Immunogenicity and Bioassay Summit, Baltimore, MD November 17-19, 2015

Technologies and Strategies for Safe and Efficacious Products in the Clinic

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Keynote Speakers:

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Immunogenicity Assessment & Clinical Relevance

Immunogenicity Prediction & Mitigation

Optimizing Bioassays for Biologics

Conferences

NOVEMBER 17-19, 2015 • HILTON BALTIMORE • BALTIMORE, MD

Maura C. Kibbey, Ph.D., Senior Scientific Liaison, Biologics & Biotechnology, United States Pharmacopeia

Valerie Quarmby, Ph.D., Staff Scientist, BioAnalytical Sciences, Genentech, Inc.

Amy Rosenberg, Ph.D., Director, Therapeutic Proteins, FDA/CDER

Xiaobin (Victor) Lu, Ph.D., Xiaobin (Victor) Lu, Ph.D., CMC Reviewer, Division of Cellular & Gene Therapies, OCTGT, CBER, FDA

“Provides access to opinion leaders in the field.” - Director, PK, Oncomed

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10 Reasons to Choose CHI’s Immunogenicity and Bioassay Summit 20151. 7 FDA experts on a range of topics: presentations,

breakout discussions and a short course

2. Addresses the real challenges in immunogenicity assessment

3. Risk assessment strategies

4. Immunogenicity for biosimilars: from the FDA, from Europe, and an industry case study

5. Models for immunogenicity prediction

6. Impact of impurities, aggregates and SVPs

7. Deimmunization and tolerance mechanisms: including a clinical case study

8. Showcases advanced technologies for bioassay development

9. Explores potency testing for gene and cell therapies

10. Provides solutions for bioassay development for molecules with multiple modes of action

PLUS: Choice of 12+ interactive breakout discussions: to help you iron out your immunogenicity and bioassay challenges

4 Short courses: assay development; risk assessment and regulatory strategy, and bioassay design and analysis

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Short Courses*

Monday, November 16

1:30 – 4:30 pm SC1: Basics of Immunogenicity Testing Instructors:Jim McNally, Ph.D., Associate Director, PDM Immunogenicity Expert, EMD SeronoAmy Loercher, Ph.D., Manager, Clinical Immunology, GlaxoSmithKlineThis interactive session will enable attendees to work out a basic immunogenicity preclinical and clinical testing strategy for various molecules including bi-functional and other novel scaffolds. Areas of difficulty will be discussed with specific case studies. Attendees are encouraged to contribute with their own experiences and to bring questions for discussion or submit to the meeting organizers in advance.

The following topics will be covered:• Current common industry practices• Basic issues regarding screening, confirmatory and titer assays• Assay methodologies and various technologies• Current approaches to data analysis and cutpoints• Preclinical and clinical considerations• Common problems

5:30 – 8:30 pm Dinner SC2: Challenges of Immunogenicity Assessment Instructors:Jim McNally, Ph.D., Associate Director, PDM Immunogenicity Expert, EMD SeronoAmy Loercher, Ph.D., Manager, Clinical Immunology, GlaxoSmithKline

This interactive session of intermediate level will focus on the potential challenges of immunogenicity testing in preclinical and clinical development and present case studies demonstrating how they can be handled. Attendees are encouraged to contribute with their own experiences and to bring questions for discussion or submit to the meeting organizers in advance.

The following topics will be covered:• Challenges and approaches to resolve commonly encountered issues• Multi-domain binding proteins• Pre-existing ADAs• Emerging trends in the development of neutralizing antibody assays• Cross reactivity to endogenous proteins• Clinical implications of ADAs

Wednesday, November 18

6:30 – 9:30 pm Dinner SC3: Immunogenicity Risk Assessment and Regulatory StrategyInstructors:Joao Pedras-Vasconcelos, Ph.D., Biotech Quality and Immunogenicity Reviewer, Office of Biotechnology Products, CDER-FDAPaul Chamberlain, NDA Advisory BoardThe objective of this short-course is to illustrate the rationale for, and application of, the regulatory approach to identifying, evaluating and mitigating immunogenicity-related risks for different product types. The agenda is designed to encourage interaction between the presenters and the participants in sharing experience of application of a multi-disciplinary, integrated approach.

