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Short Courses Training Seminars & Engineering Summit Engineering 12 – 16 November 2018 | Lisbon Congress Center | Lisbon, Portugal n Display of Biologics n Engineering n Engineering Bispecifics Plenary Keynotes n Antibody-Drug Conjugates Be part of a growing event - attendance has increased n Advancing Bispecifics Bicycles and Bicycle Drug Conjugates n Novel for Sir Gregory Winter, PhD, FRS, Master, more than 45% since 2015 Analytical Trinity College and Co-Founder and Director, Bicycle Therapeutics Network with 1,000 colleagues at Europe’s leading n Optimisation & Developability n Analytical Characterisation protein engineering event n Aggregates & Particles Paracrine Delivery: Therapeutic Immunotherapy Biomolecules Produced in Situ See unpublished data and case studies from leading n Tumour Microenvironment Andreas G. Plückthun, PhD, Professor researchers from industry & academia n CAR T, TIL & TCR and Director, Department of n Targets & Combinations Biochemistry, University of Zürich Learn from 225 speakers and 150 poster presenters Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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Short Courses MONDAY - TUESDAY WEDNESDAY - THURSDAY THURSDAY - FRIDAY (12 - 13 November) (14 - 15 November) (15 - 16 November) Training Seminars

Engineering ENGINEERING Display of Biologics Engineering Antibodies Engineering Bispecifics n Display of Biologics n Engineering Antibodies n Engineering Bispecifics ONCOLOGY Antibody-Drug Conjugates Advancing Bispecifics Novel Therapies for Cancer Oncology Optimisation & Analytical Characterisation Aggregates & Particles n Antibody-Drug Conjugates ANALYTICAL Developability n Advancing Bispecifics n Novel Therapies for Cancer Agonist Targets & IMMUNOTHERAPY Tumour Microenvironment CAR T, TIL & TCR Therapy Analytical Combinations Plenary Keynote Session n Optimisation & Developability Synthetic & Systems n Analytical Characterisation EXPRESSION Optimising Expression Purification Technologies n Aggregates & Particles Engineering

Immunotherapy ShortDinner Courses* BISPECIFICS Introduction to Bispecifics Advancing Bispecifics Engineering Bispecifics n Tumour Microenvironment n CAR T, TIL & TCR Therapy ShortPre-Conference Courses* n Agonist Targets & Combinations Basic Technologies in a Protein Rational Approaches to Potency and Comparability for Production Lab Biologics Cell and Gene Products Expression Formulation & Delivery n Synthetic & Systems Engineering Introduction to Bispecifics n Optimising Expression By Cambridge Healthtech Institute Next-Generation Sequencing for n Purification Technologies Introduction to Protein Antibody Discovery and Engineering Engineering Bispecifics n Introduction to Bispecifics By Cambridge Healthtech Institute n Advancing Bispecifics n Engineering Bispecifics * Separate registration required for short courses

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Engineering CORPORATE SPONSORS n Display of Biologics n Engineering Antibodies n Engineering Bispecifics Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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Training Seminars 16:15 Moderator’s Opening Remarks Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV Engineering n Display of Biologics n Engineering Antibodies n Engineering Bispecifics

Oncology 16:20 Bicycles and Bicycle Drug Conjugates n Antibody-Drug Conjugates Sir Gregory Winter, PhD, FRS, Master, Trinity College n Advancing Bispecifics and Co-Founder and Director, Bicycle Therapeutics n Novel Therapies for Cancer Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity Analytical with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential n Optimisation & Developability in many indications, including oncology, where Bicycles’ n Analytical Characterisation unique properties have been used to develop Bicycle Drug n Aggregates & Particles Conjugates™ (BDCs), a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is Immunotherapy expected to enter clinical trial in Q1 2018. n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression 17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ n Synthetic & Systems Engineering Andreas G. Plückthun, PhD, Professor and Director, n Optimising Expression Department of Biochemistry, University of Zürich n Purification Technologies Cancer will have to be fought with cocktails of therapeutics Bispecifics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well n Introduction to Bispecifics as cytokines to modify the tumor microenvironment. We have n Advancing Bispecifics recently developed a technology of using non-replicative n Engineering Bispecifics adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune Posters response, as a vehicle for simultaneous delivery of multiple genes of therapeutic , produced and secreted by the Sponsor & Exhibit Opportunities infected cells.

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PEGSummitEurope.com | 4 Final Days SHORT COURSES* * Separate registration required to Register! MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING THURSDAY 15 NOVEMBER | 17:30 - 20:30 | DINNER Cover SC1: Transient Protein Expression: A Key Tool to Enable Rapid SC7: Protein Aggregation: Mechanism, Characterization and Consequences Conference-at-a-Glance Protein Engineering Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Richard Altman, MS, Scientist, Protein Technologies, Amgen Interaction Technologies Center (BITC), University of New Hampshire Short Courses Henry C. Chiou, PhD, Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific Protein aggregation is recognized by regulatory agencies and the biopharmaceutical industry as a Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for key quality attribute of biotherapeutic products. Various aggregates hold the potential for adversely Training Seminars Cancer Research impacting production and patients in a variety of ways. This in-depth workshop reviews the origins and consequences of aggregation in biotherapeutics, and then examines strategies for predicting This short course introduces both the fundamental concepts and technologies needed to establish and quantifying aggregation in biopharmaceuticals. It benefits scientists engaged in development, transient protein production in mammalian cells, which has become an essential tool to enable production, analytical characterization and approval of biotherapeutics and who require a good rapid protein engineering. Transient expression allows for the rapid generation, purification and Engineering working knowledge of protein aggregation. characterization of milligram-to-gram quantities of secreted or intracellular recombinant proteins n Display of Biologics for therapeutic, functional and structural studies. The course combines instruction and case SC8: Selection, Screening and Engineering for Affinity Reagents n studies in an interactive environment. Engineering Antibodies Julia Neugebauer, PhD, Director, MorphoSys AG n Engineering Bispecifics SC2: Making Antibody Libraries in Phage and Yeast Birgit Dreier, PhD, Senior Scientist and Group Leader HT-BSF, Plückthun Lab, University of Zurich Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc. Biologics such as recombinant antibodies and alternative binding scaffolds are routinely used in Oncology In this short course, students will learn about antibody basics, including structure, genetics and a wide variety of applications from basic research to clinical indications. This success has led to the generation of diversity, as well as the creation of naive antibody libraries in the phage and the development of a vast number of different selection, screening and engineering technologies n Antibody-Drug Conjugates for these molecules. This short course will give a comprehensive overview on different display n Advancing Bispecifics yeast display formats. This will include a description of phage and yeast display technologies, the creation of naïve libraries from natural and synthetic sources. The seminar will be fully interactive technologies as well as screening approaches for the selection of specific binders. In addition, n Novel Therapies for Cancer with students provided ample opportunities to discuss technology with instructors. it will discuss engineering strategies including affinity maturation and how to implement these strategies. Classical antibodies and antibody fragments as well as alternative binding scaffolds Analytical SC3: Introduction to the Tumour Microenvironment and Response to Cancer such as will be covered. Immunotherapy n Optimisation & Developability SC9: Optimising Protein Purification Strategies in Advance: Getting Your Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Plan Right n Analytical Characterisation Sciences Unit, University of Southampton David O’Connell, PhD, Lecturer, Biotherapeutics, Biomolecular & Biomedical Science, University n Aggregates & Particles Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Autolus College Dublin The tumour microenvironment (TME) is a complex, dynamic environment in which extracellular This course addresses creating an effective strategy for purifying protein before beginning a matrix (ECM), soluble factors, immune cells, stromal cells and tumour cells interact. Each of Immunotherapy purification project. What are key considerations before you launch an expression campaign? these components is key to the establishment and growth of the tumour, as well as impacting Which host should you select and why (Bacterial/Insect/Mammalian)? We will examine ways to n Tumour Microenvironment tumour cell behaviour and response to treatment. For example, stromal cells such as fibroblasts reduce complexity in your strategy in order to efficiently increase productivity. We will also discuss and macrophages display tumour promoting properties, driving proliferation and survival whilst n CAR T, TIL & TCR Therapy how to establish redundant steps that support and guide protein purification. n Agonist Targets & Combinations propagating an immunosuppressive environment. In this short course, we will discuss the nature of the TME, how the tumour promotes an immunosuppressive environment and what opportunities SC10: Engineering of Bispecific Antibodies this presents for reversing immune suppression to deliver effective immunotherapy. Expression Nicolas Fischer, PhD, Head, Research, Novimmune SA Michela Silacci, PhD, Director, Discovery Research, Covagen AG, part of J&J n Synthetic & Systems Engineering SC4: Mutation and Selection Strategies beyond Affinity Optimisation By attending this interactive workshop, you will learn about the various approaches used for the n Optimising Expression Brian Fennell, PhD, Senior Principal Scientist, BioMedicine Design (BMD), Pfizer Dublin Fred Darmanin Sheehan, PhD, Senior Principal Scientist, Biomedicine Design, Pfizer Dublin engineering of bispecific antibodies and bispecific scaffold-based binding proteins. Different n Purification Technologies technologies will be compared, and examples for applications of bispecific antibodies in drug This course will begin with an introduction to the multiple display technology platforms, development will be presented with a focus on candidates that are currently being evaluated mutagenesis strategies and library generation options that exist to enable antibody optimization. in clinical trials. Opportunities and challenges as well as current trends in the field of bispecific Bispecifics In the simplest application, generated libraries can be selected for improved binding. antibodies will be discussed. n However, increasingly these strategies are being used for more complex applications from Introduction to Bispecifics humanization to ortholog cross-reactivity, stability, solubility and specificity optimizations. *Separate registration required. Click here for details. n Advancing Bispecifics This workshop will use case studies to help attendees navigate the complex workflows and n Engineering Bispecifics technological options available to ensure success. SC5: Surfactants in Biotherapeutics: Can’t Live with Them, Can’t Live Posters without Them Atanas Koulov, PhD, Head, Drug Product Analytical Development and Quality Control, Drug Product Sponsor & Exhibit Opportunities Services, Lonza Pharma and Biotech Hanns-Christian Mahler, PhD, Head, Drug Product Services, Lonza Pharma and Biotech Venue & Hotel Information Satish Singh, PhD, Head, Drug Product Process Development, Drug Product Services, Lonza Pharma and Biotech Registration Information Surfactants are excipients critical to the stability of most biopharmaceutical parenteral formulations. They stabilize proteins in solutions by mitigating potential adsorption and interfacial stress-induced aggregation or precipitation encountered during many stages of production, shipment and use. The most commonly used surfactants are the non-ionic excipients, Polysorbate 20 and 80. However, the PEGSummitEurope.com use of these surfactants can also lead to a number of liabilities related to stability (of the surfactant and of the active protein) as well as potential for pseudoallergenic reactions. Regulatory authorities are therefore also paying increasing attention to this critical excipient. This workshop will provide a complete perspective on the use and control of polysorbates in biotherapeutic products. PEGSummitEurope.com | 5 Final Days 12-16 November 2018 to Register! By Cambridge Healthtech Institute

Cover Cambridge Healthtech Institute Training Seminars offer real-life case studies, WEDNESDAY 14 NOVEMBER AND THURSDAY 15 NOVEMBER Conference-at-a-Glance problems encountered and solutions applied, along with extensive coverage DAY 1 of the academic theory and background. Each training seminar offers a mix of 08:30 - 17:45 Training Seminars in Session Short Courses formal lecture and interactive discussions and activities to maximize the learning 12:45 Lunch Provided experience. These training seminars are led by experienced instructors who 17:45 - 18:45 Networking Reception 18:45 - 19:45 Problem Solving Breakout Discussions Training Seminars will focus on content applicable to your current research and provide important guidance for those new to their fields. DAY 2 08:30 - 12:45 Training Seminars in Session Engineering MONDAY 12 NOVEMBER AND TUESDAY 13 NOVEMBER Refreshments breaks and exhibit hall viewing hours also provided. n Display of Biologics DAY 1 TS6B: Rational Approaches to Biologics Formulation & Delivery 13:30 -18:20 Training Seminars in Session This course will give participants an understanding of the basic principles of biologics n Engineering Antibodies 18:20 - 19:30 Welcome Reception n Engineering Bispecifics formulation development and achieving long term product stability. Participants will gain an DAY 2 understanding of biochemical and biophysical properties of proteins and peptides, and how 08:30 - 18:30 Training Seminars in Session excipients and other strategies can be used to mitigate degradation. Focus will be on maximizing Oncology 12:45 Lunch Provided efficiency while maintaining regulatory compliance. Following which, we will discuss more n Antibody-Drug Conjugates Refreshment breaks and exhibit hall viewing hours also provided. complex formulation development topics and strategies for compatibility studies. Instructor: n Advancing Bispecifics TS6A: Basic Technologies in a Protein Production Lab n Christina Vessely, PhD, Senior Consultant, CMC, Analytical and Formulation Development, Novel Therapies for Cancer This seminar is designed to introduce basic technologies, strategies and considerations in Biologics Consulting recombinant protein production in E. coli, insect and mammalian cells for multiple research and Analytical development applications. The seminar supplies a basic toolbox for management of multiple and TS7B: Next-Generation Sequencing for Antibody Discovery and Engineering diverse projects. n Part 1 of the training introduces antibody repertoires, exploring genetic background, generation Optimisation & Developability Instructors: of diversity, sequencing technologies and the computational tools available for analysis of n Analytical Characterisation Tsafi Danieli, PhD, Director, BioGiv Excubator & Head, Protein Expression Facility, The Hebrew antibody repertoire NGS data. Part 2 will focus on preprocessing and analysis of data, elucidating n Aggregates & Particles University of Jerusalem; Mario Lebendiker, PhD, Head, Protein Purification Facility, The Hebrew each step using the programming language R using examples from existing bioinformatics University of Jerusalem pipelines. Repertoire analysis content will provide statistical quantification and visualization of Immunotherapy Panelists: high-dimensional data. The course will be fully interactive with case studies. Richard Altman, MS, Scientist, Protein Technologies, Amgen; Nicola Burgess-Brown, PhD, Instructors: n Tumour Microenvironment Principal Investigator, Structural Genomics Consortium (SGC), University of Oxford; Dominic Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich, n CAR T, TIL & TCR Therapy Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Switzerland; Simon Friedensohn, MSc, Research Assistant, Biosystems Science and Engineering, n Agonist Targets & Combinations Cancer Research; Bjørn Voldborg, MSc, Director, The Novo Nordisk Foundation Center for ETH Zurich, Switzerland Biosustainability, Technical University of Denmark; Jonathan Zmuda, PhD, Director, Cell Biology, Thermo Fisher Scientific Expression THURSDAY 15 NOVEMBER AND FRIDAY 16 NOVEMBER n Synthetic & Systems Engineering TS7A: Introduction to Bispecifics: History, Engineering, and Application DAY 1 n Optimising Expression Intro to Bispecifics will be organized as an informative and practical guide to get up to speed on 14:00 - 17:00 Training Seminars in Session critical aspects of bispecific antibody therapeutics. Topics will include historical successes, failures, n Purification Technologies and lessons learned. Specific practical instruction will span mechanisms of action, engineering, DAY 2 developability, regulatory considerations, and translational guidelines. Perspectives on ideal 08:30 - 15:35 Training Seminars in Session Bispecifics implementation of bispecifics as targeted and immunomodulatory approaches will be discussed. 12:35 Lunch Provided n Introduction to Bispecifics Instructor: TS6C: Potency and Comparability for Cell and Gene Products G. Jonah Rainey, PhD, CEO, Oriole Biotech n Advancing Bispecifics Extending potency assay concepts to cell, gene and tissue products is more challenging and often the n Engineering Bispecifics TS8A: Introduction to Protein Engineering most difficult aspect of characterising these products. Whenever changes are made, it is necessary to confirm they do not adversely impact the quality and therefore safety and efficacy of the product; CHI’s Introduction to Protein Engineering training seminar offers a comprehensive tutorial in the this requires data beyond meeting current specifications. This training seminar will discuss the concepts, strategies and tools of protein engineering – and explains the role of this discipline in implementation and use of tools to enable characterisation, comparability and process development. Posters the progression of biotherapeutic research and development. The class is directed at scientists Instructor: new to the industry or working in support roles, academic scientists and career protein scientists Sponsor & Exhibit Opportunities wanting a detailed update on the current state of the field. Christopher A. Bravery, PhD, Consulting Regulatory Scientist & Director, Advbiols Instructor: Venue & Hotel Information David Bramhill, PhD, Founder, Bramhill Biological Consulting, LLC and Research Corporation Technologies Registration Information

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PEGSummitEurope.com | 6 Final Days Engineering 12-13 November 2018 to Register! 5th Annual Cover Display of Biologics Conference-at-a-Glance Empowering Novel Therapies Short Courses

Training Seminars Recommended Short Course* a pair of serine protease inhibitors from a library, in vitro and in vivo characterization and creation of a dual inhibitory bispecific antibody. Finally, we SC2: Making Antibody Libraries in Phage and Yeast will review alternate bispecific antibody formats, challenges and applications. *Separate registration required. Click here for details. Engineering 15:15 Further Advancement for Human Ab Discovery n Display of Biologics MONDAY 12 NOVEMBER Vera Molkenthin, PhD, Chief Scientist, AbCheck n Engineering Antibodies AbCheck has developed Mass Humanization to generate humanized libraries. n Engineering Bispecifics 12:00 Conference Registration This approach utilizes batch cloning of CDR3 immune repertoires from immunized rabbits into selected human frameworks containing specifically diversified CDR1 Oncology NOVEL TOOLS FOR TARGET DISCOVERY and CDR2 regions. For selecting high affinity binders from the resulting, highly n Antibody-Drug Conjugates diverse library, AbCheck routinely applies Phage or Yeast Display under various n Advancing Bispecifics 13:30 Organizer’s Welcome conditions. In this talk, AbCheck will present new technological developments n Novel Therapies for Cancer Christina Lingham, Executive Director, Conferences and Fellow, Cambridge regarding its human antibody discovery and optimization platform. Healthtech Institute 15:45 Networking Refreshment Break Analytical 13:35 Chairperson’s Opening Remarks n Optimisation & Developability Ana Barbas, PhD, Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer n Analytical Characterisation Portugal SA PLENARY KEYNOTE SESSION n Aggregates & Particles 16:15 Moderator’s Opening Remarks 13:45 Yeast Surface Display Platform for Rapid Discovery of Janine Schuurman, PhD, Corporate Vice President, Research & Immunotherapy Conformationally Selective Nanobodies Innovation, Genmab BV n Tumour Microenvironment Andrew C. Kruse, PhD, Associate Professor, Department of Biological Chemistry n CAR T, TIL & TCR Therapy and Molecular Pharmacology, Harvard Medical School 16:20 Bicycles and Bicycle Drug Conjugates n Agonist Targets & Combinations G protein-coupled receptors (GPCRs) are the largest single class of Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co- transmembrane receptors in humans, and include important drug targets for the Founder and Director, Bicycle Therapeutics Expression treatment of a broad range of diseases. We developed a synthetic VHH antibody Bicycles® are a novel therapeutic class of constrained bicyclic fragment library displayed on yeast, which allows rapid and efficient isolation peptides that combine antibody-like affinity and selectivity with small n Synthetic & Systems Engineering of antibody fragments that can bind and modulate GPCR signaling. These are molecule-like tissue penetration, tunable exposure and chemical synthesis. n Optimising Expression powerful tools to investigate GPCR structure, function, and biology. Similar They have potential in many indications, including oncology, where Bicycles’ n Purification Technologies principles can be applied to identify conventional antibodies that can serve as unique properties have been used to develop Bicycle Drug Conjugates™ surrogate , antagonists, and allosteric modulators of GPCR signaling. (BDCs), a novel toxin delivery platform which greatly improves toxin loading Bispecifics into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018. 14:15 Back to the Future: Bacteriophages as Promising n Introduction to Bispecifics n Advancing Bispecifics Therapeutic Tools 17:20 Paracrine Delivery: Therapeutic Biomolecules n Engineering Bispecifics Pilar Domingo-Calap, PhD, Postdoctoral Researcher, Department of Genetics, Produced in Situ Institute for Integrative Systems Biology, University of Valencia Andreas G. Plückthun, PhD, Professor and Director, Department of The recent emergence of multi-drug-resistant bacteria needs for alternative Biochemistry, University of Zürich Posters therapies, and bacteriophages are potential antibacterial agents. In addition, Cancer will have to be fought with cocktails of therapeutics acting Sponsor & Exhibit Opportunities bacteriophages can be used as promising tools in engineering genetics, mainly locally, which may have to include therapeutic antibodies against thanks to phage display. Drug discovery, vaccine development, antibody receptors, checkpoint inhibitors, as well as cytokines to modify the tumor Venue & Hotel Information engineering, mapping, gene/drug delivery or enzyme technology are microenvironment. We have recently developed a technology of using non- examples of the potential use of phages in clinics. Thus, phages can be used in replicative adenovirus carrying no viral genes, engineered to target desired Registration Information prevention, diagnosis and as treatment of specific diseases. cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced 14:45 Phage Display as a Tool for Bispecific Antibody Generation and secreted by the infected cells. Andrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer PEGSummitEurope.com Ingelheim Pharmaceuticals, Inc. 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing Bispecific antibodies have become an important class of antibody drugs with application in a variety of therapeutic areas. Here, we will discuss identification of 19:30 End of Day PEGSummitEurope.com | 7 Final Days Engineering 12-13 November 2018 to Register! TUESDAY 13 NOVEMBER 11:15 Discovery of a Cryptic Peptide Binding Site on PCSK9 and Design Cover of Antagonists 07:45 Registration and Morning Coffee Yingnan Zhang, PhD, Senior Scientific Manager, Early Discovery Biochemistry, Conference-at-a-Glance Genentech EMPOWERING NOVEL THERAPIES PCSK9 is a negative regulator of hepatic LDLR. Discovery of small molecule Short Courses therapeutics is hampered by the relatively flat EGF(A) binding site on PCSK9. We 08:30 Chairperson’s Remarks discovered that P’-helix of PCSK9 is flexible to reveal an N-terminal groove adjacent Training Seminars Kerry Chester, PhD, Professor, Molecular Medicine, University College London to EGF(A) binding site. Peptides accessing the groove were discovered from a Cancer Institute phage displayed anchor-peptide-directed library and were further engineered into antagonists, which encroach on the EGF(A) binding site and inhibit LDLR binding. Engineering 08:35 Virus-Like Particle Display of HER2 Induces Potent Anti-Cancer n Display of Biologics Responses 11:45 Microfluidics and Genomics for Polyclonal and Monoclonal n Engineering Antibodies Arianna Palladini, PhD, Department of Experimental Diagnostic and Specialty Antibody Drugs for Infectious Disease n Engineering Bispecifics Medicine (DIMES), University of Bologna David S. Johnson, PhD, Founder and CEO, GigaGen, Inc. Susan Thrane, MSc, PhD, Postdoc, Institute for and Microbiology, Human B cell repertoires encode a diversity of antibodies with high potential Oncology Centre for Medical Parasitology, Copenhagen University as therapeutics. Because of technical challenges, commercial groups do not n Antibody-Drug Conjugates therapy improves management of HER2-driven mammary typically make use of human B cell repertoires to identify candidates for antibody n Advancing Bispecifics carcinoma, but its utility is limited. Active vaccination represents a promising therapeutics. We have developed a suite of novel technologies to capture and alternative. Using a novel virus-like particle platform, we developed an active n Novel Therapies for Cancer express highly diverse, natively paired antibody libraries from human B cell vaccine with a high-density display of HER2. Vaccine induced anti-HER2 repertoires. We are mining these libraries for efficacious monoclonal antibodies Analytical autoantibodies were able to prevent mammary carcinoma onset in transgenic for infectious disease. We are also using the repertoires to manufacture mice and inhibit HER2-positive tumor growth in wild-type mice. This vaccine recombinant hyperimmune polyclonal gammaglobulin drug candidates. n Optimisation & Developability represents a cost-effective treatment for HER2-positive cancer. n Analytical Characterisation 12:15 Sponsored Presentation (Opportunity Available) n Aggregates & Particles 09:05 Drug Candidates Selected against Therapeutic Targets with Innovative Formats and Modes of Action 12:30 Screening Smarter to Derive Data Driven Decisions Sponsored by Immunotherapy Arne Skerra, PhD, Professor & Chair, Technical University of Munich Faster Sarah Payne, PhD, Product Manager, Marketing, TTP Labtech n Tumour Microenvironment Anticalin proteins are an emerging class of clinical stage biopharmaceuticals with n CAR T, TIL & TCR Therapy high potential as an alternative to antibodies. can be selected using There’s a smart way to increase the pace of therapeutic antibody and vaccine n Agonist Targets & Combinations phage display and bacterial surface display techniques against a wide range of discovery. Derive data driven decisions faster with no-wash, cell, or bead-based medically relevant targets, from small molecules to peptides and proteins. Their immunoassay screening workflows that can be multiplexed to combine hit Expression mode of action comprises growth factor antagonists, receptor agonists and small identification with selectivity, species cross-reactivity, viability, infectivity, or titer molecule scavengers/antidotes. Moreover, Anticalins allow molecular formatting for accelerated decision making. n Synthetic & Systems Engineering as bi- and even multispecific fusion proteins, also in combination with antibodies n Optimising Expression that provide a second specificity. 12:45 The Journey to “the” Antibody: Accessing a Sponsored by n Purification Technologies Versatile Toolbox 09:35 Direct Functional Screening for Antibody-Drug Conjugates Using Maria González-Pajuelo, PhD, CSO, FairJourney Biologics, S.A. Bispecifics Transpo-mAb Mammalian Cell Display To maximize the possibility to select “the” antibody, at FJB we have taken antibody n Introduction to Bispecifics Roger R. Beerli, PhD, CSO, NBE-Therapeutics AG discovery to an unprecedented level by creating a versatile toolbox that allows the n Advancing Bispecifics Transpo-mAb is a novel and highly efficient non-viral antibody discovery and selection by phage display of antibody fragments of different species from large n Engineering Bispecifics engineering platform, allowing for the efficient display of full-length antibodies on naïve and immune repertoires. Ultimately these fragments can be engineered and the surface of B lymphocytes. Due to a built-in switch between surface and secreted converted to mono- and bi-specific formats that are produced in CHO cells. expression, functional screening can be seamlessly integrated into the antibody Sponsored by Posters discovery workflow. A case study showcasing the direct identification of fully human 13:15 Luncheon Presentation: Accelerate your Antibody mAbs suitable as backbones of antibody-drug conjugates will be presented. Discovery and Cell Line Development Workflows with Sponsor & Exhibit Opportunities Cyto-Mine® 10:05 Problem-Solving Breakout Discussions* Venue & Hotel Information Xin Liu, PhD, Principal Scientist, Biology, Sphere Fluidics *See website for details. Cyto-Mine® is the world’s first fully integrated platform for high-throughput single Registration Information cell analysis based on microfluidic picodroplet technologies. By encapsulating 10:30 Coffee Break in the Exhibit Hall with Poster Viewing single cells in picolitre volume droplets, Cyto-Mine® enables the rapid analysis, sorting and dispensing of single cells into individual wells of microtitre plates, PEGSummitEurope.com NOVEL USES OF DISPLAY TECHNOLOGIES reducing both time and costs required compared to traditional approaches. In this talk, we will introduce the key functionalities of Cyto-Mine® and its applications for Chairperson antibody discovery and cell line development. Saravanan Rajan, PhD, Scientist II, Antibody Discovery & Protein Engineering, MedImmune PEGSummitEurope.com | 8 Final Days Engineering 12-13 November 2018 to Register! 13:45 Dessert Break in the Exhibit Hall with Poster Viewing 16:20 Refreshment Break in the Exhibit Hall with Poster Viewing Cover COMPLEX SELECTIONS AND LIBRARIES 17:00 KEYNOTE PRESENTATION: From Systems Biology to Conference-at-a-Glance Systems Biologics 14:15 Chairperson’s Remarks Short Courses Sachdev Sidhu, PhD, Professor, Molecular Genetics, The Donnelly Centre, Gregory A. Weiss, PhD, Professor, Chemistry, Molecular Biology & Biochemistry, University of Toronto University of California, Irvine Training Seminars We have established a platform to combine large-scale systems biology approaches with the discovery and development of new antibody drugs, and to develop efficient, systems-scale strategies to target intracellular signaling Engineering 14:20 KEYNOTE PRESENTATION: Single Cell Selections of networks at the protein level with ubiquitin variants and other scaffolds. This Recombinant Antibodies Binding to Circulating Tumor Cells efficient pipeline connects basic research to translational science in a new n Display of Biologics Peter Kristensen, PhD, Associate Professor, Department of Chemistry and model for drug development, which we have termed “Systems Biologics”. n Engineering Antibodies Bioscience, Aalborg University n Engineering Bispecifics Metastatic cancer is closely linked to circulating tumor cells. The mechanisms behind the dissemination of cancer through these metastatic THERAPEUTIC APPROACHES TO AUTOIMMUNE DISEASE Oncology seeds however remain incompletely understood. To reveal novel biomarkers, AND BEYOND n Antibody-Drug Conjugates and gain a better understanding of the underlying mechanisms of cancer n Advancing Bispecifics metastasis, we have used an advanced single cell selection on circulating Chairperson n Novel Therapies for Cancer tumor cells from patients diagnosed with metastatic colorectal cancer. In the Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William presentation, the potential of single cell selection of recombinant antibodies Harvey Research Institute, Queen Mary University of London will be discussed. Analytical 17:30 Novel Therapeutics for Glycoantigens – Their Role in the n Optimisation & Developability 14:50 Dual Display: Phage Selection Driven by Co-Engagement of Two Modulation of Immune Responses to Pathogens and Cancer n Analytical Characterisation Targets Paula, Videira, PhD, Assistant Professor, The Faculty of Sciences and Technology, n Aggregates & Particles Oliver Hartley, PhD, Associate Professor, Department of Pathology and Immunology, The New University of Lisbon Faculty of Medicine, University of Geneva 18:00 Discovering Antibodies against Challenging and Immunotherapy This presentation will describe the design and preliminary evaluation of a new n Tumour Microenvironment phage display approach enabling compatible pairs of antibody fragments to be co- Challenging n CAR T, TIL & TCR Therapy selected based on co-engagement of their respective targets. Phagemids encoding Ruud de Wildt, PhD, Director, Head of Lead Discovery, Biopharm, GlaxoSmithKline n Agonist Targets & Combinations a first scFv fused to phage g3p protein via a first leucine zipper are rescued in Raising antibodies to complex antigens or neo-epitopes is a considerable bacteria expressing a second scFv fused to a complementary leucine zipper, which challenge. This talk will discuss the progress with the isolation of antibodies Expression is incorporated into phage during assembly. for a number of projects in the autoimmune disease area using GSK’s Antibody platforms. Innovative design and selection approaches will be discussed, including n Synthetic & Systems Engineering 15:20 Phage Display Selection of Chemically Cyclized Peptides for the isolating antibodies against complex targets such as GPCRs and methods that n Optimising Expression Development of Therapeutics allow the isolation of antibodies against antigens that are unstable or short-lived. n Purification Technologies Christian Heinis, PhD, Professor, Laboratory of Therapeutic Peptides and Proteins, Development of CAR T therapy for non-oncology. Ecole Polytechnique Federal de Lausanne (EPFL) Bispecifics 18:30 End of Display of Biologics My laboratory is engaged in the discovery and development of cyclic peptides n Introduction to Bispecifics for therapeutic application. A major focus is the generation of ligands based on n Advancing Bispecifics bicyclic peptides by phage display. In my talk, I will present new chemical reactions n Engineering Bispecifics that we have applied to generate structurally highly diverse cyclic peptide libraries, and I will show recent data on the therapeutic activity of bicyclic peptides in vivo. Posters 15:50 Validation of Llamda, Isogenica’s Humanized Sponsored by Sponsor & Exhibit Opportunities Single Domain Antibody Library Guy Hermans, PhD, CSO, Isogenica Ltd. Venue & Hotel Information We have previously discussed the design and validation of llamdATM, Isogenica’s fully synthetic camelid single domain antibody library. Here, we will disclose novel Registration Information data on the design and validation of a humanized variant of the library. Examples will be provided on how this library, combined with our CIS Display enabled high throughput screening method, can generate high affinity lead panels in weeks PEGSummitEurope.com rather than months.

