Hodi, MD, Professor, Medicine, Harvard be explored. EXPRESSION Medical School; Professor, Medical Oncology, Dana- SC7: Translational Biotherapeutic Farber Cancer Institute; Sharon Crowley Martin Chair, 10:10 Networking Coffee Break Development Strategies Part 2: Analytical Melanoma, Dana-Farber Cancer Institute and Clinical Considerations TARGETING B7/H3: COMPARISON OF ANALYTICAL Tumor mutational burden correlates with response *Separate registration required. Click here or see to immune checkpoint blockade in multiple solid DIFFERENT APPROACHES page 5 for course details. tumors, although in microsatellite-stable tumors 10:45 Chairperson’s Remarks this association is of uncertain clinical utility. Here Soldano Ferrone, MD, PhD, Division of Surgical IMMUNOENICITY we uniformly analyzed whole-exome sequencing Oncology, Surgery, Massachusetts General Hospital & BIOASSAYS MONDAY, APRIL 8 (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to 10:50 Genetic Alteration of the Bispecific 7:00 am Registration and Morning Coffee immune checkpoint therapy including radiographic Antibody Platform to Create Trispecific NK Cell FUSIONS & response across multiple cancer types to examine CONJUGATES OPENING KEYNOTE SESSION Engagers (TriKes) Targeting B7-H3 additional tumor genomic features that contribute to Daniel A. Vallera, PhD, Lion Scholar and Professor, 8:30 Chairperson’s Opening Remarks selective response. Our analyses identified genomic Director, Section on Molecular Cancer Therapeutics; correlates of response beyond mutational burden, THERAPEUTICS & Soldano Ferrone, MD, PhD, Division of Surgical Professor of Therapeutic Radiology, University of Oncology, Surgery, Massachusetts General Hospital including somatic events in individual driver genes, Minnesota Masonic Cancer Center TECHNOLOGIES certain global mutational signatures, and specific 8:40 Using Tumor Reactive mAb and IL2 to TriKEs are trispecific natural killer (NK) cell engagers HLA-restricted neoantigens. However, these features and novel immunotherapeutic drugs. A first- Sequentially Engage Innate and Adaptive Anti- were often interrelated, highlighting the complexity generation TriKE consisting of two antibody scFV SPONSOR/EXHIBIT Tumor Immunity of identifying genetic driver events that generate an fragments each recognizing NK cells and AML INFORMATION Paul M. Sondel, MD, PhD, Reed and Carolee Walker immunoresponsive tumor environment. This study cells was cross-linked with cytokine IL-15. Recently, Professor of Pediatrics, Human Oncology, and lays a path forward in analyzing large clinical cohorts TriKes have been vastly improved by conversion of Genetics, and Director of Research, UW Division of HOTEL & TRAVEL INFORMATION in an integrated and multifaceted manner to enhance the scFVs to camelid framework. We will discuss Pediatric Hematology, Oncology and BMT, UW Carbone the ability to discover clinically meaningful predictive xenograft studies of first generation TriKE, testing of REGISTRATION INFORMATION Cancer Center and American Family Children’s features of response to immune checkpoint Hospital, University of Wisconsin the improved camelid TriKE, and clinical batch status. blockade. We will also discuss TriKEs targeting B7-H3 for solid We are developing immunotherapy regimens to tumor therapy. REGISTER ONLINE! eliminate advanced-large immunologically “cold” 9:40 The Next Era of Cancer Therapeutics: PEGSummit.com tumors in immunocompetent mice. In some models, Defining Biologic Problems, Engineering 11:20 Past, Present and Future of Omburtamab local radiation therapy combined with intratumoral Solutions for the Treatment of B7H3(+) Tumors tumor-reactive mAb+IL2 can eradicate large Daniel Chen, MD, PhD, CMO, IGM Biosciences Mahiuddin Ahmed, PhD, CSO, Y-mAbs Therapeutics established tumors with T-cell memory, enabling The opportunity for therapeutics that turn on or off a Omburtamab is a murine IgG1 that is under clinical

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REGISTER TODAY investigation for compartmental radioimmunotherapy models, CD3e humanized models. TUESDAY, APRIL 9 of B7-H3(+) tumors. Omburtamab labeled with 131- Sponsored by 1:20 Luncheon Presentation II: 8:00 am Registration and Morning Coffee or 124-Iodine can be delivered directly into 1) the Robust and Reproducible Target- COVER brain ventricles for pediatric neuroblastoma patients Biology Based Bioassays for with CNS/leptomeningeal metastases, MESOTHELIN-TARGETED THERAPIES IN Characterization and Potency Measurement of SOLID TUMORS CONFERENCE-AT-A-GLANCE Biologics Targeting Checkpoint Modulators 2) the pons for diffuse intrinsic pontine glioma, and 8:25 Chairperson’s Remarks Jane Lamerdin, PhD, Director, Research & SHORT COURSES 3) the peritoneum for desmoplastic small round cell Mitchell Ho, PhD, Chief, Antibody Therapy Section, Development, Eurofins Pharma Discovery Services tumors. New versions of omburtamab (177-Lutetium Laboratory of Molecular Biology, National Cancer TRAINING SEMINARS conjugate and humanized sequence) are currently 1:50 Session Break Institute, NIH under pre-clinical development. 2:20 Problem-Solving Breakout Discussions 8:30 A Two-in-One Approach to Target 11:50 MGC018: A Duocarmycin-Based Solid Tumors – CAR T-Cells and Checkpoint ENGINEERING Antibody Drug Conjugate Targeting B7-H3 3:20 Networking Refreshment Break Blockade Deryk Loo, PhD, Director, Targeted Therapeutics and Prasad S. Adusumilli, MD, FACS FCCP, Deputy Chief Site Operations, MacroGenics, Inc. PLENARY KEYNOTE SESSION and Associate Attending, Thoracic Surgery; Director, ONCOLOGY MGC018 is an ADC comprised of the cleavable Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial linker-duocarmycin payload, valine-citrulline-seco 4:00 Chairperson’s Remarks DUocarmycin hydroxyBenzamide Azaindole (DUBA), Sloan-Kettering Cancer Center; Associate Professor, Rakesh Dixit, PhD, DABT, Vice President, R&D, conjugated to a humanized anti-B7-H3 antibody Cardiothoracic Surgery, Weill Cornell Medical Center IMMUNOTHERAPY Global Head, Biologics Safety Assessment, The presentation will focus on cell-intrinsic and through interchain disulfides. MGC018 demonstrated Translational Sciences, AstraZeneca antitumor activity in vivo toward B7-H3-expressing extrinsic methods in overcoming checkpoint tumor xenografts at clinically relevant doses. 4:10 Vision for How Immunotherapy Will blockade in cellular immunotherapy. EXPRESSION MGC018 was tolerated in cynomolgus monkeys Shape Future of Cancer Care 9:00 Immunotoxins Targeting Mesothelin for at exposure levels exceeding those required for Leena Gandhi, MD, PhD, Vice President, Immuno- Cancer Therapy antitumor activity. Our findings support clinical Oncology Medical Development, Lilly Oncology development of MGC018 to evaluate its potential as a Raffit Hassan, MD, Senior Investigator & Chief, ANALYTICAL Immunotherapy is considered by many as a Thoracic and GI Malignancies Branch, Center for therapeutic for B7-H3-expressing solid cancers. pillar of cancer care today, but in many ways we Cancer Research, National Cancer Institute, NIH 12:20 pm Streamlined Discovery Sponsored by have only scratched the surface. Our knowledge Mesothelin is a tumor differentiation antigen with IMMUNOENICITY and Production of Therapeutic and understanding of the complexities of limited expression on normal mesothelial cells but & BIOASSAYS Antibodies immunotherapy and its mechanisms continue is highly expressed in many cancers. LMB-100 is to evolve. The future of cancer care will be Meelis Kadaja, PhD, MBA, Director of Business an anti-mesothelin immunotoxin (anti-mesothelin Development, Icosagen Cell Factory defined by our ability to systematically identify Fab linked to PE toxin) currently in clinical trials and implement opportunities for combination FUSIONS & We take advantage of the universal HybriFree for treating patients with malignant mesothelioma therapy to improve and standardize patient CONJUGATES antibody discovery engine to efficiently discover and pancreatic cancer. Our efforts are focused response. therapeutic antibodies by direct cloning from B-cells on improving anti-tumor efficacy of LMB-100 of immunized rabbit, chicken, human, or dog. 4:55 The Lassa Virus Glycoprotein: by decreasing its immunogenicity as well as THERAPEUTICS & HybriFree method is further powered by our patented Stopping a Moving Target combination studies with chemotherapy and immune TECHNOLOGIES QMCF expression platform to produce high-quality Kathryn Hastie, PhD, Staff Scientist, Immunology checkpoint inhibitors. recombinant protein antigens and antibodies and Microbiology, The Scripps Research Institute 9:30 Pancreatic Cancer Therapy with cost-effectively for pre-clinical research (including Lassa virus causes ~5000 deaths from viral Mesothelin-Redirected Chimeric Antigen SPONSOR/EXHIBIT afucosylated antibodies for enhanced ADCC). hemorrhagic fever every year in West Africa. INFORMATION Technologies and case studies will be presented and The trimeric surface glycoprotein, termed Receptor T Cells and Overcoming Barriers to discussed. GPC, is critical for infection, is the target for their Efficacy Mark O’Hara, MD, GI Malignancy Oncologist, University HOTEL & TRAVEL INFORMATION Sponsored by neutralizing antibodies, and a major component 12:50 Luncheon Presentation I: of Pennsylvania Accelerating Antibody Candidate of vaccines. Structural analysis of Lassa GPC REGISTRATION INFORMATION bound to antibodies from human survivors Pancreatic ductal adenocarcinoma (PDA) is Discovery and Development with reveals a major Achilles heel for the virus and characterized by its highly immunosuppressive Innovative Humanized Mouse Models provides the needed template for development tumor microenvironment (TME) that limits T cell REGISTER ONLINE! Qingcong Lin, PhD, CEO, Biocytogen Boston Corp of immunotherapeutics and improved vaccines. infiltration and induces T cell hypofunction. Delivery PEGSummit.com The talk will present you Biocytogen services for of mesothelin-redirected chimeric antigen receptor T your antibody discovery with case study, from in vivo cell (meso-CAR T cell) therapy in pancreatic cancer efficacy and toxicity, to in vitro PD/PD analysis of 5:40 Welcome Reception in the Exhibit Hall patients has been feasibile and safe, and though your antibody candidates, using Biocytogen IO target with Poster Viewing some efficacy has been demonstrated, antitumor humanized mouse models, B-NDG based CART, and PBMC/CD34+ human immune reconstituted mouse 7:15 End of Day REGISTER at PEGSummit.com | 23 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ONCOLOGY STREAM ANTIBODIES FOR CANCER THERAPY continued PARTICIPANTS REGISTER TODAY activity remains modest. Our efforts are focused on Morbidity and mortality associated with pediatric the purpose of conventional HxL antibodies, results improving efficacy of meso-CAR T cells, including malignant primary brain tumors remain high in in extensive diversity focused in CDR regions, and the tumor-directed infusion of meso-CAR T cells, genome- the absence of effective therapies. Macrophage- other design, for the purpose of common light chain editing of CAR T cells, and combining meso-CAR T mediated phagocytosis of tumor cells via blockade of antibody development, results in minimal diversity COVER cells with an oncolytic adenovirus expressing TNF-α the anti-phagocytic CD47-SIRPα interaction using anti- across the entire V region and IL-2. CD47 antibodies has shown promise in preclinical CONFERENCE-AT-A-GLANCE xenografts of various human malignancies. We 1:20 Ice Cream Break in the 10:00 Coffee Break in the Exhibit Hall with demonstrate the effect of a humanized anti- Exhibit Hall with Poster Viewing SHORT COURSES Poster Viewing CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 EMERGING TARGETS TRAINING SEMINARS ADDRESSING DIFFICULT TARGETS: BCMA, medulloblastoma (primary and metastatic), atypical 2:00 Chairperson’s Remarks CLL1 & CD123 teratoid rhabdoid tumor, primitive neuroectodermal Mitchell Ho, PhD, Chief, Antibody Therapy Section, 10:45 Chairperson’s Remarks tumor, pediatric glioblastoma, and diffuse intrinsic Laboratory of Molecular Biology, National Cancer pontine glioma. Hu5F9-G4 demonstrated therapeutic ENGINEERING Horacio G. Nastri, PhD, Senior Director, Antibody Institute, NIH efficacyin vitro and in vivo in patient-derived Biotherapeutics, Incyte Corporation orthotopic xenograft models. Intraventricular 2:05 Anti-BCMA Recombinant Immunotoxins administration of Hu5F9-G4 further enhanced its Are Highly Active Agents for Myeloma Therapy ONCOLOGY 10:50 Preclinical Validation of B-Cell Maturation Antigen (BCMA) as a Target for activity against disseminated medulloblastoma Ira H. Pastan, MD, Co-Chief, Laboratory of Molecular leptomeningeal disease. Notably, Hu5F9-G4 showed Biology; NIH Distinguished Investigator; Head, T-Cell Immunotherapy of Multiple Myeloma Molecular Biology Section Dexiu Bu, MD, PhD, Investigator III, Exploratory minimal activity against normal human neural BCMA is highly expressed in myeloma cells and is an IMMUNOTHERAPY Immuno-Oncology, Novartis Institute for Biomedical cells in vitro and in vivo, a phenomenon reiterated Research in an immunocompetent allograft glioma model. excellent target for myeloma therapy. We produced mAbs that recognize BCMA, but not other family Chimeric antigen receptor (CAR) targeting BCMA is Thus, Hu5F9-G4 is a potentially safe and effective members, and used them to make RITs that kill an attractive approach for treating multiple myeloma. therapeutic agent for managing multiple pediatric EXPRESSION myeloma cell lines and patient cells. To evaluate anti- We screened a set of novel, fully human scFv binding central nervous system malignancies. tumor activity, we prepared H929 cells expressing domains to BCMA. Using a series of in vitro and Sponsored by 12:20 pm Luncheon Presentation I: luciferase. Untreated mice survived 40 days, whereas pre-clinical in vivo studies, we identified a scFv with ANALYTICAL Harbour Biomed’s Fully Human treated mice were tumor-free at 90 days. high specificity for BCMA and robust anti-myeloma Transgenic HCAb Mouse Technology Presents activity. This BCMA-specific CAR is currently being a Specialized Platform to Develop a New Class 2:35 Immune-Based Therapies in AML/MDS evaluated in a Phase Ib clinical study in relapsed and IMMUNOENICITY of Biologics as Therapeutics Against Cancer Naval G. Daver, MD, Associate Professor, Leukemia refractory MM patients. Department, MD Anderson Cancer Center & BIOASSAYS And Immunological Diseases 11:20 Tumor-Specific Carbohydrate Antigens Frank Grosveld, PhD, Founding CSO, Platform 3:05 Antibody Protein Sequencing Sponsored by as Preferable Targets for Novel Bispecific Technology, Harbour BioMed with Mass Spectrometry FUSIONS & Immunotherapeutics Targeting Solid Tumors HBM’s transgenic Harbour Mice™ were used to Mingjie Xie, CEO, Rapid Novor, Inc. CONJUGATES Anika Jäkel, PhD, Director, Preclinical Pharmacology & produce Heavy Chain Only Antibodies “HCAbs” Many applications in antibody Cancer Immunology, Glycotope GmbH wherein the mouse VH loci were replaced with engineering require the direct sequencing of antibody selected human VH genes, concurrent with the CH1 THERAPEUTICS & Carbohydrates on the surface of cancer cells represent proteins. At Rapid Novor (rapidnovor.com) we preferable targets for bispecifics due to their unique gene deletion. These refinements give us the flexibility have developed a robust workflow and routinely TECHNOLOGIES tumor-specificity with lack of inaccessibility on normal of designing multitude of single molecule formats sequenced antibody proteins. Here we share the tissues and broad indication coverage. We demonstrate capable of targeting one or more antigens molecule success experiences, examine common mistakes that carbohydrates are valuable targets for different driven by in vivo biology to develop the NextGen Tx. novices make, and present our practices to ensure the SPONSOR/EXHIBIT bispecific approaches by creating a carbohydrate- Here we present one such example of HBM4003, an correctness of every amino acid. INFORMATION targeted IL-15-based immunocytokine and a bispecific anti-cancer immunotherapy with high affinity and Sponsored by T-cell engager. Both molecules are able to stimulate an robust function, currently in preclinical development, 3:20 Next Generation of Antibody HOTEL & TRAVEL INFORMATION array of effector cell responses in vitro and in vivo and leading to potentially exceptional efficacy and safety Drugs with Long Lasting Efficacy are suitable agents for mono or combinatorial therapy of profile. Le Sun, PhD, CEO & President AbMax Biotechnology REGISTRATION INFORMATION solid tumors. Co., Ltd. 12:50 Luncheon Presentation II: Sponsored by In this presentation, we will show 1) the successful 11:50 Disrupting the CD47-SIRPα Anti- Alternative Strategies to Control REGISTER ONLINE! Phagocytic Axis by a Humanized Anti-CD47 development of Me-better by removing the strong Light Chain Diversity in Transgenic B-cell epitopes in the FRs of Humira; 2) the Antibody is an Efficacious Treatment for PEGSummit.com Chickens improvement of stability and great reduction of in vivo Malignant Pediatric and Adult Brain Tumors Kathryn Ching, PhD, Senior Scientist, Ligand ADA by engineering the Fc of Tecentriq’s with better Sharareh Gholamin, MD, PhD Candidate, Division of OmniChicken® V gene diversity in B cells can be biological activity. Biology and Biological Engineering, California Institute controlled through rational design of synthetic of Technology pseudogenes inserted into the Ig loci. One design, for REGISTER at PEGSummit.com | 24 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ONCOLOGY STREAM ANTIBODIES FOR CANCER THERAPY continued PARTICIPANTS REGISTER TODAY 3:35 Refreshment Break in the Exhibit Hall with checkpoint inhibitors might be overcome by Poster Viewing identifying additional checkpoint molecules that enable tumors to evade immune surveillance. EMERGING TARGETS (CONT.) CD47 is a ubiquitously expressed receptor for COVER Chairperson’s Remarks thrombospondin-1 and the counter-receptor for signal-regulatory protein-α. The latter interaction Mitchell Ho, PhD, Chief, Antibody Therapy Section, CONFERENCE-AT-A-GLANCE Laboratory of Molecular Biology, National Cancer prevents innate immune clearance of tumor cells Institute, NIH that express elevated levels of CD47. Preclinical and SHORT COURSES clinical development of antibodies and other methods 4:25 Development of Next Generation Immune for targeting CD47 will be discussed. TRAINING SEMINARS Modulators René Hoet, PhD, CSO, Imcheck Therapeutics 5:55 End of Antibodies for Cancer Therapy: Imcheck Therapeutics, an emerging biotech, develops Driving Breakthrough Therapies ENGINEERING antibodies to novel targets in immuno-oncology and 5:30 Registration for Dinner Short Courses potentially autoimmune diseases. The presentation will cover the progress of development of two first- Recommended Short Course* in-class therapeutic antibodies (an anti-BLTA and an ONCOLOGY SC10: CAR T-Cell Therapy for Solid Tumors anti-BTN3) that have a positive effect on proliferation *Separate registration required. Click here or see of gamma delta T cells and inhibition of tumor growth page 5 for course details. that are developed towards the clinic in 2020. In IMMUNOTHERAPY addition, the company identified an additional set of novel targets that are in the antibody validation stage for treatment in immune-oncology and potentially EXPRESSION autoimmunity. 4:55 Phase I CD123 CAR T Cell Trial in Adults with Relapsed/Refractory AML ANALYTICAL Elizabeth Budde, MD, PhD, Assistant Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope IMMUNOENICITY 5:25 Strategies and Challenges for Targeting & BIOASSAYS CD47 to Enhance Antitumor Immunity David D. Roberts, PhD, Senior Investigator, Head, Biochemical Pathology Section, Laboratory of FUSIONS & Pathology, CCR, NCI CONJUGATES The resistance of many cancers to current immune

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REGISTER TODAY 7TH ANNUAL ADVANCING BISPECIFIC ANTIBODIES AND COVER COMBINATION THERAPY TO THE CLINIC CONFERENCE-AT-A-GLANCE Creating the Killer Combo

SHORT COURSES April 10-11, 2019 TRAINING SEMINARS One of the leading areas of antibody research is bispecific antibodies. The Seventh Annual Advancing Bispecific Antibodies and Combination Therapy to the Clinic conference will review recent preclinical and clinical results on a variety of bispecific and multi-specific constructs. Thought leaders in the community will review ENGINEERING progress and discuss the best strategies for improving targeting, safety and efficacy for applications in immuno-oncology, oncology, CNS and infectious disease.

TUESDAY, APRIL 9 and OX40, designed as a next-generation CTLA-4 antibody with improved benefit-risk profile. The dual 10:15 Women in Science Speed Networking in ONCOLOGY targeting directs the effect to the tumor area, allowing the Exhibit Hall Recommended Short Course* ATOR-1015 to induce enhanced anti-tumor effects with expected lower systemic toxicity compared IMMUNOTHERAPY SC11: Developability of Bispecific to CTLA-4 monotherapy. The mode-of-action is 10:55 KEYNOTE PRESENTATION: The Antibodies: Formats and Applications a combination of effector T-cell activation and Need for More Effective Combination *Separate registration required. Click here or see regulatory T cell depletion. ATOR-1015 is planned to Therapies page 5 for course details. enter clinical phase in 2018. Ronald Herbst, PhD, Vice President and Head, EXPRESSION Oncology Research, AstraZeneca 9:10 Design Meets Biology – Engineering a Combination approaches are key to improving PD-1/CTLA-4 Bispecific Antibody to Improve clinical response. From preclinical immune- ANALYTICAL WEDNESDAY, APRIL 10 Both Safety and Efficacy oncology mouse models to patients enrolled in clinical trials, novel high throughput technologies 7:15 am Registration and Morning Coffee Yariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, AstraZeneca enable us to understand the mechanisms IMMUNOENICITY MEDI5752 is a monovalent bispecific IgG1 antibody underlying the complex interactions between the & BIOASSAYS 7:25 - 8:25 PANEL DISCUSSION: Women in (DuetMab), targeting the two clinically validated immune system and cancer, identify predictive Science – Inspired Professional and Personal receptors, PD-1 and CTLA-4. The bispecific antibody biomarkers for the patients who will most likely Stories introduces novel MOAs that may provide an improved benefit from current immunotherapies, avoid FUSIONS & Moderator: Women in Bio, Boston Chapter therapeutic index when compared to the two immune-related adverse events, and guide the CONJUGATES Panelists: monotherapies and mAb combinations. MEDI5752 future combination cancer immunotherapy. Susan Richards, PhD, Presidential Scientific Fellow, is currently being clinically evaluated for safety and Translational Medicine Early Development, Sanofi R&D efficacy. THERAPEUTICS & 11:25 Bispecific Antibodies for Cancer- Joanna Brewer, PhD, Vice President, Platform 9:40 A Versatile Modular Bispecific Antibody Directed Blockade of the PD-1/PD-L1 Immune TECHNOLOGIES Technologies, AdaptImmune Platform, BiXAb, for the Development of Checkpoint Additional Panelists to be Announced Innovative Therapeutics Prof. Dr. Wijnand Helfrich, Professor of Translational Surgical Oncology, Department of Surgery, University Eugene Zhukovsky, PhD, CSO, Biomunex SPONSOR/EXHIBIT Medical Center Groningen WHAT IS WORKING IN THE CLINIC: Pharmaceuticals INFORMATION On-target/off-tumor activity of current PD-L1-blocking BiXAb platform has a tetra-Fab IgG1 antibody NEW INNOVATIONS IN BISPECIFIC antibodies potentially reduces tumor accretion and structure and enables plug-and-play bispecific HOTEL & TRAVEL INFORMATION ANTIBODIES promotes autoimmune-related toxicity. Therefore, we antibody formatting from any pair of monospecific constructed human bispecific antibody (bsAb) PD- 8:30 Chairperson’s Opening Remarks mAbs. BiXAb antibodies possess excellent REGISTRATION INFORMATION L1xEGFR which simultaneously binds to PD-L1 and Rakesh Dixit, PhD, DABT, Vice President, R&D, Global manufacturability in CHO cells and superior drug-like EGFR resulting in enhanced avidity towards PD-L1+/ Head, Biologics Safety Assessment, Translational properties (stability, lack of aggregation, predictable EGFR+ cancer cells. Importantly, PD-L1xEGFR blocks REGISTER ONLINE! Sciences, AstraZeneca PK). We will illustrate the properties of this bispecific PD-1/PD-L1 interaction in an EGFR-directed manner, antibody platform by presenting two case studies, PEGSummit.com 8:40 Bringing the Tumor-Directed CTLA-4 x blocks oncogenic EGFR-signaling, and promotes in which BiXAbs target either solid tumors or OX40 Bispecific Antibody, ATOR-1015, into the ADCC of EGFR+ tumor cells. BsAb PD-L1xEGFR may hematological malignancies. Clinic be useful to enhance selectivity, efficacy and safety Charlotte Russell, MD, PhD, CMO, Alligator Bioscience AB 10:10 Coffee Break in the Exhibit Hall with of PD-1/PD-L1 checkpoint inhibition. ATOR-1015 is a bispecific antibody targeting CTLA-4 Poster Viewing REGISTER at PEGSummit.com | 26 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ONCOLOGY STREAM ADVANCING BISPECIFIC ANTIBODIES AND ACOMBINATION THERAPY TO THE CLINIC continued PARTICIPANTS

REGISTER TODAY 11:55 Development of Novel Fully Human discovery to IND application that aligns conformity and promising early clinical data in solid tumors. Bispecific Antibodies for Oncology to the regulations for applications to FDA/CFDA/ Favorable biophysical properties and high format Eric Smith, PhD, Director, Bispecifics, Regeneron EMA. Our scientists have in-depth understanding of flexibility enable T-cell engager formats that may COVER Pharmaceuticals industrial standards of biological drug discovery and address limitations of current engagers in the clinic, This presentation will describe Regeneron’s bispecific development. Mature development platform that such as tumor selectivity or antigen coverage. We CONFERENCE-AT-A-GLANCE platform and present pre-clinical data on several saves expenses and reduces operation risks. We offer have developed a flexible T-cell engager platform new bispecifics being developed for solid and liquid flexible collaboration modes to fulfill a wide spectrum based on Designed Ankyrin Repeat Proteins binding SHORT COURSES tumor indications. In addition, status updates on of customer needs. The World’s top pharmaceuticals to human CD3. The characterization of different Regeneron’s clinical stage bispecific antibodies and academic Institutes use GenScript`s discovery multispecific formats with tailored serum half-life will TRAINING SEMINARS (REGN1979, REGN4018, and REGN5458) will be services to accelerate basic and discovery research for be presented. target validation, lead generation, lead characterization presented. and optimization. Our proprietary technology platforms 3:15 Highlighted Poster Presentation: Efficient in vivo Tumor Clearance and Minimal Cytokine ENGINEERING 12:25 pm WuXiBody™, an Innovative Sponsored by in a variety of domains make us very competitive and Versatile Bispecific Antibody in the biologics space. In this talk, key discovery Release with a Novel T-Cell Engaging Bispecific Format Opens a New Era for services will be discussed, that includes hybridoma Antibody Platform Therapeutic Antibody Development and phage display therapeutic mAb generation Speaker to be Announced, TeneoBio Inc. ONCOLOGY Jing Li, Senior Vice President, Discovery, WuXi Biologics against multi-transmembrane proteins, capable of making any bispecific format like single-domain 3:45 Refreshment Break in the Exhibit Hall with Bispecific antibodies are a growing area of monoclonal antibody (SMAB) production, humanization, Poster Viewing biotherapeutics but with many development developability assessment and affinity maturation. At IMMUNOTHERAPY challenges. Many of the new platforms have 4:45 Problem-Solving Breakout Discussions GenScript Biologics, we pride ourselves on our flexible limitations in yield, purity, stability, solubility, half-life, options for you in drug discovery and development. 5:45 Networking Reception in the Exhibit Hall and immunogenicity. Thus, a one-size-fit-all solution with Poster Viewing EXPRESSION is still desired. Aiming to solve those issues, WuXi 1:55 Session Break Biologics has generated WuXiBodyTM, a flexible, 7:00 End of Day proprietary bispecific antibody format that can reduce WHAT IS WORKING IN THE CLINIC: the development time by 6 -18 months and can ANALYTICAL NEW INNOVATIONS IN BISPECIFIC THURSDAY, APRIL 11 decrease cost of goods by 90%. ANTIBODIES (CONT.) Sponsored by 8:00 am Registration and Morning Coffee 12:55 Luncheon Presentation I: 2:10 Chairperson’s Remarks IMMUNOENICITY CANscript™: A Phenotypic-Based, Rakesh Dixit, PhD, DABT, Vice President, R&D, Global BISPECIFIC ANTIBODIES OFF THE & BIOASSAYS Tumor Modeling Platform for Head, Biologics Safety Assessment, Translational Drug Discovery and Development Sciences, AstraZeneca BEATEN PATH: FUSIONS, NON-ANTIBODY Mark Paris, PhD, Associate Director, Translational SCAFFOLDS, ETC. FUSIONS & Application, Mitra Biotech 2:15 Preclinical and Clinical Development CONJUGATES of Best-in-Class Anti-HER2 Bispecifics and 8:30 Chairperson’s Remarks Delineation of an intra-tumor microenvironment in a Frank Comer, PhD, Senior Scientist, AstraZeneca dynamic spatio-temporal setting is required owing Bispecific ADCs to its clinical relevance in many cancer indications. Tony Polverino, PhD, Executive Vice President of Early 8:35 KEYNOTE PRESENTATION: Overview THERAPEUTICS & Majority of solid cancers represent a highly complex Development and CSO, Zymeworks, Inc. TECHNOLOGIES tumor microenvironment wherein a dysregulated ZW25 is a bispecific antibody directed against two of Bispecific Antibodies Roland Kontermann, PhD, Professor, Biomedical phenotypic context impacts treatment outcomes at a distinct epitopes (biparatopic) on HER2 that has Engineering, Institute of Cell Biology and personalized level. We have developed and validated been successfully engineered using the Azymetric™ Immunology, University of Stuttgart SPONSOR/EXHIBIT an ex-vivo platform technology (CANscript™) using IgG1 antibody scaffold. In clinical studies, ZW25 Bispecific antibodies have experienced a INFORMATION patient material (tumor, autologous ligands and is well tolerated and has demonstrated promising dramatic interest and growth for therapeutic immune cells) to predict tumor efficacy in the clinic single-agent anti-tumor activity in heavily pretreated applications, with more than 70 molecules HOTEL & TRAVEL INFORMATION across several drug classes. HER2-expressing breast, gastric, and other cancers. Preclinical development of ZW49, a biparatopic in clinical development, e.g. in oncology, Sponsored by immuno-oncology, but also for non-oncology REGISTRATION INFORMATION 1:25 Luncheon Presentation II: antibody-drug conjugate based on the unique design Design and Development of of ZW25 and armed with our proprietary ZymeLink™ applications. An overview will be given on the Innovative Bispecific Antibodies cytotoxic payload, will also be discussed. making of bispecific antibodies and the various therapeutic concepts and applications, e.g. for REGISTER ONLINE! Timothy Xia, PhD, Vice President, Biologic Discovery & Development, GenScript, Inc. 2:45 Development of a Novel T-Cell Engager dual targeting strategies, retargeting of immune PEGSummit.com effector cells, and substitution therapy by Liusong Yin, PhD, Director, Antibody Drug Discovery, Platform Based on DARPin® Molecules mimicking the function of natural proteins. GenScript, Inc. Sebastian Grimm, PhD, Senior Scientist, Lead Generation, Molecular Partners AG GenScript is the world leader in biotechnology and has 15 years of experience in discovery and development T-cell-engaging therapies have shown high services. Provides One-Stop solution, offering target therapeutic efficacy in hematological malignancies REGISTER at PEGSummit.com | 27 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ONCOLOGY STREAM ADVANCING BISPECIFIC ANTIBODIES AND ACOMBINATION THERAPY TO THE CLINIC continued PARTICIPANTS

REGISTER TODAY 9:05 M7824, a Novel Therapeutic Inhibiting 11:05 A Highly Efficacious Antibody Mixture 12:05 pm Oncolytic Vaccines to Augment BiTE PDL1 and Sequestering TGF-Beta against MET-Dependent Tumors Efficacy against Solid Tumors James L. Gulley, MD, PhD, FACP, Chief, Genitourinary Thomas Tuxen Poulsen, PhD, Principal Scientist, Christine E. Engeland, MD, PhD, Head of Laboratory, COVER Malignancies Branch, Head, Immunotherapy Group, Symphogen A/S Virotherapy, National Center for Tumor Diseases GMB Director, Medical Oncology Service, Center for Activation of the receptor tyrosine kinase MET is Challenges in treating solid tumors with bispecific CONFERENCE-AT-A-GLANCE Cancer Research, NCI, NIH associated with poor clinical outcome in certain antibodies include increasing response rates M7824 is a first-in-class bifunctional fusion protein cancers. To target MET more effectively, we and decreasing toxicity. We have developed SHORT COURSES composed of a TGFβ trap fused to an anti-PD-L1 developed the antagonistic antibody mixture Sym015 tumor-selective oncolytic vectors for delivery of antibody. A first-in-human dose escalation study consisting of two humanized antibodies directed immunomodulators to avoid systemic exposure TRAINING SEMINARS demonstrated safety, saturation of peripheral PD-L1 against non-overlapping epitopes of MET. Sym015 and mitigate toxicity. Furthermore, vector-mediated and sequestration of all released plasma TGFβ1, -β2, is well tolerated and strongly inhibits growth of MET- oncolysis serves as an in situ tumor vaccine, inducing and -β3 throughout the dosing period at doses >1 mg/ dependent preclinical tumor models. An ongoing synergistic anti-tumor immune responses. This talk ENGINEERING kg. M7824 1200 mg IV has been tested in multiple clinical trial of Sym015 demonstrates promising highlights the versatility of our vector system and cohorts including in HPV-associated cancers (ORR signals of clinical activity in a subset of MET- avenues for clinical translation. 35%) and NSCLC (ORR 28% with ORR 41% in patients dependent patients. with ≥1% of tumor cells PDL1+). 12:35 End of Advancing Bispecific Antibodies ONCOLOGY 11:35 Engineering Bispecific Antibodies for and Combination Therapy to the Clinic 9:35 Highlighted Poster Presentation: CB307, Specific Targeting of Tumor Cells a Novel T-Cell Costimulatory Humabody Rajkumar Ganesan, PhD, Director, Antibody Recommended Short Course* Therapeutic for PSMA-Positive Tumours Engineering, Janssen Biotherapeutics IMMUNOTHERAPY SC12: Design Strategies and Development Brian McGuinness, PhD, Senior Director, Business Bispecific antibodies can redirect immune cells such Development, Crescendo Biologics Ltd. of ADCs as natural killer cells or cytotoxic T cells to lyse tumor *Separate registration required. Click here or see 10:05 Coffee Break in the Exhibit Hall with cells by releasing the pro-apoptotic agents. Excessive page 5 for course details. EXPRESSION levels of released cytokines can lead to a series Poster Viewing of immune-related adverse events. To circumvent toxicity issues, we adopted several design strategies ANALYTICAL such as modulation of binding affinity, geometry and valency to engineer bispecifics antibodies to discriminate healthy versus tumor cells. IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES

THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION

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REGISTER TODAY 9TH ANNUAL CLINICAL PROGRESS OF ANTIBODY-DRUG CONJUGATES COVER Advancing Novel ADC Platforms and Combinations to the Clinic CONFERENCE-AT-A-GLANCE

SHORT COURSES April 11-12, 2019 Antibody-drug conjugates (ADCs) continue to emerge as a strong and promising strategy for target cancer therapy. Companies are leveraging on lessons learned TRAINING SEMINARS from first- and second-generation trials to inform on next-generation ADC designs. PEGS Boston’s Ninth Annual Clinical Progress of Antibody-Drug Conjugates invites investigators to share their latest results from preclinical and clinical trials, lessons learned to inform drug design & dosing, and strategies to improve safety, efficacy and patient outcomes. ENGINEERING

THURSDAY, APRIL 11 2:50 Developing Antibody-Drug Conjugates 4:50 POSTER HIGHLIGHT: as Targeted Conditioning Agents for Bone Exploring the Ever-Evolving Bioanalytical ONCOLOGY 12:00 pm Registration Marrow Transplant Strategy for ADCs from Discovery to the Clinic 12:35 Luncheon in the Exhibit Hall with Poster Charlotte McDonagh, PhD, Vice President, Head, Edit Tarcsa, PhD, Director, Drug Metabolism & Viewing Biotherapeutics, Magenta Therapeutics Pharmacokinetics, AbbVie IMMUNOTHERAPY Many diseases can be cured by a bone marrow ADCs are complex therapeutic modalities with the STRATEGIES TO INFORM DRUG DESIGN transplant. Prior to transplant, patients are possibility of forming multiple analytes in vivo. A wide & DOSING, AND IMPROVE PATIENT conditioned by removing their own bone marrow stem variety of assays and multiple analytical platforms EXPRESSION OUTCOMES cells using toxic, non-selective chemotherapy and had been utilized for their characterization. How do we radiation. Many patients suffer serious side effects, chose what is appropriate to support decision making 1:40 Chairperson’s Opening Remarks and others refuse a transplant. This presentation will at the various stages of a project and how does one Thomas Held, MBA, Vice President, ADC Task Force, highlight preclinical development of antibody-drug go by balancing speed, quality and available reagents. ANALYTICAL Daiichi Sankyo conjugates that may be safer, targeted agents for Since the key questions to answer during drug discovery patient preparation with the aim of extending the use (ADC optimization), versus late stage development 1:50 Single-Cell PK/PD of Antibody-Drug of curative bone marrow transplant and improving are usually very different, therefore the analytes and IMMUNOENICITY Conjugates and Immuno-Oncology Agents to patient outcomes. assays appropriate to answer those questions could & BIOASSAYS Design More Effective Therapies also be different. A few case studies and a bioanalytical Greg Thurber, PhD, Assistant Professor, Chemical 3:20 Development and Clinical Updates on decision tree will illustrate the issues. Engineering and Biomedical Engineering, University of Sacituzumab Govitecan FUSIONS & Michigan Robert Iannone, MD, MSCE, Head, R&D, CMO, 5:20 End of Day CONJUGATES Antibody-drug conjugates and checkpoint inhibitors Immunomedics 5:20 Registration for Dinner Short Courses are powerful agents in the treatment of cancer. However, the delivery and distribution of these agents 3:50 Networking Refreshment Break THERAPEUTICS & Recommended Dinner Short Course* in the tumor microenvironment is complex. We are IMPROVING THE SAFTEY AND EFFICACY TECHNOLOGIES using single-cell measurements within the tumor to SC12: Design Strategies and Development inform better decisions on drug design and dosing. OF ADCs of ADCs 4:20 Preclinical Study of Liver Injury Induced *Separate registration required. Click here or see 2:20 Chemo-Enzymatic Glycan Conjugation of SPONSOR/EXHIBIT by T-DM1: Molecular Mechanisms of T-DM1- page 5 for course details. Toxic Payloads: Clinical-Stage GlycoConnect™ INFORMATION Induced Hepatotoxicity ADCs Demonstrate Superior Therapeutic Index Wen Jin Wu, MD, PhD, Senior Investigator, OBP, CDER, Sander van Berkel, PhD, Director, R&D Operations, HOTEL & TRAVEL INFORMATION FDA FRIDAY, APRIL 12 Synaffix B.V. Hepatotoxicity is one of the serious adverse events The native glycan of monoclonal antibodies is 8:00 am Morning Coffee REGISTRATION INFORMATION associated with T-DM1. We show that T-DM1 is evolving as a privileged site to generate ADCs internalized upon binding to cell surface HER2, 8:30 Chairperson’s Remarks with a significantly improved therapeutic index, resulting in DM1-associated cytotoxicity, including Greg Thurber, PhD, Assistant Professor, Chemical REGISTER ONLINE! as corroborated by a multitude of studies in disorganized microtubules, nuclear fragmentation/ Engineering and Biomedical Engineering, University of rodents and NHPs. While the first clinical studies PEGSummit.com multiple nuclei, and cell growth inhibition. Based Michigan with a GlycoConnect™ ADC are now underway on our data, we propose that T-DM1-induced (NCT03700294), we will discuss how mAb glycan upregulation of TNFa enhances the liver injury that structure correlates with therapeutic index, as well may be initially caused by DM1-mediated intracellular as aspects of CMC supply chain and regulatory damage. In addition, a novel target that mediates considerations towards IND filing. T-DM1-induced hepatotoxicity will also be discussed. REGISTER at PEGSummit.com | 29 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ONCOLOGY STREAM CLINICAL PROGRESS OF ANTIBODY-DRUG CONJUGATES continued PARTICIPANTS

