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Final Agenda Final Weeks to Register for the Largest PEGS Europe Ever! Ninth Annual

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Conference-at-a-Glance Short Courses Protein & Antibody Engineering Summit Training Seminars 13 – 17 November 2017 | EPIC SANA Lisboa Hotel | Lisbon, Portugal

Engineering n Display of Biologics Plenary Keynotes n Engineering Antibodies n Engineering Bispecifics Safety Considerations for Development of Be part of a growing event - attendance has increased Immune Agonist and Immune Antagonist more than 45% since 2014 Therapeutics Biotherapeutics Rakesh Dixit, Ph.D., DABT, Vice President, R&D, n Novel Immunotherapy Strategies and Global Head, Biologics Safety Assessment, Network with 800 colleagues from 35+ countries at n Advancing Bispecifics MedImmune (A member of AstraZeneca Group) Europe’s largest protein engineering event n Novel Therapies for Cancer Learning What Works from Successful Tumour See unpublished data and case studies from Analytical Infiltrating Lymphocyte Therapy industry leaders n Optimisation & Developability Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff University School of Medicine n Analytical Characterisation Learn from 200 speakers and 140 poster presenters n Aggregates & Particles Widening the Therapeutic Index: The Next Oncology Generation of Antibody-Drug Conjugates (ADCs) Choose from 9 Short Courses and 5 Training Seminars n Antibody-Drug Conjugates John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished Research Fellow, n Advancing Bispecifics ImmunoGen, Inc. n Novel Therapies for Cancer

Expression n Protein Production Technologies n Optimising Expression n Purification Technologies

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Premier A Division of Cambridge Innovation Institute Sponsor PEGSummitEurope.com Final Weeks to Register for the Largest PEGS Europe Ever! CONFERENCE-AT-A-GLANCE

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Conference-at-a-Glance Monday - Tuesday Wednesday - Thursday Thursday - Friday Short Courses 13 - 14 November 15 - 16 November 16 - 17 November

Training Seminars

Display of Biologics Engineering Antibodies Engineering Bispecifics Engineering ENGINEERING n Display of Biologics n Engineering Antibodies n Engineering Bispecifics Advancing Bispecifics Novel Immunotherapy Novel Therapies for and Combination Strategies Cancer and Emerging Therapeutics THERAPEUTICS Therapy to the Clinic Targets n Novel Immunotherapy Strategies n Advancing Bispecifics n Novel Therapies for Cancer Analytical Optimisation & Protein Aggregates Characterisation Analytical Developability and Particles ANALYTICAL of Biotherapeutics n Optimisation & Developability n Analytical Characterisation

Engineering ShortDinner Courses* n Aggregates & Particles Next-Generation Advancing Bispecifics Novel Therapies for

Pre-Conference ShortPre-Conference Courses* Antibody-Drug and Combination Cancer and Emerging ONCOLOGY Oncology Conjugates Therapy to the Clinic Targets n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Protein Production Optimising Expression Protein Purification Technologies Platforms Technologies Expression EXPRESSION n Protein Production Technologies n Optimising Expression Protein Characterisation & n Purification Technologies Production Technologies Control of Particulates Regulatory Requirements Across Product Lifecycle By Cambridge Healthtech Institute Sponsor & Exhibit Opportunities Intro to Protein Next-Generation Engineering Sequencing Hotel & Travel Information By Cambridge Healthtech Institute Registration Information

Register Online! PEGSummitEurope.com The best biologics technology meeting in Europe: a must-attend conference for novel biologics. - Rakesh D., Ph.D., VP, R&D, MedImmune

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Final Weeks to Register PREMIER SPONSOR for the Largest PEGS Europe Ever!

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Conference-at-a-Glance

Short Courses

Training Seminars CORPORATE SPONSORS Engineering n Display of Biologics n Engineering Antibodies n Engineering Bispecifics

Therapeutics n Novel Immunotherapy Strategies n Advancing Bispecifics n Novel Therapies for Cancer

Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles

Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer

Expression n Protein Production Technologies n Optimising Expression n Purification Technologies

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A Division of Cambridge Innovation Institute 3 Final Weeks to Register PLENARY KEYNOTE SESSION for the Largest PEGS Europe Ever! Monday, 13 November | 13:40 – 15:50 Cover

Conference-at-a-Glance

Short Courses Moderator Training Seminars Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA

Engineering n Display of Biologics Safety Considerations for Development of Immune n Engineering Antibodies Agonist and Immune Antagonist Biotherapeutics n Engineering Bispecifics Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment, Therapeutics MedImmune (A member of AstraZeneca Group) In this keynote presentation, the challenges of biotherapeutics impacting on n Novel Immunotherapy Strategies the immune response, and the challenges investigators face managing, dose, n Advancing Bispecifics scheduling, and satisfying the regulatory requirements will be discussed. The n Novel Therapies for Cancer checkpoint pathways modulation used for cancer immunotherapy has a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Analytical Immunotherapies in general, and technologies modifying T cell function and those involving cytokines present dangers of cytokine storm, autoimmune disease, n Optimisation & Developability cardiovascular disorders, and additional challenges, especially when used in n Analytical Characterisation combination. Strategies to manage and mitigate immune related safety events n Aggregates & Particles will be presented.

Oncology Learning What Works from Successful Tumour n Antibody-Drug Conjugates Infiltrating Lymphocyte Therapy n Advancing Bispecifics Andrew Sewell, Ph.D., Professor, Division of Infection and n Novel Therapies for Cancer Immunity, Cardiff University School of Medicine Over 20% of melanoma patients that have been refractory to other Expression treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary n Protein Production Technologies successes by examining the dominant tumor-reactive T-cell clonotypes in the n Optimising Expression TIL infusion product and patient blood after ‘cure’ has revealed some surprising, n Purification Technologies exciting new HLA-restricted and non-HLA restricted targets that are expressed by many other tumour types. Sponsor & Exhibit Opportunities Widening the Therapeutic Index: The Next Hotel & Travel Information Generation of Antibody-Drug Conjugates (ADCs) John M. Lambert, Ph.D., Executive Vice President Emeritus and Registration Information Distinguished Research Fellow, ImmunoGen, Inc. ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets Register Online! have proven susceptible to the development of effective ADCs utilizing the first PEGSummitEurope.com generation ADC chemistries. Each element in the ADC design, the antibody, the payload, and the linker (both site of attachment on antibody and payload- release mechanism) are important considerations. Application of the growing “ADC Toolbox” to current and future ADC developments will be discussed.

A Division of Cambridge Innovation Institute 4 Final Weeks to Register SHORT COURSES* * Separate registration required for the Largest PEGS Europe Ever!

Cover MONDAY, 13 NOVEMBER | 09:00 - 12:00 | MORNING THURSDAY, 16 NOVEMBER | 17:30 - 20:30 | DINNER

Conference-at-a-Glance SC1: New Directions in Cancer Immunotherapy SC6: Engineering of Bispecific Antibodies Mark Cragg, Ph.D., Professor, Experimental Cancer Biology, Antibody & Vaccine Nicolas Fischer, Ph.D., Head, Research, Novimmune SA Short Courses Group, Cancer Sciences Unit, University of Southampton Michela Silacci, Ph.D., Director, Discovery Research, Covagen AG, part of Johnson & Fred Arce Vargas, Ph.D., University College London Cancer Institute Johnson Training Seminars Recently, a number of different approaches have demonstrated unprecedented clinical You will learn about approaches for engineering bispecific antibodies and bispecific scaffold- responses and long-term benefit in patients diagnosed with several types of malignancy. based binding proteins. Different technologies will be compared, and examples for applications In addition to T-cell modulation and anti-PD-1 and anti-CTLA-4, additional pathways and of bispecific antibodies in drug development will be presented with a focus on candidates Engineering therapeutic agents are rapidly being translated to clinical practice alone or in combination currently being evaluated in clinical trials. Opportunities and challenges will be discussed. approaches. n Display of Biologics SC7: Protein Purification Strategies n Engineering Antibodies SC2: Mutation and Selection Strategies beyond Affinity Optimisation Mario Lebendiker, Ph.D., Head, Protein Purification Facility, Wolfson Center for n Engineering Bispecifics Orla Cunningham, Ph.D., Director, Global Biotherapeutic Technologies, Pfizer, Inc. Applied Structural Biology, Hebrew University William (Jonny) Finlay, Director, Protein Discovery & Optimization Group, Pfizer, Inc. This course will provide a comprehensive and detailed outline of hands-on issues for purifying Generated libraries can be selected for improved antigen binding. However, increasingly these proteins. First we will address considerations about the protein we want to produce, including Therapeutics strategies are being used for more complex applications from humanization to ortholog issues of activity, solubility, homogeneity, purity, and proper oligomeric conformation. In n Novel Immunotherapy Strategies cross-reactivity, stability, solubility and specificity optimizations. This workshop will use case addition, we will address ways to monitor and avoid aggregation, as well as how to set up protein concentration and storage. n Advancing Bispecifics studies to help attendees navigate the complex workflows and technological options available to ensure success. n Novel Therapies for Cancer SC8: Selection, Screening and Engineering for Affinity Reagents SC4: Transient Protein Expression: A Key Tool to Enable Rapid Protein Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Analytical Engineering Biochemistry, University of Zurich Richard Altman, MS, Scientist V, Protein Technologies, Amgen Julia Neugebauer, Ph.D., Associate Director, MorphoSys AG n Optimisation & Developability Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, A comprehensive overview of different display technologies as well as screening approaches n Analytical Characterisation Thermo Fisher Scientific for the selection of specific binders. In addition, it will discuss engineering strategies including n Aggregates & Particles affinity maturation and how to implement these strategies. Classical antibodies and antibody Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick National fragments as well as alternative binding scaffolds such as DARPins will be covered. Laboratory for Cancer Research Oncology This course introduces fundamental concepts and technologies for establishing transient SC9: Protein Aggregation: Mechanism, Characterisation and n Antibody-Drug Conjugates protein production in mammalian cells -- an essential tool to enable rapid protein engineering. Consequences Transient expression allows rapid generation, purification and characterization of milligram-to- n Advancing Bispecifics gram quantities of secreted or intracellular recombinant proteins for therapeutic, functional and Thomas Laue, Ph.D., Professor, Biochemistry and Molecular Biology; Director, n Novel Therapies for Cancer structural studies. Biomolecular Interaction Technologies Center (BITC), University of New Hampshire Protein aggregation is recognized by regulatory agencies and the biopharmaceutical industry SC5: The Multi-Attribute Method (MAM) for Improving Product and as a key quality attribute of biotherapeutic products. Various aggregates hold the potential Expression Process Development for adversely impacting production and patients in a variety of ways. This in-depth workshop n Protein Production Technologies reviews the origins and consequences of aggregation in biotherapeutics, and then examines Richard Rogers, Ph.D., Scientist 4, Just Biotherapeutics strategies for predicting and quantifying aggregation in biopharmaceuticals. n Optimising Expression The course offers hands on training on how to apply the Multi-Attribute Method (MAM) to n Purification Technologies mass spectrometry data. We will be performing attribute analytics (quantifying product quality SC10: New Analytical Approaches & Strategies for Comparability & attributes) and new peak detection (purity test) on mass spec data. During the course we will discuss the uses of the MAM in process development and in a QC lab. Biosimilarity Sponsor & Exhibit Opportunities Hans-Martin Mueller, Ph.D., Director, BioProcess Development, Biologics and Vaccines, MSD Hotel & Travel Information David Wylie, Ph.D., Principal Scientist, Sterile Process and Analytical Development,

Merck Research Labs Registration Information For a proper planning of novel or biosimilar development programs, it is important to understand the development costs, timelines and the authoring of CMC regulatory sections. The analytical characterization of comparability and similarity studies will form the cornerstone Register Online! for each successful marketing authorization application of these products. This short course discusses analytical development and its challenges, technical hurdles, BLA authoring, PEGSummitEurope.com timelines and costs.

A Division of Cambridge Innovation Institute 5 Final Weeks to Register for the Largest PEGS Europe Ever! 13-17 November 2017 By Cambridge Healthtech Institute Cover TS4: NEXT-GENERATION SEQUENCING FOR ANTIBODY DISCOVERY Conference-at-a-Glance 13-14 NOVEMBER 2017 AND ENGINEERING Day 1: 13:40 - 19:25 | Day 2: 08:30 - 18:15 Short Courses Instructor: TS1: BASIC TECHNOLOGIES IN A PROTEIN PRODUCTION LAB Sai Reddy, Ph.D., Assistant Professor, Biosystems Science and Engineering, Training Seminars Instructors: ETH Zurich, Switzerland Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, Protein Expression Facility, Wolfson In this training seminar, participants will learn about next-generation sequencing (NGS) of antibody Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The repertoires. Part 1 will provide an introduction to the antibody repertoires, consisting of genetic background, Hebrew University of Jerusalem generation of diversity, sequencing technologies and a hands-on session on the computational tools Engineering available for the analysis antibody repertoire NGS data. Part 2 will focus on the preprocessing and analysis n Display of Biologics Mario Lebendiker, Ph.D., Head, Protein Purification Facility, Wolfson Centre for Applied of data. Each step of the preprocessing will be elucidated using the programming platforms of R and Python, Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University along with existing bioinformatics pipelines available. Repertoire analysis content will provide statistical n Engineering Antibodies of Jerusalem quantification and visualization of high-dimensional data. The course will be fully interactive with case n studies; participants will be able to download data and example scripts. Please bring your computer. Engineering Bispecifics Panelists: Richard Altman, MS, Scientist V, Protein Technologies, Amgen Therapeutics Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, 16-17 NOVEMBER 2017 Thermo Fisher Scientific n Novel Immunotherapy Strategies Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick National Laboratory Day 1: 13:30 - 16:50 | Day 2: 08:30 - 16:35 n Advancing Bispecifics for Cancer Research TS5: REGULATORY REQUIREMENTS ACROSS THE PRODUCT n Novel Therapies for Cancer Bjørn Voldborg, MSc, Director, CHO Cell Line Development, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark DEVELOPMENT LIFECYCLE Analytical This seminar is designed to introduce basic technologies, strategies and considerations in Instructor: recombinant protein production in E. coli, insect and mammalian cells for multiple research and Christina Vessely, Ph.D., Senior Consultant, Biologics Consulting Group n Optimisation & Developability development applications. The seminar supplies a basic toolbox for management of multiple The successful development of a pharmaceutical product requires not only good science, but also n Analytical Characterisation and diverse projects. compliance with FDA regulatory expectations. This course will include a comprehensive review of n the Chemistry, Manufacturing and Controls (CMC) section of regulatory filings, with a focus on phase Aggregates & Particles appropriate requirements. The level of detail that must be included in the filing will be discussed 13-14 NOVEMBER 2017 as well as systems and controls that must be in place in the manufacturing setting. Topics such Oncology as process development, analytical development, Good Manufacturing Practices (GMP) and Good Day 1: 13:40 - 19:25 | Day 2: 08:30 - 18:15 Laboratory Practices (GLP) will be discussed in the context of the stage of drug development. n Antibody-Drug Conjugates Regulatory strategies for navigating the path to approval will also be discussed. This course is TS2: INTRODUCTION TO PROTEIN ENGINEERING n Advancing Bispecifics intended to provide participants from all facets of the pharmaceutical and biotech industry with a Instructor: broad understanding of regulatory requirements across the product development lifecycle. n Novel Therapies for Cancer David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC CHI’s Introduction to Protein Engineering training seminar offers a comprehensive tutorial in the Expression concepts, strategies and tools of protein engineering – and explains the role of this discipline in the progression of biotherapeutic research and development. The class is directed at scientists n Protein Production Technologies new to the industry or working in support roles, academic scientists and career protein n Optimising Expression scientists wanting a detailed update on the current state of the field. n Purification Technologies 15-16 NOVEMBER 2017 Sponsor & Exhibit Opportunities Day 1: 08:30 - 19:15 | Day 2: 08:30 - 12:45 Hotel & Travel Information TS3: CHARACTERISATION AND CONTROL OF PARTICULATES, FROM AGGREGATES TO VISIBLE PARTICLES Registration Information Instructor: Patricia Winter Cash, Ph.D., Independent Consultant This 1.5 day class will present a comprehensive overview of the latest research on particle Register Online! formation, analysis, and control in biopharmaceutical development and manufacturing. PEGSummitEurope.com Formation of protein particles is recognized as an inherent quality attribute. All protein therapeutics contain particles of varying sizes. This class will explore the causes of aggregate formation, mitigation strategies and regulatory expectations for all size particles, from dimers to large visible particles. Methods of characterizing the particles will be explored, as well as the latest regulations on particle control and how a company can meet those expectations. Visible and sub-visible methods used for QC release and stability testing will be discussed. The emphasis will be on practical solutions to control sub-visible and visible particles, but smaller aggregates will also be discussed. A Division of Cambridge Innovation Institute 6

15-16 NOVEMBER 2017 Day 1: 08:30 - 19:15 | Day 2: 08:30 - 12:45 Final Weeks to Register Engineering 13-14 November 2017 for the Largest PEGS Europe Ever!

4th Annual Cover Conference-at-a-Glance Display of Biologics Short Courses Empowering Novel Therapies Training Seminars cancer agents with good TI. However, not all cell-surface targets have proven Recommended Short Course* susceptible to the development of effective ADCs utilizing the first-generation ADC chemistries. Each element in the ADC design, the antibody, the payload, Engineering SC3: Genomics in the Service of Cancer Immunotherapy and the linker (both site of attachment on antibody and payload-release *Separate registration required, please click here for details n Display of Biologics mechanism) are important considerations. Application of the growing “ADC n Engineering Antibodies Toolbox” to current and future ADC developments will be discussed. n Engineering Bispecifics MONDAY 13 NOVEMBER 15:50 Refreshment Break in the Exhibit Hall with Poster Viewing Therapeutics 12:00 Registration INNOVATIVE PHAGE DISPLAY TECHNOLOGIES AND n Novel Immunotherapy Strategies APPROACHES n Advancing Bispecifics PLENARY KEYNOTE SESSION n Novel Therapies for Cancer 13:40 Welcome from PEGS Europe Team 16:50 Chairperson’s Remarks Christina C. Lingham, Team Lead, PEGS Europe David Lowe, Ph.D., Senior Director, R&D, Antibody Discovery and Protein Analytical Engineering, MedImmune Ltd 13:45 Moderator’s Opening Remarks n Optimisation & Developability Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA 16:55 Identification of Biomarkers by ORFeome Phage Display n Analytical Characterisation Michael Hust, Ph.D., Group Leader, Institute for Biochemistry, Biotechnology and 13:50 Safety Considerations for Development of Immune Agonist n Aggregates & Particles Bioinformatics, Biotechnology, Technical University of Braunschweig and Immune Antagonist Biotherapeutics The identification of biomarkers from pathogens is a prerequisite for the Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, development of vaccines and diagnostic assays. We are using phage display Oncology Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group) to identify immunogenic proteins using bacterial genome libraries. In this In this keynote presentation, the challenges of biotherapeutics impacting on n Antibody-Drug Conjugates presentation, the technology will be described and the results of our project on the immune response, and the challenges investigators face managing, dose, n Advancing Bispecifics the identification of biomarkers related to Inflammatory Bowel Disease (IBD) from scheduling, and satisfying the regulatory requirements will be discussed. The n microbiota derived metagenomic libraries will be presented. Novel Therapies for Cancer checkpoint pathways modulation used for cancer immunotherapy has a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. 17:25 Multivalent pIX Phage Display Selects for Distinct and Improved Immunotherapies in general, and technologies modifying T cell function and Expression Antibody Properties those involving cytokines present dangers of cytokine storm, autoimmune n Protein Production Technologies disease, cardiovascular disorders, and additional challenges, especially when Geir Åge Løset, Ph.D., Researcher, Centre for Immune Regulation and Department of n Optimising Expression used in combination. Strategies to manage and mitigate immune related safety Biosciences, University of Oslo n Purification Technologies events will be presented. Phage display allows for identification of a multitude of specificities, buto t identify optimal lead candidates remains a challenge. The pIX capsid is natively 14:30 Learning What Works from Successful Tumour Infiltrating Sponsor & Exhibit Opportunities expressed and assembled into the phage particle independently of a signal Lymphocyte Therapy sequence. This feature translates to pIX fusions and we show that antibody display Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff using multivalent pIX display results in substantially improved retrieval of desired Hotel & Travel Information University School of Medicine specificities with favorable biophysical properties inde novo selection. Over 20% of melanoma patients that have been refractory to other treatments Registration Information undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating 17:55 Design, Build and Validation of Isogenica’s Sponsored by lymphocytes (TILs). Dissection of these extraordinary successes by examining the Fully Synthetic Human Fab Library dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient Guy Hermans, Ph.D., CSO, Isogenica Limited Register Online! blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and PEGSummitEurope.com We will present validation data on our recently developed fully synthetic human Fab non-HLA restricted targets that are expressed by many other tumour types. library. The diverse set of heavy and light chain germlines, combined with the fully 15:10 Widening the Therapeutic Index: The Next Generation of synthetic nature of the randomized CDR1, -2 and -3 regions ensures many issues Antibody-Drug Conjugates (ADCs) with immune and naïve libraries can be overcome. Use of Colibra™ DNA library John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished build technology allowed for the removal of CMC liability motifs from both the Research Fellow, ImmunoGen, Inc. framework as well as CDR regions. ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-

A Division of Cambridge Innovation Institute 7 Final Weeks to Register Engineering 13-14 November 2017 for the Largest PEGS Europe Ever!

18:25 Welcome Reception in the Exhibit Hall with Sponsored by 11:45 Phage Display and Generation of Bispecific Antibodies Cover Poster Viewing Katarina Radošević, Ph.D., Global Head Biologics Research, Sanofi R&D, Paris, Conference-at-a-Glance France 19:25 End of Day Novel antibody formats that target multiple antigens are steadily gaining interest Short Courses in the development of new biologics. Appropriate biophysical characteristics and diversity of antibodies are some of the essential steps for obtaining highly Training Seminars efficacious and developable molecules. Library approaches, such as phage TUESDAY 14 NOVEMBER display, can significantly contribute to the design of multi-specific antibodies. The approaches Sanofi is taking in this area will be addressed during this talk. Engineering 07:45 Registration and Morning Coffee 12:15 No Wash Multiplexed Immunoassays: sol-R Sponsored by n Display of Biologics NOVEL TOOLS FOR TARGET DISCOVERY Beads and Mirrorball – Simplifying the ELISA Workflow n Engineering Antibodies Paul Wylie, Ph.D., Head of Applications, TTP Labtech n Engineering Bispecifics 08:30 Chairperson’s Remarks We have developed a range of validated bead based immunoassays that can be Ana Barbas, Ph.D., Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer easily automated in a simple workflow. Combining sol-R beads and the mirrorball, Therapeutics Portugal SA no wash cell or bead-based assays provide process efficiencies over standard Flow or ELISA assay platforms, enabling you to do more with less. n Novel Immunotherapy Strategies 08:35 The Good, the Bad and the Ugly Antigen: Deep Sequencing n Advancing Bispecifics Analysis of Selection Outputs Is Revealing Antigen-Specific Enrichment 12:30 TrueRepertoireTM: High-throughput Antibody Sponsored by n Novel Therapies for Cancer Patterns Discovery Platform by High-Fidelity NGS and Stefan Ewert, Ph.D., Senior Investigator I, NIBR Biologics Center, Novartis Pharma Clone Retrieval Analytical AG, Switzerland Hyoki Kim, President and CEO, Celemics, Inc. NGS-based antibody library analysis faces key issues of sequencing error, short n Optimisation & Developability We developed a test system to classify antigens falling into three categories of suitability in provoking antibodies and applied deep sequencing to understand read length and need of gene synthesis for binding assay. Here, we will discuss n Analytical Characterisation TM underlying sequence motifs of antibodies for each category of antigen. “Good” our developed platform, TrueRepertoire that enables to obtain accurate read n Aggregates & Particles antigens are able to provoke a robust enrichment of specific sequences while “bad” of antibody libraries and provides the corresponding scFv gene for further antigens are showing no change compared to the initial library diversity and “ugly” characterization. Oncology antigens are showing non-specific enrichment. 12:45 Luncheon Presentation: Functional Reconstruction Sponsored by n Antibody-Drug Conjugates 09:05 Generation of a Dual Protease Inhibitor Antibody of Active Protein Surfaces using CLIPS-Constrained n Advancing Bispecifics Andrew E. Nixon, Ph.D., Vice President, Biotherapeutics Molecule Discovery, Peptides n Novel Therapies for Cancer Boehringer-Ingelheim Peter Timmerman, CSO, Pepscan Therapeutics B.V. Bispecific antibodies have become an important class of antibody drugs with The lecture focusses on recent epitope mapping studies of Expression application in a variety of therapeutic areas. Here we will discuss identification of structurally complex antibody binding sites. The studies highlight a pair of serine protease inhibitors from a phage display library, in vitro and in vivo the importance and use of CLIPS-technology, a proprietary technology for n Protein Production Technologies characterization and creation of a dual inhibitory bispecific antibody. Finally, we will manufacturing and HTS-screening of conformationally-constrained peptides n Optimising Expression review alternate bispecific antibody formats, challenges and applications. as protein mimics in general. Also illustrated is the development of (CLIPS-) n Purification Technologies constrained protein-mimics as peptide-vaccins (e.g. VEGFtrunc), or for antibody 09:35 Problem-Solving Breakout Discussions* generation toward structurally complex proteins, like GPCR’s. Sponsor & Exhibit Opportunities *See website for details 13:15 Session Break 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Hotel & Travel Information 13:30 Dessert Break in the Exhibit Hall with Poster Viewing Registration Information 11:15 KEYNOTE PRESENTATION: Innovative Strategies for Antibody Lead Discovery and Optimization at Bayer NOVEL APPROACHES FOR IMMUNOTHERAPY AGAINST Rene Hoet, Ph.D., Head, Antibody Lead Discovery, Bayer AG AUTOIMMUNE DISEASE AND BEYOND Register Online! This talk will describe HT Functional IgG screening from Fab phage display PEGSummitEurope.com libraries, as well as phenotypic antibody screening used to expand the 14:00 Chairperson’s Remarks functional-epitope target space for biologics. Successful examples of Ahuva Nissim, Ph.D., Reader, Molecular Targeting, Biochemical Pharmacology, antibody phage selections and target identification for cancer cell internalizing William Harvey Research Institute, Queen Mary University of London antibodies that could be developed into antibody drug conjugates will be outlined.

A Division of Cambridge Innovation Institute 8 Final Weeks to Register Engineering 13-14 November 2017 for the Largest PEGS Europe Ever!