PEGSummitEurope.com | 9 Final Days Engineering 14-15 November 2018 to Register! 3rd Annual Cover Engineering Antibodies Conference-at-a-Glance Designing Next-Gen Molecules Short Courses Sponsored by Training Seminars WEDNESDAY 14 NOVEMBER 10:05 CRISPR Meditated Targeted Genome Editing & Extending the Reach of Transient Expression using Scalable 07:45 Registration and Morning Coffee Electroporation Technology Engineering Christopher Mann, PhD, Director, Field Applications Scientist Team, MaxCyte n Display of Biologics ANTIBODIES AGAINST INTRACELLULAR AND The way that potential biotherapeutics such as antibodies are designed, n Engineering Antibodies CHALLENGING TARGETS engineered and manufactured continues to evolve at molecular, cellular and n Engineering Bispecifics process levels. Here we present case studies to highlight how genome editing 08:30 Chairperson’s Remarks and novel therapeutic design are being combined with process optimization and Oncology Ulrich Brinkmann, PhD, Expert Scientist, Molecular Engineering, Roche scalability to enabling production of novel therapeutic formats while maintaining pressure to reduce timelines and cost. n Antibody-Drug Conjugates 08:35 KEYNOTE PRESENTATION: Grp 94, an Intracellular Target n Advancing Bispecifics 10:35 Coffee Break in the Exhibit Hall with Poster Viewing of Antibody-Based Immunotherapy of Malignant Diseases – n Novel Therapies for Cancer Opportunities and Challenges STRATEGIES TO IMPROVE TARGETING, BINDING AND Analytical Soldano Ferrone, MD, PhD, Professor, Surgery, Massachusetts General Hospital, Harvard Medical School BIOACTIVITY OF MOLECULES n Optimisation & Developability The scFv W9 has been isolated from a phage display human antibody library. n Analytical Characterisation This antibody has the unique specificity to recognize an extracellular epitope 11:15 Targeting the Matrix Metalloproteinase (MMP)-14/MMP-2/ n Aggregates & Particles of the heat shock protein Grp94. The characteristics and functional properties Integrin αvβ3 Axis with Multispecific N-TIMP2-Based Antagonists for of this antibody will be described. In addition, the obstacles to the clinical Cancer Therapy Immunotherapy applications of this and the strategies to overcome them will be discussed. Niv Papo, PhD, Group Leader, Assistant Professor, Biotechnology Engineering, Ben- n Tumour Microenvironment Gurion University n CAR T, TIL & TCR Therapy 09:05 Engineering to Target Intractable Intracellular Cancer The MMP-14/MMP-2/integrin αvβ3 axis thus constitutes a putative target for n Agonist Targets & Combinations Targets therapeutic interventions, but inhibitors that target this axis remain to be developed. Yvonne McGrath, PhD, CSO, Complix Based on screening of a N-TIMP2 mutant library, we generated efficient protein Expression Alphabodies comprise a triple helical protein scaffold that can be engineered to monomers and heterodimer antagonists that contain monovalent and bivalent binding bind target proteins with high specificity and affinity. Further modifications allow epitopes to MMP-14 and integrin αvβ3. These results enabled us to investigate the n Synthetic & Systems Engineering these biologics to traverse the cell membrane and inhibit disease-associated individual roles of the three signaling molecules in various malignant processes. n Optimising Expression intracellular targets. A panel of these Alphabodies has been engineered to bind n Purification Technologies and inhibit important oncology intracellular targets hitherto considered intractable 11:45 Multiple Mechanism of Blocking by Antibodies with conventional small molecules. Functional assessment of a selection of these Fernando Garces, PhD, Senior Scientist, Therapeutic Discovery, Amgen Bispecifics Alphabodies will be presented. Antibodies can be generated and selected to block the binding of a protein n Introduction to Bispecifics receptor to its protein ligand. In such cases, the set of molecules generated usually n Advancing Bispecifics 09:35 Generating Potent and Selective Inhibitors of Kv1.3 Ion Channel show low sequence diversity and a common inhibition mechanism. Here we n Engineering Bispecifics by Fusing Venom Derived Mini Proteins into Peripheral CDR Loops of present a case study, where we have structurally characterized multiple antibodies, Antibodies with high sequence diversity that recognize a protein receptor and block protein/ ligand binding via several inhibition mechanisms. Posters Aneesh Karatt-Vellatt, PhD, Group Leader, Antibody and Protein Engineering, IONTAS Ltd. 12:15 The Molecular Landscape of the Immune Response following Sponsor & Exhibit Opportunities Pathogenic TEM cells drive many autoimmune disorders and are uniquely Treatment with Biologics dependent on the Kv1.3 channel. A number of venom derived -rich mini- Venue & Hotel Information protein inhibitors of Kv1.3 are being developed as potential drug candidates, but Yariv Wine, PhD, Assistant Professor, School of Molecular Cell Biology and can suffer from manufacturing difficulties, short half-lives and a lack of specificity. Biotechnology, Tel Aviv University Registration Information Using proprietary KnotBody technology, IONTAS has developed a panel of potent The mechanisms that lead to the generation of ADAs and their molecular and selective Kv1.3 inhibitors that can be further developed as long acting composition are unknown. We developed a new immunoassay to determine ADA immunomodulators for the treatment of autoimmune disorders. level and their neutralizing capacity. We found that therapeutic mAb infusion PEGSummitEurope.com mounts a vaccine boost like response reflected in a rapid rise of lymphocytes post-infusion. B Cells were isolated and their repertoire features were determined

PEGSummitEurope.com | 10 Final Days Engineering 14-15 November 2018 to Register! by NGS. Collectively we found: i) an increase in lambda/kappa antibody light 15:05 Multi-Specific, Multi-Valent and Bi-Paratopic Nanobodies: Cover chain ratio in the neutralizing ADA compartment; ii) an increase in ADA clonal Progress toward the Clinic polarization post-infusion. Carlo Boutton, PhD, Director, Technology & Information Management, Ablynx NV Conference-at-a-Glance Sponsored by 12:45 An Integrated Approach to Managing Small Nanobodies with their modular design are a perfect starting point for Immunogenicity Risk and Optimum Protein Design generating multivalent and multispecific therapeutics in a wide range of human Short Courses diseases. The formatting flexibility of the platform allows the development of the Jeremy Fry, DPhil, Director, Sales, ProImmune ® Training Seminars most optimal drug formats. The development of Nanobodies and their progress Integrated platforms can be used to mitigate immunogenicity risk and characterize towards the clinic will be shown by a number of examples. immune responses during the drug design and development stages. ProImmune offers mutational activity mapping for optimal protein design, DC-T/ 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing Engineering proliferation assays for biologic lead selection/optimization, a Mass Spectrometry n Display of Biologics assay for characterization of antigen presentation; HLA-peptide binding assays to 16:15 V565 Is an Orally-Administered, Protease-Resistant, Anti-TNF n Engineering Antibodies characterize individual epitopes & undiluted whole blood cytokine storm assays. Domain Antibody for the Treatment of Inflammatory Bowel Disease n Engineering Bispecifics Kevin Roberts, PhD, Senior Scientist, VHsquared Ltd. 13:15 Luncheon Presentation I: Build Better Biologics with Sponsored by V565 is an anti-TNF domain antibody for oral administration in IBD patients, Machine Learning and Synbio Oncology engineered to resist intestinal proteases. Oral dosing of V565, formulated in Claes Gustafsson, Co-Founder and CCO, ATUM (formerly DNA2.0) n Antibody-Drug Conjugates enteric-coated minitablets, resulted in micromolar levels of active V565 in the n Advancing Bispecifics This presentation will showcase how ATUM combines recent developments in ileal fluid of volunteers fitted with ileostomy bags and in the faeces of Crohn’s genome engineering, automation, big data and product analytics to increase n Novel Therapies for Cancer disease patients. Oral administration to five ulcerative colitis patients for 6 to 7 efficiency of engineering and developability of biologics and cell lines. Cell days resulted in V565 localisation to the lamina propria and inhibition of mucosal ® Analytical lines generated using the LeapIn transposase combined with optimized vector inflammatory processes. constructs, proprietary codon optimization and QSAR-based protein engineering n Optimisation & Developability allow for an information rich and efficient optimization of mAbs, bispecifics, CAR-T 16:45 Development of mRNA-Encoded Bispecific Antibodies Targeting n Analytical Characterisation molecules, and the increasingly complex biologics approaching the market place. Solid Tumors n Aggregates & Particles Hayat Bähr-Mahmud, PhD, Deputy Head, Bispecific Antibodies, BioNTech 13:45 Luncheon Presentation II: Overcoming Tolerance by Deep Mining Successful application of many T cell-engaging bispecific antibodies is hindered Immunotherapy of Natural Immune Repertoires by manufacturing challenges and short serum half-life. We circumvented these n Tumour Microenvironment Veronique Lecault, PhD, Co-Founder, AbCellera limitations by treating mice with in vitro-transcribed (IVT) pharmacologically n CAR T, TIL & TCR Therapy Antibodies from natural immune responses are widely regarded as superior to optimized and nucleoside-modified mRNA encoding the antibody. We achieved n Agonist Targets & Combinations those generated by display technologies; however, immune tolerance poses sustained endogenous synthesis of the antibody, which eliminated advanced a serious challenge for targets with high inter-species homology. Insoluble tumors as effectively as the corresponding purified bispecific antibody. Dueo t Expression and poorly immunogenic targets such as membrane proteins exacerbate this the fast manufacturing process of pharmaceutical mRNA, the RiboMAB approach challenge. We show how AbCellera’s ultra-deep screening technology overcomes could accelerate the clinical development of novel bispecific antibodies. n Synthetic & Systems Engineering these challenges, producing hundreds of diverse rodent antibodies against targets n Optimising Expression with 100% rodent-human homology, including G protein-coupled receptors. 17:15 Development of Highly Potent T Cell Receptor Bispecifics n Purification Technologies Targeting Tumor-Specific HLA Ligands 14:15 Session Break Bispecifics Sebastian Bunk, PhD, Director, Immunology, Immatics Biotechnologies GmbH T cell receptor (TCR)-based immunotherapy has emerged as a promising treatment n Introduction to Bispecifics NOVEL FORMATS AND ALTERNATIVE PLATFORMS modality for malignant diseases. Immatic’s bispecific TCR molecules utilize n Advancing Bispecifics 14:30 Chairperson’s Remarks affinity maturated and selective TCRs for targeting of tumor-specific, human n Engineering Bispecifics leucocyte antigen (HLA)-bound peptides as identified by the target discovery engine Philip M. Kim, PhD, Associate Professor, Donnelly Centre, University of Toronto XPRESIDENT®. The TCRs are engineered into our highly active bispecific TCR Posters 14:35 Use of Small and Stable Antibody Scaffold Fv-clasp to Facilitate scaffold comprising a T cell-engaging antibody for potent redirection and activation Structural Studies of Drug-Target Molecules of T cells and resulting in stable molecules with extended serum half-life. Sponsor & Exhibit Opportunities Junichi Takagi, PhD, Professor, Laboratory, Protein Synthesis and Expression, 17:45 Networking Reception in the Exhibit Hall with Poster Viewing Institute for Protein Research, Osaka University Venue & Hotel Information “Fv-clasp’’ is an artificially designed, small (˜37 kDa) two-chain antibody 18:45 Problem-Solving Breakout Discussions* Registration Information fragment format compatible with bacterial expression and is applicable to any *See website for details. IgG antibodies. The conformational rigidity and high heat stability of Fv-clasp contributed to its superior “chaperoning” activity over conventional Fab fragment, 19:45 End of Day and facilitated the structure determination of many drug target proteins with high PEGSummitEurope.com conformational flexibility.

PEGSummitEurope.com | 11 Final Days Engineering 14-15 November 2018 to Register! THURSDAY 15 NOVEMBER 10:20 The SCORE Technology, a Novel Label-Free HTS Sponsored by Cover Tool for Drug Discovery 08:00 Registration and Morning Coffee Julia Schuette, PhD, Head, Marketing & Sales, Biametrics GmbH Conference-at-a-Glance In high-throughput screening, the more you can screen, with the most sensitive EMERGING TECHNOLOGIES IN ANTIBODY DISCOVERY technology, the higher likelihood of finding the best candidates. SCORE technology Short Courses AND ENGINEERING combines a microarray approach with kinetics to offer richer data sets that improve target identification. This results in better lead candidates, accelerating Training Seminars 08:30 Chairperson’s Remarks your drug discovery pipeline. Niv Papo, PhD, Group Leader, Assistant Professor, Biotechnology Engineering, Ben- 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Engineering Gurion University n Display of Biologics 08:35 From Antibody-Targeted Toxins to Gene Editing: Disruption of 11:15 Integrated Computational Design and Experimental Selection n Engineering Antibodies Diphthamide Synthesis Genes and Resulting Toxin Resistance as a Robust Leads to Custom Targeted Biologics n Engineering Bispecifics Technology for Quantifying and Optimizing CRISPR/Cas9 Approaches Philip M. Kim, PhD, Associate Professor, Donnelly Centre, University of Toronto Ulrich Brinkmann, PhD, Expert Scientist, Molecular Engineering, Roche I will present our technology platform on integrating a number of different Oncology computational protein strategies (including classic protein design, thermodynamic Activity of antibody fusions harboring Pseudomomas Exotoxin derivatives requires integration and machine learning) with high-throughput selection strategies n Antibody-Drug Conjugates diphthamide on eEF2. Diphthamide therefore serves as biomarker for immunotoxin (including phage display, yeast-2-hybrid and phenotypic selections in mammalian n Advancing Bispecifics efficacy; cells without diphthamide are toxin resistant. This phenotype can also cell culture) to obtain custom targeted biologics. n Novel Therapies for Cancer be applied to identify and quantify events that result from CRISPR/Cas9 editing. DPH gene editing followed by toxin selection provides a simple robust method to 11:45 Collecting Structural Data to Improve Predictions of Protein- Analytical differentiate and quantify homozygous/ heterozygous inactivation and integration Protein Interface Mutagenesis events, and to optimize specificity and efficacy of editing procedures. n Optimisation & Developability Samuel Coulbourn Flores, Docent, Dean, Swedish National Graduate School in n Analytical Characterisation 09:05 High-Throughput Antibody Engineering in Mammalian Cells by Medical Bioinformatics, Biochemistry and Biophysics, Stockholm University n Aggregates & Particles CRISPR/Cas9-Mediated Homology-Directed Mutagenesis Predicting the effect of mutations on protein-protein binding affinity is important Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich for biotechnology and could open the door to in silico affinity maturation. Immunotherapy Perturbative, empirically trained potentials such as FoldX are currently superior Homology-directed mutagenesis (HDM) extends the concept of CRISPR/Cas9- to physics-based and bioinformatical methods, but improvements in precision n Tumour Microenvironment mediated homology-directed repair to generate site-directed mutagenesis libraries have slowed. In the meantime, structural data has continued to accrue, leading to n CAR T, TIL & TCR Therapy in mammalian cells. Following cleavage by the Cas9 protein, single-stranded growing redundancy in the Protein Data Bank. I will show how homologyScanner n Agonist Targets & Combinations oligonucleotides containing degenerate codons serve as the repair template, harnesses redundant structures to diversify the conformational input to providing integration of sequence diversity into the genome. We used HDM to perturbative potentials, leading to substantial increases in precision. Expression generate libraries in the antibody CDRH3, and combined this with a mammalian n Synthetic & Systems Engineering surface display platform for high-throughput screening. 12:15 Luncheon Presentation I: Naturally Optimized Human Sponsored by n Optimising Expression 09:35 A Case Study in Adaptability: Exemplification of the Power of UCB’s Antibodies from the OmniChicken™ Platform n Purification Technologies Core Discovery Platform through the Discovery of a Potent Anti-Tau Antibody Phil Leighton, PhD, Director, Molecular Biology, Ligand Pharmaceuticals Dale Starkie, MSc, Senior Scientist, UCB Celltech Because of their phylogenetic distance from humans, chickens recognize a wider Bispecifics range of epitopes on human targets than mammalian hosts, can deliver cross-reactive Here we describe the use of a number of cutting-edge antibody discovery n antibodies for pre-clinical studies that obviate the need for surrogate antibodies, Introduction to Bispecifics technologies to efficiently interrogate the B cell repertoire of immunised animals and recognize highly conserved human proteins that may not be immunogenic in n Advancing Bispecifics and humans to identify rare antibodies with desirable characteristics. We employ mammals. The OmniChickenTM has been engineered to express an immune response n Engineering Bispecifics a high-throughput automated B cell culture screening platform to mine out the consisting of human antibodies and represents a next-generation technology for the memory B cell repertoire and a novel fluorescence-based proximity secretion discovery of monoclonal antibody therapeutic candidates. Posters assay to sample the plasma cell repertoire. We will discuss the use of multiple immunisation strategies utilising several forms of antigen and the discovery of an 12:45 Luncheon Presentation II: The Systems Immunology Sponsored by Sponsor & Exhibit Opportunities anti-tau lead antibody candidate capable of blocking uptake and aggregation of Revolution: How Computational Design has Enabled tau from three distinct human tauopathies in a novel robust and quantitative Tau Venue & Hotel Information seed uptake cellular assay. Thousands of Clinic-Ready Antibodies in Weeks Jacob G. Glanville, PhD, Founding Partner & CSO, Distributed Bio Inc Registration Information 10:05 Antibody Protein Sequencing with Mass Spectrometry Sponsored by 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Mingjie Xie, CEO, Rapid Novor Inc. Many applications in antibody engineering require the direct 14:00 End of Engineering Antibodies PEGSummitEurope.com sequencing of antibody proteins. At Rapid Novor (rapidnovor.com), we have developed a robust workflow and routinely sequenced 17:00 Dinner Short Course Registration* antibody proteins. Here we share the success experiences, examine common mistakes novices make, and present our practices to ensure the 17:30 – 20:30 Dinner Short Courses correctness of every . PEGSummitEurope.com | 12 Final Days Engineering 15-16 November 2018 to Register! 10th Annual Cover Engineering Bispecifics Conference-at-a-Glance Enhanced Targeting and Functionality Short Courses

Training Seminars THURSDAY 15 NOVEMBER 16:00 Creating a Novel T-Cell Engaging Bispecific Antibody Platform: Fine Tuning Anti-Tumor Activity with Sequence-Based Discovery and 13:00 Registration Machine Learning Engineering Nathan Trinklein, PhD, VP, Discovery, Teneobio 13:15 Dessert Break in the Exhibit Hall with Poster Viewing n Display of Biologics Using a multiple myeloma tumor cell line along with primary human PBMCs, we n Engineering Antibodies FOCUS ON T-CELL ENGAGERS demonstrate a spectrum of in vitro tumor cell killing activity with varied levels of n Engineering Bispecifics cytokine release using our bispecific molecules with diverse CD3 binding activities. 14:00 Chairperson’s Opening Remarks In summary, we have created a T-cell engaging bispecific antibody platform with tuned T-cell agonism that can be used to optimize the therapeutic index for a Oncology Thomas Van Blarcom, PhD, Associate Research Fellow, Protein Engineering, Pfizer, variety of tumor antigens. n Antibody-Drug Conjugates Inc. n Advancing Bispecifics 16:30 Developing Humabody VH Therapeutics for Immuno-Oncology n Novel Therapies for Cancer 14:05 KEYNOTE PRESENTATION: Novel T Cell Engagers for James Legg, PhD, Vice President, R&D, Crescendo Biologics Targeted Recruitment of Effector Cells to Tumors This presentation describes our approach to developing immune-oncology Analytical Yoram Reiter, PhD, Head, Molecular Immunology, Technion-Israel Institute of therapeutics, in particular Humabody VH products, small highly adaptable multi- Technology n Optimisation & Developability functional proteins which can be developed into differentiated therapeutics with We have developed a new class of recombinant chimerical molecule that n excellent characteristics for tumour targeting. It includes the development of a Analytical Characterisation serve as T cell engagers to re-direct potent immune effector functions to n Aggregates & Particles Biparatopic PD-1 inhibitor showing efficacy in a Pembrolizumab insensitivein specifically kill tumor cells. These T cell engagers are based on the genetic vivo model, a Bispecific PD-1, LAG3 inhibitor and a targeted IO approach in which fusion of antibody fragments, specific for tumor cell surface antigens to Immunotherapy T-cell co-stimulation is focused away from the periphery and into the tumour monomeric HLA molecules that carry immunodominant peptides that can microenvironment. n Tumour Microenvironment recall potent effector T cells. The molecular feature of these molecules/ n CAR T, TIL & TCR Therapy approaches and their in vitro and in vivo activities will be described. 17:00 End of Day n Agonist Targets & Combinations 14:35 Engineering of a T-Cell Dependent Bispecific to Broaden the 17:00 Dinner Short Course Registration* Expression Therapeutic Index for Solid Tumors 17:30 – 20:30 Dinner Short Courses n Synthetic & Systems Engineering Christoph Spiess, PhD, Senior Scientist, Antibody Engineering, Genentech, Inc. I will present the engineering of the bispecific to achieve selective binding to tumor n Optimising Expression Recommended Short Courses* n Purification Technologies cells and provide data demonstrating improved tumour infiltrationin vitro and in vivo and preclinical safety. SC8: Selection, Screening and Engineering for Affinity Reagents Bispecifics 15:05 Computational Framework to Address Liabilities in Sponsored by SC10: Engineering of Bispecific Antibodies n Introduction to Bispecifics Biotherapeutics *Separate registration required. Click here for details. n Advancing Bispecifics Jianxin Duan, PhD, Fellow AppScie, Schrodinger GmbH n Engineering Bispecifics As antibody generation produces an increasing number of leads, it is crucial to FRIDAY 16 NOVEMBER detect possible protein liabilities early. In particular, protein aggregation, viscosity Posters and solubility have been identified the most serious issues. Here we present 08:00 Registration and Morning Coffee an aggregation propensity scoring function, AggScore which considers both Sponsor & Exhibit Opportunities hydrophobicity and polarity of the protein structures and BioQSPR that uses FC ENGINEERING FOR ENHANCED PRODUCT PROPERTIES machine-learning techniques to address these complex issues. We demonstrate a AND FOR BRAIN DELIVERY Venue & Hotel Information computational workflow that can be applied to triage candidates rapidly. 08:30 Chairperson’s Remarks Registration Information 15:35 Networking Refreshment Break Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research and Early Development, Roche PEGSummitEurope.com

PEGSummitEurope.com | 13 Final Days Engineering 15-16 November 2018 to Register! 08:35 Glyco-Optimization of Antibodies Targeting Immune Checkpoint 11:35 Industrializing IO Therapeutic Discovery Platforms: Multispecifics, Cover Molecules: Case Studies of an Agonist and an Antagonist Engineered TCRs and CARs Christoph Goletz, PhD, Associate Director, Preclinical Pharmacology & Cancer Christoph Freiberg, PhD, Head, Science, Biologics, Genedata Conference-at-a-Glance Immunology, Glycotope GmbH Novel classes of bio-molecules are currently evaluated for their use in cancer Glyco-engineering is an established strategy to improve tumor antigen-targeting immunotherapy. Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, Short Courses antibodies, e.g. anti-CD20, anti-EGFR, regarding their ADCC activity. In two case non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR- studies of an agonistic anti-CD40 and an antagonistic anti-PD-L1 antibody, we based bispecific constructs promise significant advantages. However, these Training Seminars show that glyco-optimization can also be applied to enhance activity of antibodies highly engineered molecules pose new challenges in design, engineering, cloning, targeting immune checkpoint molecules. expression, purification, and analytics. We present an infrastructure that addresses Engineering these challenges and enables the industrialization of these various novel 09:05 Development of a Novel Fc Heterodimerization Technology therapeutic platforms. n Display of Biologics Fabian Richter, PhD, Post-Doc, Biomedical Engineering, Cell Biology and n Engineering Antibodies Immunology, University of Stuttgart 12:05 Problem-Solving Breakout Discussions with a Light Snack* n Engineering Bispecifics The innovative heterodimerization technology “Fc1k” (Fc-one-kappa) was created *See website for details. and used for the generation of monovalent as well as polyvalent and multi-specific Oncology antibody-like molecules. We demonstrated the applicability in a monovalent Fv- TECHNOLOGIES FOR DISCOVERY AND SCREENING, CMC, n Antibody-Drug Conjugates Fc1k format, used for cytokine receptor blockade and in a bispecific scFv2-Fc1k TARGETING, POTENCY AND LOW RISK OF TOX n Advancing Bispecifics molecule, simultaneously targeting two antigens. This novel platform technique n Novel Therapies for Cancer provides for covalent heterodimerization of immunoglobulin domains, based on 13:00 Chairperson’s Remarks fully human and naturally occurring sequences. Mark S. Dennis, PhD, Fellow, Denali Therapeutics Analytical 09:35 Identification of a PD-L1 Binding Fcab: A Potent Inhibitor of 13:05 Case Studies on How Digital and Automated Solutions Transform n Optimisation & Developability Immunosuppressive Signals the Discovery and Development of Next-Generation Antibodies n Analytical Characterisation Jose Munoz Olaya, PhD, Principal Scientist, Drug Discovery, F-star Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research n Aggregates & Particles Checkpoint inhibitors have been very popular and successful targets in the field and Early Development, Roche of immuno-oncology. Here we describe the isolation of an Fcab, an antibody Fc Immunotherapy We systematically introduced automated and digital solutions along our antibody domain modified to bind to a target, specific to PD-L1. The Fcab exhibits high discovery and development chain. A number of examples will be highlighted n Tumour Microenvironment affinity to human PD-L1 that translates into strong potency in cell-based functional that demonstrate how automation and data science speed up 1) developability n CAR T, TIL & TCR Therapy assays. An anti-murine surrogate molecule, with similar potency, also exhibits predictions to enable fast selection of clinical leads, 2) automation during n Agonist Targets & Combinations activity in an MC38 syngeneic tumour model. This activity is improved when the functional characterization, and 3) machine learning during cell line selection and Fcab is paired with Fabs targeting other immune checkpoint regulators. bioprocess modeling. As a consequence, output during the antibody discovery and Expression development phase increases substantially. 10:05 Networking Coffee Break n Synthetic & Systems Engineering 13:35 Simultaneously Multiple Interaction T Cell Engagers (SMITEs): n Optimising Expression 10:35 Antibody Transport Vehicle (ATV): A Novel Brain Delivery Platform Improving Bispecific Therapies through T Cell Costimulation n Purification Technologies Mark S. Dennis, PhD, Fellow, Denali Therapeutics Colin Correnti, PhD, Senior Research Scientist, Clinical Research, Fred Hutchinson The Antibody Transport Vehicle (ATV) enables the delivery of large molecule Cancer Research Center Bispecifics therapeutics to the brain for the treatment of neurological diseases. The ATV platform n Introduction to Bispecifics contains an engineered Fc domain that binds the transferrin receptor and utilizes 14:05 Redefinition of ErbB2/3 Tumor Targeting: How to Design Truly n Advancing Bispecifics receptor-mediated transcytosis to cross the BBB. Transport in nonhuman primates Potent Bispecific and Biparatopic Agents was assessed by the inhibition of β-secretase 1 (BACE1) in brain which was robustly n Engineering Bispecifics Rastislav Tamaskovic, PhD, Head, TC Facility, Senior Scientist, Biochemistry, inhibited by ATV:BACE1 leading to a sustained reduction in amyloid beta levels. University of Zurich Posters 11:05 Turning Affibody Molecules into Efficient Peptide Binders by Due to adaptiveness of oncogenic networks, tumors readily develop resistance Dimerization against targeted therapies. Recently, we have described major compensatory routes, which become activated in therapy of ErbB2-positive cancer - and Sponsor & Exhibit Opportunities John Lofblom, PhD, Associate Professor, Engineering Sciences in Chemistry, developed a new class of bispecific and biparatopic anti-ErbB2/3 targeting agents Biotechnology and Health, KTH Royal Institute of Technology Venue & Hotel Information endowed with capabilities to overcome the adaptive resistance. Analogously, Affibody molecules are small three-helical affinity proteins. Generating binders we build a new platform for tumor RTK fingerprinting aimed at identification of Registration Information for the amyloid beta peptide yielded a variant with 20-pM affinity, and with a prospective therapeutic leads and truly synergistic combination therapies. unique 2:1 stoichiometry mode of binding as well as structural rearrangements in both the affibody domains and the amyloid beta peptide that is sequestered in a PEGSummitEurope.com tunnel-like cavity. Engineered binders for other peptides show similar structural rearrangements and mode of binding, indicating that the new dimeric scaffold is well suited for such molecular recognitions.

PEGSummitEurope.com | 14 Final Days Engineering 15-16 November 2018 to Register! 14:35 Productive Common Light Chain Libraries Yield Diverse Panels of Cover High Affinity Bispecific Antibodies Thomas Van Blarcom, PhD, Associate Research Fellow, Protein Engineering, Pfizer, Conference-at-a-Glance Inc. Here we describe the design of a synthetic human antibody library based on Short Courses common light chains to generate antibodies with biochemical and biophysical properties that are indistinguishable to traditional therapeutic monoclonal Training Seminars antibodies. We used this library to generate diverse panels of well-behaved, high affinity antibodies toward a variety of epitopes across multiple antigens including Engineering mouse 4-1BB in order to investigate the therapeutic potential of biparatopic bispecific antibodies. n Display of Biologics n Engineering Antibodies 15:05 DuoBody Technology: A Versatile Platform for Bispecific Antibody n Engineering Bispecifics Discovery and Development Rick Hibbert, MBA, PhD, Assistant Director, Protein Production and Chemistry, Oncology Genmab B.V. n Antibody-Drug Conjugates The DuoBody® platform represents a versatile, elegant and robust technology n Advancing Bispecifics for generating bispecific antibodies. The post-production process is based on n Novel Therapies for Cancer controlled Fab-arm exchange and yields bispecific antibodies that retain the molecular structure and quality attributes of therapeutic IgGs. The process is Analytical robust, high-throughput compatible and shows linear scalability from bench to manufacturing scale. This presentation will highlight recent insights in the n Optimisation & Developability preclinical and CMC development of DuoBody products. n Analytical Characterisation n Aggregates & Particles 15:35 End of Summit Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics MEDIA PARTNERS n Engineering Bispecifics Lead Sponsoring Publications Sponsoring Societies Posters

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PEGSummitEurope.com | 15 Final Days Oncology 12-13 November 2018 to Register! 3rd Annual Cover Next-Generation Antibody-Drug Conjugates Conference-at-a-Glance Engineering Strategies Short Courses

Training Seminars Recommended Short Course* antibodies or alternative scaffold proteins. We have developed a concept where the primary, tumor-targeting agent is conjugated to a peptide nucleic acid (PNA) SC2: Making Antibody Libraries in Phage and Yeast strand, which binds with high affinity to a secondary, radiolabeled, complementary *Separate registration required. Click here for details. Engineering PNA strand. We also applied the same pretargeting system to tumor targeting with the monoclonal antibody trastuzumab and demonstrated a high contrast between n Display of Biologics MONDAY 12 NOVEMBER tumor and non-tumor tissue. n Engineering Antibodies n Engineering Bispecifics 12:00 Conference Registration 15:15 Antibody Fragment Drug Conjugates: Tailored Therapies for Gastric Cancer Oncology FIGHTING CANCER WITH ADCs Mahendra Deonarain, PhD, Chief Executive and Science Officer, Antikor Biopharma, Ltd. n Antibody-Drug Conjugates 15:45 Networking Refreshment Break n Advancing Bispecifics 13:30 Organizer’s Welcome n Novel Therapies for Cancer Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute 13:35 Chairperson’s Opening Remarks Analytical PLENARY KEYNOTE SESSION Christian P. R. Hackenberger, PhD, Professor and Department Head, Chemical n Optimisation & Developability Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and 16:15 Moderator’s Opening Remarks n Analytical Characterisation Humboldt University Berlin Janine Schuurman, PhD, Corporate Vice President, Research & n Aggregates & Particles Innovation, Genmab BV Immunotherapy 13:45 FEATURED PRESENTATION: Delineating the Role of Normal 16:20 Bicycles and Bicycle Drug Conjugates Tissue Target Expression on PK and Anti-Tumor Activity with a Mouse Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co- n Tumour Microenvironment Cross-Reactive ADC Founder and Director, Bicycle Therapeutics n CAR T, TIL & TCR Therapy Jan Pinkas, PhD, Vice President, Translational Research & Development, Bicycles® are a novel therapeutic class of constrained bicyclic n Agonist Targets & Combinations ImmunoGen, Inc. peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. Expression We have developed a mouse cross-reactive ADC that we have employed to understand the role of normal tissue target expression on PK and anti-tumor They have potential in many indications, including oncology, where Bicycles’ n Synthetic & Systems Engineering activity. Our findings are broadly applicable to the development of ADCs for solid unique properties have been used to develop Bicycle Drug Conjugates™ n Optimising Expression tumor targets. In this talk, I will share the data that has been generated. (BDCs), a novel toxin delivery platform which greatly improves toxin loading n Purification Technologies into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018.