REGISTER TODAY 8:35 KEYNOTE PRESENTATION: CLINICAL DEVELOPMENT AND LESSONS 1:05 Networking Refreshment Break The House of Vedotins LEARNED 1:35 Chairperson’s Remarks Robert J. Lechleider, MD, Senior Vice President, 10:35 Amanitin-based Antibody-Drug- Maureen O’Connor-McCourt, PhD, CSO, Forbius COVER Clinical Research, Seattle Genetics Antibody-drug conjugates have proven effective Conjugates as New Therapeutic Modalities for Cancer Therapy NEXT-GENERATION ADCS CONFERENCE-AT-A-GLANCE in treating an array of cancers. Among the most active drug-linker combinations is monomethyl- George Badescu, PhD, VP Scientific Affairs, 1:40 Next-Generation ADCs: Considerations Heidelberg Pharma SHORT COURSES auristatin E (MMAE) coupled to a targeting and Examples antibody via a valine-citrulline linker. MMAE Antigen-Targeted Amanitin-Conjugates (ATACs) Marc Damelin, PhD, Executive Director, Head of represent a new class of ADCs using the payload TRAINING SEMINARS conjugates have shown activity in heme and Biology, Mersana Therapeutics, Inc. Amanitin. This payload introduces a novel mode solid tumors using a number of targeting I will discuss considerations for the discovery and of action into oncology therapy, the inhibition antibodies. The role and future of MMAE drug development of next-generation ADCs as informed of RNA polymerase II. The technology platform conjugates in the treatment of cancer will be by learnings from the field’s collective experience. ENGINEERING includes Amanitin supply, site-specific conjugation, discussed. Topics will include target selection, molecular design, demonstrated safety profile and biomarker. HDP-101 and preclinical pharmacology. is the first ATAC directed against BCMA entering ONCOLOGY PRECLINICAL UPDATES AND Phase I trials by the end of 2019. 2:10 Targeting CD74 with a Novel Antibody- PROOF-OF-CONCEPT 11:05 Targeting Breast Cancer with Antibody- Drug Conjugate, STRO-001 for Treatment of 9:05 A Novel Antibody-Drug Conjugate Drug Conjugates B-Cell Malignancies IMMUNOTHERAPY Targeting ADAM9-Expressing Solid Tumors Aditya Bardia, MD, MPH, Assistant Professor, Arturo Molina, MD, MS, FACP, CMO, Sutro Biopharma Demonstrates Potent Preclinical Activity Medicine, Harvard Medical School 2:40 Antibody-Drug Conjugates Targeting Stuart Hicks, PhD, Director, Pipeline R&D, ImmunoGen Chemotherapy is the mainstay of management of Tumor Stromal Cells EXPRESSION ADAM9 is a cell surface protein that belongs to the multiple solid tumors, but can be associated with Brad St. Croix, PhD, Head, Tumor Angiogenesis Unit, ADAM (a disintegrin and metalloproteinase) family considerable adverse effects. Conceptually, antibody- Mouse Cancer Genetics Program, National Cancer of proteases and is overexpressed in multiple solid drug conjugates can be utilized for targeted delivery Institute of toxic payloads to cancer cells. However, antigen ANALYTICAL tumor indications. IMGC936 is a novel ADAM9- Targeting the tumor stromal cells in addition to targeting ADC comprised of a high-affinity humanized selection of antigen and tumor heterogeneity are tumor cells with ADCs is a promising anti-cancer antibody site-specifically conjugated to DM21, a significant challenges in clinical development of novel strategy. CD276 and TEM8 are variably expressed next-generation linker-payload that combines a antibody-drug conjugates. In this presentation, we will IMMUNOENICITY in a variety of cancers and to different extents on maytansinoid microtubule-disrupting payload with review potential therapeutic strategies and the clinical tumor stromal cells and tumor cells. Both CD276- & BIOASSAYS a stable peptide linker. IMGC936 shows compelling development of antibody-drug conjugates in breast ADC-PBD and TEM8-ADC-MMAE eradicated large efficacy in ADAM9-positive xenograft models cancer. established tumors and metastases and improved FUSIONS & and was well-tolerated following repeat dosing in long-term overall survival in several different mouse cynomolgus monkeys making IMGC936 a promising 11:35 Discovery of Next-Generation ADCs: CONJUGATES Preclinical and Clinical Development of models of cancer. The mechanistic basis for the therapeutic candidate to target a wide range of efficacy of these agents will be discussed, along with ADAM9-expressing tumors. AVID100, an EGFR-Targeting ADC implications for other vascular-targeted ADCs Maureen O’Connor-McCourt, PhD, CSO, Forbius THERAPEUTICS & 9:35 CD163 as a Target for Directing ADCs to AVID100 is an EGFR-targeting ADC which was 3:10 Tisotumab Vedotin – A Novel Tissue TECHNOLOGIES Macrophages in Cancer and Inflammation – designed by screening a library of anti-EGFR ADCs Factor-Targeting Antibody-Drug Conjugate for Preclinical Proof of Concept against both tumor and normal cells expressing the Treatment of Advanced Solid Tumors Jonas Heilskov Graversen, PhD, Associate Professor, EGFR. This approach enabled us to identify AVID100, Jeffrey Harris, PhD, Associate Director, Translational SPONSOR/EXHIBIT Molecular Medicine, University of Southern Denmark which exhibited a very promising therapeutic index Research, Genmab INFORMATION We have validated the macrophage specific in preclinical studies. AVID100 recently completed Tisotumab vedotin (TV) is an antibody-drug conjugate internalization receptor CD163 as an ADC target in a successful phase 1 clinical program and a phase (ADC) that binds and interferes with tissue factor HOTEL & TRAVEL INFORMATION cancer and inflammation. PoC studies in mice, rats 2 study has been initiated. Importantly, only modest signaling, has potent anti-tumor activity in vitro and and pigs show a strongly reduced (50-fold) effective skin toxicity was observed, as predicted by our in vivo, and minimal effect on pro-coagulant activity. REGISTRATION INFORMATION dose for anti-inflammatory effect when targeting preclinical data. TV is efficiently internalized to the lysosome of the dexamethasone to macrophages (endotoxemia and 12:05 pm [Fam-] Trastuzumab Deruxtecan (DS cell, making it an optimal ADC. TV is currently being NASH models). In cancer we observe substantially tested in multiple clinical trials evaluating the safety, 8201) Clinical Development Update REGISTER ONLINE! increased infiltration of effector T-cells and T-cell tolerability, and anti-tumor activity in patients with PEGSummit.com dependent tumor regression in a murine anti-PD-1 Thomas Held, MBA, Vice President, ADC Task Force, previously treated and advanced metastatic solid Daiichi Sankyo resistant melanoma model when eradicating tumor tumors. associated macrophages by toxin targeting. 12:35 Luncheon Presentation (Sponsorship 3:40 End of Conference 10:05 Networking Coffee Break Opportunity Available) or Enjoy Lunch on Your Own REGISTER at PEGSummit.com | 30 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS REGISTER TODAY COVER IMMUNOTHERAPY STREAM CONFERENCE-AT-A-GLANCE

SHORT COURSES

TRAINING SEMINARS

ENGINEERING Developing Next-Generation Improving Immunotherapy Targeted Cancer Immunotherapies ONCOLOGY Efficacy and Safety The Immunotherapy stream focuses on the latest science, modalities and targeting strategies driving the development of immunotherapies IMMUNOTHERAPY for solid and liquid tumors. Part One examines strategies for CAR Ts, TCRs and TILs demonstrating T cell activity, combinations, preventing toxicology, EXPRESSION dosing, and targeting the tumor microenvironment. Part Two focuses on developing and engineering adoptive cell therapies for solid and ANALYTICAL liquid tumors, especially CAR Ts, TCRs, NKs, and TILs, as well as Agonist Immunotherapy new targets of interest. Finally, Part Three examines new clinical and Targets preclinical data in agonist immunotherapy targets, as well as the IMMUNOENICITY & BIOASSAYS biology and mechanisms of these emerging therapies of interest. Together, these three units will provide a focused look at how industry FUSIONS & is applying new science and technology in developing the next CONJUGATES generation of targeted cancer immunotherapies.

THERAPEUTICS & TECHNOLOGIES

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COVER 4TH ANNUAL

CONFERENCE-AT-A-GLANCE IMPROVING IMMUNOTHERAPY EFFICACY AND SAFETY Developing Targeted, Safe Immunotherapies SHORT COURSES April 8-9, 2019 TRAINING SEMINARS

Immunotherapies represent a step-change in cancer treatment, yet questions still remain around their efficacy, targeting and toxicity. Cambridge Healthtech Institute’s ENGINEERING Improving Immunotherapy Efficacy and Safety conference details the latest developments in immunotherapy, including established and emerging targets and modalities, new engineering strategies, combinations, biomarkers, effective preclinical models and strategies to mitigate toxicity and recent clinical developments. Examples will come from the world of checkpoint inhibitors, adoptive T cell therapy and combinations. We will also investigate manipulating the tumor microenvironment and emerging IO targets. ONCOLOGY SUNNDAY, APRIL 7 9:10 Development of Pegilodecakin, a 10:50 KEYNOTE PRESENTATION: PD-1 PEGylated IL-10 Antibodies Are Transforming Cancer IMMUNOTHERAPY Recommended Short Course(s)* Martin Oft, MD, Senior Vice President, Preclinical and Treatment Both as Mono and Combination Clinical R&D, ARmo Biosciences, a Wholly Owned SC2: Translational Biotherapeutic Therapy Subsidiary of Eli Lilly Roy Baynes, MD, PhD, Senior Vice President, Development Strategies Part 1: Discovery, EXPRESSION Global Clinical Development & CMO, Merck Molecular Assessment and Early Stage 9:40 A Multiantigen-Targeting Cytotoxic Research Labs Development CD4+ T Cell Approach for Treating B Cell Pembrolizumab was initially studied in a known Malignancies SC7: Translational Biotherapeutic immune responsive cancer – melanoma. A ANALYTICAL Baochun Zhang, MD, PhD, Assistant Professor of high response rate prompted exploration of Development Strategies Part 2: Analytical Medicine, Department of Medical Oncology, Dana- addressable malignancies. A big data enabled, and Clinical Considerations Farber Cancer Institute, Harvard Medical School biologically informed phase 2 screening IMMUNOENICITY *Separate registration required. Click here or see Many B-cell tumors lose MHC-I expression, allowing program was conducted across some 30 major page 5 for course details. & BIOASSAYS their escape from recognition by CD8+ cytotoxic malignancies. Monotherapy activity is being T-lymphocytes (CTLs). CD19-targeted chimeric progressively defined across lines of therapy antigen receptor (CAR)-T cell therapy bypasses the by tumor type and also in histology agnostic FUSIONS & MONDAY, APRIL 8 need of MHC-mediated recognition but produces biomarker informed populations. Precision CONJUGATES durable remissions in less than half of treated medicine tools have been used to explore 7:00 am Registration and Morning Coffee patients. Here, we present a novel approach potential resistance biology thereby informing for generating CD4+ CTLs for targeting B-cell combination therapy choices and development. THERAPEUTICS & EMPOWERING THE IMMUNE SYSTEM malignancies through a wide range of endogenous A number of effective combinations have TECHNOLOGIES 8:30 Chairperson’s Opening Remarks tumor antigens. already been identified. Michael Curran, PhD, Assistant Professor, Department 10:10 Networking Coffee Break of Immunology, MD Anderson Cancer Centre 11:20 Best-in-Class PD-1 Pathway Blockade SPONSOR/EXHIBIT ADVANCES IN CHECKPOINT INHIBITORS with Efficacy against Cold Tumors INFORMATION 8:40 Evolutionary Dynamics of the Immune AND IO COMBINATIONS Michael Curran, PhD, Assistant Professor, Department Response to Cancer: Implications for of Immunology, MD Anderson Cancer Centre Immunotherapy HOTEL & TRAVEL INFORMATION 10:45 Chairperson’s Remarks To address the therapeutic limitations of both PD-1 Brad Nelson, PhD, Co-Director, Immunotherapy Brad Nelson, PhD, Co-Director, Immunotherapy and PD-L1 blockade, we have developed novel, fully Program, BC Cancer Agency REGISTRATION INFORMATION Program, BC Cancer Agency human antibodies which block binding of both PD- Human cancers evolve over time and space and ligands to PD-1, as well as of PD-L1 to B7-1. The in under various selective pressures, resulting in a high vitro efficacy of these therapeutics equals or exceeds REGISTER ONLINE! degree of intratumoral heterogeneity (clonal diversity) that of pembrolizumab; however, when armed with PEGSummit.com within individual patients. Using ovarian cancer as an effector function in vivo, these antibodies can regress example, I will review our current understanding of both PD-1 sensitive “hot” and PD-1 resistant “cold” the mechanisms used by the human immune system syngeneic tumors. to contend with intratumoral heterogeneity and discuss immune-based strategies that might address this challenge in a clinically impactful way. REGISTER at PEGSummit.com | 32 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOTHERAPY STREAM IMPROVING IMMUNOTHERAPY EFFICACY AND SAFETY continued PARTICIPANTS

REGISTER TODAY 11:50 Third-Generation Immune Checkpoint PLENARY KEYNOTE SESSION The continuously proliferating NK-92® cell line Inhibitors and Development of AB154, a has been developed into an off-the-shelf, broadly cytotoxic NK cell therapeutic platform. aNK and Clinical-Stage TIGIT Antibody 4:00 Chairperson’s Remarks haNK® have completed Phase I studies, while HER2 COVER Joanne B.L. Tan, PhD, Research Fellow, Arcus Rakesh Dixit, PhD, DABT, Vice President, R&D, taNK® for glioma is currently accruing patients. Biosciences, Inc. Global Head, Biologics Safety Assessment, Further genetic modifications of the haNK platform CONFERENCE-AT-A-GLANCE TIGIT and DNAM-1 (CD226), expressed on Translational Sciences, AstraZeneca include additional CARs as well as homing receptors lymphocytes, compete for intra-tumoral ligand and molecules that can positively affect the tumor SHORT COURSES CD155. TIGIT induces immune suppression, whereas 4:10 Vision for How Immunotherapy Will microenvironment. DNAM-1 mediates immune activation. AB154 is a Shape Future of Cancer Care Leena Gandhi, MD, PhD, Vice President, Immuno-Oncology TRAINING SEMINARS sub-nanomolar TIGIT mAb that activates T and NK 9:00 Enhancing the Efficacy of T Cell-Based cell function, as shown in multiple in vitro assays. Medical Development, Lilly Oncology Immunotherapy is considered by many as a Immunotherapy Through Fucosylation A flow cytometry-based assay that quantifies TIGIT Gheath Al-Atrash, DO, PhD., Associate Professor of ENGINEERING occupancy by AB154 in blood is being utilized to pillar of cancer care today, but in many ways we have only scratched the surface. Our knowledge Medicine, Section of Transplant Immunology guide dose selection in the ongoing dose escalation Department of Stem Cell Transplantation and Cellular clinical study in cancer patients. and understanding of the complexities of immunotherapy and its mechanisms continue Therapy, The University of Texas MD Anderson Cancer ONCOLOGY 12:20 pm Industrializing IO Therapeutic to evolve. The future of cancer care will be Center Discovery Platforms: Multispecifics, defined by our ability to systematically identify The homing of adoptively transferred cytotoxic Engineered TCRs and CARs and implement opportunities for combination T lymphocytes (CTL) to tumor tissue is a major limiting factor to the efficacy of adoptive cellular IMMUNOTHERAPY Andrew Lynch, PhD, Scientific Consultant, Biologics, therapy to improve and standardize patient Genedata response. therapy (ACT) for cancer. This challenge may be overcome through fucosylation, a process whereby Novel classes of bio-molecules are currently 4:55 The Lassa Virus Glycoprotein: fucosyltransferases (FTs) add fucose groups to cell evaluated for their use in cancer immunotherapy. EXPRESSION Stopping a Moving Target surface glycoproteins. Ex vivo fucosylation enhances Bi- and multi-specific antibodies, Ab-cytokine Kathryn Hastie, PhD, Staff Scientist, Immunology CTL homing to malignant bone marrow and solid fusion proteins, non-Ig scaffolds, chimeric antigen and Microbiology, The Scripps Research Institute tumor tissue and appears promising in improving the receptors (CARs), engineered TCRs and TCR-based ANALYTICAL Lassa virus causes ~5000 deaths from viral efficacy of ACT. bispecific constructs promise significant advantages. hemorrhagic fever every year in West Africa. However, these highly engineered molecules pose The trimeric surface glycoprotein, termed 9:30 Dual-Switch CAR-NK Cells; Inducible and new challenges in design, engineering, cloning, GPC, is critical for infection, is the target for Targeted Anti-Tumor Efficacy with Safety IMMUNOENICITY expression, purification, and analytics. We present an neutralizing antibodies, and a major component J. Henri Bayle, PhD, Director of Molecular & BIOASSAYS infrastructure that addresses these challenges and of vaccines. Structural analysis of Lassa GPC Biology, Research and Development, Bellicum enables the industrialization of these various novel bound to antibodies from human survivors Pharmaceuticals therapeutic platforms. reveals a major Achilles heel for the virus and Natural Killer (NK) lymphocytes possess innate FUSIONS & anti-tumor activity useful as an allogeneic CAR cell CONJUGATES 12:50 Luncheon Presentation (Sponsorship provides the needed template for development Opportunity Available) or Enjoy Lunch on Your of immunotherapeutics and improved vaccines. therapy with reduced GvHD risk relative to alpha beta T cells. To overcome poor NK cell expansion Own in vivo, we utilized a molecular switch that relies THERAPEUTICS & 1:50 Session Break 5:40 Welcome Reception in the Exhibit Hall on rimiducid-directed dimerization of inducible TECHNOLOGIES with Poster Viewing MyD88/CD40 (iMC) to control cell proliferation and 2:20 Problem-Solving Breakout Discussions cytotoxicity in vitro and in vivo. Moreover, rapamycin- 7:15 End of Day 3:20 Networking Refreshment Break inducible Caspase-9 (iRC9) provided an orthogonally SPONSOR/EXHIBIT regulated safety switch. INFORMATION TUESDAY, APRIL 9 10:00 Coffee Break in the Exhibit Hall with HOTEL & TRAVEL INFORMATION 8:00 am Registration and Morning Coffee Poster Viewing

REGISTRATION INFORMATION NK CELLS, SWITCHABLE CAR Ts 8:25 Chairperson’s Remarks Saad J. Kenderian, PhD, Assistant Professor, Medicine REGISTER ONLINE! and Oncology, Mayo Clinic College of Medicine PEGSummit.com 8:30 NK Cells: Growing up to Become Safe and Efficacious Cellular Therapeutics? Hans Klingemann, MD, PhD, Vice President, Research and Development, NantKwest, Inc. REGISTER at PEGSummit.com | 33 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOTHERAPY STREAM IMPROVING IMMUNOTHERAPY EFFICACY AND SAFETY continued PARTICIPANTS

REGISTER TODAY MITIGATING CAR T TOXICITIES Human cell microarray screening enables the 3:05 UTG-4D; Developing the Most Sponsored by 10:45 Chairperson’s Remarks discovery of both primary cell surface receptors as Rapid Patient Tumor Model in vitro well as potential off-targets for a variety of biologics Kathleen McGinness, PhD, Senior Director, Platform Prabuddha Kundu, PhD, Co-Founder & including: peptides, antibodies, proteins, CAR T and COVER Technologies, Unum Therapeutics Managing Director, Premas Biotech Pvt Ltd other cell therapies. Case studies will demonstrate UTG-4D, universal tissueoid generator, is the most CONFERENCE-AT-A-GLANCE 10:50 Novel Strategies to Mitigate Toxicities the utility of the technology in identifying novel, rapid in vitro representation of the in vivo patient after Chimeric Antigen Receptor T Cell Therapy druggable targets as well as in specificity screening tumors. We have developed scaffolds for growing SHORT COURSES Saad J. Kenderian, PhD, Assistant Professor, Medicine for antibodies, scFvs and CAR T cells to aid safety patient samples or tumor cell lines, or cell lines and and Oncology, Mayo Clinic College of Medicine assessment and provide key data to support IND converting them into rapidly growing 3D tissueoid TRAINING SEMINARS Despite the impressive responses after chimeric submissions. models, which can be studied, dosed and therapeutic antigen receptor T (CAR T) cells in hematological 12:50 Luncheon Presentation II: (Sponsorship determination can be performed. Hundred’s of malignancies, their application is limited by the Opportunity Available) tissueoids have been grown with >90% success rates. ENGINEERING development of cytokine release syndrome (CRS). The model device scaffolds enable rapid growth, The lack of relevant preclinical models for CRS after 1:20 Ice Cream Break in the Exhibit Hall with within 24-48 hrs reproducibly. CAR T cell therapy is a significant limitation for the Poster Viewing development interventions to treat or prevent CRS. In 3:35 Refreshment Break in the ONCOLOGY this presentation, we will review relevant preclinical CAR T FOR SOLID TUMORS, NON-VIRAL Exhibit Hall with Poster Viewing models of human CRS after CART cell therapy and GENOME TARGETING 4:25 Reprogramming Human T Cell Function efforts to develop and optimize preventative strategies. and Specificity with Non-Viral Genome IMMUNOTHERAPY 2:00 Chairperson’s Remarks 11:20 The Myeloid System in Cytokine Release Daniel J. Powell Jr., PhD, Associate Professor of Targeting Syndrome Pathology and Laboratory Medicine, University of Theodore Roth, MD, PhD Student, Department of Theodoros Giavridis, PhD, Center for Cell Engineering, Pennsylvania Microbiology and Immunology, University of California EXPRESSION Cellular therapies using human T cells are opening Memorial Sloan Kettering Cancer Center 2:05 Development of CAR-T Cell Therapeutics We recently described the first mouse model for new chapters in cancer and autoimmune disease for Solid Tumor therapy. These living drugs can be genetically Cytokine Release Syndrome (CRS) elicited by Zonghai Li, PhD, CSO, CARSgen anti-CD19 CAR T cell therapy, which recapitulates engineered to acquire new therapeutic functions. ANALYTICAL Great success has been made in CAR-T cell multiple aspects of clinical CRS. In this model we However, current methods to insert new genetic therapeutics for the treatment of blood cancer established that CRS is the result of a tripartite material into human T cells require viral vectors, such as acute lymphoblastic leukemia while rare interaction between CAR T cells, macrophages and slowing research and hindering therapeutic IMMUNOENICITY improvement has been made for solid tumor the tumor microenvironment. Novel insights into the development. We have developed a non-viral & BIOASSAYS treatment. In this talk, we will summarize the current interplay between the actors of CRS will inform future methodology for the targeted integration of large DNA global progress of CAR-T cell therapeutics for solid considerations for CAR T cell therapy. sequences in human T cells that has enabled rapid tumor and share the thoughts and strategies of therapeutic reprogramming of T cell function and FUSIONS & CARsgen to develop CAR-T cell therapeutics for the CONJUGATES 11:50 Next Generation Approaches for specificity. Increased Safety and Efficacy of CAR T Cells treatment of solid tumor. 4:55 Cell Therapies for HIV Daniel J. Powell Jr., PhD, Associate Professor of 2:35 Bolt-On Transgenes Improve Engineered T Conrad Russel Cruz, PhD, Director, Translational THERAPEUTICS & Pathology and Laboratory Medicine, University of Pennsylvania Cell Function in Solid Tumor Research Laboratories, Center for Emerging TECHNOLOGIES Kathleen McGinness, PhD, Senior Director, Platform Technologies in Immune Cell Therapy, Children’s T cells engineered to express chimeric antigen Technologies, Unum Therapeutics National Hospital receptors can mediate durable cancer regression in some patients with certain forms of cancer but safety The immunosuppressive features within solid 5:25 End of Improving Immunotherapy Safety SPONSOR/EXHIBIT and durability issues exist and the lack of efficacy in tumors present unique challenges to the and Efficacy Program INFORMATION other cancer types is yet to be resolved. I will discuss success of engineered T cell therapies. We have the use of modified CAR T cells approaches that employed a “bolt-on” strategy to overcome key 5:30 Registration for Dinner Short Courses HOTEL & TRAVEL INFORMATION allow for quantitative and qualitative control of T cell immunosuppressive mechanisms by co-expressing activity to address safety concerns, as well as the over 100 different novel transgenes in T cells bearing Recommended Short Course* REGISTRATION INFORMATION provision of accessory molecules that either boost chimeric receptors. We have identified several SC10: CAR T-Cell Therapy for Solid bolt-on transgenes that modulate T cell metabolism efficacy or limit CAR-associated toxicities. Tumors or costimulation and impart enhanced function to REGISTER ONLINE! *Separate registration required. Click here or see 12:20 pm Luncheon Presentation I: Sponsored by chimeric receptor T cells in preclinical models of solid page 5 for course details. tumor malignancies. PEGSummit.com Target Specificity Screening of CAR T Cells Using Human Cell Microarray Technology Alex Kelly, US Business Development Manager, Retrogenix Limited REGISTER at PEGSummit.com | 34 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOTHERAPY STREAM PARTICIPANTS

REGISTER TODAY 6TH ANNUAL CAR Ts, TCRs AND TILs COVER Latest Innovations and Developments in Adoptive Cell Therapy CONFERENCE-AT-A-GLANCE

SHORT COURSES April 10-11, 2019

TRAINING SEMINARS Novel gene editing technologies and a greater understanding of cancer biology could unleash the full power of CAR T in both blood and solid tumors. But which therapies will succeed? Cambridge Healthtech Institute’s Sixth Annual CAR Ts, TCRs and TILs conference focuses on the latest research, protein engineering and clinical strategies driving the development of adoptive cell therapies across a wide range of indications. Clinical progress with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), ENGINEERING Tumor Infiltrating Lymphocytes (TIL), and NK cells will be addressed as well as new strategies for commercialization will be reviewed.

to mechanistic aspects related to treatment TUESDAY, APRIL 9 10:15 Women in Science Speed Networking in ONCOLOGY success or failure, essential to advance next- generation therapies. In this presentation, we the Exhibit Hall Recommended Short Course* cover factors influencing clinical outcomes: SC10: CAR T-Cell Therapy for Solid product T cell fitness, integrating the 10:55 Targeting TCR-β Constant Domain for IMMUNOTHERAPY Tumors number and polyfunctionality of specialized Immunotherapy of T Cell Malignancies *Separate registration required, please see page T cell subsets, tumor burden and immune Shimobi Onuoha, PhD, Head, Protein Engineering, 5 for course details. microenvironment, and biological aspects Autolus EXPRESSION intrinsic to the cancerous process. Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. We report a new targeting strategy WEDNESDAY, APRIL 10 9:10 Resistance to CART19 Therapy: based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 ANALYTICAL 7:15 am Registration and Morning Coffee Mechanisms and Novel Therapeutic Strategies Marco Ruella, MD, Clinical Instructor, Associate (TRBC1 and TRBC2). Unlike nonselective approaches Director, Dr. June’s Laboratory, Center for Cellular targeting the entire T cell population, TRBC-targeted 7:25 - 8:25 PANEL DISCUSSION: Women in Immunotherapies, Perelman School of Medicine, immunotherapy could eradicate a T cell malignancy IMMUNOENICITY Science – Inspired Professional and Personal University of Pennsylvania while preserving sufficient normal T cells to maintain & BIOASSAYS Stories Chimeric Antigen Receptor T cell (CAR T) have cellular immunity. Moderator: Women in Bio, Boston Chapter generated impressive clinical results for CD19+ B OFF-THE-SHELF CAR Ts FUSIONS & Panelists: cell leukemia and lymphoma. However, a significant CONJUGATES Susan Richards, PhD, Presidential Scientific Fellow, subset of patients still does not respond or eventually Translational Medicine Early Development, Sanofi R&D relapses. I will discuss the mechanisms of resistance 11:25 FEATURED PRESENTATION: Joanna Brewer, PhD, Vice President, Platform to CART19 and present future developments. Allogeneic CAR T: The Next Revolution in Cell Therapy THERAPEUTICS & Technologies, AdaptImmune 9:40 Novel Targets and Technologies for CAR TECHNOLOGIES Additional Panelists to be Announced Barbra Sasu, PhD, CSO, Allogene T Cells in Multiple Myeloma and Acute Myeloid While allogeneic CAR T research is at an earlier Leukemia stage, encouraging Phase 1 clinical data CAR T MECHANISMS, RESISTANCE AND Michael Hudecek, PhD, Program Leader, Max Eder demonstrates the promise of this therapy for SPONSOR/EXHIBIT NOVEL TARGETS Research Group‚ CAR T-Cell Engineering, Department more patients. The talk will highlight the clinical INFORMATION of Medicine II, University of Hudecek data available to date and the overall research 8:30 Chairperson’s Opening Remarks Translational research in CAR T cell immunotherapy strategy to develop a pipeline of allogeneic CAR HOTEL & TRAVEL INFORMATION Bob Valamehr, PhD, Chief Development Officer, Fate involves a rapidly increasing portfolio of novel target T therapies across a range of hematological and Therapeutics antigens, CAR designs, and technologies to enhance solid tumor indications. REGISTRATION INFORMATION safety, efficacy and physician control. This talk will 8:40 KEYNOTE PRESENTATION: review the latest developments from our program Mechanisms of CAR Treatment Success including novel targets in hematology and oncology, 11:55 Gene Edited Off-the-Shelf REGISTER ONLINE! and Failure Based on Clinical Experience and novel technologies for high-throughput screening, Immunotherapies PEGSummit.com in Lymphoma and Leukemia ultra-fast manufacturing, and real-time control over Andre Choulika., PhD., Chairman & CEO, Cellectis Adrian Bot, PhD, Vice President, Translational CAR T cells after administration in vivo. Sciences, Kite Pharma, a Gilead Company As CAR T cell therapy is now standard of care 10:10 Coffee Break in the Exhibit Hall with in certain B cell malignancies, novel data point Poster Viewing REGISTER at PEGSummit.com | 35 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOTHERAPY STREAM CAR Ts, TCRs AND TILs continued PARTICIPANTS

REGISTER TODAY 12:25 pm The Functional Capacity Sponsored by OFF-THE-SHELF CAR Ts (CONT.) identifying neoepitopes and tumor-associated of Immune Cells Predicts Clinical 2:10 Chairperson’s Remarks antigens provide new targets for cancer diagnostics and enable the tracking of patient responses to Outcome Across IO Therapies Adrian Bot, PhD, Vice President, Translational treatment. ProImmune provides industry-leading COVER Will Singleterry, PhD, Director, Business Development, Sciences, Kite Pharma, a Gilead Company IsoPlexis tools for antigen characterization, epitope mapping and immune monitoring. In this presentation, case CONFERENCE-AT-A-GLANCE Using single cell proteomics to measure the 2:15 Rejection-Resistant T Cell Platform for an studies will be shared that detail how ProImmune’s functional capacity or ‘fitness’ of immune cells Off-the-Shelf Therapy integrated platform has identified novel epitopes in SHORT COURSES has correlated with and been predictive of clinical Maksim Mamonkin, PhD, Instructor, Center for Cell the immune-oncology field. outcome in CAR-T, TIL, Cancer Vaccine and and Gene Therapy, Baylor College of Medicine TRAINING SEMINARS Checkpoint Inhibitor therapy. This talk will review ‘Off-the-shelf’ (OTS) T cell products pre-manufactured 3:45 Refreshment Break in the Exhibit Hall several of these data sets and discuss applications of from healthy donors are readily available and less with Poster Viewing IsoPlexis’ single cell technology. costly than autologous products, offering similar therapeutic potency. However, immune rejection by 4:45 Problem-Solving Breakout Discussions ENGINEERING Sponsored by 12:40 Mammalian Display host T- and NK-cells may limit the persistence of OTS Antibody Discovery for Integral cells and compromise their anti-tumor activity. We 5:45 Networking Reception in the Exhibit Hall Membrane Proteins engineered alloimmune defense receptors (ADRs) with Poster Viewing ONCOLOGY Nathan Robertson, PhD, Antibodies, Oxford Genetics that enable OTS T cells to recognize and eliminate 7:00 End of Day Through co-expression of integral membrane targets alloreactive lymphocytes resulting in complete and scFv molecule libraries in a mammalian cells protection from immune rejection while retaining full IMMUNOTHERAPY we show that cells that exhibit self-labelling can functionality. be purified and lead molecules identified via NGS 2:45 Translation of Pluripotent Cell-Derived T analysis. Lead candidates are then suitable for either CAR-T or antibody reformatting. and NK Cells as a Cornerstone Approach for EXPRESSION Off-the-Shelf Cancer Immunotherapy 12:55 Luncheon Presentation I: Sponsored by Bob Valamehr, PhD, Chief Development Officer, Fate Genetically Modified Cell Lines Therapeutics ANALYTICAL for Immuno-Oncology Cell-Based Pluripotent cell technology represents a powerful Assay Development approach to make cell-based immunotherapies Stacey Ward, PhD, Senior Research & Development available to a wide range of patients through the IMMUNOENICITY Scientist, Cell Design Studio, MilliporeSigma generation of a consistent and renewable “off-the- shelf” source of cellular therapeutics. I will discuss & BIOASSAYS MilliporeSigma’s Cell Design Studio™ cell line our progress towards developing unique and effective engineering service offering is the premier research strategies to create a renewable source of genetically partner for generating customized cell-based assays engineered “off-the-shelf” T and NK cells with FUSIONS & and immunotherapy research models. Our team has augmented function. Updates on IND filings and FIH CONJUGATES generated new monoallelic HLA panel expression progress will also be given. cell lines and tumor-associated antigen panels, which express individual tumor antigens at varying levels in 3:15 Epitope Identification and Sponsored by THERAPEUTICS & biologically-relevant cell lines. In this presentation, we TECHNOLOGIES Clinical Immune Monitoring in will discuss the breadth of these lines and discuss Gene Therapy and Immune their utility in immuno-oncology and therapeutic Oncology Programs testing. Emilee Knowlton, PhD, Immunology, Sales Specialist, SPONSOR/EXHIBIT Sales, ProImmune, Inc. INFORMATION 1:25 Luncheon Presentation II (Sponsorship Opportunity Available) Epitope discovery is a crucial element in the HOTEL & TRAVEL INFORMATION development of vaccine candidates and drug 1:55 Session Break therapeutics. In the Immune-oncology space, REGISTRATION INFORMATION

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REGISTER TODAY 11:35 Tumor Infiltrating Lymphocytes Therapy for Solid Tumors THURSDAY, APRIL 11 Chantale Bernatchez, PhD, Assistant Professor, COVER Department of Melanoma Medical Oncology - 8:00 am Registration and Morning Coffee Research, Division of Cancer Medicine, The University CONFERENCE-AT-A-GLANCE of Texas MD Anderson Cancer Center CAR NK CELLS, TCRs AND TILs In TIL therapy T cells are grown from solid tumor SHORT COURSES samples and expanded to large numbers ex vivo to 8:30 Chairperson’s Remarks be infused back to the patient. The therapy has been Adrian Bot, PhD, Vice President, Translational very successful in metastatic melanoma with a 42% TRAINING SEMINARS Sciences, Kite Pharma, a Gilead Company clinical response rate at our institution and others 8:35 Combining Innate and Adaptive Immunity: with most of the responses being durable. Despite ENGINEERING NK Receptors for CAR T Cell Therapy great results we are at this point investigating why the Simon Bornschein, PhD, Scientist, Celyad other half of the patients would not respond. Through molecular and immunological assays we are trying The success of CAR T therapy against B-cell to define biomarkers that could predict response to malignancies generated high expectations for all therapy. Another focus of our research is to test the ONCOLOGY cancers, but the target remains the challenge. NKG2D efficacy of TIL therapy in other solid tumor types. binds to 8 different ligands present on a broad range of tumors yet largely absent on healthy tissue 12:05 pm Advancements in Tumor Infiltrating IMMUNOTHERAPY indicating a potential breadth of applicability of the Lymphocytes in Treatment of Solid Tumors approach. Our approache to exploring the therapeutic Kelly DiTrapani, VP, Medical Affairs, Iovance power of NKG2D CAR T cells in the autologous Biotherapeutics (CYAD-01) and allogeneic (CYAD-101) setting will be EXPRESSION Iovance is developing TIL, a one-time cell therapy discussed. treatment that leverages and enhances the body’s 9:05 Gene Editing of Stem Cells for Universal natural defenses against certain solid tumors. ANALYTICAL SPEAR T-Cell Therapy TIL is being investigated in several multi-center Joanna Brewer, PhD, Vice President, Platform Phase 2 clinical trials and preliminary results have Sciences, AdaptImmune demonstrated safety and efficacy in melanoma, head and neck and cervical cancer patients. While available IMMUNOENICITY Adoptive T cell therapy using autologous material for immunotherapies for solid tumors, such as anti-PD-1 CAR and TCR therapies show considerable promise. & BIOASSAYS antibodies have shown promise, additional agents However, an off-the-shelf product will speed up the are needed for patients who may progress on such time to treat patients and provide a consistent and therapies or are intolerant. FUSIONS & unlimited source of therapeutic cells. Stem cells are CONJUGATES also amenable to genetic modification, allowing them 12:35 End of CAR Ts, TCRs and TILs to remain hidden from the immune system for long- term persistence of differentiated T cells expressing Recommended Short Course* THERAPEUTICS & enhanced affinity TCRs. TECHNOLOGIES SC14: Subvisible Protein Particles 9:35 Sponsored Presentation (Opportunity in Immunogenicity: Measurement, Available) Characterization and Impact SPONSOR/EXHIBIT 10:05 Coffee Break in the Exhibit Hall with *Separate registration required. Click here or see page 5 for course details. INFORMATION Poster Viewing HOTEL & TRAVEL INFORMATION 11:05 Expanding the Tractable Tumor Target Universe with T Cells Carrying Engineered REGISTRATION INFORMATION TCRs Iulia Diaconu, PhD, Associate Director, Immunotherapy, Bluebird Bio REGISTER ONLINE! PEGSummit.com

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REGISTER TODAY 5TH ANNUAL AGONIST IMMUNOTHERAPY TARGETS COVER Stepping on the Gas with Costimulatory Agents CONFERENCE-AT-A-GLANCE April 11-12, 2019 SHORT COURSES The immunotherapies industry is currently dominated by antagonist antibodies such as PD-1 and CTLA-4. However, it is clear that antagonists alone are not enough to TRAINING SEMINARS elicit response in the majority of patients, hence a rising interest in agonists targets. CHI’s Agonist Immunotherapy Targets conference will examine these modalities and their treating disease. Agonists showing the most promise, including OX40, CD27, GITR, and 4-1BB, will be covered in clinical case studies by examining the data as well as the biology and mechanisms. Emerging agonists, including TNFR receptors, ICOS, STING, and VISTA will also be discussed. Focus will be given throughout ENGINEERING to potential combination immunotherapies to ensure durable antitumor response. Overall, this event will emphasize strategies for target discovery to ensure continued growth and success for immunotherapies.