14:05 Insights into the Pathogenesis of Multiple Sclerosis from 16:05 Refreshment Break in the Exhibit Hall with Poster Viewing Cover Biological Therapies Conference-at-a-Glance Monica Calado Marta, M.D., Ph.D., Neuroimmunology Unit, Neurosciences & Trauma, ION CHANNELS AND DIFFICULT TARGETS Blizard Institute QMUL, Barts & The London School of Medicine and Dentistry Chairperson’s Remarks Short Courses Current MS treatments are believed to act via T cell inhibition. However, most therapies have been shown to deplete CD19+, CD27+ memory B cells, in particular, John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd Training Seminars anti-CD52 and anti-CD20-depletion therapies. In comparison, memory B cells 16:45 Selection of Nanobodies That Block Gating of the P2X7 Ion are augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that worsen MS. The memory B cell hypothesis is consistent Channel with High Specificity and Effectivity Engineering with therapeutic, histopathological and aetiological aspects of MS. Friedrich Koch-Nolte, M.D., Professor, Immunology and Molecular Biology, Institute of Immunology, University Medical Center Hamburg n Display of Biologics 14:35 The Role of Molecular Imaging in the Development of Targeted Ion channels are important therapeutic targets, yet there remains a need for n Engineering Antibodies Biopharmaceuticals drugs with better selectivity and fewer side effects. Nanobodies, single domain n Engineering Bispecifics Jane Sosabowski, Ph.D., Senior Lecturer, Preclinical Molecular Imaging, Centre for antibodies from llamas, offer a means of developing specific biologics to ion Molecular Oncology, Barts Cancer Institute, Queen Mary University of London channels. The ATP-gated P2X7 ion channel drives inflammation by promoting the release of interleukin-1β. Using nanobody phage display libraries from P2X7- Therapeutics Molecular imaging has become an essential part of the drug development process. immunized llamas, we selected nanobodies that effectively block ATP-induced Most targeting biomolecules can be radiolabeled with metals or halogens in order n Novel Immunotherapy Strategies gating of mouse or human P2X7. to visualize and quantify their behavior in vivo. This talk will concentrate on the use n Advancing Bispecifics of whole body PET/CT and SPECT/CT imaging in evaluating single variable domain 17:15 Selection Strategies to Identify Novel Bioactive Cyclotides from n Novel Therapies for Cancer antibodies selected by phage display to target specific tissues. Phage Display Libraries Analytical 14:55 Triple Vector for Discovery of Antibody Molecules in Full William Eldridge, Ph.D., CSO, Cyclogenix, Ltd. Therapeutic Format This talk will review the work they are doing on “knottin” peptides displayed on n Optimisation & Developability Maria Pajuelo, Ph.D., CSO, Fairjourney Biologics phage and how they are doing selections on cells and selections for peptides that n Analytical Characterisation driver transport across the gut and the blood-brain barrier. A new vector not only for phage display and production of soluble antibody n Aggregates & Particles fragments fused to human Fc in bacteria, but also for production in mammalian cells 17:45 Generating Ion Channel Blocking Antibodies by Fusing Cysteine- will be described. Ultimately the selection of immunological effector function bearing Knot Miniproteins into Antibody CDR Loops Oncology bivalent molecules, bypassing the cloning into mammalian expression vectors, will accelerate the drug discovery process. The selection of anti-human CXCR4 VHH- John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd n Antibody-Drug Conjugates human Fc molecules from naïve repertoires using this vector will be presented. Using phage display, we have demonstrated that a “model” knottin (trypsin-blocking n Advancing Bispecifics EETI-II) can be inserted via short linker peptides into peripheral diversity loops n Novel Therapies for Cancer 15:15 Discovery and Development of Topically Applied Biologics for the (CDRs) of antibodies. Furthermore, we also demonstrate that binding specificity of Treatment of Mild-to-Moderate Psoriasis Based on a Transgenic Platform both antibody and peptide can be engineered. In addition, we demonstrate blocking Expression Producing 100% Human VHs, Rescued and Selected by Phage Display of Kv1.3 and ASIC1a ion channels by substituting alternative cysteine-rich peptides. Peter Pack, Ph.D., CEO, Crescendo Biologics Ltd. Thus the resulting “KnotBody” retains the advantage of ion channel blocking n Protein Production Technologies activity from the peptide while enjoying the extended half-life and additional Crescendo has developed the clinical Humabody® candidate CB001 of high n Optimising Expression specificity conferred by the antibody molecule. stability and robustness, targeting IL17 for the topical treatment of mild-moderate n Purification Technologies psoriasis. In a range of preclinical models, the anti-IL17 Humabody® effectively 18:15 End of Display of Biologics penetrates tissues and diseased skin in contrast to conventional IgGs. Positive, Sponsor & Exhibit Opportunities dose dependent readouts obtained using a range of cytokine/chemokine assays strongly indicate that psoriasis can be treated with very low concentrations of Hotel & Travel Information topically applied Humabody® VH biologics.

Registration Information 15:35 Further Advancements for Human Antibody Discovery Vera Molkenthin, Ph.D., Chief Scientist, AbCheck s.r.o. AbCheck has developed Mass Humanization to generate humanized libraries. Register Online! This approach utilizes batch cloning of CDR3 immune repertoires from immunized PEGSummitEurope.com rabbits into selected human frameworks containing specifically diversified CDR1 and CDR2 regions. For selecting high affinity binders from the resulting, highly diverse library, AbCheck routinely applies Phage or Yeast Display under various conditions. In this talk, AbCheck will present new technological developments regarding its human antibody discovery and optimization platform.

A Division of Cambridge Innovation Institute 9 Final Weeks to Register Engineering 15-16 November 2017 for the Largest PEGS Europe Ever!

2nd Annual Cover Conference-at-a-Glance Engineering Antibodies Short Courses Designing Next-Generation Therapeutics Training Seminars Sponsored by 10:05 An Integrated Approach to Managing Recommended Short Course* Immunogenicity Risk and Drug Immune Modulation Engineering SC5: The Multi-Attribute Method (MAM) for Improving Product and Jeremy Fry, D.Phil., Director, Sales, ProImmune n Display of Biologics Process Development Immunogenicity is one of the most complex issues to address in drug design n Engineering Antibodies *Separate registration required, please click here for details and development. Using case studies to illustrate, I will provide a comprehensive n Engineering Bispecifics overview of the most appropriate tools to mitigate immunogenicity risk, including WEDNESDAY 15 NOVEMBER Mass Spectrometry antigen presentation assays; DC-T and T cell proliferation assays for biologic lead selection/optimization; HLA-peptide binding assays to Therapeutics 07:45 Registration and Morning Coffee characterize individual epitopes as well as undiluted whole blood cytokine storm n Novel Immunotherapy Strategies assays. 08:30 Chairperson’s Remarks n Advancing Bispecifics 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Novel Therapies for Cancer Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich BEYOND ONCOLOGY Analytical 08:35 KEYNOTE PRESENTATION: The Human Protein Atlas and Next 11:15 Recombinant Antibody Brain Shuttles - Improved Immunotherapy n Optimisation & Developability Generation Antibody Therapeutics and Diagnostics of Neurodegenerative Diseases n Johan Rockberg, Ph.D., Assistant Professor, Proteomics and Analytical Characterisation Greta Hultqvist, Ph.D., Assistant Professor, Pharmaceutical Biosciences, Uppsala Nanobiotechnology, KTH Royal Institute of Technology n Aggregates & Particles University We have classified all the protein coding genes in humans using a The blood brain barrier (BBB) hinders large molecules like antibodies to enter combination of genomics, transcriptomics, proteomics and antibody-based the brain and hence impedes immunotherapy and diagnostics of brain diseases. Oncology profiling and used this data to study the global protein expression patterns We have developed a symmetric BBB shuttle that transports antibodies across n Antibody-Drug Conjugates in human cells, tissues and organs. A Tissue Atlas was launch in 2015, a the BBB. It increases the uptake at diagnostic doses almost 100 times and at n Cell Atlas in 2016 and a Pathology Atlas will be launched in 2017. This open Advancing Bispecifics therapeutic 10 times. We have used this shuttle with an antibody that binds to access knowledge-base can be used to explore targets for next generation n Novel Therapies for Cancer the amyloid fibrils in Alzheimer’s disease, and evaluated its performance as a antibody therapeutics. therapeutic and diagnostic marker. Expression NOVEL ANTIBODIES AND ANTIBODY SUBTYPES AS 11:45 A Bispecific Antibody Mimetic of FGF21 for the Treatment of Type n Protein Production Technologies THERAPEUTICS 2 Diabetes n Optimising Expression James A. Ernst, Ph.D., Senior Scientist, Protein Science, Genentech, Inc. n Purification Technologies 09:05 IgA as Novel Isotype to Treat Cancer This talk will describe the discovery of an antibody that binds Klotho-Beta and Jeanette Leusen, Ph.D., Associate Professor, Laboratory for Translational FGFR1, thereby stimulating the cognate FGF21 co-receptor complex in adipose Sponsor & Exhibit Opportunities Immunology, University Medical Hospital Utrecht tissues. The selection of the receptor targeting arms will be described, and a • IgA employs different effector mechanisms compared to IgG mechanism of activation of this receptor-complex is proposed. In addition, a Hotel & Travel Information • IgA both for solid and hematological tumors in preclinical models catabolic mechanism of FGF21 inactivation in serum by the Fibroblast Activation • Half-life enhancement by glycoengineering and FcRn targeting protein will be described and implications of this inactivation for recombinant and Registration Information endogenous FGF21 discussed. 09:35 Alphabodies: A Novel Class of Biologicals Acting on Intracellular 12:15 The Engineering of a HIV-1 Vaccine Targets Fernando Garces, Ph.D., Scientist, Molecular Engineering, Therapeutic Discovery, Register Online! Yvonne McGrath, Ph.D., CSO, Complix NV Amgen PEGSummitEurope.com Many attractive intracellular targets involved in disease remain beyond the reach of Previous data has suggested that the Env protein is the most immunogenic when in conventional small molecules. We will describe the development of Alphabodies, its pre-fusion state making it paramount to favor this conformation in the designing a novel class of biologics that has been designed to enter cells effectively and of a vaccine capable of triggering a broad and potent immune response. Here we interfere with key intracellular pathways. Data showing target binding, functional present the first high-resolution crystal structures of this viral spike in complex with interference and results from animal models will be exemplified.

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anti-HIV antibodies and how this molecular information provides a rational platform The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance Cover for intensive engineering. The immunogenic properties of these native like trimer are to developing targeted vaccines or treatments for specific diseases or infections. currently being tested in a variety of animal models with promising results. Thus, genomics and proteomics techniques (such as Next-Generation Sequencing Conference-at-a-Glance (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig Sponsored by sequencing and serum Ig peptide profiling in a high-throughput manner. Herein, it is Short Courses 12:45 BioXp™ 3200 System for Flexible DNA Variant Library Construction described an integrated approach for genomics and proteomics data to sequence Training Seminars Ramon Espinoza-Lewis, Ph.D., Application Scientist, Product membrane-bound Ig presented in antigen specific B-cells. Development, Synthetic Genomics 15:05 HERA: A Human Endothelial Recycling Assay for Rapid Screening The synthesis of mutant genes is a labor-intensive and costly process, especially of FcRn-Mediated Rescue from Degradation for the synthesis of variant libraries. This highly specialized and specific process is Engineering Jan Terje Andersen, Ph.D., Associate Professor & Group Leader, Immunology, often outsourced to specialized service labs, increasing cost & time with variable n Centre for Immune Regulation, Department of Biosciences, Oslo University Hospital Display of Biologics quality. Here, we describe the BioXpTM 3200 System, which enables researchers and University of Oslo n Engineering Antibodies to engineer DNA in a highly flexible manner by introduction, deletion, or mutation n Engineering Bispecifics of single nucleotides or fragments for production of antibody segments, variant IgG and albumin have a remarkably long serum half-life of three weeks in humans, peptides or libraries. which is mainly due to an efficient FcRn-mediated pH-dependent recycling Therapeutics pathway. As these ligands are increasingly utilized as therapeutics, there is an 13:15 Luncheon Presentation: Immunogenicity Sponsored by intense interest in engineering of their half-life. Here, I will discuss a novel in vitro n Novel Immunotherapy Strategies Assessment & Management – A Critical Part of a human endothelial cell-based rescue assay (HERA) that can easily be used for n Advancing Bispecifics Holistic Approach to Successful Biologic Drug Design preclinical screening of FcRn-mediated rescue of engineered ligands. n Novel Therapies for Cancer Campbell Bunce, Ph.D., Senior Vice President, Scientific Operations, Biology, 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing Abzena Analytical Understanding how therapeutic antibodies and proteins can induce an immune MAMMALIAN DISPLAY PLATFORMS FOR DISCOVERY AND response in patients leading to the development of anti-drug antibodies n Optimisation & Developability (ADAs) Accurate and sensitive ways to assess the potential immunogenicity ENGINEERING n Analytical Characterisation of proteins and antibodies ex vivo by measuring CD4+ T cell responses; Impact 16:15 A Mammalian Display Platform for Antibody Discovery and n Aggregates & Particles of functional properties of drug on selection of best ex vivo assay method to evaluate immunogenicity potential; Methods for managing and reducing potential Engineering Using Immunogenomic Engineering Oncology immunogenicity. Sai Reddy, Ph.D., Assistant Professor, Biosystems Science and Engineering, ETH Zurich In this presentation, I will show how we combine NGS-based analysis with a novel n Antibody-Drug Conjugates 13:45 Session Break mammalian hybridoma display platform for antibody screening and discovery. n Advancing Bispecifics Specifically, we use NGS to identify candidate antigen specific clones from n Novel Therapies for Cancer ANTIBODY PROFILING AND SCREENING immunized repertoires. We then integrate these antibody clonal libraries into our hybridoma platform using CRISPR-Cas9 genome editing. Flow cytometry is then Expression 14:00 Chairperson’s Remarks used to screen and isolate antigen-specific antibodies. Jeanette Leusen, Ph.D., Associate Professor, Laboratory for Translational n Protein Production Technologies Immunology, University Medical Hospital Utrecht 16:45 Mammalian Display for B- and T-Cell Receptor Discovery and n Optimising Expression Engineering 14:05 Unique Properties of Mouse IgG n Purification Technologies Marc van Dijk, Ph.D., Executive Director, Platform Technology, Agenus Joanna Bereta, Ph.D., Associate Professor, Cell Biochemistry, Faculty of Agenus has invented novel display technologies to discover and engineer BCRs Biochemistry, Biophysics and Biotechnology, The Jagiellonian University in Krakow and TCRs, and will showcase their development of lab assays and bioinformatics Sponsor & Exhibit Opportunities Contrary to the current belief that only IgMs are able to agglutinate erythrocytes, algorithms to determine TCR specificity and off target liabilities. we obtained agglutinating mouse IgG3 that recognized antigen B of the human Hotel & Travel Information ABO blood group system. The high stability and production efficacy of IgG3 point 17:15 Problem-Solving Breakout Discussions* to this molecule as a potent diagnostic tool. Mouse IgG3s efficiently neutralize *See website for details Registration Information pathogens with a polysaccharide envelope or carbohydrate-rich cell wall. However, the receptor specific for IgG3, which could participate in IgG3-based pathogen 18:15 Networking Reception in the Exhibit Hall with Poster Viewing elimination, remains undiscovered; the results of our search for this high-affinity Register Online! receptor will be presented. 19:15 End of Day PEGSummitEurope.com 14:35 A Systematic Approach for Peptide Characterization of B-Cell THURSDAY 16 NOVEMBER Receptor in Chronic Lymphocytic Leukemia Manuel Fuentes, Ph.D., Scientist, Medicine & Proteomics Unit, Cancer Research 08:00 Registration and Morning Coffee Center, University of Salamanca

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TECHNOLOGIES FOR ANTIBODY SELECTION & HIGH and effector mechanisms triggered by different antibody formats, significant Cover amounts of recombinant proteins are required. Efficient transient transfection THROUGHPUT SCREENING systems are a prerequisite for comparison of various potential candidate Conference-at-a-Glance molecules in parallel. Here, case reports of the functional characterization of IgA 08:30 Chairperson’s Remarks antibodies and different formats of bispecific antibodies produced by scalable flow Short Courses Marc van Dijk, Ph.D., Executive Director, Platform Technology, Agenus electroporation are presented. Training Seminars 10:35 Coffee Break in the Exhibit Hall with Poster Viewing 08:35 Application of Deep Mutational Scanning in Therapeutic Antibody Engineering 11:15 Technological Developments for Improved High-Throughput Engineering Patrick Koenig, Ph.D., Senior Scientist, Antibody Discovery, AbbVie Stemcentrx Binder Screenings and Validations n Display of Biologics Deep mutational scanning combines the selection of limited mutagenesis libraries Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, n Engineering Antibodies with deep sequencing. Here, I will present how information on sequence-function Biochemistry, University of Zurich relationships obtained by deep mutational scanning is a powerful resource to n Engineering Bispecifics While recombinant binder selection pipelines by now work in rather high- guide the engineering of affinity, specificity and stability of potential therapeutic throughput, the screening of suitable affinity reagents and especially the validation antibodies. of their essential features for the final applications is still laborious and time- Therapeutics intensive. To optimize the efficiency of these processes, we have improved already 09:05 Efficient Mining of the Memory B Cell & Plasma Cell Repertoire – n Novel Immunotherapy Strategies existing and developed novel methods, combining chip-, SPR- and MS-technologies, Next Generation Antibody Discovery to efficiently test candidates e.g. for crossreactivity and specificity. n Advancing Bispecifics Dale Starkie, Senior Scientist, Antibody Discovery - Variable Region Discovery and n Novel Therapies for Cancer Engineering, UCB Celltech 11:45 Droplet Microfluidics for High Throughput Antibody and Vaccine Here we describe the use of a number of cutting-edge antibody discovery Screening Analytical technologies and assays to efficiently interrogate the memory B cell and the Christoph Merten, Ph.D., Group Leader, Microfluidics, Genome Biology Unit, n Optimisation & Developability plasma cell repertoire of immunised animals and humans to identify rare European Molecular Biology Laboratory (EMBL) n Analytical Characterisation antibodies with desirable functional characteristics. At the heart of this platform We have developed droplet-based microfluidic platforms that allow the direct lies single cell isolation strategies which include both micromanipulation methods screening of >1 million primary, non-immortalized plasma cells (optionally n Aggregates & Particles and droplet microfluidics. We will present case studies to demonstrate how we from humans) in a single experiment and also facilitate assays for the effect of have applied them to discovery of antibodies against therapeutically-relevant antibodies on target cells (e.g. modulating GPCRs). In a complementary approach, Oncology targets. we use the technology to monitor the binding of neutralizing antibodies to single n Antibody-Drug Conjugates HIV particles, which allows us to derive vaccine candidates with customized 09:35 MemoMAB: Gateway to Human Antibody Repertoires antigen properties (e.g. improved stability and accessibility). n Advancing Bispecifics Christoph Esslinger, Ph.D., CSO, Memo Therapeutics AG n Novel Therapies for Cancer Sponsored by The human immune repertoire is expected to yield valuable insights into novel 12:15 Luncheon Presentation: Modular Library protective mechanisms active in infectious diseases, cancer and other diseases. Fabrication Strategies Deliver a Rapid and Cost-Effective Expression The MemoMAB microfluidics-based HT-single cell platform banks and displays Multi Use Approach n Protein Production Technologies authentic antibody repertoires from human donors in recombinant form making Emily Leproust, CEO, Twist Bioscience them directly accessible for immune repertoire analysis and antibody discovery n Twist Bioscience’s unique ability to synthesize large numbers of high quality Optimising Expression using functional screening. MemoMAB processes up to 1mio B cells and directly n Purification Technologies oligonucleotides, combined with its proprietary molecular biology protocols, allows delivers clonal cell lines expressing recombinant human antibodies. the fabrication of precise, high fidelity gene mutant libraries.With a rapid and Sponsored by cost effective approach to library fabrication, Twist Bioscience enables antibody Sponsor & Exhibit Opportunities 10:05 Case Reports on Production and Functional developers and protein engineers to alter and evolve library designs as-needed. Characterization of IgA Antibodies and Bispecific Antibody This presentation will focus on the quality of libraries generated utilizing Twist Hotel & Travel Information Formats Bioscience’s proprietary molecular biology protocols and modular fabrication Matthias Peipp, Ph.D., Professor Division, Stem Cell Transplantation and strategies. Registration Information Immunotherapy, Christian-Albrechts-University of Kiel Peer Heine, Ph.D., Field Applications Scientist, MaxCyte 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Monoclonal antibodies are widely used in the treatment of cancer patents. 13:30 End of Engineering Antibodies Register Online! To date the IgG1 isotype is predominantly used in various applications. As an PEGSummitEurope.com alternative to commonly applied IgG antibodies, IgA antibodies and bispecific antibody derivatives represent promising classes of biological agents in cancer immunotherapy. For the preclinical evaluation of structure-function relationships

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9th Annual Cover Conference-at-a-Glance Engineering Bispecifics Short Courses Advances in Targeting and Functionality Training Seminars THURSDAY 16 NOVEMBER NEW TOOL BOXES AND PLATFORMS FOR BISPECIFICS Engineering 12:30 Registration 15:50 Developing Next Generation Biologics Therapies Using a Novel Bispecific Technology FIT-Ig n Display of Biologics 13:00 Dessert Break in the Exhibit Hall with Poster Viewing n Engineering Antibodies Chengbin Wu, Ph.D., CEO, EpimAb Biotherapeutics n Engineering Bispecifics We have developed a new generation of bispecific antibody technology termed NEW TOOL BOXES AND PLATFORMS FOR BISPECIFICS FIT-Ig, which maintains the structural integrity and biological properties of the 2 13:30 Chairperson’s Opening Remarks parental mAbs, and also shows drug-like properties and high productivity in CHO Therapeutics cells. This unique design of bispecifics does not require any mutations or use of Frank S. Walsh, Ph.D., CEO, Ossianix n Novel Immunotherapy Strategies linkers, and is potentially a plug-and-play platform approach for efficient bispecific generation and development. n Advancing Bispecifics 13:35 Spy and Snoop Superglues to Engineer Diverse Protein and n Novel Therapies for Cancer Peptide Architectures 16:20 Nanofitin-Based Bispecifics Platform Mark Howarth, DPhil, Associate Professor, Protein Nanotechnology, Biochemistry, Mathieu Cinier, Ph.D., CSO, Affilogic University of Oxford Analytical Building on antibody expertise, many different bispecific formats were engineered There is need for efficient approaches for new bispecific and polyspecific n Optimisation & Developability (additional escaping pathway neutralization, recruitment of effectors) but often architectures. We created a peptide (SpyTag) spontaneously reacting with its at the expense of the overall physico-chemical properties of the biologic itself n Analytical Characterisation protein partner (SpyCatcher). Reaction is high-yielding, genetically encodable and compared to the state of the art for mAbs. Nanofitins are proposed as a novel n Aggregates & Particles specific. SpyTag generated affibody polymers for cancer cell capture from blood bispecific platform, whereby additional targeting specificities are ovidedpr with and cyclized enzymes resilient to boiling. I will describe the use of different peptide attractive physico-chemical properties. Oncology superglues for programmable synthesis of multi-functional nanobody/affibody teams, to modulate precisely signaling in cancer cell death. 16:50 End of Day n Antibody-Drug Conjugates n Advancing Bispecifics 14:05 TRACS (Trivalent Ab Conjugates): A Plug and Play Multivalent Ab 17:00 Dinner Short Course Registration n Novel Therapies for Cancer Format Diego Ellerman, Ph.D., Scientist, Protein Chemistry, Genentech 17:30 - 20:30 Recommended Dinner Short Course* Expression We describe a novel multivalent format based on protein conjugation (TRACS). SC6: Engineering of Bispecific Antibodies The building blocks are mAbs and Fabs with good expression yields and stability. *Separate registration required, please click here for details n Protein Production Technologies A conjugation site that supports high conjugation rates and an efficient process n Optimising Expression was identified. The spatial arrangement of all the Fabs allows their simultaneous FRIDAY 17 NOVEMBER n Purification Technologies binding with reduced steric hindrance. We provide examples of different TRACS that require concurrent binding of all Fabs for their biological activity. 08:00 Registration and Morning Coffee Sponsor & Exhibit Opportunities 14:35 Computational Advances in Antibody Discovery: Sponsored by Toward Earlier and Better Assessment, Triage and ENGINEERING FOR SPECIFICITY Hotel & Travel Information Optimization 08:30 Chairperson’s Remarks Registration Information Jianxin Duan, Ph.D., Bavaria Application, Scientist Applications, Science Structure- Nicolas Fischer, Ph.D., Head, Research, Novimmune based Applications, Schrödinger GmbH In the field of antibody drug discovery, there is growing realization that methods to 08:35 Structure Guided Specificity Engineering in a MAGE A3 Specific TCR Register Online! assess, triage, and avoid liabilities in potential candidates must come early in the Stephen Harper, Ph.D., Group Leader, Protein Engineering Research, Protein Science, PEGSummitEurope.com discovery process. Recent advances in computational approaches for antibody Immunocore Ltd. structure prediction, identification of protein liabilities (such as aggregation ImmTAC molecules are bispecific therapeutics that use a TCR targeting domain propensity), and in methods for protein engineering hold substantial promise in and anti-CD3 specific scFv effector function to re-direct a potent T cell response moving us closer to reaching this goal in an effective and efficient manner. to kill cancer cells. Here we present an example of structure guided engineering in a TCR targeting the HLA-A*01 -restricted epitope of MAGE-A3. Mutants were 15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

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designed to reduce off-target cross-reactivity to a structurally related peptide 11:35 Engineering Proteins of Circular Architecture Cover derived from titin, a protein expressed in cardiac tissue. Anke Steinmetz, Ph.D., Senior Scientist, Integrated Drug Discovery/Structure, Design & Infomatics, Sanofi R&D Conference-at-a-Glance 09:05 Balancing Selectivity and Efficacy of Bispecific EGFR x c-MET Design of therapeutic proteins seldom aims at circular architecture. Protein engineers Antibodies and Antibody-Drug Conjugates Short Courses in applied pharmaceutical research avoid conceptually sophisticated structural Lars Toleikis, Ph.D., Director, Protein Engineering & Antibody Technologies, Merck design due to limitations in time, resources, and the lack of user-friendly, fast, easy KGaA Training Seminars to use, reliable molecular modeling tools for such purposes. We illustrate how we Therapies targeting the tumor-associated antigen epidermal growth factor receptor designed a bispecific antibody of circular self-supporting architecture and present (EGFR) often suffer from toxicities due to basal EGFR expression in normal tissue. implications of circular versus linear domain constellation on biological effects. Furthermore, EGFR-directed inhibitors might struggle with limited efficacy because Engineering of c-MET mediated resistance mechanisms. Hence, we aim to construct bispecific 12:05 Problem-Solving Breakout Discussions with a Light Snack in the n Display of Biologics EGFR x c-MET antibodies employing affinity-optimized binding moieties to balance Foyer* n Engineering Antibodies selectivity and anti-tumor efficacy and to evaluate their potential for an innovative *See website for more details n Engineering Bispecifics antibody-drug conjugate approach. 13:35 Session Break 09:35 A Tale of Two Specificities: The Balancing Act of Tumor-Targeting Therapeutics Selectivity and Therapeutic Index in Bispecific Antibodies EARLY STAGE SELECTION / ENGINEERING FOR POTENCY, n Novel Immunotherapy Strategies Yariv Mazor, Ph.D., Senior Scientist, Antibody Discovery & Protein Engineering, SAFETY, PURITY AND YIELD n Advancing Bispecifics Medimmune, Inc. n Novel Therapies for Cancer Dual targeting of antigen double-positive cancer cells is believed to enhance 14:00 Chairperson’s Remarks therapeutic efficacy, restrict escape mechanisms and increase selectivity, leading Mark Howarth, D.Phil., Associate Professor, Protein Nanotechnology, Biochemistry, to reduced systemic toxicity and improved therapeutic index. However, the interplay University of Oxford Analytical of factors regulating target selectivity is not well understood and often overlooked. n Optimisation & Developability We show in vivo that dual targeting alone is not sufficient to endow selective tumor- 14:05 Early Stage Developability Assessment to Enable Bispecific Design n Analytical Characterisation targeting, and report the pivotal roles played by the affinity of the individual arms, Laura Lin, Ph.D., Senior Director, BioMedicine Design, Worldwide Research & n Aggregates & Particles overall avidity and format valence. Development, Pfizer, Inc. The presentation will showcase our strategies of applying early stage developability 10:05 Coffee Break with Poster Viewing assessment to enable the design and optimization of bispecific molecules. I will be Oncology sharing several case studies highlighting the impact of such assessment on lead n Antibody-Drug Conjugates BLOOD BRAIN BARRIER TRANSFER / LINKER selection and optimization, and predictability of early screens on efficacy, PK, and n Advancing Bispecifics CONFIGURATIONS manufacturability. n Novel Therapies for Cancer 10:35 KEYNOTE PRESENTATION: Optimizing Delivery of Bispecific 14:35 Towards “in Format” Selection and Screening of Bispecific Antibodies Expression Antibodies to the Brain Frank S. Walsh, Ph.D., CEO, Ossianix Nicolas Fischer, Ph.D., Head, Research, Novimmune n Protein Production Technologies Using in vitro and in vivo phage display technology, we isolated cross species Optimal geometry of the two binding sites is often important for the function of n Optimising Expression binders to the transferrin receptor 1 (TfR1) from synthetic single domain VNAR Bispecific Antibodies. In addition to combinatorial assembly followed by extensive n Purification Technologies libraries. At therapeutic (2 mg/kg) doses delivered by tail vein injection, high functional testing, we aimed at identifying appropriate binding pairs as early as levels (>5% brain/plasma ratio) of the bispecific antibodies were found in the possible, i.e. at selection and screening stages. We have developed a dual-display brain after 18 hours. We have now optimized the BBB transfer by mutagenesis technology that allows the an ‘in format’ preferential enrichment and co-selection Sponsor & Exhibit Opportunities of the VNAR CDR3 region and identified epitopes involved in transfer. of antibody fragments based on target co-engagement. Different modalities to maximize the throughput of functional screening for BiAb have been implemented Hotel & Travel Information 11:05 One Size Does Not Fit All; Opportunities and Challenges of Using to optimize the discovery process. Artificial Disulfide Bonds for the Production of Bispecific IgGs Registration Information 15:05 Using a Design of Experiments Approach to Identify Critical Itai Benhar, Ph.D., Professor, Molecular Microbiology and Biotechnology, Tel-Aviv University Residues in FcR Engagement for Both IgG1 and IgG4 Fc-Hexamers Shirley Peters, Ph.D., Senior Scientist, Protein Sciences, UCB Register Online! We present a solution for correct pairing of heavy and light chains of bispecific We have used antibody engineering and recombinant expression to produce Fc PEGSummitEurope.com IgGs; an engineered disulfide bond between the antibodies’ variable domains that asymmetrically replaces the natural interchain disulfide bond. A novel approach for with controlled hexa-valency, “Fc-multimer”. Fc-hexamer engages with FcR’s on precise evaluation of correct chain pairing by LC-MC-MS combined with chemical multiple cell types and was engineered to maximize potency whilst minimizing crosslinking is presented. Examples will be provided for some of these bsAbs and potential safety concerns. Initial in vitro and in vivo experiments showed differential future directions of the study will be discussed. efficacy for IgG1 and IgG4-hexamers and we used a statistical design approach (‘Design of Experiments’) to explore the two extremes defined by these two isotypes. A Division of Cambridge Innovation Institute 14 Final Weeks to Register Engineering 16-17 November 2017 for the Largest PEGS Europe Ever!