Bispecifics 14:15 Clinical and Preclinical Evaluation of Anti-Tumor Antibody-Toxin 17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ n Introduction to Bispecifics Fusion Proteins Andreas G. Plückthun, PhD, Professor and Director, Department of Jeannick Cizeau, PhD, Associate Director, Research, Sesen Bio n Advancing Bispecifics Biochemistry, University of Zürich n Engineering Bispecifics Anti-tumor antibody fragments genetically fused to protein toxins that block Cancer will have to be fought with cocktails of therapeutics acting translation can overcome many of the limitations of current generation ADCs. locally, which may have to include therapeutic antibodies against Posters Their ability to drive immunogenic cell death and potentially stimulate host anti- receptors, checkpoint inhibitors, as well as cytokines to modify the tumor tumor immune responses also makes them attractive candidates for combination microenvironment. We have recently developed a technology of using non- Sponsor & Exhibit Opportunities with immuno-oncology agents. Preliminary results from an ongoing mono therapy replicative adenovirus carrying no viral genes, engineered to target desired Phase III clinical trial in patients with high-grade non-muscle invasive bladder cells and also to be shielded from the immune response, as a vehicle for Venue & Hotel Information cancer will be presented along with preclinical results of earlier-stage agents. simultaneous delivery of multiple genes of therapeutic proteins, produced and secreted by the infected cells. Registration Information 14:45 Radionuclide Therapy Using Peptide Nucleic Acid (PNA)-Mediated Pretargeting of HER2-Expressing Tumors 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing Amelie Eriksson Karlström, PhD, Professor, Protein Science, Engineering Sciences PEGSummitEurope.com in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology 19:30 End of Day In vivo pretargeting is a promising approach to reduce unfavorable biodistribution leading to side effects during treatment with radiolabeled tumor-targeting

PEGSummitEurope.com | 16 Final Days Oncology 12-13 November 2018 to Register! TUESDAY 13 NOVEMBER 11:45 Preclinical Validation of Site-Specifically Conjugated ADCs with Cover Potent Anthracycline Payloads in Solid and Hematologic Tumor Models 07:45 Registration and Morning Coffee Rémy Gébleux, PhD, Scientist II, NBE-Therapeutics Ltd. Conference-at-a-Glance I will address next-generation ADC technology with an update on preclinical THE NEXT GENERATION OF ADCs development of our program NBE002, targeting ROR1 in TNBC and lung Short Courses adenocarcinoma. My talk will cover the validation of a novel ultra-potent 08:30 Chairperson’s Remarks anthracycline-toxin in ADCs, including validation of NBE’s lead ADCs in preclinical Training Seminars Pedro M.S.D. Cal, PhD, Postdoctoral Investigator, Instituto de Medicina Molecular, tumor models, and the characterization of the immuno-oncology function of NBE’s University of Lisbon ADCs. The audience will gain insights into both a novel site-specific conjugation Engineering platform as well as a highly potent payload technology. 08:35 KEYNOTE PRESENTATION: Strategies & Challenges for the Sponsored by n Display of Biologics Next Generation of ADCs 12:15 Lead-Finding and Optimization of CLIPS n Engineering Antibodies Alain Beck, PhD, Senior Director, Analytical Chemistry, NBEs, Centre Constrained Peptides using High- and Medium-throughput n Engineering Bispecifics d’Immunologie Pierre Fabre; Associate Editor, mAbs Peptide Libraries The development of ADCs has benefited from general improvements in the Michael Goldflam, PhD, Head, Peptide Discovery, Pepscan Oncology design of therapeutic mAbs and from specific improvements in methods CLIPS constrained peptides are a compound class that n Antibody-Drug Conjugates for conjugate synthesis. Diversification of linking strategies and warheads combines the specificity and high-affinity properties of antibodies with the n Advancing Bispecifics has provided new opportunities to improve drug delivery to tumors while advantageous features of small molecules, such as deep tissue penetration n Novel Therapies for Cancer reducing drug exposure to normal tissues. Protein structural characterization and low manufacturing costs. Pepscan developed a platform for the discovery tools such as mass spectrometry are allowing better understanding of ADC and optimization of CLIPS peptides suitable as therapeutics, drug conjugates, Analytical structures, stability and biotransformations. This knowledge contributes diagnostics or affinity reagents. to the identification of early-developability criteria for all of the ADC n Optimisation & Developability components. 12:45 Luncheon Presentation (Sponsorship Opportunity Available) or n Analytical Characterisation Enjoy Lunch on Your Own n Aggregates & Particles 09:05 The Power of Chemoselectivity: Powerful Conjugation Technologies for Next-Generation ADCs 13:45 Dessert Break in the Exhibit Hall with Poster Viewing Immunotherapy Christian P. R. Hackenberger, PhD, Professor and Department Head, Chemical n Tumour Microenvironment Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and BREAKTHROUGH ADC ENGINEERING n CAR T, TIL & TCR Therapy Humboldt University Berlin 14:15 Chairperson’s Remarks n Agonist Targets & Combinations We develop novel protein functionalization technologies for the generation of site-specific conjugates with high stability and defined activities. WithTub-tag Amelie Eriksson Karlström, PhD, Professor, Protein Science, Engineering Sciences Expression labeling, we recently introduced a novel and versatile chemoenzymatic method for in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology the C-terminal functionalization of biomolecules. It is based on the microtubule n Synthetic & Systems Engineering 14:20 Antibody Targeted Amanitin Conjugates (ATACs) - Expanding the modifying enzyme tubulin tyrosine ligase (TTL) and facilitates one- or two-step n Optimising Expression functionalization procedures. Moreover, we have developed a new thiol-selective ADC Landscape with a New Payload Targeting RNA Polymerase II n Purification Technologies protein conjugation chemistry, that is characterized by strongly increased Stephanie Voss, PhD, Group Leader, Bioconjugation & Protein Chemistry, Heidelberg conjugate stability compared to previous approaches. Both methods are applied Pharma Research GmbH Bispecifics for the generation of defined ADCs with improved stability and potent cytotoxicity. Antigen-Targeted Amanitin-Conjugates (ATACs) represent a new class of ADCs n Introduction to Bispecifics using the payload Amanitin. This payload introduces a novel mode of action into n Advancing Bispecifics 09:35 Problem-Solving Breakout Discussions* oncology therapy, the inhibition of RNA polymerase II. The technology platform n Engineering Bispecifics *See website for details. includes Amanitin supply, site-specific conjugation, demonstrated safety profile and biomarker. Improvements of the technology and an update of the development 10:30 Coffee Break in the Exhibit Hall with Poster Viewing of HDP-101 will be presented. HDP-101 is the first ATAC directed against BCMA Posters entering Phase I trials by the end of 2018. POTENT PAYLOAD DESIGN Sponsor & Exhibit Opportunities 14:50 Taming Random Conjugation: A General Approach for Equimolar 11:15 New Payloads for Antibody-Drug Conjugates Linking of Proteins and Payloads Venue & Hotel Information Thomas Pillow, PhD, Senior Scientist, Discovery Chemistry, Genentech, Inc. Sergii Kolodych, PhD, CSO, Syndivia SAS Registration Information This presentation will highlight the most recent work on ADCs at Genentech. It will Multiple conjugation sites are usually available on a biomolecule. Upon cover our newest effort to deliver targeted protein degraders as a new modality for conjugation, they produce a mixture of species having different degrees of ADCs as well as new linkers developed to enable this platform. conjugation (DoC). We report a general conjugation approach for achieving a PEGSummitEurope.com defined DoC, which is virtually applicable to any biological macromolecule and payload. Applied to native antibodies, the method yields highly homogenous antibody-drug conjugates, antibody-oligonucleotide conjugates as well as bispecific scaffolds. PEGSummitEurope.com | 17 Final Days Oncology 12-13 November 2018 to Register! 15:20 Drug Conjugates Based on Engineered Affibody Molecules 17:30 Site-Specific Antibody Functionalization at the Antibody NBS Cover Torbjörn Gräslund, PhD, Professor, Department of Protein Science, KTH Royal Nathan J. Alves, PhD, Assistant Professor, Emergency Medicine and Biomedical Institute of Technology Engineering, Indiana University School of Medicine Conference-at-a-Glance Affibody molecules are small (58 aa), folded and robust non-Ig based affinity Antibody modification is often necessary to endow antibodies with non-native proteins. We have recently developed drug conjugates based on engineered capabilities from antibody-drug conjugates (ADCs) for targeted therapeutics Short Courses affibody molecules with specific affinity for the HER2 receptor, coupled to the to fluorescent reporter molecules for use as diagnostic or tracking tools. This small molecule drug DM1. Affibody molecules allows for site-specific drug session will explore site-specific antibody modification through conjugation to Training Seminars attachment and easy control over DAR. We found that the drug conjugates were the conserved antibody nucleotide binding site (NBS) and will demonstrate how potent agents for treatment of xenografted human tumors in mice. various linkers and conjugation strategies can be utilized to leverage the UV-NBS technology for use in next-gen antibody pharmaceuticals. Engineering 15:50 Treating Tissue Factor-Positive with Antibody-Drug n Display of Biologics Conjugates that do not Affect Blood Clotting 18:00 Generation of Potent Anti-HER1/2 Immunotoxins by Protein n Engineering Antibodies Jan-Willem Theunissen, PhD, Director, Research, Iconic Therapeutics, Inc. Ligation Using Split Inteins n Engineering Bispecifics Antibodies against Tissue Factor (TF) that do not interfere with the coagulation Harald Kolmar, PhD, Professor and Head, Applied Biochemistry, Technical cascade were identified by using a yeast-based selection system and ariousv University of Darmstadt Oncology cell-based assays. A selection of antibodies conjugated to the prototypic cytotoxic We developed a route for the generation of immunotoxins based on full length n Antibody-Drug Conjugates agent monomethyl auristatin E (MMAE) was tested in cell- and patient-derived antibodies using self-splicing split inteins and were able to generate a set n Advancing Bispecifics xenograft models. The coagulation-inert ADCs were as efficacious as tisotumab of specific and highly potent conjugates. Our robust and generic method for n Novel Therapies for Cancer vedotin, a clinical stage MMAE-based ADC against TF that affected blood clotting. generation of immunotoxins relies on protein conjugation via split intein ligation. This strategy overcomes notorious problems with immunotoxin production and Analytical 16:20 Refreshment Break in the Exhibit Hall with Poster Viewing the resulting conjugates with intrinsic bivalency and longer in vivo half-life display promising properties for further clinical development. n Optimisation & Developability BREAKTHROUGH ADC ENGINEERING (CONT.) n Analytical Characterisation 18:30 End of Next-Generation Antibody-Drug Conjugates n Aggregates & Particles 17:00 Functional Disulfide Re-Bridging Enables Native Full Antibody DAR 2, 4 & 8 Formation, Site-Selective Orthogonal Dual Modification Immunotherapy and Homogeneous Fragment Drug Conjugates, as well as Bi- and Tri- n Tumour Microenvironment Specific Scaffolds n CAR T, TIL & TCR Therapy Vijay Chudasama, PhD, Lecturer, Chemistry, University College London n Agonist Targets & Combinations Our latest data on next-generation maleimide (NGM) and pyridazinedione (PD) reagents for the site-selective modification of antibodies will be detailed (including Expression robust serum stability, in vitro selectivity, in vivo efficacy with options for DAR 2, 4 n Synthetic & Systems Engineering & 8, dual drug conjugates and fragment drug conjugates). Also presented will be n Optimising Expression our latest work on using chemical linkers to form bi- and tri-specific scaffolds, as n Purification Technologies well as applications to nanoparticle modification. Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 18 Final Days Oncology 14-15 November 2018 to Register! 10th Annual Cover Advancing Bispecifics and Combination Conference-at-a-Glance Short Courses Therapy to the Clinic Training Seminars New Approaches with Exciting Results

WEDNESDAY 14 NOVEMBER robust and reproducible is critical for the development of antibody-based Engineering biologics. We have developed reporter bioassays that meet these criteria for n Display of Biologics 07:45 Registration and Morning Coffee a broad range of antibody modalities including Fc effector function, immune n Engineering Antibodies checkpoint modulation, bispecific antibody engagement, cytokine modulation, and n Engineering Bispecifics ENGAGEMENT OF NK CELLS / CHECKPOINT INHIBITORS others. Here we will present the latest technology advancements and demonstrate how these bioassays can be used for a broad range of applications. Oncology IN COMBINATION 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Antibody-Drug Conjugates 08:30 Chairperson’s Remarks n Advancing Bispecifics Marina Bacac, PhD, Head, , Roche Innovation Center Zurich COMBINATION THERAPIES / T-CELL ENGAGEMENT n Novel Therapies for Cancer 08:35 Multi-Specific Antibody Technology Engaging NK Cells in Oncology 11:15 KEYNOTE PRESENTATION: Development of Effective Analytical Laurent Gauthier, PhD, Senior Director, Research and Development, Innate Pharma Combination Therapies for Immuno-Oncology We report the design and generation of new multi-specific antibodies which n Optimisation & Developability Lolke de Haan, PhD, Senior Director R&D, Global Immuno-Oncology Safety selectively recruit NK cells against tumour targets (NKCE). NCKEs bind to NKp46 n Analytical Characterisation Lead, Biologics Safety Assessment, Medimmune Ltd on NK cells and can potentially co-engage other activating receptors like CD16 to n Aggregates & Particles This presentation will cover: the rationale for combination therapies in induce tumor target killing. NKCEs show good developability profile, anti-tumour immunotherapy; the challenges of selecting the combination drugs that activity in in vitro and in vivo preclinical models and provide new therapeutic Immunotherapy would give synergism; translational and precision medicine approaches in options for cancer treatment. n Tumour Microenvironment combination immune-oncology, and safety considerations in development of the combination drugs. n CAR T, TIL & TCR Therapy 09:05 ATOR-1015, a Next-Generation, Bispecific CTLA-4 x OX40 n Agonist Targets & Combinations Targeting Antibody for Tumor Directed Immunotherapy of Cancer 11:45 Development of Novel Fully Human Bispecific Antibodies for Christina Furebring, PhD, Senior Vice President, Research, Alligator Bioscience AB Oncology Expression ATOR-1015 is a next-generation CTLA-4 x OX40 bispecific immune activating Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron, Inc. n Synthetic & Systems Engineering antibody developed for tumor-directed immunotherapy. ATOR-1015 binds both This presentation will describe Regeneron’s bispecific platform and present n Optimising Expression targets simultaneously, promoting cell-cell interactions expected to enhance the preclinical data on T-cell redirecting bispecifics being developed for solid and n Purification Technologies immuno-stimulating effect of the compound. The mode of action of ATOR-1015 is a combination of regulatory T-cell (Treg) depletion and effector T-cell activation. liquid tumor indications. In addition, a brief update on the status of REGN1979, Regeneron’s CD20xCD3 bispecific in Phase I clinical trials, will be presented. Bispecifics ATOR-1015 is currently in preclinical development and clinical trials will start in the second half of 2018. n Introduction to Bispecifics 12:15 CD20 TCB (RG6026), a Novel “2:1” T-Cell Bispecific Antibody for n Advancing Bispecifics 09:35 Development of an Agonist Redirected Checkpoint, SIRPa-Fc- the Treatment of B-Cell Malignancies n Engineering Bispecifics CD40L, for Cancer Immunotherapy Marina Bacac, PhD, Head, Cancer Immunotherapy, Roche Innovation Center Zurich George Fromm, PhD, VP, R&D, Shattuck Labs We give an overview of preclinical data of CD20-TCB, a novel CD20-targeting T-cell Posters We will present the generation of a novel, two-sided human fusion protein bispecific antibody on the “2:1” IgG format that consistently demonstrated superior incorporating the extra cellular domains of SIRPα and CD40L, SL-172154. SL- potency compared to other CD20-TCBs with conventional “1:1” IgG format. In Sponsor & Exhibit Opportunities 172154 binds both CD47 and CD40 with high affinity, activates CD40 signaling in addition, we present a novel approach enabling safer administration of such potent the absence of Fc receptor cross-linking, outperforms CD47 and CD40 antibodies drug consisting of a single administration of obinutuzumab (Gazyva pre-treatment, Venue & Hotel Information in multiple tumor models and was safe in non-human primates. SL-172154 will Gpt) prior to the first infusion of CD20-TCB. enter the clinic in 2019 in multiple indications. Registration Information 12:45 Therapeutics: A Novel Human Scaffold Sponsored by 10:05 Development and Application of MOA-Based Sponsored by for the Generation of Bi-Specific Molecules Reporter Bioassays for Immunotherapy Drug Amrik Basran, PhD, CSO, Avacta PEGSummitEurope.com Development Affimer therapeutics are based on the human protein Stefin A, Mei Cong, Director, Custom Assay Services, Promega Corporation a small (12kDa) intracellular protease inhibitor. We have built large (1x1010) Having a functional bioassay that is MOA-based, accurate, precise, phage display libraries and generated highly selective Affimer binders to range of PEGSummitEurope.com | 19 Final Days Oncology 14-15 November 2018 to Register! therapeutically relevant targets such as PD-L1 and LAG-3. We have shown that 16:45 Immunostimulatory Properties of a Novel IL-15-Based Tumor- Cover the Affimer scaffold can be formatted as in-line fusions, to the Fc domain or a full Targeted Immunocytokine antibody to create bispecific molecules are able to engage both target antigens. Anika Jäkel, PhD, Director, Preclinical Pharmacology & Cancer Immunology, Conference-at-a-Glance 13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Glycotope GmbH Enjoy Lunch on Your Own Interleukin-15 (IL-15), a potent stimulator of NK and CD8 T-cells, is considered Short Courses to be one of the most encouraging immunotherapeutics for cancer treatment. We created novel IL-15-based immunocytokines with different potencies and Fc Training Seminars 14:15 Session Break effector functions binding to a tumor-specific carbohydrate antigen to potentiate COMBINATION THERAPIES / T-CELL ENGAGEMENT tumor targeting. By applying a comprehensive screening approach considering PK, Engineering PD and cytokine profile, we seek to identify a promising lead candidate suitable for (CONT.) mono or combinatorial therapy of solid tumors. n Display of Biologics n Engineering Antibodies 14:30 Chairperson’s Remarks 17:15 Development of Novel Interleukin-2 Variants for Immunotherapy n Engineering Bispecifics Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron of Cancer and Autoimmune Diseases Ekkehard Moessner, PhD, Head, Protein Engineering, Large Molecules Research, Oncology 14:35 Targeting B-Cell Malignancies with a CD3 Bispecific Antibody - Preclinical Evaluation of DuoBody-CD3xCD20 Roche Innovation Center Zurich The development of interleukin-2 muteins throughout the preclinical development n Antibody-Drug Conjugates Ida Hiemstra, PhD, Lead Scientist, Translational Research, Genmab B.V. n Advancing Bispecifics will be described, for two different approaches. In one approach the IL-2 will An overview will be presented of preclinical data identifying DuoBody-CD3xCD20 n Novel Therapies for Cancer be used for cancer immunotherapy, and in the other, the IL-2 is engineered for as the most potent B-cell-targeting CD3 bispecific antibody in anin vitro functional applications in autoimmune diseases. screen covering a comprehensive panel of B cell targets. DuoBody-CD3xCD20 Analytical induced potent T cell activation and cytotoxic activity in the presence of malignant 17:45 Networking Reception in the Exhibit Hall with Poster Viewing n Optimisation & Developability B-cells in vitro and in vivo. The capacity of DuoBody-CD3xCD20 to deplete B n Analytical Characterisation cells from blood and lymphoid organs, after intravenous or subcutaneous 18:45 Problem-Solving Breakout Discussions* n Aggregates & Particles administration, was assessed in cynomolgus monkeys as part of the non-clinical *See website for details. safety studies. A clinical study evaluating the DuoBody-CD3xCD20 is currently Immunotherapy enrolling. 19:45 End of Day n Tumour Microenvironment 15:05 APVO436: A CD3 Engager with Low Cytokine Release Profile n CAR T, TIL & TCR Therapy Targeting CD123 for AML THURSDAY 15 NOVEMBER n Agonist Targets & Combinations Catherine J. McMahan, PhD, Senior Director, Pharmacology and Cell Sciences 08:00 Registration and Morning Coffee Research and Non-Clinical Development, Aptevo Therapeutics Expression APVO436 is a CD123 x CD3 bispecific ADAPTIR antibody designed to treat AML. BISPECIFICS IN THE CLINIC n Synthetic & Systems Engineering It contains an Fc region for extended half-life and has bivalent binding to both the n Optimising Expression tumor target and CD3. APVO436 was optimized for manufacturability, specificity 08:30 Chairperson’s Remarks n Purification Technologies and low levels of cytokine release compared to other bispecific formats. APVO436 David Szymkowski, PhD, Vice President, Cell Biology, Xencor induces robust proliferation of T-cells and tumor target lysis in vitro and in vivo Bispecifics xenograft models. 08:35 Update on BiTE® Antibody Constructs Currently in Clinical Development n Introduction to Bispecifics 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics Virginie Nägele, PhD, Senior Scientist, BiTE Technology, Amgen Research (Munich) n Engineering Bispecifics IMMUNOSTIMULATORY CYTOKINES FOR TUMOUR GmbH The BiTE® technology is a clinically explored approach targeting malignant TARGETING AND CONTROL OF TOXICITY Posters cells by T-cells with blinatumomab being the first bispecific T-cell engager (BiTE) approved for the treatment of patients with relapsed or refractory B-precursor 16:15 Engineering Bispecific Cytokine-Fc Fusions to Create Safer and Sponsor & Exhibit Opportunities acute lymphoblastic leukemia (B-ALL) in the US. More recently, blinatumomab has More Effective Immuno-Oncology Therapies also received accelerated approval for the treatment of B-ALL minimal residual Venue & Hotel Information David Szymkowski, PhD, Vice President, Cell Biology, Xencor disease. This presentation will give an update on the current clinical development Immunostimulatory cytokines such as IL-2 and IL-15, while extremely potent, of BiTE antibody constructs at Amgen focusing on hematologic malignancies like Registration Information suffer from poor tolerability and rapid clearance, limiting their potential as cancer acute myeloid leukemia and multiple myeloma, and on solid tumor indications. treatments. Using our clinically-validated bispecific Fc domain, we generated a heterodimeric IL15/IL15Rα-Fc with reduced potency and longer half-life. IL15/ 09:05 DVD-Ig Platform: Clinical Lessons and Future Directions PEGSummitEurope.com IL15Rα-Fc demonstrates improved exposure and stimulates multiple effector-cell Tariq Ghayur, PhD, Distinguished Research Fellow, Foundational Immunology, responses in mice and monkeys. Such cytokine-Fc biologics may possess better AbbVie Bioresearch Center tolerability and improved efficacy with less-frequent dosing than recombinant Several DVD-Ig molecules have been tested in preclinical models and in clinic for cytokines. PEGSummitEurope.com | 20 Final Days Oncology 14-15 November 2018 to Register! autoimmune and oncology indications. Emerging data suggests that the DVD-Ig 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Cover format per se is not immunogenic. However, target biology may play an important role in anti-drug antibody response (ADA, immunogenicity). Lessons learned from 14:00 End of Advancing Bispecifics and Combination Therapy Conference-at-a-Glance these studies may be broadly applicable and will be discussed. to the Clinic

Short Courses 09:35 Development of a Potent Anti-Cancer Bispecific Antibody 17:00 Dinner Short Course Registration* Targeting VEGF and DLL4 17:30 – 20:30 Dinner Short Courses Training Seminars Weon-Kyoo You, PhD, Head, R&D, Vice President, ABL Bio, Inc. Simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways is Recommended Short Course* known to lead potent inhibition of tumor progression. In this presentation, we will Engineering talk about ABL Bio’s bispecific antibody platforms and development processes of SC10: Engineering of Bispecific Antibodies n Display of Biologics the most advanced asset, a bispecific antibody targeting VEGF and DLL4 (ABL001) *Separate registration required. Click here for details. n Engineering Antibodies which is currently ongoing a Phase I clinical study. We will cover an overview of n Engineering Bispecifics preclinical data as well as interim clinical data of ABL001. Oncology 10:05 SMAB: a Novel Bispecific Antibody Platform for Sponsored by Therapeutic Development n Antibody-Drug Conjugates Janice Jin, Head, Project Management Center, Project Management n Advancing Bispecifics Department, GenScript n Novel Therapies for Cancer Urgent demands for new therapeutic strategies, such as novel modalities are Analytical raised during explosive growth of therapeutic antibody drugs. In this presentation, we will introduce GenScript proprietary SMAB bispecific antibody platform which n Optimisation & Developability minimizes the immunogenicity and manufacture concerns of current bispecific n Analytical Characterisation antibody platforms while enabling bi-valent and multi-valent therapeutics. n Aggregates & Particles 10:20 Sponsored Presentation (Opportunity Available) Immunotherapy 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Tumour Microenvironment n CAR T, TIL & TCR Therapy DESIGN TO PROOF-OF-CONCEPT n Agonist Targets & Combinations 11:15 Case Study on New Product: Biology and Proof-of-Concept Expression Mihriban Tuna, PhD, Vice President, Drug Discovery, F-star n Synthetic & Systems Engineering 11:45 Tumor-Localized T-Cell Co-Stimulation Using Antibody-Anticalin n Optimising Expression Fusion Proteins: From Flexible Design to Proof-of-Concept and Beyond n Purification Technologies Marina Pavlidou, PhD, Project Leader, Discovery, Pieris Pharmaceuticals GmbH Bispecifics We describe the generation of bispecific molecules by fusing T-cell targeting Anticalin proteins to tumor targeting antibodies. We show superior potency n Introduction to Bispecifics of the bispecific over the combination of building blocks and the combination n Advancing Bispecifics of benchmark molecules. The activity of the bispecific is dependent on the n Engineering Bispecifics expression of the tumor target showing the potential of providing a tumor localized activation of the with high efficacy and reduced peripheral toxicity. Posters 12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Sponsor & Exhibit Opportunities Enjoy Lunch on Your Own

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PEGSummitEurope.com | 21 Final Days Oncology 15-16 November 2018 to Register! 3rdAnnual Cover Novel Therapies for Cancer and Emerging Targets Conference-at-a-Glance Improving Efficacy for Clinical Success Short Courses

Training Seminars THURSDAY 15 NOVEMBER NEW APPROACHES TO COMBINATION THERAPY 13:00 Registration Chairperson Engineering Kerry Chester, PhD, Professor, Molecular Medicine, University College London 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Cancer Institute n Display of Biologics n Engineering Antibodies NEW APPROACHES TO SOLID TUMORS 16:00 Empirical Determination of Optimal Combination Therapies n Engineering Bispecifics Targeting Immunological Pathways 14:00 Chairperson’s Opening Remarks Michael Schmidt, PhD, Vice President of Antibody Discovery & Engineering, Oncology Kerry Chester, PhD, Professor, Molecular Medicine, University College London Compass Therapeutics n Antibody-Drug Conjugates Cancer Institute At Compass, we combine high-throughput antibody discovery with proprietary n Advancing Bispecifics 14:05 TGFβ Drives Immune Evasion in Genetically Reconstituted Colon platforms for multi-specific generation and screening to empirically determine n Novel Therapies for Cancer optimal combinations for drugging immunological pathways. Here, we apply this Cancer Metastasis approach to generate novel combination therapies targeting members of the TNFR Analytical Daniele Tauriello, PhD, Institute for Research in Biomedicine (IRB Barcelona), The superfamily, Nectin/Necl checkpoint pathways, and NK cell activation. Barcelona Institute of Science and Technology n Optimisation & Developability We crossed mice bearing conditional alleles of four main colorectal cancer 16:30 Novel mAb-Fc Receptor Mechanism of Action n Analytical Characterisation mutations in intestinal stem cells. From the resulting tumours, we derived Jeremy Waight, PhD, Principal Scientist, Immunomodulatory Drug Discovery, n Aggregates & Particles organoids to transplant in syngeneic, immunocompetent mice. Cancers display Agenus Inc. key hallmarks of human microsatellite-stable colorectal cancers. Inhibition Immunotherapy of TGFβ unleashed a potent cytotoxic T-cell response against tumour cells, 17:00 End of Day n Tumour Microenvironment preventing metastatic initiation in mice with progressive liver metastatic disease, 17:00 Dinner Short Course Registration* n CAR T, TIL & TCR Therapy blockade of TGFβ signalling rendered tumours susceptible to anti-PD-1/PD-L1 therapy. n Agonist Targets & Combinations 17:30 – 20:30 Dinner Short Courses Expression 14:35 Developing an ROR1 Bispecific T-Cell Engager for Treatment of Solid Tumors Recommended Short Course* n Synthetic & Systems Engineering Amit C. Nathwani, PhD, Professor, Haematology, University College London SC8: Selection, Screening and Engineering for Affinity Reagents n Optimising Expression We have developed a humanized Bi-Specific T-Cell Engager (BiTE) targeting *Separate registration required. Click here for details. n Purification Technologies Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1), a cell surface antigen present on a broad range of malignancies, many with significant unmet therapeutic Bispecifics needs. In preclinical studies, the ROR1 BiTE-mediated T cell and tumour antigen- n Introduction to Bispecifics specific cytotoxicity against of a range of histologically distinct, ROR1 expressing n Advancing Bispecifics solid tumour cell lines at exceedingly low concentrations (0.1ng/mL) and low n Engineering Bispecifics effector to target ratios. In vivo studies showed that the ROR1-BiTE prevented engraftment of tumour in xenograft murine models and significantly reduced the size of established subcutaneous tumours. To validate its wider therapeutic Posters potential, we next demonstrated significant cytotoxicity against ovarian cancer in Sponsor & Exhibit Opportunities an in vitro and in vivo setting and T cell mediated killing. Final preclinical data to support a clinical trial will be presented together the obstacles encountered in the Venue & Hotel Information generation of clinical grade ROR1-BiTE, a promising immunotherapy approach. 15:05 Glypicans as CAR T-Cell Therapy Targets in Solid Tumors Registration Information Mitchell Ho, PhD, Senior Investigator, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH PEGSummitEurope.com 15:35 Networking Refreshment Break

PEGSummitEurope.com | 22 Final Days Oncology 15-16 November 2018 to Register! FRIDAY 16 NOVEMBER 10:35 Affinity Modulation of Various Antibodies Using Universal Cover Allosteric Switch Modules 08:00 Registration and Morning Coffee Stefan Duebel, PhD, Professor & Head, iTUBS Innovationsgesellschaft Technical Conference-at-a-Glance University Braunschweig IMMUNOCYTOKINES: CLINICAL APPLICATIONS, Insertion of mutated variants of calmodulin to substitute the linker of scFv Short Courses SUCCESSES TO DATE AND HURDLES TO BE OVERCOME fragments allowed to modulate antigen binding affinity of five different antibodies. Regulation was achieved without the need of ion concentration or pH changes, Training Seminars 08:30 Chairperson’s Remarks and worked both for VH-VL and VL-VH architecture. We expect that this switch Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts linker design provides a universal allosteric regulation principle which can easily be applied to many different scFv antibodies. Engineering General Hospital, Harvard Medical School n Display of Biologics 08:35 Clinical Approaches for Immunocytokine Therapy Based on 11:05 Recombinant Human B Cell Repertoires Enable Screening for n Engineering Antibodies Antibody and Cytokine Modifications Rare, Specific, and Natively Paired Antibodies n Engineering Bispecifics Stephen D. Gillies, PhD, Founder & President & CEO, Provenance Saravanan Rajan, PhD, Scientist II, Antibody Discovery & Protein Engineering, Biopharmaceuticals Corp. MedImmune Oncology Immunocytokines target cytokines with anti-tumor activity to the tumor The human antibody repertoire is increasingly being recognized as a valuable source of therapeutic grade antibodies. However, methods for mining primary n Antibody-Drug Conjugates microenvironment. The earliest immunocytokines to be studied in the clinic were antibody-expressing B cells are limited in their ability to rapidly isolate rare and n Advancing Bispecifics based on human IgG1 with full effector functions that, in some cases, led to dose- dependent toxicities. Later generation immuncytokines had various modifications antigen-specific binders. Here we show the encapsulation of two million primary B n Novel Therapies for Cancer in structure that eliminated effector functions, modified the bioactivity of the cells into picoliter-sized droplets, where their cognate V genes are fused in frame to form a library of scFv cassettes. We used this approach to construct natively- Analytical cytokine, or were dosed subcutaneously or intra-tumorally. The pros and cons of these approaches will be discussed. paired phage-display libraries from healthy donors and drove selection towards n Optimisation & Developability cross-reactive antibodies targeting influenza hemagglutinin. Within four weeks n Analytical Characterisation 09:05 Cancer-Targeted IL-12 Controls Human Rhabdomyosarcoma by we progressed from B cell isolation to a panel of unique monoclonal antibodies, n Aggregates & Particles Senescence Induction and Myogenic Differentiation including seven that displayed broad reactivity to different clinically-relevant Karin Schilbach, PhD, Hematology/Oncology, University Children’s Hospital, influenza hemagglutinin subtypes. Most isolated antibody sequences were not Immunotherapy Tübingen detected by next-generation sequencing of the paired repertoire, illustrating Interleukin 12 is the major Th1-polarizing cytokine for innate and adaptive how this method can isolate extremely rare leads not likely found by existing n Tumour Microenvironment technologies. n CAR T, TIL & TCR Therapy immunity. The antibody-IL-12 fusion protein NHS-IL12 binds histones of necrotic n Agonist Targets & Combinations cells. NHS-IL12 therapy of human sarcoma in humanized mice combined with 11:35 Sponsored Presentation (Opportunity Available) either IL-7 (FcIL-7) or IL-2 (IL-2MAB602) induced massive tumor infiltration Expression and innate and adaptive antitumor immunity, permanently arrested cancer cell 12:05 Problem-Solving Breakout Discussions with a Light Snack* proliferation and initiated myogenic differentiation in rhabdomyosarcoma cells. *See website for details. n Synthetic & Systems Engineering NHS-IL12 significantly improved survival and induced long-term remissions when n Optimising Expression combined with IL-2. n Purification Technologies NEW TARGETS AND STRATEGIES IN IMMUNOTHERAPY 09:35 Unexpected Effects of Directed Therapy on Immune Recognition 13:00 Chairperson’s Remarks Bispecifics of Cancer Cells Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, Mar Valés-Gómez, PhD, Spanish National Research Council, CSIC; Spanish National n Introduction to Bispecifics National Cancer Institute, NIH n Advancing Bispecifics Center for Biotechnology n Engineering Bispecifics Directed therapies can affect the recognition of tumour cells by Natural Killer cells 13:05 Identification of Functional Antitumor Antibodies from due to the modulation of NKG2D ligands. These proteins are present in cancer Immunoglobulin Sequence Repertoires of Cancer Patients patient sera both as soluble molecules and recruited to extracellular vesicles. Daniel Emerling, PhD, Senior Vice President, Research, Atreca, Inc. Posters NKG2D ligands can be used as markers of tumour progression and we propose We sequenced over a quarter million natively-paired, immunoglobulin (IgG) heavy that it is important to consider them as a factor contributing to tumour immune Sponsor & Exhibit Opportunities and light chains from the activated B cells of patients having effective anti-cancer response and evasion. responses and used both sequence and repertoire feature analyses to select Venue & Hotel Information 10:05 Networking Coffee Break specific IgG’s for recombinant expression and characterization. Remarkably, antibodies from patients across several cancer types bound to non-autologous Registration Information NEW STRATEGIES FOR LEAD GENERATION human-derived tumor tissues at a high rate, consistent with recognition of public tumor antigens. Some antibodies caused regression of, and durable immunity Chairperson toward, established tumors in mouse cancer models, with activity greater than that of an anti-PD-1 inhibitor, and these have provided leads for early development. PEGSummitEurope.com Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts This reverse translation approach, starting from effective anti-tumor responses in General Hospital, Harvard Medical School patients, establishes a discovery strategy for novel cancer therapies and targets.