ONCOLOGY THURSDAY, APRIL 11 cancer vaccine to boost the function of killer mediated depletion of T cells through ADCC. Here we CD8 T cells and cause tumor regression. We are will present novel bispecific antibody programmes 12:00 pm Registration investigating how combination immunotherapy that do not rely on FcgR binding, but instead crosslink restores the function of killer CD8 T cells that using their two target binding sites. 12:35 Luncheon in the Exhibit Hall with Poster IMMUNOTHERAPY have been paralyzed, or rendered anergic, by Viewing tumors. Additional studies seek to understand the 4:50 Development of SIRPa-Fc-CD40L for mechanisms by which immunotherapy enhances the Cancer Immunotherapy LATEST DEVELOPMENTS IN AGONIST Taylor Schreiber, PhD, CSO, Research & Development, EXPRESSION IMMUNOTHERAPY - CYTOKINES AND efficacy of conventional treatments, such as radiation therapy, with the goal of providing a path for rapid Shattuck Labs, Inc. OX40 TARGETS translation to the clinic. The CD47/SIRPa axis functions to enhance antigen 1:40 Chairperson’s Opening Remarks cross-presentation within the context of anti-tumor ANALYTICAL 2:50 OX40: Is Timing Everything? Karin Enell Smith, PhD., Senior Scientist, Immuno- immunity, which holds promise for the treatment of Brendan Curti, MD, Robert W. Franz Chair for oncology, Alligator Bioscience immune-neglected tumors. The subset of dendritic cells Clinical Research, Earle A. Chiles Research Institute, which are the most potent antigen cross-presenters Providence Cancer Institute express CD40, and stimulation of CD40 enhances IMMUNOENICITY 1:50 KEYNOTE PRESENTATION: & BIOASSAYS We now have FDA-approved checkpoint activation of CD8+ lymphocytes by these cells. SIRPa- Harnessing Potent Cytokine Agonist immunotherapy for many stage III and IV cancers, Fc-CD40L has demonstrated superiority to CD47/SIRPa Pathways by Polymer Engineering to but administration of immunotherapy before surgery blocking antibodies, CD40 agonist antibodies, and FUSIONS & Develop Novel Immune Therapeutic has not been as extensively investigated. A clinical antibody combinations in both rodent and non-human CONJUGATES Agents trial of the neoadjuvant administration of an agonist primate studies, which position this compound to Loui Madakamutil, PhD, Vice President, Head of antibody to OX40, a T cell co-stimulatory agent, will provide unique benefits to human cancer patients. Discovery, Nektar Therapeutics be discussed, along with changes in tumor infiltrating THERAPEUTICS & We have engineered cytokines using polymer CD39+CD103+ T cells that we hypothesize are 5:20 End of Day technology to enable viable medicines. NKTR- TECHNOLOGIES relevant to achieving effective anti-tumor immunity. 5:20 Registration for Dinner Short Courses 214 is in Phase 3 clinical trials and a key *Separate registration required. Click here or see page example of how polymer conjugation can bias 3:20 Sponsored Presentation (Opportunity Available) 5 for course details. SPONSOR/EXHIBIT the well-known IL-2 receptor pathway to favor INFORMATION CD8 T cell tumor infiltration over Tregs. On the 3:50 Networking Refreshment Break other hand, NKTR-358 selectively grows T regs in FRIDAY, APRIL 12 HOTEL & TRAVEL INFORMATION vivo. Finally, NKTR-255, an IL-15 receptor agonist 4:20 Agonist Bispecific Antibodies Delivering stimulates NK cells. Each agent is conjugated the Next Immuno-Oncology Breakthrough 8:00 am Morning Coffee in unique ways to elicit desirable and controlled REGISTRATION INFORMATION Mihriban Tuna, PhD, Vice President, Drug Discovery, pharmacological and immunological outcomes. F-star Biotechnology, Ltd. TNF AND 4-1BB AGONIST TARGETS Targeting T cell costimulatory pathways can strongly 8:30 Chairperson’s Remarks REGISTER ONLINE! 2:20 Agonists in Combination Immunotherapy activate the immune system due to the broad Christopher Thanos, PhD, CEO, Actym Therapeutics William L. Redmond, PhD, Associate Member, expression of receptors such as OX40 and CD137 PEGSummit.com Laboratory of Cancer Immunotherapy, Director, across multiple immune cell types. However, Fcg Immune Monitoring Laboratory, Providence Portland receptor (FcgR)-mediated crosslinking is often Medical Center required for the activity of monoclonal antibodies, Our previous studies helped elucidate the and we hypothesise that this likely limits clinical mechanisms by which OX40 agonist immunotherapy activity due to the inherently low affinity of Fc:FcgR plus checkpoint blockade synergized with a novel interactions, as well as the potential for FcgR- REGISTER at PEGSummit.com | 38 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOTHERAPY STREAM AGONIST IMMUNOTHERAPY TARGETS continued PARTICIPANTS REGISTER TODAY 8:35 The Appeal of The TNFR2 Target for induce a tumor directed immune activation in patients Ugur Eskiocak, PhD, Associate Director, Translational Immunotherapy: Tregs and Tumor Oncogenes with tumors co-expressing these FcγRs and 4-1BB. Immunology & Immunopharmacology, Compass Therapeutics Denise L. Faustman, MD, PhD, Director of Immunobiology, The preclinical data package supports a favorable COVER Massachusetts General Hospital, Associate Professor of safety/efficacy profile. Clinical studies with ATOR- CTX-471 is a fully human IgG4 agonist of CD137 Medicine, Harvard Medical School 1017 are planned for 2019. (4-1BB) that binds to a unique epitope and displays a CONFERENCE-AT-A-GLANCE Immune checkpoint inhibitors have revolutionized differentiated pharmacology and toxicology profile.In 11:35 Structure of the 4-1BB/4-1BBL Complex vitro, CTX-471 increased IFN-γ production by human cancer therapy but can exhibit variable efficacy. TNFR2 and Distinct Binding and Functional Properties is a signaling molecule found on a subset of potent T cells in an FcγR-dependent manner, displaying an SHORT COURSES of Utomilumab and Urelumab Treg cells that activates the proliferation of these cells. intermediate level of activity between two clinical- Javier Chaparro-Riggers, PhD, Senior Director, Protein TNFR2 is also abundantly expressed on the surface stage anti-CD137 antibodies. In vivo, CTX-471 TRAINING SEMINARS Engineering, Pfizer of many human tumors as an oncogene. We propose exhibited curative monotherapy activity in CT26, A20, blocking TNFR2 might target abundant TNFR2+ tumor- 4-1BB is an inducible costimulatory receptor and EMT-6 models. infiltrating Tregs and directly kill TNFR2-expressing expressed on activated T cells. Two agonist ENGINEERING antibodies, utomilumab (PF-05082566) and urelumab 2:10 ImmunoSTATs: A Novel Biologics tumors. TNFR2 inhibitors might also potentially Therapeutic Platform for Antigen-Specific constitute safer and more targeted immunotherapy. (BMS-663513), demonstrate distinct activities in the clinic. To understand these differences, we Immunotherapy ONCOLOGY 9:05 Development of TNF Superfamily Agonists solved structures of the human 4-1BB/4-1BBL Anish Suri, PhD., Cue Biopharma Andreas Raue, PhD, Associate Director, Research, complex, the 4-1BBL trimer alone, and 4-1BB bound ImmunoSTATs are proprietary biologics that Merrimack Pharmaceuticals to utomilumab or urelumab. Additionally, cell-based incorporate, in a single molecular framework, key assays demonstrate utomilumab is a milder agonist signals needed to selectively modulate antigen- IMMUNOTHERAPY Members of the TNF superfamily of costimulatory receptors have emerged as promising immuno- than urelumab. Collectively, our data provide a deeper specific T cells: namely, the pMHC-complex and oncology targets, and agonistic antibodies are understanding of the 4-1BB signaling complex, relevant co-stimulatory/co-inhibitory signals, currently being evaluated clinically. Here, we describe providing a template for future development of next dependent upon the disease indication. The EXPRESSION our STIMULI platform, which consists of novel generation 4-1BB targeted biologics. lead clinical candidate CUE-101 is comprised of multispecific and multivalent TNF receptor agonists, HLA-A*0201, genetically bound to a HPV16 epitope 12:05 pm CB307, A Novel T-Cell Agonist engineered to provide more precise activation of (E7 protein, peptide 11-20), along with affinity- Humabody Therapeutic for PSMA-Positive ANALYTICAL immune cell subsets. attenuated human interleukin-2 to selectively activate Tumours and expand HPV16 E711-20-specific CD8+ T cells for 9:35 Sponsored Presentation (Opportunity James Legg, PhD, Vice President, Research and HPV-driven malignancies. Available) Development, Crescendo Biologics IMMUNOENICITY 2:40 A Novel Systemically Delivered STING 10:05 Networking Coffee Break Crescendo Biologics has initiated clinical & BIOASSAYS development of CB307 a novel bispecific Humabody Pathway Agonist Therapy Demonstrates 10:35 IGM Antibodies with Very Potent VH targeting CD137 (4-1BB) and prostate specific Robust Anti-Tumor Efficacy in Multiple Murine Agonism to DR-5 Induced Apoptosis and as membrane antigen (PSMA). The talk will describe the Cancer Models FUSIONS & identification, mechanism of action and preclinical Christopher Thanos, PhD, CEO, Actym Therapeutics CONJUGATES Anti-Tumor Agents Bruce Keyt, PhD, CSO, IGM Biosciences characterisation of the CB307 drug candidate. The Delivery of immunotherapy to directly activate IGM Biosciences has anti-DR5 antibodies prepared as benefits of using the modular Humabody VH platform, tumor-resident immune cells is required to elicit IgG and IgM. Anti-DR5 as IgM exhibits very potent and rather than an IgG format to develop this molecule durable anti-tumor immunity. To this end, we have THERAPEUTICS & will be discussed, including optimal (monovalent) TECHNOLOGIES robust tumor cell killing in vitro and in vivo. IgM has generated an immunotherapy platform that allows for broad anti-cancer bioactivity against various epithelial engagement of both targets with small VH domains tumor-specific delivery of engineered RNAi towards and hematologic tumors, both as established tumor and the avoidance of Fc receptor interactions. The any tumor/immune target of interest (alone or in cell lines as well as PDX cells in vitro. In vivo studies unique design of CB307 enables highly potent and combination). For our initial RNAi target selection, SPONSOR/EXHIBIT show very strong positive results in single agent tumour selective T-cell co-stimulation. a therapy targeting TREX1 was designed. TREX1 is INFORMATION a 3′ exonuclease immune checkpoint that degrades treatment or in combinations with chemotherapy. 12:35 Luncheon Presentation (Sponsorship Primate models show very low to no evidence of cytosolic DNA, thereby preventing it from binding HOTEL & TRAVEL INFORMATION Opportunity Available) or Enjoy Lunch on Your cGAS and activating the STING pathway. toxicity. We are scaling these antibodies for IND Own enabling studies and FIH human trials. 3:10 Beyond PD1: Targeting STING and Other REGISTRATION INFORMATION 1:05 Networking Refreshment Break 11:05 ATOR-1017, A 4-1BB Antibody Novel Pathways Anthony Desbien, PhD., Senior Scientist, Translation REGISTER ONLINE! Developed for Tumor Directed Immunotherapy 4-1BB, TLR AND STING AGONIST of Cancer TARGETS Immunology, Aduro Biotech PEGSummit.com Peter Ellmark, PhD, Vice President, Discovery, Alligator 3:40 End of Conference Bioscience 1:35 Chairperson’s Remarks ATOR-1017 is a 4-1BB agonistic IgG4 antibody Christopher Thanos, PhD, CEO, Actym Therapeutics designed for optimal efficacy and safety. The 1:40 CTX-471, a Novel Agonistic Antibody agonistic activity of ATOR-1017 depends on Targeting CD137 engagement with certain FcγRs, and it will thereby REGISTER at PEGSummit.com | 39 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS REGISTER TODAY

COVER

CONFERENCE-AT-A-GLANCE EXPRESSION STREAM

SHORT COURSES

TRAINING SEMINARS

ENGINEERING Meeting Growing Demands Difficult-to-Express ONCOLOGY Proteins for Viable Protein The burgeoning field of protein science, and the resultant biological IMMUNOTHERAPY products, places ever growing demands on protein expression. Optimizing Protein Increasingly, researchers need to produce quality protein faster and in larger quantities to meet industry’s rising demands. Protein EXPRESSION Expression scientists must delve into genomic structure and function in order to understand and engineer expression systems, elucidate protein ANALYTICAL function and behavior, and overcome protein’s intrinsic challenges, Protein Expression such as aggregation and misfolding. Membrane and other IMMUNOENICITY System Engineering especially troublesome proteins pose even greater difficulties, yet & BIOASSAYS hold considerable promise and rewards. The week-long Expression Stream focuses on productivity, from genes and clones, through FUSIONS & production systems, and includes an examination of Difficult-to- CONJUGATES Express Proteins along with breakthrough strategies and technologies in the pursuit of viable proteins. THERAPEUTICS & TECHNOLOGIES

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14TH ANNUAL COVER DIFFICULT-TO-EXPRESS PROTEINS CONFERENCE-AT-A-GLANCE Overcoming Expression Challenges SHORT COURSES April 8-9, 2019 TRAINING SEMINARS Proteins are each unique and bring unique challenges when attempting to tame them into submission. CHI’s Fourteenth Annual Difficult-to-Express Proteins conference examines the challenges researchers encounter when striving for high-yield production of “difficult-to-express” proteins (DTEPs), and the strategies and technologies that have ENGINEERING proven successful in overcoming those challenges. Some of the difficulties encountered include solubility, proper folding, inability to crystallize, aggregation and formation of inclusion bodies. Researchers employ a range of problem-specific solutions to achieve expression, including genetic modifications, manipulating how a target protein is produced, and employing protein tags. In addition, the identification of DNA coding sequences along with the use of high-throughput approaches has brought about significant improvements. The “Difficult-to-Express Proteins” conference provides the latest developments in improving yield for DTEPs through Case Studies and breakthrough data. ONCOLOGY SUNDAY, APRIL 7 9:10 Use of a Protein Engineering Strategy BACULOVIRUS & INSECT CELLS to Overcome Limitations in the Production of 10:45 Chairperson’s Remarks IMMUNOTHERAPY “Difficult to Express” Recombinant Proteins Recommended Short Course(s)* Gargi Roy, MSc, Scientist, Antibody Discovery and SC3: Selection, Screening and Engineering Alan Dickson, PhD, Professor, Biotechnology; Director, Protein Engineering, AstraZeneca Centre of Excellence in Biopharmaceuticals (COEBP), for Affinity Reagents EXPRESSION University of Manchester 10:50 Production of Human Integral SC6: Introduction to Host Cell Proteins (HCPs) Domain engineering opens the potential to Membrane Proteins Using Baculovirus and *Separate registration required. Click here or see manufacture novel recombinant products with BacMam page 5 for course details. innovative functions. Intellectual shuffling of protein Nicola Burgess-Brown, PhD, Principal Investigator, ANALYTICAL domains/parts can be frustrated by the quality control Biotechnology, Nuffield Department of Medicine, processes in current cell factories. This presentation Structural Genomics Consortium, University of Oxford MONDAY, APRIL 8 will focus on our recent work that has localised the The SGC promotes research advancement through IMMUNOENICITY sites of limitation of production of model ‘difficult our open access policy, and in the absence of IP. & BIOASSAYS 7:00 am Registration and Morning Coffee to express’ proteins and development of molecular Globally, we have solved more than 2000 human interventions that enhance production of a desired protein structures and 10 novel integral membrane INNOVATING PROCESSES FOR DTEPs recombinant protein. FUSIONS & proteins (IMPs). We have made a significant 8:30 Chairperson’s Opening Remarks 9:40 Teaching an Old Dog New Tricks: Making contribution to structural biology and protein CONJUGATES production for functional studies, however, IMPs and Nicola Burgess-Brown, PhD, Principal Investigator, CHO Cell Line Development Ready for the protein-protein complexes still remain a challenge to Biotechnology, Nuffield Department of Medicine, Difficult-to-Express Protein Challenge Structural Genomics Consortium, University of Oxford produce. I will present our established baculovirus/ THERAPEUTICS & Simon Fischer, PhD, Head, BPAD Cell Line insect cell expression platform and our promising TECHNOLOGIES Development, Bioprocess & Analytical Development, BacMam pipeline. 8:40 KEYNOTE PRESENTATION: A High- Boehringer Ingelheim Pharma GmbH & Co. KG Throughput Platform to Express All The number of DTE therapeutic proteins appearing 11:20 13 Years of Baculovirus Protein SPONSOR/EXHIBIT Human Cell Surface Proteins in drug development pipelines of pharmaceutical Expression in a Core Facility: Evolution of an INFORMATION James Love, PhD, COO, Protein Production, companies has increased dramatically. To address Ultra-Short Protocol Institute for Protein Innovation challenges in DTE protein expression, novel cell line Sabine Suppmann, PhD, Head, Recombinant Protein HOTEL & TRAVEL INFORMATION Generating open-source monoclonal antibodies development strategies need to be implemented. Being Production, Biochemistry Core, Max Planck Institute against every extracellular and secreted protein an old workhorse within the industry, CHO cells still of Biochemistry in humans, has required the development of REGISTRATION INFORMATION represent the predominant production host for large- In the last three decades, the Baculovirus expression expression platforms capable of generating high scale manufacturing. In this talk, we will present new vector system (BEV) has evolved to one of the most quality antigens and antibodies in HT format. technologies in cell line and molecule engineering to widely used eukaryotic systems for heterologous REGISTER ONLINE! Classes of proteins show somewhat uniform enhance CLD for DTE proteins in the future. protein expression. Despite the significant characteristics in ‘expressibility’ and even PEGSummit.com 10:10 Networking Coffee Break improvements introduced during the past years, the recalcitrant proteins, such as integral membrane BEV system still has major drawbacks, primarily the proteins can be processed by rescue pathways time required to generate recombinant virus and if necessary. This talk will outline methods that have proven fruitful and present future areas for investigation. REGISTER at PEGSummit.com | 41 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EXPRESSION STREAM DIFFICULT-TO-EXPRESS PROTEINS continued PARTICIPANTS REGISTER TODAY virus instability for certain target proteins. We have targets in under 24 hours. The Beacon platform 8:00 am Registration and Morning Coffee established and validated an ultra-short BEV protocol links phenotype-to-genotype at the single-cell level, that also eliminates the risk of virus decay. simplifying downstream sequencing, cloning, and MEMBRANE PROTEINS bioinformatics analysis. COVER 11:50 Tools for Studying the RAS/RAF/ 8:25 Chairperson’s Remarks MEK Pathway: Using the BEVS to Produce 1:20 Session Break Shahram Misaghi, PhD, Senior Scientist, Cell Culture, CONFERENCE-AT-A-GLANCE Complexes and Native Proteins 1:50 Session Break Genentech, Inc. William Gillette, PhD, Principal Scientist, RAS Reagents 2:20 Problem-Solving Breakout Discussions 8:30 Structures Suggest a Mechanism for SHORT COURSES Core; Deputy Director, Protein Expression Laboratory, Energy Coupling by a Family of Organic Anion Leidos Biomedical Research, Inc., Frederick National 3:20 Networking Refreshment Break Transporters TRAINING SEMINARS Laboratory for Cancer Research (FNL) Robert M. Stroud, PhD, Professor, Biochemistry This talk will focus on progress in producing proteins PLENARY KEYNOTE SESSION and Biophysics, Pharmaceutical Chemistry, involved in the RAF activation pathway that are Macromolecular Structure Group (MSG), University of ENGINEERING suitable for in vitro structural and biochemical 4:00 Chairperson’s Remarks California, San Francisco (UCSF) studies. Recent advances in using the BEVS to Rakesh Dixit, PhD, DABT, Vice President, R&D, Members of the solute carrier 17 family use overcome stability issues and producing complexes, Global Head, Biologics Safety Assessment, divergent mechanisms to concentrate organic as well as more biologically accurate KRAS proteins Translational Sciences, AstraZeneca anions. Membrane potential drives uptake of the ONCOLOGY will be highlighted. principal excitatory neurotransmitter glutamate into 4:10 Vision for How Immunotherapy Will 12:20 pm 9g/l in 90 Hours: Sponsored by synaptic vesicles, whereas closely related proteins Shape Future of Cancer Care IMMUNOTHERAPY Development of C1 into a Next- use electroneutral cotransport to drive efflux from Generation Therapeutic Protein Leena Gandhi, MD, PhD, Vice President, Immuno- the lysosome. To identify the common features of Oncology Medical Development, Lilly Oncology Production System ionic coupling by the SLC17 family, we determined Immunotherapy is considered by many as a Ronen Tchelet, Vice President, Research & the structure of E. coli D-galactonate/H+ symporter pillar of cancer care today, but in many ways we EXPRESSION Development, Dyadic International, Inc. DgoT in two states: one open to the cytoplasmic have only scratched the surface. Our knowledge side, and the other open to the periplasmic side with This presentation will show the results of the and understanding of the complexities of development of the filamentous fungus Myceliophthora substrate bound. The structures identify residues immunotherapy and its mechanisms continue of a proton translocation pathway conserved from ANALYTICAL thermophila C1 into a next-generation therapeutic to evolve. The future of cancer care will be protein production system. bacteria to mammals. Functional analysis suggests defined by our ability to systematically identify that a transition in the role of H+ from flux coupling 12:35 Expression, Purification and Sponsored by and implement opportunities for combination to allostery may underlie the divergence in energy IMMUNOENICITY Characterization of Difficult to therapy to improve and standardize patient source. & BIOASSAYS Express Membrane Proteins response. 9:00 Modulation of STEAP2 Conformation by Anass Jawhari, PhD, CSO, Calixar 4:55 The Lassa Virus Glycoprotein: the Cholesterol Content of Cellular Membrane: Stopping a Moving Target FUSIONS & This talk will focus on strategies for optimizing An In-Depth Study of Conformational Epitope expression levels of membrane proteins using Kathryn Hastie, PhD, Staff Scientist, Immunology CONJUGATES Located in the Second Extracellular Loop the Expi293 and ExpiCHO expression systems. and Microbiology, The Scripps Research Institute Haruki Hasegawa, PhD, Principal Scientist, Biologics – Additionally, an introduction to newly developed Lassa virus causes ~5000 deaths from viral Protein Technology, Amgen, Inc. THERAPEUTICS & Expi293 engineered cell lines combined with hemorrhagic fever every year in West Africa. TECHNOLOGIES CALIXAR patented technology to improve quality The trimeric surface glycoprotein, termed Leveraging a newly-identified mAb that recognizes and quantity of challenging membrane proteins will GPC, is critical for infection, is the target for a conformation-sensitive epitope nested in the be provided. A case study of KCC2 production and neutralizing antibodies, and a major component second extracellular loop of human STEAP2, we demonstrate that the epitope formation is dependent SPONSOR/EXHIBIT characterization will be further described. of vaccines. Structural analysis of Lassa GPC bound to antibodies from human survivors on the cholesterol content of the membrane in which INFORMATION 12:50 Luncheon Presentation I: Sponsored by reveals a major Achilles heel for the virus and STEAP2 was embedded. Membrane permeabilization The Beacon™ Platform for the step and membrane cholesterol extraction treatment HOTEL & TRAVEL INFORMATION provides the needed template for development Rapid Discovery of Rare of immunotherapeutics and improved vaccines. both abrogated cell surface staining of STEAP2 Antibodies to Difficult Targets expressing cells. Given the preexisting difference REGISTRATION INFORMATION Anupam Singhal, PhD, Technology Development, in cholesterol content among different cellular Berkeley Lights, Inc. 5:40 Welcome Reception in the Exhibit Hall membranes, STEAP2 conformation appears to REGISTER ONLINE! The search of biologics to novel therapeutic targets is with Poster Viewing undergo compartment-specific modulation during hampered by current antibody discovery technologies secretory and endocytic trafficking. PEGSummit.com that are laborious, time-consuming, and generate 7:15 End of Day limited diversity. Here, I will demonstrate how Berkeley Lights’ Beacon® platform’s automated plasma cell antibody discovery workflow mines the vast immune repertoire to identify B cells producing rare, functional antibodies to difficult therapeutic TUESDAY, APRIL 9 REGISTER at PEGSummit.com | 42 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EXPRESSION STREAM DIFFICULT-TO-EXPRESS PROTEINS continued PARTICIPANTS

REGISTER TODAY 9:30 Tag-on-Demand – Exploiting ‘Switchable’ Addition of lipids or engineering of the scaffold is not generation combines the SUREtechnologyPlatform™ Expression Technology for the Enrichment of necessary. The flexibility of the peptidisc is suited for with precise selection of clones with desirable traits High-Expressing Membrane Protein Cell Lines trapping proteins of various fold, size, architecture and manipulation of specific genes. This approach COVER Zachary T. Britton, PhD, Scientist, Antibody Discovery and the reconstitution process can be embedded allows the isolation of desired clones that are rare and Protein Engineering, AstraZeneca directly within the membrane protein purification events in cell populations and has led to remarkable protocol. progress in optimized product quality & titers CONFERENCE-AT-A-GLANCE Poor expression and detection of membrane protein therapeutic targets have hampered drug discovery 11:50 Exploration of New Methods to Improve 1:20 Ice Cream Break in the Exhibit Hall with SHORT COURSES and screening efforts. To address this, we have and Streamline Expression of Difficult Poster Viewing developed the “Tag-on-Demand” approach that Membrane Proteins to Support Drug Discovery exploits ‘switchable’ expression of ‘tagged’ and TRAINING SEMINARS Noel J. Byrne, MSc, Associate Principal Scientist and BREAKTHROUGH TECHNOLOGIES TO ‘untagged’ membrane proteins in response to non- Lead, Expression Group, Target Protein Design, Merck SUPPORT DTEPs natural amino acid supplementation. Expression Research Laboratories of ‘tagged’ membrane proteins facilitate detection 2:00 Chairperson’s Remarks ENGINEERING Integral membrane proteins represent more than and selection steps, and expression of ‘untagged’ William Gillette, PhD, Principal Scientist, RAS Reagents 60% of current drug targets. Despite the clinical native proteins can be used directly in whole-cell drug Core; Deputy Director, Protein Expression Laboratory, significance, therapeutic agents that target discovery efforts. Validation of this approach using Leidos Biomedical Research, Inc., Frederick National membrane proteins have been difficult to develop. ONCOLOGY model membrane proteins will be presented. Laboratory for Cancer Research (FNL) Poor expression in recombinant systems is the most critical challenge to producing functional 10:00 Coffee Break in the Exhibit Hall with 2:05 FEATURED PRESENTATION: Poster Viewing integral membrane proteins for antibody discovery, IMMUNOTHERAPY structural and functional studies. The results from MicroED: Cryo-Electron Diffraction of 3D MEMBRANE PROTEINS – DETERGENTS & the exploration of different technologies for the Microcrystals Brent Nannenga, PhD, Assistant Professor, SOLUTIONS streamlined, efficient mammalian expression of EXPRESSION several GPCRs and Ion Channels through stable cell- Chemical Engineering, Arizona State University 10:45 Chairperson’s Remarks line generation and transient expression (DNA and The growth of large well-ordered crystals is Shahram Misaghi, PhD, Senior Scientist, Cell Culture, BacMam) will be presented. often a barrier to high-resolution biomolecular Genentech, Inc. structure determination. The cryo-electron ANALYTICAL 12:20 pm Luncheon Presentation I: Sponsored by microscopy technique of microelectron 10:50 A High-Throughput Approach for Expi293 Transient Protein diffraction, or MicroED, is capable of determining Kinetics of Membrane Protein-Detergent Expression System: New Tools for Structural high-resolution structures from extremely IMMUNOENICITY Interactions Biology and Difficult to Express Proteins small microcrystals, promising to overcome & BIOASSAYS Liviu Movileanu, PhD, Professor, Physics, Syracuse Jon Zmuda, PhD, Director of Cell Biology, R&D, this obstacle. In this presentation, the MicroED University Thermo Fisher Scientific technique and representative structures will be described, as well as new improvements aimed Interfacial interactions of the membrane protein- In this presentation, we demonstrate the performance FUSIONS & detergent complex (PDC) have implications in protein at structure determination of difficult targets. CONJUGATES of a new range of Expi293 components, including function, structure, stability, and dynamics. Current engineered Expi293 cell lines (e.g. GNTI-, Inducible methods for examining kinetics of the PDC require and Inducible/GNTI- Expi293 cell lines) to allow 2:35 Development of a High-Yielding high amounts of protein and are low throughput. Expression Platform for the Introduction of THERAPEUTICS & for regulated expression and/or glycosylation of I will talk about our recent developments on an proteins, as well as an Expi293 Methionine-Deficient Non-Natural Amino Acids TECHNOLOGIES approach for acquiring details of these interactions System for metabolic labeling of proteins for NMR Gargi Roy, MSc, Scientist, Antibody Discovery and in a scalable fashion. Further improvements of this or multiwavelength anomalous dispersion (MAD). Protein Engineering, AstraZeneca semi-quantitative method will impact physical and Together, these new tools significantly enhance the We developed an expression technology that enables SPONSOR/EXHIBIT chemical biology of membrane proteins. ability of researchers to produce difficult to express site-specific incorporation of non-natural amino acids INFORMATION (nnAA) in a protein sequence. Fully functional, high 11:20 Peptidisc: A Simple Solution for proteins for structural biology analyses. yielding IgG, in a continuous perfusion process, was Sponsored by HOTEL & TRAVEL INFORMATION Capturing Membrane Proteins without 12:50 pm Luncheon Presentation II: produced in hosts stably expressing an orthogonal Detergent Engineered Selexis CHO Cell Lines tRNA synthetase/tRNA pair. These host platforms REGISTRATION INFORMATION Franck Duong, PhD, Professor and Principal for Improved Recombinant Protein hold promise to overcome the expression challenges Investigator, Biochemistry & Molecular Biology, Production that have encumbered the developability of this University of British Columbia Ghislaine Arib, PhD, Genomic Director, Selexis SA technology for manufacturing of antibody drug REGISTER ONLINE! The peptidisc is a straightforward “one fits all” Biologics development requires stable, high- conjugates and other protein conjugates. PEGSummit.com method that allows capture of membrane proteins producing cell clones yielding high-quality product into functional, heat-stable, water-soluble particles. over years. These clones need stable chromosomal integration, elevated transcription plus optimized metabolic & secretion. Selexis CHO cell line

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REGISTER TODAY 4:55 Expression of Multivalent Antibodies that Can Cross the BBB and Detect Aggregates in 3:05 GS Xceed® Gene Expression Sponsored by Amyloid Diseases with Expi293 Cells and PEI Toolbox: Overview and the COVER Sofia Stenler, PhD, Scientist, Pharmaceutical Introduction of New Tools Biosciences, Protein Drug Design, Uppsala University Peter O’Callaghan, PhD, Principal CONFERENCE-AT-A-GLANCE Scientist, Research & Development, Lonza Pharma & I will describe a method of expressing antibodies and Biotech bispecifics in EXPI293 cells with PEI. The method SHORT COURSES is cheap and reliable. We have used the method In this presentation, we will share an overview of to express bispecific antibodies that can pass the the GS Xceed® Gene expression toolbox will be TRAINING SEMINARS BBB 80 times better than unmodified antibodies. presented with a focus on new tools that have The antibodies bind monovalently despite having recently been added. Alongside this some new two binding domains and this is what facilitated the in-house research will be presented showing the high uptake. We have shown that the antibodies ENGINEERING benefit of applying control circuits to boost protein can be used to treat or diagnose neurodegenerative expression. diseases. ONCOLOGY 5:25 End of Difficult-to-Express Proteins 3:35 Refreshment Break in the Exhibit Hall with Poster Viewing 5:30 Registration for Dinner Short Courses IMMUNOTHERAPY ANTIBODY EXPRESSION Recommended Short Course* SC9: Introduction to Biophysical Analysis 4:25 Utilizing a Regulated Targeted Integration for Antibody Discovery & Development EXPRESSION (RTI) Cell Line Development (CLD) Approach *Separate registration required. Click here or see to Systematically Investigate What Makes an page 5 for course details. Antibody Difficult to Express Shahram Misaghi, PhD, Senior Scientist, Cell Culture, ANALYTICAL Genentech, Inc. A regulated target integration (RTI) system was used to analyze causes of low protein expression for a IMMUNOENICITY difficult-to-express antibody (mAb-A). Based on our & BIOASSAYS findings, both antibody heavy chain and light chain subunits of mAb-A independently contributed to its low expression. RTI pools, generated by swapping FUSIONS & antibody chains or point-mutations, confirmed that CONJUGATES LC expression triggered ER stress and accumulation of intracellular BiP, while HC molecules had impaired degradation and clearance. THERAPEUTICS & TECHNOLOGIES

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REGISTER TODAY 9TH ANNUAL OPTIMIZING PROTEIN EXPRESSION COVER Enhancing Expression Systems CONFERENCE-AT-A-GLANCE April 10-11, 2019 SHORT COURSES Expression of heterologous proteins presents many challenges; and understanding expression systems is key. The Ninth Annual Optimizing Protein Expression TRAINING SEMINARS conference delves into protein expression by examining and enhancing expression systems, including CHO, and other mammalian systems, E. coli, yeast, and baculovirus. What is the best expression system for expressing your protein of choice? Ease and cost of scale-up must be considered to ensure successful bottom-line results. Experts will share case studies and disclose data, while divulging details of expression systems’ underlying mechanisms. Comparing and contrasting systems ENGINEERING will also be featured to increase understanding in the quest for greater productivity.

ONCOLOGY TUESDAY, APRIL 9 advanced into clinics by Roche pRED. In order 10:10 Coffee Break in the Exhibit Hall with to discover and develop differentiated biologics, Poster Viewing Roche’s strategy is based on engineering Recommended Short Course* technologies leading to new formats and IMMUNOTHERAPY SC9: Introduction to Biophysical Analysis processes which bear several challenges and 10:15 Women in Science Speed Networking in for Antibody Discovery and Development many opportunities for technical development the Exhibit Hall *Separate registration required. Click here or see towards the clinic and beyond. EXPRESSION page 5 for course details. 9:10 Site-Specific Biotinylation of Secreted OPTIMIZING CHO-BASED EXPRESSION Proteins in Mammalian Cells in vivo – Made 10:55 Combining Biophysical Analytics ANALYTICAL WEDNESDAY, APRIL 10 Viable! with Next-Generation Sequencing for Deep 7:15 am Registration and Morning Coffee Mark Trautwein, PhD, Senior Scientist, Characterization of mAb Producing CHO Cell Pharmaceuticals R&D, Preclinical Research, Lines IMMUNOENICITY Expression Technologies, Bayer AG Holger Thie, PhD, Senior Manager, Technology and & BIOASSAYS 7:25 - 8:25 PANEL DISCUSSION: Women in Site-specific biotinylation of secretory target Innovation, Biologics Development, Boehringer Science – Inspired Professional and Personal proteins is desirable to achieve in vivo during Ingelheim Pharma GmbH & Co. KG Stories protein expression in mammalian cells. However, FUSIONS & conventional techniques like the AviTag suffer from 11:25 Engineering CHO Cell Lines for the Moderator: Women in Bio, Boston Chapter Production of Hard-to-Produce Proteins CONJUGATES Panelists: serious losses in expression yields, preventing their applicability as a generic approach. In this Bjørn Voldborg, MSc, Director, CHO Cell Line Susan Richards, PhD, Presidential Scientific Fellow, presentation, I will describe how we have optimized a Development, The Novo Nordisk Foundation Center Translational Medicine Early Development, Sanofi R&D THERAPEUTICS & protein tag to solve the problem and achieve this goal. for Biosustainability, Technical University of Denmark TECHNOLOGIES Joanna Brewer, PhD, Vice President, Platform Using our high-throughput cell line engineering Technologies, AdaptImmune 9:40 SoluPro™, A Groundbreaking Sponsored by platform, we have engineered CHO cells able to Additional Panelists to be Announced E. coli Platform for Next-Generation produce therapeutic proteins that have previously not been possible to produce in CHO cells. This approach SPONSOR/EXHIBIT Antibody Scaffolds and Protein INFORMATION PROTEIN PRODUCTION STRATEGIES TherapeuticsAntibody Therapeutics may result in improved therapeutic proteins with Johan Kers PhD, Vice President, Research, AbSci better biological properties, such as increased half- 8:30 Chairperson’s Opening Remarks life, improved activity, etc. HOTEL & TRAVEL INFORMATION SoluPro™, a game-changing E. coli expression Philippe Billiald, PharmD, PhD, Professor, platform that eliminates the formation of inclusion Biochemistry, University Paris-Sud & Acticor Biotech 11:55 Importance of Appropriately REGISTRATION INFORMATION bodies, increases plant efficiencies, and drastically Glycosylated Species, and Modulation reduces COGs and CapEx outlay. Employing Efforts, to Achieve Desired Post-Translational 8:40 KEYNOTE PRESENTATION: Early proprietary assays to optimize for product titer, Modifications in CHO-Derived Monoclonal REGISTER ONLINE! Process Development: Challenges and function, and quality, SoluPro™ produces correctly Antibodies PEGSummit.com Opportunities for Emerging Therapies folded, active protein, at groundbreaking titers in Nicola Beaucamp, PhD, Head, Process Research, less than 3 months. The platform can produce a Gaurav Chauhan, MS, Associate Principal Scientist, Roche Innovation Center Munich, Pharma wide range of complex proteins including full-length BioProcess Development, Merck & Co., Inc. Research and Early Development, Roche antibodies (4 g/L), Fabs (4.4g/L), and insulin (>20g/L) The glycosylation profile of the monoclonal Diagnostics GmbH in 48 hours or less. A number of new molecules, different from standard antibody structures, have been REGISTER at PEGSummit.com | 45 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EXPRESSION STREAM OPTIMIZING PROTEIN EXPRESSION continued PARTICIPANTS