15:35 Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Cover Potency Conference-at-a-Glance Stylianos Bournazos, Ph.D., Research Assistant Professor, Molecular Genetics and Immunology, The Rockefeller University Short Courses A key immune evasion mechanism of HIV-1 is the low density of the envelope glycoprotein (Env) on the viral surface, which precludes high-avidity bivalent Training Seminars interactions of anti-Env antibodies. By engineering the hinge domain of IgG to favor heterobivalent interactions, we generated bispecific anti-Env antibodies with improved neutralization potency and therapeutic activity. These findings suggest Engineering innovative strategies for generating engineered bispecific antibodies with enhanced activity, representing ideal candidate molecules for HIV-1 and other viral infections. n Display of Biologics n Engineering Antibodies 16:05 Product Quality by Design: Cell Line Engineering to Enhance n Engineering Bispecifics Specific FAP DR5 2+2 CrossMab Yields Wolfgang Paul, Ph.D., Senior Scientist & Group Leader, Cell Culture Research Therapeutics Pharma Research and Early Development, Large Molecule Research, Roche The challenge for the production of new complex protein formats is the generation n Novel Immunotherapy Strategies of cell lines producing high yields of functional proteins with low amounts of n Advancing Bispecifics product related site products. The novel bispecific agonistic FAP-DR5 antibody n Novel Therapies for Cancer contains tetravalent binding properties (2+2 format), secreted with several product-related side products. The presented approach shows successfully the Analytical improvement of specific properties by subsequent transfection of a production cell line to decrease the formation of these side products. n Optimisation & Developability n Analytical Characterisation 16:35 End of Conference n Aggregates & Particles

Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer

Expression n Protein Production Technologies MEDIA PARTNERS n Optimising Expression n Purification Technologies Lead Sponsoring Publications

Sponsor & Exhibit Opportunities

Hotel & Travel Information Sponsoring Publications Sponsoring Societies Registration Information

A Division of Cambridge Innovation Institute 15 Final Weeks to Register Therapeutics 13-14 November 2017 for the Largest PEGS Europe Ever!

2nd Annual Cover Conference-at-a-Glance Novel Immunotherapy Strategies Short Courses Exciting Developments in this Fast Moving Field Training Seminars susceptible to the development of effective ADCs utilizing the first-generation Recommended Short Course* ADC chemistries. Each element in the ADC design, the antibody, the payload, Engineering SC1: New Directions in Cancer Immunotherapy and the linker (both site of attachment on antibody and payload-release *Separate registration required, please click here for details mechanism) are important considerations. Application of the growing “ADC n Display of Biologics Toolbox” to current and future ADC developments will be discussed. n Engineering Antibodies MONDAY 13 NOVEMBER n Engineering Bispecifics 15:50 Refreshment Break in the Exhibit Hall with Poster Viewing 12:00 Registration Therapeutics CAR-Ts AND TCRs: FOCUS ON SPECIFICITY, POTENCY AND n Novel Immunotherapy Strategies PLENARY KEYNOTE SESSION EFFICACY n Advancing Bispecifics 13:40 Welcome from PEGS Europe Team 16:50 Chairperson’s Remarks n Novel Therapies for Cancer Christina C. Lingham, Team Lead, PEGS Europe Katherine Seidl, Ph.D., Director, Immunotherapy, bluebird bio 13:45 Moderator’s Opening Remarks 16:55 Targeting B Cell Maturation Antigen (BCMA) Positive Multiple Analytical Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA Myeloma Cells with CAR-T Cell Therapy n Optimisation & Developability 13:50 Safety Considerations for Development of Immune Agonist Katherine Seidl, Ph.D., Director, Immunotherapy, bluebird bio n Analytical Characterisation and Immune Antagonist Biotherapeutics We developed chimeric antigen receptors (CARs) targeting B cell maturation n Aggregates & Particles Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, antigen (BCMA) expressed on most multiple myeloma (MM) cells. Lentiviral Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group) vectors containing anti-BCMA single chain variable fragment (scFv), 4-1BB, and Oncology In this keynote presentation, the challenges of biotherapeutics impacting on CD3zeta signaling domains were generated and a lead CAR (bb2121) was selected the immune response, and the challenges investigators face managing, dose, for clinical development (NCT02658929). Approaches for next-generation CAR-T n Antibody-Drug Conjugates scheduling, and satisfying the regulatory requirements will be discussed. The cell products, such as ex vivo culture with a PI3K inhibitor which enhances in vivo n Advancing Bispecifics checkpoint pathways modulation used for cancer immunotherapy has a natural efficacy, will be discussed. n Novel Therapies for Cancer role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Immunotherapies in general, and technologies modifying T cell function and those 17:25 Characterization of the Specificity of Novel Enhanced-Affinity Expression involving cytokines present dangers of cytokine storm, autoimmune disease, TCRs – Not All MAGEs Are the Same! cardiovascular disorders, and additional challenges, especially when used in Rachel Abbott, Ph.D., Group and Scientific Leader, Preclinical Research, n Protein Production Technologies combination. Strategies to manage and mitigate immune related safety events Adaptimmune Ltd. n Optimising Expression will be presented. Enhanced-affinity optimally engineered T Cell Receptors (TCRs) are showing n Purification Technologies 14:30 Learning What Works from Successful Tumour Infiltrating initial promise for adoptive T cell therapy of both solid and liquid tumors. With this Lymphocyte Therapy promise also comes responsibility and the risk of on- and/or off-target toxicity, Sponsor & Exhibit Opportunities Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff such as those seen in multiple differing adverse events in MAGE-A3 trials. Here University School of Medicine I will discuss the issue of cross-reactivity and present a well-defined strategy for Hotel & Travel Information Over 20% of melanoma patients that have been refractory to other treatments defining the specificity of novel TCRs and engineering for defined specificity, using undergo complete lasting remission after adoptive cell transfer of tumor- a variety of MAGE family TCRs that we have progressed to open INDs as examples. Registration Information infiltrating lymphocytes (TILs). Dissection of these extraordinary successes 17:55 Cancer Biotherapeutics - Affimers: A Novel Sponsored by by examining the dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting Scaffold for Biotherapeutics Register Online! new HLA-restricted and non-HLA restricted targets that are expressed by Amrik Basran, Ph.D., CSO, Avacta Life Sciences PEGSummitEurope.com many other tumour types. Affimers® are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the protease inhibitor Stefin A, large diverse libraries 15:10 Widening the Therapeutic Index: The Next Generation of have been created by engineering in peptide loops into the scaffold backbone. Antibody-Drug Conjugates (ADCs) Using phage display, we have identified competitive binders to a range of John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished targets, including the immune check point, PD-L1. We have shown that the Research Fellow, ImmunoGen, Inc. scaffold is amenable to being engineered with a range of half-life extension ADCs with potent tubulin-acting and DNA-acting agents can be effective anti- technologies. A Division of Cambridge Innovation Institute cancer agents with good TI. However, not all cell-surface targets have proven 16 Final Weeks to Register Therapeutics 13-14 November 2017 for the Largest PEGS Europe Ever!

18:25 Welcome Reception in the Exhibit Hall with Sponsored by Metastatic melanoma and renal cell carcinoma have a very poor prognosis. Cover Poster Viewing Immune checkpoint inhibitors such as anti-CTLA4 and anti-PD1 antibodies produce response rates in the order of 60% with 2-year survival being 64% in patients with Conference-at-a-Glance 19:25 End of Day melanoma. In renal cancer, the anti-PD1 Antibody nonvolume gave a median survival of 25.6 months as second/third line therapy. These antibodies are active Short Courses in a wide variety of human cancers. Their use is transforming the lives of cancer Training Seminars patients. TUESDAY 14 NOVEMBER 11:45 The Tumoral Immune Landscape and the Design of Immune 07:45 Registration and Morning Coffee Modulatory Antibodies Engineering Frederick Arce Vargas, M.D., Ph.D., MRCS, Research Associate, University College n Display of Biologics PRECLINICAL AND CLINICAL DEVELOPMENTS WITH London Cancer Institute n Engineering Antibodies CAR-T CELLS Modulation of the anti-tumor immune response with antibodies targeting n Engineering Bispecifics co-inhibitory and co-stimulatory molecules is a promising strategy in cancer 08:30 Chairperson’s Remarks therapy. In some cases, the effectiveness of these antibodies is not limited to receptor activation or blockade and relies on depletion of regulatory T cells Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff Therapeutics (Treg). Characterizing the expression density of these targets in different T cell University School of Medicine n Novel Immunotherapy Strategies compartments and the myeloid cells involved in Treg depletion is therefore paramount for the design of the next generation of immune-modulatory antibodies. n Advancing Bispecifics 08:35 KEYNOTE PRESENTATION: ErbB-Targeted CAR T-Cell n Novel Therapies for Cancer Sponsored by Immunotherapy of Solid Tumours 12:15 Novel Target Identification and Specificity John Maher, M.D., Ph.D., Consultant and Senior Lecturer, Immunology, Cancer Screening of Biotherapeutics Analytical Studies, King’s College London Elizabeth Kingsley, Ph.D., Consultant, Retrogenix Limited T4 immunotherapy consists of a CD28+CD3 z-based chimeric antigen n Optimisation & Developability Human cell microarray screening enables rapid discovery of primary cell surface receptor (CAR), targeted against the extended ErbB network, and which is receptors and off-targets for a variety of ligands. Case studies will demonstrate n Analytical Characterisation co-expressed with an IL-4 responsive chimeric cytokine receptor. Pre-clinical successes in identifying novel immunotherapy targets as well as in specificity n Aggregates & Particles efficacy and safety has been demonstrated in models of head and neck, screening for biotherapeutics, including CAR T cells, to aid safety assessment and ovarian, breast cancer and mesothelioma. Phase I clinical evaluation is now support IND submissions. Oncology ongoing in patients with locally advanced or recurrent head and neck cancer, employing intra-tumoural delivery to minimize toxicity. Sponsored by n Antibody-Drug Conjugates 12:30 Luncheon Presentation: The Use of in vitro Assays to Accelerate Cancer Immunotherapy Development & n Advancing Bispecifics 09:05 Exploiting Natural Killer Specificity for CAR-T Cell Therapy of Reduce the Risk of Unwanted Immunogenicity n Novel Therapies for Cancer Cancer Sofie Pattijn, Chief Technology Officer, ImmunXperts Peggy Sotiropoulou, Ph.D., Manager, R&D, Celyad During the last years, significant advancement has been made in the clinical Expression Natural Killer cells possess innate capacity to target ‘abnormal’ cells through application of cancer immunotherapies. Early evaluation of the effectiveness the recognition of a range of target ligands, many of which are present on tumor n Protein Production Technologies of candidate therapeutics and combination therapies can be done using mouse cells. Engineering NK receptors into a CAR format and expressing in T cells takes n Optimising Expression models and in vitro bioassays with mouse or human immune cells. The use advantage of both NK specificity and T cell effector functionality. This approach will of customized in vitro assays supports the candidate selection, unwanted n Purification Technologies be discussed in the context in the pre-clinical setting and discussion of on-going immunogenicity screening and functionality testing of new oncology leads. clinical trials testing this approach. Sponsor & Exhibit Opportunities 13:15 Session Break 09:35 Problem-Solving Breakout Discussions* Hotel & Travel Information *See website for details 13:30 Dessert Break in the Exhibit Hall with Poster Viewing

Registration Information 10:35 Coffee Break in the Exhibit Hall with Poster Viewing ANTAGONISTS, AGONISTS AND CYTOKINE-BASED IMMUNE CHECKPOINT INHIBITORS: IMPORTANT DESIGN IMMUNOTHERAPEUTICS Register Online! FEATURES, AND PROGRESS IN THE CLINIC 14:00 Chairperson’s Remarks PEGSummitEurope.com Peggy Sotiropoulou, Ph.D., Manager, R&D, Celyad 11:15 Modern Immunotherapy for Cancer Patients: Trials and Tribulations John Wagstaff, M.D., MB ChB, Director, South West Wales Cancer Institute & Professor, Medical Oncology, Swansea University College of Medicine

A Division of Cambridge Innovation Institute 17 Final Weeks to Register Therapeutics 13-14 November 2017 for the Largest PEGS Europe Ever!

14:05 Identification and Development of Antagonist Anti-TIGIT Cover ALTERNATIVE APPROACHES FOR THE MANY PATIENTS Monoclonal Antibody: In vitro and in vivo Mode of Action UNRESPONSIVE TO KNOWN IMMUNOTHERAPY Conference-at-a-Glance Gregory Driessens, Ph.D., Head, In Vivo Pharmacology, iTeos Therapeutics SA TIGIT is a co-inhibitory immune receptor expressed by T and NK cells. iTeos TREATMENTS Short Courses Therapeutics has developed a high affinity anti-TIGIT antagonist antibody 16:45 Development of Anti-APRIL Antibody for Multiple Myeloma cross-reactive to mouse and cynomolgous TIGIT. This antibody increases the Leading up to First-in-Man Studies Training Seminars effector function of CD8 T cells and inhibits tumor growth as monotherapy and in combination with checkpoint inhibitor. We will present data characterizing the John Dulos, Ph.D., Director, Aduro Biotech Europe development and mechanism of action of anti-TIGIT antibody in vitro and in vivo. Studies with APRIL, a proliferation-induced ligand / TNFSF 13, demonstrate strong Engineering selectivity as a marker for multiple myeloma. I will describe the mode of action of 14:35 MEDI1873: A Potent, Stabilized Hexameric Agonist of Human GITR the anti-APRIL antibody, a regular humanized antibody, in regulating resistance to n Display of Biologics with Regulatory T-Cell Targeting Potential chemotherapy and immuno-suppressive activity, and present in vitro and in vivo n Engineering Antibodies Lisa Bamber, Ph.D., Scientist I, ADPE, MedImmune data, and demonstration of in vivo activity. n Engineering Bispecifics MEDI1873, a novel hexameric human GITR agonist was optimized through 17:15 Overcoming Tumour Resistance to Antibody-Mediated systematic testing. This optimized format exhibits oligomeric heterogeneity and Immunotherapy Therapeutics superiority to an anti-GITR antibody, with respect to evoking robust GITR agonism. In vitro testing recapitulates several aspects of GITR targeting described in mice. Mark Cragg, Ph.D., Professor, Experimental Cancer Research, Antibody & Vaccine n Novel Immunotherapy Strategies We have demonstrated that MEDI1873 is a potent T-cell agonist in vivo, reinforcing Group, Cancer Sciences, University of Southampton n Advancing Bispecifics the potential of targeting the GITR pathway as a therapeutic approach to cancer. Monoclonal antibodies are transforming the way we treat cancer. However, despite n Novel Therapies for Cancer their undoubted impact, responses remain variable and require improvement. The 15:05 Use of IL-2 Immunotherapy in Cancer: Efficacy, Resistance, and focus of our current research is therefore to unravel the principal modes of action Analytical Combinations of these reagents, identify the ways in which tumours subvert their activities and Onur Boyman, M.D., Professor and Chair Immunology University Hospital Zurich, design strategies to overcome them to improve efficacy. Using lymphoma as a n Optimisation & Developability University of Zurich paradigm, I will outline how FcgR modulation is central to the success of these n Analytical Characterisation endeavours. The recent impact of immune checkpoint inhibitors on advanced cancer has firmly n Aggregates & Particles established the importance of tumor immunotherapy. However, current approaches 17:45 Cancer Vaccines Inducing High Avidity T Cells and Modified are limited to immunogenic tumors that can acquire adaptive resistance. Vaccines Inducing Proinflammatory CD4 T Cells Oncology Interleukin-2 (IL-2) immunotherapy can result in remarkable long-term responses in some cancer patients, however, this approach is limited by its adverse effects. IL-2 Lindy Durrant, Ph.D., Professor, Cancer Immunotherapy, University of Nottingham; n Antibody-Drug Conjugates complexes overcome these adverse effects and potentiate IL-2 immunotherapy. Joint CEO and CSO, Scancell n Advancing Bispecifics Data will be presented on efficacy, adaptive resistance, and use in combinations of High avidity of T cells to epitopes is achieved by focusing the immune response on n Novel Therapies for Cancer IL-2 complexes. a small selection of tumour rejection epitopes, encoding them within the antibody CDR region and using the Fc region to target high affinity receptors on DCsin vivo. Expression 15:35 AptaAnalyzerTM - A New NGS Analysis Tool for Sponsored by Clinical studies have shown good tumour clearance in resected patients. This Improved Identification of Peptide and Antibody Ligands approach combines well with checkpoint inhibition. Vaccines targeted citrullinated n Protein Production Technologies Michael Blank, Ph.D., CSO, AptaIT GmbH epitopes, stimulate killer CD4 T cells without the need for checkpoint inhibition. n Optimising Expression AptaAnalyzer™ is an intuitive software tool enabling the improved identification of 18:15 End of Novel Immunotherapy Strategies n Purification Technologies ligands from biopanning experiments or of B-cell receptors derived from defined stages of the immune system. AptaAnalyzer™ enables archiving of experiments Sponsor & Exhibit Opportunities as well as improved identification and optimization of rare but relevant peptide or antibody ligands. Hotel & Travel Information 16:05 Refreshment Break in the Exhibit Hall with Poster Viewing Registration Information

A Division of Cambridge Innovation Institute 18 Final Weeks to Register Therapeutics 15-16 November 2017 for the Largest PEGS Europe Ever!

9th Annual Cover Conference-at-a-Glance Advancing Bispecifics and Combination Short Courses

Training Seminars Therapy to the Clinic Combinations Showing Enhanced Efficacy Engineering approach, which accounts for the bispecific target binding, was explored to n Display of Biologics Recommended Short Courses* understand the exposure-response relationship and to project the MABEL dose. n Engineering Antibodies SC6: Engineering of Bispecific Antibodies The current approach could potentially be implemented for other bispecifics. n Engineering Bispecifics *Separate registration required, please click here for details 10:05 Development and Application of MOA-based Sponsored by Reporter Bioassays for Immunotherapy Drug Development Therapeutics WEDNESDAY 15 NOVEMBER Jey Cheng, Senior Research Scientist, Research & Development, n Novel Immunotherapy Strategies Promega Corporation n Advancing Bispecifics 07:45 Registration and Morning Coffee Having a functional bioassay that is MOA-based, accurate, precise, robust and n Novel Therapies for Cancer reproducible is critical for the development of antibody-based biologics. We BISPECIFICS FOR T CELL RECRUITMENT / TARGETING have developed reporter bioassays that meet these criteria for a broad range of IMMUNOTHERAPY AGONISTS antibody modalities including Fc effector function, immune checkpoint modulation, Analytical bispecific antibody engagement, cytokine modulation, and others. Here we n Optimisation & Developability 08:30 Chairperson’s Remarks will present the latest technology advancements and demonstrate how these n Analytical Characterisation Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA bioassays can be used for a broad range of applications n Aggregates & Particles 08:35 Bispecific T-cell Engagers (BiTE) in Hematology and Beyond 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Matthias Klinger, Ph.D., Principal Scientist, BiTE Technology, Amgen Research Oncology (Munich) GmbH 11:15 KEYNOTE PRESENTATION: A Novel FAP-Targeted 4-1BB n Antibody-Drug Conjugates Following the approval of blinatumomab in relapsed/refractory ALL multiple Agonist and Its Combination with T Cell Bispecific Antibodies n Advancing Bispecifics BiTE candidates have or are about to enter the clinic in various indications. Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, n Novel Therapies for Cancer This presentation will give an update on Amgen’s BiTE pipeline at the discovery, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early translational, and early clinical stage of development. Development, Roche Innovation Center Zurich Immune co-stimulation via 4-1BB agonism is an important element of next Expression 09:05 Tumor-Specific Carbohydrate Antigens as Preferable Targets for generation CAR-T cell therapy. The clinical development of first generation 4-1BB n Protein Production Technologies Novel Bispecific Antibody Constructs agonistic antibodies has been hampered by hepatic toxicity. Here we describe a n Optimising Expression Patrik Kehler, Associate Director, Immuno-Oncology, Preclinical & Immunological novel FAP-targeted 4-1BB agonist for combination with T cell bispecific antibodies which may represent an off-the-shelf alternative to CAR-T cell therapies. n Purification Technologies Research, Glycotope GmbH Carbohydrates on the surface of cancer cells represent preferable targets for bispecifics due to their unique tumor-specificity with lack or inaccessibility on 11:45 Multi-Functional Designed Ankyrin Repeat Protein Drugs: MP0250 Sponsor & Exhibit Opportunities normal tissues and broad indication coverage. Multiple constructs were generated and Beyond to demonstrate the feasibility of carbohydrates as valuable targets for different H. Kaspar Binz, Ph.D., Vice President & Co-Founder, Molecular Partners Hotel & Travel Information bispecific approaches such as T cell recruitment. A comprehensive screening The use of the robust designed ankyrin repeat protein technology enables the nimble program was performed to identify the most preferable construct combining testing and establishment of drugs acting on multiple disease pathways. MP uses the Registration Information highest tumor specificity, anti-tumor functionality and adequate safety. platform to establish a portfolio of innovative drugs for the treatment of cancer. The latest clinical data including MP0250 along with novel drug concepts will be presented. 09:35 Mechanistic Projection of First-in-Human Dose for Bispecific Register Online! Immunomodulatory P-Cadherin LP-DART 12:15 ATOR-1015, a Bispecific Immunomodulatory Antibody Targeting PEGSummitEurope.com Xiaoying Chen, Ph.D., Senior Manager, Early Oncology Development & Clinical OX40 and CTLA-4 Research, Pfizer, Inc. Christina Furebring, Ph.D., Senior Vice President, R&D, Alligator Bioscience An immunomodulatory bispecific molecule (P-cadherin LP-DART) was developed Alligator Bioscience has developed a bispecific antibody targeting OX40 and as a potential antitumor treatment. Because of its immune agonistic properties, CTLA-4 for immunotherapy of cancer. The mode of action of ATOR-1015 includes a minimal anticipated biological effect level (MABEL) approach was applied to depletion/suppression of regulatory T cells as well as activation of effector T cells. project the first-in-human (FIH) dose. Particularly, a mechanistic PK/PD-driven The design and the pharmacodynamics properties, as well as the biochemical A Division of Cambridge Innovation Institute 19 Final Weeks to Register Therapeutics 15-16 November 2017 for the Largest PEGS Europe Ever!

properties and manufacturability, will be presented. ATOR-1015 is currently in pre- 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing Cover clinical development for clinical trials. IMMUNOMODULATORY BISPECIFICS Conference-at-a-Glance 12:45 Carbohydrate Targeted Cancer Immunotherapy Using a Recombinant Malaria Protein 16:15 Simultaneous Blockade of Multiple Immune Checkpoints with Short Courses Mie Anemone Nordmaj, M.Sc., PhD Student, Immunology and Microbiology, Medical Bispecific Antibodies Training Seminars Parasitology, University of Copenhagen David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc. A unique malaria protein, VAR2CSA, binds to a distinct type of chondroitin sulfate Combinations of checkpoint-blocking antibodies are more efficacious then single found exclusively on a broad repertoire of cancer cells and in the cancer associated inhibitors, but also generate greater immune-related adverse events. We reasoned Engineering extracellular matrix. Here we describe the construction of an “armed” rVAR2 that a single bispecific antibody could achieve dual blockade to selectively target molecule, capable of simultaneous recognition of cancer cells via rVAR2 and tumor-reactive lymphocytes, possibly improving safety and efficacy. We have n Display of Biologics cytotoxic T-lymphocytes via anti-CD3. In vitro and in vivo efficacy showed significant generated multiple dual-checkpoint inhibitors such as XmAb20717 (PD1 x CTLA4) n Engineering Antibodies anti-tumor effects, demonstrating the feasibility of using rVAR2 as a component in that display compelling in vitro and in vivo activity relative to combinations of n Engineering Bispecifics a bispecific antibody. monospecific antibodies, suggesting that checkpoint bispecifics may veha clinical advantages for the treatment of human malignancies. 13:15 Enjoy Lunch on Your Own Therapeutics 16:45 FS118: An Anti-LAG-3/PD-L1 Bispecific Antibody Which 13:45 Session Break n Novel Immunotherapy Strategies Modulates T Cell Activity and Inhibits Tumour Growth n Advancing Bispecifics BISPECIFICS TARGETING B CELLS FOR ONCOLOGY Mihriban Tuna, Ph.D., Vice President, Drug Discovery, F-star n Novel Therapies for Cancer A bispecific antibody (mAb2) which binds murine LAG-3 and PD-L1 simultaneously 14:00 Chairperson’s Remarks with high affinity was engineered and characterised. The anti-LAG-3/PD-L1 mAb2 Analytical Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron inhibits LAG-3 binding to MHCII and PDL1 binding to PD-1 and CD80, resulting Pharmaceuticals in T cell activation in vitro. This translates into in vivo efficacy, where the mAb2 n Optimisation & Developability significantly decreased tumour burden in the MC38 colon carcinoma tumour n Analytical Characterisation 14:05 Development of Anti-FcRH5/CD3 T Cell Dependent Bispecific model. Thus, the preclinical data supports developing an anti-human LAG-3/PD-L1 n Aggregates & Particles (TDB) Antibody for the Treatment of Multiple Myeloma mAb2 for the treatment of cancer. Teemu Junttila, Ph.D., Senior Scientist, Genentech, Inc. 17:15 Problem-Solving Breakout Discussions* Oncology We have developed a novel T-cell dependent bispecific (TDB) antibody, anti- *See website for details FcRH5/CD3 TDB, targeting the B cell lineage marker FcRH5 for multiple myeloma. n Antibody-Drug Conjugates This demonstrated cytotoxicity against human plasma cells and patient derived 18:15 Networking Reception in the Exhibit Hall with Poster Viewing n Advancing Bispecifics myeloma, and induced immunosuppressive feedback signaling, including PD1 n Novel Therapies for Cancer up-regulation, which can be overcome by PD-L1 antibodies. Data demonstrate the 19:15 End of Day potential for anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD1/ PDL1 signaling in the treatment of multiple myeloma and other B-cell malignancies. Expression THURSDAY 16 NOVEMBER n Protein Production Technologies 14:35 CD20 TCB (RG6026), a Novel “2:1” T Cell Bispecific Antibody for n Optimising Expression the Treatment of B Cell Malignancies 08:00 Registration and Morning Coffee n Purification Technologies Sara Colombetti, Ph.D., Head, Oncology Discovery, Pharmacology, Roche Innovation Center, Zurich INNOVATIVE BISPECIFIC COMBINATIONS Sponsor & Exhibit Opportunities The talk will focus on preclinical data of CD20 TCB, a novel differentiated CD20- 08:30 Chairperson’s Remarks targeting T cell bispecific antibody on the “2:1” IgG format that consistently David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc. Hotel & Travel Information demonstrated superior potency compared to other CD20 TCBs with a conventional “1:1” IgG format. This translated into superior efficacy in vitro, ex vivo and in vivo, 08:35 Bispecific Antibodies and Antibody-Drug Conjugates (ADCs) Registration Information which could not be matched by increasing doses of the “1:1” TCBs. Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs 15:05 Therapeutically Targeting B Cells in Autoimmune Disease and Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Register Online! Cancer Using a CD47xCD19 biAb Approach Pharmaceuticals There is a need for HER2-directed ADCs effective in patients expressing low/ Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA PEGSummitEurope.com moderate levels of HER2. Cross-linking HER2 to constitutively internalizing PRLR, Novimmune is developing a biAb approach to safely yet effectively treat B cell using a HER2xPRLR bispecific ADC, dramatically enhances lysosomal degradation malignancies by targeting CD19 and CD47 with one molecule. CD47 restrains of HER2. Accordingly, bispecific ADC improve upon T-DM1 efficacy in cells antibody dependent phagocytosis and CD19 covers a broad spectrum of the B cell expressing intermediate levels of HER2. These results demonstrate that coupling lineages. Thus, in addition to cancer, we are exploring the utility to use the biAb a tumor-specific ADC target to a rapidly internalizing protein may be a useful in autoimmunity, as the efficacy of B cell depletion in these patients positively approach to enhance efficacy of ADCs. correlates with clinical outcomes. A Division of Cambridge Innovation Institute 20 Final Weeks to Register Therapeutics 15-16 November 2017 for the Largest PEGS Europe Ever!