PEGSummitEurope.com | 23 Final Days Oncology 15-16 November 2018 to Register! 13:35 Targeting the Intracellular Proteome: Antibodies with T-Cell Cover Receptor-Like Specificity towards the MHC-Peptide Complex Yoram Reiter, PhD, Professor and Head of the Laboratory of Molecular Immunology, Conference-at-a-Glance Faculty of Biology, Technion-Israel Institute of Technology We have generated unique recombinant antibodies that mimic the fine specificity Short Courses of the T-cell receptor and recognize tumor and viral specific class I peptide- Training Seminars MHC complexes, as well as class II complexes associated with autoimmunity and inflammation. The molecular feature of these molecules/approaches and their in vitro and in vivo activities will be described. The future development of Engineering these approaches as new modalities to immunotherapy, bridging antibody and T lymphocyte attack on cancer cells, will be discussed in the context of their n Display of Biologics development path to clinical trials humans. The use of these novel molecules to n Engineering Antibodies study basic questions of tolerance will be described as well, demonstrating the n Engineering Bispecifics bridge between basic and translational immunological research. Oncology 14:05 Targeting p53 in Cancer Using T-Cell Receptor Mimic Antibodies n Antibody-Drug Conjugates Demin Li, MBBS, MSc, PhD, University Research Lecturer, Senior Research Fellow, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, n Advancing Bispecifics University of Oxford n Novel Therapies for Cancer Dysregulated tumour suppressor p53 presents in over half of all malignancies Analytical and is an attractive target for immunotherapy. We developed an antibody that recognises a p53-derived peptide presented by human major histocompatibility n Optimisation & Developability complex HLA-A*0201. The antibody recognises a wide range of cancers, induces n Analytical Characterisation cancer cell death in vitro and delays tumour growth in vivo without any detectable n Aggregates & Particles toxicity. Antibodies of such may represent promising new agents for future cancer immunotherapy. Immunotherapy 14:35 CAR-Expressing NK-Cell-Based Immunotherapy for Cancer n Tumour Microenvironment Retargeting n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Prof. Dr. Ulrike Köhl, Head of Fraunhofer Institute of Cellular Therapeutics and Immunology (IZI); Director, Institute of Clinical Immunology, University and Expression University Hospital of Leipzig; and Director, Institute of Cellular Therapeutics, GMP Development Unit and Cellular Therapy Centre, Hannover Medical School (MHH) n Synthetic & Systems Engineering Based on both our previous clinical phase I/II trials with allogeneic NK cells and n Optimising Expression our experience in manufacturing of CAR expressing T cells, we are working on CAR n Purification Technologies expressing NK cells for cancer retargeting as an “off the shelf product”. Results on next generation CAR NK cells to improve cytotoxicity against leukemia and tumors Bispecifics with the possibility to lower side effects will be presented. n Introduction to Bispecifics 15:05 A Novel Multi-Specific Antibody Targeting PD-L1-Overexpressing n Advancing Bispecifics n Engineering Bispecifics Cancers that Stimulates Antigen-Committed CD8+ T Cells through Concomitant Engagement of a T Cell Costimulatory Receptor Stefan Warmuth, PhD, Director CMC, Numab Innovation AG Posters To maximize potency and improve the safety of ICM combination approaches, Sponsor & Exhibit Opportunities we designed a multi-specific molecule bearing two ICM domains that depletes PD-L1-overexpressing cancer cells via selective recruitment and stimulation of Venue & Hotel Information tumor-reactive effector T cells in the tumor microenvironment. The multi-specific antibody format potently blocks PD-L1/PD-1 signaling and elicits further T cell Registration Information activation through its costimulatory domain solely in the presence of cells that overexpress PD-L1.

PEGSummitEurope.com 15:35 End of Summit

PEGSummitEurope.com | 24 Final Days Analytical 12-13 November 2018 to Register! 9thAnnual Cover Optimisation & Developability Conference-at-a-Glance Moving the Right Molecules Forward Short Courses

Training Seminars Recommended Short Course* 15:15 Computational Approaches for Optimizing the Sponsored by Developability of Biotherapeutics SC4: Mutation and Selection Strategies beyond Affinity Optimisation Nels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group Engineering *Separate registration required. Click here for details. n Display of Biologics A candidate integrin α11-binding mAb was optimized for developability using molecular modeling and hydrophobic interaction chromatography (HIC). 97 variants n Engineering Antibodies MONDAY 12 NOVEMBER n Engineering Bispecifics of the residues primarily responsible for predicted hydrophobic regions were expressed and their HIC retention times measured. 3-dimensional protein property 12:00 Conference Registration Oncology descriptors were used to train a QSPR model, producing improved correlation. n Antibody-Drug Conjugates MOLECULAR INSIGHTS DURING DEVELOPABILITY 15:30 Sponsored Presentation (Opportunity Available) n Advancing Bispecifics SCREENING n Novel Therapies for Cancer 15:45 Networking Refreshment Break 13:30 Organizer’s Welcome Analytical Mimi Langley, Senior Conference Director, Cambridge Healthtech Institute PLENARY KEYNOTE SESSION n Optimisation & Developability 13:35 Chairperson’s Opening Remarks n Analytical Characterisation 16:15 Moderator’s Opening Remarks Lars Linden, PhD, Head, Protein Biochemistry, Biologics-Research, Cell and Protein n Aggregates & Particles Janine Schuurman, PhD, Corporate Vice President, Research & Science, Bayer AG Innovation, Genmab BV Immunotherapy 13:45 New Insights into the Mechanistics of Antibody Pharmacokinetics n Tumour Microenvironment Hubert Kettenberger, PhD, Senior Principal Scientist, Large Molecule Research, 16:20 Bicycles and Bicycle Drug Conjugates n CAR T, TIL & TCR Therapy Roche Innovation Center Munich Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co- n Founder and Director, Bicycle Therapeutics Agonist Targets & Combinations Therapeutic antibodies with nearly identical Fc domains may show >10-fold ® differences in clearance. We systematically identified properties of the Fv domain Bicycles are a novel therapeutic class of constrained bicyclic Expression that can cause atypical pharmacokinetic behavior. Using protein engineering, peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. n Synthetic & Systems Engineering we created Fab mutants with defined biophysical properties and tested them in biochemical PK prediction assays and for in vivo clearance. Our results may pave They have potential in many indications, including oncology, where Bicycles’ n Optimising Expression ® the way for predicting and improving in vivo PK based on biophysical properties unique properties have been used to develop Bicycle Drug Conjugates n Purification Technologies and biochemical assay data. (BDCs); a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018. Bispecifics 14:15 Presentation to be Announced n Introduction to Bispecifics 17:20 Paracrine Delivery: Therapeutic Biomolecules n Advancing Bispecifics 14:45 Multi-Parameter Ultra-High-Throughput Antibody Developability Produced in Situ n Engineering Bispecifics Screening by Mammalian Display Andreas G. Plückthun, PhD, Professor and Director, Department of Mike Dyson, PhD, CTO and Co-Founder, IONTAS Ltd. Biochemistry, University of Zürich Cancer will have to be fought with cocktails of therapeutics acting Posters Using directed integration of antibody genes by CRISPR/Cas9 or TALE nucleases, we have constructed large libraries of monoclonal stable cell lines. IgG-formatted locally, which may have to include therapeutic antibodies against Sponsor & Exhibit Opportunities antibodies are displayed on the cell surface permitting selection from the library receptors, checkpoint inhibitors, as well as cytokines to modify the tumor of clones encoding desirable affinity, specificity, species cross-reactivity and microenvironment. We have recently developed a technology of using non- Venue & Hotel Information “developability” properties. Two case studies will be presented where antibodies replicative adenovirus carrying no viral genes, engineered to target desired with well documented poor biophysical characteristics were modelled to identify cells and also to be shielded from the immune response, as a vehicle for Registration Information surface hydrophobic and positive charge patches, and mammalian display used to simultaneous delivery of multiple genes of therapeutic proteins, produced select for antibodies with a superior developability profile. and secreted by the infected cells.

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PEGSummitEurope.com | 25 Final Days Analytical 12-13 November 2018 to Register! 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing 11:45 Purification Technologies to Tackle Complex Therapeutic Proteins Cover during Lead Selection 19:30 End of Day Philipp Amsler, MSc, Functional Lead, Integrated Biologics Profiling, Conference-at-a-Glance Institutes for BioMedical Research TUESDAY 13 NOVEMBER Lead selection of therapeutic proteins requires careful characterization of a variety Short Courses of molecule properties to reduce the risk for encountering unexpected obstacles 07:45 Registration and Morning Coffee during technical development. The developability assessment concept applied Training Seminars at Novartis combines information about expression, aggregation propensity, DEVELOPABILITY ASSESSMENT TO GUIDE process fit, stability, physicochemical properties, and other parameters of potential Engineering candidates. The presentation will provide an overview of the concept and focus CANDIDATE SELECTION on examples for different purification approaches enabling the production and n Display of Biologics characterization of complex protein formats. n Engineering Antibodies 08:30 Chairperson’s Remarks n Engineering Bispecifics Surjit Dixit, PhD, Vice President, Technology, Zymeworks, Inc. 12:15 Avidity Kills Cancer – The Biophysical Analysis of Sponsored by Bispecific Antibodies with the SwitchSENSE® Biosensor Oncology 08:35 KEYNOTE PRESENTATION: Developability Strategies to Ulrich Rant, PhD, CEO, Dynamic Biosensors GmbH n Antibody-Drug Conjugates Support Fast to FTIH Studies The measurement of binding rates and avidity effects in the simultaneous n Advancing Bispecifics Mike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process engagement of two antigens by a bispecific antibody is key for optimizing target Research, GlaxoSmithKline n Novel Therapies for Cancer specificity early in the development process. I will describe the utilization of the Two key deliverables for a successful path to First time in Human (FTIH) studies switchSENSE® biosensor to emulate the display of two different target antigens on Analytical are the selection of a quality molecule and a stable cell line. This presentation a cancer cell surface. will give an insight into how a combination of biophysical characterisation and n Optimisation & Developability accelerated stress delivers a much better understanding of product attributes 12:45 Luncheon Presentation I: Screening for Inhibitors Sponsored by n Analytical Characterisation during the discovery phase of drug development. This workflow is used for of T-cell Receptor Signaling n Aggregates & Particles screening novel lead panel molecules with respect to their developability, John O’Rourke, Head, Product Development, Cell Analytics, Sartorius ensuring that the right molecule is progressed to cell line development. T cells play a critical role in the adaptive immune response. In naive T cells, binding Immunotherapy of the T cell receptor (TCR) to peptides complexed with major histocompatibility 09:05 Efficient Identification of mAb Therapeutics with Optimal n Tumour Microenvironment complex (MHC) triggers an intricate signaling mechanism leading to T cell n CAR T, TIL & TCR Therapy Developability activation, proliferation and production of cytokines. Modulating the TCR signaling n Agonist Targets & Combinations Fang Yi, PhD, Principal Scientist, Biologics Discovery Sciences, Janssen pathway using biologics, small molecules or is highly relevant Biotherapeutics, Johnson & Johnson to many therapeutic areas including cancer immunotherapy, adoptive cell therapy, Expression We share our strategies of implementing a matrix of high throughput orthogonal vaccine development and autoimmune disease. biophysical screening assays during early mAb discovery to identify candidates n Synthetic & Systems Engineering with not only the high-potency and specificity towards their biological targets, 13:15 Luncheon Presentation II (Sponsorship Opportunity Available) n Optimising Expression but also desired “developability”, e.g. feasibility of the manufacturability, good n Purification Technologies solubility and stability, and absence of off-target binding. Such strategies help 13:45 Dessert Break in the Exhibit Hall with Poster Viewing minimize the downstream optimization efforts, leading to efficient lead selection Bispecifics with optimal functional and biophysical properties. RATIONAL APPROACHES TO IMPROVE BIOLOGICS n Introduction to Bispecifics DESIGN, DEVELOPABILITY AND FORMULATION n Advancing Bispecifics 09:35 Problem-Solving Breakout Discussions* 14:15 Chairperson’s Remarks n Engineering Bispecifics *See website for details. Mike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process 10:30 Coffee Break in the Exhibit Hall with Poster Viewing Research, GlaxoSmithKline Posters 11:15 Assessing and Addressing Biopharmaceutical Aggregation for 14:20 Optimising Developability – Learning from Experimental Data Sponsor & Exhibit Opportunities Developability Lars Linden, PhD, Head, Protein Biochemistry, Biologics-Research, Cell and Protein David Brockwell, PhD, Associate Professor, School of Molecular and Cellular Science, Bayer AG Venue & Hotel Information Biology, University of Leeds This presentation will discuss how to address developability early on in lead discovery and later in lead optimization phase. We will feed in experimental data Registration Information Protein-based biopharmaceuticals are susceptible to unfolding, mis-folding and aggregation by environmental perturbations that include hydrodynamic and machine learning concepts, and bring in examples showcasing predictivity of flow. Aggregation thus poses an enormous challenge to biopharmaceutical higher throughput in vitro methods. development, production, formulation and storage. To address this problem we PEGSummitEurope.com describe an in vivo method to rapidly assess candidates for developability and an 14:50 Rational Structure Guided Approaches to Biologics Design & in vitro method to assess candidate manufacturability or process suitability for the Optimization manufacture of aggregation-prone biopharmaceuticals. Surjit Dixit, PhD, Vice President, Technology, Zymeworks, Inc. PEGSummitEurope.com | 26 Final Days Analytical 12-13 November 2018 to Register! Our growing understanding of disease biology and the need for personalized medicine 18:00 A Case Study for Developing a High Concentration Formulation for Cover is driving the design and development of fit for purpose, multispecific, multifunctional a Proof-of-Concept Clinical Trial therapeutics. Protein engineering of biologics provides the opportunity to create such Lorène Bernasconi, PhD, Analytical Development Lab Manager, Novimmune SA tailored therapeutic candidates and test their functional relevance. The presentation Conference-at-a-Glance A monoclonal antibody (mAb) that binds and neutralizes human Toll-like receptor will highlight opportunities for rational engineering in the early stages of therapeutic 4 is intended to be used for the treatment of immune-related disorders. After a design and its impact on developability of the drug candidates. Short Courses successful intravenous dosing in the Phase I study using a low concentration formulation, a high concentration formulation suitable for subcutaneous Training Seminars 15:20 Using Molecular Modelling Tools to Optimize Ligand Presentation in Target Secretion Inhibitors (TSI) administration was needed in order to initiate the Phase II clinical trial. The strategy developed to rapidly achieve this goal, including a description from Teresa Silva Barata, PhD, Senior Scientist, Product Design and Characterization, Engineering the scale up for the manufacture to the adaptation of the analytical tools and Neurology R&D, Ipsen Bioinnovation optimization of the formulation, will be presented. n Display of Biologics Botulinum neurotoxins provide effective treatment for a wide range of n Engineering Antibodies neuromuscular and autonomic conditions, although their inherent toxicity limits 18:30 End of Optimisation & Developability n Engineering Bispecifics use. Recombinant strategies allow development of next-generation BoNTs with new binding domains that provide novel and differentiated cell targeting and Oncology specificity characteristics and potentially lower toxicity. Here, molecular modelling tools are utilized to evaluate different engineering strategies for the presentation n Antibody-Drug Conjugates of a ligand targeting nociceptive neurons. Characterization of molecular n Advancing Bispecifics interactions, together with molecular dynamics simulations, is leading to a rational n Novel Therapies for Cancer and optimized approach for new TSI design and development.

Analytical 15:50 High Affinity Guinea Pig mAbs Development: Sponsored by n Optimisation & Developability Application to Small Molecules Detection with a Multiplex n Analytical Characterisation Label-Free Platform n Aggregates & Particles Yannick NIZET, CSO, Monoclonal Antibody Manufacturing Center, Synabs Immunotherapy 16:20 Refreshment Break in the Exhibit Hall with Poster Viewing n Tumour Microenvironment 17:00 The CAMSOL Method of Rational Design of Protein Solubility n CAR T, TIL & TCR Therapy Michele Vendruscolo, PhD, Professor, Chemistry, University of Cambridge n Agonist Targets & Combinations CamSol is an in silico method developed for the rational design of mAbs developability. This method can provide accurate evaluations of key parameters of mAbs by replacing Expression in vitro screening assays that are more demanding in both time and resources. CamSol n Synthetic & Systems Engineering thus enables the prediction of late-stage failures in early discovery phases. n Optimising Expression 17:30 Rational Design of Monoclonal Antibodies with High n Purification Technologies Developability Potential Bispecifics Adriana-Michelle Wolf Pérez, MSc, PhD Student, Large Protein Biophysics, Novo Nordisk n Introduction to Bispecifics We will present an in silico predictor assisted rational design method. This n Advancing Bispecifics method can be applied for the rational design of developable antibodies, for the n Engineering Bispecifics re-engineering of troublesome lead candidates, and for the early screening and ranking of variant libraries. Consequently, the method potentially increases the Posters chances of a faster identification of lead candidates with high developability potential. Sponsor & Exhibit Opportunities

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PEGSummitEurope.com | 27 Final Days Analytical 14-15 November 2018 to Register! 5thAnnual Cover Analytical Characterisation of Biotherapeutics Conference-at-a-Glance Harnessing Technologies to Speed Innovation Short Courses

Training Seminars WEDNESDAY 14 NOVEMBER 10:35 Coffee Break in the Exhibit Hall with Poster Viewing 07:45 Registration and Morning Coffee 11:15 KEYNOTE PRESENTATION: Integrating Analytical Strategies Engineering into a Comprehensive Development Strategy n Display of Biologics CHARACTERISING NEW AND COMPLEX MOLECULES Thomas Spitznagel, PhD, Senior Vice President, Biopharmaceutical Development & Manufacturing, MacroGenics n Engineering Antibodies 08:30 Chairperson’s Remarks Appropriately selected and developed analytics are critical to ensure process n Engineering Bispecifics Bernice Yeung, PhD, Global Head of Characterization, Analytical Development, Shire development and manufacturing are effectively implemented. Phase Oncology appropriate strategies and approaches to developing analytical release, 08:35 Developing, Qualifying and Validating Analytical Methods for characterization, and in-process methods will be presented that balance n Antibody-Drug Conjugates Novel Biologics speed, risk, and thoroughness. A variety of case studies across different n Advancing Bispecifics Declan Lowney, MSc, Associate Director, Analytical Development, Janssen R&D protein platforms will be used to illustrate examples that ensure the overall n Novel Therapies for Cancer The presentation will cover the analytical strategies deployed for the development strategy is supported by the appropriate set of analytical tools. characterization of novel biologics and the analytical approaches taken for release, Analytical stability and characterisation. 11:45 Cutting-Edge Analytical and Structural Methods for the Characterization of Antibodies and Antibody-Drug Conjugates n Optimisation & Developability 09:05 Multi Attribute Method and Native Intact Mass Spectrometry n Elsa Wagner-Rousset, PhD, Senior Scientist, NBEs, Analytical Chemistry, Centre Analytical Characterisation for Characterization of Quality Attributes during Pharmaceutical n Aggregates & Particles d’Immunologie Pierre Fabre Development of mAb Mixtures mAbs and ADCs are one of the fastest growing classes of oncology therapeutics. Immunotherapy Dan Bach Kristensen, PhD, Principal Scientist, Analytical Development, Symphogen Their development and optimization rely on improving their analytical A/S characterization by assessing critical quality attributes (CQAs) such as sequence n Tumour Microenvironment Symphogen develops anti-cancer mAb mixtures, which are inherently complex liabilities, drug load distribution, drug to antibody ratio and residual small n CAR T, TIL & TCR Therapy and difficult to characterize using conventional technologies (e.g. methods relying molecular drugs. Therefore, early-developability assessment requires state-of-the- n Agonist Targets & Combinations exclusively on chromatographic resolution). To address product complexity art analytical methods, such as native and ion mobility mass spectrometry (MS), and meet regulatory demands, Symphogen is looking increasingly to mass 2D liquid chromatography and capillary electrophoresis coupled to MS. Expression spectrometry for qualitative and quantitative control of critical quality attributes n Synthetic & Systems Engineering (CQAs). Case studies employing LC MS (Multiple-Attribute Method, MAM) and 12:15 Product and Process Characterisation of Novel High-Potency n Optimising Expression native mass spectrometry for characterization and control of CQAs during Neurotoxin Therapeutics n Purification Technologies biopharmaceutical development will be presented. David Spencer, MSc, Characterization Manager, Ipsen

® Distinct molecular attributes can critically modulate the physicochemical and Bispecifics 09:35 Identification and Quantitation of Duobody Bispecific IgG1 Using pharmacological properties of protein biotherapeutics. Due to their highly potent Mass Spectrometry and Automated Data Processing and Analysis nature, and resultant low dose, toxin-based therapeutics present some unique n Introduction to Bispecifics Workflow analytical challenges. Case studies will be presented where insight into quality n Advancing Bispecifics Ewald van den Bremer, PhD, Senior Scientist, Analytical Sciences, Genmab B.V. attributes and key degradation pathways has been gained using novel, highly n Engineering Bispecifics The characterization of bispecific antibodies (BsAbs) by mass spectrometry sensitive analytical characterisation techniques. Application of this knowledge to (MS) offers several advantages over traditional chromatographic techniques (e.g. determine toxin manufacturing critical process parameters will also be discussed. Posters HIC, CEX). MS provides unambiguous identification and relevant quantitative information, and combined with automated data processing and analysis, it can 12:45 Array-Based SPR Imaging as a Powerful Tool at Sponsored by Sponsor & Exhibit Opportunities be employed in a high-throughput environment. We present a software solution Multiple Stages in Candidate Selection Cascades and the related workflows that enabled us to accelerate BsAb research batch Alex van der Kooi, Manager Interaction Laboratory, IBIS Technologies Venue & Hotel Information characterization and release, achieving high quality results and significant time An immunization campaign often results in hundreds to thousands and cost savings. of lead candidates. A number of tests is applied to narrow down Registration Information the best possible candidate(s). In this presentation we demonstrate that the IBIS 10:05 Reproducible LC/MS in Biopharma: A New Paradigm Sponsored by MX96, an array-based SPR imaging platform, can be used at multiple stages in John Gebler, PhD, Director, Biopharma Business Development, such a screening cascade. PEGSummitEurope.com Pharmaceutical Business, Waters Corporation

PEGSummitEurope.com | 28 Final Days Analytical 14-15 November 2018 to Register! 13:00 Recent Advances in the Use of Capillary Sponsored by 16:15 Characterization of Complex Glycosylation Patterns Sponsored by Cover Electrophoresis for Biopharmaceutical Analysis for Biopharmaceuticals Jim Thorn, Senior Manager, Marketing & Applications Separations, Urs Lohrig, PhD, Labhead AL1, Global Drug Development / Technical, Conference-at-a-Glance SCIEX Research & Development, Novartis We will present a case study of the rapid and complete characterization of the NIST Glycosylation remains a major challenge when probing the molecular structure Short Courses mAb. Then, we will present the identification of biopharmaceutical modifications of biopharmaceuticals. Tools for the in-depth characterization of N- and by the connection of CE to MS, and we will preview the acceleration of cell line O-glycosylations have been developed over the years and were employed Training Seminars development and process control through high throughput glycan screening. on various levels within the industry. Here, we present approaches including hyphenated LC-MS/MS on various levels to tackle the complexity of glycan Sponsored by Engineering 13:15 Luncheon Presentation I: A Quick Check of Protein modifications within biosimilar characterization workflows. This enables a suitable Quality that will Improve Biotherapeutic Candidate depth of knowledge for manufacturing process development as well as supporting n Display of Biologics Purification/Characterization Workflow final biosimilarity evaluation. n Engineering Antibodies Peter Fung, Senior Manager, Product Marketing, Marketing, NanoTemper Technologies n Engineering Bispecifics 16:45 Characterization of Variants of a Clinical Antibody Candidate Starting with material of questionable quality for protein purification and Using Alternative and Novel Separation Methods characterization leads to irreproducible or ambiguous results. Transitioning between Oncology upstream and downstream workflows can be challenging for bioprocessing David Eisen, PhD, Scientist, Technical R&D, Technical Development Biosimilars, Novartis n Antibody-Drug Conjugates researchers, especially when the quality of the sample material is not known. This talk focuses on the characterization of charged variants of an analytically n Advancing Bispecifics We offer a new platform that identifies sample quality and relative functionality in challenging monoclonal antibody candidate. We enriched the charged protein n Novel Therapies for Cancer minutes complementing and guiding bioprocessing workflows-making go/no go variants for analytical testing using OFFGEL electrophoresis. By applying specific decisions easy and quick-saving time, effort and producing more consistent results. RP-UPLC-MS and wide-pore HILIC-UPLC-MS methods, we could characterize these Analytical variants on intact, subunit and peptide level with enhanced resolution. These 13:45 Luncheon Presentation II (Sponsorship Opportunity Available) analyses helped to elucidate the degradation mechanism and criticality of an n Optimisation & Developability aspartate isomerization site in the variable domain of the antibody. n Analytical Characterisation 14:15 Session Break n Aggregates & Particles 17:15 Poster Highlight: Rapid Online and Inprocess Characterization of STRUCTURE-FUNCTION ANALYSIS Cetuximab Fd-Glycoprofile by Direct Monitoring and Control Immunotherapy Martin Hedstrom, PhD, Head, Bioanalysis, Division of Biotechnology, Lund 14:30 Chairperson’s Remarks n Tumour Microenvironment University Mario Lebendiker, PhD, Head, Protein Purification Facility, Wolfson Centre for n CAR T, TIL & TCR Therapy An automated analytical platform is developed for real time in-process monitoring Applied Structural Biology, Hebrew University of Jerusalem n Agonist Targets & Combinations of monoclonal antibody quality. The system was adapted to continuously monitor 14:35 Structure-Function Characterization of Sulfated Glycans in a simulated mammalian cell cultivation for the profiling of the cetuximab Fd- Expression glycosylation profile using HR-QTOF-MS as detection method. With this novel Recombinant Idursulfase technique, the Fc and F(ab’)2 subunits are completely separated and sequentially n Synthetic & Systems Engineering Bernice Yeung, PhD, Global Head of Characterization, Analytical Development, Shire eluted and analysed, allowing for a reliable assignment and profiling of minor n Optimising Expression Recombinant Idursulfase is used in enzyme replacement therapy for treatment glycoforms and other PTMs. n Purification Technologies of Hunter Syndrome. Characterization of Idursulfase has been performed to understand its structure-function relationships. In this highly glycosylated 17:45 Networking Reception in the Exhibit Hall with Poster Viewing Bispecifics protein, it has been recognized that phosphorylated glycans are critical for 18:45 Problem-Solving Breakout Discussions* n Introduction to Bispecifics facilitating cellular uptake of Idursulfase, while sialylated glycans are needed for n Advancing Bispecifics pharmacokinetic effects. The discovery of sulfated glycans in Idursulfase has led *See website for details. to unexpected understanding of the role of glycosylation on its function. n Engineering Bispecifics 19:45 End of Day 15:05 HOS in QC Environment - Could Native Peptide Mapping Support/ Posters Replace Bioassay for Stability Monitoring of Biopharmaceuticals? THURSDAY 15 NOVEMBER Michel Degueldre, Scientist, Analytical Sciences Biologicals, UCB Pharma SA Sponsor & Exhibit Opportunities Higher Order Structure is one of the critical quality attributes to be controlled for 08:00 Registration and Morning Coffee Venue & Hotel Information therapeutic proteins. Current HOS techniques are hardly amenable to QC. The potential of a novel peptide mapping method for routine monitoring of HOS will be NOVEL METHODS AND NEW APPLICATIONS Registration Information presented. This presentation will show how promising this QC-friendly method is to understand the link between structure (HOS) and function (biological activity) 08:30 Chairperson’s Remarks and the degradation pathways under different stress conditions. Dan Bach Kristensen, PhD, Principal Scientist, Analytical Development, Symphogen A/S PEGSummitEurope.com 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

PEGSummitEurope.com | 29 Final Days Analytical 14-15 November 2018 to Register! 08:35 A New Application of Multi Angle Light Scattering Coupled to Ion 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Cover Exchange Chromatography (IEX-MALS) for Protein Characterization 11:15 Highly Glycosylated Therapeutic Proteins Neorecormon® and Mario Lebendiker, PhD, Head, Protein Purification Facility, Wolfson Centre for ® Conference-at-a-Glance Applied Structural Biology, Hebrew University of Jerusalem Mircera : Novel Methods for Sample Generation, Structural and We present here a new analytical tool for protein characterization that combines Functional Characterization Short Courses the high resolution ion exchange (IEX) chromatography method with multi-angle Alexander Buettner, PhD, Scientist, Analytical Development and Quality Control, light scattering (MALS). The limited resolution of SEC interferes in some cases Pharma Technical Development Europe, Roche Diagnostics GmbH Training Seminars with the accurate analysis that can be achieved by MALS. Here we show that NeoRecormon® and Mircera® are therapeutic proteins for the treatment of combining MALS with the higher resolution separation technique IEX (IEX-MALS) anaemia and contain highly complex glycans. Glycan variety in combination with Engineering allows a precise analysis of samples that cannot be resolved by SEC-MALS. We presence of multiple glycosylation sites makes CQA assessment cumbersome. conclude that IEX-MALS is a valuable technique for proteins that have limited We have been developing and applying sample generation techniques as well n Display of Biologics analysis achieved with SEC-MALS. as structural and functional analysis methods to examine structure function n Engineering Antibodies relationships in this complex situation. The talk will address selected topics from n Engineering Bispecifics 09:05 Multiple Attribute Monitoring – Optimization of Automated these fields and present results of structure function case studies. Sample Preparation Oncology Anja Pfenninger, PhD, Lab Head, Mass Spectrometry, Bioanalytics/ 11:45 Establishing High Throughput, Low Protein Consuming n Antibody-Drug Conjugates Biopharmaceutical Development, Sanofi Biophysical Platform for Biologics Characterization n Advancing Bispecifics Automated sample preparation of tryptic digests using a liquid-handling roboter Saskia Villinger, PhD, Scientist, Formulation & Process Development/Biologics Drug n Novel Therapies for Cancer is key for successful multiple-attribute monitoring in medium-throughput mode Product Development, Sanofi R&D (100-200 samples per week). The optimization procedure will be discussed with The presentation will cover new biophysical applications for biologics Analytical regards to different aspects such as digest quality, costs of goods, speed and characterization using 1) Second Harmonic Generation (SHG); 2) Nano Differential reproducibility. Scanning Fluorimetry (nano-DSF); and 3) Micro Scale Thermophoresis (MST). It n Optimisation & Developability will also discuss the kinetics for thermal stability and activation energy barrier n Analytical Characterisation 09:35 Energetic Epitope Mapping of an Antibody/Interleukin-23 determination for biologics stability assessment, as well as present long-term n Aggregates & Particles Interaction stability prediction by computational biophysical approaches. Lumelle A. Schneeweis, PhD, Protein Science, Molecular Discovery Technologies, Immunotherapy Bristol-Myers Squibb 12:15 Luncheon Presentation (Sponsorship Opportunity Available) or n Tumour Microenvironment Identification of the energetic epitope of the hot-spot residues which dominate Enjoy Lunch on Your Own n CAR T, TIL & TCR Therapy the binding affinity of an antibody supports mechanistic interpretation, antibody 13:15 Dessert Break in the Exhibit Hall with Poster Viewing n Agonist Targets & Combinations optimization, and intellectual property claims. Complementary mass spectrometry, computational analysis, mutagenesis, and binding analytics provide a clear picture 14:00 End of Analytical Characterisation of Biotherapeutics Expression of the discontinuous interfacial hot-spot epitope on interleukin-23 (IL-23) that dominates its binding affinity for an anti-IL-23 antibody. n Synthetic & Systems Engineering 17:00 Dinner Short Course Registration* n Optimising Expression 10:05 Next Steps in Biophysical Characterization Sponsored by 17:30 – 20:30 Dinner Short Courses n Purification Technologies and Screening: RPC/IEX-MALS and HT-SLS Bispecifics Daniel Some, PhD, Principal Scientist, Marketing, Wyatt Technology Corp n Introduction to Bispecifics SEC-MALS and high-throughput DLS (HT-DLS) are widely implemented across n Advancing Bispecifics biopharma to characterize molar mass, aggregation, oligomerization and n Engineering Bispecifics fragmentation, and to screen candidates and formulations for aggregation and stability. Recent extensions of light scattering will be presented: a light-scattering Posters plate reader that measures both dynamic and static light scattering, to determine size, molar mass, kD, A2, thermal stability and viscosity; and the use of multi-angle Sponsor & Exhibit Opportunities light scattering with reversed-phase and ion-exchange chromatography.