REGISTER TODAY antibodies has major impact on the efficacy and 1:25 Luncheon Presentation II: Sponsored by Novo Nordisk Foundation Center for Biosustainability safety of the drug and is therefore an important Generation of High-Yielding (CFB), Technical University of Denmark parameter to control during protein production. Since Stable Pools Expressing Difficult Target Chinese hamster ovary (CHO) cells are one of the COVER glycosylation is an important parameter for IgG Proteins Through Maxcyte’s Transfection major hosts for production of complex therapeutic function, several strategies to modify glycosylation System® proteins. Efficient synthetic biology tools are of great profiles of human IgG or to select the most efficient CONFERENCE-AT-A-GLANCE Kevin Guay, Associate Scientist, Jounce Therapeutics interest to improve production in CHO cell factories. glycoforms have been explored. Further, considerable Here, our latest development of these tools will The transient transfection of Human Embryonic efforts have been made to understand how these be demonstrated. Together with high-throughput SHORT COURSES Kidney (HEK) cells has long been a workhorse glycoforms can be modulated as desired. I would like technologies and systems biology approaches, for protein production. Often, however, these to present on current understandings of such efforts. synthetic biology can pave the way toward TRAINING SEMINARS reagents suffer from poor yields and high amounts accelerated generation of desirable CHO cell factories Sponsored by of aggregate formation. Furthermore, multiple 12:25 pm New Tools for Screening with predicted culture performance. & Harvesting Solutions for CHO & production runs can introduce different post- ENGINEERING HEK293 Cells, for both Transient translation modification patters, which could 3:15 Scaling Up and Scaling Out: Sponsored by and Stable Cells potentially lead to discrepancies in protein activity. Pushing the Boundaries of Samuel Ellis, Vice President, Thomson Instrument We have employed the route of stable-pool generation Transient Protein Production Company to mitigate these issues, providing a great tool for Ian Wilkinson, PhD, CSO, Absolute Antibody, Ltd. ONCOLOGY programs in all stages of drug development. Evaluation of different transfection tools, product Whilst transient yields have improved drastically in the quality, and titer for both CHO and HEK293 cell lines. 1:55 Session Break last decade, scalable systems are time-consuming IMMUNOTHERAPY Data will be presented on techniques and technology and costly to implement. Absolute Antibody has that mimic large-scale bioreactors in non-controlled GENETICALLY ENGINEERING CHO CELLS developed systems which scale up and scale out devices from 1mL-3L. Technologies presented protein expression and purification, enabling the rapid include well plates and culture tube systems with 2:10 Chairperson’s Remarks and cost-effective production of milligram to gram EXPRESSION incorporated filtration methodology. A new direct Nicola Beaucamp, PhD, Head, Process Research, quantities of large panels of proteins. harvesting technique will also be introduced that Roche Innovation Center Munich, Pharma Research eliminates centrifugation while maintaining 0.2um and Early Development, Roche Diagnostics GmbH 3:45 Refreshment Break in the Exhibit Hall with Poster Viewing ANALYTICAL sterile filtration. All of these tools will be presented 2:15 Generation of Superior Host Cell Lines for with case studies from scientists. Biomanufacturing Sponsored by 4:45 Problem-Solving Breakout Discussions 12:55 Luncheon Presentation I: Margaret Lai, MS, Investigator II, Novartis Institutes for BioMedical Research 5:45 Networking Reception in the Exhibit Hall IMMUNOENICITY Scaling Flexibility with Fed-Batch with Poster Viewing & BIOASSAYS Expression in 96-Well Plates and Shaken CHO cells are the most widely used host for large- Single-Use Bioreactors scale production of recombinant therapeutic proteins. 7:00 End of Day Annie Ngo, Technical Scientist, Kuhner Shaker Inc Using transcriptomic approaches, we have identified FUSIONS & target genes involved in productivity and product Simple and unique, Kuhner Shaken Bioreactors (SB) CONJUGATES quality. Subsequently, a variety of novel parental mimic shake flask conditions for robust and scalable CHO cell lines were generated applying cell line process development. From advanced 96-well fed-batch engineering techniques as ZFN or TALEN. These screening plates to single-use disposables of 2500L w/v, THERAPEUTICS & novel knockout CHO cell lines are superior in respect orbital shaking scales easily based on kLa and mixing TECHNOLOGIES to productivity and/or product quality. time. Shaken processes offer further advantages of low- shear stress and less foaming – especially beneficial 2:45 Achieving Predictable Recombinant for sensitive cell types. Here we present data for small Gene Expression in CHO Cells Using CRISPR- SPONSOR/EXHIBIT scale controlled-release fed-batch and data from users INFORMATION Mediated Genome Engineering of the 3L-12L SB10 bioreactor. Nuša Pristovšek, PhD, Postdoctoral Researcher, The HOTEL & TRAVEL INFORMATION

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REGISTER TODAY THURSDAY, APRIL 11 highest binding affinity among all affinity tag systems, technologies was a priority in process development. the technology fulfills the demands of mammalian Today’s moss process relies on the latest single-use 8:00 am Registration and Morning Coffee expression systems (e.g. Expi) and is well suited for technologies and follows the established routines COVER downstream applications like SPR. of mammalian cell-based production. Thus, moss- COMPARE/CONTRAST EXPRESSION based production fits easily into existing cleanroom SYSTEMS 10:05 Coffee Break in the Exhibit Hall with environments and offers rapid changeover and CONFERENCE-AT-A-GLANCE Poster Viewing 8:30 Chairperson’s Remarks flexible configuration. SHORT COURSES Bjørn Voldborg, MSc, Director, CHO Cell Line NON-MAMMALIAN EXPRESSION 12:35 End of Optimizing Protein Expression Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark SYSTEMS TRAINING SEMINARS 5:45-8:45 pm Recommended Short 11:05 Rational Engineering of an Improved 8:35 Microbial or Mammalian Cells for Course* Secretion Signal for Pichia pastoris Expression of Therapeutic Antibody SC15: Transient Protein Production in ENGINEERING Fragments: Making the Choice with the End in Benjamin Glick, PhD, Professor, Molecular Genetics and Cell Biology, University of Chicago Mammalian Cells Mind *Separate registration required. Click here or see The yeast Pichia pastoris is widely employed Philippe Billiald, PharmD, PhD, Professor, page 5 for course details. to secrete heterologous proteins. Typically, the Biochemistry, University Paris-Sud & Acticor Biotech ONCOLOGY N-terminal portion of pre-pro-alpha-factor is used as Because antibody fragments are usually a secretion signal. This secretion signal promotes aglycosylated proteins, many host cell expression posttranslational translocation into the ER, so proteins IMMUNOTHERAPY platforms can be used for production, including that fold in the cytosol are poorly secreted. The alpha- bacteria, yeast and mammalian cells. However, all factor pro region can also promote aggregation in the these expression systems are not equivalent in terms ER. We applied cell biological principles to address of cell line development, culture time, product quality EXPRESSION both issues. The resulting improved secretion signal and cost of production. We will report differences that confers dramatic benefits. may have to be considered before pharmaceutical development and moving forward to the clinic. 11:35 Titer Estimation for Quality Control (TEQC) Method: A Practical Approach for ANALYTICAL 9:05 Using Non-Coding RNA for Improving Optimal Production of Protein Complexes Recombinant Protein Expression and Growth Using the Baculovirus Expression Vector from Mammalian Cells and Microorganisms System IMMUNOENICITY Joseph Shiloach, PhD, Director, Biotechnology Core & BIOASSAYS Lab, NIDDK, NIH Yuichiro Takagi, PhD, Associate Professor, Department of Biochemistry and Molecular Biology, Indiana Non-coding RNAs, including microRNA and siRNA University School of Medicine in eukaryotes, and small RNA in prokaryotes, FUSIONS & The baculovirus expression vector system (BEVS) are regulatory molecules that can affect protein CONJUGATES is becoming the method of choice for expression of expression through interactions with specific sections many eukaryotic proteins and protein complexes. of the host mRNA in mammalian cells, and mRNA However, what influences the overall production and proteins in bacteria. The utilization of mammalian THERAPEUTICS & of proteins or protein complexes remains largely microRNA and siRNA to enhance growth and protein TECHNOLOGIES unclear. We developed the Titer Estimation for Quality expression from HEK and CHO cells and affecting Control (TEQC) method, which enables researchers to E. coli metabolism using bacterial small RNA will be quantitatively optimize protein expressions utilizing presented. SPONSOR/EXHIBIT BEVS in a highly reproducible fashion. INFORMATION 9:35 Sponsored Presentation (Opportunity 12:05 pm BryoTechnology: Large-Scale GMP- Available) HOTEL & TRAVEL INFORMATION Manufacturing of Glyco-Designed Proteins with Moss 9:50 Overcoming Limitations of Sponsored by REGISTRATION INFORMATION Andreas Schaaf, PhD, CSO, Greenovation Biotech Conventional Tag Systems – GmbH Strep-Tactin®XT Applications BryoTechnology, i.e., moss-based production Dennis Karthaus, MSc, IBA Lifesciences REGISTER ONLINE! of biopharmaceuticals, has evolved into a GMP The Strep-Tactin®XT:Twin-Strep-tag®-purification PEGSummit.com manufacturing technology with products already in system enables protein purification at high yields and clinical development. While leveraging the mosses purity under physiological conditions. Providing the advantages, comparability to mammalian cell-based

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CONFERENCE-AT-A-GLANCE April 11-12, 2019 SHORT COURSES CHI’s Fifth Annual Protein Expression System Engineering conference examines the functioning of the cellular machinery harnessed during protein biosynthesis, and how to engineer hosts to efficiently express a protein of interest. The intricate steps required to achieve properly folded protein will be discussed, including verification and sequence TRAINING SEMINARS analysis of the gene, codon optimization, vector construction, selecting and optimizing a clone, and selecting a host system. In addition, engineering host cells to sustain expression for longer time periods will be discussed, along with overcoming cellular stress response to produce and secrete functionally active recombinant proteins. ENGINEERING THURSDAY, APRIL 11 We are developing tools of “biofabrication” that DNA into well-characterized genomic loci would enable facile assembly of biological components have broad applications for mammalian synthetic 12:00 pm Registration within devices, including microelectronic devices, biology, recombinant protein production, and ONCOLOGY that preserve their native biological function. We biomanufacturing. Using multi-gene payload vectors, 12:35 Luncheon in the Exhibit Hall with Poster have created redox-based synthetic biology to cell lines with multiple landing pads, and recombinase Viewing sample, interpret and report on biological information technology, we demonstrated controlled integration IMMUNOTHERAPY contained in molecular communications circuitry. We of up to nine copies of a monoclonal antibody (about SYNTHETIC BIOLOGY & GENETIC have also developed synthetic genetic circuits that 100 kb of heterologous DNA), and a corresponding ENGINEERING enable electronic actuation of gene expression. These linear increase in antibody expression. 1:40 Chairperson’s Opening Remarks tools enable unparalleled means to control genetic EXPRESSION Susan Sharfstein, PhD, Professor, Nanobioscience, circuits, creating new and exciting means to actuate 4:50 Implementing Next-Generation Nanoscale Science and Engineering, SUNY and control biology. Sequencing for DNA-Based Sequence Variant Polytechnic Institute Analysis of Recombinant Proteins ANALYTICAL 2:50 Steering N-Glycosylation of Recombinant Ulrich Göpfert, PhD, Principal Scientist, Cell Line & 1:50 KEYNOTE PRESENTATION: Proteins Using Systems Engineering Molecular Development, Roche Innovation Center Munich Mammalian Synthetic Biology: Michael J. Smanski, PhD, Assistant Professor, Biochemistry, Molecular Biology & Biophysics, IMMUNOENICITY Foundations and Application to Cell Line Sequence variants are unintended amino acid Biotechnology Institute, University of Minnesota substitutions in biopharmaceuticals, which can either & BIOASSAYS Engineering Chinese Hamster Ovary cells are used for industrial be due to the manufacturing process or mutations of Ron Weiss, PhD, Professor, Biological production of protein-based therapeutics (i.e. Engineering, Massachusetts Institute of the transgene. Transgene mutations are permanent ‘biologics’), but systems-level genetic engineering FUSIONS & Technology (MIT) properties of affected cell lines and may give rise to of beneficial traits is slow, difficult, and empirically- CONJUGATES In this research, we appropriate from established critical quality attributes. Therefore, mutated cell lines guided. We exploit systems- and synthetic- engineering fields proven design principles such need to be identified and excluded from development. biology approaches to design, build, and screen as abstraction, standardization, modularity, We will share our experience with next-generation multi-gene constructs that rationally perturb the THERAPEUTICS & and computer aided design. But we also spend sequencing as an efficient and highly sensitive post-translational glycosylation of a secreted TECHNOLOGIES considerable effort towards understanding method to detect DNA-based sequence variants. Immunoglobulin G (IgG) towards high galactose what makes synthetic biology different from incorporation. Our approach allows for rapid 5:20 End of Day all other existing engineering disciplines and hypothesis testing and quantification of synergistic discovering new design rules that are effective 5:20 Registration for Dinner Short Courses SPONSOR/EXHIBIT behavior from genetic perturbations. INFORMATION for the biological substrate. Building on this foundation, I will describe our recent application 3:20 Fusion Partners for Robust Sponsored by 5:45-8:45 pm Recommended Short HOTEL & TRAVEL INFORMATION of synthetic biology tools and principles towards Peptide Production in Course* the improvement of cell line engineering and Pseudomonas Fluorescens SC15: Transient Protein Production in biomanufacturing. REGISTRATION INFORMATION Diane Retallack, PhD, Senior Director, Upstream Mammalian Cells Processing and Intellectual Property, Pfenex *Separate registration required. Click here or see page 5 for course details. REGISTER ONLINE! 2:20 Communicating with and Controlling 3:50 Networking Refreshment Break Gene Expression via Redox-Linked PEGSummit.com Bioelectronics 4:20 A Multi-Landing Pad DNA Integration William E. Bentley, PhD, Robert E. Fischell Platform for Mammalian Cell Engineering Distinguished Chair, Engineering; Inaugural Director, Liliana Wroblewska, PhD, Principal Scientist, Robert E. Fischell Institute for Biomedical Devices, Biomedicine Design, Pfizer, Inc. Chemical and Biomolecular Engineering, University of Reliable, large-scale engineering of CHO cells through Maryland, College Park precise insertion of large amounts of heterologous REGISTER at PEGSummit.com | 48 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EXPRESSION STREAM PROTEIN EXPRESSION SYSTEM ENGINEERING continued PARTICIPANTS REGISTER TODAY FRIDAY, APRIL 12 high-end biologics with authentic post-translational discuss our recent efforts to engineer encapsulin modifications and tailor-made glycosylation patterns. nanocompartment systems to enhance expression of 8:00 am Morning Coffee AMPs in Escherichia coli. 10:05 Networking Coffee Break COVER ANALYZING & IMPROVING PRODUCTIVITY 12:35 Luncheon Presentation: Sponsored by 10:35 Synonymous Codon Selection for Strategies to Increase the Speed 8:30 Chairperson’s Remarks Enhanced Yield of Functional Proteins CONFERENCE-AT-A-GLANCE of Cell Line Generation for Christopher H. Gray, PhD, Staff Scientist & Team Patricia Clark, PhD, John Cardinal O’Hara, C.S.C. Leader, Structural Biology, Drug Discovery Program, Biomanufacturing Whilst Maintaining SHORT COURSES Professor, Chemistry & Biochemistry, University of CRUK Beatson Institute Notre Dame Performance Fay Saunders, PhD, Head, Mammalian Cell Culture, PD, TRAINING SEMINARS Historically, “optimizing” a gene for heterologous 8:35 FEATURED PRESENTATION: expression consisted of substituting rare codons FUJIFILM Diosynth Biotechnologies Methylation Analysis of Cell Lines with with synonymous common codons. This strategy Increasing efforts are focused towards reducing the time taken to move from gene to GMP manufacturing. ENGINEERING Varying Productivities can increase the amount of protein produced but Susan Sharfstein, PhD, Professor, at the expense of adversely affecting the yield of In this study we demonstrate how to leverage (i) Nanobioscience, Nanoscale Science and active, functional protein. This talk will focus on our host cell line directed evolution strategies to improve Engineering, SUNY Polytechnic Institute recent discoveries regarding rare codon distribution bioprocess relevant phenotypes and increase mAb ONCOLOGY DNA methylation plays a critical role in in naturally occurring coding sequences and rational titres up to 2-fold; and (ii) key technology enablers that regulating gene expression, and it is well known strategies for rare codon placement to enhance allow intensification of cell line development timelines. that the CMV promoter contains a CpG island folding yield. 1:05 Networking Refreshment Break that is subject to silencing by methylation. Using IMMUNOTHERAPY 11:05 Cell-Free Synthetic Biology for a novel next-generation sequencing approach, IMPROVING EXPRESSION SYSTEMS we have analyzed the methylation status of Therapeutics, Sensing, and Remediation the CMV promoter for cell lines with varying David Karig, PhD, Associate Professor, Systems and 1:35 Chairperson’s Remarks EXPRESSION productivity to provide insight into the role of Synthetic Biology, Bioengineering, Clemson University David Karig, PhD, Associate Professor, Systems and methylation in control of transgene expression. Cell-free protein expression systems offer a number Synthetic Biology, Bioengineering, Clemson University of advantages for implementing synthetic biology 1:40 Molecular Approaches that Improve applications. They simplify system composition ANALYTICAL 9:05 Improving Cytidine and Adenine Base and tuning, avoid evolution away from the intended Soluble Protein Yields from Bacterial Editors by Expression Optimization and function, and alleviate safety concerns associated Expression Systems Ancestral Reconstruction with the spread of engineered living cells. Key Christopher H. Gray, PhD, Staff Scientist & Team IMMUNOENICITY Luke Koblan, PhD, Scientist, Chemical Biology, developments in the preservation and ruggedization Leader, Structural Biology, Drug Discovery Program, & BIOASSAYS Chemistry & Chemical Biology, Harvard University of cell-free reagents will enable therapeutics CRUK Beatson Institute Base editors enable targeted single-nucleotide production in the field as well as environmental Expression systems targeting well folded products FUSIONS & conversions in genomic DNA. The usefulness of base sensing and remediation. often employ contradictory strategies, pushing editors for research and therapeutic applications production with strong promoters and codon- CONJUGATES strongly depends on the efficiency with which they 11:35 Identification of ADP-Ribosylation by enhanced cDNAs, while simultaneously slowing the modify target nucleotides. Optimizations to improve Tandem Mass Spectrometry process by titrating back inducing reagents or culture editor expression, nuclear localization, and the Guy Poirier, PhD, Professor, Faculty of Medicine, temperature. Often, elevated total expression levels THERAPEUTICS & component deaminase domain enable substantially Scientific Advisor, Proteomics Platform CHU of aren’t matched by a similar increase in the recovery TECHNOLOGIES improved editing by both cytidine and adenine base Quebec, Université Laval of soluble protein. We compare a series of alterations editors in a variety of mammalian cell types. BE4max, We have developed a new method to identify all to key codons and expression-vector sequence AncBE4max, and ABEmax represent the current state- the ADP-ribosylation sites independent of the elements that attenuate protein production rates and SPONSOR/EXHIBIT of-the-art base editors. acceptor amino acid. This method uses tandem maximise soluble recovery. INFORMATION mass spectrometry amenable to CID or other Sponsored by 9:35 Development and Production modes of fragmentation. The mass spectrometry 2:10 Engineering CHO Metabolic Essential HOTEL & TRAVEL INFORMATION of Biologics Beyond Antibodies signature is very unique and is stable in any mode of Gene for Efficient and High Expressing Clones Ulrich Kettling, Vice President, Business fragmentation. Suited for Perfusion Processes REGISTRATION INFORMATION Development, CEVEC Pharmaceuticals GmbH Hatim Motiwala, PhD, Head, Cell Line Engineering and While antibodies have become standard, now more 12:05 pm Production of Antimicrobial Peptides Bio-Analytical Sciences, Enzene Biosciences Limited and more complex, glycosylated proteins get into Using Protein-Cage Carrier Proteins A double knock-out cell line for two important metabolic REGISTER ONLINE! the focus of biopharma research, as cell therapy Mimi Cho Yung, PhD, Staff Scientist, Biosciences and genes was created using CRISPR/Cas. This allows for PEGSummit.com reagents and therapeutics. While such complex Biotechnology Division, Physical and Life Sciences a strong clonal selection of a monomeric or dimeric proteins represent a large portion of the human Directorate, Lawrence Livermore National Laboratory protein. The cell line is also tested in continuous proteome they are notoriously difficult to express (LLNL) upstream process for significantly higher expression. in CHO or microbials. The presentation discusses The bioproduction of antimicrobial peptides (AMPs) the CAP cell lines and CAP-Go expression platform in bacterial expression systems remains a challenging which are specifically designed for production of problem due to host toxicity and proteolysis. We will REGISTER at PEGSummit.com | 49 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EXPRESSION STREAM PROTEIN EXPRESSION SYSTEM ENGINEERING continued PARTICIPANTS REGISTER TODAY 2:40 Recombinant (Membrane) Protein Production in Yeast Roslyn M. Bill, DPhil, Professor, Biotechnology; COVER Associate Dean, Research, Aston University My lecture will focus on methods that are available CONFERENCE-AT-A-GLANCE for protein synthesis in yeasts, which are an important source of recombinant eukaryotic membrane SHORT COURSES proteins. I will provide an overview of approaches to optimize the expression plasmid, host cell and culture TRAINING SEMINARS conditions, as well as the extraction and purification of functional protein for further study. 3:10 Development of the Filamentous Fungus ENGINEERING Myceliophthora thermophila C1 into a Next- Generation Therapeutic Protein Production System ONCOLOGY Anne Huuskonen, MSc, Research Scientist, VTT Technical Research Centre of Finland, Ltd. We are utilizing the vast protein production IMMUNOTHERAPY capability of the filamentous fungus Myceliophthora thermophila to construct a highly potent therapeutic protein production platform. Superb productivities of full-length antibodies, up to 2.5 g/l/day, have EXPRESSION been reached. We have also successfully produced several difficult-to-express proteins such as bispecific antibodies and vaccine proteins in titers superior to ANALYTICAL other expression systems. Our work also aims at humanizing the glycosylation pathway of this fungus, and the first steps in this research line have been IMMUNOENICITY successful. & BIOASSAYS 3:40 End of Conference

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COVER

CONFERENCE-AT-A-GLANCE ANALYTICAL STREAM

SHORT COURSES

TRAINING SEMINARS

ENGINEERING Best Practices and Solutions Characterization of for Analytical Characterization, ONCOLOGY Biotherapeutics Biophysical/Structural Analysis and IMMUNOTHERAPY Drug Product Development for Biophysical and Next-Generation Biotherapeutics EXPRESSION Structural Analysis The Analytical Stream focuses on the application of biochemical, biophysical and structural characterization tools to help gain a ANALYTICAL detailed knowledge of proteins from discovery through all the stages Analytical Support for Drug of development, and for 2019 presents a new meeting exploring IMMUNOENICITY the analytical challenges of drug product development. This three- & BIOASSAYS Product Development meeting stream offers a range of best practice case studies from industry and academic perspectives on the characterization of new FUSIONS & CONJUGATES modalities (including CAR-Ts and gene therapy), emerging analytical methods and responses to regulatory requirements related to THERAPEUTICS & analytical characterization. TECHNOLOGIES

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9TH ANNUAL COVER

CONFERENCE-AT-A-GLANCE CHARACTERIZATION OF BIOTHERAPEUTICS Exploring the Analytical Challenges of Today’s Complex Biologics SHORT COURSES

TRAINING SEMINARS April 8-9, 2019 | Seaport World Trade Center | Boston, MA

As new product formats progress through development and into the regulatory process, the role of analytical characterization is taking on new meaning. Very new ENGINEERING modalities present challenges to both analytical scientists and regulatory agencies alike, and this steep learning curve requires a near-constant cycle of adaptation and innovation. The agencies are requiring sponsors to provide ever more complex data across a wide range of analytical methods, and instrumentation suppliers are striving to support this new era with unique product features, software and feature combinations. The PEGS Characterization of Biotherapeutics conference explores the progression of analytical development for an exciting range of emerging modalities and offer a case study forum for those working in the field to share ideas, ONCOLOGY experiences and solutions that support the preclinical and clinical development of new biotherapeutics.

SUNDAY, APRIL 7 found truncation problem in early production stage. REGULATORY CHALLENGES IMMUNOTHERAPY MS, especially Top-down MS, was able to provide 10:50 The Regulatory Path for Breakthrough Recommended Short Course(s)* sequencing information with high efficiency, quick turnover and independency. Designations and Orphan Drugs SC2: Translational Biotherapeutic William C. Motel, PhD, Director, Regulatory Affairs, EXPRESSION Development Strategies Part 1: Discovery, 9:10 Characterization of Novel and Complex IQVIA Global Regulatory Affairs Molecular Assessment and Early Stage Antibody Formats The U.S. Food and Drug Administration (FDA) offers Development Markus Haberger, PhD, Senior Scientist, Roche, Germany several special designations to aid in progression ANALYTICAL SC7: Translational Biotherapeutic The number of novel biotherapeutic antibody- of a drug’s approval. The orphan drug designation Development Strategies Part 2: Analytical based formats in drug development is continuously specifically targets products that treats a rare disease and Clinical Considerations increasing. Characterization of these formats is or condition affecting fewer than 200,000 Americans, IMMUNOENICITY *Separate registration required. Click here or see challenging. Since established physiochemical while the breakthrough therapy designation applies & BIOASSAYS page 5 for course details. and mass spectrometric methods show limited to a drug that is aimed at treating a serious or capabilities for characterization of product related life-threatening disease or that may demonstrate impurities, new analytical strategies have to be substantial improvement over existing therapies. FUSIONS & MONDAY, APRIL 8 developed. Here, we present a native MS based 11:20 CMC Analytical Strategies Designed for CONJUGATES analytical approach which successfully assisted Regulatory Dialog Intended for Early Phase 7:00 am Registration and Morning Coffee in the elucidation of size and charge variants of IND Filings CHARACTERIZATION OF COMPLEX complex antibody formats such as bispecific THERAPEUTICS & antibodies or antibody fusion proteins. Vaneet K. Sharma, PhD, Manager, Analytical TECHNOLOGIES FORMATS Development, Vaccine Development & Manufacturing, 9:40 Expanding Role of Mass Spectrometry in International AIDS Vaccine Initiative (IAVI) 8:30 Chairperson’s Opening Remarks Development of Biotherapeutics This presentation will outline phase appropriate William C. Motel, PhD, Director, Regulatory Affairs, CMC analytical strategies intended for successful IQVIA Global Regulatory Affairs Dhaval Nanavati, PhD, Senior Scientist, AbbVie SPONSOR/EXHIBIT regulatory submissions, especially for exploratory INFORMATION The versatility of mass spectrometer has made it the 8:40 Identifying Early Production Truncated prevailing analytical platform for understanding the and phase 1 programs. A case study will be presented to demonstrate the application of the HOTEL & TRAVEL INFORMATION Drug Candidates by Top-Down Mass distribution, target interaction, off target interaction Spectrometry of biotherapeutics. The role of mass spectrometry regulatory accepted phase appropriate analytical characterization to support HIV vaccine development. REGISTRATION INFORMATION Zhe Zhang, PhD, Senior Scientist, Novartis Institutes in dissecting post translational modified variants for BioMedical Research of a putative target is also critical in identification Mass spectrometry has shown to be a powerful tool of unique targets and development of novel bio REGISTER ONLINE! to characterize different therapeutic protein formats. therapeutics. In this work, we show specific examples PEGSummit.com With intact MS and peptide mapping, identification of enhanced foot print of mass spectrometry in early and site-specific characterization can be achieved. stages of development of biotherapeutics. Top-down mass spectrometry, however, can provide 10:10 Networking Coffee Break added value, for example avoiding digestion and artifact generation, sequence coverage on special regions, etc. Two case studies from different projects REGISTER at PEGSummit.com | 52 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM CHARACTERIZATION OF BIOTHERAPEUTICS continued PARTICIPANTS

REGISTER TODAY 11:50 KEYNOTE PRESENTATION: Planning sample, enabling you to move on to the next steps in provides the needed template for development the Extent and Timing of Analytical your workflow with confidence. of immunotherapeutics and improved vaccines. Studies: What is the Risk to Benefit Impact Sponsored by COVER 1:20 Luncheon Presentation II: in Relation to Drug Development Stage? MS-Based Characterization of Jennifer F. Nemeth, PhD, SCPM, Director, Biophysics, 5:40 Welcome Reception in the Exhibit Hall CONFERENCE-AT-A-GLANCE Structural Characterization, Biologics Discovery Biotherapeutics and HCPs in with Poster Viewing Production Bioprocesses Using a Single Sciences, Janssen Research & Development 7:15 End of Day SHORT COURSES New biologic drug development is costly, and Software Platform where money is spent impacts a company’s Xiaojuan Li, PhD, Associate Principal Scientist, Protein TRAINING SEMINARS pipeline. Upfront spend can allow for Mass Spectrometry Department, Merck & Co., Inc TUESDAY, APRIL 9 quicker Go/NoGo decisions or while limited This presentation describes application of automated 8:00 am Registration and Morning Coffee development allows for a faster path to PoC. MS data processing workflows for intact mass ENGINEERING This talk will focus on the benefits/risks of analysis, released N-glycan analysis, and peptide CELL AND GENE THERAPY applying analytical assays before vs after mapping that provide efficient, in-depth characterization New Molecular Entity Declaration, and which of biotherapeutic products. In addition, we present a 8:25 Chairperson’s Remarks assay were found to be the most impactful for workflow that automatically detects and quantifies host Qin Zou, PhD, Group Leader, Analytical Research and Development, Pfizer Inc. ONCOLOGY selection to justify the spend and time. cell proteins in bioprocess monitoring while reducing the number of false positive identifications. Sponsored by 8:30 Regulatory Expectations for Gene 12:20 pm ProteinMentor Therapy CMC Information 1:50 Session Break IMMUNOTHERAPY Developability Assessment: Case Michelle Joubert, Scientist, Analytical Development, Sanofi Studies for Therapeutic Proteins 2:20 Problem-Solving Breakout Discussions An increasing number of gene therapy products are Belinda Pastrana, PhD, CEO, Protein Dynamic Solutions 3:20 Networking Refreshment Break entering clinical development, and several approvals EXPRESSION Two case studies will be presented on developability are anticipated in the near future. As a consequence of analysis of therapeutic proteins. An array-based this intense activity, regulatory guidance has evolved to biophysical platform was used for deamination PLENARY KEYNOTE SESSION become more specific for these advanced therapies. assessment, stability and higher order structure This was highlighted by the recent publication by the ANALYTICAL determination. Drug substance and drug products 4:00 Chairperson’s Remarks FDA of several draft guidance documents for cell and were evaluated and the data generated can be used for Rakesh Dixit, PhD, DABT, Vice President, R&D, gene therapies. We will discuss current thinking for computational modeling for logic-driven protein design. Global Head, Biologics Safety Assessment, gene therapy CMC packages and expectations for an IMMUNOENICITY Translational Sciences, AstraZeneca IND filing. We will also share experiences and feedback Sponsored by & BIOASSAYS 12:35 Cryo-EM Unveils Antibody- we have encountered. Mediated Neutralization 4:10 Vision for How Immunotherapy Will Mechanism of Enteroviruses Shape Future of Cancer Care 9:00 Application of Analytical Ultracentrifugation: FUSIONS & Xiaodong Yan, PhD, Executive Director, Biortus Leena Gandhi, MD, PhD, Vice President, Immuno- from Protein Therapeutics to Gene Therapy CONJUGATES Biosciences Co., Ltd. Oncology Medical Development, Lilly Oncology Qin Zou, PhD, Group Leader, Analytical Research and Cryo-electron microscopy (cryo-EM) becomes a very Immunotherapy is considered by many as a Development, Pfizer Inc. powerful tool for epitope-mapping. We hereby present pillar of cancer care today, but in many ways we This presentation will intend to provide an overview on THERAPEUTICS & near-atomic cryo-EM structures of three Enteroviruses have only scratched the surface. Our knowledge using analytical ultracentrifugation in biotherapeutic TECHNOLOGIES (CVA6, CVA10 and D-68) and their immune complexes. and understanding of the complexities of development. Specific case studies will be provided to The ensemble of structures reveals molecular immunotherapy and its mechanisms continue to highlight these applications to various modalities. A mechanisms of antibody-mediated neutralization and evolve. The future of cancer care will be defined stage-tailored strategy in using the technology during SPONSOR/EXHIBIT will facilitate the development of effective vaccines and by our ability to systematically identify and drug development is discussed. implement opportunities for combination therapy INFORMATION therapeutics against Enterovirus infections. to improve and standardize patient response. 9:30 Leveraging High-Dimensional ‘-omics’ 12:50 Luncheon Presentation I: Sponsored by HOTEL & TRAVEL INFORMATION 4:55 The Lassa Virus Glycoprotein: Technologies for Comprehensive Profiling of Boost Your Protein Quantification Stopping a Moving Target CAR T Cells to Resolve Drug Product Complexity with Same-Time Quality REGISTRATION INFORMATION Kathryn Hastie, PhD, Staff Scientist, Immunology Eric S. Alonzo, PhD, Scientist, Process and Analytical Lisa Adamiak, PhD, Product Manager, Marketing, and Microbiology, The Scripps Research Institute Development, bluebird bio Unchained Labs Lassa virus causes ~5000 deaths from viral Clinical-grade CAR T cell drug products contain a REGISTER ONLINE! There are many reasons to assess the quality of hemorrhagic fever every year in West Africa. heterogenous mixture of phenotypically and functionally protein samples prior to downstream analysis, such PEGSummit.com The trimeric surface glycoprotein, termed distinct cells. Such heterogeneity necessitates innovative as comparing batches of purified material, changing GPC, is critical for infection, is the target for and comprehensive strategies to characterize CAR T formulation conditions, or checking the integrity neutralizing antibodies, and a major component cell therapy investigational drug products. A case study of thawed or stressed samples. With Stunner, of vaccines. Structural analysis of Lassa GPC will be presented to demonstrate how high dimensional you can now perform painless quality checks by bound to antibodies from human survivors ‘-omics’ is used in CAR T manufacturing and beyond to determining the concentration, hydrodynamic size, reveals a major Achilles heel for the virus and and polydispersity at the same time with just 2 µL of REGISTER at PEGSummit.com | 53 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM CHARACTERIZATION OF BIOTHERAPEUTICS continued PARTICIPANTS resolve drug product complexity and identify potentially Driven by increasing industry demand for a robust We present a workflow system that enables REGISTER TODAY key clinical correlates. accurate mass MS system for routine biotherapeutic systematic developability and manufacturability 10:00 Coffee Break in the Exhibit Hall with analysis within the process, development and quality assessments, using both in silico and high throughput Poster Viewing organizations, a new small footprint bench-top LC-MS analytical confirmatory methods, over the entire COVER system was purposefully designed and developed biologics R&D process from initial discovery all the 10:50 Analytical Challenges During CAR T to offer simplified operational modes, and optimized way to final candidate selection. We show use cases CONFERENCE-AT-A-GLANCE Process Development automation with accurate and reproducible mass for mAbs and other complex multi/bispecific formats Ken Prentice, Independent Consultant measurements for proteins, peptides and released and discuss building predictive developability models SHORT COURSES 11:20 Challenges Associated with glycans. In this work, we show specific examples of utilizing this system. We also present the underlying Manufacturing and Release of Autologous Cell deploying this compliance-ready bench-top system in molecule and task management needed for analytical TRAINING SEMINARS Therapy Products late stage development of biotherapeutics. organizations to accomplish this. Kuldip Sra, PhD, Senior Director, CRISPR Therapeutics 1:20 Ice Cream Break in the Exhibit Hall with 3:35 Refreshment Break in the Exhibit Hall An autologous cell therapy product to treat B cell Poster Viewing with Poster Viewing ENGINEERING malignancies was approved in the USA in 2017 and in the EU in September 2018. Since cell therapy products CHARACTERIZATION CHALLENGES OF ADCS AND CONJUGATED PROTEINS manufacturing takes 6-7 days and to deliver the final BISPECIFICS 4:25 Characterization of Antibody Drug Conjugates ONCOLOGY product to sick patient within 2-3 wks of leukophoresis, Liqiang (Lisa) Zhou, PhD, Senior Scientist, Protein rapid and robust analytical methods must be adapted to 2:00 Chairperson’s Remarks Analytics, AbbVie release final products in less than one week. Zhimei Du, PhD, Director, Bioprocess, Merck & Antibody-drug conjugates (ADCs) are becoming Company, Inc. an increasingly important class of biotherapeutics. IMMUNOTHERAPY 11:50 Lentiviral Vector Engineering and Different levels of heterogeneity contributed by mAbs Characterization of Vector Potency for Cell Therapy 2:05 Domain Characterization of Protein Therapeutics In Vivo by Multiplexed NanoLC- and the conjugated drugs lead to complexity in ADC Marc-André Robert, PhD, Scientist, Technology characterization. In-depth understanding of the HRMS Approaches EXPRESSION Development, BioMarin Pharmaceuticals physicochemical properties of ADCs is essential to drug Lentiviral vectors (LV) are currently investigated for Jessy Fan, PhD, Scientist, Amgen development and process control. A wide variety of cell therapy because they can integrate into the cell Next generation protein therapeutics are designed to analytical methods have been used in the characterization genome and provide sustainable gene expression. enable enhanced pharmacology, greater selectivity, ANALYTICAL of an interchain cysteine-conjugated ADC, with particular Thus, they can be used to replace a defective gene and altered drug disposition for an overall improved focus on the charge variants and size variants. by providing a functional version of it. The model therapeutic profile. Engineering efforts entail addition presented here is hematopoietic stem cells used to of nonconventional domains that require robust 4:55 Impurity characterization, Control IMMUNOENICITY treat blood disorders. The presentation will focus characterization of molecular instabilities. Online Strategy and Specification Justification in & BIOASSAYS on improving and characterizing the potency of LV, a multiplexed Peptide Immuno-affinity Enrichment (PIE) Small Molecules (Payload and Linker) critical quality attribute of LV. LC-MS workflow enables simultaneous assessment Jane Zhao, PhD, Principal Scientist, Immunogen of molecular integrities through detection of DM4 and Sulfo-SPDB are payload and linker in the ADC Sponsored by FUSIONS & 12:20 pm Luncheon Presentation I: individual domains of the therapeutic proteins. Case manufacturing process of mirvetuximab soravtansine CONJUGATES In-depth Evaluation of Maurice studies presented herein demonstrate different drug substance. Impurities in these two small CE-SDS System for Method properties of therapeutic proteins in vivo. molecule intermediates are well characterized and Development and QC Environment specified with acceptance criteria that are based on THERAPEUTICS & Pegah Abadian, PhD, Scientist II, Biologics 2:35 The Roadmap of Bispecific Recombinant manufacturing capability, downstream clearance and TECHNOLOGIES Development (Analytical Method Development), Protein Drug Development clinical exposure. Impurity fate mapping and trending Bristol Myers Squibb Zhimei Du, PhD, Director, Bioprocess, Merck & Company, Inc. in each step of the synthetic route and during process CE-SDS method is employed in biologics DS/DP control. Bispecific recombinant proteins are emerging development and PAR studies enable better control of SPONSOR/EXHIBIT The SCIEX PA800+ is the current standard instrument fields in biological drug development. These new impurities and hence improve product quality. INFORMATION and provides repeatable results. However, next- modalities have significantly expanded the functions 5:25 End of Characterization of Biotherapeutics generation CE SDS instruments such as ProteinSimple of conventional mAbs as biotherapeutics. There are 5:30 Registration for Dinner Short Courses HOTEL & TRAVEL INFORMATION Maurice can increase throughput and decrease cost per many protein scaffolds in bispecifics field. Besides injection, among other benefits. This project provides targeting two antigens simultaneously, different Recommended Short Course* REGISTRATION INFORMATION an in-depth comparison of the Maurice with the PA800+ molecule designs have very different features and using BMS biologics assets in regard to 1) Onboard challenges in bioactivity, pharmacokinetics, and SC9: Introduction to Biophysical Analysis for Stability, 2) Reported Purity, 3) Method Robustness, and manufacturability. We will discuss challenge details Biotherapeutics: Development Applications REGISTER ONLINE! 4) Flexibility of applying Custom Gels to QC Space. and solutions in various CMC development areas that *Separate registration required. Click here or see directly impact product yield and product qualities. page 5 for course details. PEGSummit.com 12:50 Luncheon Presentation II: Sponsored by Enabling Routine and Reproducible 3:05 A Platform Approach to Manage Biotherapeutic Analysis when Data Developability and Manufacturability Risks of Integrity Matters Biologics Molecules Henry Shion, Principal Scientist, Waters Corporation Amanda Fitzgerald, PhD, Senior Scientific Consultant, Biologics, Genedata REGISTER at PEGSummit.com | 54 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM PARTICIPANTS REGISTER TODAY 7TH ANNUAL BIOPHYSICAL AND STRUCTURAL ANALYSIS COVER Implementing Emerging Technologies for Improved Product Quality and Accelerated Development Timelines

CONFERENCE-AT-A-GLANCE April 10-11, 2019 SHORT COURSES Biophysical and structural analysis is now playing increasingly important roles in the discovery and development of next generation biotherapeutics. Developability TRAINING SEMINARS assessment is now standard practice across the industry, and understandings gained at this step are now being applied in the optimization of candidates at early stages of the pipeline. Higher resolution tools are enabling better understandings of how to characterize and control aggregation and particulates and are increasingly allowing these methods to be used in a quantitative, rather than qualitative way. The PEGS Biophysical and Structural Analysis conference brings together an international ENGINEERING audience of protein scientists and analytical specialists to explore the latest technologies and methods for problem solving in this dynamic field and identify ways of optimizing the studies performed in support of regulatory filings and manufacturing.