09:05 Advances with Bispecifics and Multi-Specifics in the Clinic – 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Cover Lessons Learned Conference-at-a-Glance Tariq Ghayur, Ph.D., Distinguished Research Fellow, Foundational Immunology, MULTIVALENT BISPECIFICS Immunology Discovery, AbbVie 11:15 The Biology of IgG Hexamerization – Translating Basic Science to Short Courses Several bispecific DVD-Ig molecules have now been tested in preclinical models and in clinic. The emerging data show that these molecules behave like monoclonal Antibody Therapeutics Training Seminars antibodies and that the DVD-Ig format per se is not immunogenic. However, Rob N. de Jong, Ph.D., Associate Director, CMC Research & Protein Chemistry, target biology may play an important role anti-drug antibody response (ADA, Genmab BV immunogenicity). Lessons learned from these studies will be discussed. In this presentation, we will present our understanding of the requirements of IgG Engineering hexamer formation at the submolecular level; functional aspects of antigen- and Fc- 09:35 Preclinical Development of MCLA-158, a Bispecific Antibody dependent IgG hexamer formation, the development of the Hexabody technology; n Display of Biologics Targeting Lgr5 and EGFR and progress towards clinical translation of Hexabody-based therapeutics. n Engineering Antibodies Berina Eppink, Ph.D., Project Manager, Merus, NV 11:45 Tetravalent Bispecific Antibodies with Unique CD16A-Binding n Engineering Bispecifics Biclonics is a robust and validated platform for the development of human full length IgG bispecific antibodies. MCLA-158 is a Biclonics that binds the wnt target Properties to Treat Non-Solid and Solid Tumors Therapeutics gene Lgr5 and the growth factor receptor EGFR. MCLA-158 demonstrates superior Michael Tesar, Ph.D., Head, R&D, Affimed GmbH activity in both in vitro and in vivo tumor organoid based assays regardless of Affimed has developed a unique NK-cell engager platform which delivers novel n Novel Immunotherapy Strategies KRAS status and was shown to be well tolerated in non-human primates. These antibodies that not only activate innate immunity, but have also shown evidence n Advancing Bispecifics preclinical data suggest MCLA-158 could benefit patients with metastatic CRC. of facilitating cross-talk with T-cell effectors. New data will be presented including n Novel Therapies for Cancer description of the technology, mode of action and potential combination strategies. 10:05 Design and Evaluation of Next-Generation Biologics Analytical for Cancer Immunotherapy 12:15 Enjoy Lunch on Your Own Maria Wendt, PhD, Head of Science, Genedata n Optimisation & Developability 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, n Analytical Characterisation chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific 13:30 End of Advancing Bispecifics and Combination Therapy to the n Aggregates & Particles constructs can provide significant advantages for use in cancer immunotherapy. Clinic However, as highly engineered molecules they pose new design, engineering, Oncology cloning, expression, purification, and analytics challenges. Genedata Biologics enables the automated design, screening, production, and testing of large panels of n Antibody-Drug Conjugates these candidate therapeutic molecules and includes built-in tools for developability n Advancing Bispecifics and manufacturability assessments. n Novel Therapies for Cancer

Expression n Protein Production Technologies n Optimising Expression n Purification Technologies

Sponsor & Exhibit Opportunities PRESENT A POSTER and Save €50 Hotel & Travel Information POSTER SPACE IS LIMITED AND IN HIGH DEMAND. Registration Information Posters will be accepted on a first-come basis! Please see website for important details. Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the Register Online! poster sessions. To secure a poster board and inclusion in the conference materials, your abstract must be PEGSummitEurope.com submitted, approved and your registration paid in full by 6 October 2017. • Your research will be seen by leaders from top pharmaceutical, biotech, academic and government institutes • Your poster abstract will be published in the conference materials • Receive €50 off your registration fee A Division of Cambridge Innovation Institute 21 Final Weeks to Register Therapeutics 16-17 November 2017 for the Largest PEGS Europe Ever!

2nd Annual Cover Conference-at-a-Glance Novel Therapies for Cancer and Short Courses

Training Seminars Emerging Targets Improving Efficacy for Clinical Success Engineering n Display of Biologics THURSDAY 16 NOVEMBER NEW THINKING FOR CHECKPOINT BLOCKADE n Engineering Antibodies 15:50 Combination of PD-1/PD-L1 Blockade and Targeting of a Tumor- n Engineering Bispecifics 12:30 Registration Specific Carbohydrate Antigen in a Novel Trifunctional Antibody as a 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Therapeutics Strategy to Improve Anti-PD-L1 Therapy Johanna Rühmann, Ph.D., Senior Director, Internal project strategy & Cooperations, n Novel Immunotherapy Strategies NEW T CELL THERAPIES: OUT OF THE BOX THINKING Glycotope GmbH n Advancing Bispecifics 13:30 Chairperson’s Opening Remarks We developed a trifunctional antibody which combines targeting of TA-MUC1 and PD-L1 with a functional Fc-part (PM-PDL). By focusing PD-1/PD-L1 blockade to n Novel Therapies for Cancer Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular the tumor and multiplying different modes of action, PM-PDL has the potential to Biology, National Cancer Institute, NIH Analytical increase efficacy and broaden patient coverage giving additional benefit compared 13:35 Shared Target Antigens on Cancer Cells and Tissue Stem Cells: Go to the respective monospecific antibody. The results further underline the potential n Optimisation & Developability or No-Go for CAR T Cells? of Fc glyco-optimization to enhance not only cytotoxic but also immunomodulatory antibody effector functions. n Analytical Characterisation Hinrich Abken, Ph.D., Professor, Genetics & Immunology, Center for Molecular n Aggregates & Particles Medicine Cologne, University of Cologne 16:20 IO Treatments of Renal Cell Carcinoma: The Changing Landscape ‘On-target off-tumor’ toxicity raises serious safety concerns when the target antigen Hans Hammers, M.D. Ph.D., Eugene P. Frenkel M.D. Scholar, Clinical Medicine; Oncology is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Associate Professor, Internal Medicine, Hematology and Oncology, Kidney Cancer We discuss CAR T cell targeting of activation antigens versus lineage associated n Antibody-Drug Conjugates Program, University of Texas Southwestern antigens on the basis of recent experimental and animal data, in particular in the The presentation will outline key features of the currently approved n Advancing Bispecifics context of targeting CD30. n Novel Therapies for Cancer immunotherapies like nivolumab and IL2 in RCC. Additionally, the emerging 14:05 The UniCAR Platform Technology: Turning CAR T Cells On and Off treatment landscape with combination immunotherapies such as other immune checkpoints and VEGF pathway inhibitors will be discussed. Expression Michael P. Bachmann, Ph.D., Director, Institute of Radiopharmaceutical Cancer Research; Head, Radioimmunology, Helmholtz Zentrum Dresden Rossendorf HZDR n Protein Production Technologies 16:50 End of Day Adoptively transferred conventional CAR T cells remain active in patients and n Optimising Expression can cause life threatening side effects. In contrast, activity of UniCAR T cells is 17:00 Dinner Short Course Registration n Purification Technologies dependent on the administration of a target module (TM). TMs are bispecific fusion molecules consisting of an epitope recognized by the UniCAR and a binding 17:30-20:30 Recommended Dinner Short Course* Sponsor & Exhibit Opportunities domain directed to the respective tumor antigen. After elimination of TMs UniCAR SC6: Engineering of Bispecific Antibodies T cells automatically switch off again. *Separate registration required, please click here for details Hotel & Travel Information Sponsored by 14:35 Can Severe Adverse Events of CAR-Ts be FRIDAY 17 NOVEMBER Registration Information mitigated through Product Design? Paula Salmikangas, Director, Biopharmaceuticals and ATMPs, NDA Advisory Board, NDA Group 08:00 Registration and Morning Coffee Register Online! Clinical development and commercialization of CAR-T products has been WHY DOESN’T CAR T THERAPY WORK IN SOLID PEGSummitEurope.com hampered by the SAEs caused by high activity of the CART-cells and simultaneous lysis of large tumor loads. This has led to search for technologies to better control TUMOURS YET? the products but little attention has been given to the product design. Is it time to look into the cell products and discuss whether the most severe AEs could be 08:30 Chairperson’s Remarks prevented through proactive product design without compromising efficacy? Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School 15:05 Refreshment Break in the Exhibit Hall with Poster Viewing A Division of Cambridge Innovation Institute 22 Final Weeks to Register Therapeutics 16-17 November 2017 for the Largest PEGS Europe Ever!

08:35 The clinical efficacy of first-generation carcinoembryonic antigen 11:35 Strategies to Inhibit the Intracellular Target Ras with Potent Cover (CEACAM5)-specific CAR T cells is limited by poor persistence and Antibody Mimetic Proteins Conference-at-a-Glance transient pre-conditioning-dependent respiratory toxicity Ralph Minter, Ph.D., Director, Fellow, Antibody Discovery and Protein Engineering, Robert Hawkins, Ph.D., FRCP, Professor, Cancer Research, University of Manchester; MedImmune Short Courses Honorary Consultant, Medical Oncology Ras mutations are strong oncogenic drivers of many cancers but the target Ras is still not addressed by any current therapies. Inhibition of Ras nucleotide Training Seminars 09:05 CAR T Manufacturing Made Simple exchange is a novel approach to blocking Ras signaling by locking it in an inactive Andrew Kaiser, Ph.D., R&D Manager, Cell & Gene Immunotherapy/Clinical Cell conformation. We describe an antibody mimetic, DARPin K27, which blocks Ras Processing, Research & Development, Miltenyi Biotec GmbH using such a mechanism and inhibits downstream signaling and tumour cell Engineering This presentation will focus on advances in the field of automation applied to growth. K27 and other antibody-like molecules enable us to explore novel strategies cellular therapies and describe how T cells can easily be enriched from blood to (i) deliver functional macromolecules into cells and (ii) understand the biological n Display of Biologics products, activated, gene-modified, expanded and formulated on a single closed implications of Ras inhibition. n Engineering Antibodies platform with minimal user interactions or liquid handling. Attributes of the n Engineering Bispecifics produced cells, such as composition, phenotype in vitro and in vivo function will 12:05 Problem-Solving Breakout Discussions with a Light Snack in the be shown. Recent developments will demonstrate that such complex procedure Foyer* Therapeutics can be carried out in serum free conditions and allow for flexible means of gene- *See website for more details modification that can further enable the field. n Novel Immunotherapy Strategies 13:35 Session Break n Advancing Bispecifics 09:35 The Role of CD28 in the Rescue of CD8 T Cells by PD-1 Targeted n Novel Therapies for Cancer Therapies IMPROVEMENTS IN TARGETING CANCER Rathi Pillai, M.D., Assistant Professor, Department of Hematology and Oncology, Analytical Winship Cancer Institute, Emory University 14:00 Chairperson’s Remarks Programmed cell death-1 (PD-1) directed therapies activate exhausted CD8 T Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London n Optimisation & Developability cells and have become effective treatments in cancer. The costimulatory CD28/ Cancer Institute n Analytical Characterisation B7 pathway is essential for the rescue of exhausted T cells in mouse models of 14:05 Heterocellular Oncogenic Signaling n Aggregates & Particles chronic viral infection and cancer. Most proliferating CD8 T cells in the blood of lung cancer patients treated with PD-1 inhibitors express CD28. CD28 costimulation Christopher J. Tape, Ph.D., CRUK Career Development Fellow, University College plays an integral role in T cell rescue by PD-1 therapies. London Cancer Institute Oncology Cancer is a heterocellular disease comprised of mutated cancer cells, stromal n Antibody-Drug Conjugates 10:05 Coffee Break with Poster Viewing fibroblasts, and multiple immune cells. Each of these cell types contribute to n Advancing Bispecifics tumour biology, but the signaling mechanisms underpinning their malignant n Novel Therapies for Cancer DIFFICULT AND NEXT GOOD TARGETS: ARE WE USING THE behaviour are poorly understood. We have established cell-specific proteomic technologies to measure cell signaling in heterocellular systems. Using these RIGHT STRATEGIES TO TARGET TUMOURS? technologies, we demonstrate how oncogenic driver mutations ‘spread’ their Expression Chairperson’s Remarks signals across multiple cell types to drive tumours. n Protein Production Technologies Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte 14:35 Ultra-Selective T-Cell Engaging Antibody Circuits (TEAC): A New n Optimising Expression Corporation Approach to Cancer Immunotherapy n Purification Technologies 10:35 Design and Construction of Antibody Phage Display Libraries for Mark Cobbold, M.D., Ph.D., Associate Professor, Massachusetts General Hospital, Therapeutic Antibody Discovery Harvard Medical School Sponsor & Exhibit Opportunities Juan Carlos Almagro, Ph.D., Founder and Director, GlobalBio, Inc. Cytotoxic T-cells are amongst the most potent arms of the immune response and immunotherapies harnessing these exhibit powerful effects against cancer. Display technologies have had a profound impact in engineering antibodies to treat Hotel & Travel Information Separating toxicity from efficacy remains an ongoing challenge for both CAR T unmet medical needs, in particular, in the oncology field. This talk will discuss the and bispecific T-cell engaging biologics. Here we describe a new antibody-based design and implementation of novel phage display libraries with improved functionality Registration Information approach to selectively engage T-cells at tumor sites using Boolean operator logic and capabilities for discovery and optimization of therapeutic antibodies. based upon antigen and protease target site expression. By applying logic gating, we obviate many of the current challenges with T-cell engaging antibodies. Register Online! 11:05 Single Domain Antibodies Targeting Glypicans for Cancer Therapy Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular PEGSummitEurope.com 15:05 Improving CAR T Cell Function by Reversing the Biology, National Cancer Institute, NIH Immunosuppressive Tumor Environment of Pancreatic Cancer We develop inhibitory antibodies that target signaling pathways (e.g. Wnt) Juan Fernando Vera Valdes, M.D., Associate Professor, Medicine, Baylor College of responsible for the growth of cancer. This can be done by using single domain Medicine antibodies that bind cryptic and buried functional regions in receptors or signaling complexes. We have studied glypicans (e.g. GPC2, GPC3) as a new class of targets in cancer and made immunotoxins and CAR T cells for the treatment of liver cancer

A Division of Cambridge Innovation Institute and pediatric cancers. 23 Final Weeks to Register Therapeutics 16-17 November 2017 for the Largest PEGS Europe Ever!

To target pancreatic ductal adenocarcinoma (PDAC), we generated a CAR Cover targeting PSCA. However, PDAC tumors produce inhibitory cytokines (e.g. IL4), which limit CAR T cell persistence and effector function. Thus, to protect our CAR Conference-at-a-Glance T cells we co-expressed a custom inverted cytokine receptor (ICR) linking the IL4 receptor exodomain with the IL7 receptor endodomain. The current presentation Short Courses will summarize the in vitro and in vivo results achieved when combining these Training Seminars modifications. 15:35 New Bispecific Antibodies Targeting Members of the EGFR Engineering Receptor Family Roland Kontermann, Ph.D., Professor, Biomedical Engineering, Institute of Cell n Display of Biologics Biology & Immunology, University of Stuttgart n Engineering Antibodies Tetravalent, bispecific antibodies, based on a single-diabody Fc format (scDb- n Engineering Bispecifics Fc), were generated using a novel neutralizing anti-HER3 antibody recognizing a novel epitope formed domain III and IV combined with antibodies against other Therapeutics members of the EGFR receptor family. A scDb-Fc targeting HER3 and EGFR potently inhibited activation of both receptors and downstream signals, with n Novel Immunotherapy Strategies possible applications to overcome resistance against EGFR monotherapy by n Advancing Bispecifics compensatory HER3 signaling. n Novel Therapies for Cancer 16:05 End of Conference Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles

Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer

Expression n Protein Production Technologies n Optimising Expression n Purification Technologies

Sponsor & Exhibit Opportunities

Hotel & Travel Information

Registration Information

A Division of Cambridge Innovation Institute 24 Final Weeks to Register Analytical 13-14 November 2017 for the Largest PEGS Europe Ever!

8th Annual Cover Conference-at-a-Glance Optimisation & Developability Short Courses Improving Candidate Selectivity Training Seminars ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer Recommended Short Course* agents with good TI. However, not all cell-surface targets have proven susceptible to the Engineering development of effective ADCs utilizing the first-generation ADC chemistries. Each element SC5: The Multi-Attribute Method (MAM) for Improving Product and in the ADC design, the antibody, the payload, and the linker (both site of attachment on n Display of Biologics Process Development antibody and payload-release mechanism) are important considerations. Application of the n Engineering Antibodies *Separate registration required, please click here for details growing “ADC Toolbox” to current and future ADC developments will be discussed. n Engineering Bispecifics MONDAY 13 NOVEMBER 15:50 Refreshment Break in the Exhibit Hall with Poster Viewing Therapeutics 12:00 Registration RISK ASSESSMENT AND PREDICTIVE ASSAYS TO GUIDE n Novel Immunotherapy Strategies n Advancing Bispecifics CANDIDATE SELECTION n Novel Therapies for Cancer PLENARY KEYNOTE SESSION 16:50 Chairperson’s Remarks 13:40 Welcome from PEGS Europe Team Lars Linden, Ph.D., Head, Protein Biochemistry, Biologics Research, Cell and Protein Analytical Christina C. Lingham, Team Lead, PEGS Europe Science, Bayer AG n Optimisation & Developability 13:45 Moderator’s Opening Remarks 16:55 Developability Risk Assessments to Select Preclinical Antibody n Analytical Characterisation Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA Candidates n Aggregates & Particles 13:50 Safety Considerations for Development of Immune Agonist Dorina Saro, Ph.D., Senior Scientist, Cell and Developability Sciences, Janssen R&D, Pharmaceutical Development and Manufacturing Sciences and Immune Antagonist Biotherapeutics An overview of the developability assessment of preclinical candidates at Oncology Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Janssen will be given at the presentation. Specific case studies with a focus of the n Antibody-Drug Conjugates Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group) assessment of bispecific candidates will be included. n Advancing Bispecifics In this keynote presentation, the challenges of biotherapeutics impacting on n Novel Therapies for Cancer the immune response, and the challenges investigators face managing, dose, 17:25 Predictive Assays for Pharmacokinetics to Guide Lead Selection scheduling, and satisfying the regulatory requirements will be discussed. The checkpoint pathways modulation used for cancer immunotherapy has a natural and Engineering Expression role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Hubert Kettenberger, Ph.D., Senior Principal Scientist, Large Molecule Research, Roche Innovation Center Munich n Protein Production Technologies Immunotherapies in general, and technologies modifying T cell function and those For most biotherapeutics, long in vivo half-live and thus long durability is desired. n Optimising Expression involving cytokines present dangers of cytokine storm, autoimmune disease, cardiovascular disorders, and additional challenges, especially when used in Comparing many different monoclonal antibodies, we and several other authors n Purification Technologies combination. Strategies to manage and mitigate immune related safety events observed large differences in their pharmacokinetics which cannot be explained will be presented. by different Fc:FcRn interactions alone. Unspecific, low-affinity interactions with Sponsor & Exhibit Opportunities highly abundant targets may, however, negatively impact PK. We present predictive 14:30 Learning What Works from Successful Tumour Infiltrating assays to identify mAbs with fast clearance during the lead selection and protein Hotel & Travel Information Lymphocyte Therapy engineering phase. Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff Sponsored by Registration Information University School of Medicine 17:55 Epitope Binning Studies May Reveal Displacement Over 20% of melanoma patients that have been refractory to other treatments in mAb Libraries undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating Alex van der Kooi, Manager, Interaction Laboratory, IBIS Technologies lymphocytes (TILs). Dissection of these extraordinary successes by examining the Register Online! Array-based SPR-imaging devices (MX96 SPR imager, IBIS Technologies) are ideally dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient suited for epitope binning experiments with large panels.Within these large panels, PEGSummitEurope.com blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and antibodies may be identified that target closely adjacent or minimally verlappingo non-HLA restricted targets that are expressed by many other tumour types. epitopes. These mAbs can displace one another. Data is presented illustrating the displacement process. 15:10 Widening the Therapeutic Index: The Next Generation of Antibody-Drug Conjugates (ADCs) John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished

A Division of Cambridge Innovation Institute Research Fellow, ImmunoGen, Inc. 25 Final Weeks to Register Analytical 13-14 November 2017 for the Largest PEGS Europe Ever!

18:10 QPix Select HT – Seamless Integration into Sponsored by • How to address developability early on in lead discovery Cover Larger Automation Workstations • Towards in silico and higher throughput in vitro methods Conference-at-a-Glance Dagmar Zunner, Ph.D., Field Application Scientist, BioProduction • Developability in LO Phase and how to extend an antibody platform to non- Development, Molecular Devices platform molecules Short Courses The QPix™ 400 series colony pickers offer the unique option to simultaneously • Specialties for Antibody-drug conjugates or targeted Thorium Conjugates detect colonies and quantify fluorescent markers in a pre-screening step before (Radiotherapy) Training Seminars picking. The QPix Select HT System integrates seamlessly into larger automation 10:05 Integration of Developability Assessment and Protein Engineering workstations. It can be incorporated into an existing automated system, or delivered automation-ready for future integration. for Optimization of Therapeutic Antibodies Engineering Chetan Patel, Ph.D., Principal Research Scientist, Biotherapeutics Discovery 18:25 Welcome Reception in the Exhibit Hall with Sponsored by Research, Eli Lilly & Company n Display of Biologics Poster Viewing This presentation will discuss the analytical characterization of developability n Engineering Antibodies attributes of therapeutic molecules during discovery and provide case studies of n Engineering Bispecifics 19:25 End of Day engineering strategies to mitigate developability risks.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing Therapeutics TUESDAY 14 NOVEMBER n Novel Immunotherapy Strategies DEVELOPABILITY ASSESSMENT FOR EARLY LEAD 07:45 Registration and Morning Coffee n Advancing Bispecifics SELECTION n Novel Therapies for Cancer ENGINEERING & DESIGN TO IMPROVE DEVELOPABILITY AND DRUG-LIKE PROPERTIES 11:15 KEYNOTE PRESENTATION: Developability Assessment of Analytical Biologics – A Concept for Early Lead Selection n Optimisation & Developability 08:30 Chairperson’s Remarks Thorsten Lorenz, Ph.D., Global Head, Developability Assessment, Integrated Biologics Profiling, Novartis Pharma AG n Analytical Characterisation Chris Lloyd, Senior Scientist, Protein Engineering, Antibody Discovery and Protein Engineering (ADPE), MedImmune Early lead selection of biotherapeutics during preclinical development requires n Aggregates & Particles careful characterization of a variety of molecule properties to reduce the risk 08:35 Fc Engineering for Improved Developability and Retained for encountering unexpected obstacles during technical development. The Oncology Biological Activity developability assessment concept applied at Novartis combines information about expression, aggregation propensity, process fit, stability, solubility, n Antibody-Drug Conjugates M. Jack Borrok, Ph.D., Scientist II, Antibody Discovery and Protein Engineering, physicochemical properties, in vivo fitness and immunogenicity of potential MedImmune (AstraZeneca) n Advancing Bispecifics candidates. The presentation will provide an overview about the concept and n Novel Therapies for Cancer Modifications of the IgG Fc have allowed for serum persistence and immune highlight the success with selected examples. engagement to become tunable properties for therapeutic monoclonal antibodies and Fc fusion proteins. These mutation combinations however are rarely “plug- 11:45 Developability Assessment for Bispecific Antibodies Expression and-play” and can introduce developability problems not present in the parental Sagit Hindi-Jacoel, Ph.D., Research Advisor, Biologics Technology, Eli Lilly and n Protein Production Technologies antibody. This talk will focus on strategies to assess the stability of Fc mutants Company n Optimising Expression and outline our engineering approach to improve the developability of antibodies containing Fc mutations while retaining tailored biological activity. Bispecific antibodies offer dual epitope targeting with the potential for enhanced n Purification Technologies therapeutic benefit. However, their development can present unique challenges due 09:05 Rational Design of an Fc-Fusion Therapeutic with Optimal Drug- to their unnatural assembly. The development and optimization of BsABs requires Sponsor & Exhibit Opportunities Like Properties a comprehensive assessment of their critical quality attributes at an early stage of discovery and relies heavily on bioanalytical characterization. This presentation will William Somers, Ph.D., Vice President, Biomedicines Design, Pfizer, Inc. discuss our integrated bioanalytical strategy to enable an efficient developability Hotel & Travel Information Fusion of endogenous proteins with an antibody Fc region has successfully led assessment of IgG-like bispecific antibodies. to dramatic improvements in pharmacokinetics. Unfortunately, these will often Registration Information have poor drug-like properties that limit their utility and increase risk of failure. 12:15 Improving Protein Validation and Characterization Sponsored by These challenges include production cell culture clipping, complex purification Workflows with Faster Sample Quality Analysis schemes, unusual formulations, and in vivo aggregation/stability. We will present Dennis Breitsprecher, Ph.D., Product Manager, Product Development, Register Online! a systematic process to discover therapeutic leads with dramatically improved NanoTemper Technologies GmbH PEGSummitEurope.com properties along with case studies. 12:30 Computational Approaches for Assessing Sponsored by 09:35 Developability: Looking for “Drug-Like Properties” Right from the Developability and Optimization of Biotherapeutics Start of Antibody Lead Discovery Nels Thorsteinson, Scientific Services Manager, Biologics, Chemical Lars Linden, Ph.D., Head, Protein Biochemistry, Biologics Research, Cell and Protein Computing Group, Inc. Science, Bayer AG A Division of Cambridge Innovation Institute 26 Final Weeks to Register Analytical 13-14 November 2017 for the Largest PEGS Europe Ever!

Protein surface hydrophobic patches can lead to aggregation, poor solubility, Analysis of antibody CDR-H3 structures by simulation and informatics approaches Cover and cross-reactivity. We present methods where homology models of sets of enabled us to set up high resolution antibody modeling, and eventually identify antibodies and related biologics with their calculated hydrophobic patches and “design-able” antibodies which are relatively easy for model building and Conference-at-a-Glance charge properties may be used to perform solubility predictions. Liability reduction engineering. Designability is related to CDR-H3 versatility, and the choice of and solubility optimization while maintaining affinity are discussed. undesignable antibody would waste time/cost for antibody optimization. Short Courses 12:45 Luncheon Presentation: Optimizing Drug Dosing Sponsored by 15:35 The Affimer® Scaffold: a Flexible Platform for the Sponsored by Training Seminars by PK Modulation - The Potential of Veltis® Engineered Generation of Affinity Reagents Albumins Geoff Platt, Ph.D., Senior Applications Scientist, Avacta Life Sciences Engineering Nicholas Joseph Martin, Ph.D., Research Scientist Bioprocess Characterisation, Affimer proteins are next-generation affinity scaffolds with multiple properties Albumedix that make them amenable as a platform for immunoassay and biotherapeutics n Display of Biologics Albumin has been used for decades to enhance the pharmacokinetic and development. Benefits include speed to discovery, ease of production, batch- n Engineering Antibodies pharmacodynamic properties of drug candidates. We will describe rationally to-batch reproducibility, specificity, and stability. Using phage display, Affimer n Engineering Bispecifics engineered albumins that further enhance these properties; variants with modified binders have been identified to a wide range of targets (including ZikaNS1, Toxin affinity to FcRn offer more than double the half-life extension to a drug candidate B, Trastuzumab and PD-L1) XelPleX is used as a label-free screening system to compared to that achieved with native albumin. We also present new engineered assess Affimer binding to a target of interest. Therapeutics albumin variants with additional free thiol groups that allow multi-valent site n Novel Immunotherapy Strategies specific drug loading. 16:05 Refreshment Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics 16:45 Highly Efficacious Effector Function Attenuating Mutations that n 13:15 Session Break Novel Therapies for Cancer Maintain Antibody Stability and Reduce Toxicity in Mice 13:30 Dessert Break in the Exhibit Hall with Poster Viewing Travis W. Bainbridge, MSc, Senior Scientific Researcher, Protein Chemistry, Analytical Genentech, Inc. n Optimisation & Developability OPTIMISATION BY DESIGN We demonstrate that commonly used effector function variants that are efficacious in attenuating cytotoxicity in primates, retain potent complement activation n Analytical Characterisation 14:00 Chairperson’s Remarks n Aggregates & Particles capacity in mice. We describe a novel combination of variants that eliminates William Somers, Ph.D., Vice President, Biomedicines Design, Pfizer, Inc. complement binding, fixation and Fcγ-dependent ADCC in both murine IgG2a and human IgG1, unlike aglycosylated antibodies. We further demonstrate that human 14:05 Engineering the Surface Properties of Antibodies to Reduce Self- Oncology and murine antibodies containing these variants have typical pharmacokinetics in Association and Aggregation n Antibody-Drug Conjugates rodents and retain thermostability. Chris Lloyd, Senior Scientist, Protein Engineering, Antibody Discovery and Protein n Advancing Bispecifics Engineering (ADPE), MedImmune 17:15 Advancing the Discovery and Development of Sponsored by n Novel Therapies for Cancer Undesirable physicochemical properties, such as aggregation and chemical Immunotherapeutics with Large, Multiplexed Experiments degradation, may preclude the development of therapeutic antibodies, due to on Suspension Cells Expression potential issues during manufacturing, storage and in vivo administration. Avoiding Mark Carter, New Mexico Senior Assay Consulting Scientist, such properties early on in drug discovery is therefore desirable. My presentation n Protein Production Technologies IntelliCyt, A Sartorius Company will highlight practical screening and antibody engineering strategies that are Benjamin Tyrrell, TS Scientist, Sartorius Stedim, BioOutsource Limited n Optimising Expression effective in identifying lead candidates suitable for development as a drug. n Purification Technologies Exciting advances are being made in novel immunotherapies for treatment of 14:35 Rational Optimization of Peptide Aggregation by in silico Modeling cancer and other diseases. The discovery and development of these therapies and Efficient Experimental Profiling requires new tools that can evaluate their effect on cells and proteins of the Sponsor & Exhibit Opportunities immune. This presentation will highlight how the iQue Screener PLUS platform Andreas Evers, Ph.D., Senior Scientist, Structure, Design & Informatics, Integrated is being used to discover new antibodies, to understand functional efficacy of Drug Discovery, Sanofi Hotel & Travel Information immunotherapies, and to screen for highly productive clones during the cell line Orthogonal experimental methods and different in silico approaches are generation process. Registration Information continuously applied in an iterative manner for the prediction of aggregation tendency, considering requirements of the final formulation, such as compatibility 17:45 Optimization of Biologics Using mRNA Display and NGS with phenolic preservatives and the targeted pH range. The presentation includes Linhui Julie Su, Ph.D., Senior Research Investigator II, Molecular Discovery Register Online! an example demonstrating how aggregation events were correlated with structural Technologies, Bristol-Myers Squibb features and the learnings were prospectively translated into the design of new PEGSummitEurope.com In this talk, I will describe library design, selection strategies, and data analysis molecules that do not exhibit aggregation tendency. using next-generation sequencing (NGS) for discovery of biologic leads. 15:05 Structural Versatility of CDR-H3 as a Risk Factor 18:15 End of Optimisation & Developability Hiroki Shirai, Ph.D., Executive Fellow, Modality Research Laboratories, Astellas Pharma Co., Ltd.

