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1 IBC s 16th Annual IMMUNOGENICITY FOR BIOTHERAPEUTICS Advance Risk Assessment Strategies and Optimize the Prediction of Immune Response to Accelerate the Process from Concept to Approval November 9-10, 2015 Hyatt Regency Reston Reston, VA Improve your drug safety analysis with improved, specific, and accurate immunogenicity information so you can minimize the time it takes to gain regulatory approval and increase speed to market n Hear first-hand perspectives from the FDA & NIST, and leave with all your questions answered n Collaborate with peers and industry experts to develop solutions for predicting, anticipating, and mitigating risks created by potential immune responses n Discover cutting-edge technologies to improve immunogenicity testing n Improve the accuracy of your risk assessment by understanding how protein aggregation impacts immunogenic responses Co-Located with WELL-CHARACTERIZED BIOLOGICALS see details inside Hear Expert Guidance on Bringing Safe and Effective Therapeutics to the Patient Faster Samantha Maragh National Institute of Standards & Technology Zuben E. Sauna Center for Biologics Evaluation and Research, Food and Drug Administration Bonnie Wu Janssen Research and Development Cara Fiore CBER, FDA Register Early for Best Rates!

2 NEW BACK BY POPULAR DEMAND Insights on Protein Aggregation to Improve Your Immunogenicity Assessment Learn how protein aggregation impacts immunogenic responses to improve the accuracy of your risk assessment Elevate your strategy to the next level with brand new data and case studies on mitigating the risk of immunogenicity with protein aggregation and managing protein aggregation Break Through Roadblocks with the Roundtable Lunch Discussions Back by popular demand, our lively roundtables are your chance to discuss challenges, roadblocks, and solutions to the biggest issues in characterization, immunogenicity, and biosimilars. Discuss emerging hot topics during lunch on both days. See pages 3 and 4 for more information and a list of discussion topics. NEW SHOWCASE NOVEL RESEARCH Get Your Questions Answered with the Regulatory Town Hall Get clarification and insights from the regulators to clear the pathway to approvals, faster Plus, you will have the opportunity to ask your questions directly to the regulators in an engaging town hall format featuring CDER, CBER, and the NIST. Present a Poster to Showcase Your Novel Research Share your latest research by presenting a scientific poster during the event. All posters will be displayed at the conference for fellow attendees to view and discuss. The deadline to submit your poster abstract is October 9, For more details and to submit your poster abstract, visit Introducing our New Neighbor: Now co-located with Well Characterized Biologicals, we re combining the leading events for efficacy and safety to jumpstart your CMC submissions and accelerate the approval process. Learn about the all access pass and see registration details on pages 5 and 6. For up-to-date program information, visit: 2

3 MONDAY, NOVEMBER 9, :00 Registration and Coffee 8:00 Opening Remarks John Alvino, Senior Manager, Global Regulatory CMC, AstraZeneca Keynote Presentations 8:15 Predicting and Circumventing the Immunogenicity of Therapeutic Coagulation Proteins Zuben Sauna, Principal Investigator, Laboratory of Hemostasis, Division of Hematology, CBER, FDA 9:00 Points to Consider for Serologic Assays Cara Fiore, Ph.D., Microbiologist, Master Reviewer, Division of Vaccines and Related Products Applications OVRR, CBER, FDA 9:45 Technology Workshops Quantify Stability and Determine Aggregation Pathways for Biologics Stability optimization and aggregation minimization are two of the most important hurdles in the development of biologics. Isothermal chemical denaturation is the most accurate way to measure intrinsic protein stability and determine the impact of formulation conditions. The HUNK is a fully automated chemical denaturation platform, which enables the direct determination of protein structural stability (ΔG) and a quantitative assessment of protein aggregation in the native or denatured states. The HUNK is ideally suited to optimize the formulation of mabs, bispecific antibodies and antibody drug conjugates. We will discuss the fundamentals of chemical denaturation and its application to the evaluation of protein stability and formulation condition optimization. Richard K. Brown, Ph.D., Unchained Labs Improved De Novo Identification and Profiling of Disulfide Bonds in Biopharmaceuticals Including Analysis of DSB Scrambling The determination of disulfide bridges in biopharmaceuticals is a time-consuming process. The location of disulfide