ONCOLOGY TUESDAY, APRIL 9 used technique for assessing protein higher order or liquid chromatography, which are used for structure (HOS) but remains difficult to assess HOS batch release, are well-suited and sufficient with high fidelity due to lack of sensitivity towards to assess HOS, especially during early clinical Recommended Short Course* IMMUNOTHERAPY subtle structural perturbations. This presentation development. SC9: Introduction to Biophysical Analysis will discuss these challenges and an effective for Biotherapeutics: Development experimental method for CD measurements with the Applications relevant examples from analytical comparability for 10:10 Coffee Break in the Exhibit Hall with EXPRESSION *Separate registration required. Click here or see process change and forced degradation studies for Poster Viewing page 5 for course details. establishing critical quality attributes. 10:15 Women in Science Speed Networking in 9:10 Ion Mobility Spectrometry Mass ANALYTICAL the Exhibit Hall WEDNESDAY, APRIL 10 Spectrometry (IMS-MS) for HOS Characterization IMPLEMENTING THE MULTI-ATTRIBUTE 7:15 am Registration and Morning Coffee Brandon Ruotolo, PhD, Professor, Chemistry, IMMUNOENICITY University of Michigan METHOD (MAM) & BIOASSAYS 7:25 - 8:25 PANEL DISCUSSION: Women in The next generation of medicines will rely heavily 10:55 MAM Method Development and Science – Inspired Professional and Personal upon our ability to quickly assess the structures Qualification FUSIONS & Stories and stabilities of large, complex macromolecular Jihong Wang, PhD, Principal Scientist, AstraZeneca CONJUGATES Moderator: Women in Bio, Boston Chapter machines, as well as the influence of large libraries Several multi-attribute monitoring methods (MAM) Panelists: of conformationally-selective small molecule binders have been developed in the biopharmaceutical Susan Richards, PhD, Presidential Scientific Fellow, and protein-based biotherapeutics. Such endeavors industry in recent years. We reported MAM method THERAPEUTICS & Translational Medicine Early Development, Sanofi R&D are nearly insurmountable with current tools. In this based on Quadrupole Dalton (QDa) mass detector presentation, I will discuss recent developments in TECHNOLOGIES Joanna Brewer, PhD, Vice President, Platform to selectively monitor and quantitate PTMs in a Technologies, AdaptImmune ion mobility-mass spectrometry (IM-MS) technology therapeutic monoclonal antibody. In this talk, case that seek to bridge this gap. Additional Panelists to be Announced studies will be presented on applications and SPONSOR/EXHIBIT implementation of QDa-based QC friendly MAM INFORMATION 9:40 KEYNOTE PRESENTATION: methods from supporting process characterization to CHARACTERIZING HIGHER ORDER The Underestimated Power of Well- product release. STRUCTURE Established Methods to Assess Protein HOTEL & TRAVEL INFORMATION 11:25 Implementing the Multi-Attribute Higher Order Structure 8:30 Chairperson’s Opening Remarks Method in a Multi-Site Analytical Development REGISTRATION INFORMATION Jessy Fan, PhD, Scientist, Amgen Alejandro Carpy, PhD, Senior Scientist, Large Molecule Research, Roche Diagnostics GmbH, Organization: Successes and Challenges 8:40 Characterization of Therapeutic Germany Kristin Boggio, PhD., Senior Scientist, Protein Mass REGISTER ONLINE! Proteins by Circular Dichroism Spectroscopy: Proper higher order structure (HOS) is essential Spectrometry, Pfizer Biotherapeutics development requires thorough PEGSummit.com Application to Process Comparability and for the function and stability of biologics. A Establishment of Critical Quality Attributes large number of biochemical or biophysical understanding of product quality attributes (PQAs) to ensure that clinical materials meet the desired safety/ Gurusamy Balakrishnan, PhD, Scientist, Bristol-Myers methods are available to assess HOS, which efficacy profile. Numerous routine assays are used to Squibb differ in sensitivity and specificity. We will show that approaches based on combination characterize and monitor PQAs; however, execution Circular dichroism (CD) spectroscopy is a widely of conventional methods such as bioassays REGISTER at PEGSummit.com | 55 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM BIOPHYSICAL AND STRUCTURAL ANALYSIS continued PARTICIPANTS REGISTER TODAY of multiple methods becomes time and resource quality metric. Currently it is almost impossible to 3:45 Refreshment Break in the Exhibit Hall with intensive, often providing indirect measurements of obtain this vital info during early stage formulation Poster Viewing biologically-relevant PQAs. We have incorporated the development. Come see how the new HORIZON mass spectrometry-based multi-attribute method at system from Halo Labs uses Backgrounded 4:45 Problem-Solving Breakout Discussions COVER various stages in non-GMP product development to Membrane Imaging (BMI) to measure subvisible 5:45 Networking Reception in the Exhibit Hall monitor multiple PQAs within a single experiment. particles, including translucent protein aggregates. The with Poster Viewing CONFERENCE-AT-A-GLANCE measurement is fully automated for up to 96 samples 11:55 Development of MS-Based Multi- and uses 1/10th the volume of other techniques. 7:00 End of Day SHORT COURSES Attribute Methods for ADC Process Support Lintao Wang, Ph.D., Associate Director, Analytical and 1:55 Session Break TRAINING SEMINARS Pharmaceutical Development, ImmunoGen, Inc. THURSDAY, APRIL 11 Antibody-drug conjugates (ADCs) are complex METHODS AND INSTRUMENTS 8:00 am Registration and Morning Coffee anti-cancer biomolecules that have multiple quality 2:10 Chairperson’s Remarks ENGINEERING attributes. A mass spectrometry based multi-attribute Brandon Ruotolo, PhD, Professor, Chemistry, University SPECTROMETRY METHODS method (MAM) was developed for monitoring of Michigan 8:30 Chairperson’s Remarks quality attributes (such as deamidation, oxidation, 2:15 Leveraging Force Degraded Material glycosylation, disulfide mispairing, etc.) to support Iain D. G. Campuzano, Principal Scientist, Discovery to Increase the Throughput of Peptide Map Attribute Sciences, Amgen ONCOLOGY process development of an ADC with engineered cysteine linkage. Characterization 8:35 Cutting-Edge Chromatographic, Romesh Rao, Research Associate, Analytical Sciences, Electrophoretic and Mass Spectrometry of Sponsored by Seattle Genetics IMMUNOTHERAPY 12:25 pm A Three-Pronged mAbs, Fc-Fusion Proteins and ADCs Characterization Tool That Makes Appropriately degraded samples can increase Alain Beck, PhD, Senior Director, Biologics CMC and Unstable Proteins Cry “Uncle” the throughput of peptide map characterization Developability, Pierre Fabre Laboratories, France by facilitating data analysis. Post-translational Kevin Lance, PhD, Product Manager, Marketing, Developability and comparability assessment of EXPRESSION modifications (PTMs) in a highly degraded sample Unchained Labs current and next generation of biologics such as were identified and site localized, enabling rapid, Optimizing protein stability and developing the best engineered mAbs, Fc-fusion proteins, BsAbs and 2 site-specific assignments of PTMs during subsequent formulations for avoiding aggregation is important or 3G-ADCs requires state-of-the-art analytical and analysis of nominal samples by comparison. This ANALYTICAL throughout the biologics development pathway. structural methods. Case studies will be presented approach can also support lower resolution, higher Uncle’s unique combination of static light scattering, based on native and ion mobility MS, multi-level 2- throughput workflows. dynamic light scattering, and fluorescence gives you to 4 LC-MS, multiplexed Top and Middle-Down MS, IMMUNOENICITY the flexibility needed to tease out the right answers 2:45 PULSE-SPR and its Applications in multiple fragmentation techniques, comprising high & BIOASSAYS and understand the whole story. Developability Assessment energy collisional-, electron-transfer and ultraviolet Li Zhou, PhD, Senior Scientist, Global Biologics, AbbVie photo-dissociation (HCD, ETD and UVPD) and CE-MS. 12:55 Luncheon Presentation I: Sponsored by Downstream purification of therapeutic antibodies FUSIONS & The Perfect Recipe for Protein 9:05 The Application of Fourier Transform requires candidates to be stable under various stress Characterization Starts with CONJUGATES conditions such as low pH. Here we report a high Ion Cyclotron Resonance MS and Spectral Tycho and Knowing Protein Quality throughput method that measures protonation induced Deconvolution Algorithms within Biopharma Peter A. Fung, Senior Manager Product Marketing, Research THERAPEUTICS & unfolding of ligand binding sites for stability evaluation NanoTemper Technologies by surface plasmon resonance, or PULSE SPR. Iain D. G. Campuzano, Principal Scientist, Discovery TECHNOLOGIES Starting with material of questionable quality for Attribute Sciences, Amgen 3:15 Advances in High-Throughput Sponsored by protein purification and characterization leads to Native-MS analyses for accurate antibody, protein and Screening for Development and irreproducible or ambiguous results. Tycho tells nanodisc MW and DAR confirmation have traditionally SPONSOR/EXHIBIT you so much about the quality of your protein—its Formulation of Biologics been performed using oa-ToF instrumentation and INFORMATION presence, purity, concentration, functionality and John Champagne, PhD, Senior Applications Scientist, more recently the extended mass range Orbitrap similarity — in a single experiment. These can all be Northeast Regional Manager, Sales, Wyatt Technology analyzer with incremental improvements in data HOTEL & TRAVEL INFORMATION measured simply by determining whether your protein Light scattering addresses many key analytical quality. Analysis of mAbs, ADCs, nanodiscs and a is structurally intact or properly folded. Tycho fits into challenges in drug nanoparticle R&D, including PEGylated biotherapeutics used FT-ICR MS under REGISTRATION INFORMATION any step of a purification or characterization workflow accurate size distributions, conformation, payload, both native and denaturing LC-MS conditions. Also to easily monitor protein quality and help researchers and formulation. We review light scattering demonstrated is the use of a new parsimonious to get more consistent results. fundamentals and then present examples illustrating deconvolution algorithm that can efficiently REGISTER ONLINE! how. Wyatt’s unique light scattering instrumentation 1:25 Luncheon Presentation II: Sponsored by deconvolve highly polydisperse MS spectra. PEGSummit.com facilitates rapid and effective development of High Throughput Low Volume controlled release vehicles including liposomes, VLPs, Subvisible Particle Analysis polymer-encapsulated nanoparticles, and nanogels. John Proctor, PhD, Vice President, Marketing, Halo Labs Subvisible particle analysis is a key predictor of protein drug stability and an essential drug product REGISTER at PEGSummit.com | 56 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM BIOPHYSICAL AND STRUCTURAL ANALYSIS continued PARTICIPANTS REGISTER TODAY 9:35 Considerations of the Use of Sponsored by interactions of L-proline, L-arginine.HCl and NaCl Analytical Ultracentrifugation for with the native state of three IgG1 mAbs that differ Characterization of AAV Gene in their physical stability attributes. We also highlight Delivery Vectors differences amongst the excipients in terms of their COVER effect on the aggregation and viscosity of these Christopher Sucato, PhD, Senior Scientist, Biophysical antibodies at high protein concentration. CONFERENCE-AT-A-GLANCE Characterization, Charles River Analytical Ultracentrifugation (AUC) in the 12:05 pm Impact of Non-Ideal Analyte SHORT COURSES biopharmaceutical industry has traditionally been Behavior on the Separation of Protein employed in the analysis of aggregation and Aggregates by Asymmetric Flow Field-Flow TRAINING SEMINARS higher order structure in protein drug products, Fractionation where monomeric or dimeric protein is commonly Björn Boll, Ph.D., Head, Particle Lab and Higher Order the analyte. More recently, the rise of gene Structure Protein Analytics, Novartis Pharma AG, ENGINEERING delivery vectors as a means to treat a number of Switzerland conditions has opened new avenues for AUC-based Asymmetric flow field-flow fractionation (AF4) is characterization and QC lot release methodologies. a valuable tool for the characterization of protein ONCOLOGY 10:05 Coffee Break in the Exhibit Hall with aggregates owing to its broad size range and unique Poster Viewing separation principle. In practice, AF4 is non-trivial to use due to deviations from theory. This presentation AGGREGATION AND STABILITY gives an overview about non-ideal effects that IMMUNOTHERAPY influence AF4 separation including new approaches 11:05 Ultrafast High-Resolution Protein to minimize non-ideal behavior and drastically Analysis Unconventional Devices improving AF4 resolution by adjusting the mobile EXPRESSION Raja Ghosh, PhD, Professor, Chemical Engineering, phase. McMaster University, Canada High-speed, high-resolution analytical separation is 12:35 End of Biophysical and Structural one of the current needs with biopharmaceuticals. Analysis ANALYTICAL Separations using ultrafine particulate chromatographic media require ultra-high pressures Recommended Short Course* which could have detrimental effects on the SC14: Subvisible Protein Particles IMMUNOENICITY molecules being analyzed. In this presentation, in Immunogenicity: Measurement, & BIOASSAYS membrane-based devices suitable for rapid, high- Characterization and Impact resolution analytical protein separation are discussed. *Separate registration required. Click here or see Using these devices, high-resolution separation of page 5 for course details. FUSIONS & proteins could be carried out in minutes at less than 1 CONJUGATES MPa backpressure. 11:35 Effect of L-proline, L-arginine.HCl THERAPEUTICS & and NaCl on the Aggregation and Viscosity TECHNOLOGIES Behavior of High-Concentration Antibody Formulations Chaitanya Sudrik, PhD, Postdoctoral Associate, SPONSOR/EXHIBIT Molecular Engineering, Massachusetts Institute of INFORMATION Technology Development of subcutaneous formulations for HOTEL & TRAVEL INFORMATION monoclonal antibodies is hindered by several physical instabilities. In this study, we compare preferential REGISTRATION INFORMATION

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REGISTER TODAY INAUGURAL ANALYTICAL SUPPORT FOR DRUG PRODUCT DEVELOPMENT COVER Overcoming the Analytical and Formulation Challenges of a New Generation of Drug Products CONFERENCE-AT-A-GLANCE April 11-12, 2019 SHORT COURSES Advances in protein science, drug combinations, delivery technology and analytical methods are supporting an unprecedented wave in novelty in the design of biologic TRAINING SEMINARS drug products. With these new products comes the urgent need for analytical support of product development, regulatory filings and manufacturing – in ways that require a constant adaptation by analytical and formulation groups to new modalities and technologies. New for 2019, the PEGS Analytical Support for Drug Product Development conference provides a best practices exchange for scientists now working to develop these new products – or for those wishing to be prepared for ENGINEERING forthcoming programs in their organization’s pipelines.

THURSDAY, APRIL 11 were then evaluated to understand more about the 4:20 Method Development and ONCOLOGY potential to critically assess monoclonal antibody Characterization of Product Specific Host Cell 12:00 pm Registration sequences early in development. Proteins 12:35 Luncheon in the Exhibit Hall with Poster Jennifer Kessler, Senior Development Associate, IMMUNOTHERAPY Viewing 2:50 KEYNOTE PRESENTATION: Design MacroGenics, Inc. and Analytical Challenges of In Use Monoclonal antibodies and bispecific DART® KEY ASSAYS AND ISSUES IN DP Stability Studies for Biologics molecules are being developed for a variety of DEVELOPMENT Pierre Wils, PhD, Head, Biologics Formulation indications including immune-oncology. These EXPRESSION and Process Development, Sanofi, France biopharmaceuticals contain residual host cell proteins 1:40 Chairperson’s Opening Remarks The early clinical development of highly potent (HCPs) from production cell lines that can pose a risk Vijay Dhawan, PhD, Associate Director, Analytical biologics is usually performed by intravenous to product safety and stability. This presentation will ANALYTICAL Development, Sanofi administration requiring very low starting doses discuss the development of process specific HCP 1:50 Developability Evaluation: Right Tools at and wide dose ranging. We will present case methods and the characterization of product specific studies about in use stability studies, related the Right Time? HCPs using this novel class of molecules and other IMMUNOENICITY to the quantification of biologics in very dilute antibody molecules as case studies. Lasse Stach, Investigator, Drug Design and Selection, solutions, and means to minimize protein GlaxoSmithKline, United Kingdom & BIOASSAYS adsorption onto the infusion material. We 4:50 Phase Appropriate Potency Assays: What The talk will focus on the interface between discovery will also discuss trends in the preparation of Is Needed and When? and development, timing of the various developability FUSIONS & infusion solutions in hospital settings. Sheila G. Magil, PhD, Principal Consultant, BioProcess studies and deployment of the available tools. Early Technology Consultants, Inc. CONJUGATES lead selection of biotherapeutics requires meticulous Sponsored by Regulatory expectations for potency assays include assessment of a variety of molecule properties 3:20 A Platform Technology for their being related to the mode of action in vivo. There to minimize risk during development. However, the Rapid Generation Of Robust are many ways to measure potency and what method THERAPEUTICS & increased complexity of non-standard protein formats Anti-Idiotypic Binders for Clinical TECHNOLOGIES is best also depends on the phase of development. requires an adaptation from former platform-based PK Assays This presentation will describe approaches to screening to project specific strategies to select Matt Johnson, CTO, Avacta Life Sciences the development of acceptable potency assays quality candidates. Affimer proteins are next-generation affinity scaffolds throughout development including when and how to SPONSOR/EXHIBIT with great potential for the generation of both novel validate potency assays. INFORMATION 2:20 Approaches to Optimizing Manufacturability of Monoclonal Antibodies biotherapeutics and research tools. It is possible to generate highly-specific anti-idiotypic Affimer binders 5:20 End of Day Michael Anyadiegwu, PhD, Senior Scientist, HOTEL & TRAVEL INFORMATION using a 14-week development process. In comparison Downstream Processing, Center for Process 5:20 Registration for Dinner Short Courses to commercially available anti-idiotypic Fab REGISTRATION INFORMATION Innovation, National Biologics Manufacturing Center, United Kingdom fragments we have shown it is possible to develop Recommended Dinner Short Course* high-performing antibody PK assays (and ligand Molecules can fail to transition from discovery to SC14: Subvisible Protein Particles binding assays) in complex samples using only a REGISTER ONLINE! commercialisation due to developability issues in Immunogenicity: Measurement, single, specific capture Affimer and generic antibody such as instability, aggregation etc. A collaborative PEGSummit.com detection minimising assay complexity. Characterization and Impact project set out to systematically explore the *Separate registration required. Click here or see developability landscape of monoclonal antibodies 3:50 Networking Refreshment Break page 5 for course details. using experimental data. Sequences were expressed and purified allowing datasets of biochemical and biophysical quality attributes to be generated. These REGISTER at PEGSummit.com | 58 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM ANALYTICAL SUPPORT FOR DRUG PRODUCT DEVELOPMENT continued PARTICIPANTS

REGISTER TODAY FRIDAY, APRIL 12 analytical methods coupled with computational 1:05 Networking Refreshment Break approaches, was established and utilized to perform 8:00 am Morning Coffee high-throughput screening at early discovery stage to COMPARABILITY ANALYSIS COVER facilitate the discovery, selection, and optimization of DRUG PRODUCT DEVELOPMENT the most promising mAb molecules. Here we discuss 1:35 Chairperson’s Remarks Abbie Esterman, PhD, Senior Scientist, Methods and CONFERENCE-AT-A-GLANCE CHALLENGES case studies on improving mAb developability applying the principal of Quality by Design at Analytical Development, Bristol-Myers Squibb 8:30 Chairperson’s Remarks discovery stage. SHORT COURSES Gerald Gellermann, PhD, Senior Fellow, Novartis, 1:40 Method Bridging: Fit or Mis-fit Switzerland 11:05 IV Set Compatibility Studies for ADCs Abbie Esterman, PhD, Senior Scientist, Methods and TRAINING SEMINARS Analytical Development, Bristol-Myers Squibb 8:35 Dual mAb Therapies: Co-Administration Alexandra (Sasha) Zaitsev, Development Associate, Analytical & Pharmaceutical Sciences, ImmunoGen Technologies used for release and stability testing of and Co-Formulation Challenges and Solutions biologics are rapidly evolving to meet the ever-increasing Compatibility studies with administration sets of Jasper Lin, PhD, Scientist and Group Leader, challenges in drug development. Consequently, one or ENGINEERING the drug product are performed during early stage Genentech more analytical methods will need amendment during development to determine the propensity of the the product life cycle. Before new methods can be filed, Recently, there has been a surge of clinical trials antibody-drug conjugate (ADC) to become altered bridging studies are required to establish comparability using multiple mAbs to bring about synergistic upon contact with the infusion set materials. Possible ONCOLOGY and confirm the new method is fit for its intended use. efficacy. Sequential IV administration is burdensome alterations include adsorption to the infusion Two case studies bridging novel and conventional for the patient, leading to interest in developing CMC set, aggregation, particulate formation, etc. This methods for purity and charge heterogeneity analyses solutions by means of co-administration and fixed presentation will discuss challenges associated with will be examined. IMMUNOTHERAPY dose combinations (FDCs). FDCs provide a great deal study set up and interpretation of the acquired data. of promise, but also present new challenges. This talk will highlight formulation, process, and analytical 11:35 Device Considerations in Drug Product 2:10 Strategies for Comparability Testing to Support Process/Product or Manufacturing EXPRESSION challenges accompanying the development of co- Development – Case Study of Ophthalmic administration and co-formulation strategies. Injections of Anti-VEGF Therapies Site Changes Vijay Dhawan, PhD, Associate Director, Analytical Susan Dounce, PhD, Principal SME, Prefilled Syringes, 9:05 Tools for Developing a Mechanistic Development, Sanofi West Pharmaceutical Services ANALYTICAL Understanding of Specificity in Post- Accelerated timelines for clinical programs and an Frequent Injections into the eye can introduce Translational Modification Targeting increased reliance on external contract manufacturers particulate matter or biologic contaminants that can Antibodies during the different project stages have resulted in an lead to inflammation, infection, floaters in the vision or increased need to perform analytical comparability to IMMUNOENICITY Yongku Cho, PhD, Assistant Professor, Chemical and vision loss. It is therefore critical to understand how the Biomolecular Engineering, University of Connecticut support use of the post-change material in the clinic & BIOASSAYS delivery device itself can impact the safety of the drug while avoiding non-clinical or clinical bridging studies. Validation of antibody specificity is critical for product so that the proper material selections are made Approaches for establishing and executing analytical biotherapeutics development. In particular, antibodies for primary packaging to maximize patient safety. In this comparability plans will be discussed during the FUSIONS & targeting site-specific post-translational modifications talk, we will explore the critical device considerations for presentation. CONJUGATES (PTMs) require utmost specificity, due to their ophthalmic drug delivery. heterogeneous and transient nature. However, recent validation efforts reveal an alarming lack of specificity 12:05 pm Oligomericity Status Changes and its ANALYTICAL ISSUES IN QUALITY AND THERAPEUTICS & in PTM-targeting antibodies. This presentation Effects on the Stability of Proteins in Solution PROCESS CONTROL TECHNOLOGIES will showcase our recent efforts to overcome this Bettina Bommarius, PhD, Senior Research Scientist, 2:40 Development of Process and Product problem, by understanding the origin of specificity Chemical and Biomolecular Engineering, Georgia and applying protein engineering strategies to Institute of Technology Understanding: Use of Prior Knowledge and SPONSOR/EXHIBIT improve specificity. We have investigated protein activity and stability as Challenges for Setting of Specifications INFORMATION a function of the oligomeric status of a protein. Our Gerald Gellermann, PhD, Senior Fellow, Novartis, 9:35 Sponsored Presentation (Opportunity results indicate that activity and stability correlate Switzerland Available) HOTEL & TRAVEL INFORMATION with a uniform oligomeric presence and that the Applications for design space are rare as the risk 10:05 Networking Coffee Break proteins investigated can exist as a mixture of benefit of a full QbD application is not clear and QbD REGISTRATION INFORMATION different oligomers and aggregates. Factors that based applications usually receive more scrutiny 10:35 Bridging Discovery and Development by influence the percentages of each given oligomer/ than traditional once. In this presentation, we will Early Developability Assessment aggregate will be presented as well as effects of discuss the use of prior knowledge and compare REGISTER ONLINE! Qing Chai, PhD, Principal Research Scientist, Protein oligomeric mixtures on specific activities. Protein consequences on specifications setting and process PEGSummit.com BioSciences, Eli Lilly & Co. oligomericity is an underappreciated link between parameter criticality for the different development Biopharmaceutical development is often challenging. protein concentration and its activity or stability. approaches. Among those challenges is antibody “developability,” such as solubility, viscosity, manufacturability, 12:35 Luncheon Presentation (Sponsorship and formulation suitability. Multidimensional Opportunity Available) or Enjoy Lunch on Your developability assessment platform, including Own REGISTER at PEGSummit.com | 59 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL ANALYTICAL STREAM ANALYTICAL SUPPORT FOR DRUG PRODUCT DEVELOPMENT continued PARTICIPANTS

REGISTER TODAY 3:10 Theoretical Constraints on Design Space for High Concentration Filling: Minimizing Clogging and Increasing Filling Precision COVER Richard Galas, PhD, Senior Scientist, Takeda The fluid properties of many biologic formulations CONFERENCE-AT-A-GLANCE designed for pre-filled syringes are unique and create engineering challenges for filling systems. These SHORT COURSES products often clog the filling lines, causing costly delays while components are replaced. A theoretical TRAINING SEMINARS fluid mechanics approach to the filling process was taken to define key parameters that impact filling accuracy and clogging. This approach identified ENGINEERING a theoretical design space that minimizes filling variability and clogging. 3:40 End of Conference ONCOLOGY

IMMUNOTHERAPY

EXPRESSION

ANALYTICAL

IMMUNOENICITY & BIOASSAYS

FUSIONS & CONJUGATES

THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION

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COVER IMMUNOGENICITY CONFERENCE-AT-A-GLANCE & BIOASSAYS STREAM SHORT COURSES

TRAINING SEMINARS

ENGINEERING Immunogenicity Ensuring the Safety and Efficacy ONCOLOGY Case Studies and of Biologics Clinical Management This year’s Immunogenicity & Bioassay Stream focuses on the latest IMMUNOTHERAPY science, technologies and strategies to ensure the safety and efficacy of novel biologics, with particular focus on immunogenicity clinical management and assay life cycles. Part One looks at new case EXPRESSION Immunogenicity studies and how to use immunogenicity data in clinical settings; Part Assessment and Regulatory Two examines immunogenicity assessment for novel biologics such ANALYTICAL as ADCs, bispecifics, CAR-T and mAbs along with an emphasis on Approval of Biologics new regulatory guideline for cell and gene therapies; and Part Three IMMUNOENICITY will showcase emerging technologies and strategies for day-to-day & BIOASSAYS challenges when developing bioassays to evaluate potency, function and robustness of novel biologics. FUSIONS & CONJUGATES Optimizing Bioassays for Biologics THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION

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COVER 12TH ANNUAL

CONFERENCE-AT-A-GLANCE IMMUNOGENICITY CASE STUDIES AND CLINICAL MANAGEMENT Interpretation and Understanding of Immunogenicity Data in Clinical Settings SHORT COURSES

TRAINING SEMINARS April 8-9, 2019

As the immunogenicity field is moving forward, closing the gap between clinicians and assay developers is essential in the success of biologic development and ENGINEERING accelerates the adoption of new biologic therapies in patient treatments. This year, CHI’s Immunogenicity Case Studies and Clinical Management conference will focus on new case studies of novel biologics and emphasize closing this gap by providing multiple viewpoints from clinicians, technology developers and regulators on how to use immunogenicity data in clinical settings. ONCOLOGY SUNDAY, APRIL 7 disease population, drug MoA. Study designs to RISK ASSESSMENT AND WORK FLOW incorporate specific immunogenicity questions, PROCEDURE characterization of ADA responses, type of Recommended Short Course(s)* IMMUNOTHERAPY analyses to characterize the impact on PK, 10:45 Chairperson’s Remarks SC1: Preclinical and Clinical Assessment on PD, efficacy and safety and risk-benefit Vibha Jawa, PhD, Director and Lead, Predictive and of Immunogenicity: Multidomain perspective to decide if further mitigation Clinical Immunogenicity, PPDM,, Merck & Co Inc EXPRESSION Therapeutics and New Modalities, strategies are needed will also be discussed. Including Gene Therapy and CAR T 10:50 Increased Immunogenicity Associated with Combination Regimens with Immune SC5: In silico Immunogenicity Predictions 9:10 Relationship Between ADA and PK Modulatory Biologics ANALYTICAL (Hands-on) Workshop Assays: Is There an Impact? Jad Maamary, PhD, Associate Principal Scientist, *Separate registration required. Click here or see Marcela M. Araya, PhD, Principal Scientist, Group Predictive and Clinical Immunogenicity, PPDM, Merck page 5 for course details. Leader, BioMedicine Design, Pfizer and Co Inc IMMUNOENICITY The assessment of immunogenicity of therapeutics The use of immune modulatory biologics to augment & BIOASSAYS drugs is a requirement for regulatory filings. The functionality of immune cells can also augment MONDAY, APRIL 8 ADA formation may have an impact on the efficacy, the risk of immunogenicity. The quality of such an dosing schedules and sampling schedules. Current immune response and its clinical relevance will be FUSIONS & 7:00 am Registration and Morning Coffee gaps include a limited knowledge of the effect explored through this talk. Whether the activation CONJUGATES of endogenous ADA on PK/PD profiles, and the of immune cells can break tolerance to otherwise THE IMPACT OF IMMUNOGENICITY ON inconsistency of reported types of ADA responses tolerant sequences will also be explored. SAFETY AND EFFICACY (e.g., titers, concentration, isotypes, etc). The THERAPEUTICS & 11:20 ADA Testing in Clinical Routine: Where 8:30 Chairperson’s Opening Remarks presentation will cover the impact of immunogenicity TECHNOLOGIES induction on PK assays. Are We and Where Are We Heading? Sandra Garces, MD, PhD, Senior Medical Advisor Anna Fogdell-Hahn, PhD, Associate Professor, for Immunogenicity, GPS Medical and Benefit-Risk 9:40 Applying Modeling Methodologies to Karolinska Institutet, Clinical Neuroscience, Clinical Management, Eli Lilly Analyze the Impact of Immunogenicity on Neuroimmunology, Center for Molecular Medicine SPONSOR/EXHIBIT (CMM), Stockholm, Sweden INFORMATION Exposure and Efficacy 8:40 KEYNOTE PREESENTATION: How to Vibha Jawa, PhD, Director and Lead, Predictive and Whereas ADA testing is now a requirement for drugs Characterize ADA Responses and Assess HOTEL & TRAVEL INFORMATION Clinical Immunogenicity, PPDM, Merck & Co Inc to be approved, the use of them in clinical settings Their Clinical Impact to Better Inform the Understanding immunogenicity’s effect on the PK are only partially applied. This is unfortunate since Clinical Relevance of ADA Using a Risk- it would enable identification of patients that have REGISTRATION INFORMATION and PD of a therapeutic protein is important during Based Approach drug discovery, as it allows for the identification of reacted and become tolerant against their treatment Sandra Garces, MD, PhD, Senior Medical Advisor clinically relevant anti-drug antibody reactions. The before clinical symptoms appear. In this talk I will REGISTER ONLINE! for Immunogenicity, GPS Medical and Benefit- goal of this work is to use modeling methodologies present a feasible process for translating the ADA Risk Management, Eli Lilly to understand the effect of immunogenicity, testing from the industry, through academy to applied PEGSummit.com Practical cases will be used to better illustrate streamlining the early drug discovery process and clinical routine. the specific questions and some of the informing clinical decisions. limitations we sometimes face and to discuss potential ways to overcome challenges in pre- 10:10 Networking Coffee Break clinical risk assessment of expected clinical consequences according to type of biologic, REGISTER at PEGSummit.com | 62 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOGENICITY & BIOASSAYS STREAM IMMUNOGENICITY CASE STUDIES AND CLINICAL MANAGEMENT continued PARTICIPANTS

REGISTER TODAY Bioanalytical Sciences, Genentech 11:50 Post-hoc assessment of the PLENARY KEYNOTE SESSION immunogenicity of three antibodies reveals The advent of increasingly complex and novel distinct immune stimulatory mechanisms protein therapeutic modalities requires non-standard COVER Robin E. Walsh, MS, Toxicologist, Toxicology and 4:00 Chairperson’s Remarks approaches to assessing immunogenic responses. Immunosafety Lab, Eli Lilly & Co Rakesh Dixit, PhD, DABT, Vice President, R&D, Bispecific antibodies are one such novel modality in Global Head, Biologics Safety Assessment, CONFERENCE-AT-A-GLANCE In this study, we present the post-hoc analysis which two different target specificities are engineered Translational Sciences, AstraZeneca of three monoclonal antibodies with high into a single protein. This presentation will discuss SHORT COURSES immunogenicity in clinic. Two of the three antibodies 4:10 Vision for How Immunotherapy Will our bioanalytical strategy and its implementation were capable of eliciting a CD4[+] T cell proliferative Shape Future of Cancer Care using two such molecule programs. These case studies will illustrate how these strategies were TRAINING SEMINARS response with multiple donors in a peripheral blood Leena Gandhi, MD, PhD, Vice President, Immuno- implemented, their outcome and impact on clinical mononuclear cell (PBMC) assay, but required Oncology Medical Development, Lilly Oncology development. different experimental conditions to induce these Immunotherapy is considered by many as a ENGINEERING responses. The third antibody did not trigger any T pillar of cancer care today, but in many ways we 9:30 Case Study: Clinical Immunogenicity and cell response in this assay. These distinct capacities have only scratched the surface. Our knowledge Its Impact to promote CD4[+] T cell responses in vitro were and understanding of the complexities of Deborah Finco, PhD, President, Deborah Finco mirrored by different capacities to stimulate innate immunotherapy and its mechanisms continue Consulting LLC ONCOLOGY immune cells. Only one out of the three antibodies to evolve. The future of cancer care will be Multiple companies developed therapeutic was capable of inducing human monocyte-derived defined by our ability to systematically identify monoclonal antibodies to the same target for dendritic cell (moDC) maturation; the second antibody and implement opportunities for combination lowering low-density lipoprotein (LDL). However, the IMMUNOTHERAPY promoted monocyte activation while the third one therapy to improve and standardize patient immunogenicity profiles varied considerably between did not induce any innate cell activation in vitro. response. the different companies monoclonal antibodies. This However, all three antibodies exhibited a moderate talk will discuss the different therapeutic antibodies, to high internalization by human moDCs and MHC- 4:55 The Lassa Virus Glycoprotein: EXPRESSION the immunogenicity assays, clinical results, and associated peptide proteomics (MAPPs) analysis Stopping a Moving Target the impact of immunogenicity and efficacy on one revealed the presence of potential T cell epitopes Kathryn Hastie, PhD, Staff Scientist, Immunology program. that were later confirmed by PBMC T cell proliferation and Microbiology, The Scripps Research Institute ANALYTICAL assay using peptides instead of whole antibodies. Lassa virus causes ~5000 deaths from viral 10:00 Coffee Break in the Exhibit Hall with Collectively, these findings highlight the existence hemorrhagic fever every year in West Africa. Poster Viewing of distinct immune stimulatory mechanisms of The trimeric surface glycoprotein, termed IMMUNOENICITY immunogenic antibodies. These approaches and GPC, is critical for infection, is the target for CASE STUDIES OF BIOLOGICS (CONT.) findings might have implications for the preclinical neutralizing antibodies, and a major component & BIOASSAYS 10:45 Chairperson’s Remarks screening of therapeutic proteins and help lower the of vaccines. Structural analysis of Lassa GPC immunogenicity risk of therapeutic proteins. bound to antibodies from human survivors Darshana Jani, PhD, Associate Director & Global Lead FUSIONS & reveals a major Achilles heel for the virus and Biologics, Pfizer Inc Sponsored by CONJUGATES 12:20 pm Bioanalytical Strategy provides the needed template for development 10:50 Immunogenicity Assessment of an to support CAR-T Therapies: of immunotherapeutics and improved vaccines. Enzyme Replacement Therapy Administered Where are the Challenges? via the Intracerebroventricular Route in THERAPEUTICS & Corinna Fiorotti, PhD, CSO, BioAgilytix Patients with CLN2 Disease TECHNOLOGIES 5:40 Welcome Reception in the Exhibit Hall 12:50 Luncheon Presentation (Sponsorship with Poster Viewing Anu Cherukuri, PhD, Associate Director, Immunogenicity Opportunity Available) or Enjoy Lunch on Your Assessment, BioMarin Pharmaceutical Inc. Own 7:15 End of Day We have characterized immunogenicity of a novel SPONSOR/EXHIBIT ERT directly delivered to the CNS in patients with INFORMATION 1:50 Session Break TUESDAY, APRIL 9 a life-threatening neurodegenerative disease. The 2:20 Problem-Solving Breakout Discussions consequences of both a systemic and CNS-specific HOTEL & TRAVEL INFORMATION 8:00 am Registration and Morning Coffee immune response on the safety and efficacy profiles 3:20 Networking Refreshment Break of the drug will be presented. Implications of ADA REGISTRATION INFORMATION CASE STUDIES OF BIOLOGICS impact on systemic and CSF PK will be included. Lastly, regulatory feedback on the risk assessment 8:25 Chairperson’s Remarks approach and learnings from the program that can be REGISTER ONLINE! Darshana Jani, PhD, Associate Director & Global Lead applied to assess immunogenicity risks of future ICV- PEGSummit.com Biologics, Pfizer Inc delivered ERT therapeutics will be presented. 8:30 Attend Concurrent Track 9:00 Nonclinical and Clinical Immunogenicity Assessment of Bispecific Protein Therapeutics Eric Wakshull, PhD, Principal Scientist/Group Leader, REGISTER at PEGSummit.com | 63 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOGENICITY & BIOASSAYS STREAM IMMUNOGENICITY CASE STUDIES AND CLINICAL MANAGEMENT continued PARTICIPANTS

REGISTER TODAY 11:20 Immunogenicity Testing – The Next Are there common themes? Will they provide PREEXISTING ADA & IMMUNE Frontier: Gene Therapies, Nanoparticles and learnings for future biologics development? TOLERANCE INDUCTION (CONT.) Beyond • How will the newer guidances and incorporating a COVER Renuka Pillutla, PhD, Executive Director, Lead, risk-based immunogenic assessment approach in 4:25 New Updates on the Use of Low Dose Bioanalytical Sciences at Bristol-Myers Squibb programs impact future PMR/PMCs? Transient Methotrexate CONFERENCE-AT-A-GLANCE Advances in molecular engineering and our Lauren Bailey Flueckinger, MS, CGC, Genetic Counselor, Medical Genetics, Duke University Medical Center understanding of biological mechanisms are 12:20 pm Luncheon Presentation (Sponsorship SHORT COURSES resulting in increasingly novel therapeutics. In the Opportunity Available) or Enjoy Lunch on your Prophylactic immune tolerance induction (ITI) has been standard of care in CRIM-negative infantile realm of large molecules, we have gone beyond Own TRAINING SEMINARS the traditional antibody and protein therapeutics to Pompe disease (IPD) patients. However, the side unique modalities with innovative delivery systems. 1:20 Ice Cream Break in the Exhibit Hall with effects and cost of rituximab has resulted in its use Increasing complexity of novel modalities has led Poster Viewing on in CRIM-negative IPD. We have developed an ENGINEERING to increases in the complexity of immunogenicity immune modulation protocol using transient low-dose testing strategies. This presentation will discuss the PRE-EXISTING ADA & IMMUNE methotrexate. We will present data on our experience challenges of assessing immunogenicity risk and TOLERANCE INDUCTION with transient low-dose methotrexate in infantile developing appropriate testing strategies as we move Pompe disease. ONCOLOGY 2:00 Chairperson’s Remarks into this next frontier. Two case studies will be used to 4:55 Immune Tolerance Induction Approaches illustrate some of the challenges. In one example, the Sophie Tourdot, PhD, Senior Principal Scientist, Immunogenicity, Pfizer for Immunogenicity Mitigation therapeutic is a lipid nanoparticle that encapsulates Sophie Tourdot, PhD, Senior Principal Scientist, IMMUNOTHERAPY siRNA as the active pharmaceutical ingredient. Based 2:05 Impact of Presence of Pre-Existing Immunogenicity, Pfizer on a thorough assessment and careful consideration, Antibodies on Immunogenicity Assessment I will talk about rationale for mitigating an immunogenicity assay development strategy Strategy was developed and implemented for this complex immunogenicity through tolerance induction (the EXPRESSION Joleen White, PhD, Director and Head, NBE case of ERT and gene therapy, and beyond). Current molecule. In another example, immunogenicity DMPK Project Support, EMD Serono Research & considerations in gene therapy and the potential practice in the clinic (ITI, methotrexate, … ) and new Development Institute Inc. approaches such as antigen- specific and non-antigen impact of pre-existing antibodies to the vector will be While all biotherapeutics have the potential to induce ANALYTICAL discussed. specific (nanoparticles, proteasome inhibitors, anti- an antidrug antibody response (ADA), for some, CD20, …) will also be discussed. pre-existing ADAs are observed in drug-naïve matrix. POST MARKETING COMMITMENTS The presence of pre-existing ADAs may influence 5:25 End of Immunogenicity Case Studies and IMMUNOENICITY the bioanalytical approach and data analysis, both Clinical Management & BIOASSAYS preclinically and clinically. Clinical case studies 11:50 PANEL DISCUSSION: Characterization 5:30 Registration for Dinner Short Courses and Impact of Post Marketing Commitment of biotherapeutic candidates in development for FUSIONS & Requirements for New Biologics Approved by Oncology or non-Oncology indications for which pre- existing ADA were detected will be presented. Recommended Dinner Short Course* CONJUGATES the FDA SC14: Subvisible Protein Particles Moderator: Susan Richards, PhD, Presidential 2:35 The Origin of Antidrug Antibodies in Immunogenicity: Measurement, Scientific Fellow, Translational Medicine Early Jack A. Ragheb, MD, PhD, Co-Chair, Immunogenicity/ Characterization and Impact THERAPEUTICS & Development, Sanofi R&D Immunosafety Working Group, Senior Medical Fellow *Separate registration required. Click here or see TECHNOLOGIES Panelists: for Immunogenicity, Global Patient Safety, Eli Lilly and page 5 for course details. Eric Wakshull, PhD, Principal Scientist/Group Leader, Company, Lilly Corporate Center Bioanalytical Sciences, Genentech Many factors influence the immunogenicity of SPONSOR/EXHIBIT Jack A. Ragheb, MD, PhD, Co-Chair, Immunogenicity/ therapeutic proteins. This presentation will review INFORMATION Immunosafety Working Group, Senior Medical Fellow basic aspects of immune tolerance and discuss for Immunogenicity, Global Patient Safety, Eli Lilly and the implications for the development of ADA to HOTEL & TRAVEL INFORMATION Company, Lilly Corporate Center therapeutic monoclonal antibodies. Darshana Jani, PhD, Associate Director & Global Lead 3:05 Sponsored Presentation (Opportunity REGISTRATION INFORMATION Biologics, Pfizer Inc • Gain an awareness of postmarketing requirements Available) and commitments, how they differ and what gaps 3:35 Refreshment Break in the Exhibit Hall with REGISTER ONLINE! are generally addressed? Poster Viewing PEGSummit.com • Discuss the various immunogenicity-related commitments that have been issued by the FDA.