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PEGSummitEurope.com | 30 Final Days Analytical 15-16 November 2018 to Register! 5thAnnual Cover Protein Aggregates & Particles Conference-at-a-Glance Detect. Quantify. Control. Short Courses

Training Seminars THURSDAY 15 NOVEMBER 16:30 Weak, Promiscuous IgG Self- and Hetero-Association: Implications for Aggregation and Viscosity 13:00 Registration Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Engineering Director, Biomolecular Interaction Technologies Center (BITC), University of New 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Hampshire n Display of Biologics n Engineering Antibodies MECHANISMS OF AND IMPLICATIONS FOR PARTICLE The interactions between seven fluorescently labelled tracer IgG mAbs differing in n Engineering Bispecifics V and C regions were detected and characterized by analytical ultracentrifugation. FORMATION All interactions were found to be attractive, variable in strength, affected by both Oncology the variable and constant regions, but indiscriminate with respect to IgG subclass. 14:00 Chairperson’s Opening Remarks Furthermore, weak attractive interactions were observed for all the mAbs with n Antibody-Drug Conjugates Christian Schoneich, PhD, Professor, Pharmaceutical Chemistry, University of freshly purified human poly-IgG. The universality of the weak interactions suggests n Advancing Bispecifics Kansas that they may contribute to effector function cooperativity in the normal immune n Novel Therapies for Cancer response, and could be important contributors to viscosity. 14:05 Regulatory Considerations for Impurity Characterization and Analytical Control for Biological Products 17:00 End of Day n Optimisation & Developability Audrey Jia, PhD, Principal Consultant, DataRevive LLC and exFDA Senior CMC Reviewer 17:00 Dinner Short Course Registration* n Analytical Characterisation n Aggregates & Particles Impurity characterization and impact to the product quality is important for both 17:30 – 20:30 Dinner Short Courses novel biologic and biosimilar development. To what extent the impurity needs to be characterized and analyzed to satisfy the regulatory need will be discussed. Immunotherapy Recommended Short Course* n Tumour Microenvironment 14:35 Factors Influencing Biotherapeutic mAb Aggregation SC7: Protein Aggregation: Mechanism, Characterization and n CAR T, TIL & TCR Therapy Linda Yi, PhD, Senior Scientist, Analytical Development, Biogen Consequences n Agonist Targets & Combinations Aggregation has been identified as one of the major degradation pathways that *Separate registration required. Click here for details. may affect safety, quality and efficacy of therapeutic mAbs. Aggregate present Expression in mAb products can be complex, varying by size, type and origin, with underlying FRIDAY 16 NOVEMBER n Synthetic & Systems Engineering mechanisms not always being well-understood. This presentation will provide an n Optimising Expression overview of the factors that may influence biotherapeutic mAb aggregation. A case 08:00 Registration and Morning Coffee n Purification Technologies study will follow on impact of a chemical modification catalyzed by metals on aggregation of mAbs. AGGREGATE DETECTION, QUANTIFICATION AND Bispecifics 15:05 Get Peace of Mind with Quick and Reliable Sponsored by CONTROL n Introduction to Bispecifics Protein Quality Checks n Advancing Bispecifics Dina Finan, PhD, Marketing Manager, Analytics Marketing, Unchained 08:30 Chairperson’s Remarks n Engineering Bispecifics Labs Joël Richard, PhD, Head, Technical & Pharmaceutical Operations, MedinCell There are many good reasons to quickly assess the quality of protein samples 08:35 Detecting and Separating Sub-Visible Protein Aggregates from Posters prior to downstream analysis, such as comparing batches of purified material, Other Particulates changing formulation conditions, or checking the integrity of frozen samples after Sponsor & Exhibit Opportunities thawing. Physical or chemical stress, like agitation or oxidation, can also lead to Alain Pluen, PhD, FHEA, Lecturer, Director, BSc Pharma Science, Division of protein aggregation. We will discuss methods for doing painless quality checks, Pharmacy and Optometry, School of Health Sciences, University of Manchester Venue & Hotel Information enabling you to save time and ensure the homogeneity of your samples. 09:05 A New Alternative to Conventional Aggregate Quantitation and Registration Information 15:35 Networking Refreshment Break Sizing Oliver Bannach, PhD, CEO, Attyloid GmbH 16:00 KEYNOTE PRESENTATION: Protein Gelation at Interfaces: According to a recent FDA guideline, subvisible aggregates ranging from 0.1-1 PEGSummitEurope.com Implications for Aggregation and Particle Formation µm are of special concern regarding immunogenicity of biologicals. The FDA Theodore W. Randolph, PhD, Kenneth and Genevieve Gillespie Professor, further emphasizes the need for quantitative methods covering this size range. Department of Chemical and Biological Engineering, University of Colorado sFIDA fills this gap by quantitating aggregates from 10 nm to 50 µm. sFIDA is a PEGSummitEurope.com | 31 Final Days Analytical 15-16 November 2018 to Register! novel platform technology for quantitation and sizing of protein aggregates. The Here we show how to account for the high concentration of denaturants in the Cover technology combines the selectivity of immunological assays with the sensitivity data analysis, which if unaccounted for, could lead to data misinterpretation. We of high-resolution fluorescence microscopy. then correlate light scattering measurements of five monoclonal antibodies at Conference-at-a-Glance high denaturant concentration with their shelf stability. The results indicate there 09:35 Scale-Down Models for Freezing/Thawing Process to Control is a window of denaturant concentration over which the self association behaviour Short Courses Aggregation provides an indicator for the aggregation propensity upon storage. Karoline Bechtold-Peters, PhD, Senior Strategy and Technology Leader, Biologics Training Seminars Technical Development & Manufacturing, Novartis Pharma AG 13:35 Prediction of Aggregation Propensity at Early Development Stage Using Orthogonal Characterization Methods 10:05 Networking Coffee Break Joël Richard, PhD, Head, Technical & Pharmaceutical Operations, MedinCell Engineering 10:35 Development Strategy of Fibril-Prone Peptide Therapeutics: In the perspective of accelerating early stage protein formulation development, n it has become key to anticipate and predict formulation, storage and processing Display of Biologics Aggregation Kinetics, Predictive Methods, and Detection Methods n Engineering Antibodies conditions that will lead to aggregation. To anticipate aggregation propensity, Jingtao Zhang, PhD, Principal Scientist, Pharmaceutical Sciences, MSD n Engineering Bispecifics evaluate aggregation rate under critical conditions and mitigate associated Peptide aggregation such as fibrillation presents significant challenges for DS immunogenicity risks, it is proposed to focus on the very early steps of Oncology and DP development of peptide therapeutics. Different development criteria aggregation, often involving higher order structure (HOS) alterations and loss of and control strategy is required for fibril development in contrast to protein colloidal stability, using a set of orthogonal characterization techniques. n Antibody-Drug Conjugates aggregation. Approaches to close gaps in these areas will be shared in the n Advancing Bispecifics presentation, which includes the investigation on the aggregation kinetics 14:05 Using Physics-Based Simulations to Understand the Determinants n Novel Therapies for Cancer of a fibril-prone peptide, the projection of physical stability shelf-life, and the of Viscosity in Concentrated Antibody Solutions development of highly sensitive characterization methods for fibrils. Saeed Izadi, PhD, Scientist, Early Stage Pharmaceutical Development, Analytical Genentech, Inc. 11:05 Capreomycin Inhibits the Initiation of Amyloid Fibrillation and n Optimisation & Developability We have developed a physics-based multi-scale coarse-grained approach Suppresses Amyloid Induced Cell Toxicity n Analytical Characterisation to explore how high viscosity can emerge from weak self-interactions. Key n Aggregates & Particles Rizwan Khan, PhD, Professor, Interdisciplinary Biotechnology Unit, Aligarh Muslim developments that enabled this approach are discussed, including our novel University strategies to preserve electrostatic fields and hydrophobicity features. Our method Immunotherapy Protein aggregation and amyloid fibrillation are responsible for several serious improves on currently available approaches, evidenced by its accuracy when pathological conditions (like type II diabetes, Alzheimer’s and Parkinson’s diseases, compared against experimental data, along with providing unexpected insights n Tumour Microenvironment etc.) and protein drugs ineffectiveness. Therefore, a molecule that can inhibit the into the problem that enable consideration of mitigation strategies before material n CAR T, TIL & TCR Therapy amyloid fibrillation and potentially clear amyloid fibrils is of great therapeutic value. is available for testing. n Agonist Targets & Combinations In this manuscript, we investigated the antiamyloidogenic, fibril disaggregating, as well as cell protective effect of an anti-tuberculosis drug, Capreomycin (CN). Expression DEGRADATION MONITORING FOR STABILITY AND Sponsored by FORMULATION DEVELOPMENT n Synthetic & Systems Engineering 11:35 New Tools to Anticipate and Prevent Protein Aggregation Undergoing Freeze-Thaw n Optimising Expression 14:35 Stability of Protein Disulfides: Sensitive Targets for Oxidation and n Purification Technologies Miguel Rodrigues, Professor, Co-Founder, SmartFreez Light-Induced Degradation 11:50 Sponsored Presentation (Opportunity Available) Christian Schoneich, PhD, Professor, Pharmaceutical Chemistry, University of Bispecifics Kansas n Introduction to Bispecifics 12:05 Problem-Solving Breakout Discussions with a Light Snack* Protein disulfides are important for the structural integrity of proteins. n Advancing Bispecifics *See website for details. Nevertheless, they are sensitive targets for multiple pathways of protein n Engineering Bispecifics degradation, where specific degradation products have been detected in PREDICTIONS OF AGGREGATION PROPENSITY immunogenic protein samples. Hence, a thorough characterization of disulfide Posters degradation pathways of biotherapeutics presents an important task. Recently, we 13:00 Chairperson’s Remarks detected about 60 different degradation products resulting from the light-induced Sponsor & Exhibit Opportunities Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; degradation of a small protein, human growth hormone, and significantly more Director, Biomolecular Interaction Technologies Center (BITC), University of New products may be expected from the degradation of monoclonal antibodies. Venue & Hotel Information Hampshire 15:05 Quantification and Degradation Monitoring of PS80 in One Single Registration Information 13:05 Using Chemical Denaturants to Improve Predictions of Analysis Using QDa Mass Detector Biopharmaceutical Aggregation during Storage Pierre Guibal, PhD, Deputy Head, Analytical Development, BioAnalytics, Sanofi Robin Curtis, PhD, Senior Lecturer, Chemical Engineering and Analytical Science, Different methods already exist for PS80 monitoring, but to our knowledge, no PEGSummitEurope.com University of Manchester method is able to quantify intact PS80 and monitor its potential degradation

PEGSummitEurope.com | 32 Final Days Analytical 15-16 November 2018 to Register! – oxidation or hydrolysis – in one single analysis. We present here a new Cover chromatographic method based on ion source versatility of QDa, a single quadrupole mass detector. Using specific single ion recording signals, this is Conference-at-a-Glance the first method allowing quantification of intact PS80 and covering all known degradation in one single analysis. Short Courses 15:35 Protein-Excipient Interactions Evaluated via NMR Studies in Training Seminars Polysorbate-Based Multi-Dose Protein Formulations: Influence on Antimicrobial Efficacy and Potential Study Approach Riccardo Torosantucci, PhD, Lab Head, Formulation Development, Pharmaceutical Engineering Development Biologics, Sanofi-Aventis Deutschland GmbH n Display of Biologics Preservatives are excipients needed in biopharmaceutical multi-dose formulations n Engineering Antibodies to prevent microbial growth; however, they are known to interact with non-ionic n Engineering Bispecifics surfactants like polysorbate and potentially with the active pharmaceutical ingredient (API). In the current study those interactions were successfully Oncology quantified via NMR and correlated to the antimicrobial activity of the formulations. NMR represents therefore a powerful tool to support formulation development of n Antibody-Drug Conjugates multi-dose formulations. n Advancing Bispecifics n Novel Therapies for Cancer 16:05 End of Summit Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 33 Final Days Immunotherapy 12-13 November 2018 to Register! Inaugural Cover Targeting the Tumour Microenvironment Conference-at-a-Glance Factors Influencing the Therapeutic Response Short Courses Sponsored by Training Seminars Recommended Short Course* 15:15 Abcam’s Custom Services Capabilities – from Development to Commercialization SC3: Introduction to the Tumour Microenvironment and Response to Cancer Immunotherapy Jamie Campbell, Head of Custom Services, Custom Manufacturing, Abcam Engineering *Separate registration required. Click here for details. n Display of Biologics Abcam’s comprehensive approach to developing antibodies against challenging targets leverages three antibody discovery platforms: RabMAb®, NGS-based n Engineering Antibodies MONDAY 12 NOVEMBER n Engineering Bispecifics antibody discovery, and phage display, used in combination with comprehensive assay cascades. We partner with biopharma and diagnostic companies to develop 12:00 Conference Registration Oncology antibodies as key reagents in drug discovery, in vitro diagnostics and therapeutics. n Antibody-Drug Conjugates APPROACHES TO TARGET THE TUMOUR STROMA 15:30 Sponsored Presentation (Opportunity Available) n Advancing Bispecifics n Novel Therapies for Cancer 13:30 Organizer’s Welcome 15:45 Networking Refreshment Break Nicole Lyscom, PhD, Senior Conference Director, Cambridge Healthtech Institute Analytical 13:35 Chairperson’s Opening Remarks PLENARY KEYNOTE SESSION n Optimisation & Developability Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General n Analytical Characterisation Hospital; Associate Professor, Medicine, Harvard Medical School 16:15 Moderator’s Opening Remarks n Aggregates & Particles Janine Schuurman, PhD, Corporate Vice President, Research & 13:45 Novel Approaches to Target the Tumor Stroma for Cancer Innovation, Genmab BV Immunotherapy Immunotherapy n Tumour Microenvironment Christina Claus, PhD, Senior Scientist, Oncology, Immunotherapy, pRED, Roche 16:20 Bicycles and Bicycle Drug Conjugates n CAR T, TIL & TCR Therapy Innovation Center, Zurich Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co- Founder and Director, Bicycle Therapeutics n Agonist Targets & Combinations This presentation will examine the prevalence of FAP expression in tumors and the design of our FAP-IL2v and FAP-4-1BBL fusion proteins including the preclinical Bicycles® are a novel therapeutic class of constrained bicyclic Expression mechanism of action, and their application in combination therapy. peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. n Synthetic & Systems Engineering 14:15 Impact of Cytokine Fusion Proteins Delivered to the Tumour They have potential in many indications, including oncology, where Bicycles’ n Optimising Expression Microenvironment unique properties have been used to develop Bicycle Drug Conjugates™ n Purification Technologies Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, (BDCs), a novel toxin delivery platform which greatly improves toxin loading ETH Zürich into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018. Bispecifics Certain pro-inflammatory cytokines (e.g., IL2, IL12, TNF) can potently activate 17:20 Paracrine Delivery: Therapeutic Biomolecules n Introduction to Bispecifics the immune system, but are often toxic at low doses, preventing escalation to n Advancing Bispecifics therapeutically active regimens. The fusion of suitable cytokine payloads to tumor- Produced in Situ n Engineering Bispecifics homing antibodies leads to a dramatic increase in therapeutic index. In this lecture, I Andreas G. Plückthun, PhD, Professor and Director, Department of will present preclinical and clinical results, obtained in collaboration with Philogen. Biochemistry, University of Zürich Cancer will have to be fought with cocktails of therapeutics acting Posters 14:45 Selective IL-2 Immunotherapy to Fuel the Anti-Tumor Immune locally, which may have to include therapeutic antibodies against Response receptors, checkpoint inhibitors, as well as cytokines to modify the tumor Sponsor & Exhibit Opportunities microenvironment. We have recently developed a technology of using non- Onur Boyman, MD, Professor and Chair, Immunology University Hospital Zurich, replicative adenovirus carrying no viral genes, engineered to target desired University of Zurich Venue & Hotel Information cells and also to be shielded from the immune response, as a vehicle for Following the impact of immune checkpoint inhibitors, novel immunotherapies are simultaneous delivery of multiple genes of therapeutic proteins, produced Registration Information entering clinical testing in patients with advanced cancer, including interleukin-2 and secreted by the infected cells. (IL-2)-based approaches. But what are the mechanisms of action, benefits, and differences of IL-2-based immunotherapies in comparison to immune checkpoint PEGSummitEurope.com inhibitors? This presentation will discuss these aspects of IL-2 immunotherapy by 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing presenting data on selective and improved IL-2 formulations. 19:30 End of Day

PEGSummitEurope.com | 34 Final Days Immunotherapy 12-13 November 2018 to Register! TUESDAY 13 NOVEMBER cells for cancer immunotherapy. Evidence that IgA antibodies result in a reduction Cover in tumour size in mouse models will be presented together with preclinical 07:45 Registration and Morning Coffee evidence that IgA causes fewer side effects in the treatment of neuroblastoma. Conference-at-a-Glance TARGETING MYELOID CELLS TO OVERCOME IMMUNO- 10:30 Coffee Break in the Exhibit Hall with Poster Viewing Short Courses SUPPRESSION Training Seminars ANTAGONISTIC APPROACHES 08:30 Chairperson’s Remarks Len Seymour, PhD, Professor, Gene Therapies, Oncology, University of Oxford 11:15 KEYNOTE PRESENTATION: TNFR2 Antagonism: It Doesn’t Get Engineering Any Better - A Treg and Oncogene Targeted Therapy n Display of Biologics Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School n Engineering Antibodies 08:35 Engineering, Efficacy and Functional Evaluation of a First In Class Tumor necrosis factor receptor-2 (TNFR2) is a signaling molecule found on n Engineering Bispecifics IgE Antibody for Cancer Therapy the surface of the most potent regulatory T-cells; signaling through TNFR2 Sophia N. Karagiannis, BA, MS, PhD, Reader, Translational Cancer Immunology, Oncology proliferates cell through NF-kB. TNFR2 is also abundantly expressed on the St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s surface of many human tumors as on oncogene. We propose that blocking n Antibody-Drug Conjugates College London TNFR2 selectively targets abundant TNFR2+ tumor-infiltrating Tregs and n Advancing Bispecifics Fc region engineering to enhance antibody effector functions could be an directly kill TNFR2-expressing tumors. With multi-year efforts we have created n Novel Therapies for Cancer important determinant of clinical efficacy. Engineering anti-tumour antibodies with TNFR2 antagonistic antibodies with tumor microenvironment specificity. IgE class Fc regions may harness known properties of IgE that mediate immune Analytical clearance of parasites. Anti-tumour IgE potentiated monocyte/macrophage 11:45 A-TIGIT Antagonist Antibody EOS884448 Shows Dual Mechanism recruitment and re-education against tumours. A first-in-class antibody has n Optimisation & Developability of Action by Restoration of T-Cell Effector Functions and Preferential reached clinical testing in patients with solid tumours and may offer opportunities Depletion of Treg n Analytical Characterisation to extend the current IgG-only class of monoclonal antibodies. n Aggregates & Particles Gregory Driessens, PhD, Project Leader & Head, in vivo Pharmacology, iTeos 09:05 Manipulation of Myeloid Cells for Optimal Antibody Therapeutics Immunotherapy Immunotherapy TIGIT is a co-inhibitory receptor expressed by lymphoid populations. Antagonist anti-TIGIT antibodies have the potential to restore effector functions of T and NK n Tumour Microenvironment Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine cells by blocking TIGIT-ligand interaction and by depleting Treg that express high n Group, University of Southampton CAR T, TIL & TCR Therapy TIGIT level. This presentation will focus on the clinical development of EOS884448 Tumours are multicellular organs containing a plethora of host cell types. Amongst n Agonist Targets & Combinations a new antagonist anti-TIGIT Ab that induces potent monotherapy antitumor activity these, cells of the myeloid lineage are attracted and co-opted for tumour growth through different mechanisms of action and offers strong therapeutic potential in and survival – and critically, are altered to help deliver immune suppression. In Expression clinic. this presentation, I will detail the various stimuli that drive myeloid cell alterations n Synthetic & Systems Engineering in this microenvironment and discuss strategies to elicit their repolarization to n 12:15 Sponsored Presentation (Opportunity Available) Optimising Expression augment antibody immunotherapy. n Purification Technologies 12:45 Luncheon Presentation (Sponsorship Opportunity Available) or 09:35 Breaking the Truce between Macrophages and Cancer in Order to Enjoy Lunch on Your Own Bispecifics Conquer Solid Tumors n Introduction to Bispecifics Nicolas Fischer, PhD, Head, Research, Novimmune SA 13:45 Dessert Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics In the war on cancer, tumors exploit the immune checkpoint, CD47, to induce n Engineering Bispecifics a truce with macrophages and even dendritic cells. To reinstate the anti-tumor IMPACT OF CHECKPOINT INHIBITORS capacity of innate and adaptive immunity, we target blockade of CD47 to the tumor, 14:15 Chairperson’s Remarks Posters avoiding collateral damage of healthy cells. Combining a blocking CD47 arm with an anti-mesothelin arm in a bispecific antibody reprograms these immune cells Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Sponsor & Exhibit Opportunities toward a proinflammatory activation state leading to effective killing of ovarian Group, University of Southampton cancer cell lines in vivo. 14:20 Targeting Immune Checkpoints in Cancer: Mechanistic Insights Venue & Hotel Information 10:05 IgA as Novel Isotype to Treat Cancer, Enhancement by Targeting Frederick Arce Vargas, MD, PhD, MRCS, Group Leader, Translational Research, Registration Information Neutrophil Checkpoint Inhibitors Autolus Jeanette Leusen, PhD, Associate Professor, Translational Immunology, University Preclinical data in mouse models has suggested that the mechanism of action of Medical Center Utrecht antibodies targeting co-stimulatory and co-inhibitory molecules in T-cells might PEGSummitEurope.com This presentation will discuss the importance of neutrophils as a massive source extend beyond engagement of blockade of these receptors, relying upon their of effector cells, and how they can be activated in the tumour environment. It will additional capacity to deplete regulatory T-cells through antibody-dependent be demonstrated how antibodies of IgA isotype effectively engage myeloid effector cell-mediated cytotoxity. There is evidence that human Fc gamma receptors also

PEGSummitEurope.com | 35 Final Days Immunotherapy 12-13 November 2018 to Register! mediate this mechanism in the case of anti-CTLA-4 and anti-CD25 antibodies. 17:30 Studies with the Oncolytic Virus VSV-GP, Cancer Vaccines and Cover This evidence supports the importance of understanding the immune landscape Immune-Modulation: The Yin and the Yang in the tumour microenvironment for the design of the next generation of immune Philipp Mueller, PhD, Principal Scientist, Cancer Immunology & Immune Modulation, Conference-at-a-Glance regulatory antibodies. Boehringer Ingelheim Pharma GmbH & Co. KG 14:50 Broad Impact of anti-PD-LI on the Tumour Microenvironment The talk will provide a short introduction to the MoA of oncolytic virotherapies, Short Courses selective replication of the oncolytic virus VSV-GP in tumor cells, tumor cell Yan Qu, PhD, Senior Principal Scientist, Rinat Pfizer lysis and reshaping of the tumor microenvironment. It will further outline the Training Seminars 15:20 Targeted Delivery of Endosomal Toll-Like Receptor Agonists to the effectiveness of VSV-GP as an IO enabler in the poorly “T-cell inflamed” tumour Tumour Microenvironment for the Promotion of Anti-Tumour Immunity space for a broad range of cancers and highlight VSV-GP as a non-mutagenic virus, which can be armed with transgenes and synergizes with other (non)-IO Engineering Diana Corogeanu, Scientist, Biotherapeutics, NIBSC (National Institute for therapies. n Display of Biologics Biological Standards and Control); King’s College London n Engineering Antibodies Endosomal toll-like receptor (TLR) agonists have been shown to promote anti- 18:00 Targeting Immunotherapy to the Tumour Microenvironment Using n Engineering Bispecifics tumour immune responses when administered to the tumour site. However, Bispecific Antibodies systemic administration has shown limited clinical efficiency and dose-dependent Len Seymour, PhD, Professor, Gene Therapies, Oncology, University of Oxford Oncology immune-mediated adverse effects. We are exploring targeted delivery of endosomal TLR agonists to the tumour microenvironment by attaching them to Oncolytic viruses replicate selectively within cancer cells and kill them, amplifying n Antibody-Drug Conjugates tumour-homing antibodies used in cancer therapy. This presentation will discuss themselves selectively within tumour tissue. They can be ‘armed’ to produce n Advancing Bispecifics methods of biochemical conjugation, but also complex formation with a cationic specific biologics (such as bispecific T-cell engager antibodies, BiTEs) and secrete n Novel Therapies for Cancer peptide fusion antibody, and their respective advantages and caveats. them into the tumour microenvironment, where the BiTEs can activate endogenous T-cells to kill chosen target cells. This paper will discuss using BiTEs that target Analytical 15:50 Sponsored Presentation (Opportunity Available) tumour cells and also tumour-associated fibroblasts for reversal of tumour-related immunosuppression n Optimisation & Developability 16:20 Refreshment Break in the Exhibit Hall with Poster Viewing n Analytical Characterisation 18:30 End of Targeting the Tumour Microenvironment n Aggregates & Particles ADVANCES IN THE CLINIC / IMPACT OF ONCOLYTIC Immunotherapy VIRUSES AND VECTOR VACCINES ON IMMUNE n Tumour Microenvironment MODULATION n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations 17:00 Clinical Advances with Entinostat HDAC Inhibitors in Metastatic Breast Cancer Expression Michael L. Meyers, MD, PhD, CMO, Syndax Pharmaceuticals, Inc. n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 36 Final Days Immunotherapy 14-15 November 2018 to Register! Inaugural Cover Winning Strategies for CAR T, TIL and TCR Therapy Conference-at-a-Glance Improving Designs and Accelerating to the Clinic Short Courses

Training Seminars WEDNESDAY 14 NOVEMBER treatment with CYAD-01, a CAR T cell employing NKG2D for targeting, provides support for the potential for this approach. Our clinical plans to fully explore 07:45 Registration and Morning Coffee NKG2D involve autologous approaches and also allogeneic CAR T approaches that Engineering do not involve gene editing methodologies and these will be discussed. ADVANCING T-CELL THERAPIES TO THE CLINIC n Display of Biologics 10:05 Target Specificity Screening of CAR T-Cells Using Sponsored by n Engineering Antibodies 08:30 Chairperson’s Remarks Human Cell Microarray Technology n Engineering Bispecifics John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Mark Aspinall-O’Dea, EMEA, Business Development Manager, Studies, King’s College London Retrogenix Limited Oncology Human cell microarray screening enables the discovery of both primary cell n Antibody-Drug Conjugates 08:35 T4 Pan-ERB-Targeted CAR T-Cell Immunotherapy of Head and surface receptors as well as potential off-targets for a variety of biologics n Advancing Bispecifics Neck Cancer: Phase I Trial Results including: peptides, antibodies, proteins, CAR T and other cell therapies. Case n Novel Therapies for Cancer John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer studies will demonstrate the utility of the technology in identifying novel, druggable Studies, King’s College London targets as well as in specificity screening for antibodies, scFvs and CAR T cells to Analytical T4 immunotherapy comprises T-cells that have been engineered to co-express (i) aid safety assessment and provide key data to support IND submissions. T1E28ζ, a CD28+CD3ζ CAR that engages 8 of 9 ErbB homo- and heterodimers and n Optimisation & Developability (ii) 4αβ, a chimeric cytokine receptor consisting of the IL-4Rα ectodomain coupled 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Analytical Characterisation to the IL-2Rβ endodomain. To de-risk T4 immunotherapy, a dose-escalation n 11:15 Targeting the Tumour Vasculature with CAR T-Cells Aggregates & Particles intra-tumoral Phase I clinical trial was commenced in SCCHN patients, without Steven P. Lee, PhD, Senior Cancer Research Fellow and Training Lead for the lymphodepletion. An update on the trial will be provided. Immunotherapy Birmingham CRUK Cancer Centre, Institute of Immunology and Immunotherapy, University of Birmingham n Tumour Microenvironment 09:05 Imaging CAR T-Cell Migration and Activation in Human Tumor n CAR T, TIL & TCR Therapy Explants To improve CAR T-cell therapy for solid tumours, rather than targeting malignant cells directly, we are developing CARs to target markers on the tumour n Agonist Targets & Combinations Emmanuel Donnadieu, PhD, Department of Infection, Immunity and Inflammation, vasculature. Having identified the C-type lectin CLEC14A to be selectively Institut Cochin, Université Paris Descartes overexpressed on tumor vasculature, we have generated CARs targeting this Expression Chimeric antigen receptor (CAR) T-cell immunotherapy has demonstrated very marker that are safe and effective at inhibiting tumour growth in three mouse promising results in haematological malignancies. However, significant challenges n Synthetic & Systems Engineering models of cancer. We are currently developing the approach for a Phase I trial. n Optimising Expression remain to obtain similar results for solid tumors. To attack a tumor, CAR T-cells n Purification Technologies need to enter into the malignant tissue, navigate within the tumor environment and 11:45 Imaging CAR T-Cells then mediate their effector functions to cause destruction of cancer cells. All of Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, these criteria that rely on proper migration of T-cells must be met for a treatment Bispecifics King’s College London to be effective. In my presentation, I will describe the approach based on fresh n Introduction to Bispecifics tumor slices that we use to image T-cells and look at their dynamic activities in solid Clinical translation of CAR/TCR T-cell therapy would be enhanced if we could n Advancing Bispecifics tumors. This approach enabled us to make significant progress in the understanding reliably trace the behavior in vivo of the cell product after infusion. Ideally, this n Engineering Bispecifics of how T-cells are blocked in their migratory activities with the identification of the non-invasive assessment of T-cell biodistribution would utilise a non-immunogenic extracellular matrix and macrophages as having a negative influence on T-cells. We reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer. Here we demonstrate the utility of the human sodium Posters have recently adapted this approach to monitor EGFR CAR T-cell functions in solid tumors. Our results indicate that the spatial orientation of tumor cells from epithelial iodide symporter for temporal and spatial monitoring of CAR T-cell behavior. Sponsor & Exhibit Opportunities origin dictates the migration and activation of CAR T-cells. 12:15 Resistance to Chimeric Antigen Receptor T-Cells for Hematological Malignancies Venue & Hotel Information 09:35 NKG2D CAR T-Cell Therapy: Developing an Autologous and Allogeneic CAR T Approach Exploiting the Targeting Capacity of the Marco Ruella, MD, Assistant Professor of Medicine, Scientific Dir. Lymphoma Program, Division of Hematology and Oncology, Center for Cellular Registration Information Innate Immune System Immunotherapies (CCI), University of Pennsylvania Perelman Center for Advanced Alexandre Michaux, PhD, R&D Associate, Celyad Medicine The ability of the Natural Killer activatory receptor NKG2D to bind eight different Anti-CD19 chimeric antigen receptor T cells (CART19) is now an FDA-approved PEGSummitEurope.com ligands that are frequently over-expressed in tumors makes this receptor an drug for relapsed leukemia and lymphoma. The approval by the FDA of the first attractive candidate for CAR T cell development. Our initial observations of clinical adoptive T cell therapy, the UPenn/Novartis CART19 (CTL019), represents a huge response in patients with relapsed/refractory Acute Myeloid Leukemia after

PEGSummitEurope.com | 37 Final Days Immunotherapy 14-15 November 2018 to Register! achievement for cancer treatment and paves the way to the use of the CART Effective gene transfer platforms can redirect the specificity of patient T-cells using Cover technology in other cancers and in combination with other agents. However, chimeric antigen receptors (CARs) or T-cell receptors (TCRs). In this presentation, a significant subset of patients treated with CART19 still does not respond we will demonstrate that optimal TCR expression in engineered T-cells is essential Conference-at-a-Glance or relapses. In his talk Dr. Ruella will present novel findings in the mechanism for optimal antigen-specific function. We will combine TCR transfer with the of CART19 resistance and show recent data on the development of CART engineering of T-cell effector function and show that this combination approach Short Courses combination strategies to overcome resistance. provides best cancer immunity in a murine model.