bridges (DSBs) in biologics, such as antibodies, affects their spatial structures and can impact their safety and efficacy. DSB analysis is therefore indispensable during the characterization of biologics. It is often performed by a time- intensive, data-processing approach, involving the comparison of peptide maps of reduced and non-reduced samples. In order to avoid this differential approach, a workflow analyzing non-reduced protein digests by LC-MALDI-MS/ MS was investigated where the disulfide bonded peptides are reduced in the mass spectrometer. These Innovations in LC-MALDI MS and new processing software make it possible to determine disulfide linkages much faster and without prior knowledge about their positions (de novo). This method was applied to adalimumab, a likely target for biosimilar development. Additionally, a disulfide scrambling experiment was performed on adalimumab, and the results presented. Jason S. Wood, Ph.D., Market Manager, Pharmaceuticals and Biopharmaceuticals, Bruker Daltonics 10:15 Networking and Refreshment Break in Poster and Exhibit Hall Immunogenicity Risk Assessment 10:55 Chairman s Opening Remarks Sam Song, M.D., Manager, Immunogencity Group, Translational Medicine, Takeda Pharmaceuticals 11:00 Panel Discussion: Improving Risk Assessment to Streamline Immunogenicity Testing Bonnie Wu, Ph.D., Principal Scientist, Biologics Clinical Pharmacology, Janssen Research and Development Zuben Sauna, Principal Investigator, Laboratory of Hemostasis, Division of Hematology, CBER, FDA Chloe Ackaert, Ph.D., Postdoctoral Researcher, Immunology, Bio-Engineering Sciences, Free University of Brussels 11:30 Clinical Immunogenicity Risk Assessment and Testing Strategy Clinical immunogenicity risk assessment and mitigation has become one of the most critical considerations in clinical studies for biotherapeutics. This presentation will provide an overview of clinical immunogenicity risk assessment and mitigation and focus on the riskbased immunogenicity testing strategy. Case examples will be presented to share how we have managed the common issues and challenges in clinical immunogenicity assessment. Sam Song, M.D., Manager, Immunogencity Group, Translational Medicine, Takeda Pharmaceuticals 12:00 Phase I Study of a Bi-specific mab/vk Domain Mole Pre-existing antibodies in treatment-naïve subjects have been often detected during clinical ADA assessments. However, limited information on prevalence, physiological effect, and impact on post-treatment ADA induction is available. This talk will address pre-existing antibody characterization and implications for immunogenicity management and strategies during clinical studies. Thomas N. Lee, Investigator, GSK 12:30 Lunch Roundtable Discussions in Poster and Exhibit Hall Take a break from PowerPoint slides to discuss current challenges with your peers. Have one on one access to industry experts as you discuss the hottest topics. Sign-up sheets will be available at the registration desk on site. Each table is first come, first serve until each table is full. Table A: How Similar is Similar Enough: Strategies for Proving Comparability Moderator: Santosh Yadav, Associate Principal Scientist, Sterile Product and Analytical Development, Merck Table B: Predicting Immunogenicity for Biosimilars: What Can be Correlated from the Originator Biologic Moderator: Bonnie Wu, Principal Scientist, Biologics Clinical Pharmacology, Janssen Research and Development Table C: Assessing How Protein Aggregates and Sub-visible Particles Impact Immunogenicity Moderator: Mark Krebs, Senior Scientist, Protein Pharmaceutical Development, Biogen Idec Table D: Strategies for Developing Bioassays Capable of Handling Complex Mechanisms of Action Moderator: Liming Shi, Senior Research Scientist, Eli Lilly and Company Mechanics of ADA Assays 1:25 Chairman s Opening Remarks Kelli Phillips, Group Leader and Research Scientist, PPD 1:30 Improving Bioanalytical Methods for Assay Development Kelli Phillips, Group Leader and Research Scientist, PPD Advancing Mouse Models 2:00 A Case Study of Immunogenicity Considerations in Using Non-Naïve Monkeys for Preclinical PK Studies Antibody Drug Conjugates (ADCs) have been established as effective for treatment of malignancies. This presentation describes development of a cell-based neutralizing antibody (NAb) assay for an ADC designed to combine the selective targeting capacity of a monoclonal antibody (mab) specific to a tumor antigen with the cytotoxic potency of a toxin. Technical challenges and considerations for NAb assays will be discussed. A general guidance on selection of NAb assay format for antibody therapeutics will also be presented. Yanmei Lu, Scientist, Genentech 2:30 Humanized