A Division of Cambridge Innovation Institute 27 Final Weeks to Register Analytical 15-16 November 2017 for the Largest PEGS Europe Ever!

4th Annual Cover Conference-at-a-Glance Analytical Characterisation of Short Courses

Training Seminars Biotherapeutics Novel Approaches & Best Practices Engineering Hydrogen/deuterium exchange mass spectrometry has become an important n Display of Biologics Recommended Short Course* method to monitor conformational properties of biopharmaceuticals and is n Engineering Antibodies increasingly used for structure-function characterization and epitope mapping. n Engineering Bispecifics SC10: New Analytical Approaches & Strategies for Comparability & Here we present capability and case studies for the use of HDX-MS in analytical Biosimilarity comparability studies during biosimilar development. *Separate registration required, please click here for details Therapeutics 10:05 MAM, It’s More than Peptide Mapping Sponsored by n Novel Immunotherapy Strategies WEDNESDAY 15 NOVEMBER David Lascoux, Business Development Manager, Waters Corporation n Advancing Bispecifics Peptide-centric monitoring of multiple product variants (Peptide n Novel Therapies for Cancer 07:45 Registration and Morning Coffee map based MAM) has recently generated great interest and concerns. Currently, there is progression and validating of subunit mass based MAM methods for Analytical COMPARABILITY & BIOSIMILARITY high throughput process monitoring and QC release assays. This seminar will discuss the benefits of applying a compliant ready LC/MS platform for effective n Optimisation & Developability 08:30 Chairperson’s Remarks deployment of both subunit mass and peptide map based MAM assays. n Analytical Characterisation Alistair Kippen, Ph.D., Vice President, Biologics Development, Ipsen n Aggregates & Particles 10:35 Coffee Break in the Exhibit Hall with Poster Viewing 08:35 Preparation of a Strong and Convincing Biosimilar File Supported Oncology by Sophisticated Analytical Characterization CHARACTERISING COMPLEX BIOLOGICS Hans-Martin Mueller, Ph.D., Director, Bioprocess Development, Biologics & Vaccines, 11:15 Analytical Characterization of Novel High Potency Toxin- n Antibody-Drug Conjugates MSD Therapeutics n Advancing Bispecifics Demonstrating comparability for a commercial biosimilar product may present Daniel Higazi, Ph.D., Director, Analytical Development, Biologics Development, Ipsen n Novel Therapies for Cancer the greatest challenge of an analytical scientist’s career. This presentation will Biopharm talk about the preparation of a robust analytical package for US and EU health Expression authorities, in particular, how to be successful with demonstrating comparability A detailed understanding of key structural features and degradation pathways is through batch testing, extended characterization, stability studies and forced required to enable protein design and CMC development to proceed in a rational n Protein Production Technologies degradation. manner, whereby quality attributes are understood and appropriately controlled. n Optimising Expression Due to their highly potent nature, and resultant low dose, toxin-based therapeutics n Purification Technologies 09:05 Analytical Biosimilarity and Comparability – A Regulatory present some unique analytical challenges. Case studies will be presented where Perspective insight into quality attributes for toxin therapeutics has been gained using tailored analytical characterisation techniques. Sponsor & Exhibit Opportunities Christina Vessely, Ph.D., Senior Consultant, Biologics Consulting The focus of this discussion is on the regulatory expectations with respect to the 11:45 Probing Protein Higher Order Structure with Mass Spectrometry establishment of biosimilarity or comparability. This includes a discussion on the Hotel & Travel Information Vivian Lindo, Ph.D., Associate Director, Product Characterisation, MedImmune selection of appropriate methods for release and extended characterization, as • Light scattering analyses Registration Information well as the development of protocols for the establishment of comparability or biosimilarity. Both activities require a thorough assessment of the biochemical, • HDX-MS higher order structure determination biological, and biophysical properties of the product in comparison with a reference • Protein folding and conformational dynamics Register Online! material. • Characterisation of non-covalent interactions PEGSummitEurope.com 09:35 Approaches to Demonstrate Higher Order Structure Comparability 12:15 High Resolution Methods to Evaluate Structure of Antibodies and of Biosimilars by HDX-MS Antibody-Antigen Complexes Christian Graf, Ph.D., Scientist, Novartis BTDM-Technical Development Biosimilars, Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Biophysical Novartis Pharma AG Chemistry, AbbVie Bioresearch Center

A Division of Cambridge Innovation Institute 28 Final Weeks to Register Analytical 15-16 November 2017 for the Largest PEGS Europe Ever!

This presentation will focus on the application of transmission electron 14:35 Using Quantitative Proteomics to Link Critical Quality Attributes Cover microscopy and other techniques to characterize biopharmaceuticals and will to Critical Process Parameters demonstrate power of such approaches to understand structure and solution Conference-at-a-Glance Jonathan Bones, Ph.D., Principal Investigator, National Institute for Bioprocessing behavior of antibodies and antibody-antigen complexes. Research & Training (NIBRT), University College Dublin Short Courses 12:45 Development of Biotherapeutics: The Importance Sponsored by Quantitative proteomics is a powerful tool to understand cellular behaviour at of Applying Orthogonal Analytics during Protein Stability the molecular level. Quantitative proteomics of an IgG1 mAb producing CHO Training Seminars cell line was performed following systematic alteration of bioprocess conditions Profiling using a limited Plackett-Burman design of experiments approach. In addition Natalia Markova, Ph.D., Principal Scientist - MicroCal BioScience, to investigating changes in cellular behaviour, complete characterization of the Engineering Malvern Panalytical expressed mAb was also performed to investigate the link between product critical As the biopharmaceutical industry develops ever-more structurally complex quality attributes and alterations in critical process parameters. n Display of Biologics molecules, there is a growing requirement for complementary analytics to n Engineering Antibodies ensure detailed and robust characterization profiles. Here, we’ll demonstrate two 15:05 QbD in Formulation Development - Advancements in the Use n Engineering Bispecifics case studies where single-pass analytics proved insufficient in elucidating and of High-Throughput Characterization and Strategies to Determine the understanding protein behavior at a molecular level. We’ll discuss small 2-domain Biorelevance of Critical Quality Attributes Therapeutics recombinant protein contructs, and also biosimilar molecules, which both needed Michael Siedler, Ph.D., Head, NBE High-Throughput and Advanced Formulation characterization using a variety of analytical technologies to reveal a complete Sciences, Drug Product Development, AbbVie Deutschland GmbH & Co KG n picture of their stability profiles. Novel Immunotherapy Strategies This talk will review how we are implementing QbD in formulation development of n Advancing Bispecifics 13:15 Luncheon Presentation: A Smart Microfluidic Sponsored by biologics by understanding the impact of formulation parameter on Critical Quality n Novel Therapies for Cancer Technology for Early Discovery and Analytics Attributes and their respective biorelevance. We will show examples of high throughput characterization methods and how they can de-risk challenges of novel Anubhav Tripathi, Ph.D., Professor, Bioengineering and Medical Analytical molecule formats in early development. We will describe the use of predictive in Science, Brown University vivo models to guide formulation development. n Optimisation & Developability Protein purity analysis by microfluidic separation offers distinct advantages n Analytical Characterisation over traditional capillary electrophoresis in sample consumption, ease of use, 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing n Aggregates & Particles and speed of analysis. Using a smart microfluidic platform for high throughput quantitation and quality screening of proteins. The method utilizes a microchip 16:15 Quantitative LC MS in Biopharmaceutical Development – Case which utilizes real-time electro-hydrodynamic optimization to eliminate variability Studies from the Industry Oncology in reported results, i.e. run-to-run and day-to-day variability, which may be caused Dan Bach Kristensen, Ph.D., Principal Scientist, Analytical Development, n Antibody-Drug Conjugates by micro-scale fluctuations in the physical properties of chips, reagents, or Symphogen n Advancing Bispecifics instrument components. At Symphogen, quantitative LC MS is being used extensively during biopharmaceutical development for analysis of critical quality attributes, including n Novel Therapies for Cancer 13:45 Session Break chemical degradants (oxidation, deamidation, etc.), disulphide scrambling and glycan distribution. Here the technological platform is presented together with Expression ASSESSING CQAs AND HIGHER-ORDER STRUCTURES case studies from projects in preclinical and clinical development. n Protein Production Technologies 14:00 Chairperson’s Remarks n Optimising Expression 16:45 QC Testing of Biopharmaceutical Higher Order Structure Hans-Martin Mueller, Ph.D., Director, Bioprocess Development, Biologics & Carl Jone, Ph.D., Senior Director, Head, Analytical Sciences Biologicals, UCB n Purification Technologies Vaccines, MSD Is biopharmaceutical Higher Order Structure (HOS) a critical quality attribute? If so, how do we monitor HOS in a QC environment? A case study will be presented on Sponsor & Exhibit Opportunities 14:05 Tailoring Analytical Methods for the Assessment of Critical Quality Attributes of Antibodies how native peptide mapping is being evaluated to determine if it is appropriate for a QC setting. Hotel & Travel Information Christoph Roesli, Ph.D., Analytical Project Leader, Biologics Technical Development and Manufacturing, Novartis Pharma AG 17:15 Problem-Solving Breakout Discussions* Registration Information Distinct product-related variants originating from the manufacturing process or *See website for details formed during storage have to be isolated or enriched to assess their bioactivity/ potency and PK/PD. Here we present analytical strategies for the assessment 18:15 Networking Reception in the Exhibit Hall with Poster Viewing Register Online! of CQAs. Having tailored analytical methods and preparative tools to isolate PEGSummitEurope.com or enrich product-related variants enables an early identification of CQAs. The 19:15 End of Day CQA assessment is the starting point for a fit-for-purpose control strategy and subsequently a streamlined testing strategy.

A Division of Cambridge Innovation Institute 29 Final Weeks to Register Analytical 15-16 November 2017 for the Largest PEGS Europe Ever!

10:35 Coffee Break in the Exhibit Hall with Poster Viewing Cover THURSDAY 16 NOVEMBER 11:15 Screening for Potent T-Cell Dependent Bispecific Antibodies for 08:00 Registration and Morning Coffee Conference-at-a-Glance Inducing Cytotoxicity of Tumor Cells Using an Impedance-Based Assay Short Courses TECHNOLOGIES & APPROACHES TO IMPROVE Platform Elaine Mai, MSc, Senior Scientific Researcher, Biochemical and Cellular Training Seminars CHARACTERISATION - COMPARE & CONTRAST Pharmacology, Genentech, Inc. 08:30 Chairperson’s Remarks Compared with IncuCyte assay using caspase-3/7 readout, the impedance-based assay is more sensitive in detecting killing of low target expressing cells. Also, the Michael Siedler, Ph.D., Head, NBE High-Throughput and Advanced Formulation impedance assay has a similar potency ranking for different TDB clones to the Engineering Sciences, Drug Product Development, AbbVie Deutschland GmbH & Co KG cell titer glo assay. In addition, the assay generated similar EC50s to FACS using n Display of Biologics propidium iodide staining. In conclusion, the impedance platform is superior to the n Engineering Antibodies 08:35 KEYNOTE PRESENTATION: Leveraging the Multi-Attribute other assay methods in supporting TDB candidate selection with the advantages of n Engineering Bispecifics Method (MAM) to Improve Biotherapeutic Characterization being label free and having better sensitivity. Richard Rogers, Ph.D., Scientist 4, Just Biotherapeutics Therapeutics Characterization of complex biotherapeutics using highly resolving mass 11:45 Integrating Novel Tools into Development Workflow of Biologics: spectrometry has resulted in a better understanding of the post-translational nanoDSF and MST for Discovery, Development and QC n Novel Immunotherapy Strategies modifications that are crucial for safety and efficacy. These modifications Alexey Rak, Ph.D., Head, Biostructure and Biophysics, Integrated Drug Discovery, n Advancing Bispecifics are used to guide the manufacturing process and the release strategy for Sanofi R&D n Novel Therapies for Cancer biotherapeutics. We have developed and implemented a mass spectrometry- Modern drug discovery operations require characterization of biomolecular based multi-attribute method (MAM) that monitors known modifications but interactions to be both time- and cost-effective as well as to be highly precise and also has the ability to identify new modifications on the biotherapeutics. Analytical reproducible. Here we report applications of two novel methods, nano-Differential Scanning Fluorimetry (nanoDSF) and MicroScale Thermophoresis (MST), that n Optimisation & Developability 09:05 Poster Highlights: we are applying in our biologics discovery and characterization operations. The n Analytical Characterisation Poster Highlight I: Site-Specific O-Glycan Analysis Using a Novel examples of the demonstrated effectiveness of the nanoDSF and MST will be n Aggregates & Particles O-Glycan Protease and LC-MS/MS presented and discussed. Maria Nordgren, MSc., Senior Scientist, Application Development & Support, Sponsored by Oncology Genovis AB 12:15 Luncheon Presentation: Development of Key Characterization of O-glycosylated proteins have suffered from a lack of specific Characteristics of Biopharmaceuticals Accelerated using n Antibody-Drug Conjugates enzymes and new tools have been needed. This work presents analytical workflows SPR n Advancing Bispecifics for site-specific O-glycan characterization of proteins using a new O-glycan specific Åsa Frostell, Senior Scientist, Purification and Analysis, n Novel Therapies for Cancer protease. The enzyme, discovered in Akkermansia muciniphila, binds specifically to GE Healthcare Life Sciences O-glycans on native glycoproteins and digests the peptide backbone N-terminally of Reliable analytical tools are important for economical process development, Expression S and T residues. As an example, O-glycopeptides of Etanercept, a Fc-fusion protein production and batch release of therapeutic antibodies and new emerging with an O-glycosylated hinge region, has been characterized using LC-MS/MS. n Protein Production Technologies drug formats. This presentation will discuss the benefits that surface plasmon resonance (SPR) technology brings to the development process, taking into n Optimising Expression 09:35 SEC-MS for Characterization of Product-Related Impurities of account regulatory expectations. In particular, accelerating effective antibody n Purification Technologies Monoclonal Antibody drug conjugate (ADC) design, increasing obtained information regarding relative Li Zang, Ph.D., Associate Director, Analytical Development, Biogen potency, and examples of simplified analyses of FcRn and Fcγ receptor binding will Sponsor & Exhibit Opportunities Case studies will be shared for applying an SEC-MS method to characterization of be presented. high-molecular weight and low-molecular weight species in monoclonal antibody Hotel & Travel Information biotherapeutics. 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Sponsored by 13:30 End of Analytical Characterisation of Biotherapeutics Registration Information 10:05 Pyrogen Detection by Monocyte Activation Test in Antibody Formulations Roger Grau, Ph.D., Head, Research & Development, BU Confarma, Solvias AG Register Online! Detection of pyrogens - fever inducing substances - relies predominantly on PEGSummitEurope.com the rabbit pyrogen test. In preparations where endotoxin is the only potential contaminant, the rabbit test can be replaced by a specific endotoxin test. The Monocyte Activation Test provides a sensitive, reliable alternative for those cases, where potential contaminants other than endotoxin might be present. It monitors the release of cytokines induced by pyrogens present in the sample using human cells as test system.

A Division of Cambridge Innovation Institute 30 Final Weeks to Register Analytical 16-17 November 2017 for the Largest PEGS Europe Ever!

4th Annual Cover Conference-at-a-Glance Protein Aggregates & Particles Short Courses Reducing Immunogenicity Risks Training Seminars THURSDAY 16 NOVEMBER QUANTIFYING AND CHARACTERISING AGGREGATES

Engineering 12:30 Registration 15:50 KEYNOTE PRESENTATION: Regulatory Perspective in New n Display of Biologics 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Analytical Methods for Protein Aggregates Quantification and n Engineering Antibodies Characterization n Engineering Bispecifics SOURCES AND MECHANISMS OF PROTEIN AGGREGATION Ewa Marszal, Ph.D., CMC Reviewer, Plasma Derivatives Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Therapeutics 13:30 Chairperson’s Opening Remarks Center for Biologics Evaluation and Research, US FDA Paul Dalby, MA, Ph.D., FRSC, AMIChemE, Deputy Head of Department (Research), n Novel Immunotherapy Strategies Biochemical Engineering, University College London 16:20 A Semi-Quantitative Method for Visible Particles in n Advancing Bispecifics Biotechnological Solutions – Why Do We Care? n Novel Therapies for Cancer 13:35 Microscopic Mechanisms Underlying the Effect of Surfaces and Patricia Winter Cash, Ph.D., Independent Consultant Mechanical Agitation on Protein Aggregation Presence of particulates is a common reason for Product Recalls. Formation Analytical Paolo Arosio, Ph.D., Professor, Institute of Chemical and Bioengineering, ETH Zurich of protein particles is recognized as an inherent quality attribute. All proteins Despite the fact that empirical effects of surfaces and mechanical forces on contain particles. There is an industry-wide need for particle standards so n Optimisation & Developability protein aggregation are well documented, the molecular details of the mechanisms biopharmaceutical manufacturers can monitor and control the presence of n Analytical Characterisation underlying this behaviour are still largely elusive. In this work, we design an particles in their protein products. This talk will explain the need for particle n Aggregates & Particles experimental assay based on nanoparticles to investigate independently the standards, describe one method for estimating particles and introduce new particle effect of surfaces and mechanical forces on the formation of amyloid fibrils from standards in development. Oncology human insulin, and we apply a chemical kinetic platform to analyse the molecular mechanisms at the origin of this effect. 16:50 End of Day n Antibody-Drug Conjugates n Advancing Bispecifics 14:05 Review on Silicone as Source for Subvisible/Visible Particles and 17:00 Dinner Short Course Registration n Novel Therapies for Cancer Potential Protein Aggregation Promoter 17:30-20:30 Recommended Dinner Short Course* Karoline Bechtold-Peters, Ph.D., Senior Strategy & Technology Leader, Expression Pharmaceutics, Biologics Technical Development & Manufacturing, Novartis SC9: Protein Aggregation: Mechanism, Characterisation and While silicone is toxicologically safe, the use of silicone as a lubricant in packaging Consequences n Protein Production Technologies materials for injection purposes is associated with the increase of subvisible as *Separate registration required, please click here for details n Optimising Expression well as visible particles and is also described as a source of protein aggregation for n Purification Technologies biologics. The talk will discuss various published studies and describe analytical methods to characterize silicone layers, which can be used within the context of a FRIDAY 17 NOVEMBER control strategy. Sponsor & Exhibit Opportunities 08:00 Registration and Morning Coffee 14:35 See Stability in Hi-Def with Hunky Sponsored by Hotel & Travel Information Greg Manley, Senior Applications Specialist, Unchained Labs IMPACT OF AGGREGATES ON PRODUCT PROPERTIES Registration Information Developing biologics requires identifying ideal constructs and assessing a wide range of formulation space to ensure stability and minimize 08:30 Chairperson’s Remarks aggregation. Assessing ΔG is a powerful approach for the quantitative assessment Vasco Filipe, Ph.D., Unit Head, Formulation Development of Biopharmaceuticals, Register Online! of conformational stability and aggregation. Unchained Labs automates the Sanofi tedious and manual task of determining ΔG, allowing for quantitative stability and PEGSummitEurope.com aggregation assessment throughout biologic development. We’ll discuss how automated chemical denaturation can be used with more traditional approaches to assess stability.

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

A Division of Cambridge Innovation Institute 31 Final Weeks to Register Analytical 16-17 November 2017 for the Largest PEGS Europe Ever!

11:05 Aggregation of Monoclonal Antibodies: Causes, Bioavailability and Cover 08:35 KEYNOTE PRESENTATION: Approaches to Predict Protein- Immunogenicity Conference-at-a-Glance Protein Interactions, and Their Impact on Product Properties Vasco Filipe, Ph.D., Unit Head, Formulation Development of Biopharmaceuticals, Sanofi Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, The mechanisms and factors influencing protein aggregation will be reviewed. Short Courses University of Delaware Some examples and interesting cases from Sanofi and literature will be shown. There is increasing interest in the development of experimental approaches A review of the current knowledge and ongoing initiatives on aggregate-induced Training Seminars and computational models to predict product properties such as high immunogenicity will be presented. solution viscosity, solubility limits, and aggregation rates from low- to high- concentration conditions. This presentation focuses on a combination of 11:35 Mechanisms Behind Immunogenicity Risk due to Aggregates and experimental and modeling approaches to predict protein-protein interactions Impurities during Biologics Development Engineering and their impact on stability and viscosity for monoclonal antibody products, Vibha Jawa, Ph.D., Director, Biologics & Vaccines Bioanalytics, MSD n Display of Biologics illustrating both successes and outstanding challenges. Human immune system is not exposed to aggregated proteins endogenously. There n Engineering Antibodies is an uncertainty around potential risk of aggregates associated with biologics in n Engineering Bispecifics 09:05 Combining Stability and Surface Aggregation Predictions to Design Protein Solubility clinic as there are confounding factors like dose, frequency, route that can also contribute to risk. To address this uncertainty, it is important to identify attributes Therapeutics Salvador Ventura, Ph.D., Chair, Professor of Biochemistry & Molecular Biology, that can cause a clinically relevant response, establish the threshold of activation of Institute of Biotechnology and Biomedicine, Universitat Autonoma de Barcelona such a response that will support establishing ranges and understand the extent and n Novel Immunotherapy Strategies Mutations that increase protein stability usually result in reduced aggregation- nature of the response and how close it is to physiological relevance. n Advancing Bispecifics propensity. The same effect can be attained with amino acid changes that increase n Novel Therapies for Cancer the solubility of structural surfaces. Very often these changes result in decreased 12:05 Sponsored Presentation (Opportunity Available) protein stability or even a gain in protein aggregation-propensity. AGGRESCAN3D is Analytical a software that is able to forecast simultaneously these two effects and to select 12:35 Problem-Solving Breakout Discussions with a Light Snack in the Foyer* protein variants with higher probabilities to be evolved into soluble drugs. *See website for more details n Optimisation & Developability n Analytical Characterisation 09:35 A New Strategy to Assess Ligand or Solution-Based Stability of 13:35 Session Break n Aggregates & Particles Aggregation-Prone Proteins Using an Automated Chaperonin Biolayer Interferometry Platform FORMULATION TO IMPROVE STABILITY AND REDUCE Oncology Mark T. Fisher, Ph.D., Professor, University of Kansas Medical Center AGGREGATION Stabilizing the folded state of metastable and/or aggregation-prone proteins n Antibody-Drug Conjugates through ligand binding is an appealing strategy to decrease disease pathologies 14:00 Chairperson’s Remarks n Advancing Bispecifics brought on by deleterious protein folding defects. This presentation describes an Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, n Novel Therapies for Cancer automated GroEL chaperonin-based biolayer interferometry (BLI) denaturant-pulse University of Delaware platform for assessing the kinetic stability of aggregation prone proteins and 14:05 Impact of Protein Mutational Variability upon Formulation Designs Expression allows us to validate the effects of ligand stabilization or destabilization of these kinetically unstable proteins. Paul Dalby, MA, Ph.D., FRSC, AMIChemE, Deputy Head of Department (Research), n Protein Production Technologies Biochemical Engineering, University College London n Optimising Expression 10:05 Coffee Break with Poster Viewing Protein stability is a critical factor for the successful development of non- n Purification Technologies aggregating biopharmaceuticals. Routes to predictably engineer protein stability AGGREGATE-INDUCED IMMUNOGENICITY RISKS are therefore crucial. We have used a wide range of biophysical analyses to characterise the aggregation landscape of proteins, and used this understanding to Sponsor & Exhibit Opportunities 10:35 Probing Protein Aggregation and Immunogenicity by Epitope inform both better formulation design strategies, and improved protein engineering Profiling strategies. The relationships between the conformational stabilities imparted by Hotel & Travel Information Tim Eyes, Ph.D., Research Associate, Immunology and Biotechnology, University of protein engineering and formulation excipients will be discussed. Manchester Registration Information Aggregation is thought to be a significant risk factor in promoting the unwanted immunogenicity of therapeutic protein products. Our work has examined the Register Online! relationship between oxidation, aggregation and the influence of heat shock proteins, as prominent HCPs, on the quality and vigor of the immune response to PEGSummitEurope.com selected model biotherapeutic proteins. More recently we have demonstrated how B-cell epitope profiling can shed light on how antibodies specifically target protein aggregates.

A Division of Cambridge Innovation Institute 32 Final Weeks to Register Analytical 16-17 November 2017 for the Largest PEGS Europe Ever!

14:35 When Standard Biological Drug Formulation Sponsored by Cover Strategies Fail? Conference-at-a-Glance Eleonora Cerasoli, Ph.D., Senior Research Scientist, Bioprocess Characterisation, Albumedix Short Courses The expanding field of peptide and protein therapeutics gives promise for improvement of treatments against several diseases. Many of the Training Seminars biopharmaceuticals found to be efficacious, however continue to face ex vivo instability challenges despite advancements in protein and peptide engineering. What novel formulation strategies and stabilization agents are emerging? Engineering Advantages and disadvantages with new stabilization and solubilization agents? Regulatory and clincial challenges with using proteinous excipients in drug n Display of Biologics formulation? n Engineering Antibodies n Engineering Bispecifics 15:05 The Role of Poloxamer 188 in Protecting Protein Formulations Christoph Grapentin, Ph.D., Postdoctoral Fellow, Pharmaceutical Development & Therapeutics Supplies, PTD Biologics Europe, (PTDE-P), F. Hoffmann-La Roche, Ltd. The liabilities of polysorbates have become a hot industry topic recently. Attention n Novel Immunotherapy Strategies has been enhanced to the use of alternative surfactants like poloxamer 188 (P188). n Advancing Bispecifics The presentation will evaluate a range of state-of-the-art techniques to study the n Novel Therapies for Cancer interplay of P188 and proteins at interfaces (air, silicone oil) plus the characteristics of P188 in solution (i.a. dilation rheology, small angle x-ray scattering). Similarities Analytical and differences of P188 to polysorbates will be discussed. n Optimisation & Developability 15:35 Tackling “Tornado-Like” Particle Formation Issues with an IgG1 n Analytical Characterisation Molecule by Formulation Optimisation n Aggregates & Particles Peng Ke, Ph.D., Scientist I, Formulation Sciences, MedImmune, a member of the AstraZeneca Group Oncology During formulation development of an IgG1 molecule, “tornado-like” particles were observed in the solutions after storage for a certain period of time. The onset of n Antibody-Drug Conjugates particle formation was variable and difficult to predict using common analytical n Advancing Bispecifics techniques. Therefore, significant formulation development challenges were n Novel Therapies for Cancer presented and in order to solve the particle issues, systematic investigational works and formulation optimisation were conducted.