Training Seminars 12:45 Preclinical Selection of Optimal TCR Candidates for Sponsored by 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing Cancer Immonotherapy Claudia Wagner, PhD, Associate Director, Immunology, Immatics OPTIMIZING ADOPTIVE IMMUNOTHERAPY Engineering Biotechnologies GmbH 16:15 Adoptive Cell Therapy-Based on TILs in the Era of Check Point n Display of Biologics TCR-based immunotherapy is emerging as promising alternative to CAR-T Inhibitors n Engineering Antibodies approaches, especially for solid cancers. Our proprietary TCR platform generates n Engineering Bispecifics TCRs highly specific for XPRESIDENT®-validated tumor antigens. We use unique Marco Donia, MD, PhD, Staff Physician and Scientist, Medical Oncology, Herlev Hospital information from the large XPRESIDENT® collection of healthy tissues and tumor TIL ACT approach can mediate complete and durable responses in 10%-20% of Oncology biopsies for the selection of efficient and safe TCR candidates. patients with metastatic melanoma, and can also yield clinical responses in other selected types of solid tumors. The presentation will include data on predictive n Antibody-Drug Conjugates 13:00 Sponsored Presentation (Opportunity Available) markers for response, the role of neo-epitopes, immune escape mechanisms, as n Advancing Bispecifics well as data on TIL ACT in anti-PD1 refractory patients and TIL ACT in combination Sponsored by n Novel Therapies for Cancer 13:15 Luncheon Presentation I: Digital to DNA: Using with check point inhibitors. Automation for Rapid Assembly of Synthetic DNA Analytical Kurt Klimpel, Senior Director, Global Product Management, Clinical 16:45 New Broadly Expressed Cancer Targets from Successful TIL Therapy n Optimisation & Developability Solutions, Product Management, SGI-DNA. Inc. Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior n Analytical Characterisation Identifying new CAR T cell therapies requires screening many CAR candidates Investigator, Infection & Immunity, Cardiff University School of Medicine n Aggregates & Particles for optimal biophysical and immunological properties. This process can be We have developed two new techniques that allow rapid determination of the ligand streamlined with the BioXp™ 3200 System, an automated genomic workstation recognised by any ‘orphan’ T-cell clone. These techniques have enabled discovery of Immunotherapy that builds DNA libraries and constructs. In this presentation, we will describe the novel cancer-associated epitopes that are present on the surface of most cancers. use of the instrument for building constructs containing specificity-conferring n Tumour Microenvironment extracellular antibody single-chain variable fragments (scFv) and an accelerated PANEL DISCUSSION: CELLULAR THERAPY VS. n CAR T, TIL & TCR Therapy workflow for building CAR constructs. n Agonist Targets & Combinations SOLUBLE (ANTIBODY AND TCR) 13:45 Luncheon Presentation II (Sponsorship Opportunity Available) Expression 17:15 Moderator 14:15 Session Break Moderator: Andrew Sewell, PhD, Distinguished Research Professor and Wellcome n Synthetic & Systems Engineering Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine n Optimising Expression UNCONVENTIONAL APPROACHES TO TCR ENGINEERING Panelists: Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, n Purification Technologies Lymphoma Program, Division of Hematology and Oncology, Center for Cellular 14:30 Chairperson’s Remarks Immunotherapies (CCI), University of Penn-sylvania Perelman Center for Advanced Bispecifics Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Medicine n Introduction to Bispecifics Investigator, Infection & Immunity, Cardiff University School of Medicine Marco Donia, MD, PhD, Staff Physician and Scientist, Medical Oncology, Herlev n Advancing Bispecifics Hospital n Engineering Bispecifics 14:35 KEYNOTE PRESENTATION: The ImmTAC Platform: How Far We Have Come and Where We Are Going 17:45 Networking Reception in the Exhibit Hall with Poster Viewing Posters Bent K. Jakobsen, PhD, CSO, Immunocore Ltd. 18:45 Problem-Solving Breakout Discussions* Immune mobilizing monoclonal TCRs against cancer (ImmTAC™) molecules *See website for details. Sponsor & Exhibit Opportunities are a novel class of immunotherapy agent comprised of a soluble T cell receptor (TCR) fused to a T-cell redirecting scFv anti-CD3. ImmTAC molecules 19:45 End of Day Venue & Hotel Information offer distinct advantages over antibody- and cell-based formats, including access to a much larger pool of antigens in a soluble platform. The lead Registration Information ImmTAC molecule, IMCgp100, has demonstrated encouraging preliminary THURSDAY 15 NOVEMBER anti-tumour activity in patients with metastatic uveal melanoma. 08:00 Registration and Morning Coffee PEGSummitEurope.com 15:05 Genetic Engineering of Therapeutic T-Cells Hans J. Stauss, MD, PhD, Director & Professor, Tumor Immunology, Infection & IMPROVING SAFETY AND EFFICACY OF CAR T THERAPY Immunity & Transplantation, Royal Free Hampstead NHS Trust

PEGSummitEurope.com | 38 Final Days Immunotherapy 14-15 November 2018 to Register! 08:30 Chairperson’s Remarks that signature-H shows high sensitivity for evaluating T-cell infiltration in healthy Cover Paul Maciocia, PhD, Clinical Training Fellow/BRC Clinical Lecturer in Haematology, tissues. Among the 32 tumors investigated, based on the expression of signature-H, Research Department of Haematology, Faculty of Medical Sciences, University 5 and 11 tumors were heavily and moderately infiltrated by T-cells, respectively, Conference-at-a-Glance College London as compared to healthy tissues (no heavily infiltrated tumors and a lower number of moderately infiltrated tumors were described by the other signatures). We Short Courses 08:35 Applying Reporter Gene Imaging to Assessing T Cell CAR Therapy also tested signature-H in the precision medicine perspective and demonstrated in Cancer that signature-H works as well as immunohistochemistry methods (the currently Training Seminars Tammy L. Kalber, PhD, Principle Research Fellow, Center for Advanced Biomedical accepted standard) for assessing the prognosis of neuroblastoma. Finally, we Imaging, University College London used a multiparametric tool that includes T-cell infiltration based on signature-H to predict the response of melanoma to the anti-PD-1 antibody nivolumab and obtained Engineering 09:05 Targeting the T-Cell Receptor β-Chain Constant Region for positive preliminary results. n Immunotherapy of T-Cell Malignancies Display of Biologics 10:20 Binders for Challenging Tasks - A High-Throughput DARPin n Engineering Antibodies Paul Maciocia, PhD, Clinical Training Fellow/BRC Clinical Lecturer in Haematology, Selection Pipeline n Engineering Bispecifics Research Department of Haematology, Faculty of Medical Sciences, University College London Joana Marinho, Research Associate, University of Zurich Oncology T-cell cancers have a poor prognosis with few effective treatments available. 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Antibody-Drug Conjugates We developed a novel immunotherapy based on targeting T-cell receptor β-chain constant domain 1 (TRBC1) or 2 (TRBC2). While normal T-cells contain both n Advancing Bispecifics TRBC1+ and TRBC2+ compartments, malignancies are restricted to only one. We PANEL DISCUSSION: CELL THERAPY, MAKING IT AN n Novel Therapies for Cancer engineered anti-TRBC1 CAR T-cells, which killed normal and malignant TRBC1+, “OFF THE SHELF” THERAPY but not TRBC2+, T-cells in vitro and in vivo. Thus, anti-TRBC immunotherapy could Analytical eradicate a T-cell cancer while preserving T-cell immunity. 11:15 Moderator n Optimisation & Developability G. Jonah Rainey, PhD, CEO, Oriole Biotech, Inc. n Analytical Characterisation 09:35 CAR T-Cells –What’s Next? From Personalized to • Comparison of efficacy: Approved and pipeline molecules. What is the best n Aggregates & Particles “Off the Shelf” CARs clinical endpoint? Anat Globerson Levin, PhD, Senior Researcher & Immunology Lab Manager, • Costimulation: Included as part of the CAR, but what about bispecifics? Immunotherapy Immunology Research Lab, Tel-Aviv Sourasky Medical Center • Toxicity: Mechanisms of CRS/cytokine storm and ways to prevent and manage them n Tumour Microenvironment CAR (chimeric antibody receptors) T-cell therapy, pioneered in our lab, is a powerful tool • On/off target activation: Runaway CAR T proliferation, off-target effects, and n CAR T, TIL & TCR Therapy for cancer treatment. This approach has proven very effective in clinical trials in leukemia antigen-independent T-cell activation and lymphoma patients and has recently gained FDA approval to treat certain types of n Agonist Targets & Combinations Panelists: large B-cell lymphoma. Today, the major challenge in the CAR T-cell field is to prevent Sophie Papa, PhD, Senior Lecturer and Honorary Consultant Medical Oncologist, Expression ‘off-tumor on-target’ toxicity, namely, the risk of damage to the patient’s healthy tissue King’s College London which expresses the target antigen of the selected CAR. Furthermore, the manufacturing Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, n Synthetic & Systems Engineering of CAR T-cells under GMP is a focal point for this promising therapeutic modality. Lymphoma Program, Division of Hematology and Oncology, Center for Cellular n Optimising Expression As personalized therapies, autologous cell-based therapies pose a distinct set of Immunotherapies (CCI), University of Pennsylvania Perelman Center for Advanced n Purification Technologies manufacturing challenges. Protocols must be developed to reduce the number of CAR Medicine T-cells needed for a therapeutic effect and treating patients with allogeneic CAR T-cells Bispecifics can facilitate the procedures needed for manufacturing and make CAR T-cell therapy Tariq Ghayur, PhD, Distinguished Research Fellow, Foundational Immunology, more available for patients. Here, we will present our solution for these three obstacles. AbbVie Bioresearch Center n Introduction to Bispecifics We took advantage of the surface expression of several antigens that are widely n Advancing Bispecifics 12:15 Luncheon Presentation (Sponsorship Opportunity Available) or expressed on multiple myeloma cells and are poorly expressed by hematopoietic stem n Enjoy Lunch on Your Own Engineering Bispecifics cells, and generated CAR T-cells with dual specificity, expressing two complementary CARs (double CARs) for the specific and effective treatment of MM and to overcome 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Posters the ‘off-tumor on-target’ toxicity. We will also present the optimization of CAR T-cell treatments in order to minimize the number of cells administered. Finally, we will present 14:00 End of Winning Strategies for CAR T, TIL and TCR Therapy Sponsor & Exhibit Opportunities our solution for “Off the Shelf” CARs. 17:00 Dinner Short Course Registration* Venue & Hotel Information 10:05 SELECTED POSTER PRESENTATION: A New T-Cell Signature to Study T-Cell Infiltration of Human Cancers: Prognostic and Predictive Value 17:30 – 20:30 Dinner Short Courses Registration Information Giuseppe Nocentini, MD, PhD, Associate Professor, Medical School, Chair of Pharmacology, Member EASA (Eur Academy Sciences Arts) and EAACI (Eur Recommended Short Course* Academy Allergy Clin Immunol), Department of Medicine, University of Perugia PEGSummitEurope.com SC10: Engineering of Bispecific Antibodies The poster describes the development by bioinformatic analysis of a new human *Separate registration required. Click here for details. T-cell signature (signature-H). It comprises 15 genes that are over-expressed at least tenfold in resting and activated T-cells as compared to non-lymphoid tissues and cell lines. We compared signature-H with published signatures and demonstrated PEGSummitEurope.com | 39 Final Days Immunotherapy 15-16 November 2018 to Register! Inaugural Cover Agonist Immunotherapy Targets and Conference-at-a-Glance Short Courses Combination Therapies Training Seminars Accelerating T-Cell Response

Engineering THURSDAY 15 NOVEMBER 15:20 POSTER HIGHLIGHT: Novel Multimers of Bicyclic Peptides Cluster and Activate CD137 (4-1BB): A Costimulatory T Cell Checkpoint Receptor n Display of Biologics 13:00 Registration Liuhong Chen, PhD, Group Leader, Discovery, Bicycle Therapeutics Ltd n Engineering Antibodies Bicycles represent a new therapeutic class - fully synthetic, constrained bicyclic 13:15 Dessert Break in the Exhibit Hall with Poster Viewing n Engineering Bispecifics peptides that combine the drug-like attributes of antibodies, small molecules, and peptides. Panning against CD137 with a hugely diverse library of Bicycles yielded hits Oncology IL2, TNFR-SF, and STING SIGNALING that were affinity matured to ~80nM Kd. These monomeric Bicycles were antagonists n Antibody-Drug Conjugates 14:00 Chairperson’s Opening Remarks of CD137 signaling as they bound at the ligand binding site and competed with the natural homotrimeric ligand CD137L (4-1BBL). Monomeric Bicycles were then coupled n Advancing Bispecifics Patrick Mayes, PhD, Executive Director, Head of I-O Biotherapeutics, Incyte n Novel Therapies for Cancer chemically to PEG spacers at different positions and assembled into multimers 14:05 Interleukin-2: Releasing an Immune System Brake to Attack Tumors with different central hub molecules. Multimerization of the Bicycles resulted in a significant increase in affinity and in addition, the multimeric Bicycles elicited a range Analytical Rodrigo Vazquez-Lombardi, PhD, Postdoc Fellow, Laboratory for Systems and of activities in a reporter gene assay. The mono and di-valent Bicycles were inactive Synthetic Immunology, Department of Biosystems Science & Engineering, ETH n Optimisation & Developability whilst trimeric and tetrameric Bicycles gave activations equivalent or superior to Zurich n Analytical Characterisation soluble CD137L. In vivo profiling of these multimers is in progress. In summary the n Aggregates & Particles Interleukin-2 is an established therapeutic agent used for cancer immunotherapy. novel Bicycle platform enabled the identification and optimisation of the first small It is generally believed that treatment efficacy is mediated by CD8+ and NK cell molecule, fully synthetic agonists of CD137. Immunotherapy activity, and considerable efforts have focused on generating IL-2 variants that expand these subsets systemically. Here we describe a second and unexpected 15:35 Networking Refreshment Break n Tumour Microenvironment mechanism, namely the selective depletion of CD25+ CD4+ regulatory T-cells n CAR T, TIL & TCR Therapy (Tregs), as a major determinant of antitumour activity. Our results outline 16:00 HERA: Engineering Next-Generation TNFR-SF Agonists for Cancer n Agonist Targets & Combinations mechanisms of action and provide important guidance for the development of Immunotherapy next-generation cytokine therapeutics. Expression Oliver Hill, PhD, Vice President, Molecular Biology/Protein Engineering, Apogenix AG 14:35 Extrinsic Phagocyte-Dependent STING Signaling Dictates the The HERA technology platform developed by Apogenix is based on trivalent n Synthetic & Systems Engineering but single-chain molecular mimics of the TNF-SF Receptor binding domains n Optimising Expression Immunogenicity of Dying Cells (scTNFSF-RBDs) fused to a dimerization scaffold. Being hexavalent by design, n Purification Technologies Jeonghyun Ahn, PhD, Research Asst Prof, Cell Biology, University of Miami the HERA fusion proteins are potent TNFR-SF agonists on their own and do not need secondary crosslinking events for their activity. The underlying engineering 15:05 POSTER HIGHLIGHT I: Anti-TNFRSF Receptor Antibody Fusion Bispecifics concept as well as selected in vitro and in vivo data obtained with HERA-CD40L, Proteins with Targeting Controlled Agonistic Activity Independent of FcgRs n Introduction to Bispecifics HERA-CD27L and HERA-GITRL will be presented. Juliane Medler, PhD, Scientist, Molecular Internal Medicine, Department of Internal n Advancing Bispecifics Medicine II, University Hospital Würzburg 16:30 Agonistic Activation of TNFR-SF Receptors by HexaBody IgG- n Engineering Bispecifics We’ve developed antibody fusion proteins harboring domains allowing FcgR- induced Oligomerization independent cell surface anchoring. These antibody fusion proteins were analyzed Rob de Jong, PhD, Assistant Director, Protein Chemistry & CMC, Genmab BV Posters in cocultures of cell lines, which respond to TNFRSF receptor stimulation with 17:00 End of Day IL-8 production, and cells expressing the target of the anchoring domain or, as a Sponsor & Exhibit Opportunities control, target negative cells. TNFRSF receptor activation was then determined 17:00 Dinner Short Course Registration* by measuring the production of the cytokine IL-8 by ELISA. The results show that 17:30 – 20:30 Dinner Short Courses Venue & Hotel Information the TNFRSF specific antibody fusion proteins act as strong agonists provided that they have access to their target. This finding defines a general possibility to Recommended Short Course* Registration Information generate anti-TNFRSF receptor antibodies with FcgR-independent agonistic activity. Moreover, anti-TNFRSF receptor antibody fusion proteins with an anchoring domain SC10: Engineering of Bispecific Antibodies promise superior applicability to conventional systemically active agonists when an *Separate registration required. Click here for details. PEGSummitEurope.com anchoring target with localized, disease-associated expression can be addressed.

PEGSummitEurope.com | 40 Final Days Immunotherapy 15-16 November 2018 to Register! FRIDAY 16 NOVEMBER 11:05 What’s Next for GITR and OX40 Agonists? Cover Patrick Mayes, PhD, Executive Director, Head of I-O Biotherapeutics, Incyte 08:00 Registration and Morning Coffee A discussion of combination approaches for GITR and OX40 agonist antibodies in Conference-at-a-Glance OX40, GITR AND 4-1BB AGONISTS cancer. Integration of tumor biomarker analyses in response to agonist antibody treatment to inform upon GITR and OX40 combinations. Short Courses 08:30 Chairperson’s Remarks 11:35 POSTER HIGHLIGHT I: Anti-Tumor Efficacy of Anti-GITR in Training Seminars Rodrigo Vazquez-Lombardi, PhD, Postdoc Fellow, Laboratory for Systems and Synthetic Immunology, Department of Biosystems Science & Engineering, ETH Preclinical hGITR Model Zurich Julie Chiax, PhD, Project Manager, genOway Engineering We have developed immune-competent mouse model that express ICP humanized 08:35 KEYNOTE PRESENTATION: NKTR-214: Cytokine Engineering protein: Glucocorticoid-induced TNFR family related gene (GITR). Here, using our newly n Display of Biologics to Access the IL-2 Pathway generated humanized GITR (hGITR) mouse model, we show that hGITR expression n Engineering Antibodies follows a pattern similar to mGITR. hGITR is functional ex vivo and in vivo. In particular, Jonathan Zalevsky, PhD, Senior Vice President, Research, CSO, Nektar Therapeutics n in vivo: agonist GITR mAb treatment drastically reduces tumor growth in MB49 bladder Engineering Bispecifics NKTR-214 is a CD-122-biased agonist that targets the IL-2 pathway to provide tumor model. hGITR model thus provides new opportunities for immune intervention sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβɣ). based on GITR modulation. By enabling the assessment of GITR modulating drug Oncology NKTR-214 preferentially activates and expands NK and effector CD8+ T cells and their mechanisms of action, this model would be of value not only in immuno- n Antibody-Drug Conjugates over T-regulatory cells in the tumor microenvironment. In addition, NKTR-214 oncology, but also as a tool for testing new antagonizing GITR drugs for the treatment of n Advancing Bispecifics promotes an invigorated immune phenotype and drives cell surface expression autoimmune/inflammatory diseases. n Novel Therapies for Cancer of costimulatory molecules, such as ICOS, and coinhibitory receptors, such as PD-1 on the surface of newly proliferating lymphocytes. The immune 11:50 POSTER HIGHLIGHT II: HERA-CD40L: A Unique Hexavalent CD40 Analytical replenishing mechanism of action of NKTR-214 makes it an ideal combination Agonist for Cancer Immunotherapy partner with multiple immune oncology mechanisms. n Optimisation & Developability Katharina Bilian-Frey, PhD, Senior Scientist, Drug Discovery, Apogenix AG n Analytical Characterisation 09:05 ATOR-1017 – An Agonistic Tumor Directed Fcγ-Receptor Cross The hexavalent HERA-CD40L is a member of a novel class of TNFR superfamily agonists n having the natural ligand conformation in common. The biological in vitro and in vivo Aggregates & Particles Linking Dependent CD137 Antibody activities of HERA-CD40L - determined by immune cell activation, repolarization of M2 Immunotherapy Anna Säll, PhD, Scientist, Alligator Bioscience macrophages and anti-tumor efficacy in mouse models - demonstrated superiority over ATOR-1017 is an agonistic CD137 IgG4 antibody with a unique functional other agonistic formats and bivalent antibodies without requiring crosslinking events. n Tumour Microenvironment profile compared to the 4-1BB antibodies currently in clinical development. The Therefore, HERA-CD40L is an excellent candidate for further development into a next n CAR T, TIL & TCR Therapy functional activity depends on cross-linking mediated by Fcγ receptors, which generation CD40 agonistic immuno-oncology drug. n Agonist Targets & Combinations directs the immune activation to the tumor area and reduces the risk of inducing systemic immune activation and liver toxicity. ATOR-1017 is currently in preclinical 12:05 Problem-Solving Breakout Discussions with a Light Snack* Expression development and clinical trials will start in the second half of 2019. *See website for details. n Synthetic & Systems Engineering 09:35 Tumor-Targeted DARPin® Drug Candidates for Tumor-Restricted n NOVEL AGONISTS AND COMBINATION THERAPIES Optimising Expression Immune Cell Co-Activation n Purification Technologies Christian Reichen, PhD, Senior Scientist Lead Generation, Protein Engineering, 13:00 Chairperson’s Remarks Bispecifics AG Jonathan Zalevsky, PhD, Senior Vice President, Resesarch, CSO, Nektar Therapeutics Dose-limiting toxicity can hamper effective dosing and combination with checkpoint n Introduction to Bispecifics inhibitors and other immune stimulating drugs. By using the DARPin® toolbox, we have 13:05 CB307, a Novel T-Cell Agonist Humabody Therapeutic for PSMA- n Advancing Bispecifics developed a set of multi-specific molecules that enable tumor-restricted immune cell Positive Tumours n Engineering Bispecifics activation, thereby largely reducing the risk of systemic side effects. Data from the James Legg, PhD, Vice President, R&D, Crescendo Biologics preclinical development of tumor-restricted agonists will be presented on MP0310, a 13:35 AcTakines: A Novel Class of Cancer Immunotherapeutics Posters 4-1BB/FAP bispecific DARPin drug candidate promoting T cell expansion in a strictly FAP-dependent manner. FAP is highly expressed in human tumor stroma cells. Erik Depla, PhD, Director, Biology, Orionis Biosciences Sponsor & Exhibit Opportunities Type I IFN-derived AcTakines targeting dendritic cells displayed strong antitumor 10:05 Networking Coffee Break activity in murine melanoma, breast carcinoma, and lymphoma models and Venue & Hotel Information 10:35 Multispecific and Multivalent Antibodies as OX40 Agonists against human lymphoma in humanized mice without detectable toxic side Bryan Glaser, PhD, Vice President, Research, Invenra Inc. effects. Combined with immune checkpoint blockade or chemotherapy, complete tumor regression and long-lasting tumor immunity were observed. Our findings Registration Information OX40 agonists have demonstrated significant therapeutic potential in preclinical indicate that AcTakines targeted to dendritic cells provide a novel class of highly models; however, their efficacy in clinical trials is minimum. We hypothesize efficient, safe, and broad-spectrum cancer immunotherapeutics. the efficacy in humans is limited by insufficient crosslinking in the tumor PEGSummitEurope.com microenvironment. Thus, we aimed for biparatopic antibody to directly crosslink OX40 and successfully developed soluble agonists, which are potent in the absence additional crosslinker. This strategy together with high-throughput bispecific antibody screening is applicable to agonist discovery for a wide range of receptors. PEGSummitEurope.com | 41 Final Days Immunotherapy 15-16 November 2018 to Register! 14:05 Presentation cancelled. Please attend a presentation in one of our Cover other conference programs.

Conference-at-a-Glance 14:35 Tumor-Targeted Combination of TNFSF Agonists and IL-15 for Cancer Immunotherapy Short Courses Dafne Muller, PhD, Group Leader, Institute of Cell Biology and Immunology, University of Stuttgart Training Seminars Costimulatory members of the TNF-superfamily and IL-15 have shown great potential to support the generation and development of an antitumor immune Engineering response. In order to improve the efficacy of such molecules at the tumor site, we designed different formats of bi- and -fusion proteins, n Display of Biologics focusing on tumor-targeted presentation and combined mode of action of diverse n Engineering Antibodies immunomodulatory molecules, demonstrating enhanced immune responsiveness n Engineering Bispecifics in vitro and antitumor activity in a mouse model in vivo. Oncology 15:05 Oncorus Oncolytic HSV, a Platform for Combination Immunotherapy Christophe Queva, PhD, CSO, Oncorus n Antibody-Drug Conjugates n Advancing Bispecifics Oncorus is developing the next generation HSV-based oncolytic virus with n Novel Therapies for Cancer enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor Analytical cells, while preventing replication in healthy tissue. Oncorus’ oHSV are armed with multiple immunomodulatory payloads to synergistically increase recruitment and n Optimisation & Developability effector function of immune cells, thus harnessing the full potential of OVs to n Analytical Characterisation evoke an abscopal immune response. n Aggregates & Particles 15:35 End of Summit Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 42 Final Days Expression 12-13 November 2018 to Register! Inaugural Cover Systems Engineering and Synthetic Biology Conference-at-a-Glance Expanding the Protein Engineering and Production Toolbox Short Courses

Training Seminars Recommended Short Course* many other T. ni cell lines in recombinant protein production. We describe ongoing systems biology efforts to better understand how this cell line functions and to SC1: Transient Protein Expression: A Key Tool to Enable Rapid improve characteristics related to higher protein yield and quality. Engineering Protein Engineering *Separate registration required. Click here for details. 15:15 Selected Poster Presentation: MultiDrosi - A New Tool for n Display of Biologics Multigene Applications in S2 Insect Cells n Engineering Antibodies MONDAY 12 NOVEMBER Ralf Thoma, PhD, Group Leader, Protein Science, Chemical Biology, Discovery n Engineering Bispecifics Technologies, F. Hoffmann-La Roche AG 12:00 Conference Registration Oncology 15:45 Networking Refreshment Break n Antibody-Drug Conjugates ENGINEERING EFFICIENT EXPRESSION n Advancing Bispecifics PLENARY KEYNOTE SESSION n Novel Therapies for Cancer 13:30 Organizer’s Welcome Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute 16:15 Moderator’s Opening Remarks Analytical Janine Schuurman, PhD, Corporate Vice President, Research & 13:35 Chairperson’s Opening Remarks Innovation, Genmab BV n Optimisation & Developability Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National n Analytical Characterisation Laboratory for Cancer Research 16:20 Bicycles and Bicycle Drug Conjugates n Aggregates & Particles Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co- 13:45 Expanding the Synthetic Biology Toolbox for CHO Cell Factories Founder and Director, Bicycle Therapeutics Immunotherapy Nuša Pristovšek, Postdoctoral Researcher, The Novo Nordisk Foundation Center for Bicycles® are a novel therapeutic class of constrained bicyclic n Tumour Microenvironment Biosustainability, Technical University of Denmark peptides that combine antibody-like affinity and selectivity with small n CAR T, TIL & TCR Therapy Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical molecule-like tissue penetration, tunable exposure and chemical synthesis. n Agonist Targets & Combinations industry as a host for the production of complex therapeutic proteins. Thus, They have potential in many indications, including oncology, where Bicycles’ efficient synthetic biology tools to improve CHO cell factories are of great interest. unique properties have been used to develop Bicycle Drug Conjugates™ Expression Here, our latest development of these tools will be demonstrated. Together with (BDCs); a novel toxin delivery platform which greatly improves toxin loading high-throughput technologies and systems biology approaches, synthetic biology into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018. n Synthetic & Systems Engineering can pave the way for accelerated generation of desirable CHO cell factories with n Optimising Expression predicted culture performance. 17:20 Paracrine Delivery: Therapeutic Biomolecules n Purification Technologies 14:15 CRISPR-Cas Implementation and Novel Expression Tools for Non- Produced in Situ Bispecifics Andreas G. Plückthun, PhD, Professor and Director, Department of Conventional Yeasts Biochemistry, University of Zürich n Introduction to Bispecifics Thomas Vogl, PhD, Researcher, Department of Computer Science and Applied Cancer will have to be fought with cocktails of therapeutics acting n Advancing Bispecifics Mathematics & Department of Molecular Cell Biology, Weizmann Institute of locally, which may have to include therapeutic antibodies against n Engineering Bispecifics Science receptors, checkpoint inhibitors, as well as cytokines to modify the tumor The setup of efficient CRISPR/Cas systems and the toolbox of advanced CRISPR- microenvironment. We have recently developed a technology of using non- related applications will be illustrated by the example of the methylotrophic yeast Posters replicative adenovirus carrying no viral genes, engineered to target desired Pichia pastoris (doi:10.1016/j.biotechadv.2018.01.006). Furthermore, synthetic cells and also to be shielded from the immune response, as a vehicle for Sponsor & Exhibit Opportunities biology and metabolic engineering experiments frequently require the fine- simultaneous delivery of multiple genes of therapeutic proteins, produced tuning of gene expression to balance and optimize protein levels of regulators or and secreted by the infected cells. Venue & Hotel Information metabolic enzymes. Here also novel strategies for the transcriptional fine-tuning of gene co-expression will be presented. 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing Registration Information 14:45 Engineering the Trichoplusia ni Insect Cell Line Tni-FNL to 19:30 End of Day Improve Recombinant Protein Production PEGSummitEurope.com Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research Tni-FNL is a fully sequenced insect cell line which is capable of outproducing

PEGSummitEurope.com | 43 Final Days Expression 12-13 November 2018 to Register! TUESDAY 13 NOVEMBER requires multidisciplinary expertise from physics, chemistry and biology. Advances Cover and developments of new methods and techniques, i.e., cell-free protein synthesis 07:45 Registration and Morning Coffee as well as microfabrication, showed great potential to resolve challenges and to Conference-at-a-Glance accelerate the development of minimal cells. CELL-FREE SYSTEMS Short Courses 12:15 Sponsored Presentation (Opportunity Available) 08:30 Chairperson’s Remarks Training Seminars Fernando López-Gallego, PhD, ARAID Tenured Scientist, Institute of Synthetic 12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Chemistry, University of Zaragoza Enjoy Lunch on Your Own Engineering 08:35 Cloning-Free Template DNA Preparation for a Wheat Germ Cell- 13:45 Dessert Break in the Exhibit Hall with Poster Viewing Free System with Short 3’-UTR n Display of Biologics ENGINEERING SYSTEMS-SCALE STRATEGIES n Engineering Antibodies Yasuomi Tada, PhD, Professor, Center for Gene Research, Nagoya University n Engineering Bispecifics Wheat germ cell-free protein synthesis (CFPS) systems are highly applicable 14:15 Chairperson’s Remarks for proteomics but require laborious and time-consuming cloning procedures. Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC Oncology We developed a novel, effective short 3’-UTR sequence that facilitates in vitro (CNRS/INSERM/UdS) translation. The short 3’-UTR enables the cloning-free generation of various n Antibody-Drug Conjugates transcription templates from the same plasmid, including fusion proteins with N- 14:20 Design of Intracellular Inhibitors – A Platform for Target n Advancing Bispecifics or C-terminal tags, and truncated proteins. Thus, our method provides a versatile Validation and Drug Development n Novel Therapies for Cancer platform for preparing DNA templates. Andreas Ernst, PhD, Group Leader, Institute of Clinical Pharmacology, Goethe Analytical 09:05 Expanding One-Pot Cell-Free Protein Synthesis and University Frankfurt Immobilization for On-Demand Manufacturing of Biomaterials Targeting protein-protein interaction for therapeutic benefit represents one of n Optimisation & Developability the great challenges in the development of small molecule drugs. To address n Analytical Characterisation Fernando López-Gallego, PhD, ARAID Tenured Scientist, Institute of Synthetic this problem, we have combined the design of intracellular inhibitors based on n Aggregates & Particles Chemistry, University of Zaragoza alternative protein scaffolds with the development of high-throughput small Fabrication of biomaterials containing protein-based biomolecules requires the molecule screening assays. Additionally, the engineered intracellular affinity Immunotherapy expression and purification of proteins followed by the immobilization process. reagents allow characterization and validation of new intracellular drug targets. An emerging alternative is the cell-free protein synthesis (CFPS) in solution. In n Tumour Microenvironment this work, we propose the fabrication of protein-based biomaterials by coupling 14:50 Top-Down and Bottom-Up Strategies for Production of Human n CAR T, TIL & TCR Therapy in vitro protein synthesis and immobilization in the same pot. To this aim, we n Agonist Targets & Combinations Multi-Protein Complexes have expanded the toolbox of peptide-tags to selectively immobilize proteins on Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC different solid materials. Expression (CNRS/INSERM/UdS) Macromolecular complexes are vital cornerstones of most, if not all, biological n 09:35 Problem-Solving Breakout Discussions* Synthetic & Systems Engineering processes in cells. We illustrate how the CRISPR/Cas9 editing technology allows us *See website for details. n Optimising Expression to label and isolate native protein assemblies from their natural cellular environment n Purification Technologies 10:30 Coffee Break in the Exhibit Hall with Poster Viewing and the potential of the baculovirus expression vector system for reconstitution of multi-subunit complexes. As model systems, we use transcription regulators such Bispecifics 11:15 Cell-Free Protein Synthesis from Resting versus Ultra-Fast pTefb, nuclear receptors or the 10 subunits transcription factor TFIIH. n Introduction to Bispecifics Growing Cells: Findings from Systems Biology 15:20 Engineering the Evolution of Bacteria for Protein Production n Advancing Bispecifics Martin Siemann-Herzberg, PhD, Professor, Biotechnology, Institute of Biochemical n Engineering Bispecifics Engineering, University of Stuttgart Morten Nørholm, PhD, Principal Investigator & Senior Scientist, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark In vitro protein synthesis allows rapid expression of proteins without the need to Posters maintain a viable cell. Nevertheless, its effectivity depends on the activity of the Microorganisms have for centuries shown great capacity to produce useful former living cell. Consequently, standard in vitro systems are generated from materials. However, they are also naturally intolerant to dedicating all resources Sponsor & Exhibit Opportunities fast-growing cells, premising most-active translational fidelity. Based on systems to a specialized metabolic task and inherently prone to evade stress and evolve biology attempts, we examined the integrity of the in vitro protein synthesis new properties. We have explored natural and synthetic evolution of bacteria for Venue & Hotel Information machinery, e.g., generated from ultra-fast and non-growing cells. production of pharmaceutical proteins and industrial enzymes. 15:50 Selected Poster Presentation: Designing an Artificial Golgi Registration Information 11:45 Minimal Cell: Cell-Free Protein Synthesis in Micro-Compartments Lei Kai, PhD, Group Leader, Department of Cellular and Molecular Biophysics, Max Reactor for Cell-Free Glycosylation Planck Institute of Biochemistry Elli Makrydaki, Research Scientist, Chemical Engineering, Imperial College London PEGSummitEurope.com The construction of a minimal cell that exhibits the essential characteristics of 16:20 Refreshment Break in the Exhibit Hall with Poster Viewing life is a great challenge in the field of synthetic biology. Assembling a minimal cell

PEGSummitEurope.com | 44 Final Days Expression 12-13 November 2018 to Register! 17:00 KEYNOTE PRESENTATION: From Systems Biology to Systems Cover Biologics Sachdev Sidhu, PhD, Professor, Molecular Genetics, The Donnelly Centre, Conference-at-a-Glance University of Toronto We have established a platform to combine large-scale systems biology Short Courses approaches with the discovery and development of new antibody drugs, and to develop efficient, systems-scale strategies to target intracellular signaling Training Seminars networks at the protein level with ubiquitin variants and other scaffolds. This efficient pipeline connects basic research to translational science in a new model for drug development, which we have termed “Systems Biologics”. Engineering n Display of Biologics 17:30 CLOSING PANEL DISCUSSION: Tools for Expanding the Protein n Engineering Antibodies Engineering and Production Toolbox n Engineering Bispecifics Moderator: Oncology Tsafi Danieli, PhD, Director, BioGiv Excubator & Head, Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life n Antibody-Drug Conjugates Sciences, The Hebrew University of Jerusalem n Advancing Bispecifics Panelists: n Novel Therapies for Cancer Richard Altman, MS, Scientist, Protein Technologies, Amgen Analytical Nicola Burgess-Brown, PhD, Principal Investigator, Biotechnology, Structural Genomics Consortium (SGC), University of Oxford n Optimisation & Developability Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National n Analytical Characterisation Laboratory for Cancer Research n Aggregates & Particles Mario Lebendiker, PhD, Head, Protein Purification Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Immunotherapy Hebrew University of Jerusalem n Tumour Microenvironment Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk n CAR T, TIL & TCR Therapy Foundation Center for Biosustainability, Technical University of Denmark n Agonist Targets & Combinations Jonathan Zmuda, PhD, Director, Cell Biology, Thermo Fisher Scientific Expression 18:30 End of Systems Engineering and Synthetic Biology n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 45 Final Days Expression 14-15 November 2018 to Register! 11th Annual Cover Optimising Expression Platforms Conference-at-a-Glance Employing Cell Factories for the Production of Therapeutic Proteins Short Courses