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SHORT COURSES April 10-11, 2019 TRAINING SEMINARS Immunogenicity has always been a critical safety concern, especially when many biotherapeutics are becoming increasingly complex. Understanding and controlling immunogenicity-related risks are essential in the development of biotherapeutics to ensure meeting the regulatory requirements. CHI’s Twelfth Annual Immunogenicity Assessment and Regulatory Approval of Biologics conference brings industry, regulatory and scientific experts together to share best practices in assessing ENGINEERING immunogenicity of novel biologics along with biosimilar products. The session will also discuss the challenges and solutions for addressing new regulatory guidelines in assay development and validation for cell and gene therapies.

ONCOLOGY TUESDAY, APRIL 9 approaches to cut point calculation in which pre- existing positive samples are identified and removed, 10:15 Women in Science Speed Networking in while forgoing any additional outlier analysis to retain the Exhibit Hall Recommended Short Course* IMMUNOTHERAPY natural variability. The resulting cut points should SC11: Developability of Bispecific better reflect meaningful immunogenicity. Antibodies: Formats and Applications IMMUNOGENICITY PREDICTION AND *Separate registration required. Click here or see 9:10 Strategies for Setting Cut-Points for ADA ASSESSMENT EXPRESSION page 5 for course details. Assays in Multi-Tier vs Single-Tier Testing in a 10:55 Chairperson’s Remarks Routine Clinical Setting Kay Stubenrauch, PhD, Expert Scientist, Pharma WEDNESDAY, APRIL 10 Theo Rispens, PhD, Principle Investigator, Antibody Research & Early Development pRED, Pharmaceutical ANALYTICAL structure and function, Sanquin Sciences, Large Molecule Bioanalytical R&D, Roche 7:15 am Registration and Morning Coffee Immunogenicity testing may be a useful tool to Innovation Center Munich assess reasons for non-response during e.g. anti- TNF therapy. Current guidelines for ADA assays 10:55 FEATURED PRESENTATION: FDA’s IMMUNOENICITY 7:25 - 8:25 PANEL DISCUSSION: Women in focus on early stages of testing new (or biosimilar) Current Thinking on Immunogenicity & BIOASSAYS Science – Inspired Professional and Personal drugs in the clinic, but may not be optimally tailored Assessment of Biosimilars Stories towards practical implementation of ADA testing in William Hallett, PhD, Biologist, OPQ/OBP, CDER, FUSIONS & Moderator: Women in Bio, Boston Chapter the context of routine care. This presentation will FDA CONJUGATES Panelists: address different strategies for calculating cut-points An overview of immunogenicity assessment of Susan Richards, PhD, Presidential Scientific Fellow, in relation to single vs multi-tier assay strategies biosimilars will be presented: current landscape Translational Medicine Early Development, Sanofi R&D and discuss case studies comparing these different of biosimilar products, success rate versus THERAPEUTICS & Joanna Brewer, PhD, Vice President, Platform approaches failure rate and best practices to improve the Technologies, AdaptImmune TECHNOLOGIES 9:40 Orthogonal Approaches and Utility of quality of immunogenicity assessment for Additional Panelists to be Announced ADA Assays biosimilars from an FDA’s perspective. Soumi Gupta, PhD, Director, Immunogenicity SPONSOR/EXHIBIT Assessment, BioMarin Pharmaceutical Inc. 11:25 Towards a fit for purpose approach for INFORMATION MITIGATING STRATEGIES FOR ADA CUT- We will demonstrate using Pegvaliase (a PEGylated evaluating relevant immunogenicity of mAbs POINT AND EFFECTIVENESS bacterially derived enzyme substitution therapeutic) in oncology human clinical trials HOTEL & TRAVEL INFORMATION 8:30 Chairperson’s Opening Remarks as a case study, how to evaluate appropriateness Mohamed Hassanein, PhD, Staff scientist, Zhandong Don Zhong, PhD, Associate Director, of the ADA assays based on integrated analysis Bioanalytical Scienices, Regeneron Pharmaceuticals REGISTRATION INFORMATION Specialty Bioanalytics, Teva Pharmaceuticals of immunological laboratory data generated by Recent data from oncology trials indicated that orthogonal approaches as well as clinical safety data. 8:40 Novel, Simplified Approaches to ADA Cut human mAbs (h-mAbs) elicit low treatment-emergent We will present data generated from two different immunogenicity. In this presentation, we will provide REGISTER ONLINE! Point Calculation ADA assays developed against Pegvaliase, one a tailored approach for assessing immunogenicity PEGSummit.com John Kamerud, PhD, AR Fellow, Director, Bioanalytical, for the detection of drug-specific IgE and the other of therapeutic mAbs in oncology trails that factors Pfizer for the detection of anti-PEG IgG/IgM antibodies, in both the low risk profile of h-mAbs as well as the Investigators across the industry indicate problems alongside laboratory and clinical safety data. immunity status of the target population. The with very low ADA cut point factors, which can lead to elevated rates of reported positives, many of which 10:10 Coffee Break in the Exhibit Hall with Poster Viewing are not biologically relevant. This talk will describe REGISTER at PEGSummit.com | 65 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOGENICITY & BIOASSAYS STREAM IMMUNOGENICITY ASSESSMENT AND REGULATORY APPROVAL OF BIOLOGICS continued PARTICIPANTS REGISTER TODAY goal of this “fit-for-purpose” approach is to provide 2:45 Detection of Drug-Specific IgE Antibodies 9:05 Streamlining Preclinical and Clinical immunogenicity data that is relevant to health-care to Biotherapeutics: Challenges and Advances Assessment for Immunogenicity providers and patients. Susan Richards, PhD, Presidential Scientific Fellow, Shara M. Dellatore, PhD, Director, Regulated Translational Medicine Early Development, Sanofi R&D Immunogenicity and Molecular Biology Bioanalytics, COVER 11:55 Application of Mechanistic Modelling to Most focus on immunogenicity has been on the Merck & Co., Inc. Prediction of Immunogenicity CONFERENCE-AT-A-GLANCE development of IgG/IgM ADA. However, a more The titer method has been widely used for reporting Timothy Hickling, PhD, Immunogenicity Sciences challenging assessment is the detection of drug immunogenicity magnitude as part of a three tiered Lead, Biomedicine Design, Pfizer, Inc. SHORT COURSES specific IgE antibodies. When IgE specific ADA strategy for immunogenicity assay development This presentation will introduce an immunogenicity present on the surface of mast cells or basophils and validation. Through multiple case studies, we consortium that coordinates vitro data to predict TRAINING SEMINARS is cross-linked by binding specific antigen, a compared traditional titer to a streamlined strategy immunogenicity in the clinic. The wide range of data series of events unfolds including the release using signal-to-noise (S/N). Overall there was a is integrated into mechanistic models for prediction, of pharmacologic mediators leading to the strong correlation between titer and S/N methods PK and ADA characterization which then allows for symptoms experienced by patients. This can result and proved comparable for interpretation of relevant ENGINEERING better decision-making when translating to the clinic. in hypersensitivity reactions and at an extreme impact. The S/N approach has multiple advantages of reduced sample volume, time, resource, cost and 12:25 pm The Role of Product and Sponsored by anaphylaxis. Sensitive and highly specific assays are needed to detect low levels of drug specific IgE may be a future alternative to titer-based method. Process-Related Impurities in the ONCOLOGY ADA in the presence of total IgE and also presence of Sponsored by Innate Immune Response to any drug specific IgG antibodies. This presentation 9:35 An Integrated Approach to Biotherapeutic Proteins will discuss the challenges and progress made in Managing Immunogenicity Risk Noel Smith, PhD, Principal Group Leader, Applied detecting specific IgE ADA. and Optimum Protein Design IMMUNOTHERAPY Protein Services, Lonza Pharma & Biotech Emilee Knowlton, PhD, Immunology, Sales Specialist, Immunogenicity is a common problem for 3:15 Attend Concurrent Track Sales, ProImmune Inc. biotherapeutic proteins and can impact both efficacy 3:45 Refreshment Break in the Exhibit Hall Integrated platforms can be used to mitigate EXPRESSION and safety. Human in vitro assays are now routinely with Poster Viewing immunogenicity risk and characterize immune used during early development to assess the risk responses during the drug design and development of a biotherapeutic protein inducing both an innate 4:45 Problem-Solving Breakout Discussions stages. ProImmune offers mutational activity and adaptive immune response. This presentation ANALYTICAL 5:45 Networking Reception in the Exhibit Hall mapping for optimal protein design, DC-T/T cell will focus on the use of highly sensitive human proliferation assays for biologic lead selection/ primary cell assays for the assessment of product with Poster Viewing optimization, a Mass Spectrometry assay for and process-related impurities that may contribute to 7:00 End of Day characterization of antigen presentation; HLA-peptide IMMUNOENICITY driving an unwanted immune response. binding assays to characterize individual epitopes & & BIOASSAYS undiluted whole blood cytokine storm assays. 12:55 Enjoy Lunch on Your Own THURSDAY, APRIL 11 1:20 Session Break 10:05 Coffee Break in the Exhibit Hall with FUSIONS & 8:00 am Registration and Morning Coffee Poster Viewing CONJUGATES DRUG SPECIFIC IGE ANTIBODIES NEW ASSAY FORMAT FOR 11:05 Assay Strategies to Monitor 2:10 Chairperson’s Remarks IMMUNOGENICITY ASSESSMENT Immunogenicity of New Antibody Therapeutics in Preclinical and Clinical Studies THERAPEUTICS & Kay Stubenrauch, PhD, Expert Scientist, Pharma 8:30 Chairperson’s Remarks Kay Stubenrauch, PhD, Expert Scientist, Pharma TECHNOLOGIES Research & Early Development pRED, Pharmaceutical Theo Rispens, PhD, Principle Investigator, Antibody Research & Early Development pRED, Pharmaceutical Sciences, Large Molecule Bioanalytical R&D, Roche structure and function, Sanquin Innovation Center Munich Sciences, Large Molecule Bioanalytical R&D, Roche SPONSOR/EXHIBIT 8:35 Impact of Impurities on Bioactivity Assays Innovation Center Munich INFORMATION 2:15 Development and Clinical Utility of a Daniela Verthelyi, PhD, Chief, Immunology Lab, Bridging immunoassays are currently the Novel Drug-Specific IgE Assay Therapeutic Proteins, CDER, FDA predominant assay format for immunogenicity HOTEL & TRAVEL INFORMATION Zhandong Don Zhong, PhD, Associate Director, Product immunogenicity has emerged as one of the assessment. The assay allows for high throughput Specialty Bioanalytics, Teva Pharmaceuticals critical roadblocks in the development of biologics, testing and simple implementation. However, REGISTRATION INFORMATION Evaluation of drug-specific IgE is important complex generics and biosimilars. This talk will focus the reliability of bridging assays can suffer in during biotherapeutic development, as anti-drug on the impact of process-related innate immune the presence of i) an oligomeric target reducing IgE formation has been reported to potentially response modulating impurities and aggregates specificity or ii) residual drug reducing sensitivity. REGISTER ONLINE! correlate with hypersensitivity events (anaphylaxis). on the milieu where the products are delivered Thus, there is a need for alternative assay formats PEGSummit.com Nevertheless, detection of drug-specific IgE remains highlighting the complex interplay of different or approaches that can overcome these inherent challenging due to its low levels in circulation, impurities on product immunogenicity risk. weaknesses. In addition, some methods are numerous potential interfering endogenous introduced to further characterize ADA responses. substances, and difficulty in generating a surrogate positive control. The purpose of this presentation is to demonstrate the development and clinical utility of a novel anti-drug IgE assay platform. REGISTER at PEGSummit.com | 66 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOGENICITY & BIOASSAYS STREAM IMMUNOGENICITY ASSESSMENT AND REGULATORY APPROVAL OF BIOLOGICS continued PARTICIPANTS REGISTER TODAY 11:35 Characterization of Critical Reagents Using LBA, LCMS, and Chromatography for Use in Regulated Bioanalysis COVER Robert Kernstock, PhD, Senior Group Leader, R&D, Immunochemistry, PPD® Laboratories CONFERENCE-AT-A-GLANCE According to the new bioanalytical guidance released by the FDA in 2018, there is an expectation SHORT COURSES to characterize critical reagents for use in regulated bioanalysis. According to the guidance, TRAINING SEMINARS characterization includes: Identity, Purity, and Stability. We have developed a menu of services to provide reagent characterization using various analytical tools such as ligand binding assays, mass ENGINEERING spectroscopy and protein purification to provide address the guidance recommendations.

ONCOLOGY 12:05 pm Preclinical Immunogenicity Assessment of Therapeutic Protein and Antibody: Applications of a Novel ADA Assay IMMUNOTHERAPY Platform Based on Capillary Electrophoresis and Immunodetection Shuli Zhang, PhD, Principal Scientist, PPDM Global Bioanalytics, Merck Research Laboratories EXPRESSION Peggy Sue is a capillary-based western/ immunoassay platform that can separate proteins by size or charge. It uses a HRP-conjugated secondary ANALYTICAL antibody for detection and quantitation. In his work, this platform provides comparable ADA results to traditional bridging assays with distinct advantages. IMMUNOENICITY These include no requirement for labeled capture & BIOASSAYS and detection reagents, reduced sample volume, and valuable charge/size characterization of the immunogenic agent. Most importantly, Peggy Sue FUSIONS & is an ideal platform for characterization of ADA CONJUGATES specificity against complex biologics such as bispecific or multi-specific biotherapeutics. 12:35 End of Immunogenicity Assessment and THERAPEUTICS & TECHNOLOGIES Regulatory Approval of Biologics Recommended Short Course* SPONSOR/EXHIBIT SC14: Subvisible Protein Particles INFORMATION in Immunogenicity: Measurement, Characterization and Impact HOTEL & TRAVEL INFORMATION *Separate registration required. Click here or see page 5 for course details. REGISTRATION INFORMATION

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REGISTER TODAY 5TH ANNUAL OPTIMIZING BIOASSAYS FOR BIOLOGICS COVER Case Studies Demonstrating Successful Bioassay Development CONFERENCE-AT-A-GLANCE April 11-12, 2019 | Seaport World Trade Center | Boston, MA SHORT COURSES

TRAINING SEMINARS As the bioassay field continues to move forward, challenges are evolving from new drug formats such as antibody therapies, cell therapy and gene therapy. There are numerous considerations to keep in mind during assay development such as lifecycle management and planning for lot release. At the Fifth Annual Optimizing Bioassays for Biologics, bioassay experts will address the top challenges in bioassay design including novel technologies, increasing complex mechanisms-of-action, regulation and the application of statistics in assay development. Case studies and best practices for handling the most common issues in biological assay design will ENGINEERING be presented. Overall, this event will showcase ways to continue moving a biologic forward in the discovery pipeline.

THURSDAY, APRIL 11 improvements in assay performance. It has become This presentation provides an overview of strategies ONCOLOGY clear during this assay optimization that the changes and general considerations for developing MOA 12:00 pm Registration will not only significantly improve robustness, reflective, accurate, precise, QC-friendly and phase precision, and accuracy, but also increase ease of appropriate potency assays. Potency is a critical 12:35 Luncheon in the Exhibit Hall with Poster IMMUNOTHERAPY execution. quality attribute of biological products. The main Viewing problem of bioassays is a very high variability. In the 2:50 Strategic Ways to Meet Bioassay presentation, I will demonstrate approaches that BUILDING A BETTER BIOASSAY Performance Requirements with Modular reduce the test variability, increase consistency of EXPRESSION 1:40 Chairperson’s Opening Remarks Design and Analyses analysis and significantly improve the lab efficiency. David Lansky, PhD, President, Precision Bioassay, Inc. David Lansky, PhD, President, Precision Bioassay, Inc. Reportable values (geometric mean) of potency 5:20 End of Day 1:50 Statistical Approaches and ANALYTICAL from bioassays of lots are compared to product 5:20 Registration for Dinner Short Courses Considerations for QbD in Bioassay specifications. Process control limits for log potency Development are narrower than product specifications. Assay Recommended Dinner Short Course* Ryan Yamagata, US Function Head, CMC Statistical performance requirements and their control limits IMMUNOENICITY SC13: Bioassay Quality by Design & BIOASSAYS Sciences, Vaccines Technical Research & (on appropriate measures of assay performance) Development, GSK guide assay development and monitoring. Modular *Separate registration required. Click here or see ICH Q8(R2) does not explicitly refer to analytical design and appropriate analyses support efficient page 5 for course details. FUSIONS & method development. However, a Quality by Design and flexible development and validation as well as CONJUGATES (QbD) approach can also be applied to bioassay alternate assay formats for alternate intended uses. development, as discussed in USP <1032>. FRIDAY, APRIL 12 This presentation will review relevant statistical 3:20 Extended Q&A with Session Speakers 8:00 am Morning Coffee THERAPEUTICS & considerations and approaches when applying QbD 3:50 Networking Refreshment Break TECHNOLOGIES principles to method development and will include examples from bioassay development. 4:20 Improving the Robustness of a Bioassay BEST PRACTICES through Outlier ID and Removal 8:30 Chairperson’s Remarks 2:20 Optimization of a Complement Thomas Little, PhD, President and CEO, Bioassay Perceval Sondag, Senior Manager, Statistics, SPONSOR/EXHIBIT Dependent Cytotoxicity Assay INFORMATION Sciences, Thomas A. Little Consulting PharmaLex Kristin Abrams, Scientist, Amgen, Inc. Bioassays are known for being more variable Complement Dependent Cytotoxicity assays are 8:35 FEATURED POSTER: A Case Study: HOTEL & TRAVEL INFORMATION compared to other analytical methods. Variation in used to measure complement cascade activation the dose response is generally one of the primary root Addressing Assay Curve Shifts in a Bioassay for many biopharmaceuticals. These assays can for a Late Stage Therapeutic Antibody REGISTRATION INFORMATION causes. The presentation will discuss within dose be used for characterization of the ability of the and between dose outlier and removal concepts and Tongyun (Tony) Dang, PhD, Senior Scientist, product to activate the complement cascade to avoid how it will impact curve fitting, confidence intervals BioTherapeutics Development, Discovery, Product REGISTER ONLINE! undesired safety concerns or these can be used to and general bioassay performance. Four Parameter Development, & Supply, Janssen Research & measure the mechanism of activation of the targeted Logistics and Parallel Line Analysis type bioassays Development PEGSummit.com pathway. When these assays are used as part of will be included in the discussion. Here we present a case study involving a cell-based product release, controlling variability is imperative. bioassay for an IgG1 monoclonal product that had When run in QC, the CDC assay exhibited a moderate 4:50 Strategies and Approaches for Building a been successfully validated and degree of variability. As part of method lifecycle Better Bioassay management, the method was closely evaluated, and Alexandra Zakharova, Head, Cell-Based Assay, minor changes were implemented which led to major BIOCAD REGISTER at PEGSummit.com | 68 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL IMMUNOGENICITY STREAM& BIOASSAYS STREAM OPTIMIZING BIOASSAYS FOR BIOLOGICS continued PARTICIPANTS

REGISTER TODAY transferred to multiple testing sites. During late methodologies for a successful bridging are widely increase invalid and re-test rates, or worse, cause stage development, a shift of the assay curve was misunderstood. This talk presents an overview of the a manufacturing process to appear out of control identified and investigated, and a root cause was statistical methods applied to assay bridging. or a drug product to appear unstable. Identifying COVER determined. Through review of historical data and and mitigating sources of variability begins during evaluation of critical reagents, it was determined 11:35 Analytical Bridging: How to Cross on initial assay design, as part of QbD for method the Wire Stretched Between Two Bioassay CONFERENCE-AT-A-GLANCE that a single critical reagent was responsible for the development, and should continue to be a focus assay shift. As corrective actions, the method was Methods? A Case Study through life cycle management. Here, we will discuss Gaël Debauve, PhD, Head, Bioassay Development, SHORT COURSES updated to reduce impact on future assay shifts expected and unexpected sources of variability and and the critical reagent qualification procedure was Analytical Sciences for Biologics, UCB control strategies through presentative case studies. TRAINING SEMINARS improved. Strategies are discussed to prevent future Biological products rely on a wide range of analytical occurrences of assay curve shifts. methods for lot release and stability testing. As 2:10 Challenges in Developing Bioassays for method improvement is a continued effort during Novel Therapeutics: Focus on Antibody Drug 9:05 PANEL DISCUSSION: Best Practices to lifecycle management of biopharmaceuticals, Conjugates ENGINEERING Overcome Bioassay Development Challenges bridging studies are key to demonstrate comparability Adrienne Wildt, PhD, Associate Director, Bioanalytical Moderator: Perceval Sondag, Senior Manager, between old and new methods. Through case studies, Sciences, Immunogen Statistics, PharmaLex we will attempt to clear the way, sometimes complex, 2:40 Cytotoxicity Assay Development for ONCOLOGY Panelists: Gaël Debauve, PhD, Head, Bioassay allowing to conclude to method equivalence. Development, Analytical Sciences for Biologics, UCB CAR-T Steven Walfish, MBA, Principal Scientific Liaison, USP 12:05 pm Statistical Considerations for Design Ashley Mullan, Scientist, Development, Analytical and Analysis of Assay Bridging Studies Sciences, AstraZeneca IMMUNOTHERAPY Alexandra Zakharova, Head, Cell-Based Assay, BIOCAD Harry Yang, Ph.D., Senior Director, Statistical Sciences, 3:10 The Rare Case: Bioassay Method • Statistical considerations at each stage of bioassay Medimmune, LLC Development and Two Happy Customers, PD development Biological products rely on a wide array of analytical and Quality methods for product characterization, lot release, EXPRESSION • Challenges presented by new modalities and Craig Kaftan, Senior Scientist, Analytical Development, emerging therapies and stability testing. As method improvement Pharmaceutical Sciences, Shire HGT, a Member of the • Best practices in ensuring quality control, lot is a continued effort during the lifecycle of a Takeda Group of Companies biopharmaceutical product, bridging studies are often management, and release The goal of cell-based potency methods is to ANALYTICAL conducted to demonstrate comparability of the old • Implementing new technologies and techniques in provide meaningful insights into a therapeutic’s and new methods. In this presentation, we discuss structural integrity and intended physiological assay design and validation statistical considerations in the design and analysis role. Both development and implementation come IMMUNOENICITY 10:05 Networking Coffee Break of bridging studies for analytical methods. & BIOASSAYS with challenges inherent when working with living 10:35 Demystifying USP Bioassay Chapters 12:35 Luncheon Presentation (Sponsorship organisms. Additionally, potency methods need Steven Walfish, MBA, Principal Scientific Liaison, USP Opportunity Available) or Enjoy Lunch on Your to satisfy two very different customers, PD and Quality. For product development, the methods need FUSIONS & Many companies do not have access to statistical Own to be specific, precise, robust and sensitive to be CONJUGATES support for bioassay design and development relying 1:05 Networking Refreshment Break effective tools to support Process and Formulation on USP General Chapters for guidance. This talk Development and Regulatory Filings while gives insights into the chapters and explains some BIOASSAYS FOR EMERGING MODALITIES concurrently simple in execution and management THERAPEUTICS & common misconceptions with them. The importance to support routine GMP lot release. However, when TECHNOLOGIES of dilutional similarity and bioassay analysis will be 1:35 Chairperson’s Remarks successful, it may come with great reward such highlighted. Craig Kaftan, Senior Scientist, Analytical Development, Pharmaceutical Sciences, Shire HGT, a Member of the as more comprehensive product and process SPONSOR/EXHIBIT ASSAY BRIDGING Takeda Group of Companies understanding improving the likelihood of successful, INFORMATION expedient new product development. 11:05 Statistical Approaches for Successful 1:40 Identifying and Controlling Sources of 3:40 End of Conference HOTEL & TRAVEL INFORMATION Assay Bridging Variation in Cell-Based Potency Assays Perceval Sondag, Senior Manager, Statistics, Emily Lowe, PhD, Senior Scientist, Analytical Sciences, Kite Pharma, a Gilead Company REGISTRATION INFORMATION PharmaLex To calculate a relative potency of a vaccine batch, a Cell-based potency assays are essential for reference batch is needed. The problem is that the engineered cell therapy products to demonstrate that REGISTER ONLINE! reference batch has a life span of 3-4 years (before drug product activity is linked to biological critical PEGSummit.com running out of stock, for example), and a vaccine quality attributes. One of the biggest challenges in has a commercial life of about 30 years. Bridging designing and executing cell-based potency assays studies are used to estimate a correction factor is identifying and controlling variability. A poorly between a new and an old reference batch. Statistical controlled and highly variable potency assay can

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COVER FUSIONS & CONFERENCE-AT-A-GLANCE CONJUGATES STREAM SHORT COURSES

TRAINING SEMINARS

ENGINEERING Bioconjugates as Therapeutics: Fusion Protein ONCOLOGY from R&D to Clinical Development Therapeutics The Bioconjugation Stream investigates the ongoing design and IMMUNOTHERAPY R&D efforts, along with the challenges of producing such complex bioconjugates as fusion proteins and antibody-drug conjugates, while ensuring stability, specificity and efficacy. The “Fusion Protein EXPRESSION Engineering Therapeutics” conference examines the varying constructs achieved Antibody-Drug by combining modular building blocks to reach targets not accessible ANALYTICAL to antibodies, and discusses engineering and conjugation strategies to Conjugates improve efficacy, safety and clinical success. The “Engineering Antibody- IMMUNOENICITY Drug Conjugates” conference reveals the exciting third-generation ADC & BIOASSAYS formats, and explores new cytotoxic drugs, linkers and conjugation chemistries that enhances the homogeneity and stability of the ADC; while FUSIONS & Clinical Progress of the “Clinical Progress of Antibody-Drug Conjugates” conference addresses CONJUGATES Antibody-Drug ADCs in preclinical to clinical development, and showcases lessons learned to improve drug design and patient outcomes. THERAPEUTICS & Conjugates TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION

HOTEL & TRAVEL INFORMATION

REGISTRATION INFORMATION

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5TH ANNUAL COVER

CONFERENCE-AT-A-GLANCE FUSION PROTEIN THERAPEUTICS Developing and Optimizing Fusion Proteins for Oncology and Beyond SHORT COURSES April 8-9, 2019 TRAINING SEMINARS Chimeric fusion proteins, with their ability to extend plasma half-life and prolong therapeutic activity, offer exciting benefits over antibody-based therapeutics. Companies are intensely investigating into fusion protein therapeutics as a promising alternative to antibodies. The Fiftth Annual Fusion Protein Therapeutics will explore the latest ENGINEERING developments and future prospects of this exciting modality, by inviting researchers to present their novel fc-fusion platforms, present updates from preclinical and clinical trials, and discuss engineering and conjugation strategies to improve efficacy, safety and clinical success.

ONCOLOGY SUNDAY, APRIL 7 to Design Truly Potent anti-ErbB Bispecific and 11:20 Leveraging FcRn-Blocking Therapeutic Biparatopic Fusion Therapeutics Utility for Autoantibody Mediated Disease Recommended Short Course* Rastislav Tamaskovic, PhD, Head, TC Facility, through a Minimized Affibody Fusion Format Biochemistry, University of Zurich IMMUNOTHERAPY SC8: Gene Therapy Products: Phase- Fredrik Frejd, PhD, CSO, Affibody AB Appropriate Analytical Development Recently, we have described major compensatory Several diseases are mediated by autoantibodies. Strategies routes, which become activated in therapy of HER2- Reduction of antibody plasma levels by positive cancer, and developed a new class of bispecific pharmacologic interference with the neonatal FcRn *Separate registration required. Click here or see EXPRESSION and biparatopic anti-ErbB/Met/Axl fusion protein agents receptor can reduce disease burden and save lives. page 5 for course details. endowed with capabilities to overcome the adaptive Antibodies are suboptimal drugs as they rely on FcRn resistance. These novel targeting vehicles achieve their for long plasma half-life. ABY-039 is an FcRn blocking ANALYTICAL superior tumoricidal activity by trapping tumor-driving affibody molecule that overcomes limitations of MONDAY, APRIL 8 receptor tyrosine kinases in inactive conformations antibody-based approaches to achieve very long and/or supramolecular assemblies. Analogously, we half-life and outpatient subcutaneous administration. IMMUNOENICITY 7:00 am Registration and Morning Coffee build a new platform for tumor RTK fingerprinting aimed Engineering, development and clinical data will be at identifying prospective therapeutic leads and truly presented. & BIOASSAYS NOVEL FORMATS AND APPLICATIONS synergistic combination therapies. 11:50 Antibody-Targeted Superantigens and 8:30 Chairperson’s Opening Remarks 10:10 Networking Coffee Break FUSIONS & Antibody Directed Enzyme Prodrug Therapy Celine Monnet, PhD, Head of Laboratory, Research, for Improved Safety and Efficacy for Cancer CONJUGATES LFB Biotechnologies 10:50 KEYNOTE PRESENTATION: Treatment 8:40 Antibody-Cytokine Fusion Proteins: From Preconditioning the Tumor Sayed Goda, PhD, Professor, Senior Scientist, Anti- THERAPEUTICS & Discovery to Pivotal Clinical Trials Microenvironment to Enable Effective Doping Lab Qatar, Cairo University TECHNOLOGIES Dario Neri, PhD, Professor, Chemistry and Applied Immunotherapy Using Antibody Fusion I will present novel data for cancer treatment using Biosciences, Swiss Federal Institute of Technology Proteins Antibody Directed Enzyme Prodrug Therapy (ADEPT) (ETH Zurich) Alan Epstein, MD, PhD, Professor, Keck School of and Tumor Targeted Superantigens (TTS). For ADEPT, Antibody-cytokine fusions allow to concentrate Medicine, University of Southern California we successfully produced an ultra-active glucarpidase SPONSOR/EXHIBIT In the last 10 years, my laboratory has INFORMATION immunomodulatory activities at the site of disease, that degrades MTX with a very high efficiency, and helping spare normal tissues. I will present preclinical explored the potential of antibody fusion produced novel fusion with our newly discovered proteins consisting of cytokines, chemokines, HOTEL & TRAVEL INFORMATION and clinical work, conducted in collaboration between enzyme for targeted cancer therapy. For TTS, we my laboratory at ETH Zürich and Philogen in the field and co-stimulatory molecules to alter the successfully produced truncated superantigens of cancer and of chronic inflammation. tumor microenvironment as a new direction with much less lethality; and novel variants of REGISTRATION INFORMATION of cancer immunotherapy. In addition to superantigens with less toxicity. We are developing 9:10 Novel Fc Platform Development and targeting adaptive immunity, the laboratory is cancer specific antibody-superantigen fragment REGISTER ONLINE! Application for Fc-Fusion Proteins currently exploring the potential application fusion complex for further study. Lu Shan, PhD, Scientist II, ADPE, AstraZeneca of targeted innate immunity using toll-like PEGSummit.com Monovalent fusion proteins are often a necessary receptor agonists chemically linked to tumor drug format for optimal structure and activity profiles. targeting antibodies. In addition, biobetter We present our novel monovalent fusion platform in checkpoint inhibitors are being prepared that target validation and lead discovery. alter immunodominant pathways required for successful immunotherapy. 9:40 Redefinition of RTK Tumor Targeting: How REGISTER at PEGSummit.com | 71 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSIONS & CONJUGATES STREAM FUSION PROTEIN THERAPEUTICS continued PARTICIPANTS

REGISTER TODAY 12:20 pm Utilizing Fusion Platforms for the GPC, is critical for infection, is the target for moiety itself and did not modify the binding affinity Development of Efficient Hemin Scavengers neutralizing antibodies, and a major component to the neonatal Fc receptor (FcRn). This polarized Towards Therapeutic Use in Sickle Cell of vaccines. Structural analysis of Lassa GPC glycosylation is achieved using a novel Fc mutation, a COVER Disease and Other Hemolytic Disorders bound to antibodies from human survivors glutamate-residue deletion at position 294 (Del) that reveals a major Achilles heel for the virus and endows therapeutic antibodies with an up to 9-fold Elena Karnaukhova, PhD, Research Scientist, Center CONFERENCE-AT-A-GLANCE for Biologics Evaluation and Research, US FDA provides the needed template for development increase in serum lifespan. of immunotherapeutics and improved vaccines. Detrimental effects of extracellular hemin released 9:30 Potential Applications of A New SHORT COURSES from hemoglobin are critically involved in hemolytic Recombinant Protein Format: Self-Assembling disorders. In the US alone, more than 100,000 people Nanoclusters for Protein Delivery and Protein TRAINING SEMINARS 5:40 Welcome Reception in the Exhibit Hall have homozygous sickle cell disease, however, with Poster Viewing Purification Purposes currently there is no treatment to prevent or minimize Elena Garcia Fruitós, PhD, Researcher, Ruminant the adverse consequences induced by the hemin 7:15 End of Day Production, Institute of Agriculture and Food Research ENGINEERING release. This presentation focuses on the biophysical and Technology evaluation of hemin scavengers, utilizing fusion TUESDAY, APRIL 9 The reduction of production costs and stability platforms, in collaboration with our colleagues from improvement of recombinant soluble proteins CSL Limited, Bio21 Institute, Parkville, Australia and 8:00 am Registration and Morning Coffee remains a challenge. In this scenario, we have ONCOLOGY University Hospital of Zurich, Switzerland. been working on the development of a new protein ENGINEERING AND OPTIMIZATION OF 12:50 Luncheon Presentation (Sponsorship format based on self-assembling nanoclusters as a FUSION PROTEINS IMMUNOTHERAPY Opportunity Available) or Enjoy Lunch on Your promising alternative in terms of stability and slow Own 8:25 Chairperson’s Remarks release for protein delivery and protein purification Dario Neri, PhD, Professor, Chemistry and Applied purposes. For that, we are working with endotoxin- 1:50 Session Break free expression systems such as Lactococcus lactis EXPRESSION Biosciences, Swiss Federal Institute of Technology 2:20 Problem-Solving Breakout Discussions (ETH Zurich) and Lactobacillus plantarum. 3:20 Networking Refreshment Break 8:30 Synergistic Cytotoxicity Promoted by 10:00 Coffee Break in the Exhibit Hall with Poster Viewing ANALYTICAL Human Serum Albumin Fusion Protein and PLENARY KEYNOTE SESSION Fatty Acid-Modified 5-Fluorouracil Zhiyu Li, PhD, Associate Professor of Pharmaceutical FUSION PROTEINS FOR NON-ONOLOGY Sciences, Director, Pharmacology and Toxicology INDICATIONS IMMUNOENICITY 4:00 Chairperson’s Remarks Undergraduate Program, Department of 10:50 Next-Generation Antibody-Guided & BIOASSAYS Rakesh Dixit, PhD, DABT, Vice President, R&D, Pharmaceutical Sciences, Philadelphia College of Global Head, Biologics Safety Assessment, Pharmacy Enzyme Replacement Therapy for Lysosomal Translational Sciences, AstraZeneca Diseases Human serum albumin and p53-derived peptide FUSIONS & Katherine Cygnar, PhD, Senior Staff Scientist, fusion protein (rHSA-p53i) and recombinant wild type CONJUGATES 4:10 Vision for How Immunotherapy Will Shape Genome Engineering Technologies, Regeneron albumin (rHSA) exhibited similar biodistributions Future of Cancer Care Pharmaceuticals in mice; however, rHSA-p53i accumulated much Leena Gandhi, MD, PhD, Vice President, Immuno- Enzyme replacement therapy revolutionized treatment THERAPEUTICS & Oncology Medical Development, Lilly Oncology more in tumor tissue. This fusion protein could also induce cytotoxicity irrespective of p53 status and for lysosomal diseases, but many patients still show TECHNOLOGIES Immunotherapy is considered by many as a progressive disease on therapy mainly due to poor pillar of cancer care today, but in many ways we display synergistic cytotoxicity with 5-fluorouracil (5FU) in cancer cells. Therefore, fatty acid-modified enzyme uptake in critical tissues. Here we show a have only scratched the surface. Our knowledge fusion protein between the enzyme and an antibody and understanding of the complexities of 5FU (FA-5FU) was synthesized to form stable non- SPONSOR/EXHIBIT covalent complexes with rHSA-p53i. FA-5FU showed binding an internalizing protein improves enzyme INFORMATION immunotherapy and its mechanisms continue delivery to critical tissues, and completely/near- to evolve. The future of cancer care will be cytotoxicity comparable with that of 5FU and FA-5FU/ rHSA-p53i complexes together achieved a profound completely corrects disease phenotypes in a mouse HOTEL & TRAVEL INFORMATION defined by our ability to systematically identify model of Pompe disease. This platform is amenable to and implement opportunities for combination synergistic anticancer efficacyin vitro and in vivo in SJSA-1 and MDA-MB-231 xenograft mouse models. both protein therapeutics and gene therapy. REGISTRATION INFORMATION therapy to improve and standardize patient response. 9:00 Fc Sialylation Prolongs Serum Half-Life of 11:20 Platform Technology for Treatment of the Brain in Lysosomal Storage Disorders with 4:55 The Lassa Virus Glycoprotein: Therapeutic Antibodies REGISTER ONLINE! Celine Monnet, PhD, Head of Laboratory, Research, IgG-Fusion Proteins: Preclinical and Clinical Stopping a Moving Target Update PEGSummit.com Kathryn Hastie, PhD, Staff Scientist, Immunology LFB Biotechnologies Ruben Boado, PhD, Vice President, R&D and Co- and Microbiology, The Scripps Research Institute We demonstrated a hitherto unrecognized impact Founder, ArmaGen, Inc. Lassa virus causes ~5000 deaths from viral of Fc hyper-sialylation of the Asparagine 297 on Protein therapeutics can be re-engineered as brain hemorrhagic fever every year in West Africa. the prolongation of IgG1 serum persistence. The The trimeric surface glycoprotein, termed enhanced longevity was due to the sialylated sugar REGISTER at PEGSummit.com | 72 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSIONS & CONJUGATES STREAM FUSION PROTEIN THERAPEUTICS continued PARTICIPANTS