Expression 16:05 A Rational Strategy for the Reduction of Protein Aggregation in n Protein Production Technologies Mammalian Cell Cultures n Optimising Expression Friedemann Hesse, Ph.D., Professor, Institute for Applied Biotechnology, Biberach n Purification Technologies University of Applied Sciences Although protein aggregation is a well-known quality issue in the production of Sponsor & Exhibit Opportunities recombinant biopharmaceuticals which can already occur in early stages of the manufacturing process, only few studies address protein aggregation during Hotel & Travel Information upstream processing. Therefore, this study was performed in order to establish a rational approach for the optimization of upstream bioprocesses to reduce protein Registration Information aggregation in mammalian cell cultures. 16:35 End of Conference Register Online! PEGSummitEurope.com

A Division of Cambridge Innovation Institute 33 Final Weeks to Register Oncology 13-14 November 2017 for the Largest PEGS Europe Ever!

2nd Annual Cover Conference-at-a-Glance Engineering Next-Generation Short Courses

Training Seminars Antibody-Drug Conjugates Into the Clinic and Beyond Engineering 15:10 Widening the Therapeutic Index: The Next Generation of n Display of Biologics Recommended Short Course* Antibody-Drug Conjugates (ADCs) n Engineering Antibodies SC2: Mutation and Selection Strategies beyond Affinity Optimisation John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished n Engineering Bispecifics *Separate registration required, please click here for details Research Fellow, ImmunoGen, Inc. ADCs with potent tubulin-acting and DNA-acting agents can be effective anti- Therapeutics cancer agents with good TI. However, not all cell-surface targets have proven MONDAY 13 NOVEMBER susceptible to the development of effective ADCs utilizing the first-generation n Novel Immunotherapy Strategies ADC chemistries. Each element in the ADC design, the antibody, the payload, n Advancing Bispecifics 12:00 Registration and the linker (both site of attachment on antibody and payload-release n Novel Therapies for Cancer mechanism) are important considerations. Application of the growing “ADC PLENARY KEYNOTE SESSION Toolbox” to current and future ADC developments will be discussed. Analytical 13:40 Welcome from PEGS Europe Team 15:50 Refreshment Break in the Exhibit Hall with Poster Viewing n Optimisation & Developability Christina C. Lingham, Team Lead, PEGS Europe n Analytical Characterisation 13:45 Moderator’s Opening Remarks ANALYSING QUALITY & MANUFACTURING ADCs n Aggregates & Particles Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA 16:50 Chairperson’s Remarks Oncology 13:50 Safety Considerations for Development of Immune Agonist Roger R. Beerli, Ph.D., CSO, NBE-Therapeutics, Ltd. and Immune Antagonist Biotherapeutics n Antibody-Drug Conjugates Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, 16:55 High-Throughput Optimization and Mass Spectrometric Analysis n Advancing Bispecifics Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group) of Covalently Labeled Proteins and Antibody-Drug Conjugates n Novel Therapies for Cancer In this keynote presentation, the challenges of biotherapeutics impacting on Chawita (Jelly) Netirojjanakul, Ph.D., Scientist, Hybrid Modality Engineering Group, the immune response, and the challenges investigators face managing, dose, Therapeutic Discovery Research, Amgen, Inc. scheduling, and satisfying the regulatory requirements will be discussed. The The use of automated high throughput screening in large molecule discovery Expression checkpoint pathways modulation used for cancer immunotherapy has a natural research still lags behind that of small molecule discovery. Here, we developed an n Protein Production Technologies role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. automated platform to complete a bioconjugation optimization workflow in one n Optimising Expression Immunotherapies in general, and technologies modifying T cell function and those setting. Given LC-MS is a widespread analytical bottleneck, we also established n Purification Technologies involving cytokines present dangers of cytokine storm, autoimmune disease, an HTS-MS platform to accurately detect and rapidly quantitate mAb and Fc cardiovascular disorders, and additional challenges, especially when used in conjugates with acquisition time of 20 sec/sample, 10-50x improvement over combination. Strategies to manage and mitigate immune related safety events traditional LC-MS methods. Sponsor & Exhibit Opportunities will be presented. 17:25 ADC Manufacturing for Clinical Supply in Multi-Purpose Facilities Hotel & Travel Information 14:30 Learning What Works from Successful Tumour Infiltrating – Challenges and Solutions Lymphocyte Therapy Ulrich Rümenapp, Ph.D., Head, Launch Preparation and Coordination, Bayer AG Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff Registration Information The manufacturing of ADCs for clinical supply (or the commercial market after University School of Medicine launch) has its special challenges due to the toxicity of the ADC molecule and its Over 20% of melanoma patients that have been refractory to other treatments payload. This includes, e.g., the need to protect the personnel in the working area Register Online! undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating and the environment, measures to avoid cross-contamination, as well as appropriate lymphocytes (TILs). Dissection of these extraordinary successes by examining the PEGSummitEurope.com waste handling. Bayer’s Biologics Development approach for the GMP production of dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient ADCs in its pilot facilities in Wuppertal, Germany up to a 100L-scale will be presented. blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and With the combination of single-use systems, closed processing and isolator non-HLA restricted targets that are expressed by many other tumour types. technologies, ADCs can be manufactured in classical multi-purpose pilot-scale facilities without jeopardizing work safety or higher risk of cross-contamination. This avoids the investment in construction of a dedicated ADC facility. A Division of Cambridge Innovation Institute 34 Final Weeks to Register Oncology 13-14 November 2017 for the Largest PEGS Europe Ever!

17:55 POSTER SPOTLIGHT Abdurins are a novel antibody-like scaffold that can be engineered to bind to targets Cover Biopolymeric Scaffold for High Antibody Drug Ratios Using Site-Specific of interest and, due to an FcRn binding motif within the scaffold, Abdurins have a circulating half-life longer than any other protein scaffold of similar size. We have Conjugation Strategies Conference-at-a-Glance isolated high-affinity Abdurin binders to a number of cancer targets and engineered Aileen Ebenig, PhD Student, Biochemie, Technische Universitat Darmstadt various attachment sites for drug conjugation. Abdurin-drug conjugates retained Short Courses 18:25 Welcome Reception in the Exhibit Hall with Sponsored by high affinity binding to their targets and FcRn, killed cells with low nM to pM IC50’s, and had in vivo half-life up to 70 hours for certain conjugates. This presentation will Training Seminars Poster Viewing contain data for both Abdurin-drug conjugates and Abdurin-SarcinDI fusions. 19:25 End of Day 11:45 Fragment (Antibody) Drug Conjugates (FDCs): A Unique Drug Engineering Class of Just Smaller ADCs? TUESDAY 14 NOVEMBER n Display of Biologics Mahendra Deonarain, Ph.D., CSO, Antikor Biopharma, Ltd. n Engineering Antibodies FDCs can carry more payload than ADCs whilst retaining excellent 07:45 Registration and Morning Coffee pharmacodynamic and pharmacokinetics properties. They are better tolerated than n Engineering Bispecifics ADCs while carrying equivalent payloads, and show promise as a new drug class NEXT-GEN ENGINEERING for oncology therapeutics. Therapeutics 08:30 Chairperson’s Remarks 12:15 Utilizing RESPECT™ (REsidue-SPEcific Conjugation Sponsored by n Novel Immunotherapy Strategies Philip Howard, Ph.D., Senior Fellow, MedImmune, Inc. and CSO, Spirogen, Ltd. Technology) for the Generation of Homogeneous n Advancing Bispecifics Antibody-Drug Conjugates n Novel Therapies for Cancer 08:35 Antibody-Drug Conjugates for Treatment of Triple Negative Breast Jared Spidel, Ph.D., Principal Scientist Antibody, Core Development, Morphotek, Inc. Analytical Cancer Morphotek’s REsidue SPEcific Conjugation Technology (RESPECT™) is a Aditya Bardia, M.D., MPH, Attending Physician, Massachusetts General Hospital transglutaminase-based conjugation technology that targets specific lysine n Optimisation & Developability Cancer Center, and Assistant Professor, Harvard Medical School residues in IgG. Whereas other enzymatic-based conjugation techniques require n Analytical Characterisation Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer extensive antibody modification by either deglycosylation or addition of multiple- amino acid enzyme-recognition tags, RESPECT™ requires just a single amino acid n Aggregates & Particles that tends to affect young patients and is associated with high risk of recurrence and mortality. Currently, there is no FDA-approved targeted therapy for TNBC. addition or substitution to efficiently produce homogeneous site-specific antibody conjugates. Oncology Consequently, there is considerable interest in identification of potentially actionable molecular alterations in TNBC, including potential targets for antibody 12:45 Luncheon Presentation: Abcam’s Custom Sponsored by n Antibody-Drug Conjugates drug conjugates (ADCs). In this talk, we will review the current landscape of ADCs Services Capabilities – from Development to n Advancing Bispecifics for treatment of triple negative breast cancer, as well as future directions. Commercialization n Novel Therapies for Cancer 09:05 HuMax-AXL-ADC, a Novel Antibody-Drug Conjugate for the Joyce L. Young, Ph.D., Vice President, Custom Services Division, Abcam Treatment of Solid Cancers In this talk, we will discuss Abcam’s three antibody development platforms Expression Esther Breij, Ph.D., Associate Director, Antibody Science, Genmab BV (recombinant RabMAb®, Next Gen Sequencing, and phage display), which offer a n Protein Production Technologies Axl is aberrantly expressed in solid cancers, and expression has been associated comprehensive approach to developing antibodies against challenging targets. We n Optimising Expression with poor prognosis and resistance to therapy. HuMax-AXL-ADC, a novel antibody- partner with biopharma and diagnostic companies to develop antibodies as key n Purification Technologies drug conjugate that targets Axl-positive cancers, showed promising anti-tumor reagents in drug discovery, in vitro diagnostics and therapeutics. activity in a variety of solid cancer xenograft models. Moreover, HuMax-AXL-ADC showed cytotoxic activity in solid cancer models that showed enhanced Axl 13:15 Session Break Sponsor & Exhibit Opportunities expression upon acquired resistance to kinase inhibitors. 13:30 Dessert Break in the Exhibit Hall with Poster Viewing Hotel & Travel Information 09:35 Problem-Solving Breakout Discussions* *See website for details BREAKTHROUGH PAYLOAD TECHNOLOGY Registration Information 14:00 Chairperson’s Remarks 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Ronit Mazor, Ph.D., Post-Doctoral Fellow, Lab for Molecular Biology, National Cancer Register Online! NEXT-GEN ENGINEERING (CONT.) Institute (NIH) PEGSummitEurope.com 11:15 Abdurin-Drug Conjugates: Small Size and Long Half-life to Improve Drug Concentration in the Target Tissue Silvia Peretti, Ph.D., Senior Research Scientist, Biochemistry, IRBM Science Park SpA

A Division of Cambridge Innovation Institute 35 Final Weeks to Register Oncology 13-14 November 2017 for the Largest PEGS Europe Ever!

14:05 KEYNOTE PRESENTATION: IMGN632: A CD123-Targeting 16:05 Refreshment Break in the Exhibit Hall with Poster Viewing Cover Antibody-Drug Conjugate (ADC) with a Novel DNA-Alkylating Conference-at-a-Glance Payload ENHANCING THE IMMUNE RESPONSE Jan Pinkas, Ph.D., Executive Director, ImmunoGen, Inc. 16:45 Anthracycline-Based Antibody-Drug Conjugates with Potent Short Courses • CD123 is an attractive target in hematologic malignancies; • IMGN632 is an antibody-drug conjugate created by site-specific conjugation Immune-Stimulatory Functions Training Seminars to the DNA-alkylating agent, DGN549-C, to the CD123-targeting antibody Roger R. Beerli, Ph.D., CSO, NBE-Therapeutics, Ltd. G4723A; We employed enzymatic, site-specific conjugation to generate homogenous ADCs • CD123-dependent cytotoxicity was demonstrated against a panel of AML based on a derivative of the highly potent anthracycline toxin PNU-159682 and a Engineering cell lines in vitro including cell lines that have poor prognostic markers and non-cleavable peptide linker, using the anti-HER-2 antibody trastuzumab (part of against leukemic progenitors from AML patients; trastuzumab emtansine) and the anti-CD30 antibody cAC10 (part of brentuximab n Display of Biologics • The concentrations of IMGN632 required to kill leukemic progenitors from vedotin). Characterization of the resulting ADCs in vitro and in vivo showed that n Engineering Antibodies healthy donors are at least 100-fold higher than the concentrations needed they were highly stable and exhibited potencies exceeding those of ADCs based on n Engineering Bispecifics to kill leukemic progenitors from AML patients; and conventional tubulin-targeting payloads. • IMGN632 was highly active against a range of sub-cutaneous and Therapeutics disseminated AML tumor xenograft models in mice. 17:15 Immunotoxins with Low Immunogenicity for Cancer Therapy Ronit Mazor, Ph.D., Post-Doctoral Fellow, Lab for Molecular Biology, National Cancer n Novel Immunotherapy Strategies Institute (NIH) n Advancing Bispecifics 14:35 PBD-ADC Update 2017 Recombinant Immunotoxins (RITs) are a genetically engineered category of ADC n Novel Therapies for Cancer Philip Howard, Ph.D., Senior Fellow, MedImmune, Inc. and CSO, Spirogen, Ltd. that was developed in our lab to treat cancer. Because they contain a bacterial Pyrrolobenzodiazepine (PBD) dimers are potent DNA crosslinking agents that have toxin that kills the cancer cells, RITs are very immunogenic to cancer patients with Analytical been adapted for use as payloads in antibody drug conjugates (ADCs). A range of a normal immune system. This talk will discuss the clinical results achieved so far, PBD payloads has been designed, synthesized and conjugated to antibodies and and methods we used to make next-generation immunotoxins by identifying and n Optimisation & Developability currently there are 13 ADCs containing PBD payloads in Phase I, II and III clinical eliminating of T cell epitopes. Furthermore, we will describe a novel approach to n Analytical Characterisation trials. The presentation will provide an update on the development of PBD payloads induce immunological tolerance that allows multiple treatment cycles. n Aggregates & Particles and their clinical progress. 17:45 Novel Calicheamicin Antibody-Drug Conjugates Oncology 15:05 HDP-101 – A BCMA-Targeted Amanitin-Based ADC Julia Gavrilyuk, Ph.D., Principal Scientist, Discovery Chemistry, AbbVie Stemcentrx Christian Breunig, Ph.D., Group Leader, Biomarker & Cell Biology, Heidelberg Pharma Calicheamicin has a long history as an ADC payload, yet only one linker-drug n Antibody-Drug Conjugates GmbH design has been utilized for clinical ADCs. Design of the novel stable linkers for n Advancing Bispecifics Antigen-Targeted Amanitin-Conjugates (ATACs) represent a new class of ADCs calicheamicin payload may lead to the calicheamicing ADCs with improved efficacy n Novel Therapies for Cancer using the payload Amanitin. This payload introduces a novel mode of action into and safety profile. I will present lessons learned in design and optimization of novel oncology therapy, the inhibition of RNA polymerase II. The technology platform calicheamicin-based ADCs. I will also discuss the influence of the linker stability on Expression around ATACs includes Amanitin supply, site-specific conjugation, demonstrated ADC cytotoxicity in vitro, and efficacy and tolerabilityin vivo. safety profile and biomarker. A BCMA-ATAC has been selected based on favorable n Protein Production Technologies preclinical data to start the clinical development of the first ATAC. 18:15 End of Engineering Next-Generation Antibody-Drug Conjugates n Optimising Expression n Purification Technologies 15:35 Current Status of Clinical Stage Antibody-Drug Conjugates William R. Strohl, Ph.D., President and Owner, BiStro Biotech Consulting, LLC Sponsor & Exhibit Opportunities Currently there are over 850 different antibody-based drug candidates being tested in clinical trials, approximately 10% of which are antibody drug conjugates (ADCs). ADCs represent the second largest group of non-traditional naked IgG- Hotel & Travel Information based antibody drug candidates, behind the category of antibody-based chimeric antigen receptor (CAR)-T cells, but ahead of bispecific antibodies. ADCs make up Registration Information about 16% of all anti-cancer antibody-based drug candidates. ADCs being studied in clinical trials currently target over 50 different cell surface antigens, the most Register Online! popular of which include HER2 and CD19 (with 4 ADCs targeting each), and CD22, CD33, and mesothelin (3 ADCs targeting each). The ADC field is rapidly maturing, PEGSummitEurope.com and with the “rules” for design and use of ADCs currently being elucidated, it is expected that ADCs will play a significant, and perhaps expanded, oler in cancer therapy in the future.

A Division of Cambridge Innovation Institute 36 Final Weeks to Register Oncology 15-16 November 2017 for the Largest PEGS Europe Ever!

9th Annual Cover Conference-at-a-Glance Advancing Bispecifics and Combination Short Courses

Training Seminars Therapy to the Clinic Combinations Showing Enhanced Efficacy Engineering project the first-in-human (FIH) dose. Particularly, a mechanistic PK/PD-driven n Display of Biologics Recommended Short Course* approach, which accounts for the bispecific target binding, was explored to n Engineering Antibodies SC6: Engineering of Bispecific Antibodies understand the exposure-response relationship and to project the MABEL dose. The current approach could potentially be implemented for other bispecifics. n Engineering Bispecifics *Separate registration required, please click here for details 10:05 Development and Application of MOA-based Sponsored by Therapeutics WEDNESDAY 15 NOVEMBER Reporter Bioassays for Immunotherapy Drug Development n Novel Immunotherapy Strategies Jey Cheng, Senior Research Scientist, Research & Development, 07:45 Registration and Morning Coffee n Advancing Bispecifics Promega Corporation n Novel Therapies for Cancer Having a functional bioassay that is MOA-based, accurate, precise, robust and BISPECIFICS FOR T CELL RECRUITMENT / TARGETING reproducible is critical for the development of antibody-based biologics. We IMMUNOTHERAPY AGONISTS have developed reporter bioassays that meet these criteria for a broad range of Analytical antibody modalities including Fc effector function, immune checkpoint modulation, n Optimisation & Developability 08:30 Chairperson’s Remarks bispecific antibody engagement, cytokine modulation, and others. Here we will present the latest technology advancements and demonstrate how these n Analytical Characterisation Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA bioassays can be used for a broad range of applications n Aggregates & Particles 08:35 Bispecific T-Cell Engagers (BiTE) in Hematology and Beyond Matthias Klinger, Ph.D., Principal Scientist, BiTE Technology, Amgen Research 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Oncology (Munich) GmbH n Antibody-Drug Conjugates Following the approval of blinatumomab in relapsed/refractory ALL multiple 11:15 KEYNOTE PRESENTATION: A Novel FAP-Targeted 4-1BB n Advancing Bispecifics BiTE candidates have or are about to enter the clinic in various indications. Agonist and Its Combination with T Cell Bispecific Antibodies This presentation will give an update on Amgen’s BiTE pipeline at the discovery, Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, n Novel Therapies for Cancer translational, and early clinical stage of development. Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich Expression 09:05 Tumor-Specific Carbohydrate Antigens as Preferable Targets for Immune co-stimulation via 4-1BB agonism is an important element of next generation CAR-T cell therapy. The clinical development of first generation 4-1BB n Protein Production Technologies Novel Bispecific Antibody Constructs agonistic antibodies has been hampered by hepatic toxicity. Here we describe a n Optimising Expression Patrik Kehler, Associate Director, Immuno-Oncology, Preclinical & Immunological Research, Glycotope GmbH novel FAP-targeted 4-1BB agonist for combination with T cell bispecific antibodies n Purification Technologies Carbohydrates on the surface of cancer cells represent preferable targets for which may represent an off-the-shelf alternative to CAR-T cell therapies. bispecifics due to their unique tumor-specificity with lack or inaccessibility on Sponsor & Exhibit Opportunities normal tissues and broad indication coverage. Multiple constructs were generated 11:45 Multi-Functional Designed Ankyrin Repeat Protein Drugs: MP0250 to demonstrate the feasibility of carbohydrates as valuable targets for different and Beyond Hotel & Travel Information bispecific approaches such as T cell recruitment. A comprehensive screening H. Kaspar Binz, Ph.D., Vice President & Co-Founder, Molecular Partners program was performed to identify the most preferable construct combining The use of the robust designed ankyrin repeat protein technology enables the Registration Information highest tumor specificity, anti-tumor functionality and adequate safety. nimble testing and establishment of drugs acting on multiple disease pathways. MP uses the platform to establish a portfolio of innovative drugs for the treatment 09:35 Mechanistic Projection of First-in-Human Dose for Bispecific of cancer. The latest clinical data including MP0250 along with novel drug Register Online! Immunomodulatory P-Cadherin LP-DART concepts will be presented. PEGSummitEurope.com Xiaoying Chen, Ph.D., Senior Manager, Early Oncology Development & Clinical Research, Pfizer, Inc. 12:15 ATOR-1015, a Bispecific Immunomodulatory Antibody Targeting An immunomodulatory bispecific molecule (P-cadherin LP-DART) was developed OX40 and CTLA-4 as a potential antitumor treatment. Because of its immune agonistic properties, Christina Furebring, Ph.D., Senior Vice President, R&D, Alligator Bioscience a minimal anticipated biological effect level (MABEL) approach was applied to Alligator Bioscience has developed a bispecific antibody targeting OX40 and

A Division of Cambridge Innovation Institute 37 Final Weeks to Register Oncology 15-16 November 2017 for the Largest PEGS Europe Ever!

CTLA-4 for immunotherapy of cancer. The mode of action of ATOR-1015 includes lineages. Thus, in addition to cancer, we are exploring the utility to use the biAb Cover depletion/suppression of regulatory T cells as well as activation of effector T cells. in autoimmunity, as the efficacy of B cell depletion in these patients positively The design and the pharmacodynamics properties, as well as the biochemical correlates with clinical outcomes. Conference-at-a-Glance properties and manufacturability, will be presented. ATOR-1015 is currently in preclinical development for clinical trials. 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing Short Courses 12:45 Carbohydrate Targeted Cancer Immunotherapy Using a Training Seminars IMMUNOMODULATORY BISPECIFICS Recombinant Malaria Protein Mie Anemone Nordmaj, M.Sc., PhD Student, Immunology and Microbiology, Medical 16:15 Simultaneous Blockade of Multiple Immune Checkpoints with Bispecific Antibodies Engineering Parasitology, University of Copenhagen A unique malaria protein, VAR2CSA, binds to a distinct type of chondroitin sulfate David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc. n Display of Biologics found exclusively on a broad repertoire of cancer cells and in the cancer associated Combinations of checkpoint-blocking antibodies are more efficacious than single n Engineering Antibodies extracellular matrix. Here we describe the construction of an “armed” rVAR2 inhibitors, but also generate greater immune-related adverse events. We reasoned n Engineering Bispecifics molecule, capable of simultaneous recognition of cancer cells via rVAR2 and that a single bispecific antibody could achieve dual blockade to selectively target cytotoxic T-lymphocytes via anti-CD3. In vitro and in vivo efficacy showed significant tumor-reactive lymphocytes, possibly improving safety and efficacy. We have anti-tumor effects, demonstrating the feasibility of using rVAR2 as a component in generated multiple dual-checkpoint inhibitors such as XmAb20717 (PD1 x CTLA4) Therapeutics a bispecific antibody. that display compelling in vitro and in vivo activity relative to combinations of n Novel Immunotherapy Strategies monospecific antibodies, suggesting that checkpoint bispecifics may veha clinical n Advancing Bispecifics 13:15 Enjoy Lunch on Your Own advantages for the treatment of human malignancies. n Novel Therapies for Cancer 13:45 Session Break 16:45 FS118: An Anti-LAG-3/PD-L1 Bispecific Antibody Which Modulates T Cell Activity and Inhibits Tumour Growth Analytical BISPECIFICS TARGETING B CELLS FOR ONCOLOGY Mihriban Tuna, Ph.D., Vice President, Drug Discovery, F-star n Optimisation & Developability 14:00 Chairperson’s Remarks A bispecific antibody (mAb2) which binds murine LAG-3 and PD-L1 simultaneously with high affinity was engineered and characterised. The anti-LAG-3/PD-L1 mAb2 n Analytical Characterisation Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron inhibits LAG-3 binding to MHCII and PDL1 binding to PD-1 and CD80, resulting n Aggregates & Particles Pharmaceuticals in T cell activation in vitro. This translates into in vivo efficacy, where the mAb2 significantly decreased tumour burden in the MC38 colon carcinoma tumour Oncology 14:05 Development of Anti-FcRH5/CD3 T Cell Dependent Bispecific (TDB) Antibody for the Treatment of Multiple Myeloma model. Thus, the preclinical data supports developing an anti-human LAG-3/PD-L1 mAb2 for the treatment of cancer. n Antibody-Drug Conjugates Teemu Junttila, Ph.D., Senior Scientist, Genentech, Inc. n Advancing Bispecifics We have developed a novel T-cell dependent bispecific (TDB) antibody, anti- 17:15 Problem-Solving Breakout Discussions* n Novel Therapies for Cancer FcRH5/CD3 TDB, targeting the B cell lineage marker FcRH5 for multiple myeloma. *See website for details This demonstrated cytotoxicity against human plasma cells and patient derived Expression myeloma, and induced immunosuppressive feedback signaling, including PD1 18:15 Networking Reception in the Exhibit Hall with Poster Viewing up-regulation, which can be overcome by PD-L1 antibodies. Data demonstrate the n Protein Production Technologies potential for anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD1/ 19:15 End of Day n Optimising Expression PDL1 signaling in the treatment of multiple myeloma and other B-cell malignancies. n Purification Technologies 14:35 CD20 TCB (RG6026), a Novel “2:1” T Cell Bispecific Antibody for THURSDAY 16 NOVEMBER the Treatment of B Cell Malignancies Sponsor & Exhibit Opportunities 08:00 Registration and Morning Coffee Sara Colombetti, Ph.D., Head, Oncology Discovery, Pharmacology, Roche Innovation Hotel & Travel Information Center, Zurich INNOVATIVE BISPECIFIC COMBINATIONS The talk will focus on preclinical data of CD20 TCB, a novel differentiated CD20- Registration Information targeting T cell bispecific antibody on the “2:1” IgG format that consistently 08:30 Chairperson’s Remarks demonstrated superior potency compared to other CD20 TCBs with a conventional David Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc. “1:1” IgG format. This translated into superior efficacy in vitro, ex vivo and in vivo, Register Online! which could not be matched by increasing doses of the “1:1” TCBs. 08:35 Bispecific Antibodies and Antibody-Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs PEGSummitEurope.com 15:05 Therapeutically Targeting B Cells in Autoimmune Disease and Julian Andreev, Ph.D., Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Cancer Using a CD47xCD19 biAb Approach Pharmaceuticals Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA There is a need for HER2-directed ADCs effective in patients expressing low/ Novimmune is developing a biAb approach to safely yet effectively treat B cell moderate levels of HER2. Cross-linking HER2 to constitutively internalizing PRLR, malignancies by targeting CD19 and CD47 with one molecule. CD47 restrains using a HER2xPRLR bispecific ADC, dramatically enhances lysosomal antibody dependent phagocytosis and CD19 covers a broad spectrum of the B cell degradation of HER2. Accordingly, bispecific ADC improve upon T-DM1 A Division of Cambridge Innovation Institute 38 Final Weeks to Register Oncology 15-16 November 2017 for the Largest PEGS Europe Ever!

efficacy in cells expressing intermediate levels of HER2. These results demonstrate MULTIVALENT BISPECIFICS Cover that coupling a tumor-specific ADC target to a rapidly internalizing protein may be a useful approach to enhance efficacy of ADCs. Conference-at-a-Glance 11:15 The Biology of IgG Hexamerization – Translating Basic Science to Antibody Therapeutics 09:05 Advances with Bispecifics and Multi-Specifics in the Clinic – Short Courses Rob N. de Jong, Ph.D., Associate Director, CMC Research & Protein Chemistry, Lessons Learned Genmab BV Training Seminars Tariq Ghayur, Ph.D., Distinguished Research Fellow, Foundational Immunology, In this presentation, we will present our understanding of the requirements of IgG Immunology Discovery, AbbVie hexamer formation at the submolecular level; functional aspects of antigen- and Fc- Several bispecific DVD-Ig molecules have now been tested in preclinical models dependent IgG hexamer formation, the development of the Hexabody technology; Engineering and in clinic. The emerging data show that these molecules behave like monoclonal and progress towards clinical translation of Hexabody-based therapeutics. antibodies and that the DVD-Ig format per se is not immunogenic. However, n Display of Biologics target biology may play an important role anti-drug antibody response (ADA, 11:45 Tetravalent Bispecific Antibodies with Unique CD16A-Binding n Engineering Antibodies immunogenicity). Lessons learned from these studies will be discussed. Properties to Treat Non-Solid and Solid Tumors n Engineering Bispecifics 09:35 Preclinical Development of MCLA-158, a Bispecific Antibody Michael Tesar, Ph.D., Head, R&D, Affimed GmbH Targeting Lgr5 and EGFR Affimed has developed a unique NK-cell engager platform which delivers novel Therapeutics antibodies that not only activate innate immunity, but have also shown evidence Berina Eppink, Ph.D., Project Manager, Merus, NV of facilitating cross-talk with T-cell effectors. New data will be presented including n Novel Immunotherapy Strategies Biclonics is a robust and validated platform for the development of human full description of the technology, mode of action and potential combination strategies. n Advancing Bispecifics length IgG bispecific antibodies. MCLA-158 is a Biclonics that binds the wnt target n Novel Therapies for Cancer gene Lgr5 and the growth factor receptor EGFR. MCLA-158 demonstrates superior 12:15 Enjoy Lunch on Your Own activity in both in vitro and in vivo tumor organoid based assays regardless of KRAS status and was shown to be well tolerated in non-human primates. These 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Analytical preclinical data suggest MCLA-158 could benefit patients with metastatic CRC. n Optimisation & Developability 13:30 End of Advancing Bispecifics and Combination Therapy to the n Analytical Characterisation 10:05 Design and Evaluation of Next-Generation Biologics Clinic n Aggregates & Particles for Cancer Immunotherapy Maria Wendt, PhD, Head of Science, Genedata Oncology Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific n Antibody-Drug Conjugates constructs can provide significant advantages for use in cancer immunotherapy. n Advancing Bispecifics However, as highly engineered molecules they pose new design, engineering, n Novel Therapies for Cancer cloning, expression, purification, and analytics challenges. Genedata Biologics enables the automated design, screening, production, and testing of large panels of these candidate therapeutic molecules and includes built-in tools for developability Expression and manufacturability assessments. n Protein Production Technologies n Optimising Expression 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Purification Technologies

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A Division of Cambridge Innovation Institute 39 Final Weeks to Register Oncology 16-17 November 2017 for the Largest PEGS Europe Ever!