Training Seminars WEDNESDAY 14 NOVEMBER Selexis’ SUREscan utilizes NGS technologies and proprietary bioinformatics to comprehensively assess the genomic architecture of Selexis-generated cell 07:45 Registration and Morning Coffee lines. SUREsignature is a unique, genome-wide collection of genetic markers that Engineering establishes cell line clonality to a probability significance not previously achievable TRANSIENT EXPRESSION AND PRODUCTION and determines cell line-specific barcodes for better master cell bank quality n Display of Biologics control. These technologies minimize risk and accelerate biologics development n Engineering Antibodies 08:30 Chairperson’s Remarks by allowing for optimal clone selection and monitoring. n Engineering Bispecifics Richard Altman, MS, Scientist, Protein Technologies, Amgen 10:35 Coffee Break in the Exhibit Hall with Poster Viewing Oncology 08:35 KEYNOTE PRESENTATION: Transient Protein (Gene) 11:15 Tracking the Evolution of Transiently Transfected Individual Cells n Antibody-Drug Conjugates Expression: From R&D towards Pharmaceutical Manufacturing in a Microfluidic Platform n Advancing Bispecifics Florian M. Wurm, Dr. rer. nat., Professor Emeritus, Swiss Federal Institute of Sébastien Sart, PhD, Research Associate, Genome and Genetics – Laboratory n Novel Therapies for Cancer Technology Lausanne (EPFL); Founder, Chairman, ExcellGene SA of Physical Microfluidics and Bioengineering, Institut Pasteur; Laboratoire Transient protein (gene) expression (TGE) delivers products in days. HEK-293 d’Hydrodynamique, École Polytechnique Analytical cell TGE helped to identify a “better than nature” thrombolytic resulting in A droplet microfluidic platform was used to assess the heterogeneities of CHO-S the approval of (TNKase “Tenecteplase”). Scale-up R&D resulted in the first n Optimisation & Developability transiently transfected with cationic liposomes. A single cell analysis of the GFP 100 Liter–scale production in the late 1990s. Recent progress in transient n Analytical Characterisation production kinetics revealed the presence of a subpopulation producing higher protein expression, including viral vector production, delivers grams and tens n Aggregates & Particles levels of GFP, which was dependent on the cell size, the charge and the amount of of grams of high-quality protein/virus vector for preclinical research and, for plasmid DNA carried by the lipoplexes. This study demonstrates the potential of clinical use soon? Immunotherapy time resolved single cell measurements to explain population dynamics. n Tumour Microenvironment 09:05 Stable versus Transient Gene Expression: A Case Study on 11:45 Discovery of Novel Enhancers for Antibody Expression by n CAR T, TIL & TCR Therapy Antibody Glycosylation Transcriptomics-Based Pathway Analysis n Agonist Targets & Combinations Cleo Kontoravdi, PhD, Reader, Biosystems Engineering, Department of Chemical Markus Neubauer, PhD, Head, Cell Culture Research, Pharma Research & Engineering, Imperial College London Expression Development, Roche Innovation Center Munich In this case study, we explored the differences in CHO cell metabolism, antibody Expression of antibodies by transient transfection (TT) represents a widely used n Synthetic & Systems Engineering productivity and N-linked glycosylation between stable and transient gene technology in basic research and drug discovery. Small molecule enhancers of n Optimising Expression expression at physiological temperature and under mild hypothermia. For each expression are applied to maximize protein yield. This study demonstrates a n Purification Technologies system, we identified bottlenecks for improving antibody quality and have successful strategy for identification of expression enhancers using comparative attempted to address them using cell and process engineering. transcriptomics in conjunction with bioinformatics pathway analysis. Both Bispecifics pathways affecting antibody expression and molecules enhancing antibody 09:35 How Do We Assemble an Effective and Efficient Protein n expression have been discovered. This strategy may also be relevant for Introduction to Bispecifics Production Toolbox? n Advancing Bispecifics development and optimization of bioprocesses beyond TT. Richard Altman, MS, Scientist, Protein Technologies, Amgen n Engineering Bispecifics A robust, flexible transient protein production facility provides critical support to 12:15 High-Throughput Antigen and Antibody Production at the IPI drug discovery efforts. We review the ongoing evolution of our protein production James Love, PhD, COO, Institute for Protein Innovation, Harvard Institutes of Posters endeavors focusing on two critical components. The first is the strategic assembly Medicine of mammalian expression “tools” that gives us a toolbox capable of expressing In order to generate open-source monoclonal antibodies against every extracellular Sponsor & Exhibit Opportunities diverse and challenging candidate proteins. The second is the harmonization and secreted protein in humans, we have developed expression platforms capable of the entire protein production process thereby reducing turnaround times and of generating high-quality antigens and antibodies in HT format. Optimized Venue & Hotel Information increasing throughput. transient transfection is performed via automated processes at 1ml and 30ml scales, and semi-automated for larger scales in HEK and CHO cells. Novel Registration Information Sponsored by 10:05 Selexis’ SUREscan and SUREsignature: DNA preparation, protein purification and characterization platforms have been Technologies for Assessment of Cell Line Integrity and implemented to support the expression pipeline. PEGSummitEurope.com Clonality Igor Fisch, CEO, Selexis SA

PEGSummitEurope.com | 46 Final Days Expression 14-15 November 2018 to Register! 12:45 Scaling Up and Scaling Out: Pushing the Sponsored by 14:35 Synonymous Codon Selection for Enhanced Yield of Functional Cover Boundaries of Transient Protein Production Proteins Ian Wilkinson, CSO, Research and Development, Absolute Antibody Ltd. Patricia L. Clark, PhD, O’Hara Professor of Chemistry & Biochemistry; Concurrent Conference-at-a-Glance Whilst transient yields have improved drastically in the last decade, scalable Professor of Chemical & Biomolecular Engineering, University of Notre Dame systems are time-consuming and expensive to implement. Absolute Antibody We have developed a sensitive system to detect effects of synonymous Short Courses has developed systems which scale up and scale out protein expression and codon substitutions on the co-translational folding of proteins expressed in purification, enabling the rapid and cost-effective production of milligram to gram E. coli, coupling the success of folding to E. coli fitness. We find that position- Training Seminars quantities of large panels of proteins. specific synonymous codon changes can have dramatic effects on folding yield, particularly at those positions that correspond to sub-domain “motif” Sponsored by Engineering 13:00 Value Adding Microbial-Based Solutions for structures.15:05 Development of Myceliophthora thermophila into a the GMP-Production of Recombinant Proteins Highly Productive Biologics Production Host n Display of Biologics Nicole Peuker, PhD, Principal Expert USP Development, BioProcess n Engineering Antibodies Marika Vitikainen, PhD, Senior Scientist, Industrial Biotechnology and Food Development, Wacker Biotech GmbH Solutions, VTT Technical Research Centre of Finland Ltd. n Engineering Bispecifics Wacker Biotech, known as THE MICROBIAL CDMO, handles several GMP Myceliophthora thermophila is well known as a hyper-productive platform for production sites in Europe with capacities to deliver multiple hundred grams Oncology industrial enzymes. We are further developing a high-level, low-cost production of drug substance per batch. We will present case studies for our innovative host for biotherapeutics, such as antibodies, Fc-fusion proteins and vaccines. We n Antibody-Drug Conjugates and cost-saving E. coli technologies for the production of difficult-to-make have adapted it by modifying regulatory genes, reducing secreted proteases and n Advancing Bispecifics biopharmaceuticals. altering glycosylation pathways needed for adding mammalian glycoforms. As a n Novel Therapies for Cancer result, this system has reached antibody productivity levels over 1.7 g/L/day, much 13:15 Luncheon Presentation I: Host Cell Line Directed Sponsored by higher than current best-in-class platforms. Analytical Evolution as a Tool to Increase Titres and Reduce Cell Line Development Timelines 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing n Optimisation & Developability Leon Pybus, PhD, Staff Scientist, Mammalian Cell Culture, R&D, n Analytical Characterisation FUJIFILM Diosynth Biotechnologies 16:15 Identification and Visualization of Production Bottlenecks in CHO Cells n Aggregates & Particles Can directed evolution strategies yield ‘fit-for-purpose’ host cell lines with improved Kerstin Otte, PhD, Professor, Biotechnology, Biberach University of Applied Sciences Immunotherapy biomanufacturing relevant phenotypes? In this study we audition different With the advance of complex format proteins, mammalian expression systems strategies and identify those that lead to recombinant cell lines with improved often show low performance. Determining factors may be the accumulation or n Tumour Microenvironment growth and expression capability whilst maintaining stable production of product haltering of heterologous proteins within the different cellular compartments, thus n CAR T, TIL & TCR Therapy with acceptable product quality attributes. disturbing transport or secretion. We established a streamlined microscopy-based n Agonist Targets & Combinations methodology for CHO production cells investigating the distribution of difficult-to- 13:45 Luncheon Presentation II: Accelerating Timelines Sponsored by express proteins within organelles of the secretory pathway to enable identification Expression by Integrating Cell Line Development and Manufacturing of rate-limiting steps. This method was adapted for automated detection of production bottlenecks during industrial cell line development processes. n Synthetic & Systems Engineering Programs n Optimising Expression Nicole Wakes, Ms, Group Leader, Cell Line Development, Abzena 16:45 Streamlining Monoclonal CHO Cell Line Generation Using Droplet n Purification Technologies The start of cell line development represents a significant milestone for biologics Microfluidics innovators, it’s a commitment to a specific molecule, and the start of the journey Bispecifics towards IND. By using the latest technologies such as automated multiple micro- James White, Senior Scientist, Protein Sciences, UCB Biopharma scale bioreactors and high-throughput analytics, it is possible to interrogate clones To increase the efficiency and speed of selecting high productivity monoclonal n Introduction to Bispecifics more closely to determine productivity, manufacturability and predict performance stable CHO cell lines, we have evaluated a droplet microfluidics device. This device n Advancing Bispecifics at scale at an early stage. In addition the data generated can be used to inform screens for secreted antibody from millions of single CHO cells in their own pL n Engineering Bispecifics process and analytical development. By viewing CLD and manufacturing as one volume droplets and to deposit the highest producers at a single cell per well. Our integrated continuum, it is possible to de-risk manufacturing at scale as well as data demonstrates that high productivity clones similar to those generated in our Posters reduce overall time to IND. standard processes can be selected, but with reduced resource needs and time to therapeutic clone selection. Sponsor & Exhibit Opportunities 14:15 Session Break 17:15 PANEL DISCUSSION: Transient, Stable, or Both? Venue & Hotel Information TOOLS FOR INCREASING EXPRESSION AND PRODUCTION Moderator: Henry C. Chiou, PhD, Director, Cell Biology, Life Science Solutions, Thermo Fisher Registration Information 14:30 Chairperson’s Remarks Scientific Henry C. Chiou, PhD, Director, Cell Biology, Life Science Solutions, Thermo Fisher Panelists: Scientific Richard Altman, MS, Scientist, Protein Technologies, Amgen PEGSummitEurope.com Cleo Kontoravdi, PhD, Reader, Biosystems Engineering, Department of Chemical Engineering, Imperial College London James Love, PhD, COO, Institute for Protein Innovation, Harvard Institutes of Medicine

PEGSummitEurope.com | 47 Final Days Expression 14-15 November 2018 to Register! Markus Neubauer, PhD, Head, Cell Culture Research, Pharma Research & possible to perform more complex cellular engineering. In terms of industrial Cover Development, Roche Innovation Center Munich biotechnological exploitation, these tools, coupled with systems biology analyses, Florian M. Wurm, Dr. rer. nat., Professor Emeritus, Swiss Federal Institute of have facilitated improvements in E. coli for the production of protein products. Conference-at-a-Glance Technology Lausanne (EPFL); Founder, Chairman, ExcellGene SA This talk focuses on engineered E. coli for the production of glycosylated proteins. Limitations and opportunities are presented. Short Courses 17:45 Networking Reception in the Exhibit Hall with Poster Viewing 10:05 Advanced CHO Cell Expression System for Sponsored by Training Seminars 18:45 Problem-Solving Breakout Discussions* Increased Transient Protein Production *See website for details. Mathieu PORTE, Senior Scientist, Bioproduction, Polyplus- 19:45 End of Day transfection Engineering Transient expression in CHO cells is commonly used to rapidly produce antibodies n Display of Biologics but is unfortunately limited by transfection efficiency and inherent productivity. n Engineering Antibodies THURSDAY 15 NOVEMBER To overcome this issue, we developed an advanced transient expression system n Engineering Bispecifics consisting in the synergistic association of a novel CHO chemically defined 08:00 Registration and Morning Coffee medium and a powerful transfection reagent. Oncology 10:20 Sponsored Presentation (Opportunity Available) n Antibody-Drug Conjugates DIFFICULT-TO-EXPRESS PROTEINS n Advancing Bispecifics 08:30 Chairperson’s Remarks 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Novel Therapies for Cancer Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk 11:15 Making and Testing the Human Secretome Analytical Foundation Center for Biosustainability, Technical University of Denmark Rick Davies, PhD, Associate Director, Discovery Biology, AstraZeneca Pharmaceuticals The objective of the Human Secretome Project is to produce and screen all n Optimisation & Developability human secreted proteins to unlock biology leading to new hypotheses and target n Analytical Characterisation 08:35 FEATURED PRESENTATION: High-Throughput Expression and discovery. Over 1,000 secreted proteins have been expressed and purified using a n Aggregates & Particles Screening of Human Integral Membrane Proteins mammalian expression system and screened in a number of cell-based phenotypic Nicola Burgess-Brown, PhD, Principal Investigator, Biotechnology, Structural assays. The results of this work have revealed differential activities of protein Immunotherapy Genomics Consortium (SGC), University of Oxford family members in different biological contexts and provided some learning on n Tumour Microenvironment The SGC promotes research advancement through our open access policy, and successes and failures of recombinant expression of secreted proteins. n CAR T, TIL & TCR Therapy in the absence of IP. Globally, we have solved more than 2000 human protein n Agonist Targets & Combinations structures and 10 novel integral membrane proteins (IMPs). Although we have made a significant contribution to structural biology and protein production for 11:45 FEATURED PRESENTATION: Engineering CHO Cells for Production Expression functional studies, IMPs and protein-protein complexes still remain a challenge to of Hard-to-Produce Proteins produce. Here, I present our established approaches for eukaryotic expression and n Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk Synthetic & Systems Engineering screening IMPs using baculovirus/insect cells and BacMam technology. n Optimising Expression Foundation Center for Biosustainability, Technical University of Denmark n Purification Technologies Through extensive systems biology-based cell line engineering, we have 09:05 Challenging Molecules in Biopharmaceutical Development: engineered CHO cells for the production of therapeutically relevant proteins that were previously not possible to produce using CHO cells. Bispecifics Innovative Tools for Cell Line Development n Introduction to Bispecifics Martin Gamer, PhD, Associate Director, Early Stage Bioprocess Development, n Advancing Bispecifics Boehringer Ingelheim Pharma GmbH & Co. KG 12:15 Luncheon Presentation I: Streamlined Discovery Sponsored by n Engineering Bispecifics The increasing number of engineered, often antibody-derived molecule formats and Production of Therapeutic Antibodies entering into biopharmaceutical development poses significant challenges on the Meelis Kadaja, PhD, MBA, Director, Business Development, Icosagen generation of high-yielding CHO cell factories. My talk highlights the most recent Posters Cell Factory advances at Boehringer Ingelheim to improve cell line development of DTE proteins. We take advantage of the universal HybriFree antibody discovery engine to efficiently Sponsor & Exhibit Opportunities Our toolbox comprises in silico methods to assess molecule developability leading to tailored development, a rationally designed novel host cell line ensuring high discover therapeutic antibodies by direct cloning from B-cells of immunized rabbit, Venue & Hotel Information performances, robustness and scalability as well as innovative genetic elements and chicken, human, or dog. HybriFree method is further powered by our patented QMCF screening tools to select for outstanding CHO production cell lines. expression platform to produce premium-quality recombinant protein antigens, and antibodies cost-effectively for preclinical research (including afucosylated antibodies Registration Information 09:35 Producing a Glycosylating Cell Factory for enhanced ADCC). Technologies and case studies will be presented and discussed. Phillip Wright, PhD, Faculty Pro-Vice-Chancellor, Faculty of Science, Agriculture & 12:45 Luncheon Presentation II (Sponsorship Opportunity Available) PEGSummitEurope.com Engineering, Newcastle University With advances in metabolic engineering and synthetic biology, it has become 13:15 Dessert Break in the Exhibit Hall with Poster Viewing

PEGSummitEurope.com | 48 Final Days Expression 14-15 November 2018 to Register! 14:00 End of Optimising Expression Platforms Cover 17:00 Dinner Short Course Registration* Conference-at-a-Glance 17:30 – 20:30 Dinner Short Courses Short Courses Recommended Short Course* Training Seminars SC9: Optimising Protein Purification Strategies in Advance: Getting Your Plan Right Engineering *Separate registration required. Click here for details. n Display of Biologics n Engineering Antibodies n Engineering Bispecifics Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 49 Final Days Expression 15-16 November 2018 to Register! 4th Annual Cover Protein Purification Technologies Conference-at-a-Glance Streamlining Processes Short Courses

Training Seminars THURSDAY 15 NOVEMBER 15:20 Sponsored Presentation (Opportunity Available) 13:00 Registration 15:35 Networking Refreshment Break Engineering 13:15 Dessert Break in the Exhibit Hall with Poster Viewing HARNESSING THE POWER OF SMALL n Display of Biologics n Engineering Antibodies INNOVATING PURIFICATION PROCESSES 16:00 HTP Production of a New Human PDZome Allows Quantitative n Engineering Bispecifics PDZ-Peptide Interaction Screening Through HTP Holdup Assay 14:00 Chairperson’s Opening Remarks Renaud Vincentelli, PhD, Head, IBIsA Facility for High-Throughput Cloning, Oncology Dorota Antos, PhD, Professor, Chemical and Process Engineering, Rzeszow Expression and Purification of Proteins, Architecture et Fonction des n Antibody-Drug Conjugates University of Technology Macromolécules Biologiques (AFMB), CNRS-AMU UMR n Advancing Bispecifics Using our custom E. coli HTP protein production pipeline (Saez et al, JOVE 2014), n Novel Therapies for Cancer 14:05 KEYNOTE PRESENTATION: How Problems of Protein we could produce soluble the 266 human PDZ domains. To characterize in detail, Purification Are Being Addressed across Structural Laboratories the HPV E6 - PDZome binding interaction profile, we automated the Hold-up assay Analytical in Europe: Insights from the European Research Infrastructure (Vincentelli et al, Nature Methods 2015) a quantitative and versatile in vitro protein- Consortium protein interaction assay. The protocols and some new results on this application n Optimisation & Developability will be detailed during the seminar. n Analytical Characterisation Ray Owens, PhD, Professor, Molecular Biology and Head, Oxford Protein n Aggregates & Particles Production Facility, University of Oxford 16:30 Protein Purification and Detection with Nanobodies Technology developments to streamline the production of proteins for Ulrich Rothbauer, PhD, Professor, Pharmaceutical Biotechnology, Natural and structural biology have been largely driven by the demands of structural Immunotherapy Medical Sciences Institute, University of Tübingen proteomics. However, the purification of increasingly complex proteins and n Tumour Microenvironment protein assemblies has challenged traditional high-throughput structural Nanobodies are attractive tools for protein purification, detection and analysis n CAR T, TIL & TCR Therapy proteomic workflows. The response of a number of academic centres in as they are small, highly stable, and are easily producible thereby offering n Agonist Targets & Combinations Instruct, a distributed European Research Infrastructure Consortium (www. an unlimited supply of consistent binding molecules. Recent advances in structuralbiology.eu) will be reviewed and common trends highlighted. identification of target-specific nanobodies from synthetic gene libraries makes Expression these tools broadly available. Here, we present our latest progress in nanobody generation, functionalization and application for protein purification and detection. n Synthetic & Systems Engineering 14:35 Simplification of Purification Strategies for Mammalian Proteins n Optimising Expression from Single Targets to High-Throughput Projects Using an Enhanced 17:00 End of Day n Purification Technologies Biochemical Code David O’Connell, PhD, Lecturer, Biotherapeutics, Biomolecular & Biomedical 17:30 Dinner Short Course Registration* Bispecifics Science, University College Dublin 17:30 – 20:30 Dinner Short Courses n Introduction to Bispecifics We are investigating the sequences of amino acids and their associated post- n Advancing Bispecifics translational modifications that confer superior transport characteristics upon secreted proteins to move through and across gradients. With one eye on creating Recommended Short Course* n Engineering Bispecifics new protein engineering design principles, we are aiming to understand the SC9: Optimising Protein Purification Strategies in Advance: Getting elements of encoded behaviour of proteins including IgG, cytokines, interferons Your Plan Right Posters and the very many proteins that make up our secretome using a high-throughput *Separate registration required.Click here for details. expression and interrogation model in HEK293. Establishing high-throughput Sponsor & Exhibit Opportunities expression, purification and transport assays will be described.

Venue & Hotel Information 15:05 Overcoming Limitations of Conventional Tag Sponsored by Systems – Strep-Tactin®XT Applications Registration Information Dennis Karthaus, MSc, IBA Lifesciences The Strep-Tactin®XT:Twin-Strep-tag®-purification system enables protein purification at high yields and purity under physiological PEGSummitEurope.com conditions. Providing the highest binding affinity among all affinity tag systems, the technology fulfills the demands of mammalian expression systems (e.g. Expi) and is well suited for downstream applications like SPR. PEGSummitEurope.com | 50 Final Days Expression 15-16 November 2018 to Register! FRIDAY 16 NOVEMBER 11:05 Tailor Made Affinity Adsorbents for Selective Capture and Recovery Cover Ana Cecília Roque, PhD, Principal Investigator and Associate Professor, Sciences 08:00 Registration and Morning Coffee and Technology, University Nova of Lisbon Conference-at-a-Glance Biological and chemical libraries containing a high diversity or designed to fit a PURIFYING MEMBRANE PROTEINS target biopharmaceutical, are powerful tools to develop robust peptidomimetics Short Courses based on different scaffold molecules. The scaffold molecules range from small 08:30 Chairperson’s Remarks synthetic ligands, to artificial β-hairpin peptides and small protein domains Training Seminars Maximilian Hartl, PhD, Senior Scientist, Roche Pharma Research & Early produced chemically. We study the potential of these scaffold affinity reagents Development (pRED), Large Molecule Research, Roche Innovation Center Munich to find binding partners against several targets (e.g. recombinant proteins, Engineering phosphorylated peptides, and virus-like particles), and to develop mild and 08:35 Structural Biology of Membrane Proteins: Expression Tricks, and selective affinity-based purification processes. n Display of Biologics to Solubilize or Not to Solubilize n Engineering Antibodies Dirk Linke, PhD, Professor, Genetics and Evolutionary Biology, Biosciences, 11:35 Increased Productivity with Membrane-Based Sponsored by n Engineering Bispecifics University of Oslo Protein A Columns in mAb Purification In recent work, we have designed expression systems for bacterial outer William Barrett, PhD, Chromatography, Gore & Associates Oncology membrane and surface proteins. These can be used to express and purify, Traditional protein purification processes may be time-consuming, e.g., important vaccine candidates for bacterial diseases, but also for studying n Antibody-Drug Conjugates causing slow-downs in the screening process. The GORE™ Protein membrane protein structure directly in the membrane with solid-state NMR n Advancing Bispecifics Capture Device with Protein A eliminates those constraints by combining a high methods. n Novel Therapies for Cancer dynamic binding capacity of greater than or equal to 30mg/mL at 20 seconds residence time (3.0mL/min). The membrane-based pre-packed column may help 09:05 Adaptive Automated Membrane Protein Purification Using AkTA Analytical produce a more highly-concentrated elution pool in less time and may help increase Avant productivity by eliminating the need for additional downstream concentration steps. n Optimisation & Developability Jonas Lee, PhD, Scientist, Protein Technologies, Amgen, Inc. n Analytical Characterisation Transmembrane proteins are key targets in drug discovery. However, they are 12:05 Problem-Solving Breakout Discussions with a Light Snack* n Aggregates & Particles difficult to purify due to complex buffer requirements to solubilize. We use various *See website for details. high-throughput methods to screen for best detergent conditions followed Immunotherapy by innovative methods to purify multiple targets in different buffer conditions IMPROVING AND SCALING UP PURIFICATION PROCESSES n Tumour Microenvironment automatically. n 13:00 Chairperson’s Remarks CAR T, TIL & TCR Therapy 09:35 Nanoparticles to Stabilize Membrane Proteins in a Lipid n Agonist Targets & Combinations Ulrich Rothbauer, PhD, Professor, Pharmaceutical Biotechnology, Natural and Environment Medical Sciences Institute, University of Tübingen Expression André Heuer, PhD, Senior Scientist, Salipro Biotech AB More than 60% of all current drugs target membrane proteins. However, membrane 13:05 Process Development of the Antibody-Drug Conjugate (ADC) n Synthetic & Systems Engineering proteins are very unstable, which is a major challenge for the pharmaceutical SYD985 – A Case Study n Optimising Expression industry. Here we present the latest results on a novel system to stabilize Xiaonan Li, PhD, Senior Scientist, Downstream Processing, Synthon n Purification Technologies membrane proteins using Salipro nanoparticles. Salipro nanoparticles stabilize Biopharmaceuticals BV membrane proteins in a lipid environment that allows them to work in detergent- SYD985 is an antibody-drug conjugate (ADC) based on trastuzumab and a Bispecifics free buffer systems. cleavable linker-duocarmycin payload. A case study will be presented in which a n Introduction to Bispecifics hydrophobic interaction chromatography (HIC) purification process was developed n Advancing Bispecifics 10:05 Networking Coffee Break allowing removal of the undesired antibody species together with unbound linker- n Engineering Bispecifics drug. It was possible to elute the product (SYD985) using mild conditions without NEXT-GEN CHROMATOGRAPHY requirement for any organic solvent. The HIC purification step was scaled up demonstrating consistency and robustness. Posters 10:35 Potential of Centrifugal Partition Chromatography for the Separation of Proteins 13:35 New Formats, New Experiences - DSP Feedback for Carefully Sponsor & Exhibit Opportunities Mirjana Minceva, PhD, Assistant Professor, Biothermodynamics, Life and Food Selecting a Molecule for Development Venue & Hotel Information Sciences Weihenstephan, Technische Universität München Maximilian Hartl, PhD, Senior Scientist, Roche Pharma Research & Early Centrifugal partition chromatography (CPC) is a solid support-free chromatography Development (pRED), Large Molecule Research, Roche Innovation Center Munich Registration Information method in which both stationary and mobile phase are liquid. This technology Biopharmaceuticals evolved from copying natural molecules to tailor-made, highly combines advantages of liquid-liquid extraction and chromatography, such as high engineered drugs with disease specific action modes. The impressive ideas of loading capacity, high recovery and high resolution. Moreover, as a result of the our molecule designers often result in promising early in vivo data that challenge PEGSummitEurope.com liquid nature of the stationary phase, problems associated with column packing technical-scale drug development. In this talk, we show examples of non-predicted are avoided. CPC can be used with aqueous two-phase systems (ATPS) providing challenges we faced during purification of novel drugs. We present solutions and a mild environment for the separation of proteins. In this talk, the potential of CPC feedback from purification for the selection process of next-generation drugs. will be demonstrated for the separation of model mixture of proteins. PEGSummitEurope.com | 51 Final Days Expression 15-16 November 2018 to Register! 14:05 The Effect of New Stabilizers in Downstream mAb Process Cover Intermediates Irina Ramos, PhD, Downstream Process Scientist, MedImmune, Inc. Conference-at-a-Glance The stability of downstream process intermediates is extremely important to Short Courses define fit-to-plant parameters and keep product quality attributes within the acceptance criteria. Here we present the impact of adding small novel organic Training Seminars molecules, designed to stabilize a protein’s molecular structure, in the context of important downstream steps. In this work, we used a monoclonal antibody (mAb) that showed (1) aggregation during viral inactivation at low pH conditions and (2) Engineering low flux throughput during viral filtration. Both steps are traditionally part of the downstream process platform used in mAbs as dedicated virus reduction steps n Display of Biologics and contribute to the virus safety for mAb-based medicines. Our analysis identifies n Engineering Antibodies novel protein stabilizers that can significantly improve mAb process intermediates n Engineering Bispecifics stability and manufacturing throughput. Oncology 14:35 Pitfalls in Design and Scaling Up Protein Chromatography n Antibody-Drug Conjugates Dorota Antos, PhD, Professor, Chemical and Process Engineering, Rzeszow n Advancing Bispecifics University of Technology n Novel Therapies for Cancer Because of the complexity of thermodynamic, kinetic, and hydrodynamic effects accompanying protein chromatography, design and scaling up of the process Analytical is often impossible without understanding underlying adsorption mechanism. Specific effects that can occur in protein chromatography will be discussed. The n Optimisation & Developability phenomena of band deformation due to mass transport resistances, protein n Analytical Characterisation unfolding, sample solvent effect, and dispersion in extra column volumes will be n Aggregates & Particles illustrated. The solvent gradient and temperature mediated separations will be considered. Immunotherapy n Tumour Microenvironment 15:05 Monoclonal Antibody Reduction and Re-Oxidation by Copper n CAR T, TIL & TCR Therapy Sulfate during Manufacturing and Impact on Product Quality n Agonist Targets & Combinations Green Guihang Zhang, PhD, Associate Director, Large Molecule Purification Development, Global Product and Process Development, Incyte Corporation Expression Significant disulfide bond reduction of an IgG1 monoclonal antibody was observed during the late stage of the CHO cell culture in manufacturing, leading to the batch n Synthetic & Systems Engineering failure due to significant amount of low molecular weight species and aggregates. n Optimising Expression Two methods of copper sulfate spiking were investigated to prevent and reverse n Purification Technologies the product disulfide bond reduction during manufacturing. Both methods could re-oxidize the reduced product and prevent further reduction throughout the Bispecifics manufacturing process. n Introduction to Bispecifics n Advancing Bispecifics 15:35 End of Summit n Engineering Bispecifics

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PEGSummitEurope.com | 52 Final Days Bispecifics 12-13 November 2018 to Register! Cover Introduction to Bispecifics: Conference-at-a-Glance History, Engineering, and Application Short Courses By Cambridge Healthtech Institute

Training Seminars Intro to Bispecifics will be organized as an informative and practical guide to get up to speed on critical aspects of bispecific antibody therapeutics. Topics will include Engineering historical successes, failures, and lessons learned. Specific practical instruction will span mechanisms of action, engineering, developability, regulatory considerations, n Display of Biologics and translational guidelines. Perspectives on ideal implementation of bispecifics as n Engineering Antibodies targeted and immunomodulatory approaches will be discussed. n Engineering Bispecifics Instructor: Oncology G. Jonah Rainey, PhD, Executive Director, Head of Antibody Research, MabVax Therapeutics Holdings, Inc. n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Analytical n Optimisation & Developability n Analytical Characterisation Click Here for More Training Seminars n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 53 Final Days Bispecifics 14-15 November 2018 to Register! 10th Annual Cover Advancing Bispecifics and Combination Conference-at-a-Glance Short Courses Therapy to the Clinic Training Seminars New Approaches with Exciting Results