Mouse Models: Applicability and Potential Use in Immunogenicity Studies Because the immune system of different species can distinguish orthologous proteins as foreign, the immunogenicity of therapeutic proteins in humans cannot be assessed by testing these drug products in non-human species as an immune response will invariably be elicited. The use of non-human primates to perform such testing would most closely approximate the human response to a therapeutic protein, but this is generally not feasible for a number of reasons. Various efforts have been made to generate humanized mouse models that would more accurately reflect the human experience. We have focused on the humanized BLT mouse model. Numerous publications have shown that fully human immune responses can be generated in such mice in response to vaccination or natural infection. We hope to address whether biologic drug product attributes that are thought to be immunogenic in vivo can be predicted utilizing this novel humanized mouse model. The qualification of an animal model that will accurately predict the clinical immunogenicity of therapeutic proteins would be expected to result. Jack A. Ragheb, M.D. Ph.D., Chief Medical Research Officer, OBP/OPQ/CDER/FDA 3:00 Networking and Refreshment Break in Poster and Exhibit Hall For up-to-date program information, visit: 3

4 Mitigate Risk of Immunogenicity 3:30 Use of Tolerogenic Nanoparticles to Prevent the Formation of Anti-Drug Antibodies The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and adverse events associated with biologic therapies. We have developed Synthetic Vaccine Particles (SVP) to induce durable antigenspecific immune tolerance for the prevention of ADAs. We will provide specific case studies for coagulation factors in mouse models of hemophilia and adalimumab (Humira) in a model of arthritis. Tolerogenic SVP technology has the potential to improve the safety and efficacy profile of existing biologic drugs and the potential to reduce late stage clinical failure of promising candidates due to ADAs. Takashi Kei Kishimoto, Chief Scientific Officer, Selecta Biosciences 4:00 TBA Immunogenicity of Novel Structures 4:30 Immunogenicity Assessment Strategy of Peptide- Fusion/Peptibody Proteins Peptibodies are engineered proteins that consist of peptides fused to an Fc domain. This modality combines the biological activity of a peptide with the extended activity duration of an antibody. Despite advantages, approved peptibody therapies are limited. Immunogenicity risk factors may include 1) cross reactive components to endogenous proteins or 2) fusion of peptides to an Fc domain with a linker can lead to new epitopes. Case studies are presented to provide an overview of peptibody immunogenicity and an assessment strategy in clinical studies. Troy Barger, Scientist, Pharmacokinetics & Drug Metabolism, Amgen 5:00 Immunogenicity of Nano Bodies Nanobodies are the smallest antigen-binding antibody fragments derived from unique heavy-chain-only camelid antibodies, with exceptional characteristics. However, they have a sequence foreign to human. Thus, humanization of the Nanobodies might be required to decrease their potential immunogenicity. However, recent findings show that antibodies against humanized Nanobodies/human VH domains are found in about 50% of the healthy population. Is humanization in this case the right approach? One Nanobody which successfully passed the Phase I clinical trial, is a nonhumanized, radiolabeled Nanobody used as an in vivo imaging diagnostic tool for HER2+ breast cancer differentiation. The immunogenicity data are presented here. Chloe Ackaert, Ph.D., Postdoctoral Researcher, Immunology, Bio-Engineering Sciences, Free University of Brussels 5:30 Networking Reception in Poster and Exhibit Hall 7:30 Registration and Coffee 8:00 Opening Remarks Michele Fiscella, Scientific Director, Immunochemistry Services, Covance Keynote Presentation 8:15 Assessing Sources of Assay Variability and Improving Confidence At its core, scientific research relies upon making measurements. Understanding which variables impact a measurement is therefore critical to performing high quality research. Variables of interest span pipelines from pre-analytical through analytical processes and data interpretation. NIST serves as the metrology institute of the United States, partnering with other government agencies, academia, pharma and the private sector to support commerce by meeting measurement, technology and standards needs. We will present data and real world examples on how to identify important variables that contribute to measurement variation, uncertainty and bias as well as and ways to improve measurement confidence. Samantha