2nd Annual Cover Conference-at-a-Glance Novel Therapies for Cancer and Short Courses

Training Seminars Emerging Targets Improving Efficacy for Clinical Success Engineering n Display of Biologics THURSDAY 16 NOVEMBER NEW THINKING FOR CHECKPOINT BLOCKADE n Engineering Antibodies 15:50 Combination of PD-1/PD-L1 Blockade and Targeting of a Tumor- n Engineering Bispecifics 12:30 Registration Specific Carbohydrate Antigen in a Novel Trifunctional Antibody as a 13:00 Dessert Break in the Exhibit Hall with Poster Viewing Strategy to Improve Anti-PD-L1 Therapy Therapeutics Johanna Rühmann, Ph.D., Senior Director, Internal project strategy & Cooperations, n Novel Immunotherapy Strategies NEW T CELL THERAPIES: OUT-OF-THE-BOX THINKING Glycotope GmbH n Advancing Bispecifics 13:30 Chairperson’s Opening Remarks We developed a trifunctional antibody which combines targeting of TA-MUC1 and PD-L1 with a functional Fc-part (PM-PDL). By focusing PD-1/PD-L1 blockade to n Novel Therapies for Cancer Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular the tumor and multiplying different modes of action, PM-PDL has the potential to Biology, National Cancer Institute, NIH Analytical increase efficacy and broaden patient coverage giving additional benefit compared 13:35 Shared Target Antigens on Cancer Cells and Tissue Stem Cells: Go to the respective monospecific antibody. The results further underline the potential n Optimisation & Developability or No-Go for CAR T Cells? of Fc glyco-optimization to enhance not only cytotoxic but also immunomodulatory antibody effector functions. n Analytical Characterisation Hinrich Abken, Ph.D., Professor, Genetics & Immunology, Center for Molecular n Aggregates & Particles Medicine Cologne, University of Cologne 16:20 IO Treatments of Renal Cell Carcinoma: The Changing Landscape ‘On-target off-tumor’ toxicity raises serious safety concerns when the target antigen Hans Hammers, M.D. Ph.D., Eugene P. Frenkel M.D. Scholar, Clinical Medicine; Oncology is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Associate Professor, Internal Medicine, Hematology and Oncology, Kidney Cancer We discuss CAR T cell targeting of activation antigens versus lineage associated n Program, University of Texas Southwestern Antibody-Drug Conjugates antigens on the basis of recent experimental and animal data, in particular in the The presentation will outline key features of the currently approved n Advancing Bispecifics context of targeting CD30. n Novel Therapies for Cancer immunotherapies like nivolumab and IL2 in RCC. Additionally, the emerging 14:05 The UniCAR Platform Technology: Turning CAR T Cells On and Off treatment landscape with combination immunotherapies such as other immune checkpoints and VEGF pathway inhibitors will be discussed. Expression Michael P. Bachmann, Ph.D., Director, Institute of Radiopharmaceutical Cancer Research; Head, Radioimmunology, Helmholtz Zentrum Dresden Rossendorf HZDR n 16:50 End of Day Protein Production Technologies Adoptively transferred conventional CAR T cells remain active in patients and n Optimising Expression can cause life threatening side effects. In contrast, activity of UniCAR T cells is 17:00 Dinner Short Course Registration n Purification Technologies dependent on the administration of a target module (TM). TMs are bispecific fusion molecules consisting of an epitope recognized by the UniCAR and a binding 17:30-20:30 Recommended Dinner Short Course* Sponsor & Exhibit Opportunities domain directed to the respective tumor antigen. After elimination of TMs UniCAR SC6: Engineering of Bispecific Antibodies T cells automatically switch off again. *Separate registration required, please click here for details Sponsored by Hotel & Travel Information 14:35 Can Severe Adverse Events of CAR-Ts be mitigated through Product Design? FRIDAY 17 NOVEMBER Registration Information Paula Salmikangas, Director, Biopharmaceuticals and ATMPs, NDA Advisory Board, NDA Group 08:00 Registration and Morning Coffee Register Online! Clinical development and commercialization of CAR-T products has been WHY DOESN’T CAR T THERAPY WORK IN SOLID PEGSummitEurope.com hampered by the SAEs caused by high activity of the CART-cells and simultaneous lysis of large tumor loads. This has led to search for technologies to better control TUMOURS YET? the products but little attention has been given to the product design. Is it time to look into the cell products and discuss whether the most severe AEs could be 08:30 Chairperson’s Remarks prevented through proactive product design without compromising efficacy? Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School 15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

A Division of Cambridge Innovation Institute 40 Final Weeks to Register Oncology 16-17 November 2017 for the Largest PEGS Europe Ever!

08:35 The clinical efficacy of first-generation carcinoembryonic antigen 11:35 Strategies to Inhibit the Intracellular Target Ras with Potent Cover (CEACAM5)-specific CAR T cells is limited by poor persistence and Antibody Mimetic Proteins Conference-at-a-Glance transient pre-conditioning-dependent respiratory toxicity Ralph Minter, Ph.D., Director, Fellow, Antibody Discovery and Protein Engineering, Robert Hawkins, Ph.D., FRCP, Professor, Cancer Research, University of Manchester; MedImmune Short Courses Honorary Consultant, Medical Oncology Ras mutations are strong oncogenic drivers of many cancers but the target Ras is still not addressed by any current therapies. Inhibition of Ras nucleotide Training Seminars 09:05 CAR T Manufacturing Made Simple exchange is a novel approach to blocking Ras signaling by locking it in an inactive Andrew Kaiser, Ph.D., R&D Manager, Cell & Gene Immunotherapy/Clinical Cell conformation. We describe an antibody mimetic, DARPin K27, which blocks Ras Processing, Research & Development, Miltenyi Biotec GmbH using such a mechanism and inhibits downstream signaling and tumour cell Engineering This presentation will focus on advances in the field of automation applied to growth. K27 and other antibody-like molecules enable us to explore novel strategies cellular therapies and describe how T cells can easily be enriched from blood to (i) deliver functional macromolecules into cells and (ii) understand the biological n Display of Biologics products, activated, gene-modified, expanded and formulated on a single closed implications of Ras inhibition. n Engineering Antibodies platform with minimal user interactions or liquid handling. Attributes of the n Engineering Bispecifics produced cells, such as composition, phenotype in vitro and in vivo function will 12:05 Problem-Solving Breakout Discussions with a Light Snack in the be shown. Recent developments will demonstrate that such complex procedure Foyer* Therapeutics can be carried out in serum free conditions and allow for flexible means of gene- *See website for more details modification that can further enable the field. n Novel Immunotherapy Strategies 13:35 Session Break n Advancing Bispecifics 09:35 The Role of CD28 in the Rescue of CD8 T Cells by PD-1 Targeted n Novel Therapies for Cancer Therapies IMPROVEMENTS IN TARGETING CANCER Rathi Pillai, M.D., Assistant Professor, Department of Hematology and Oncology, Analytical Winship Cancer Institute, Emory University 14:00 Chairperson’s Remarks Programmed cell death-1 (PD-1) directed therapies activate exhausted CD8 T Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London n Optimisation & Developability cells and have become effective treatments in cancer. The costimulatory CD28/ Cancer Institute n Analytical Characterisation B7 pathway is essential for the rescue of exhausted T cells in mouse models of 14:05 Heterocellular Oncogenic Signaling n Aggregates & Particles chronic viral infection and cancer. Most proliferating CD8 T cells in the blood of lung cancer patients treated with PD-1 inhibitors express CD28. CD28 costimulation Christopher J. Tape, Ph.D., CRUK Career Development Fellow, University College plays an integral role in T cell rescue by PD-1 therapies. London Cancer Institute Oncology Cancer is a heterocellular disease comprised of mutated cancer cells, stromal n Antibody-Drug Conjugates 10:05 Coffee Break with Poster Viewing fibroblasts, and multiple immune cells. Each of these cell types contribute to n Advancing Bispecifics tumour biology, but the signaling mechanisms underpinning their malignant n Novel Therapies for Cancer DIFFICULT AND NEXT GOOD TARGETS: ARE WE USING THE behaviour are poorly understood. We have established cell-specific proteomic technologies to measure cell signaling in heterocellular systems. Using these RIGHT STRATEGIES TO TARGET TUMOURS? technologies, we demonstrate how oncogenic driver mutations ‘spread’ their Expression Chairperson’s Remarks signals across multiple cell types to drive tumours. n Protein Production Technologies Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation 14:35 Ultra-Selective T-Cell Engaging Antibody Circuits (TEAC): A New n Optimising Expression Approach to Cancer Immunotherapy n Purification Technologies 10:35 Design and Construction of Antibody Phage Display Libraries for Therapeutic Antibody Discovery Mark Cobbold, M.D., Ph.D., Associate Professor, Massachusetts General Hospital, Harvard Medical School Juan Carlos Almagro, Ph.D., Founder and Director, GlobalBio, Inc. Sponsor & Exhibit Opportunities Cytotoxic T-cells are amongst the most potent arms of the immune response Display technologies have had a profound impact in engineering antibodies to treat and immunotherapies harnessing these exhibit powerful effects against cancer. unmet medical needs, in particular, in the oncology field. This talk will discuss the Hotel & Travel Information Separating toxicity from efficacy remains an ongoing challenge for both CAR T design and implementation of novel phage display libraries with improved functionality and bispecific T-cell engaging biologics. Here we describe a new antibody-based and capabilities for discovery and optimization of therapeutic antibodies. Registration Information approach to selectively engage T-cells at tumor sites using Boolean operator logic 11:05 Single Domain Antibodies Targeting Glypicans for Cancer Therapy based upon antigen and protease target site expression. By applying logic gating, Register Online! Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular we obviate many of the current challenges with T-cell engaging antibodies. Biology, National Cancer Institute, NIH PEGSummitEurope.com 15:05 Improving CAR T Cell Function by Reversing the We develop inhibitory antibodies that target signaling pathways (e.g. Wnt) Immunosuppressive Tumor Environment of Pancreatic Cancer responsible for the growth of cancer. This can be done by using single domain antibodies that bind cryptic and buried functional regions in receptors or signaling Juan Fernando Vera Valdes, M.D., Associate Professor, Medicine, Baylor College of complexes. We have studied glypicans (e.g. GPC2, GPC3) as a new class of targets Medicine in cancer and made immunotoxins and CAR T cells for the treatment of liver cancer To target pancreatic ductal adenocarcinoma (PDAC), we generated a CAR targeting and pediatric cancers. PSCA. However, PDAC tumors produce inhibitory cytokines (e.g. IL4), which A Division of Cambridge Innovation Institute 41 Final Weeks to Register Oncology 16-17 November 2017 for the Largest PEGS Europe Ever!

limit CAR T cell persistence and effector function. Thus, to protect our CAR T cells Cover we co-expressed a custom inverted cytokine receptor (ICR) linking the IL4 receptor exodomain with the IL7 receptor endodomain. The current presentation will summarize Conference-at-a-Glance the in vitro and in vivo results achieved when combining these modifications. Short Courses 15:35 New Bispecific Antibodies Targeting Members of the EGFR Training Seminars Receptor Family Roland Kontermann, Ph.D., Professor, Biomedical Engineering, Institute of Cell Biology & Immunology, University of Stuttgart Engineering Tetravalent, bispecific antibodies, based on a single-diabody Fc format (scDb-Fc), were generated using a novel neutralizing anti-HER3 antibody recognizing a novel n Display of Biologics epitope formed domain III and IV combined with antibodies against other members n Engineering Antibodies of the EGFR receptor family. A scDb-Fc targeting HER3 and EGFR potently inhibited n Engineering Bispecifics activation of both receptors and downstream signals, with possible applications to overcome resistance against EGFR monotherapy by compensatory HER3 signaling. Therapeutics 16:05 End of Conference n Novel Immunotherapy Strategies n Advancing Bispecifics n Novel Therapies for Cancer

Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles

Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer

Expression n Protein Production Technologies n Optimising Expression n Purification Technologies

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A Division of Cambridge Innovation Institute 42 Final Weeks to Register Expression 13-14 November 2017 for the Largest PEGS Europe Ever!

Cover Basic Technologies in a By Cambridge Healthtech Institute Conference-at-a-Glance Short Courses Protein Production Lab Training Seminars DAY 1: 13:40 - 19:25 | DAY 2: 08:30 - 18:15 Engineering n Display of Biologics Instructors: Who should attend the training seminar? n Engineering Antibodies Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, Protein Expression Facility, The seminar is designed for researchers, lab managers, graduate students, n Engineering Bispecifics Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life postdocs, technicians and engineers wishing to expand their knowledge and Sciences, The Hebrew University of Jerusalem implement basic and advanced technologies in recombinant protein production in Therapeutics Mario Lebendiker, Ph.D., Head, Protein Purification Facility, Wolfson Centre for their work. n Novel Immunotherapy Strategies Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem n Advancing Bispecifics Instructor Biographies: n Novel Therapies for Cancer Panelists: Tsafi Danieli, Ph.D., Director, BioGiv Excubator & Head, Protein Expression Facility, Richard Altman, MS, Scientist V, Protein Technologies, Amgen Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Analytical Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, Sciences, The Hebrew University of Jerusalem Thermo Fisher Scientific n Optimisation & Developability Tsafi Danieli is the head of the Protein Expression Core Facility at the Wolfson Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick National n Analytical Characterisation Centre for Applied Structural Biology at the Hebrew University of Jerusalem, Israel. Laboratory for Cancer Research The core facility functions as a biotechnology research center for the development n Aggregates & Particles Bjørn Voldborg, MSc, Director, CHO Cell Line Development, Novo Nordisk Foundation and implementation of novel technologies in recombinant DNA, molecular biology Center for Biosustainability, Technical University of Denmark and protein production. It also operates as a training centre supporting individual Oncology research projects and conducting workshops and courses for scientists from n Antibody-Drug Conjugates This seminar is designed to introduce basic technologies, strategies and academic institutes and from the Biomed & Biotech industry. Dr. Danieli is also the founder and director of “BioGiv”, a specialised university-based center for n Advancing Bispecifics considerations in recombinant protein production in E. coli, insect and mammalian promoting and supporting entrepreneurs and inventors to translate ideas into new n Novel Therapies for Cancer cells for multiple research and development applications. The seminar supplies a basic toolbox for management of multiple and diverse projects. products and bring new technologies to market, while using the infrastructure of the Hebrew University in Jerusalem. Dr. Danieli holds a BSc in Biology and MSc in Expression human genetics from Tel Aviv University, and a Ph.D. in molecular virology from the University of California, San Francisco Pharmacology Department, in collaboration n Brief Description: Protein Production Technologies with the Biochemistry Department at Tel Aviv University. n Optimising Expression • Overview of recombinant protein production: initiating a project, design and n Purification Technologies options for various downstream applications, requirements from customer/ collaborator, and matching expectations. Mario Lebendiker, Ph.D., Head, Protein Purification Facility, Wolfson Centre for • Introduction to expression systems; covering the differences between the Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Sponsor & Exhibit Opportunities standard expression systems: E. coli, insect cells and mammalian cells, in Hebrew University of Jerusalem protein quality, quantity and downstream applications, cost considerations, Dr. Mario Lebendiker is in charge of the Protein Purification Facility at the Wolfson Hotel & Travel Information implementation time, required expertise and more. Centre for Applied Structural Biology, The Hebrew University of Jerusalem. He is • Basic principles in affinity chromatography, ion exchange, hydrophobic actively involved in many collaborations for structural and biochemical studies Registration Information exchange, size exclusion and mixed mode chromatography. Protein purification within the Hebrew University, others Universities in Israel, as well as with biotech strategies: input for purification protocol development, guidelines for protein and pharmaceutical companies. Dr. Lebendiker received a Ph.D. in Biochemistry purification, selection and combination of purification techniques. in 1982 from the Animal Virology Center (CEVAN), in Buenos Aires University, Register Online! • Connection between expression and protein quality; dealing with prone-to- Argentina. Together with many other laboratories, he found the Protein Production PEGSummitEurope.com aggregate proteins; selection and combination of purification techniques; and Purification Partnership in Europe (P4EU) network, a platform for the exchange major requirements for purification of proteins for structural, biophysical and of information, knowhow and materials between core facility labs in the field of biochemical studies; minimal quality control parameters and quality control protein expression and purification. workflow. • Troubleshooting and case studies.

A Division of Cambridge Innovation Institute 43 Final Weeks to Register Expression 15-16 November 2017 for the Largest PEGS Europe Ever!

10th Annual Cover Conference-at-a-Glance Optimising Expression Platforms Short Courses Meeting the Demand for Engineered Proteins Training Seminars Deducing generic causal relations between features of the genetic material and Recommended Short Course* various aspects related to the gene expression dynamic is a fundamental scientific Engineering objective with ramifications for disciplines such as biotechnology, human health, SC4: Transient Protein Expression: A Key Tool to Enable Rapid and functional genomics. In this talk I show how, on the one hand, the analysis n Display of Biologics Protein Engineering of endogenous gene expression data with molecular evolution and biophysical n Engineering Antibodies *Separate registration required, please click here for details modeling tools contributes towards model-based gene expression engineering. n Engineering Bispecifics On the other hand, I demonstrate how the design and tailoring of synthetic biology WEDNESDAY 15 NOVEMBER experiments can be used for accurately estimating the direct effect of genomic Therapeutics features on gene expression. n Novel Immunotherapy Strategies 07:45 Registration and Morning Coffee 10:05 The Strep-Tag® Technology - The Superior Tag Sponsored by n Advancing Bispecifics ENGINEERING EXPRESSION PLATFORMS System for the Entire Protein Production Workflow n Novel Therapies for Cancer Dennis Niermeier, MSc, IBA Lifesciences 08:30 Chairperson’s Remarks IBA is focused on a comprehensive product portfolio around its Analytical Tsafi Danieli, Ph.D., Director, BioGivExcubator & Head, Protein Expression Facility, proprietary Strep-tag® technology that covers the entire protein Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life production workflow from cloning, expression and purification n Optimisation & Developability Sciences, The Hebrew University of Jerusalem as well as protein immobilization for assays. Especially our Strep-Tactin®XT is n Analytical Characterisation superior to other systems due to its extremely high affinity while maintaining n Aggregates & Particles 08:35 Bottom-Up Strategies for Reconstitution of Multi-Protein reversibility. Complexes Using the Baculovirus Expression System Sponsored by Oncology Arnaud Poterszman, Ph.D., Research Director (CNRS), Integrated Structural Biology, 10:20 Difficult to Express Proteins: Novel Plasmid Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/UdS) Technology to Significantly Increase Product Yield n Antibody-Drug Conjugates Many eukaryotic proteins function as macromolecular complexes whose subunits in CHO Cells n Advancing Bispecifics act in concert to catalyze specific activities. We illustrate how genome editing Marco Cacciuttolo, Ph.D., Director, Operations, Batavia Biosciences n Novel Therapies for Cancer technologies allow purified native assemblies from cells and how the baculovirus expression system emerged as a powerful tool for reconstitution of multi-subunit 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Expression complexes, focusing on strategies to facilitate manipulation of the baculoviral genome and assemble multi-gene constructs. As model systems, we will use 11:15 How to Tune Recombinant Protein Expression in E. coli for n Protein Production Technologies transcription regulators such as pTefb, nuclear receptors or the 10 subunits Enhanced Production of Biopharmaceuticals n Optimising Expression transcription factor TFIIH. David Johannes Wurm, Ph.D., Postdoctoral Researcher, Institute of Chemical, n Purification Technologies Environmental and Biological Engineering, Integrated Bioprocess Development, TU Vienna 09:05 Nature as a Blueprint to Convert Yeast into an Antibody Factory Strong induction of recombinant protein expression in E. coli can lead to Sponsor & Exhibit Opportunities Alexander Frey, Ph.D., Associate Professor, Molecular Biotechnology, Department of agglomeration of inactive product. We developed a feeding strategy to tune Bioproducts and Biosystems, School of Chemical Engineering, Aalto University recombinant protein expression on a cellular level which leads to higher yields Hotel & Travel Information We have previously created glycoengineered Saccharomyces cerevisiae strains of soluble and active product and applied this system to the production of the producing human-like comlex N-glycans. Considering the production of antibodies, model protein GFP and an industrially relevant antibody fragment. Furthermore, Registration Information a major hindrance lies in the yeast endoplasmic reticulum, as it is not equipped we developed a fast and effective method for strain characterization, which is a for efficient folding. By rational strain design and high-throughput screening prerequisite for this feeding strategy. applications we were able to increase the specific secreted antibody yields of Register Online! S. cerevisiae, providing a promising strain for further process optimization and 11:45 An Ongoing Evaluation of Our Transient Expression Systems: Can platform development for antibody production. We Predict the Appropriate Expression System for Any Drug Modality? PEGSummitEurope.com Richard Altman, MS, Scientist V, Protein Technologies, Amgen 09:35 Combining Synthetic Biology and Molecular Evolution for A robust, flexible transient protein production facility provides critical support to Optimizing and Understanding Gene Expression drug discovery efforts. We review the ongoing evolution of our protein production Hadas Zur, Ph.D., Researcher, Department of Biomedical Engineering, Tel Aviv endeavors focusing on two critical components. The first is the strategic assembly University of mammalian expression “tools” that gives us a toolbox capable of expressing

A Division of Cambridge Innovation Institute 44 Final Weeks to Register Expression 15-16 November 2017 for the Largest PEGS Europe Ever!

diverse and challenging candidate proteins. The second is the harmonization of 15:05 Eukaryotic Cell-Free Systems: A Novel Source for Functional Cover the entire protein production process, thereby reducing turnaround times and Antibodies increasing throughput. Conference-at-a-Glance Marlitt Stech, Ph.D., Research Scientist, Cell-Free and Cell-Based Bioproduction, 12:15 In-Depth Process and Systems Characterization via PAT/QbD Fraunhofer Institute for Cell Therapy and Immunology Short Courses Generates Understanding the Base for New Host Design Concepts Since antibodies are indispensable tools for diagnostic and therapeutic Gerald Striedner, Ph.D., Associate Professor, Department of Biotechnology, applications, the development of alternative manufacturing strategies that Training Seminars University of Natural Resources and Life Sciences circumvent the hurdles connected to conventional antibody production technologies is of enormous interest. To address this issue, we have developed a Implementation of PAT/QbD concepts provides the basis for advanced bioprocess novel antibody production technology based on a microsome-containing CHO cell- understanding. This fundamental knowledge based on systems behavior under free system that combines the advantages of the eukaryotic expression host with Engineering production conditions allows for innovative process-relevant host and process the benefits of cell-free systems in general. n Display of Biologics engineering concepts. The talk focuses on such host design strategies for different n Engineering Antibodies systems (CHO, insect cells/baculo system) and process types. 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing n Engineering Bispecifics 12:45 Approaches for the Rapid Development of Sponsored by ENGINEERING HOSTS: CHO CELL LINES (CONT.) Therapeutics Recombinant E.coli Strains for Large Scale GMP Production of Biotherapeutics 16:15 Automation and High-Density Mammalian Cultures to Maximize n Novel Immunotherapy Strategies Christopher Lennon, Ph.D., Staff Scientist, Research & Development, Protein Productivity n Advancing Bispecifics FUJIFILM Diosynth Biotechnologies Kinjal Mehta, Ph.D., Principal Scientist, Protein Sciences, Jounce Therapeutics n Novel Therapies for Cancer Platform processes are key in controlling the approach to Biopharmaceutical While CHO has proven to be a promising cell line for desirable post-translational process development. Large numbers of variations on strains need to be screened modification patterns, HEK293 maintains its role as a conventional mammalian Analytical quickly and efficiently in a manner that directly models large scale commercial host with regards to desired specifications on product quality and faster turnaround manufacturing. Fujifilm Diosynth Biotechnology use the Ambr250(tm) in concert times in isolated cases. In this presentation, we describe optimized protocols for n Optimisation & Developability with the pAVEway expression system to rapidly establish a fermentation process. ExpiCHO and Expi293 cell lines, to demonstrate automated procedures from HTP n Analytical Characterisation transfections through purifications enabling generation of several milligrams of n Aggregates & Particles 13:15 Enjoy Lunch on Your Own antibody or reagent proteins from smaller cultures with shorter turnaround times. 13:45 Session Break 16:45 Mitochondrial-Derived Small RNAs as Powerful Tools to Boost Oncology CHO Cell Productivity n Antibody-Drug Conjugates ENGINEERING HOSTS: CHO CELL LINES Lisa Alexandra Pieper, Postdoctoral Researcher, Early Stage Bioprocess n Advancing Bispecifics 14:00 Chairperson’s Remarks Development, Boehringer Ingelheim Pharma GmbH & Co. KG n Novel Therapies for Cancer In this study we show that ectopic expression of a human mitochondrial-derived Henry Chiou, Ph.D., Associate Director, Cell Biology, Thermo Fisher Scientific small RNA (mitosRNA-1978) in IgG expressing CHO cells strongly improved Expression specific productivity by functioning in a microRNA-like fashion. By next-generation 14:05 KEYNOTE PRESENTATION: Engineering CHO Cells sequencing we identified Ceramide Synthase 2 (CerS2) and Tbc1 domain family n Protein Production Technologies Bjørn Voldborg, MSc, Director, CHO Cell Line Development, Novo Nordisk member 20 (Tbc1D20) as target genes of mitosRNA-1978. Knockdown of CerS2 n Optimising Expression Foundation Center for Biosustainability, Technical University of Denmark and Tbc1D20 in CHO-IgG cells resulted in increased antibody production, thus n Purification Technologies Using high-throughput (HT) technologies, the CHO Cell Line Engineering recapitulating the mitosRNA-1978 phenotype. project at the Center for Biosustainability is genetically modifying CHO cells based on experimental and in silico generated data to engineer CHO cell lines 17:15 Problem-Solving Breakout Discussions* Sponsor & Exhibit Opportunities optimised for the production of therapeutic proteins. We have engineered *See website for details cells resulting in tailormade glycoprofiles and non-lactate producing cell lines, Hotel & Travel Information thereby improving the bioprocess. 18:15 Networking Reception in the Exhibit Hall with Poster Viewing

Registration Information 14:35 Generation of Superior Host Cell Lines for Biomanufacturing 19:15 End of Day Holger Laux, Ph.D., Fellow, Cell Line Development, Novartis CHO cells are the most widely used host for large-scale production of recombinant THURSDAY 16 NOVEMBER Register Online! therapeutic proteins. Using transcriptomic approaches we have identified target PEGSummitEurope.com genes involved in productivity and product quality. Subsequently a variety of novel 08:00 Registration and Morning Coffee parental CHO cell lines were generated applying cell line engineering techniques. These novel knockout CHO cell lines are superior in respect to productivity and/or CASE STUDIES: PROTEIN TO PRODUCT product quality. 08:30 Chairperson’s Remarks Richard Altman, MS, Scientist V, Protein Technologies, Amgen A Division of Cambridge Innovation Institute 45 Final Weeks to Register Expression 15-16 November 2017 for the Largest PEGS Europe Ever!