WEDNESDAY 14 NOVEMBER Having a functional bioassay that is MOA-based, accurate, precise, robust and Engineering reproducible is critical for the development of antibody-based biologics. We n Display of Biologics 07:45 Registration and Morning Coffee have developed reporter bioassays that meet these criteria for a broad range of n Engineering Antibodies antibody modalities including Fc effector function, immune checkpoint modulation, n Engineering Bispecifics ENGAGEMENT OF NK CELLS / CHECKPOINT INHIBITORS bispecific antibody engagement, cytokine modulation, and others. Here we will present the latest technology advancements and demonstrate how these Oncology IN COMBINATION bioassays can be used for a broad range of applications. n Antibody-Drug Conjugates 08:30 Chairperson’s Remarks 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics Marina Bacac, PhD, Head, Cancer Immunotherapy, Roche Innovation Center Zurich n Novel Therapies for Cancer 08:35 Multi-Specific Antibody Technology Engaging NK Cells in COMBINATION THERAPIES / T-CELL ENGAGEMENT Oncology Analytical 11:15 KEYNOTE PRESENTATION: Development of Effective Laurent Gauthier, PhD, Senior Director, Research and Development, Innate Pharma n Optimisation & Developability Combination Therapies for Immuno-Oncology We report the design and generation of new multi-specific antibodies which n Analytical Characterisation Rakesh Dixit, PhD, Vice President, Safety Assessment, Medimmune, Inc. selectively recruit NK cells against tumour targets (NKCE). NCKEs bind to NKp46 n Aggregates & Particles This presentation will cover: the rationale for combination therapies in on NK cells and can potentially co-engage other activating receptors like CD16 to immunotherapy; the challenges of selecting the combination drugs that induce tumor target killing. NKCEs show good developability profile, anti-tumour Immunotherapy would give synergism; translational and precision medicine approaches in activity in in vitro and in vivo preclinical models and provide new therapeutic combination immune-oncology, and safety considerations in development of n Tumour Microenvironment options for cancer treatment. the combination drugs. n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations 09:05 ATOR-1015, a Next-Generation, Bispecific CTLA-4 x OX40 11:45 Development of Novel Fully Human Bispecific Antibodies for Targeting Antibody for Tumor Directed Immunotherapy of Cancer Oncology Expression Christina Furebring, PhD, Senior Vice President, Research, Alligator Bioscience AB Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron, Inc. n Synthetic & Systems Engineering ATOR-1015 is a next-generation CTLA-4 x OX40 bispecific immune activating This presentation will describe Regeneron’s bispecific platform and present n Optimising Expression antibody developed for tumor-directed immunotherapy. ATOR-1015 binds both preclinical data on T-cell redirecting bispecifics being developed for solid and n Purification Technologies targets simultaneously, promoting cell-cell interactions expected to enhance the immuno-stimulating effect of the compound. The mode of action of ATOR-1015 liquid tumor indications. In addition, a brief update on the status of REGN1979, Regeneron’s CD20xCD3 bispecific in phase 1 clinical trials, will be presented. Bispecifics is a combination of regulatory T-cell (Treg) depletion and effector T-cell activation. ATOR-1015 is currently in preclinical development and clinical trials will start in the 12:15 CD20 TCB (RG6026), a Novel “2:1” T-Cell Bispecific Antibody for n Introduction to Bispecifics second half of 2018. n Advancing Bispecifics the Treatment of B-Cell Malignancies n Engineering Bispecifics 09:35 Development of an Agonist Redirected Checkpoint, SIRPa-Fc- Marina Bacac, PhD, Head, Cancer Immunotherapy, Roche Innovation Center Zurich CD40L, for Cancer Immunotherapy We give an overview of preclinical data of CD20-TCB, a novel CD20-targeting T-cell Posters George Fromm, PhD, VP, R&D, Shattuck Labs bispecific antibody on the “2:1” IgG format that consistently demonstrated superior We will present the generation of a novel, two-sided human fusion protein potency compared to other CD20-TCBs with conventional “1:1” IgG format. In Sponsor & Exhibit Opportunities incorporating the extra cellular domains of SIRPα and CD40L, SL-172154. SL- addition, we present a novel approach enabling safer administration of such potent 172154 binds both CD47 and CD40 with high affinity, activates CD40 signaling in drug consisting of a single administration of obinutuzumab (Gazyva pre-treatment, Venue & Hotel Information the absence of Fc receptor cross-linking, outperforms CD47 and CD40 antibodies Gpt) prior to the first infusion of CD20-TCB. in multiple tumor models and was safe in non-human primates. SL-172154 will 12:45 Affimer Therapeutics: A Novel Human Scaffold Sponsored by Registration Information enter the clinic in 2019 in multiple indications. for the Generation of Bi-Specific Molecules 10:05 Development and Application of MOA-Based Sponsored by Amrik Basran, PhD, CSO, Avacta PEGSummitEurope.com Reporter Bioassays for Immunotherapy Drug Affimer therapeutics are based on the human protein Stefin A, Development a small (12kDa) intracellular protease inhibitor. We have built large (1x1010) Mei Cong, Director, Custom Assay Services, Promega Corporation phage display libraries and generated highly selective Affimer binders to range of PEGSummitEurope.com | 54 Final Days Bispecifics 14-15 November 2018 to Register! therapeutically relevant targets such as PD-L1 and LAG-3. We have shown that 16:45 Immunostimulatory Properties of a Novel IL-15-Based Tumor- Cover the Affimer scaffold can be formatted as in-line fusions, to the Fc domain or a full Targeted Immunocytokine antibody to create bispecific molecules are able to engage both target antigens. Anika Jäkel, PhD, Director, Preclinical Pharmacology & Cancer Immunology, Conference-at-a-Glance 13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Glycotope GmbH Enjoy Lunch on Your Own Interleukin-15 (IL-15), a potent stimulator of NK and CD8 T-cells, is considered Short Courses to be one of the most encouraging immunotherapeutics for cancer treatment. We created novel IL-15-based immunocytokines with different potencies and Fc Training Seminars 14:15 Session Break effector functions binding to a tumor-specific carbohydrate antigen to potentiate COMBINATION THERAPIES / T-CELL ENGAGEMENT tumor targeting. By applying a comprehensive screening approach considering PK, Engineering PD and cytokine profile, we seek to identify a promising lead candidate suitable for (CONT.) mono or combinatorial therapy of solid tumors. n Display of Biologics n Engineering Antibodies 14:30 Chairperson’s Remarks 17:15 Development of Novel Interleukin-2 Variants for Immunotherapy n Engineering Bispecifics Eric Smith, PhD, Director, Bispecific Antibodies, Regeneron of Cancer and Autoimmune Diseases Ekkehard Moessner, PhD, Head, Protein Engineering, Large Molecules Research, Oncology 14:35 Targeting B-Cell Malignancies with a CD3 Bispecific Antibody - Preclinical Evaluation of DuoBody-CD3xCD20 Roche Innovation Center Zurich The development of interleukin-2 muteins throughout the preclinical development n Antibody-Drug Conjugates Ida Hiemstra, PhD, Lead Scientist, Translational Research, Genmab B.V. n Advancing Bispecifics will be described, for two different approaches. In one approach the IL-2 will An overview will be presented of preclinical data identifying DuoBody-CD3xCD20 n Novel Therapies for Cancer be used for cancer immunotherapy, and in the other the Il-2 is engineered for as the most potent B-cell-targeting CD3 bispecific antibody in anin vitro functional applications in autoimmune diseases. screen covering a comprehensive panel of B cell targets. DuoBody-CD3xCD20 Analytical induced potent T cell activation and cytotoxic activity in the presence of malignant 17:45 Networking Reception in the Exhibit Hall with Poster Viewing n Optimisation & Developability B-cells in vitro and in vivo. The capacity of DuoBody-CD3xCD20 to deplete B n Analytical Characterisation cells from blood and lymphoid organs, after intravenous or subcutaneous 18:45 Problem-Solving Breakout Discussions* n Aggregates & Particles administration, was assessed in cynomolgus monkeys as part of the non-clinical *See website for details. safety studies. A clinical study evaluating the DuoBody-CD3xCD20 is currently Immunotherapy enrolling. 19:45 End of Day n Tumour Microenvironment 15:05 APVO436: A CD3 Engager with Low Cytokine Release Profile n CAR T, TIL & TCR Therapy Targeting CD123 for AML THURSDAY 15 NOVEMBER n Agonist Targets & Combinations Catherine J McMahan, PhD, Senior Director, Pharmacology and Cell Sciences 08:00 Registration and Morning Coffee Research and Non-Clinical Development, Aptevo Therapeutics Expression APVO436 is a CD123 x CD3 bispecific ADAPTIR antibody designed to treat AML. BISPECIFICS IN THE CLINIC n Synthetic & Systems Engineering It contains an Fc region for extended half-life and has bivalent binding to both the n Optimising Expression tumor target and CD3. APVO436 was optimized for manufacturability, specificity 08:30 Chairperson’s Remarks n Purification Technologies and low levels of cytokine release compared to other bispecific formats. APVO436 David Szymkowski, PhD, Vice President, Cell Biology, Xencor induces robust proliferation of T-cells and tumor target lysis in vitro and in vivo Bispecifics xenograft models. 08:35 Update on BiTE® Antibody Constructs Currently in Clinical Development n Introduction to Bispecifics 15:35 Refreshment Break in the Exhibit Hall with Poster Viewing n Advancing Bispecifics Virginie Nägele, PhD, Senior Scientist BiTE Technology Amgen Research (Munich) n Engineering Bispecifics IMMUNOSTIMULATORY CYTOKINES FOR TUMOUR GmbH The BiTE® technology is a clinically explored approach targeting malignant TARGETING AND CONTROL OF TOXICITY Posters cells by T-cells with blinatumomab being the first bispecific T-cell engager (BiTE) approved for the treatment of patients with relapsed or refractory B-precursor 16:15 Engineering Bispecific Cytokine-Fc Fusions to Create Safer and Sponsor & Exhibit Opportunities acute lymphoblastic leukemia (B-ALL) in the US. More recently, blinatumomab has More Effective Immuno-Oncology Therapies also received accelerated approval for the treatment of B-ALL minimal residual Venue & Hotel Information David Szymkowski, PhD, Vice President, Cell Biology, Xencor disease. This presentation will give an update on the current clinical development Immunostimulatory cytokines such as IL-2 and IL-15, while extremely potent, of BiTE antibody constructs at Amgen focusing on hematologic malignancies like Registration Information suffer from poor tolerability and rapid clearance, limiting their potential as cancer acute myeloid leukemia and multiple myeloma, and on solid tumor indications. treatments. Using our clinically-validated bispecific Fc domain, we generated a heterodimeric IL15/IL15Rα-Fc with reduced potency and longer half-life. IL15/ 09:05 DVD-Ig Platform: Clinical Lessons and Future Directions PEGSummitEurope.com IL15Rα-Fc demonstrates improved exposure and stimulates multiple effector-cell Tariq Ghayur, PhD, Distinguished Research Fellow, Foundational Immunology, responses in mice and monkeys. Such cytokine-Fc biologics may possess better AbbVie Bioresearch Center tolerability and improved efficacy with less-frequent dosing than recombinant Several DVD-Ig molecules have been tested in preclinical models and in clinic for cytokines. PEGSummitEurope.com | 55 Final Days Bispecifics 14-15 November 2018 to Register! autoimmune and oncology indications. Emerging data suggests that the DVD-Ig 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Cover format per se is not immunogenic. However, target biology may play an important role in anti-drug antibody response (ADA, immunogenicity). Lessons learned from 14:00 End of Advancing Bispecifics and Combination Therapy Conference-at-a-Glance these studies may be broadly applicable and will be discussed. to the Clinic

Short Courses 09:35 Development of a Potent Anti-Cancer Bispecific Antibody 17:00 Dinner Short Course Registration* Targeting VEGF and DLL4 17:30 – 20:30 Dinner Short Courses Training Seminars Weon-Kyoo You, PhD, Head, R&D, Vice President, ABL Bio, Inc. Simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways is Recommended Short Course* known to lead potent inhibition of tumor progression. In this presentation, we will Engineering talk about ABL Bio’s bispecific antibody platforms and development processes of SC10: Engineering of Bispecific Antibodies n Display of Biologics the most advanced asset, a bispecific antibody targeting VEGF and DLL4 (ABL001) *Separate registration required. Click here for details. n Engineering Antibodies which is currently ongoing a phase 1 clinical study. We will cover an overview of n Engineering Bispecifics preclinical data as well as interim clinical data of ABL001. Oncology 10:05 SMAB: a Novel Bispecific Antibody Platform for Sponsored by Therapeutic Development n Antibody-Drug Conjugates Janice Jin, Head, Project Management Center, Project Management n Advancing Bispecifics Department, GenScript n Novel Therapies for Cancer Urgent demands for new therapeutic strategies, such as novel modalities are Analytical raised during explosive growth of therapeutic antibody drugs. In this presentation, we will introduce GenScript proprietary SMAB bispecific antibody platform which n Optimisation & Developability minimizes the immunogenicity and manufacture concerns of current bispecific n Analytical Characterisation antibody platforms while enabling bi-valent and multi-valent therapeutics. n Aggregates & Particles 10:20 Sponsored Presentation (Opportunity Available) Immunotherapy 10:35 Coffee Break in the Exhibit Hall with Poster Viewing n Tumour Microenvironment n CAR T, TIL & TCR Therapy DESIGN TO PROOF-OF-CONCEPT n Agonist Targets & Combinations 11:15 Case Study on New Product: Biology and Proof-of-Concept Expression Mihriban Tuna, PhD, Vice President, Drug Discovery, F-star n Synthetic & Systems Engineering 11:45 Tumor-Localized T-Cell Co-Stimulation Using Antibody-Anticalin n Optimising Expression Fusion Proteins: From Flexible Design to Proof-of-Concept and Beyond n Purification Technologies Marina Pavlidou, PhD, Project Leader, Discovery, Pieris Pharmaceuticals GmbH Bispecifics We describe the generation of bispecific molecules by fusing T-cell targeting Anticalin proteins to tumor targeting antibodies. We show superior potency n Introduction to Bispecifics of the bispecific over the combination of building blocks and the combination n Advancing Bispecifics of benchmark molecules. The activity of the bispecific is dependent on the n Engineering Bispecifics expression of the tumor target showing the potential of providing a tumor localized activation of the immune system with high efficacy and reduced peripheral toxicity. Posters 12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Sponsor & Exhibit Opportunities Enjoy Lunch on Your Own

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PEGSummitEurope.com | 56 Final Days Bispecifics 15-16 November 2018 to Register! 10th Annual Cover Engineering Bispecifics Conference-at-a-Glance Enhanced Targeting and Functionality Short Courses

Training Seminars THURSDAY 15 NOVEMBER This presentation describes our approach to developing immune-oncology therapeutics, in particular Humabody VH products, small highly adaptable multi- 13:00 Registration functional proteins which can be developed into differentiated therapeutics with Engineering excellent characteristics for tumour targeting. It includes the development of a 13:15 Dessert Break in the Exhibit Hall with Poster Viewing Biparatopic PD-1 inhibitor showing efficacy in a Pembrolizumab insensitivein n Display of Biologics vivo model, a Bispecific PD-1, LAG3 inhibitor and a targeted IO approach in which n Engineering Antibodies FOCUS ON T-CELL ENGAGERS T-cell co-stimulation is focused away from the periphery and into the tumour n Engineering Bispecifics microenvironment. 14:00 Chairperson’s Opening Remarks Oncology Thomas Van Blarcom, PhD, Associate Research Fellow, Protein Engineering, Pfizer, 17:00 End of Day Inc. n Antibody-Drug Conjugates 17:00 Dinner Short Course Registration* n Advancing Bispecifics n Novel Therapies for Cancer 14:05 KEYNOTE PRESENTATION: Novel T Cell Engagers for 17:30 – 20:30 Dinner Short Courses Targeted Recruitment of Effector Cells to Tumors Analytical Yoram Reiter, PhD, Head, Molecular Immunology, Technion-Israel Institute of Recommended Short Courses* Technology n Optimisation & Developability We have developed a new class of recombinant chimerical molecule that SC8: Selection, Screening and Engineering for Affinity Reagents n Analytical Characterisation serve as T cell engagers to re-direct potent immune effector functions to SC10: Engineering of Bispecific Antibodies n Aggregates & Particles specifically kill tumor cells. These T cell engagers are based on the genetic *Separate registration required. Click here for details. fusion of antibody fragments, specific for tumor cell surface antigens to Immunotherapy monomeric HLA molecules that carry immunodominant peptides that can n Tumour Microenvironment recall potent effector T cells. The molecular feature of these molecules/ FRIDAY 16 NOVEMBER n CAR T, TIL & TCR Therapy approaches and their in vitro and in vivo activities will be described. n Agonist Targets & Combinations 08:00 Registration and Morning Coffee 14:35 Engineering of a T-Cell Dependent Bispecific to Broaden the Expression Therapeutic Index for Solid Tumors FC ENGINEERING FOR ENHANCED PRODUCT PROPERTIES n Synthetic & Systems Engineering Christoph Spiess, PhD, Senior Scientist, Antibody Engineering, Genentech, Inc. AND FOR BRAIN DELIVERY I will present the engineering of the bispecific to achieve selective binding to tumor n Optimising Expression 08:30 Chairperson’s Remarks n Purification Technologies cells and provide data demonstrating improved tumour infiltrationin vitro and in vivo and preclinical safety. Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research Bispecifics Sponsored by and Early Development Roche 15:05 Presentation to be Announced n Introduction to Bispecifics 08:35 Glyco-Optimization of Antibodies Targeting Immune Checkpoint n Advancing Bispecifics 15:35 Networking Refreshment Break Molecules: Case Studies of an Agonist and an Antagonist n Engineering Bispecifics Christoph Goletz, PhD, Associate Director, Preclinical Pharmacology & Cancer 16:00 Creating a Novel T-Cell Engaging Bispecific Antibody Platform: Immunology, Glycotope GmbH Fine Tuning Anti-Tumor Activity with Sequence-Based Discovery and Posters Glyco-engineering is an established strategy to improve tumor antigen-targeting Machine Learning antibodies, e.g. anti-CD20, anti-EGFR, regarding their ADCC activity. In two case Sponsor & Exhibit Opportunities Nathan Trinklein, PhD, Vice President, Teneobio studies of an agonistic anti-CD40 and an antagonistic anti-PD-L1 antibody, we Using a multiple myeloma tumor cell line along with primary human PBMCs, we show that glyco-optimization can also be applied to enhance activity of antibodies Venue & Hotel Information demonstrate a spectrum of in vitro tumor cell killing activity with varied levels of targeting immune checkpoint molecules. cytokine release using our bispecific molecules with diverse CD3 binding activities. Registration Information In summary, we have created a T-cell engaging bispecific antibody platform with 09:05 Development of a Novel Fc Heterodimerization Technology tuned T-cell agonism that can be used to optimize the therapeutic index for a Fabian Richter, PhD, Post-Doc, Biomedical Engineering, Cell Biology and variety of tumor antigens. Immunology, University of Stuttgart PEGSummitEurope.com The innovative heterodimerization technology “Fc1k” (Fc-one-kappa) was created 16:30 Developing Humabody VH Therapeutics for Immuno-Oncology and used for the generation of monovalent as well as polyvalent and multi-specific James Legg, PhD, Vice President, R&D, Crescendo Biologics antibody-like molecules. We demonstrated the applicability in a monovalent Fv-

PEGSummitEurope.com | 57 Final Days Bispecifics 15-16 November 2018 to Register! Fc1k format, used for cytokine receptor blockade and in a bispecific scFv2-Fc1k 12:05 Problem-Solving Breakout Discussions with a Light Snack* Cover molecule, simultaneously targeting two antigens. This novel platform technique *See website for more details. provides for covalent heterodimerization of immunoglobulin domains, based on Conference-at-a-Glance fully human and naturally occurring sequences. TECHNOLOGIES FOR DISCOVERY AND SCREENING, CMC, Short Courses 09:35 Identification of a PD-L1 Binding Fcab: A Potent Inhibitor of TARGETING, POTENCY AND LOW RISK OF TOX Immunosuppressive Signals 13:00 Chairperson’s Remarks Training Seminars Jose Munoz Olaya, PhD, Principal Scientist, Drug Discovery, F-star Mark S. Dennis, PhD, Fellow, Denali Therapeutics Checkpoint inhibitors have been very popular and successful targets in the field of immuno-oncology. Here we describe the isolation of an Fcab, an antibody Fc Engineering 13:05 Case Studies on How Digital and Automated Solutions Transform domain modified to bind to a target, specific to PD-L1. The Fcab exhibits high the Discovery and Development of Next-Generation Antibodies n Display of Biologics affinity to human PD-L1 that translates into strong potency in cell-based functional Martin Bader, PhD, Head, Biochemical and Analytical Research, Pharma Research n assays. An anti-murine surrogate molecule, with similar potency, also exhibits Engineering Antibodies and Early Development, Roche n Engineering Bispecifics activity in an MC38 syngeneic tumour model. This activity is improved when the Fcab is paired with Fabs targeting other immune checkpoint regulators. We systematically introduced automated and digital solutions along our antibody Oncology discovery and development chain. A number of examples will be highlighted 10:05 Networking Coffee Break that demonstrate how automation and data science speed up 1) developability n Antibody-Drug Conjugates predictions to enable fast selection of clinical leads, 2) automation during n Advancing Bispecifics 10:35 Antibody Transport Vehicle (ATV): A Novel Brain Delivery Platform functional characterization, and 3) machine learning during cell line selection and n Novel Therapies for Cancer Mark S. Dennis, PhD, Fellow, Denali Therapeutics bioprocess modeling. As a consequence, output during the antibody discovery and The Antibody Transport Vehicle (ATV) enables the delivery of large molecule development phase increases substantially. Analytical therapeutics to the brain for the treatment of neurological diseases. The ATV 13:35 Talk Title to be Announced n Optimisation & Developability platform contains an engineered Fc domain that binds the transferrin receptor and n Analytical Characterisation utilizes receptor-mediated transcytosis to cross the BBB. Transport in nonhuman 14:05 Redefinition of ErbB2/3 Tumor Targeting: How to Design Truly primates was assessed by the inhibition of β-secretase 1 (BACE1) in brain which n Aggregates & Particles Potent Bispecific and Biparatopic Agents was robustly inhibited by ATV:BACE1 leading to a sustained reduction in amyloid beta levels. Rastislav Tamaskovic, PhD, Head, TC Facility, Senior Scientist, Biochemistry, Immunotherapy University of Zurich n Tumour Microenvironment 11:05 Turning Affibody Molecules into Efficient Peptide Binders by Due to adaptiveness of oncogenic networks, tumors readily develop resistance n CAR T, TIL & TCR Therapy Dimerization against targeted therapies. Recently, we have described major compensatory n Agonist Targets & Combinations John Lofblom, PhD, Associate Professor, Engineering Sciences in Chemistry, routes, which become activated in therapy of ErbB2-positive cancer - and Biotechnology and Health, KTH Royal Institute of Technology developed a new class of bispecific and biparatopic anti-ErbB2/3 targeting agents endowed with capabilities to overcome the adaptive resistance. Analogously, Expression Affibody molecules are small three-helical affinity proteins. Generating binders we build a new platform for tumor RTK fingerprinting aimed at identification of n for the amyloid beta peptide yielded a variant with 20-pM affinity, and with a Synthetic & Systems Engineering prospective therapeutic leads and truly synergistic combination therapies. n Optimising Expression unique 2:1 stoichiometry mode of binding as well as structural rearrangements in n Purification Technologies both the affibody domains and the amyloid beta peptide that is sequestered in a 14:35 Productive Common Light Chain Libraries Yield Diverse Panels of tunnel-like cavity. Engineered binders for other peptides show similar structural High Affinity Bispecific Antibodies Bispecifics rearrangements and mode of binding, indicating that the new dimeric scaffold is well suited for such molecular recognitions. Thomas Van Blarcom, PhD, Associate Research Fellow, Protein Engineering, Pfizer, n Introduction to Bispecifics Inc. n Advancing Bispecifics 11:35 Industrializing IO Therapeutic Discovery Platforms: Multispecifics, Here we describe the design of a synthetic human antibody library based on n Engineering Bispecifics Engineered TCRs and CARs common light chains to generate antibodies with biochemical and biophysical Christoph Freiberg, PhD, Senior Scientific Consultant, Biologics, Genedata properties that are indistinguishable to traditional therapeutic monoclonal antibodies. We used this library to generate diverse panels of well-behaved, high Posters Novel classes of bio-molecules are currently evaluated for their use in cancer affinity antibodies toward a variety of epitopes across multiple antigens including immunotherapy. Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, mouse 4-1BB in order to investigate the therapeutic potential of biparatopic Sponsor & Exhibit Opportunities non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR- bispecific antibodies. based bispecific constructs promise significant advantages. However, these Venue & Hotel Information highly engineered molecules pose new challenges in design, engineering, cloning, 15:05 DuoBody Technology: A Versatile Platform for Bispecific Antibody expression, purification, and analytics. We present an infrastructure that addresses Discovery and Development Registration Information these challenges and enables the industrialization of these various novel therapeutic platforms. Rick Hibbert, MBA, PhD, Assistant Director, Protein Production and Chemistry, Genmab B.V. PEGSummitEurope.com The DuoBody® platform represents a versatile, elegant and robust technology for generating bispecific antibodies. The post-production process is based on controlled Fab-arm exchange and yields bispecific antibodies that retain the

PEGSummitEurope.com | 58 Final Days Bispecifics 15-16 November 2018 to Register! molecular structure and quality attributes of therapeutic IgGs. The process is Cover robust, high-throughput compatible and shows linear scalability from bench to manufacturing scale. This presentation will highlight recent insights in the Conference-at-a-Glance preclinical and CMC development of DuoBody products.

Short Courses 15:35 End of Summit

Training Seminars

Engineering n Display of Biologics n Engineering Antibodies n Engineering Bispecifics Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 59 Final Days to Register! SPONSOR & EXHIBITOR INFORMATION

Cover Comprehensive sponsorship packages allow you to achieve your objectives before, during, and long after the event. Signing on

Conference-at-a-Glance earlier will allow you to maximize exposure to hard-to-reach decision-makers.

Short Courses Podium Presentations — Available within Invitation-Only Dinner / Hospitality Suite Looking for additional ways to drive leads Main Agenda! Sponsors will select their top prospects from the confer- Training Seminars to your sales team? Showcase your solutions to a guaranteed, targeted audi- ence pre-registration list for an evening of networking at the ence. Package includes a 15 or 30-minute podium presenta- hotel or at a choice local venue. CHI will extend invitations, CHI’s Lead Generation Programs will help you to tion on the scientific agenda, exhibit space, branding, full conduct follow-up and confirm attendees. The evening will obtain more targeted, quality leads throughout the Engineering year. We will mine our database of over 800,000 life conference registrations, use of the event mailing list be customized to meet with your specific objectives. science professionals to your specific needs. We n Display of Biologics and more. n guarantee a minimum of 100 leads per program! Engineering Antibodies Additional branding & promotional Opportunities include: n Engineering Bispecifics Luncheon Presentations opportunities include: • White Papers Opportunity includes a 30-minute podium presentation in • Webinars • Hotel Room Keys Oncology the main session room. Lunch will be served to all del- • Custom Market Research Survey • Focus Groups egates in attendance. A limited number of presentations are • Podcasts n Antibody-Drug Conjugates • Conference Tote Bags available for sponsorship and they will sell out quickly. Sign n Advancing Bispecifics • Literature Distribution (Tote Bag Insert or Chair Drop) on early to secure your talk! n Novel Therapies for Cancer • Badge Lanyards • Notebooks To learn more about sponsorship and exhibit One-on-One Meetings Analytical • Program Guide Advertisement opportunities, please contact: Select your top prospects from the pre-conference registra- n Optimisation & Developability tion list. CHI will reach out to your prospects and arrange EXHIBIT n Analytical Characterisation the meeting for you. A minimum number of meetings will Companies A-K Exhibitors will enjoy facilitated networking opportunities n Aggregates & Particles be guaranteed, depending on your marketing objectives Jason Gerardi and needs. A very limited number of these packages will with over 900 qualified delegates, making it the perfect Senior Manager, Business Development opportunity to launch a new product, collect feedback, and be sold. 781-972-5452 Immunotherapy generate new leads from around the world. Exhibit space [email protected] n Tumour Microenvironment sells fast, so reserve yours today. n CAR T, TIL & TCR Therapy Companies L-Z n Agonist Targets & Combinations Carol Dinerstein Senior Manager, Business Development Expression 781-972-5471 n Synthetic & Systems Engineering 2017 ATTENDEE DEMOGRAPHICS [email protected] n Optimising Expression n Purification Technologies Services/Societies 2% Asia Professor Bispecifics Other 2% Healthcare 5% Rest of World 7% 5% 4% Manager n Introduction to Bispecifics France 10% Other VIEW LATEST n Advancing Bispecifics 7% 7% n Engineering Bispecifics Sales & SPONSOR/EXHIBITOR Switzerland Marketing Academic 9% Rest of 12% FLOORPLAN Posters 15% Europe 22% Sponsor & Exhibit Opportunities United Venue & Hotel Information Biotech + Pharma Germany Kingdom Scientist/ 76% 15% 20% Executive + Technologist Director 38% Registration Information USA 26% 18% PEGSummitEurope.com COMPANY TYPE GEOGRAPHIC LOCATION DELEGATE TITLE

PEGSummitEurope.com | 60 Final Days to Register! Cover PRESENT Conference-at-a-Glance Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. To secure a poster board and inclusion Short Courses in the conference materials, your abstract must be submitted, approved and your A POSTER registration paid in full by 5 October 2018. Training Seminars AND SAVE Reasons you should present your research poster at this conference: Engineering • Your research will be seen by our international delegation, representing leaders n Display of Biologics from top pharmaceutical, biotech, academic and government institutions n Engineering Antibodies • Receive €50 off your registration n Engineering Bispecifics • Your poster abstract will be published in our conference materials Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer €50 Analytical n Optimisation & Developability n Analytical Characterisation n Aggregates & Particles Immunotherapy n Tumour Microenvironment n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations Expression n Synthetic & Systems Engineering n Optimising Expression n Purification Technologies Bispecifics n Introduction to Bispecifics n Advancing Bispecifics n Engineering Bispecifics

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PEGSummitEurope.com | 61 Final Days to Register! VENUE & HOTEL INFORMATION

Cover CONFERENCE VENUE: Conference-at-a-Glance Lisbon Congress Center Short Courses (Centro de Congressos de Lisboa) Praca Das Industrias Training Seminars Lisbon, 1300-307, Portugal Tel: +351 218-921-400 Engineering n Display of Biologics n Engineering Antibodies n Engineering Bispecifics Oncology n Antibody-Drug Conjugates n Advancing Bispecifics n Novel Therapies for Cancer Analytical n Optimisation & Developability n Analytical Characterisation HOST HOTELS: n Aggregates & Particles Immunotherapy HOTEL VILA GALE OPERA Travessa do Conde da Ponte 141 n Tumour Microenvironment n CAR T, TIL & TCR Therapy Lisbon, 1300-141, Portugal n Agonist Targets & Combinations Tel: +351-213-605-400 Discounted Room Rate: Expression €200 SINGLE/€208 DOUBLE n Synthetic & Systems Engineering **Includes breakfast and n Optimising Expression complimentary Internet** n Purification Technologies Discounted Cut-off Date: 10 September 2018 Bispecifics n Introduction to Bispecifics n Advancing Bispecifics PESTANA PALACE HOTEL LISBON n Engineering Bispecifics Rua Jau, 54 Lisbon, 1300-314, Portugal Posters Tel: +351-213-615-600 Discounted Room Rate: Sponsor & Exhibit Opportunities For additional information €175 SINGLE/€190 DOUBLE Venue & Hotel Information go to the travel page of **Includes breakfast and complimentary Internet** Registration Information PEGSummitEurope.com Discounted Cut-off Date: 22 September 2018 PEGSummitEurope.com

PEGSummitEurope.com | 62 Alumni Discount 20% Off Final Days CONFERENCE PRICING *Pre-doctoral, full-time student Poster Discount €50 Off to Register! SHORT COURSES Commercial Academic, Government, Student* Hospital-affiliated WANT TO REGISTER BY PHONE? Cover One short course €625 €375 €125 Contact our Registration department at Conference-at-a-Glance Two short courses €895 €625 €195 781-972-5400 or Toll-free in the US 888-999-6288. Short Courses Monday, 12 November | Morning, 9:00 – 12:00 Thursday, 15 November | Dinner, 17:30 – 20:30 WAYS TO SAVE! Training Seminars SC1: Transient Protein Expression: A Key Tool to Enable Rapid Protein Engineering SC7: Protein Aggregation: Mechanism, Characterization and Consequences

SC2: Making Antibody Libraries in Phage and Yeast SC8: Selection, Screening and Engineering for Affinity Reagents Alumni Discount - SAVE 20%: CHI appreciates your past participation at PEGS. As a result of the great Engineering SC3: Introduction to the Tumour Microenvironment and Response to SC9: Optimising Protein Purification Strategies in Advance: Getting Your Plan Right loyalty you have shown us, we are pleased to extend to Cancer Immunotherapy you the exclusive opportunity to save an additional 20% n Display of Biologics off the registration rate. n Engineering Antibodies SC4: Mutation and Selection Strategies beyond Affinity Optimisation SC10: Engineering of Bispecific Antibodies Register 3 - 4th is Free! n Engineering Bispecifics SC5: Surfactants in Biotherapeutics: Can’t Live with Them, Can’t Live without Them Individuals must register for the same conference or conference combination and submit completed Oncology registration form together for discount to apply. CONFERENCE PRICING n Antibody-Drug Conjugates GROUP DISCOUNTS: PREMIUM PACKAGE - Best Value (Includes access to all conferences/Training Seminars Monday-Friday, excludes short courses) Group Discounts are Available! Special rates are n Advancing Bispecifics available for multiple attendees from the same n Novel Therapies for Cancer Registration Rate after 12 October and on-site €3299 €1799 €695 organization. For more information on group discounts contact Bill Mote at 781-972-5479. Analytical STANDARD PACKAGE (Includes access to two conferences/Training Seminars, excludes short courses) ADDITIONAL REGISTRATION DETAILS 23% VAT will be added to each registration n Optimisation & Developability Registration Rate after 12 October and on-site €2949 €1399 €525 n Analytical Characterisation *Alumni, Group, Protein Society or Antibody Society BASIC PACKAGE (Includes access to one conference/Training Seminar, excludes short courses) n Aggregates & Particles Membership, Twitter, LinkedIn, Facebook or any other Registration Rate after 12 October and on-site €2249 €1049 €375 promotional discounts cannot be combined. Discounts not applicable on Event Short Courses. Immunotherapy n Tumour Microenvironment Monday - Tuesday Wednesday - Thursday (am) Thursday (pm) - Friday 12 - 13 November 14 - 15 November 15 - 16 November TRAINING SEMINARS n CAR T, TIL & TCR Therapy n Agonist Targets & Combinations ENGINEERING C1A: Display of Biologics C1B: Engineering Antibodies C1C: Engineering Bispecifics CHI Training Seminars Offer: • 1.5 day instruction C2A: Next-Generation Antibody-Drug C2B: Advancing Bispecifics and Combination C2C: Novel Therapies for Cancer and ONCOLOGY • Morning and afternoon refreshments (as applicable; Expression Conjugates Therapy to the Clinic Emerging Targets specific times included in the onsite agendas) n Synthetic & Systems Engineering C3A: Optimisation & Developability C3B: Analytical Characterisation of C3C: Protein Aggregates & Particles ANALYTICAL Registered Attendees Receive: n Optimising Expression Biotherapeutics • Lunch on the full-day of instruction n Purification Technologies C4A: Targeting the Tumour Microenvironment C4B: Winning Strategies for CAR T, TIL and C4C: Agonist Immunotherapy Targets and IMMUNOTHERAPY • A hard copy handbook for the specific seminar TCR Therapy Combination Therapies of registration (limited additional handbooks are Bispecifics available for non-registered attendees) EXPRESSION C5A: Systems Engineering and Synthetic Biology C5B: Optimising Expression Platforms C5C: Protein Purification Technologies n Introduction to Bispecifics CHI requests that Training Seminars not be interrupted once they have begun. TS7A: Introduction to Bispecifics C2B: Advancing Bispecifics and Combination C1C: Engineering Bispecifics n BISPECIFICS We ask that attendees commit to attending the entire program so as to not Advancing Bispecifics Therapy to the Clinic disturb the hands-on style instruction being offered to other participants. n Engineering Bispecifics TS6A: Basic Technologies in a Protein Production Lab TS6B: Rational Approaches to Biologics TS6C: Potency and Comparability for Cell and VIDEO AND/OR AUDIO RECORDING OF By Cambridge Healthtech Institute Formulation & Delivery Gene Products ANY KIND IS PROHIBITED ONSITE AT Posters ALL CHI EVENTS. TS7A: Introduction to Bispecifics TS7B: Next-Generation Sequencing for Antibody Discovery and Engineering Sponsor & Exhibit Opportunities TS8A: Introduction to Protein Engineering How to Register: Venue & Hotel Information PEGSummitEurope.com Registration Information [email protected] P: 781.972.5400 PEGSummitEurope.com or Toll-free in the U.S. 888.999.6288