Maragh, Ph.D., Human Geneticist & Molecular Biologist, National Institute of Standards & Technology 9:00 NEW! Regulatory Town Hall This town-hall style format gives attendees the opportunity to ask their questions concerning regulations for process variants and impurities, biologicals, biosimilars, and immunogenicity. Jeffrey C. Baker, Ph.D., Deputy Director, Office of Biotechnology Products, CDER, US FDA Cara Fiore, Ph.D., Microbiologist, Master Reviewer, Division of Vaccines and Related Products Applications OVRR, CBER, FDA Lokesh Bhattacharyya, Lab Chief, Laboratory of Analytical Chemistry and Blood Related Products, Division of Biological Standards and Quality Control, CBER, FDA 9:45 Networking and Refreshment Break in Poster and Exhibit Hall TUESDAY, NOVEMBER 10, 2015 Featured Presentation 10:15 Managing Immunogenicity in an Evolving Biotherapeutics Landscape Michele Fiscella, Scientific Director, Immunochemistry Services, Covance Panel Discussion 11:00 Developing a Characterization Strategy for Proving Comparability with BioSimilars As the first approved biosimilars hit the market, it is critical to understand how to establish comparability and strategies for demonstrating a high degree of similarity. This panel discusses the challenges with proving comparability and helps develop strategies to overcome those challenges Car Santosh Yadav, Ph.D., Associate Principal Scientist, Sterile Product and Analytical Development, Merck Athena Nagi, Director, Biologics Analytical Sciences, Merck Renuka Sivendran, Senior Scientist, Biosimilars Analytical Sciences, Amgen Inc. Predicting Immunogenicity Responses 11:30 Overcome Drug and Soluble Target Interfences in Immunogenicity Sample Analysis for Antibody Therapy Linglong Zou, Ph.D., Director of Experimental Immunology Global Bioassays and Technology, Teva Pharmaceuticals Register Early for Best Savings

5 TUESDAY, NOVEMBER 10, 2015 (continued) Keynote Presentation 12:00 Accelerated or Abbreviated Review Processes and the Development of Commercial Process Control Strategies The endgame of a successful bioprocess development program is the provision of a manufacturing process that not only has been shown to reproducibly supply biopharmaceuticals that meet patient needs but that is also very likely to continue to meet these needs. In an effort to speed these drugs to the patient, FDA has provided several risk-based review pathways which can, in turn, impact the data driven development of process control strategies and lifecycle management plans. This talk will provide an overview of the types of accelerated and abbreviated reviews for therapeutic proteins and discuss the impact on CMC development. Jeffrey C. Baker, Ph.D., Deputy Director, Office of Biotechnology Products, CDER, US FDA 12:45 Lunch Roundtable Discussions in Poster and Exhibit Hall Take a break from PowerPoint slides to discuss current challenges with your peers. Have one on one access to industry experts as you discuss the hottest topics. Sign-up sheets will be available at the registration desk on site. Each table is first come, first serve until each table is full. Table A: Tactics for Identifying and Characterizing Contaminants Moderator: Richard Cavicchi, Ph.D., Physicist, Bioprocess Measurements Group, NIST Table B: Streamlining the Approval Process: What Techniques are Most Useful in Minimizing the Time from Concept to Approval Moderator: John Alvino, Senior Manager, Global Regulatory CMC, AstraZeneca Table C: De-Risking Immune Responses: How Much Risk Can Be Mitigated Moderator: Linglong Zou, Ph.D., Director of Experimental Immunology Global Bioassays and Technology, Teva Pharmaceuticals Table D: Strategies for Minimizing the Occurrence of Variants and Contaminants Moderator: Jon Schiel, Research Chemist, National Institute of Standards and Technology Table E: Regulatory Issues for Biosimilarity Moderator: Jeffrey C. Baker, Ph.D., Deputy Director, Office of Biotechnology Products (OBP), CDER, U.S. FDA New Approaches to Understanding Immunogenicity 1:40 Chairman s Opening Remarks Sofie Pattijn, Chief Technology Officer, ImmunXperts Featured Presentation 11:00 Tools for Early Immunogenicity Risk Assessment Several tools and technologies for the prediction and assessment of an immune response have been developed. Today, more and more drug developers combine in silico and in vitro immunogenicity assessment tools as a criterion to shorten the list of drug candidates and to reduce the development costs later on. Despite various efforts and initiatives to optimize and validate these tools, no real guidelines and recommendations are available to direct optimal usage, application and output. This talk will provide technical details on the in silico and in vitro tools