10:35 Coffee Break in the Exhibit Hall with Poster Viewing Cover

Conference-at-a-Glance 08:35 Bioprocess Engineering of Insect Cells for Accelerating Vaccines CASE STUDIES: PROTEIN TO PRODUCT (CONT.) Development 11:15 A Recombinant Human Anti-Platelet scFv Antibody Produced in Short Courses Antonio Roldao, Ph.D., Senior Scientist, Animal Cell Technology Unit, Instituto de Pichia pastoris for Atheroma Targeting Biologia Experimental e Tecnológica (iBET) Abdelmajid Noubhani, Ph.D., Associate Professor, Microbiology, Institute Training Seminars Technological breakthroughs are urgently needed to accelerate biologics of Chemistry and Biology of Membrane & Nano-Objects (ENSTBB), Institut manufacturing process. In this talk, two case studies will be presented where Polytechnique de Bordeaux bioprocess engineering assisted/accelerated vaccine development: CS1. Multivalent Engineering Influenza VLPs: (i) combining stable and baculovirus-mediated expression, (ii) We describe the cloning, expression, purification, and immunoreactivity assessment of a recombinant scFv derived from a human anti-αIIbβ3 antibody n Display of Biologics identifying best infection strategy through DoE, and (iii) ALE of insect cells; CS2. HIV- Gag VLPs: (i) generating stable insect cell lines using RMCE technology, (ii) ALE of selected to target atheromatous lesions for the presence of platelets considered n Engineering Antibodies stable insect cells, and (iii) productivity enhancers supplementation. as relevant biomarkers of atherosclerotic progression. The improved conditions n Engineering Bispecifics allowed for the recovery of highly purified and biologically active scFv fragments ready to be grafted in a site-directed way to nanoparticles for the imaging of 09:05 Expression of Influenza Antigens in Conventional and Non- atherosclerotic plaques. Therapeutics Conventional Eukaryotic Expression Systems n Novel Immunotherapy Strategies Isabelle Legastelois, Ph.D., Research Unit Head, Virology and Expression Systems, 11:45 Tuning the Co-Expression of Multiple Polypeptides to Optimize n Advancing Bispecifics Sanofi Pasteur Assembly of Bispecific Antibodies and Other Formats n Novel Therapies for Cancer The trimeric transmembrane haemagglutinin, the tetrameric transmembrane Giovanni Magistrelli, Head, Protein Engineering, Novimmune SA neuraminidase of influenza virus or Virus Like Particles (VLPs) are very good The inadequate expression of one or several polypeptide components can Analytical candidates to assess expression systems as they are recognized as very significantly affect the assembly and secretion of multi-protein complexes. We challenging to express, particularly if high yields are targeted. It is the reason why found that codon de-optimization - instead of optimization - of an over expressed n Optimisation & Developability we assessed several conventional but also non-conventional expression systems chain can lead to significant increase in the assembly of bispecific antibodies and n Analytical Characterisation to obtain the best expression of these candidates in the perspective to develop overall yield in CHO cells. This approach to tune the ratio of different polypeptides n Aggregates & Particles reagents but also new vaccines. can be applied to optimize different multispecific antibody formats. 09:35 Reaching the High-Hanging Fruit: Expression and Purification 12:15 Enjoy Lunch on Your Own Oncology Optimization Tools for Production of High-Value Drug Discovery Protein n Antibody-Drug Conjugates Targets 13:00 Dessert Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics Dominic Esposito, Ph.D., Director, Protein Expression Laboratory, Frederick National 13:30 End of Optimising Expression Platforms n Novel Therapies for Cancer Laboratory for Cancer Research As part of the NCI RAS Initiative, we are working on a series of complicated targets involved in the MAP kinase activation pathway, and have developed process and Expression technology improvements to increase protein yield, protein quality, and proper n Protein Production Technologies PTMs. We discuss our enhancements to insect and mammalian expression n Optimising Expression systems and their applications to high-level production of other clinically relevant n Purification Technologies proteins, using the RAF kinase protein as a particularly challenging example. 10:05 Genome-Wide Signals Detection for Enhanced Sponsored by Sponsor & Exhibit Opportunities Cell Line Productivity and Stability Pierre-Alain Girod, CSO, Selexis Hotel & Travel Information Stable, high-quality production cell lines secreting optimal levels of recombinant protein require stable integration of the recombinant DNA, elevated gene Registration Information transcription, optimized secretion and metabolic machinery to handle the increased protein loads along with cellular phenotypic stability. Using the extensive genomic Register Online! (SNPs) and FISH-RNA/DNA data we have generated for our host (CHO-M) and manufacturing cell lines, we will describe how we are significantly boosting PEGSummitEurope.com production capabilities and cell line stability of our CHO-M cell line.

A Division of Cambridge Innovation Institute 46 Final Weeks to Register Expression 16-17 November 2017 for the Largest PEGS Europe Ever!

3rd Annual Cover Conference-at-a-Glance Protein Purification Technologies Short Courses Streamlining Processes to Achieve Quality Training Seminars THURSDAY 16 NOVEMBER 15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

Engineering 12:30 Registration ANTIBODY PURIFICATION (CONT.) n Display of Biologics 13:00 Dessert Break in the Exhibit Hall with Poster Viewing 15:50 Streamlining Antibody Purification: A Novel Approach by Caprylic n Engineering Antibodies Acid-Based Impurity Precipitation n Engineering Bispecifics ANTIBODY PURIFICATION Anja Trapp, M.Sc., Scientist, Bioprocessing Technology & Innovation, Rentschler Biopharma SE 13:30 Chairperson’s Opening Remarks Therapeutics Benefits of implementing caprylic acid- (CA-) based precipitation in antibody Christopher H. Gray, Team Leader, Structural Biology, Drug Discovery Program, purification are presented. Combining the common low pH viral inactivation step n Novel Immunotherapy Strategies Cancer Research UK, The Beatson Institute with CA precipitation greatly improves HCP clearance in different mAb processes. n Advancing Bispecifics We show that CA precipitation can be applied as an excellent alternative to a n Novel Therapies for Cancer 13:35 KEYNOTE PRESENTATION: Protein Production Needs for polishing chromatography using case studies. The step constitutes a simple, Therapeutic Antibody Discovery and Development robust and economic step in a mAb purification process resulting in increased Karin Felderer, Ph.D., Associate Director, Protein Production, Protein Sciences purification performance and higher safety of two-column processes. Analytical & CMC, MorphoSys AG n Optimisation & Developability Protein production needs for therapeutic antibody projects are manifold. They 16:20 A Microfluidic Toolbox for Screening and Downstream Process n Analytical Characterisation span a wide range of scales from small scale high-throughput for early in vitro Optimization n Aggregates & Particles characterization up to gram scale productions for in vivo characterization M. Raquel Aires-Barros, Ph.D., Professor, Institute for Bioengineering and and manufacturability assessment. In addition to antibodies and antibody Biosciences (IBB), Bioengineering, Instituto Superior Técnico, Universidade de Oncology fragments, various high quality antigens and tool proteins are required to Lisboa facilitate successful projects. Case studies and strategies will be presented Antibodies and other protein products are biopharmaceuticals of critical n Antibody-Drug Conjugates covering this spectrum of applications. importance that need to be purified in a cost effective and efficient manner. Here, n Advancing Bispecifics a methodology for the rapid screening of antibody extraction conditions using 14:05 Exploration of an Atypical ‘Platform’ mAb and Resolution of Its n Novel Therapies for Cancer a microfluidic channel-based toolbox is presented which can also be used for Non-Ideal Behaviour during Downstream Process Development process development. A first microfluidic structure allows a simple negative- Karolina Les, Ph.D., Scientist II, Purification Process Sciences, Biopharmaceutical pressure driven rapid screening of up to 8 extraction conditions simultaneously, Expression Development, MedImmune, Ltd. while a second microfluidic structure allows the integration of multi-step extraction n Protein Production Technologies Efficient development of monoclonal antibodies (mAbs) is often founded on steps. n Optimising Expression platform-based optimization of processes, allowing timely delivery of scalable and 16:50 End of Day n Purification Technologies robust processes. While existing developability frameworks allow progression of best candidates into development and typically assure a good platform fit, cases of 17:00 Dinner Short Course Registration low platform compliance are unavoidable. The talk will discuss reasons behind an Sponsor & Exhibit Opportunities atypical behaviour of an antibody during purification and its mitigations. The main challenges included severe precipitation during purification and unusually high host 17:30-20:30 Recommended Short Course* Hotel & Travel Information cell protein (HCP) levels observed during early development. SC7: Protein Purification Strategies *Separate registration required, please click here for details Registration Information 14:35 Process Optimisation for Manufacturing of Sponsored by ScFv-Class Antibody with FOLDTEC® Katrin Schweinitzer, Head, Downstream Processing Development, Register Online! BioProcess Development, Wacker Biotech GmbH PEGSummitEurope.com Wacker Biotech will present a case study for development and optimization of a scalable process employing microbial system to produce the scFv-class antibody for commercial application. Using its E. coli-based FOLDTEC® technology, WACKER completely overhauled a process employed by customers to facilitate production on an industrial scale. WACKER’s proprietary refolding technology was able to produce the desired product in enhanced yields and streamline the purification process with achieving higher purity than was hitherto possible. A Division of Cambridge Innovation Institute 47 Final Weeks to Register Expression 16-17 November 2017 for the Largest PEGS Europe Ever!

FRIDAY 17 NOVEMBER of small molecule human therapeutics. There are numerous literature examples Cover of failed clinical drug trials due to a lack of preclinical testing of potential drug 08:00 Registration and Morning Coffee exposure to AO activity. This presentation summarizes the numerous design, Conference-at-a-Glance expression and purification experiments that were undertaken in order to optimize the production of recombinant human AO for deployment in Pfizer’s screening Short Courses PURIFYING MEMBRANE PROTEINS cascade. Training Seminars 08:30 Chairperson’s Remarks Anja Trapp, M.Sc., Scientist, Bioprocessing Technology & Innovation, Rentschler 11:05 Human Heparanase: Lessons Learned from a Self-Destructing Biopharma SE Project Mario Lebendiker, Ph.D., Head, Protein Purification Facility, Wolfson Center for Engineering 08:35 Do We Need to Purify Membrane Proteins? Expression Tricks and Applied Structural Biology, Hebrew University of Jerusalem n Display of Biologics Solid-State NMR Spectroscopy in Native Membranes Our case study describes the challenges encountered in each step of crystallizing n Engineering Antibodies Dirk Linke, Ph.D., Professor, Molecular Microbiology, Biosciences, University of Oslo Human Heparanase (hHep), an endo-beta-D-glucuronidase. We needed to n Engineering Bispecifics In recent work, we have developed E. coli expression strains that lack multiple of overcome irreproducible expression productivity of this “self-destructing” protein in the most abundant outer membrane proteins. This enables us to perform solid- insect cells, followed by optimizing a purification strategy for this non-tagged target Therapeutics state NMR spectroscopy directly on native membranes after overexpression of with conventional chromatography. We then faced batch-to-batch variability in targets in 13C/15N labeling medium. Membrane protein purification becomes crystallization, and finally, an inability to solve collected data from crystals, until we n Novel Immunotherapy Strategies obsolete in this procedure, and the proteins can be studied in their native produced a fusion protein construct with known structure to obtain phases. n Advancing Bispecifics environment without risk of denaturation. 11:35 High-Throughput Knockout of Difficult-to-Remove and n Novel Therapies for Cancer 09:05 The Salipro Lipid Nanoparticle System for Detergent-Free Troublesome CHO Host Cell Proteins to Create a Clean CHO Cell Line Analytical Stabilization of Membrane Proteins Stefan Kol, Ph.D., Protein Biochemist, Novo Nordisk Foundation Center for Jens Frauenfeld, Ph.D., CEO, Salipro Biotech AB Biosustainability, Technical University of Denmark n Optimisation & Developability More than 60% of all current drugs target membrane proteins. However, membrane The CHO Cell Line Engineering department is addressing the need to obtain high n Analytical Characterisation proteins are very unstable, which is a major challenge for the pharmaceutical yields and quality of biopharmaceuticals produced in optimized CHO cells through n Aggregates & Particles industry. Salipro Biotech has developed a novel system to reconstitute membrane genome-scale-based methodologies. Although many host cell protein (HCP) proteins into self-assembling lipid nanoparticles. The Salipro system is applicable impurities are effectively removed in downstream purification processes, a small Oncology for various classes of membrane proteins (channels, receptors, transporters, etc). population of HCPs are particularly challenging. Here, we present our efforts to Salipro nanoparticles stabilize membrane proteins in a lipid environment and allow identify and knock out several CHO HCPs and our characterization of the resulting n Antibody-Drug Conjugates working in detergent-free buffer systems. cell line. Sponsored by n Advancing Bispecifics 12:05 Improve Throughput and Productivity in n Novel Therapies for Cancer 09:35 Membrane Proteins: From Lab-Scale towards Large-Scale Production Small-Scale Affinity Purification of mAbs Expression Julie Bomholt, Ph.D., Head, Downstream Processing and Quality Control, William Barrett, Ph.D., Chromatography, Gore & Associates Downstream Processing, Golgi ApS Protein purification can be a time-consuming process in drug discovery and n Protein Production Technologies By use of the physiologically important trans-membrane protein family of research applications. Utilizing our understanding of fluoropolymer science, we’ve n Optimising Expression aquaporins as model proteins, we developed a S. cerevisiae based expression developed the GORE™ Protein Capture Device with Protein A. This column offers n Purification Technologies system, and identified conditions that allowed us to substantially increase the higher binding capacity at short residence time, enabling faster processing times membrane density of recombinant functional aquaporin. We further developed a and potential for more highly concentrated elution pools. purification scheme that allowed us to isolate high-yield preparations of pure and Sponsor & Exhibit Opportunities 12:35 Problem-Solving Breakout Discussions with a Light Snack in the functional aquaporin. Based on this, we conducted a comparative study of human aquaporins from expression level to functional reconstitution of purified detergent Foyer* Hotel & Travel Information stabilized protein. *See website for more details

Registration Information 10:05 Coffee Break with Poster Viewing 13:35 Session Break EMERGING TECHNOLOGIES Register Online! OVERCOMING PURIFICATION CHALLENGES PEGSummitEurope.com 10:35 Production of Human Aldehyde Oxidase (AO) in Baculovirus- 14:00 Chairperson’s Remarks Infected Insect Cells (BEVS) Jens Frauenfeld, Ph.D., CEO, Salipro Biotech AB Ciarán N. Cronin, Ph.D., Associate Research Fellow, Head, Parallel Protein Production Group, and Group Leader, Gene-to-Structure, Pfizer Global R&D Aldehyde oxidase (AO) is a key enzyme activity to consider during the development

A Division of Cambridge Innovation Institute 48 Final Weeks to Register Expression 16-17 November 2017 for the Largest PEGS Europe Ever!

14:05 Novel Single-Column Simulated Moving-Bed Chromatography for 16:05 Tandem-Tag Vectors for Enhanced Soluble Yield, Expression Cover Quasi-Continuous Purification of Biomolecules Monitoring and Streamlined Purification Conference-at-a-Glance Abimaelle Chiberio, Graduate Student, Chemistry, Science & Technology, University Christopher H. Gray, Team Leader, Structural Biology, Drug Discovery Program, Nova de Lisboa Cancer Research UK, The Beatson Institute Short Courses Our suite of novel, tandem-tagged Escherichia coli vectors offers multiple options 14:35 Parallel Rapid Expression & Purification of Proteins for for increased soluble expression, and highly efficient purification. Dual omoterspr Training Seminars Crystallography (PREPX) allow the simultaneous expression of an MBP-target fusion and a tag cleaving Michael Fairhead, Ph.D., PDRA, Structural Genomics Consortium, University of protease. Similarly, this in vivo cleavage system functions with GFP-target fusions Oxford allowing fluorescent tracking of recombinant expression during culture. Finally, we Engineering Pipelines for high-throughput cloning and small-scale expression and purification have designed a set of tandem-affinity tagged vectors generating protein that can are well established. However, subsequent scale-up and purification often involves be highly purified in a single step. n Display of Biologics only working with a few pipeline hits (usually the easiest to produce) and these are n Engineering Antibodies not always suitable for crystallography. PREPX is a medium-throughput approach 16:35 End of Conference n Engineering Bispecifics to evaluate larger numbers of clones (48 per week), and their suitability for producing diffraction quality crystals. Therapeutics 15:05 Expressed Protein Ligation: A New Paradigm as a Reagent n Novel Immunotherapy Strategies Platform for Preclinical Drug Discovery n Advancing Bispecifics Rosalie Matico, Associate Fellow, Investigator, Protein Cellular and Structural n Novel Therapies for Cancer Sciences, GlaxoSmithKline plc Expressed protein ligation (EPL) utilizes genetically engineered inteins to join two Analytical protein (peptide) fragments via a native peptide bond. Ligation occurs through an intein mediated C-terminal thioester on one protein fragment and an N-terminal n Optimisation & Developability Cys-SH on a second protein or peptide fragment. We developed a reagent n Analytical Characterisation platform by harnessing (EPL) to specifically label proteins at the C-terminus with a n Aggregates & Particles cysteine-lysine dipeptide chemically modified at the lysine with biotin, fluorescein, peglyation, etc., prior to ligation. Oncology IMPROVING PURIFICATION PROCESSES n Antibody-Drug Conjugates n Advancing Bispecifics 15:35 Optimization of Secreted Target Protein Yields by Introduction of n Novel Therapies for Cancer in silico Designed Stabilizing Mutations Svend Kjær, Ph.D., Deputy Head, Structural Biology Science Technology Platform, Expression Francis Crick Institute Protein stability is a fundamental and crucial parameter in a range of applications n Protein Production Technologies from crystallization to biotherapeutics. We present data of how a few stabilizing n Optimising Expression mutations, designed by the PROSS algorithm based on crystal structures and n Purification Technologies multiple sequence alignments, increase the Tm of a misfolding-sensitive secreted protein by 20°C. We present data showing how protein expression in higher Sponsor & Exhibit Opportunities eukaryotic systems is significantly improved by the stabilization.

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A Division of Cambridge Innovation Institute 49 Final Weeks to Register for the Largest PEGS Europe Ever! SPONSOR & EXHIBITOR INFORMATION 2016 ATTENDEE DEMOGRAPHICS

Cover Government Comprehensive sponsorship packages allow you to achieve your objectives before, during, 1% Conference-at-a-Glance Other (Financial, Healthcare Services, Societies) 4% and long after the event. Signing on earlier will allow you to maximize exposure to hard-to- 1% Short Courses reach decision-makers. Training Seminars Academic Presentations — Available within Main Agenda! Looking for additional ways to drive leads to 18% Engineering Showcase your solutions to a guaranteed, targeted audience. your sales team? n Display of Biologics Package includes a 15 or 30-minute podium presentation on CHI’s Lead Generation Programs will help you to obtain Commercial the scientific agenda, exhibit space, branding, full conference (Biotech, n Engineering Antibodies more targeted, quality leads throughout the year. We will registrations, use of the event mailing list and more. Pharma, CRO) n Engineering Bispecifics mine our database of over 1,000,000 life science profes- 76% sionals to your specific needs. We guarantee a minimum of 100 leads per program! Therapeutics Luncheon Presentations Opportunity includes a 30-minute podium presentation Opportunities include: n Novel Immunotherapy Strategies in the main session room. Lunch will be served to all del- • White Papers COMPANY TYPE n Advancing Bispecifics egates in attendance. A limited number of presentations • Webinars n Novel Therapies for Cancer are available for sponsorship and they will sell out quickly. • Custom Market Research Survey Asia 5% Sign on early to secure your talk! • Podcasts Rest of World Analytical 4% n Optimisation & Developability One-on-One Meetings Exhibits are sold as part of n Analytical Characterisation Select your top prospects from the pre-conference sponsorship packages only! n Aggregates & Particles registration list. CHI will reach out to your prospects USA 18% and arrange the meeting for you. A minimum number of Oncology meetings will be guaranteed, depending on your marketing objectives and needs. A very limited number of these View Latest Exhibitor n Antibody-Drug Conjugates packages will be sold. List & Floorplan Europe n Advancing Bispecifics 72% n Novel Therapies for Cancer Invitation-Only Dinners / Hospitality Suites Expression Sponsors will select their top prospects from the conference preregistration listfor an evening of networking at the n Protein Production Technologies hotel or at a choice local venue. CHI will extend invitations, FOR MORE INFORMATION, GEOGRAPHIC LOCATION n Optimising Expression conduct follow-up and confirm attendees. The evening will PLEASE CONTACT: n Purification Technologies be customized to meet with your specific objectives. Professor 7% Companies A-K Sales & Marketing Sponsor & Exhibit Opportunities Additional branding & promotional Jason Gerardi Assistant 11% 6% opportunities include: Senior Manager, Business Development Manager Other Hotel & Travel Information • Hotel Room Keys 781-972-5452 12% 1% • Focus Groups [email protected] Registration Information • Conference Tote Bags • Literature Distribution (Tote Bag Insert or Chair Drop) Companies L-Z • Badge Lanyards Carol Dinerstein Scientist/ Register Online! Executive & • Notebooks Senior Manager, Business Development Technologist PEGSummitEurope.com • Program Guide Advertisement Director 38% 781-972-5471 25% [email protected]

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A Division of Cambridge Innovation Institute 50 Final Weeks to Register for the Largest PEGS Europe Ever! HOTEL & TRAVEL INFORMATION

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Conference-at-a-Glance Conference Venue and Hotel: Discounted Room Rate: Short Courses EPIC SANA Lisboa Hotel €155 SINGLE/€175 DOUBLE Training Seminars Avenida Engenheiro Duarte Pacheco 15 ** includes complimentary breakfast & internet 1070-100 Lisbon, Portugal Engineering Phone: +351-211-597-300 Discounted Cut-off Date: n Display of Biologics 9 October 2017 n Engineering Antibodies Reservations: n Engineering Bispecifics Go to the travel page of PEGSummitEurope.com Therapeutics n Novel Immunotherapy Strategies n Advancing Bispecifics n Novel Therapies for Cancer Top Reasons to stay at the EPIC SANA Lisboa Hotel

Analytical • Breakfast and complimentary internet is included in the room rate. n Optimisation & Developability • Located just minutes from the city’s downtown Baxia, where you can n Analytical Characterisation admire Augusta Street, Russio and Commercio Square (shopping, n Aggregates & Particles galleries & theaters) • 15 minutes from Lisbon’s Portela International Airport Oncology • Minutes from local attractions like Avenida da Liberdade, Praca do n Antibody-Drug Conjugates Comercio (magnificent Square by the River), Estrelas Basilicia, and n Advancing Bispecifics Belem Tower to name a few n Novel Therapies for Cancer • Close to Bairro Alto - one of Lisbon’s Old Quarters with great dining Expression options and site seeing n Protein Production Technologies • The hotel offers Sayanna Wellness, a world-class Spa and 24 hour n Optimising Expression Fitness Centre n Purification Technologies

Sponsor & Exhibit Opportunities Hotel & Travel Information For additional information Registration Information go to the travel page of

A Division of Cambridge Innovation Institute 51 CONFERENCE PRICING Alumni Discount 20% Off Final Weeks to Register Poster Discount €50 Off for the Largest PEGS Europe Ever! SHORT COURSES Commercial Academic, Government, Student* Hospital-affiliated If you are unable to attend but would Cover One short course €625 €375 €125 like to purchase the PEGS Europe CD Two short courses €895 €625 €195 for €600 (plus shipping), please visit Conference-at-a-Glance PEGSummitEurope.com. Massachusetts delivery will include sales tax. Short Courses Monday, 13 November (Morning Short Courses) Thursday, 16 November (Dinner Short Courses) CONFERENCE DISCOUNTS SC1: New Directions in Cancer Immunotherapy SC6: Engineering of Bispecific Antibodies Training Seminars Poster Submission - Discount (€50 Off): SC2: Mutation and Selection Strategies Beyond Affinity Optimisation SC7: Protein Purification Strategies POSTER SPACE IS LIMITED AND IN HIGH DEMAND. SC3: Genomics in the Service of Cancer Immunotherapy SC8: Selection, Screening and Engineering for Affinity Reagents Posters will be accepted on a first-come basis! Engineering Please see website for important details. SC4: Transient Protein Expression: A Key Tool to Enable Rapid Protein Engineering SC9: Protein Aggregation: Mechanism, Characterisation and Consequences Poster abstracts are due by 6 October 2017. Once your n Display of Biologics registration has been fully processed, we will send an n Engineering Antibodies SC5: The Multi-Attribute Method (MAM) for Improving Product and Process Development SC10: New Analytical Approaches & Strategies for Comparability & Biosimilarity email containing a unique link allowing you to submit your poster abstract. If you do not receive your link within n Engineering Bispecifics 5 business days, please contact [email protected]. CONFERENCE PRICING *CHI reserves the right to publish your poster title and abstract in various marketing materials and products. Therapeutics PREMIUM PACKAGE - Best Value (Includes access to all 18 conferences/Training Seminars Monday-Friday, excludes short courses) REGISTER 3 -4th IS FREE: n Novel Immunotherapy Strategies Registration Rate after 6 October and on-site €3199 €1749 €695 Individuals must register for the same conference n Advancing Bispecifics or conference combination and submit completed registration form together for discount to apply. n Novel Therapies for Cancer STANDARD PACKAGE (Includes access to two conferences/Training Seminars, excludes short courses) ALUMNI DISCOUNT: Registration Rate after 6 October and on-site €2849 €1349 €525 CHI appreciates your past participation at PEGS. As a result of the great loyalty you have shown us, we are Analytical pleased to extend to you the exclusive opportunity to n Optimisation & Developability BASIC PACKAGE (Includes access to one conference/Training Seminar, excludes short courses) save an additional 20% off the registration rate. n Analytical Characterisation Registration Rate after 6 October and on-site €2199 €999 €375 GROUP DISCOUNTS: n Aggregates & Particles Special rates are available for multiple attendees from the same organization. For more information on group discounts contact Cheryle Rosenberg, crosenberg@ Monday - Tuesday Wednesday - Thursday (am) Thursday (pm) - Friday healthtech.com, 781-972-5489. *Alumni, Group, Protein Oncology 13 - 14 November 15 - 16 November 16 - 17 November Society or Antibody Society Membership, Twitter, n LinkedIn, Facebook or any other promotional discounts Antibody-Drug Conjugates ENGINEERING 1A: Display of Biologics 1B: Engineering Antibodies 1C: Engineering Bispecifics cannot be combined. Discounts not applicable on Event n Advancing Bispecifics STREAM Short Courses. n Novel Therapies for Cancer THERAPEUTICS 2A: Novel Immunotherapy Strategies 2B: Advancing Bispecifics and Combination 2C: Novel Therapies for Cancer and STREAM Therapy to the Clinic Emerging Targets ADDITIONAL REGISTRATION DETAILS Each registration includes all conference sessions, Expression ANALYTICAL 3A: Optimisation & Developability 3B: Analytical Characterisation of 3C: Protein Aggregates & Particles posters and exhibits, food functions, and access to the n Protein Production Technologies STREAM Biotherapeutics conference proceedings link. Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech n Optimising Expression ONCOLOGY 4A: Engineering Next-Generation 2B: Advancing Bispecifics and Combination 2C: Novel Therapies for Cancer and Institute is pleased to arrange special accommodations n STREAM Antibody-Drug Conjugates Therapy to the Clinic Emerging Targets for attendees with special needs. All requests for such Purification Technologies assistance must be submitted in writing to CHI at least EXPRESSION TS1: Basic Technologies in a Protein 4B: Optimising Expression Platforms 4C: Protein Purification Technologies 30 days prior to the start of the meeting. To view Production Lab our Substitutions/ Cancellations Policy, go to Sponsor & Exhibit Opportunities STREAM www.healthtech.com/regdetails TS2: Introduction to Protein Engineering TS3: Characterisation and Control of Particulates, TS5: Regulatory Requirements across the VIDEO AND/OR AUDIO RECORDING OF Hotel & Travel Information By Cambridge Healthtech Institute From Aggregates to Visible Particles Product Development Lifecycle ANY KIND IS PROHIBITED ONSITE AT ALL CHI EVENTS. Registration Information TS4: Next-Generation Sequencing for TS6: Future Pharmaceutical Biotechnology Antibody Discovery and Engineering – From Antibody Engineering to Gene and How to Register: Recombinant Cell Therapy Register Online! PEGSummitEurope.com PEGSummitEurope.com [email protected] P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

*Pre-doctoral, full-time student. Limited to the first 50 registrants. A Division of Cambridge Innovation Institute