REGISTER TODAY penetrating IgG-fusion proteins for the CNS treatment obtained for HERA-CD40L, HERA-CD27L, and HERA- membrane-associated targets. We have developed of rare disorders, like Lysosomal Storage Disorders GITRL will be presented. a site-specific bioconjugation strategy that links (LSD). The BBB-penetration of enzyme therapeutics anionic polypeptides to native IgGs, allowing them 2:35 Development of a Novel Multi-Specific COVER is enabled by re-engineering the recombinant enzyme to be complexed with lipids and polymers originally as bi-functional IgG fusion proteins. The enzyme Antibody Targeting PD-L1-Overexpressing developed for nucleic acid delivery. The resulting Cancers by Engagement of Antigen- CONFERENCE-AT-A-GLANCE therapeutic domain of the fusion protein exerts the complexes can efficiently deliver antibodies that pharmacological effect in brain once across the BBB. Committed CD8+ T Cells via the Costimulatory inhibit drug targets into the cytoplasm, demonstrating SHORT COURSES Several brain penetrating IgG-LSD fusion proteins Receptor 4-1BB that cytoplasmic antibodies are a viable new class of have been engineered and validated. First-in-human Sebastian Meyer, PhD, COO, Numab Innovation AG therapeutics. POC Phase II clinical trial in LSD will be discussed. TRAINING SEMINARS Targeting PD-L1 and 4-1BB with a multi-specific II. Utlizing Bioorthogonal Chemistry for antibody format holds the promise of increased 11:50 Protein Engineering by Directed improving the Pharmacokinetic Properties and potency while improving the safety profile compared Evolution to Derive ALPN-101, a Dual ICOS/ Inhibitory Activity of N-TIMP2 ENGINEERING to combination therapy. Numab develops a molecule CD28 Antagonist ICOSL Variant Ig Domain that potently blocks PD-L1/PD-1 signaling and elicits Hezi Hayun, PhD, Biotechnology Engineering, Ben (vIgD)-Fc Fusion Protein for the Treatment of further T cell activation through its costimulatory Gurion University Inflammatory Diseases domain. Preclinical data show efficacy on tumor Matrix metalloproteinases (MMPs) are a family ONCOLOGY Mark Rixon, PhD, Senior Director, Protein Therapeutics, growth in combination with an enhanced intratumoral of zinc-dependent enzymes that regulate the Alpine Immune Sciences CD8+ T cell activation when compared to the degradation of the extracellular matrix (ECM) ALPN-101 is an Fc fusion protein designed to inhibit combination of the PD-L1 and 4-1BB modalities. components, in biological processes such as angiogenesis and wound healing. MMPs activity IMMUNOTHERAPY simultaneously the CD28 and ICOS costimulatory pathways. Through directed evolution of the ICOSL 3:05 IL-DR2 Fc Is a Novel Regulator of Immune is regulated by natural Tissue Inhibitors of extracellular variable Ig domains, Alpine Immune Homeostasis and Inducer of Antigen-Specific Metalloproteinases (TIMPs) that can inhibit MMP’s Sciences has engineered ALPN-101 to have increased Tolerance activity, but some can also mediate activation of EXPRESSION affinity to the natural counter structure ICOS and gain Stephen D. Miller, PhD, Judy Gugenheim Research some pro-MMPs. Synthetic MMP inhibitors exhibit of binding to the non-cognate ligand CD28. Preclinical Professor, Director, Interdepartmental Immunobiology great inhibition by chelating the MMP catalytic data demonstrate superior in vitro and in vivo efficacy Center, Microbiology-Immunology, Northwestern Zn2+, but have some drawbacks such as poor ANALYTICAL and corroborate the dual ICOS/CD28 antagonism of T University Medical School pharmacokinetics and severe adverse effects, which cell costimulatory signaling. ILDR2 is a member of the Ig superfamily and limit their use as therapeutic drugs.Engineering has a putative role in pancreatic islet health and approach showed that the N-terminal domain of 12:20 pm Luncheon Presentation (Sponsorship survival. We recently found a novel role for ILDR2 TIMP-2 (N-TIMP2) is sufficient to inhibit MMPs IMMUNOENICITY Opportunity Available) or Enjoy Lunch on your in delivering inhibitory signals to T cells. ILDR2- activity, without leading to pro-MMP-2 activation. & BIOASSAYS Own Fc displays a unique mode of action, combining Thus, we have decided to use bioorthogonal chemistry to incorporate a non-canonical amino 1:20 Ice Cream Break in the Exhibit Hall with immunomodulation, regulation of immune homeostasis, and re-establishment of Ag-specific acid (NCAA) into N-TIMP2, allowing a site-specific FUSIONS & Poster Viewing PEGylation and a better control for this modification. CONJUGATES immune tolerance via induction of regulatory T cells. FUSION PROTEINS AS IMMUNOTHERAPY These findings support the potential of ILDR-Fc as a We have managed to incorporate propargyl lysine AGENTS promising therapeutic approach for the treatment of (PrK) into N-TIMP2 in different positions. This residue autoimmune diseases. is aimed to be conjugated with PEG-azide in a click THERAPEUTICS & 2:00 Chairperson’s Remarks chemistry reaction, followed by examination of the TECHNOLOGIES Alan Epstein, MD, PhD, Professor, Keck School of 3:35 Refreshment Break in the Exhibit Hall inhibition activity towards MMP-14 as well as the Medicine, University of Southern California with Poster Viewing pharmacokinetic properties of the modified variants in in vitro and in vivo studies. SPONSOR/EXHIBIT 2:05 Engineering Hexavalent TNFR-SF IMPROVING CYTOPLASMIC DELIVERY INFORMATION Agonists for Cancer Immunotherapy: A Unique AND PK PROPERTIES 5:25 End of Fusion Protein Therapeutics Class of Biologics 4:25 The Evolving Science and Long-Term 5:30 Registration for Dinner Short Courses HOTEL & TRAVEL INFORMATION Oliver Hill, PhD, Vice President, Molecular Biology/ Outcomes of Fc Fusion Factors Protein Engineering, Apogenix AG Joe Salas, PhD, Executive Director, Protein Recommended Dinner Short Course* Apogenix’s Hexavalent TNFR-SF agonist (HERA) is REGISTRATION INFORMATION Therapeutics, Bioverativ Inc. SC11: Developability of Bispecific based on trivalent but single-chain molecular mimics of the TNF-SF receptor binding domains fused to a 4:55 POSTER HIGHLIGHTS Antibodies: Formats and Applications REGISTER ONLINE! dimerization scaffold. The resulting hexavalent fusion I: Cytoplasmic Delivery of Inhibitory Antibodies *Separate registration required. Click here or see PEGSummit.com proteins are potent TNFR-SF agonists that activate Andrew Tsourkas, PhD, Professor, Bioengineering, page 5 for course details. distinct immune cell populations involved in the University of Pennsylvania anti-tumor immune reaction thereby enabling exciting Antibodies can directly neutralize their antigen’s opportunities for combination treatment with other biological activity, but their inability to cross the I-O drugs. The engineering details and recent results plasma membrane has limited them to secreted or REGISTER at PEGSummit.com | 73 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSIONS & CONJUGATES PARTICIPANTS REGISTER TODAY 9TH ANNUAL ENGINEERING ANTIBODY-DRUG CONJUGATES COVER Innovations in Next-Generation ADC Design CONFERENCE-AT-A-GLANCE April 10-11, 2019 SHORT COURSES In this first installment of our 2-part ADC program, PEGS Boston’s Ninth Annual Engineering Antibody-Drug Conjugates invites scientists to present their design strategies TRAINING SEMINARS to increase therapeutic index through novel payloads, alternative platforms and new linker conjugation technologies.

ENGINEERING WEDNESDAY, APRIL 10 metabolism, a tumor associated protease with a changes induced by ADCs and highlight avenues for unique cleavage sequence is utilized for lysosomal rational combination strategies. 7:15 am Registration and Morning Coffee ADC cleavage and release of active metabolites with an appropriate profile matching the KSPi mode of 11:25 Drug Conjugates Based on Engineered ONCOLOGY action. Affibody Molecules 7:25 - 8:25 PANEL DISCUSSION: Women in Torbjörn Gräslund, PhD, Professor, Protein Science, Science – Inspired Professional and Personal 9:40 NAMPT Inhibitors as a Novel Payload KTH Royal Institute of Technology Class for Antibody-Drug Conjugates IMMUNOTHERAPY Stories Affibody molecules are small (58 aa), folded and Moderator: Women in Bio, Boston Chapter Chris Neumann, PhD, Principal Scientist, Medicinal robust non-Ig based affinity proteins. We have Panelists: Chemistry, Seattle Genetics recently developed drug conjugates based on Susan Richards, PhD, Presidential Scientific Fellow, ADC technology is limited by the diversity of engineered affibody molecules with specific affinity EXPRESSION Translational Medicine Early Development, Sanofi R&D chemical payloads that retain activity in this targeted for the HER2 receptor, coupled to the small molecule Joanna Brewer, PhD, Vice President, Platform delivery format. Our group has identified NAMPT drug DM1. Affibody molecules allow for site-specific Technologies, AdaptImmune inhibitors as an ADC-compatible drug class with a drug attachment and easy control over DAR. We ANALYTICAL Additional Panelists to be Announced distinctive mechanism targeting cellular metabolism. found that the drug conjugates were potent agents We report the development of a hydrophilic, for treatment of xenografted human tumors in mice. cleavable linker for NAMPT inhibitors that enables NOVEL PAYLOADS AND NEW 11:55 Bispecific ADCs for Improved Tumor IMMUNOENICITY targeted delivery. The favorable activity and PLATFORMS toxicity profiles of the ADCs in preclinical models Targeting Specificity & BIOASSAYS demonstrates a promising advance in the field with David V. Liu, PhD, Director, Protein Engineering, Abbvie 8:30 Chairperson’s Opening Remarks potential clinical utility. The combination of two specificities against targets Anton Neschadim, PhD, MBA, CEO, ImmunoBiochem co-expressed on cancer cells has the potential to FUSIONS & Corporation 10:10 Coffee Break in the Exhibit Hall with CONJUGATES improve specificity of targeting and increase the 8:40 Enabling Silvestrol as a Novel Payload for Poster Viewing therapeutic index of antibody-drug conjugates. In Antibody-Drug Conjugates this presentation, data will be presented on a 1+1 THERAPEUTICS & Thomas Pillow, PhD, Senior Scientist, Discovery 10:15 Women in Science Speed Networking in bispecific antibody-drug conjugate against two cancer stem cell associated targets. The discovery, TECHNOLOGIES Chemistry, Genentech the Exhibit Hall in vitro screening and in vivo validation of this This talk will focus on the discovery and optimization construct will be presented. of silvestrol analogs as a novel class of antibody- 10:55 Towards a Deeper Understanding of the Sponsored by SPONSOR/EXHIBIT drug conjugate payloads. The key learnings around 12:25 pm Computational Immune Modulatory Properties of Cytotoxic INFORMATION drug metabolism will be discussed and how this can Approaches for Optimizing the Antibody-Drug Conjugates be avoided through engineering of the antibody or Developability of Biotherapeutics Tony D’Alessio, PhD, Senior Research Investigator, HOTEL & TRAVEL INFORMATION small molecule. Finally, several stable conjugates Nels Thorsteinson, Scientific Services Manager, Oncology Biotherapeutics, Novartis Institutes for were advanced into in vivo studies and efficacy and Biologics, Chemical Computing Group safety data will be presented. Biomedical Research REGISTRATION INFORMATION mAb candidates identified from high-throughput Antibody-drug conjugates (ADCs) are multi- screening or binding affinity optimization often 9:10 ADCs with Novel Kinesin Spindle Protein component drugs that leverage several mechanisms present liabilities for developability, such as Inhibitor Payloads and a Tailor-Made Linker of action including immune-modulation of the REGISTER ONLINE! aggregation-prone regions or poor solution behavior. Chemistry tumor microenvironment. Our investigations In this work, we optimized an integrin α11 binding PEGSummit.com Hans-Georg Lerchen, PhD, Chief Scientist, Drug have focused on dissecting the role played by the mAb for developability using homology modeling Discovery, MedChem, Bayer AG antibody component vs. that of the payload and the and rational design where reducing hydrophobic Inhibitors of kinesin spindle protein (KSPi) have been specific molecular mechanisms that drive immune- surface developed as a novel payload class in antibody-drug modulation by anti-mitotic ADCs. Our data further conjugates. To increase tumor selectivity of ADC our understanding of the complex pharmacodynamic REGISTER at PEGSummit.com | 74 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSIONS & CONJUGATES STREAM ENGINEERING ANTIBODY-DRUG CONJUGATES continued PARTICIPANTS

REGISTER TODAY patches improved HIC behavior. A retrospective data 3:15 Modular coiled-coil masking domains for 9:05 Disulfide Re-Bridging with analysis demonstrates that 3D descriptors and multi- tumor-specific antibody activation Pyrrolobenzodiazepine Dimers Enable the parameter models can screen candidates and enrich Vivian Trang, PhD, Scientist, Protein Sciences, Seatte Formation of Homogeneous, Potent and COVER libraries with favorable developability properties for a Genetics Differentiated Full-Length Antibody and Fab- range of biotherapeutics. Monoclonal antibody therapeutics are powerful due Fragments Drug Conjugates CONFERENCE-AT-A-GLANCE 12:55 Luncheon Presentation (Sponsorship to their remarkable selectivity for a chosen antigen; Nazzareno Dimasi, PhD, Associate Director R&D, Opportunity Available) or Enjoy Lunch on Your however, antibody therapies can still be limited by AstraZeneca target-mediated toxicity. An emerging concept in SHORT COURSES Own Homogeneous full-length antibodies and Fab- the field of ADCs is to restrict antibody binding in fragments pyrrolobenzodiazepine conjugates TRAINING SEMINARS 1:55 Session Break a disease-specific manner by restricting binding to with a drug to antibody ratio of one are presented. healthy tissues. This was previously accomplished These ADCs are prepared using dual-maleimide ADCS TARGETING THE TUMOR by fusing custom masking groups to the antibody pyrrolobenzodiazepine dimers that have been ENGINEERING MICROENVIRONMENT through cleavable sequences that can be activated engineered to re-bridge two adjacent cysteines at upon hydrolysis by disease-associated proteases. 2:10 Chairperson’s Remarks the antibody hinge, at an engineered position in the Here, we describe a modular masking domain that CH2 domain and at the Fab cysteines forming the Philipp Spycher, PhD, PSI Founder Fellow, Center for is able to prevent antibody binding to antigen until intrachain disulfide bond. ONCOLOGY Radiopharmaceutical Sciences (CRS), Paul Scherrer the mask is removed using proteases. This modular Institute approach represents an advance in the field of 9:35 POSTER HIGHLIGHT: Tri-Mannosyl antibody pro-drugging as the domain can be applied Antibody: A Novel Site-Specific and Dual IMMUNOTHERAPY 2:15 KEYNOTE PRESENTATION: Using to an array of therapeutic antibodies and ADCs. Payload Glycoengineering Antibody Drug Matrix Protein Affinity to Modulate the Conjugation Platform by Glycoengineering Tumor Microenvironment 3:45 Refreshment Break in the Exhibit Hall with Shih-Chong Tsai, PhD, Sr Research Scientist, Deputy Jeffrey A. Hubbell, PhD, Eugene Bell Professor Poster Viewing EXPRESSION Executive Director, Institute of Biologics Development in Tissue Engineering, Institute of Molecular 4:45 Problem-Solving Breakout Discussions Center for Biotechnology Engineering, University of Chicago We report a high efficiency glycogengineering Cancer immunotherapy with immune 5:45 Networking Reception in the Exhibit Hall technology by using a GnT-I (UDP N-Acetyl ANALYTICAL checkpoint inhibitors (CPI) and interleukin with Poster Viewing glucosamine transferase I) and a GnT-II (UDP N-Acetyl (IL)-2 has demonstrated clinical efficacy but is 7:00 End of Day glucosamine transferase II) as enzymes to conjugate frequently accompanied with severe adverse a tri-mannosyl core antibody and produce a novel IMMUNOENICITY events caused by excessive and systemic format ADC. Our results show that a tri-mannosyl & BIOASSAYS immune system activation. Here, we addressed THURSDAY, APRIL 11 Trastuzumab 2(GlcNAc-triazole-DBCO-(PEG)4-DM1)- this need by targeting both the CPI antibodies 2(GlcNAc-triazole-DBCO-PEG4-Vc- PAB- (PEG)2- αCTLA4 + αPD-L1 and the cytokine IL-2 to 8:00 am Registration and Morning Coffee Duocarmycin SA) is generated with the conversion FUSIONS & tumors via conjugation or recombinant fusion OPTIMIZING LINKERS AND efficiency over 90% and 40% recovery rate. The CONJUGATES to a collagen-binding domain derived from the biological activities of tri-mannosyl ADC products blood protein von Willebrand factor A3 domain, CONJUGATION TECHNOLOGIES produced were further confirmed by the Her2 ECD harnessing the exposure of tumor stroma 8:30 Chairperson’s Remarks binding ELISA assay and the cytotoxicity assay. Our THERAPEUTICS & collagen to blood components due to the results indicate that the tri-mannosyl ADC product leakiness of the tumor vasculature. Thomas Pillow, PhD, Senior Scientist, Discovery TECHNOLOGIES Chemistry, Genentech does not only have a similar KD to that of commercial Kadcyla, but also has cytotoxic activities to Her2/ 2:45 Overcoming Cancer Heterogeneity with 8:35 Taming Random Conjugation: A General Neu low-expression and Kadcyla-resistant cell line SPONSOR/EXHIBIT Tumor Microenvironment-Targeted Antibody- Approach for Equimolar Conjugation of MDA-MB-175VI I. These studies suggest that GnT-1 INFORMATION Drug Conjugates Proteins and Payloads and GnT-2 have very good potentials to develop a Anton Neschadim, PhD, MBA, CEO, ImmunoBiochem Sergii Kolodych, PhD, CSO, Syndivia dual payload and site-specific ADC platform when a HOTEL & TRAVEL INFORMATION Corporation Multiple conjugation sites are usually available on tri-mannosyl antibody is used as start material. In the future a large scale preparation will be applied. Solid tumors are evasive and heterogeneous, a biomolecule. Upon conjugation, they produce a mixture of species having different degrees of REGISTRATION INFORMATION lacking surface tumor markers that are expressed 10:05 Coffee Break in the Exhibit Hall with conjugation (DoC). We report a general conjugation consistently and abundantly. Unlike surface-based Poster Viewing targets, levels of certain proteins in the cancer cell approach for achieving a defined DoC, which is REGISTER ONLINE! secretomes are selectively increased in the tumor virtually applicable to any biological macromolecule PEGSummit.com microenvironment, but not normal environment. and payload. Applied to native antibodies, the ImmunoBiochem is leveraging these targets for the method yields highly homogenous antibody-drug selective delivery of highly-potent payloads directly conjugates, antibody-oligonucleotide conjugates as to all cancer cells in the tumor, as well as various well as bispecific scaffolds. tumor-supporting cells, overcoming the challenges of heterogeneity, resistance and poor tumor penetration. REGISTER at PEGSummit.com | 75 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSIONS & CONJUGATES STREAM ENGINEERING ANTIBODY-DRUG CONJUGATES continued PARTICIPANTS

REGISTER TODAY 11:05 Site-Selective, Serum Stable ADCs Using binding properties, are highly cytotoxic to target over- Next-Generation Maleimide Linkers expressing cell-lines and are stable with no drug-loss James Baker, PhD, Associate Professor, Chemistry, over extended periods. COVER University College London 12:05 pm ALT-P7: Development of HER-2 This talk will describe the development and Targeting ADC for Treatment of Breast/Gastric CONFERENCE-AT-A-GLANCE application of the next-generation maleimide class of reagents for the construction of ADCs. It will Cancer by Use of Site-Specific Conjugation SHORT COURSES include a discussion of optimized dibromomaleimide (Nexmab) Technology and monobromomaleimide platforms for the Sunbae Lee, PhD, Senior Research Scientist, Alteogen TRAINING SEMINARS rapid formation of robustly stable ADCs, by either In NexMab conjugation technology, metal-ion binding rebridging the native disulfide bonds or conjugating peptide motif is introduced at the C-terminus of to ThiomabsTM respectively. Insights into the antibody heavy chain for the site-specific conjugation ENGINEERING application of these approaches for the construction of payload. This talk will present the high structural of multispecifics will also be made, along with new stability and in intro/vivo efficacy of HER-2 targeting enabling conjugation platforms. ADC, constructed by NexMab conjugation method with DAR 2. ONCOLOGY 11:35 Straightforward Site-Specific Payload Attachment to Native Antibodies without 12:35 End of Engineering Antibody-Drug Antibody Engineering Conjugates IMMUNOTHERAPY Philipp Spycher, PhD, PSI Founder Fellow, Center for Radiopharmaceutical Sciences (CRS), Paul Scherrer Recommended Short Course* Institute SC12: Design Strategies and Development We will introduce a new antibody-conjugation of ADCs EXPRESSION technology that enables site-specific payload *Separate registration required. Click here or see attachment to native antibodies without engineering. page 5 for course details. Using this approach, well-defined ADCs can be ANALYTICAL generated directly from antibodies ‘off-the-shelf’ within less than two days and that have a drug- to-antibody ratio (DAR) of 2. We will provide a IMMUNOENICITY comprehensive set of data demonstrating that the & BIOASSAYS ADCs generated with our new technology retain their

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REGISTER TODAY 9TH ANNUAL CLINICAL PROGRESS OF ANTIBODY-DRUG CONJUGATES COVER Advancing Novel ADC Platforms and Combinations to the Clinic CONFERENCE-AT-A-GLANCE April 11-12, 2019 SHORT COURSES Antibody-drug conjugates (ADCs) continue to emerge as a strong and promising strategy for target cancer therapy. Companies are leveraging on lessons learned TRAINING SEMINARS from first- and second-generation trials to inform on next-generation ADC designs. PEGS Boston’s Ninth Annual Clinical Progress of Antibody-Drug Conjugates invites investigators to share their latest results from preclinical and clinical trials, lessons learned to inform drug design & dosing, and strategies to improve safety, efficacy and patient outcomes. ENGINEERING THURSDAY, APRIL 11 2:50 Developing Antibody-Drug Conjugates 4:50 POSTER HIGHLIGHT: as Targeted Conditioning Agents for Bone Exploring the Ever-Evolving Bioanalytical ONCOLOGY 12:00 pm Registration Marrow Transplant Strategy for ADCs from Discovery to the Clinic 12:35 Luncheon in the Exhibit Hall with Poster Charlotte McDonagh, PhD, Vice President, Head, Edit Tarcsa, PhD, Director, Drug Metabolism & Viewing Biotherapeutics, Magenta Therapeutics Pharmacokinetics, AbbVie IMMUNOTHERAPY Many diseases can be cured by a bone marrow ADCs are complex therapeutic modalities with the STRATEGIES TO INFORM DRUG DESIGN transplant. Prior to transplant, patients are possibility of forming multiple analytes in vivo. A wide & DOSING, AND IMPROVE PATIENT conditioned by removing their own bone marrow variety of assays and multiple analytical platforms OUTCOMES stem cells using toxic, non-selective chemotherapy had been utilized for their characterization. How do we EXPRESSION and radiation. Many patients suffer serious side chose what is appropriate to support decision making 1:40 Chairperson’s Opening Remarks effects, and others refuse a transplant. This at the various stages of a project and how does one Thomas Held, MBA, Vice President, ADC Task Force, presentation will highlight preclinical development of go by balancing speed, quality and available reagents. ANALYTICAL Daiichi Sankyo antibody-drug conjugates that may be safer, targeted Since the key questions to answer during drug discovery agents for patient preparation with the aim of (ADC optimization), versus late stage development 1:50 Single-Cell PK/PD of Antibody-Drug extending the use of curative bone marrow transplant are usually very different, therefore the analytes and Conjugates and Immuno-Oncology Agents to and improving patient outcomes. assays appropriate to answer those questions could IMMUNOENICITY Design More Effective Therapies & BIOASSAYS also be different. A few case studies and a bioanalytical Greg Thurber, PhD, Assistant Professor, Chemical 3:20 Development and Clinical Updates on decision tree will illustrate the issues. Engineering and Biomedical Engineering, University of Sacituzumab Govitecan FUSIONS & Michigan Robert Iannone, MD, MSCE, Head, R&D, CMO, 5:20 End of Day CONJUGATES Antibody-drug conjugates and checkpoint inhibitors Immunomedics 5:20 Registration for Dinner Short Courses are powerful agents in the treatment of cancer. However, the delivery and distribution of these agents 3:50 Networking Refreshment Break in the tumor microenvironment is complex. We are Recommended Dinner Short Course(s)* THERAPEUTICS & IMPROVING THE SAFTEY AND EFFICACY SC12: Design Strategies and Development TECHNOLOGIES using single-cell measurements within the tumor to inform better decisions on drug design and dosing. OF ADCs of ADCs 4:20 Preclinical Study of Liver Injury Induced *Separate registration required. Click here or see 2:20 Chemo-Enzymatic Glycan Conjugation of by T-DM1: Molecular Mechanisms of T-DM1- page 5 for course details. SPONSOR/EXHIBIT Toxic Payloads: Clinical-Stage GlycoConnect™ Induced Hepatotoxicity INFORMATION ADCs Demonstrate Superior Therapeutic Index Wen Jin Wu, MD, PhD, Senior Investigator, OBP, CDER, Sander van Berkel, PhD, Director, R&D Operations, FDA FRIDAY, APRIL 12 HOTEL & TRAVEL INFORMATION Synaffix B.V. Hepatotoxicity is one of the serious adverse events The native glycan of monoclonal antibodies is 8:00 am Morning Coffee associated with T-DM1. We show that T-DM1 is REGISTRATION INFORMATION evolving as a privileged site to generate ADCs internalized upon binding to cell surface HER2, 8:30 Chairperson’s Remarks with a significantly improved therapeutic index, resulting in DM1-associated cytotoxicity, including Greg Thurber, PhD, Assistant Professor, Chemical as corroborated by a multitude of studies in disorganized microtubules, nuclear fragmentation/ Engineering and Biomedical Engineering, University of REGISTER ONLINE! rodents and NHPs. While the first clinical studies multiple nuclei, and cell growth inhibition. Based Michigan PEGSummit.com with a GlycoConnect™ ADC are now underway on our data, we propose that T-DM1-induced (NCT03700294), we will discuss how mAb glycan upregulation of TNFa enhances the liver injury that structure correlates with therapeutic index, as well may be initially caused by DM1-mediated intracellular as aspects of CMC supply chain and regulatory damage. In addition, a novel target that mediates considerations towards IND filing. T-DM1-induced hepatotoxicity will also be discussed. REGISTER at PEGSummit.com | 77 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL FUSION & CONJUGATES STREAM continued PARTICIPANTS

REGISTER TODAY 8:35 KEYNOTE PRESENTATION: The CLINICAL DEVELOPMENT AND LESSONS 1:05 Networking Refreshment Break House of Vedotins LEARNED 1:35 Chairperson’s Remarks Robert J. Lechleider, MD, Senior Vice President, 10:35 Amanitin-based Antibody-Drug- Maureen O’Connor-McCourt, PhD, CSO, Forbius COVER Clinical Research, Seattle Genetics Antibody-drug conjugates have proven effective Conjugates as New Therapeutic Modalities for Cancer Therapy NEXT-GENERATION ADCS CONFERENCE-AT-A-GLANCE in treating an array of cancers. Among the most active drug-linker combinations is monomethyl- George Badescu, PhD, VP Scientific Affairs, 1:40 Next-Generation ADCs: Considerations Heidelberg Pharma SHORT COURSES auristatin E (MMAE) coupled to a targeting and Examples antibody via a valine-citrulline linker. MMAE Antigen-Targeted Amanitin-Conjugates (ATACs) Marc Damelin, PhD, Executive Director, Head of represent a new class of ADCs using the payload TRAINING SEMINARS conjugates have shown activity in heme and Biology, Mersana Therapeutics, Inc. Amanitin. This payload introduces a novel mode solid tumors using a number of targeting I will discuss considerations for the discovery and of action into oncology therapy, the inhibition antibodies. The role and future of MMAE drug development of next-generation ADCs as informed of RNA polymerase II. The technology platform conjugates in the treatment of cancer will be by learnings from the field’s collective experience. ENGINEERING includes Amanitin supply, site-specific conjugation, discussed. Topics will include target selection, molecular design, demonstrated safety profile and biomarker. HDP-101 and preclinical pharmacology. is the first ATAC directed against BCMA entering ONCOLOGY PRECLINICAL UPDATES AND Phase I trials by the end of 2019. 2:10 Targeting CD74 with a Novel Antibody- PROOF-OF-CONCEPT 11:05 Targeting Breast Cancer with Antibody- Drug Conjugate, STRO-001 for Treatment of 9:05 A Novel Antibody-Drug Conjugate Drug Conjugates B-Cell Malignancies IMMUNOTHERAPY Targeting ADAM9-Expressing Solid Tumors Aditya Bardia, MD, MPH, Assistant Professor, Arturo Molina, MD, MS, FACP, CMO, Sutro Biopharma Demonstrates Potent Preclinical Activity Medicine, Harvard Medical School 2:40 Antibody-Drug Conjugates Targeting Stuart Hicks, PhD, Director, Pipeline R&D, ImmunoGen Chemotherapy is the mainstay of management of Tumor Stromal Cells EXPRESSION ADAM9 is a cell surface protein that belongs to the multiple solid tumors, but can be associated with Brad St. Croix, PhD, Head, Tumor Angiogenesis Unit, ADAM (a disintegrin and metalloproteinase) family considerable adverse effects. Conceptually, antibody- Mouse Cancer Genetics Program, National Cancer of proteases and is overexpressed in multiple solid drug conjugates can be utilized for targeted delivery Institute of toxic payloads to cancer cells. However, antigen ANALYTICAL tumor indications. IMGC936 is a novel ADAM9- Targeting the tumor stromal cells in addition to targeting ADC comprised of a high-affinity humanized selection of antigen and tumor heterogeneity are tumor cells with ADCs is a promising anti-cancer antibody site-specifically conjugated to DM21, a significant challenges in clinical development of novel strategy. CD276 and TEM8 are variably expressed next-generation linker-payload that combines a antibody-drug conjugates. In this presentation, we will IMMUNOENICITY in a variety of cancers and to different extents on maytansinoid microtubule-disrupting payload with review potential therapeutic strategies and the clinical tumor stromal cells and tumor cells. Both CD276- & BIOASSAYS a stable peptide linker. IMGC936 shows compelling development of antibody-drug conjugates in breast ADC-PBD and TEM8-ADC-MMAE eradicated large efficacy in ADAM9-positive xenograft models cancer. established tumors and metastases and improved FUSIONS & and was well-tolerated following repeat dosing in long-term overall survival in several different mouse cynomolgus monkeys making IMGC936 a promising 11:35 Discovery of Next-Generation ADCs: CONJUGATES Preclinical and Clinical Development of models of cancer. The mechanistic basis for the therapeutic candidate to target a wide range of efficacy of these agents will be discussed, along with ADAM9-expressing tumors. AVID100, an EGFR-Targeting ADC implications for other vascular-targeted ADCs Maureen O’Connor-McCourt, PhD, CSO, Forbius THERAPEUTICS & 9:35 CD163 as a Target for Directing ADCs to AVID100 is an EGFR-targeting ADC which was 3:10 Tisotumab Vedotin – A Novel Tissue TECHNOLOGIES Macrophages in Cancer and Inflammation – designed by screening a library of anti-EGFR ADCs Factor-Targeting Antibody-Drug Conjugate for Preclinical Proof of Concept against both tumor and normal cells expressing the Treatment of Advanced Solid Tumors Jonas Heilskov Graversen, PhD, Associate Professor, EGFR. This approach enabled us to identify AVID100, Jeffrey Harris, PhD, Associate Director, Translational SPONSOR/EXHIBIT Molecular Medicine, University of Southern Denmark which exhibited a very promising therapeutic index Research, Genmab INFORMATION We have validated the macrophage specific in preclinical studies. AVID100 recently completed Tisotumab vedotin (TV) is an antibody-drug conjugate internalization receptor CD163 as an ADC target in a successful phase 1 clinical program and a phase (ADC) that binds and interferes with tissue factor HOTEL & TRAVEL INFORMATION cancer and inflammation. PoC studies in mice, rats 2 study has been initiated. Importantly, only modest signaling, has potent anti-tumor activity in vitro and and pigs show a strongly reduced (50-fold) effective skin toxicity was observed, as predicted by our in vivo, and minimal effect on pro-coagulant activity. REGISTRATION INFORMATION dose for anti-inflammatory effect when targeting preclinical data. TV is efficiently internalized to the lysosome of the dexamethasone to macrophages (endotoxemia and 12:05 pm [Fam-] Trastuzumab Deruxtecan (DS cell, making it an optimal ADC. TV is currently being NASH models). In cancer we observe substantially tested in multiple clinical trials evaluating the safety, 8201) Clinical Development Update REGISTER ONLINE! increased infiltration of effector T-cells and T-cell tolerability, and anti-tumor activity in patients with PEGSummit.com dependent tumor regression in a murine anti-PD-1 Thomas Held, MBA, Vice President, ADC Task Force, previously treated and advanced metastatic solid Daiichi Sankyo resistant melanoma model when eradicating tumor tumors. associated macrophages by toxin targeting. 12:35 Luncheon Presentation (Sponsorship 3:40 End of Conference 10:05 Networking Coffee Break Opportunity Available) or Enjoy Lunch on Your Own REGISTER at PEGSummit.com | 78 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS REGISTER TODAY

COVER EMERGING THERAPEUTICS CONFERENCE-AT-A-GLANCE & TECHNOLOGIES STREAM SHORT COURSES

TRAINING SEMINARS

ENGINEERING Cutting-Edge Science and Emerging Indications for ONCOLOGY Technology to Deliver New Therapeutic Antibodies Therapeutic Applications IMMUNOTHERAPY The Emerging Therapeutics & Technologies stream comprises of 3 unique topics, offering an interdisciplinary approach for protein scientists EXPRESSION from discovery, microbiology, genomics, chemistry and engineering to Oncolytic come together to uncover new therapeutic applications and cutting-edge technologies. Emerging Indications for Therapeutic Antibodies will reveal ANALYTICAL Viral Therapy new targets and novel mechanisms of actions for development of next- generation therapeutics beyond oncology. New this year is the Oncolytic IMMUNOENICITY Viral Therapy conference, which will showcase the latest research, & BIOASSAYS translational and clinical development in this fast-emerging field. The week FUSIONS & closes with a CRISPR Genome Editing training seminar that will provide CONJUGATES Genome Editing a comprehensive review of gene editing strategies and applications in with CRISPR disease modeling, discovery and development. THERAPEUTICS & TECHNOLOGIES

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COVER 2ND ANNUAL

CONFERENCE-AT-A-GLANCE EMERGING INDICATIONS FOR THERAPEUTIC ANTIBODIES R&D Advances in Non-Cancer Indications for Antibodies and Other Biotherapeutics SHORT COURSES

TRAINING SEMINARS April 8-9, 2019

Significant scientific advances in the fields of immunology and protein science are driving the development of biotherapeutic drugs in a growing range of therapeutic ENGINEERING areas beyond oncology. These advances are driving the identification of new and unique targets, new approaches to developing biotherapeutics for unserved medical needs, methods of binding to illusive targets and translational science for patient stratification and drug development for niche indications. The PEGS Emerging Indications for Therapeutic Antibodies conference provides a forum for research organizations with diverse portfolios to explore new science and technology in the development of a next generation of safe and effective therapeutics in an important set of emerging indications. ONCOLOGY

SUNDAY, APRIL 8 modulate selective functions in cellular context. AUTOIMMUNITY AND INFLAMMATION IMMUNOTHERAPY 9:10 Production of Inhibitory Antibody Against 10:50 Amplifying Antibody Function with Recommended Short Course(s)* Claudin-5 using Engineered Membrane Protein Nanomaterials for Inflammation and SC2: Translational Biotherapeutic Antigens Autoimmune Therapy Development Strategies Part 1: Discovery, EXPRESSION Hiroyuki Takeda, Ph.D., Associate Professor and Tarek Fahmy, PhD, Associate Professor of Biomedical Molecular Assessment and Early Stage Principal Investigator, Division of Protea-Drug- Engineering and Immunobiology, Yale University Development Discovery Sciences, Proteo-Science Center, Ehime Antibody therapy (armed or unarmed) as a “magic ANALYTICAL SC7: Translational Biotherapeutic University, Japan bullet” dates back to Paul Ehlirch in the late 1800’s. To Development Strategies Part 2: Analytical The production of antibodies against extracellular date, the “magic bullet” continues to be challenging and Clinical Considerations regions (ECR) of membrane proteins is notably to implement in a general manner for treatment of difficult because of the low productivity and inflammation and autoimmune disease remission. IMMUNOENICITY *Separate registration required. Click here or see immunogenicity of membrane proteins. We overcome I’ll discuss a paradigm-shift in amplifying antibody & BIOASSAYS page 5 for course details. these problems by using protein engineering and function using small packages called, “nanoparticles” cell-free protein production technology. Immunization loaded with drugs or biologics and targeted to FUSIONS & of engineered claudin-5 (CLDN-5) ECR antigens regulatory immunity. The methodology overcomes CONJUGATES MONDAY, APRIL 8 induced CLDN-5 ECR-binding antibodies with a high several limitations with conventional antibody rate. Five monoclonal antibodies against CLDN-5 therapy. 7:00 am Registration and Morning Coffee ECR were produced from immunized mice, and one clone successfully inhibited CLDN-5-dependent tight 11:20 Novel Anti-CD20 Antibodies for Treating THERAPEUTICS & GPCR AND ION CHANNEL TARGETS Autoimmune Disease and Hematologic TECHNOLOGIES junctions. 8:30 Chairperson’s Opening Remarks Malignancies 9:40 Pipeline Update on GPCR and Ion Channel Alexey Misorin, Senior Research Associate, Antibody Catherine Hutchings, PhD, Independent Consultant, Antibodies Discovery, BIOCAD, Russian Federation United Kingdom SPONSOR/EXHIBIT Catherine Hutchings, PhD, Independent Consultant, We have developed monoclonal antibodies against INFORMATION 8:40 Synthetic Antibody Fragments as Sensors United Kingdom CD20 for treating autoimmune diseases – BCD- and Modulators of GPCR Activation and G protein-coupled receptors (GPCRs) and ion 132, and for treating hematologic malignancies HOTEL & TRAVEL INFORMATION Signaling channels represent some of the most important – BCD-171. BCD-132 and BCD-171 interact with Arun K. Shukla, PhD, Chair, Professor and EMBO target classes for therapeutic drug discovery across extracellular part of CD20 antigen with nanomolar REGISTRATION INFORMATION Young Investigator Intermediate Fellow, Wellcome a wide range of diseases. The progress made by affinity and demonstrate desirable properties in Trust DBT India Alliance, Indian Institute of antibody-based therapeutics directed to these target vitro. We will present results from a phase I study of Technology, India classes will be reviewed outlining the breadth and BCD132 in which we evaluated pharmacokinetics, REGISTER ONLINE! G protein-coupled receptors (GPCRs) constitute diversity of antibody molecules, target opportunities pharmacodynamics, safety and immunogenicity of PEGSummit.com the largest class of cell surface receptors and they in R&D and the clinical pipeline, including recent our antibodies. are targeted by majority of currently prescribed development to the expansion of opportunities medicines. We have developed and characterized afforded by next-generation modalities. a series of synthetic antibody fragments through Phage Display technology platform that can report 10:10 Networking Coffee Break GPCR activation with spatio-temporal resolution and REGISTER at PEGSummit.com | 80 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EMERGING THERAPEUTICS & TECHNOLOGIES EMERGING INDICATIONS FOR THERAPEUTIC ANTIBODIES continued PARTICIPANTS STREAM