and highlight the limitations and strengths to allow optimal use and data interpretation. Sofie Pattijn, Chief Technology Officer, ImmunXperts 2:15 Influence of Aggregates on In Vitro T Cell Responses The potential for aggregates to form can occur during any stage of the life cycle of a protein therapeutic. New data will be presented showing that protein aggregates can trigger innate responses leading to distinct antigen presenting cell phenotypes which can enhance T cell activation. The importance of this activation in the form of T cell help has been widely accepted as a significant risk factor in the development of anti-drug antibodies (immunogenicity). Data from recent studies highlighting the impact of aggregates with specific properties on drug immunogenicity will also be discussed. Gary Bembridge, Director, Scientific Affairs, Immunology, Antitope Advancing Adjuvants 2:45 Perspective: Regulatory Considerations in the Safety Assessment of Vaccine Adjuvants and Adjuvanted Vaccines The Office of Vaccines Research and Review (OVRR) is responsible for regulatory review of new Investigational New Drug Applications (INDs) and Biologics License Applications (BLAs) for preventive vaccines and therapeutic vaccines for infectious disease indications. Through this review process, OVRR ensures that vaccines are safe, effective, pure, and potent, as specified in Title 21 of the Code of Federal Regulations, Sections 312, 600, and 610. This presentation will review the key components in nonclinical and clinical safety assessment of investigational vaccines regulated by OVRR, with a focus on product testing and characterization and pharmacology and toxicology study design considerations for vaccines with novel adjuvants. In addition, updates on clinical trial design considerations, including demonstration of the added benefit of the adjuvant, adjuvant dose selection and safety monitoring will be discussed briefly. Kirk Prutzman, Primary Reviewer/Regulatory Project Manager, FDA 3:15 Networking and Refreshment Break in Poster and Exhibit Hall Accelerating the Pathway to Regulatory Approval through Immunogenicity Testing 4:00 Approaches to Improve Drug and Drug Target Tolerance of NAb Assays for Accurate Assessment of Clinical Relevant NAb Responses Bonnie Wu, Ph.D., Principal Scientist, Biologics Clinical Pharmacology, Janssen Research and Development Characterization of Product Variants and Impurities 4:30 Panel Discussion: Aggregation after Administration of Biotherapeutics in Human Plasma: Possible Implications for Immunogenicity and Toxicity Development of not-aggregated formulations of biopharmaceutics is currently based on studies in the application container (e.g., vials, syringes). However, large aggregates may form when such not-aggregated formulations are mixed with human serum or blood. Thus, the formulation carries a definitive risk of adverse events due to sub-micron and micron-size aggregates, such as blocking f blood capillaries and increased immunogenicity. Tudor Arvinte, Professor of Biopharmaceutics and CEO, President, Therapeomic Inc., University of Geneva, Switzerland 5:00 Close of Conference Register Early for Best Savings

6 IBC s 16th Annual IMMUNOGENICITY FOR BIOTHERAPEUTICS Co-Located with WELL-CHARACTERIZEDBIOLOGICALS November 9-10, 2015 Hyatt Regency Reston Reston, VA Accelerate the process from concept to approval with: Unlock Your Path to Accelerated Approval with the All Access Pass Upgrading to the all access pass unlocks more than 35 presentations from the leaders in characterization, CMC, and analytical method development with presentations from Pfizer, Merck, MedImmune, Genentech, Biogen Idec, the Food and Drug Administration, National Institute of Health, National Institute of Standards and Technology, and more; this pass provides you with the tools to streamline the approval process and optimize speed to market. See page 5 for registration details. Media Partners: n Never before heard case studies and new data on protein aggregation n Insights from the Regulatory Town Hall featuring CDER, CBER and NIST n Intimate roundtables to collaborate on emerging hot topics IBC s 16th Annual IMMUNOGENICITY FOR BIOTHERAPEUTICS November 9-10, 2015 Hyatt Regency Reston Reston, VA Advance Risk Assessment Strategies and Optimize the Prediction of Immune Response to Accelerate the Process from Concept to Approval Learn strategies for predicting immune responses and drug tolerance levels Improve your drug safety analysis with improved, specific, and accurate immunogenicity information Gain insights from industry thought leaders on managing and reducing toxicity concerns Register Early for Best Value! All Access and Individual Conference Passes Available