The following topics will be covered:• Regulator’s perspective• Overview of multi-disciplinary, integrated approach to identifying,

evaluating and mitigating immunogenicity-related risks• Examples that illustrate the “why” and “how to” for different product

types / risk levels: • Bacterial-derived proteins• Enzyme replacement therapies• Bone morphogenic proteins• Allogeneic cell-based therapies

• Yeast-derived glycoproteins• PEGylated uricase

• Novel antibody constructs

6:30 – 9:30 pm Dinner SC4: Strategic Bioassay Design and AnalysisInstructor: Liming Shi, MS, MA, Senior Research Scientist, Bioassay Development, Eli Lilly and Company This course will focus on the fundamentals of statistics and simple methodology that are routinely applied in bioassay laboratories. Covered topics will include review of statistical concepts and calculations, study design, assessing bioassay measurement quality and comparative studies.

The following topics will be covered:

• Uniqueness of bioassay, especially cell-based potency assay• Considerations in bioassay development and validation • Bioassay measurements and calculations • Quality control of bioassay performance• Comparative studies for bioassay development and transfer

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TUESDAY, NOVEMBER 17

7:30 am Registration and Morning Coffee

8:30 Chairperson’s Opening RemarksLakshmi Amaravadi, Ph.D., Senior Director, Translational Medicine, Biogen Idec, inc.

KEYNOTE PRESENTATION: 8:35 A Harmonized Approach to Interpretation and Reporting of Clinical Immunogenicity Data

Valerie Quarmby, Ph.D., Staff Scientist, BioAnalytical Sciences, Genentech, Inc.A recent “White Paper” (Shankar et al 2014 AAPSJ) has provided a common set of terms and definitions to describe clinical immunogenicity data. The paper also provides a

harmonized approach to the interpretation of immunogenicity results in the context of pharmacokinetics, efficacy, and safety. Industry-wide use of these recommendations will enable the clinical relevance of immunogenicity to be assessed consistently.

REGULATORY EXPECTATIONS REGARDING IMMUNOGENICITY ASSESSMENT FOR

INNOVATORS AND BIOSIMILARS

9:05 How Product Quality Attributes of Biotherapeutics Affect Immunogenicity: A Regulatory PerspectiveWilliam Hallett, Ph.D., Product Quality & Immunogenicity Reviewer, CDER/OPQ/OBP FDASeveral quality attributes of biopharmaceuticals can significantly impact its immunogenic potential. Critical quality attributes of biopharmaceuticals that affect immunogenicity include molecular structure, glycosylation, aggregates, subvisible particulates, mechanism of action, etc. Manufacturing changes made during product life cycle, e.g. scale up, fermentation, raw materials, formulation, dosage form, etc. may affect a product’s immunogenic potential. This presentation discusses the regulatory perspective on product quality management and its effect on immunogenicity.

9:35 Regulatory Perspectives on Setting up the Clinical Immunogenicity Study for a BiosimilarSusan Kirshner, Ph.D., Associate Chief, Laboratory of Immunology, Therapeutic Proteins, Biotechnology, CDER/FDA

10:05 Multiplexing Immunogenicity Assays with the MSD U-PLEX® PlatformLaure Moller, Ph.D., Director, Scientific Support North America, Meso Scale Discovery

Sponsored by

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

11:15 Lessons Learnt from the European Experience Regarding Biosimilars and ImmunogenicityPaul Chamberlain, NDA Advisory Board The experience gained during the 10-year period following the implementation of the EU biosimilars pathway indicates that a suitably cautious approach was applied, insofar as no immunogenicity-related issues have emerged for the approved applications of the different biosimilar products. In some cases, product quality-related issues were identified in the pre-authorization setting as being potential relevant for heightened risk of immunogenicity and were duly taken into account for the biosimilarity decision.

11:45 Experiences with Immunogenicity Assessment in Biosimilar Trails with a Monoclonal AntibodyNiklas Czeloth, Ph.D., Head, Biosciences, Biosimilars, Boehringer IngelheimImmunogenicity assessment of biosimilar products is an important aspect of the overall development process while the experience with monoclonal antibody biosimilars still remains limited. The presentation will share experiences in setting up immunogenicity assays for a biosimilar product and will discuss on relevance of differences observed for the same product in two independent trials using healthy volunteers.