REGISTER TODAY 11:50 KEYNOTE PRESENTATION: Lessons informs sequence, structural, formulation and PLENARY KEYNOTE SESSION Learned from Humira process refinements to select the best candidate for Jochen Salfeld, PhD, Vice President, Global manufacture. 4:00 Chairperson’s Remarks Biologics; Distinguished Research Fellow, AbbVie COVER 1:20 Luncheon Presentation II: Sponsored by Rakesh Dixit, PhD, DABT, Vice President, R&D, The presentation will focus on the evolution of Global Head, Biologics Safety Assessment, Development of Active and CONFERENCE-AT-A-GLANCE therapeutic Anti-TNF approaches, the history Translational Sciences, AstraZeneca of adalimumab and will start to answer the Passive Immunization Strategies for Preventing HIV Infection 4:10 Vision for How Immunotherapy Will SHORT COURSES question how to explain some of the apparent clinical differences between the Anti-TNF agents Mauricio Martins, PhD, Assistant Professor, Biology, Shape Future of Cancer Care University of Miami Leena Gandhi, MD, PhD, Vice President, Immuno- TRAINING SEMINARS in clinical use today. In this context the learnings about TNF biology and the mechanism of action Despite improvements in prevention strategies Oncology Medical Development, Lilly Oncology of TNF antagonists will be discussed and how and antiretroviral therapy coverage, thousands of Immunotherapy is considered by many as a those learnings impact the development of novel new HIV infections are still occurring every day, pillar of cancer care today, but in many ways we ENGINEERING therapeutics. underscoring the need for effective anti-HIV immune have only scratched the surface. Our knowledge interventions. Here I will describe how my laboratory and understanding of the complexities of has been developing and testing immunization immunotherapy and its mechanisms continue to 12:20 pm A Multiplatform Strategy Sponsored by ONCOLOGY strategies against HIV in rhesus macaques (RMs). evolve. The future of cancer care will be defined for the Discovery of Modulating In the first part of the talk, I will show how we by our ability to systematically identify and Antibodies Against Ion Channel used a new vaccine modality to elicit protective implement opportunities for combination therapy Targets IMMUNOTHERAPY immunity against a highly pathogenic simian to improve and standardize patient response. Yelena Bisharyan, Director, External Alliances, immunodeficiency virus (SIV) molecular clone. This Tetragenetics, Inc. vaccine regimen consisted of DNA plasmids delivered 4:55 The Lassa Virus Glycoprotein: Identifying antibodies that block ion channels is a by intramuscular electroporation and replication- Stopping a Moving Target EXPRESSION challenging endeavor exacerbated by difficulties in competent forms of rhesus monkey rhadinovirus Kathryn Hastie, PhD, Staff Scientist, Immunology producing recombinant ion channels in amounts (RRV)–a herpesvirus that establishes persistent and Microbiology, The Scripps Research Institute that support drug discovery programs. We have infection in RMs. In the second part of the talk, I will Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. ANALYTICAL developed a strategy to address this challenge by go over our plans to gene therapy to prevent mother- combining high-level expression of these proteins to-child transmission (MTCT) of HIV. Specifically, The trimeric surface glycoprotein, termed with immunization of diverse species and unique we will use adeno-associated virus (AAV) vectors to GPC, is critical for infection, is the target for screening tools. transfer genes encoding HIV-specific broadly-reactive neutralizing antibodies, and a major component IMMUNOENICITY neutralizing monoclonal antibodies (bnMAbs) of vaccines. Structural analysis of Lassa GPC Sponsored by & BIOASSAYS 12:35 Longitudinal, Event-Based, newborn RMs. AAV vectors have emerged as safe bound to antibodies from human survivors Same-Day Sample Collection: and versatile gene therapy tools that can transduce reveals a major Achilles heel for the virus and The Implications for Biomarker both dividing and non-dividing cells. Given the long provides the needed template for development FUSIONS & Development of immunotherapeutics and improved vaccines. CONJUGATES lifespan of muscle cells (average: 15 years), skeletal Brian Neman, CEO, Sanguine Biosciences muscle is a preferred tissue for AAV-mediated gene Sanguine partners with patients and leverages transfer. Thus, a single intramuscular injection of their health data to accelerate your research for AAV/bnMAb vectors at birth might result in long-term 5:40 Welcome Reception in the Exhibit Hall THERAPEUTICS & with Poster Viewing TECHNOLOGIES their condition. By working together with patients, production of bnMAbs for years, possibly decades. directly, Sanguine is able to perform home visits, and Achieving this outcome in infants would dramatically 7:15 End of Day to easily retrieve medical records, on their behalf. simplify efforts to prevent MTCT of HIV. We hope that 500+ completed studies. 20/40 top pharma. 30,000+ the HIV immunization approaches described here will SPONSOR/EXHIBIT patients. provide new insights into how to generate persistent TUESDAY, APRIL 9 INFORMATION immunity against HIV. 12:50 Luncheon Presentation I: Sponsored by 8:00 am Registration and Morning Coffee HOTEL & TRAVEL INFORMATION Developability: Evaluating 1:50 Session Break INNOVATIVE MOLECULAR AND PRODUCT Specificity, Immunogenicity, 2:20 Problem-Solving Breakout Discussions REGISTRATION INFORMATION Functionality & Manufacturability For Lead FORMATS Candidate Selection 3:20 Networking Refreshment Break 8:25 Chairperson’s Remarks REGISTER ONLINE! Campbell Bunce, Senior Vice President, Scientific Ahuva Nissim, PhD, Professor, Antibody and Operations, Abzena Therapeutic Engineering, Biochemical Pharmacology, PEGSummit.com Understand the latest series of in silico computational Queen Mary University, United Kingdom models, analytics, in vitro and ex vivo experiments used in developability assessment. Characterise a molecules Specificity, Immunogenicity, Safety, Functionality and Manufacturability. Data generated REGISTER at PEGSummit.com | 81 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EMERGING THERAPEUTICS & TECHNOLOGIES EMERGING INDICATIONS FOR THERAPEUTIC ANTIBODIES continued PARTICIPANTS STREAM

REGISTER TODAY 8:30 Direct Targeting Cytosolic Proteins by Immunology Research, Committee on Immunology, 2:05 Anti-Cytokine Therapy for Atherosclerosis IgG-Format Antibody University of Chicago Paul M. Ridker, MD, MPH, Eugene Braunwald Yong Sung Kim, PhD, Professor, Molecular Science & Influenza infections are a leading cause of death and Professor of Medicine, Harvard Medical School; COVER Technology, Ajou University, Korea illness. Current vaccines to influenza are insufficient Director, Center for Cardiovascular Disease Our group recently developed a platform technology because of changes in viral antigenicity. Recent Prevention, Brigham and Women’s Hospital CONFERENCE-AT-A-GLANCE of a cytosol-penetrating antibody (cytotransmab), work will be discussed on the characterization of Recently, the Canakinumab Anti-inflammatory which in the IgG format can reach the cytosolic space human B cell and antibody responses to influenza. Thrombosis Outcomes Study (CANTOS) has SHORT COURSES of living cells owing to its endosomal escaping ability This work has led to key insights that should demonstrated that specific targeting of interleukin- after receptor-mediated endocytosis. Based on the allow improvements to influenza vaccines and to 1beta can significantly lower cardiovascular event TRAINING SEMINARS cytotransmab technology, we have engineered a identify monoclonal antibodies that could be used rates with no effect on cholesterol or blood pressure. human IgG1 format antibody, named iMab, which therapeutically. Moreover, the magnitude of clinical benefit was related to the robustness of inflammation inhibition. specifically internalizes into the cytosol of tumor 11:20 Antibody-Antibiotic Conjugate against cells and then selectively binds to targeted cytosolic Thus, we now have proof of principle for the ENGINEERING Staphylococcus Aureus: Mechanism and proteins, including oncogenic Ras mutants. inflammation hypothesis of atherothrombisis and a Modulation of Activity signal for multiple new treatment targets. 9:00 Targeting Microvesicles Loaded with Wouter Hazenbos, PhD, Scientist, Infectious Diseases, ONCOLOGY Drugs to Arthritic Joints Using Antibodies Genentech 2:35 Targeting FcRn in IgG Autoantibody- Specific to Arthritic Cartilage Complicated Staphylococcus aureus infections can be Driven Diseases Ahuva Nissim, PhD, Professor, Antibody and difficult to treat, as bacteria may reside in intracellular Anthony Shock, PhD, Director, Immunology Research, UCB, United Kingdom IMMUNOTHERAPY Therapeutic Engineering, Biochemical Pharmacology, reservoirs, limiting antibiotic access. We generated an Queen Mary University, United Kingdom antibody-antibiotic conjugate, comprising an antibody The neonatal Fc receptor, FcRn is responsible for Microvesicles (MV) are extracellular vesicles released binding S. aureus, conjugated to a rifamycin-analog rescuing IgG from lysosomal degradation and is from the plasma membrane of cells. We loaded MV through a cathepsin-cleavable linker. This molecule responsible for the long half-life of this protein in vivo, EXPRESSION with antibody specific to damaged arthritic cartilage kills S. aureus inside host cells, and is superior to but FcRn is also responsible for recycling pathogenic (anti-ROS-CII). After assessing incorporation and standard antibiotics in mouse infection. Current work IgG autoantibodies. Rozanolixizumab is a high affinity in vitro functional validation, in vivo localization focuses on MOA; new technology to enhance activity; IgG4P mAb targeting FcRn, developed to specifically ANALYTICAL and treatment experiments using mouse model of applicability to other pathogens. inhibit the recycling of IgG and is demonstrating clinical efficacy in patients with IgG autoantibody- arthritis were successfully performed. MV targeted 11:50 Structure-Based Approaches for the by anti-ROS-CII loaded with combined treatment driven diseases. significantly accelerated resolution of inflammation. Discovery of Potent Antibodies against Malaria IMMUNOENICITY Antigens 3:05 MutaMap®, a Mutational Sponsored by & BIOASSAYS Thus, targeted MV may be developed as a ‘magic bullet’ to safely treat diseases. Jean- Philippe Julien, PhD, Canada Research Chair in Activity Map for Optimum Protein Structural Immunology, The Hospital for Sick Children Design 9:30 V565, an Oral Anti-TNFα Domain Antibody Research Institute Emilee Knowlton, PhD, Immunology, Sales Specialist, FUSIONS & Sales, ProImmune Inc. CONJUGATES for IBD Reverse vaccinology holds promise to design Tim Carlton, PhD, Associate Director, Research, effective immunogens for the development of malaria MutaMap® is an in vitro assay system that helps VHSquared, United Kingdom vaccines. This concept is based on interrogating B explore the effect of substituting each amino acid THERAPEUTICS & V565 is an anti-TNFα domain antibody for oral cell repertoires to identify inhibiting antibodies that in at each position in a protein sequence one by one TECHNOLOGIES administration in IBD patients, derived from a will guide immunogen design. Our research focuses with all 19 possible substitutions and find out the llama single domain antibody and engineered for on characterizing protective antibodies of high effect on protein activity. MutaMap® allows you to intestinal protease resistance. Ex vivo biopsy studies, potency against malaria antigens at the bottlenecks of make informed protein engineering decisions for measuring changes in phosphoprotein levels, and transmission between the mosquito vector and human a range of key developability objectives, including; SPONSOR/EXHIBIT oral dosing studies in man demonstrate that V565 host. These studies also have implications for the Improving activity/affinity, de-immunization, altering INFORMATION is highly potent, stable throughout the intestine and development of antibody interventions against malaria. cross reactivity, improving humanization and able to penetrate the disrupted colonic mucosa and prolonging half-life of your protein. 12:20 pm Luncheon Presentation (Sponsorship HOTEL & TRAVEL INFORMATION neutralize membrane and soluble TNFα at the site of active disease. Opportunity Available) or Enjoy Lunch on your 3:35 Refreshment Break in the Exhibit Hall with REGISTRATION INFORMATION Own Poster Viewing 10:00 Coffee Break in the Exhibit Hall with 1:20 Ice Cream Break in the Exhibit Hall with 4:25 Completing the Immunity Cycle by Poster Viewing REGISTER ONLINE! Poster Viewing Developing Myeloid Immunotherapies INFECTIOUS DISEASES Tatiana Novobrantseva, PhD, Co-Founder, Head of PEGSummit.com OTHER EMERGING INDICATIONS Research and Development, Verseau Therapeutics 10:50 Antibody Responses to Influenza in 2:00 Chairperson’s Remarks Macrophages/DCs are biologically optimized to either Context induce or suppress an immune response. Anthony Shock, PhD, Director, Immunology Research, Patrick C. Wilson, PhD, Professor, Medicine & UCB, United Kingdom Rheumatology, Knapp Center for Lupus and REGISTER at PEGSummit.com | 82 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EMERGING THERAPEUTICS & TECHNOLOGIES EMERGING INDICATIONS FOR THERAPEUTIC ANTIBODIES continued PARTICIPANTS STREAM

REGISTER TODAY Targeting pro-tumorigenic macrophages has been repeatedly identified as a very important next step of development for the field of immuno-oncology. COVER Similarly, myeloid cell suppression has been long realized to be fueling the vicious cycle of the CONFERENCE-AT-A-GLANCE autoimmune disease. The talk will describe Verseau Therapeutics’ approaches to tweaking myeloid cell SHORT COURSES functionality in human disease. 4:55 Antagonistic Antibodies Used to Establish TRAINING SEMINARS the Key Role for IL-13 Signaling Via the Type 2 IL-4 Receptor in Experimental Atopic Dermatitis ENGINEERING Itai Benhar, PhD, Professor, Molecular Cell Biology and Biotechnology. Tel-Aviv University IL-13 and IL-4 are potent mediators of type ONCOLOGY 2-associated inflammation such as asthma and atopic dermatitis (AD) and share a receptor subunit, IL-13Ra1 which is part of IL-4R. The role of the type IMMUNOTHERAPY 2 IL-4R in AD remains to be defined. We show that oxazolone-induced AD in mice is dependent on the type 2 IL-4R and targeting of the type 2 IL-4R using an IL-13Ra1-neutralizing antibody alleviates oxazolone- EXPRESSION induced AD. 5:25 End of Emerging Indications for Therapeutic Antibodies ANALYTICAL 5:30 Registration for Dinner Short Courses

IMMUNOENICITY Recommended Dinner Short Course* & BIOASSAYS SC11: Developability of Bispecific Antibodies: Formats and Applications *Separate registration required. Click here or see FUSIONS & page 5 for course details. CONJUGATES

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REGISTER at PEGSummit.com | 83 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EMERGING THERAPEUTICS & TECHNOLOGIES STREAM PARTICIPANTS REGISTER TODAY INAUGURAL ONCOLYTIC VIRAL THERAPY COVER Engineering, Translational and Clinical Strategies CONFERENCE-AT-A-GLANCE April 10-11, 2019 SHORT COURSES PEGS Boston’s Inaugural Oncolytic Viral Therapy invites speakers to discuss their exciting research and development in the growing oncovirotherapy field, from TRAINING SEMINARS mechanistic understanding of viruses and tumor biology, to engineering and optimization strategies, preclinical and translational sciences, clinical trial updates and challenges.

ENGINEERING WEDNESDAY, APRIL 10 Oncolytic virus potency can be favorably impacted Patrik Erlmann, PhD, Head, R&D, ViraTherapeutics GmbH by concomitant immunosuppressive drug therapy VSV-GP combines the tumor cell killing efficacy 7:15 am Registration and Morning Coffee to retard the host antiviral response and accelerate of Vesicular Stomatitis Virus with an enhanced ONCOLOGY intratumoral spread. But without stringent targeting safety profile, making it an excellent oncolytic virus of virus tropism, increased OV potency is associated candidate for clinical development. Here we show 7:25 - 8:25 PANEL DISCUSSION: Women in with an increased risk of off-target toxicity. To that VSV-GP mediated cell lysis releases tumor Science – Inspired Professional and Personal address this limitation, Vyriad is developing a derived antigens, which in combination with the viral IMMUNOTHERAPY Stories new generation of retargeted viruses whose components, such as the viral RNA genome unleash a Moderator: Women in Bio, Boston Chapter attachment, cell entry and cytotoxic potential are strong anti-tumor immune response. Panelists: fully reprogrammed through surface display of single EXPRESSION Susan Richards, PhD, Presidential Scientific Fellow, chain antibody targeting domains. 11:55 pm POSTER HIGHLIGHT: Stealth Translational Medicine Early Development, Sanofi R&D Targeted Nano Coatings for Oncolytic Viruses 9:40 Oncolytic Virus Vaccines Joanna Brewer, PhD, Vice President, Platform for Repeat Systemic Administration Technologies, AdaptImmune John C. Bell, PhD, Professor, Medicine & Biochemistry, Inanc Ortac, PhD, CTO, DevaCell, Inc. ANALYTICAL Microbiology & Immunology, Ottawa Hospital Additional Panelists to be Announced Research Institute, University of Ottawa Systemic delivery and repeat administration of oncolytic viruses have been shown to be crucial for 10:10 Coffee Break in the Exhibit Hall with strong efficacy and anti-tumor immunity of oncolytic IMMUNOENICITY ENGINEERING NEXT-GEN ONCOLYTIC Poster Viewing virotherapy. However, rapid neutralization and & BIOASSAYS VIRUSES clearance of oncolytic viruses limits the promise of the therapy. Surface modifications of viruses such 8:30 Chairperson’s Opening Remarks 10:15 Women in Science Speed Networking in as blocking and removing immunogenic antigens FUSIONS & Timothy Cripe, MD, PhD, Professor and Chief, Division the Exhibit Hall of Hem/Onc/BMT, Nationwide Children’s Hospital often have negative impacts on the infectivity of the CONJUGATES virus. This poster describes a novel approach, which 10:55 Engineering Viruses to Deliver their is based on forming a removable organic/inorganic 8:40 KEYNOTE PRESENTATION: Next Maximum Potential: Two Examples from the hybrid nanolayer, ONCoat™, formed around the virus THERAPEUTICS & Generation OV and New Combinational Turnstone Portfolio surface that releases the unmoEdified virus inside TECHNOLOGIES Approaches for Treatment of Solid Tumors Caroline Breitbach, PhD, Vice President, R&D the infected cell. Such encapsulation provides flexible Paola Grandi, PhD, CSO, Cold Genesys Programs and Strategy, Turnstone Biologics surface functionalization to the virus while allowing In the last few years, oncolytic vectors have An overview of the development of MG1 Maraba viruses to be stealth to the immune system, enabling SPONSOR/EXHIBIT become one of the most promising immuno- an SKV vaccinia oncolytic viral immunotherapy targeted syste mic delivery and repeat administration. INFORMATION therapy agents for the treatment of cancer. platforms will be provided. MG1 is a novel Following application of ONCoat™, the infectivity of Leaders from academia and industry have rhabdovirus engineered to express tumor antigens, the virus is not negatively affected. Furthermore, HOTEL & TRAVEL INFORMATION made advances in vector engineering, explored thereby eliciting anti-tumor immune responses while virus, when released within the cell, is unmodified can advantages and limitations of preclinical modifying the tumor immune microenvironment. still engage its own mechanisms for gene expression, REGISTRATION INFORMATION models, discussed updates from combination SKV is a novel engineered vaccinia platform being replication and oncolysis. trials, as well as shared challenges and potential used to deliver multiple immune-modulatory strategies of systemic delivery. In this talk, I agents. These therapeutic agents are designed 12:25 Luncheon Presentation (Sponsorship REGISTER ONLINE! will present an overview of the Phase II clinical to re-program the tumor microenvironment to Opportunity Available) or Enjoy Lunch on Your trial with CG0070 for the treatment of BCG- abrogate immunosuppressive networks, thereby Own PEGSummit.com unresponsive bladder cancer. re-establishing endogenous anti-tumor immunity to 1:55 Session Break achieve an effective in situ vaccination. 9:10 Antibody Targeted Viruses: The Next 11:25 VSV-GP Eradicates the Tumor and Generation of Oncolytics Stimulates an Immune Response Stephen J. Russell, MD, PhD, CEO, Vyriad, Inc. REGISTER at PEGSummit.com | 84 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL EMERGING THERAPEUTICS & TECHNOLOGIES ONCOLYTIC VIRAL THERAPY continued PARTICIPANTS STREAM

REGISTER TODAY PRECLINICAL AND CLINICAL PROGRESS 8:35 T-SIGn Virus Approach to Cancer Gene We have been investigating a gene therapy agent 2:10 Chairperson’s Remarks Therapy – Driving the Tumor Cells to Express based on a non-replicating adenoviral vector to deliver the Herpes virus Thymidine kinase gene to Patrik Erlmann, PhD, Head, R&D, ViraTherapeutics GmbH Combinations of Biological Therapeutics COVER within the Tumor Microenvironment glioblastoma by intratumoral injection. Our studies 2:15 Development of Patient-Derived Brian Champion, PhD, CSO, PsiOxus have shown that this results in high local IFNg levels, and upregulation of PD-L1 on tumor cells, microglia, CONFERENCE-AT-A-GLANCE Glioblastoma Model Systems to Predict This presentation will cover the T-SIGn oncolytic and macrophages in the tumor microenvironment. Response to OV Therapy adenovirus platform: gene therapy for cancer; T-SIGn Combination of immune checkpoint blockade with SHORT COURSES Martine Lamfers, PhD, Associate Professor, viruses for combination immunotherapy and NG-641 an anti-PD1 antibody overcomes this potential Neurosurgery, Erasmus Medical Center Rotterdam T-SIGn virus designed for targeting the treatment of resistance mechanism and leads to a high cure rate TRAINING SEMINARS Oncolytic viral therapies are showing promising stromal-rich cancers. in experimental murine glioblastoma models. This results in early clinical trials, however, response rates combination is now being advanced towards Phase I are suboptimal. Preclinical studies suggest that 9:05 Inflaming the Tumor Microenvironment to clinical trials in primary glioblastoma. ENGINEERING tailoring the selected OV strain to the tumor subtype Augment Oncolytic Virotherapy may markedly improve response rates. Patient-derived Timothy Cripe, MD, PhD, Professor and Chief, Division 11:35 Oncolytic Poliovirus Combined with model systems may offer a tool to identify the most of Hem/Onc/BMT, Nationwide Children’s Hospital PD1/PDL1 Blockade for Cancer Therapy optimal oncolytic virus for a specific patient and could Cancer immunotherapies hold great promise, but ONCOLOGY Smita Nair, PhD, Professor, Surgery, Neurosurgery and aid in the design of future stratified trials for OV therapy. scores of disappointing studies highlight our relative Pathology, Duke University School of Medicine ignorance in understanding the immunosuppressive Oncolytic poliovirus PVSRIPO targets and kills tumor 2:45 Lessons Learned from a Phase I Trial of microenvironment within solid tumors. Because of their cells and induces sustained type I IFN-dominant Intratumoral and Intravenous Oncolytic Herpes central role in mediating immunosuppression, tumor IMMUNOTHERAPY activation of antigen presenting cells, which overcomes Virus in Children and Young Adults associated macrophages (TAMs), typically “polarized” the immunosuppressive tumor microenvironment Keri Streby, MD, Pediatric Oncologist, Hematology & to a so-called M2-like phenotype, are thought to be an to stimulate antitumor immunity. Preclinical data Oncology, Nationwide Children’s Hospital important therapeutic target. I will discuss our work in murine models demonstrate that: 1] Intratumor EXPRESSION to modulate TAMs and TGFb to enhance antitumor 3:15 Engineering Vaccinia Virus for PVSRIPO administration causes oncolysis and efficacy of oncolytic herpes virotherapy. Intratumoral Delivery to Generate “in situ inflammation, which stimulates innate and adaptive ANALYTICAL Vaccination” against Cancer 9:35 Oncolytic Herpes Simplex Virus immunity; 2] Immune activation triggers adaptive Liang Deng, MD PhD, Associate Member, Associate Combinations Boosting Immunovirotherapy immune resistance via the PD1/PDL1 axis; 3] Blocking Attending Physician, Memorial Sloan Kettering Cancer Samuel D. Rabkin, PhD, Thomas A. Pappas Prof of PD1/PDL1 with PVSRIPO eliminates adaptive Center resistance and potentiates durable antitumor immunity. IMMUNOENICITY Neurosciences, Prof of Neurosurgery (Microbiology), Vaccinia virus is a large cytoplasmic DNA virus. Harvard Medical School and Massachusetts General 12:05 pm Combination of Adenovirus & BIOASSAYS Modified vaccinia virus Ankara (MVA) is a highly Hospital Oncolytic Virotherapy with CDK4/6 Inhibitors: attenuated vaccinia virus, an important vaccine Oncolytic herpes simplex virus (oHSV) acts by direct An Unexpected and Incredible Strong vector. I will discuss our published study on the tumor cell killing and the induction of anti-tumor FUSIONS & Treatment Alliance CONJUGATES intratumoral delivery of inactivated MVA to induces immune responses, immunovirotherapy. The virus systemic antitumor immunity and to overcome can also be ‘armed’ with therapeutic transgenes, such Per Sonne Holm, PhD, Head, Virotherapy Research Group, Urology, Technical University Munich resistance to immune checkpoint blockade. as cytokines, to improve efficacy by modulating the tumor microenvironment. We will describe preclinical It is widely accepted that adenovirus E1A drives THERAPEUTICS & 3:45 Refreshment Break in the Exhibit Hall with TECHNOLOGIES studies to boost immunovirotherapy using oHSV human cells into S-phase by displacing the Poster Viewing combinations with approved pharmacological agents Retinoblastoma (RB) proteins from E2F transcription 4:45 Problem-Solving Breakout Discussions targeting oncogenic pathways (MEK inhibitors) factors to de-repress cell cycle genes and viral gene and the tumor microenvironment (axitinib). These expression. However, CDK4/6 inhibitors led to strong SPONSOR/EXHIBIT 5:45 Networking Reception in the Exhibit Hall combinations can interact with immune checkpoint synergistic effects with regards to viral replication and INFORMATION with Poster Viewing blockade and are translatable to the clinic. cell killing, resulting in new unexpected insights into Rb/E2F regulation of adenovirus life cycle. These new HOTEL & TRAVEL INFORMATION 7:00 End of Day 10:05 Coffee Break in the Exhibit Hall with perspectives in the Rb/E2F mediated regulation of the Poster Viewing adenoviral life cycle will have great impact for the use REGISTRATION INFORMATION THURSDAY, APRIL 11 of oncolytic adenoviruses with cell cycle inhibitors. COMBINATION VIROTHERAPY WITH 8:00 am Registration and Morning Coffee 12:35 End of Oncolytic Viral Therapy REGISTER ONLINE! IMMUNOTHERAPY PEGSummit.com 11:05 Exploring Virotherapy/Immunotherapy Combinations for the Treatment of TARGETING THE TUMOR Glioblastoma MICROENVIRONMENT Sean Lawler, PhD, Assistant Professor, Managing Director, Harvey Cushing Neurosurgery Laboratories, 8:30 Chairperson’s Remarks Brigham and Women’s Hospital Paola Grandi, PhD, CSO, Cold Genesys REGISTER at PEGSummit.com | 85 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS Also part of REGISTER TODAY EMERGING THERAPEUTICS & TECHNOLOGIES STREAM By Cambridge Healthtech Institute COVER

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SHORT COURSES THURSDAY, APRIL 11: 1:40-5:20 PM - FRIDAY, APRIL 12: 8:30 AM - 3:40 PM

TRAINING SEMINARS Genome Editing with CRISPR: ENGINEERING Towards Novel Research, Translational and Clinical Applications ONCOLOGY This rigorous day and a half program compiled for specialists interested in applying genome editing technologies for both basic and translational research will comprehensively review the state-of-art information on gene editing IMMUNOTHERAPY strategies and applications in various areas, such as disease modelling, drug discovery and development. Beginning from introductory level basic technology aspects, key molecular features, strengths and shortcomings of CRISPR/Cas9 EXPRESSION systems, the instructor will advance towards sharing in-depth knowledge related to virtually all facets of present day genome editing applications, such as constructing of cell culture-based experimental platforms, engineering disease models for in vivo research supporting preclinical drug development workflows, rational design and functional screening ANALYTICAL of sgRNA libraries, application of CRISPR/Cas9 technology for diagnostic and therapeutic purposes and many others. The instructor will strive to achieve a balance between presenting theory information and conducting some practical IMMUNOENICITY tasks in exploring available digital resources for designing and enabling CRISPR/Cas9 studies, as well as assist in & BIOASSAYS troubleshooting specific complex experimental scenarios and conduct Q&A sessions.

FUSIONS & Instructor: CONJUGATES Serguei V. Kozlov, PhD, MBA, PMP, Principal Scientist/PM, Team Leader PTO, Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research (NCI) THERAPEUTICS & TECHNOLOGIES

SPONSOR/EXHIBIT INFORMATION Cambridge Healthtech Institute Training Seminars offer real-life case studies, problems encountered and solutions applied, and extensive coverage of the basic science underlying each topic. Experienced Training Seminar instructors offer a mix of formal HOTEL & TRAVEL INFORMATION lectures, interactive discussions and activities to help attendees maximize their learning experiences. These immersive trainings will be of value to scientists from industry and academic research groups who are entering new fields – and to REGISTRATION INFORMATION those working in supporting roles that will benefit from an in-depth briefing on a specific aspect of the industry.

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REGISTER TODAY Comprehensive sponsorship packages allow you to achieve your objectives before, during, and long after the event. Signing on earlier will COVER allow you to maximize exposure to hard-to-reach decision-makers.

CONFERENCE-AT-A-GLANCE SPONSORED PRESENTATIONS Available within Main Agenda! Showcase your solutions to a guaranteed, targeted audience. Package SHORT COURSES includes a 15 or 30-minute podium presentation on the scientific agenda, exhibit space, branding, full conference registrations, use of the event TRAINING SEMINARS mailing list and more. LUNCHEON PRESENTATIONS ENGINEERING Opportunity includes a 30-minute podium presentation in the main session room. Lunch will be served to all delegates in attendance. A limited number of presentations are available for sponsorship and they will sell out quickly. 2018 ATTENDEE DEMOGRAPHICS ONCOLOGY Sign on early to secure your talk! ONE-ON-ONE MEETINGS COMPANY TYPE Select your top prospects from the pre-conference registration list. CHI will nn Biotech 60% IMMUNOTHERAPY reach out to your prospects and arrange the meeting for you. A minimum nn Pharma 20% number of meetings will be guaranteed, depending on your marketing nn Academic + Government 12% objectives and needs. A very limited number of these packages will be sold. nn Services 3% EXPRESSION INVITATION-ONLY DINNERS / HOSPITALITY SUITES nn Healthcare 3% nn Financial, Press, Societies 2% Select specific delegates from the pre-registration list to attend a private function at an upscale restaurant or a reception at the hotel. From DELEGATE TITLE ANALYTICAL extending invitations, to venue to suggestions, CHI will deliver your prospects and help you make the most of this invaluable experience. nn Scientist/Technologist 37% nn Executive + Director 32% IMMUNOENICITY EXHIBIT nn Sales & Marketing 15% & BIOASSAYS Exhibitors will enjoy facilitated networking opportunities with qualified nn Manager 7% delegates, making it the perfect platform to launch a new product, collect nn Professor 6% FUSIONS & feedback, and generate new leads. Exhibit space sells out quickly, so reserve nn Assistant 3% CONJUGATES yours today! Additional Opportunities Available for Sponsorship Include: GEOGRAPHIC LOCATION • Poster Awards • Badge Lanyards – SOLD! THERAPEUTICS & nn USA 77% TECHNOLOGIES • Footprints • Conference Notebook • Focus Groups • Padfolios nn Europe 15% • User Group Meetings • Program Guide Advertisement nn Asia 6% SPONSOR/EXHIBIT • Conference Tote Bags – SOLD! • …and More! nn Rest of World 2% INFORMATION Looking for additional ways to drive leads to your sales team? HOTEL & TRAVEL INFORMATION CHI’s Lead Generation Programs will help you obtain more targeted, quality US BREAKDOWN leads throughout the year. We will mine our database of over 800,000 life nn VIEW CURRENT EXHIBITOR East Coast 65% REGISTRATION INFORMATION science professionals to your specific needs. We guarantee a minimum of nn West Coast 27% 100 leads per program! Opportunities include: LIST AND FLOOR PLAN nn Midwest 8% • White Papers • Web Symposia REGISTER ONLINE! • Custom Market Research Survey • Podcasts PEGSummit.com

For more information on sponsorship COMPANIES A-K: Jason Gerardi COMPANIES L-Z: Carol Dinerstein and exhibit opportunities, please contact: Senior Manager, Business Development Senior Manager, Business Development 781-972-5452 | [email protected] 781-972-5471 | [email protected]

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CONFERENCE-AT-A-GLANCE SHORT COURSES EVENT FEATURES TRAINING SEMINARS • 22 Conferences, Training Seminars and Short Courses covering protein and antibody engineering, cancer immunotherapy, ENGINEERING Well organized, oncology, and emerging therapeutics, and more as usual, but particularly • Over 350+ Speakers representing top pharma, biotech, academia, ONCOLOGY and government institutions – In 2018 there were over 100 in regard to the breadth presentations from top 10 pharma companies IMMUNOTHERAPY of topics covered and the • 2,600+ International Delegates focusing on biotherapeutic connections made between protein drug development opportunities EXPRESSION • Short Courses providing additional training and education to brush diciplines was nice to see – up on your knowledge or expand your horizons from world-renowned experts ANALYTICAL • Inspiring Keynote Presentations very forward and visionaries

IMMUNOENICITY looking. • NEW Women in Science panel discussion and dedicated & BIOASSAYS - Research Scientist, networking events! AbbVie • Lively Exhibit Hall featuring 150+ companies showcasing FUSIONS & novel technologies and solutions CONJUGATES • Poster Sessions featuring cutting-edge, ongoing research – nearly THERAPEUTICS & 300 posters in 2018! TECHNOLOGIES • Valuable Networking through breakout discussion groups, dedicated poster viewing sessions, interactive panels and more SPONSOR/EXHIBIT INFORMATION • 1-on-1 Networking App to easily build connections with fellow life science professional, schedule meetings and expand your network HOTEL & TRAVEL INFORMATION • Student Fellowships offering discounted registration for young REGISTRATION INFORMATION researchers looking to make a difference and share their research • Sponsored Talks by leading technology and service providers REGISTER ONLINE! showcasing new offerings PEGSummit.com

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Reservations: Go to the Travel Page IMMUNOTHERAPY Conference Venue: Host Hotel: Seaport World Trade Center Seaport Hotel of PEGSUMMIT.com One Seaport Lane 200 Seaport Boulevard $294 s/d Boston, MA 02210 Discounted Room Rate: EXPRESSION Boston, MA 02210 T: 1-877-SEAPORT Discounted Room Rate Cutoff: (1-877-732-7678) March 1, 2019 ANALYTICAL Please visit the Travel Page of PEGSUMMIT.com for additional Information IMMUNOENICITY & BIOASSAYS MEDIA SPONSORS FUSIONS & CONJUGATES Lead Sponsoring Publications THERAPEUTICS & Sponsoring Organizations TECHNOLOGIES

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REGISTER at PEGSummit.com | 89 A Division of Cambridge Innovation Institute JOIN 2,600 GLOBAL PARTICIPANTS Please use keycode How to Register: PEGSummit.com PEG F REGISTER TODAY [email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288 when registering!

COVER Complimentary news delivered to your inbox CONFERENCE-AT-A-GLANCE PRICING AND REGISTRATION INFORMATION News on the data deluge in petascale SHORT COURSES SHORT COURSE ONLY PRICING computing and the tools to deliver individualized medicine. TRAINING SEMINARS Academic, Government, Bio-ITWorld.com Commercial Hospital-affiliated 1 Short Course $699 $349 ENGINEERING Insights on the innovation between clinical 2 Short Courses $999 $599 trial management and delivery of care. 3 Short Courses $1,199 $699 ClinicalInformaticsNews.com

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Advance - Registration Rate Until March 15, 2019 $3,199 $1,699 Reports designed to keep life science EXPRESSION professionals informed of the salient trends Registrations After March 15, 2019 and On-Site $3,399 $1,799 in pharma technology, business, clinical development, and therapeutic disease markets STANDARD PACKAGE (Includes access to 2 conferences and/or Training Seminars. Excludes short courses.) InsightPharmaReports.com ANALYTICAL Contact Adriana Randall, Advance - Registration Rate Until March 15, 2019 $2,799 $1,349 [email protected], +1-781-972-5402. Registrations After March 15, 2019 and On-Site $3,049 $1,449 IMMUNOENICITY & BIOASSAYS BASIC PACKAGE (Includes access to 1 conference or Training Seminar. Excludes short courses.) Advance - Registration Rate Until March 15, 2019 $1,899 $949 FUSIONS & Registrations After March 15, 2019 and On-Site $2,099 $1,099 Barnett is a recognized leader in clinical education, training, and reference guides CONJUGATES for life science professionals involved in the drug development process. For more CONFERENCE DISCOUNTS information, visit BarnettInternational.com. THERAPEUTICS & TECHNOLOGIES POSTER SUBMISSION - DISCOUNT ($50 OFF): Poster abstracts are due by March 1, 2019. Once your registration has been fully processed, we will send an email containing a unique link allowing you to ADDITIONAL REGISTRATION submit your poster abstract. If you do not receive your link within 5 business days, please contact [email protected]. DETAILS *CHI reserves the right to publish your poster title and abstract in various marketing materials and products. Each registration includes all SPONSOR/EXHIBIT conference sessions, posters and INFORMATION REGISTER 3 - 4TH IS FREE: exhibits, food functions, and access Individuals must register for the same conference or conference combination and submit completed registration form together for discount to apply. to the conference proceedings link. Handicapped Equal Access: HOTEL & TRAVEL INFORMATION ALUMNI DISCOUNT - SAVE 20%: Cambridge Healthtech Institute (CHI) appreciates your participation at its events. As a result of the great loyalty you have In accordance with the ADA, shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate. Cambridge Healthtech Institute REGISTRATION INFORMATION is pleased to arrange special GROUP DISCOUNTS: Discounts are available for multiple attendees from the same organization. For more information on group rates contact David accommodations for attendees with Cunningham at +1-781-972-5472 or [email protected]. special needs. All requests for such assistance must be submitted in REGISTER ONLINE! writing to CHI at least 30 days prior PEGSummit.com If you are unable to attend but would like to purchase the PEGS Summit CD for $750 (plus shipping), please visit PEGSummit.com. to the start of the meeting. Massachusetts delivery will include sales tax. To view our Substitutions/ Cancellations Policy, go to healthtech.com/regdetails Video and or audio recording of any kind is prohibited onsite at all CHI events.

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