12:15 pm Sponsored Presentations (Opportunities Available)

12:45 LUNCHEON PRESENTATION: Challenges Associated with the Immunogenicity Assessment of Pegylated Products

Sponsored by

Marie-Soleil Christin-Piché, Ph.D., Scientific Director, Immunology, Charles River MontrealEnd User to be Announced

1:45 Session Break

PRECLINICAL STUDIES AND RISK ASSESSMENT

2:15 Chairperson’s RemarksTheo Rispens, Ph.D., Senior Scientist, Immunopathology, Sanquin

2:20 Strategies for Immunogenicity Risk AssessmentBonita Rup, Ph.D., Biotechnology Consultant, Bonnie Rup Consulting LLCImmunogenicity risk assessments typically consider an established set of risk factors relating to the product and recipient population, and treatment regimens. As the number of biopharmaceuticals under development increase, competitive and regulatory risk should also be considered. To assure the value of these assessments, it is important to continuously re-examine the “generally accepted” risk factors, particularly to better understand how they interact and determine how to improve their reliability. This presentation will overview the current practices of risk assessment and mitigation and discuss potential options for continuous improvement.

Immunogenicity Assessment & Clinical RelevanceStrategies, Overcoming Hurdles and Interpreting Results November 17-18, 2015

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2:50 Case Studies in Non-Clinical Immunogenicity Testing with Fit for Purpose Assays: Isotype Control Assays for Overcoming Target Interference Michael Partridge, Ph.D., Staff Scientist, Bioanalytical Sciences, Regeneron, Inc.The industry standard for ADA detection, the bridging immunoassay, requires the production of specific reagents and may be susceptible to target interference. We evaluated fit for purpose assays in non-clinical studies as alternatives for ADA detection. These methods included bridging assays that detect ADA generated to the constant regions of mAb drugs as well as ELISAs. This presentation will discuss the advantages and limitations of these approaches in several non-clinical studies.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Choosing an Appropriate ADA Assay for Preclinical Studies: Comparison of Different ADA Assays in NHP Case StudiesJianyong (Jerry) Wang, Ph.D., Scientist, Biochemical and Cellular Pharmacology, Genentech, Inc.Sensitive and fast ADA testing methods play important roles in preclinical studies. Different plate-based ADA assays were compared in multiple NHP studies involving bispecific antibodies, IgG1 and IgG4 mAbs. The attractive features and limitations of each method, and critical factors on assay development will be discussed to provide a general guidance for selecting an appropriate ADA assay for preclinical studies.

4:30 Problem Solving Roundtable Discussions

Table1: Meeting Regulatory Expectations Moderator: William Hallett, Ph.D., Product Quality & Immunogenicity Reviewer, CDER/OPQ/OBP FDA

Table 2: Challenges in Developing Neutralizing Antibody (Nab) AssaysModerator: Yuling Wu, Ph.D., Principal Scientist, Translational Sciences, MedImmune

Table 3: Overcoming Target Interference in ADA assaysModerator: Jim McNally, Ph.D., Associate Director, PDM Immunogenicity Expert, EMD Serono

Table 4: Dealing with Pre-Existing Positive ADA Activity Moderator: Lakshmi Amaravadi, Ph.D., Senior Director, Translational Medicine, Biogen Idec, Inc.

Table 5: Critical Issues in ADA Assay Validation Moderator: Amy Loercher, Ph.D., Manager, Clinical Immunology, GSK

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day One of Immunogenicity Assessment & Clinical Relevance

WEDNESDAY, NOVEMBER 18


8:00 am Chairperson’s RemarksJim McNally, Ph.D., Associate Director, PDM Immunogenicity Expert, EMD Serono

DIFFERENT ASSAY FORMATS AND TECHNOLOGIES FOR IMMUNOGENICITY ASSESSMENT

8:05 Replacing Legacy ADA Assays with New and Better Methods to Support Routine Patient CareYongchang Qiu, Ph.D., Senior Director, Head, Bioanalytical and Biomarker Development, Research & Nonclinical Development, ShireLegacy ADA testing used to support early clinical trials are often limited by technologies and guidance available at that time and can be very complex with many methods. As a result, these assays have presented many challenges, such as slow turn-around time and high cost, for ADA testing to support routine patient care. Here we present our effort on development of new and better assays to replace legacy methods and address “data continuity” issues before and after method switch.

CHALLENGES WITH IMMUNOGENICITY ASSESSMENT

8:35 A Neutralizing Antibody Assay Based on a Reporter of Antibody Dependent Cell-Mediated CytotoxicityYuling Wu, Ph.D., Principal Scientist, Translational Sciences, MedImmuneImmunogenicity assessment is an essential component of safety evaluation in biopharmaceutical clinical development. Benralizumab (MEDI-563, anti-IL5Rα mAb) is a humanized afucosylated mAb against IL5Rα with enhanced effector function. It potently induces ADCC (antibody-dependent cell-mediated cytotoxicity) of eosinophils and basophils. To support benrulizumab clinical development, we developed an ADCC cell-based neutralizing antibody (NAb) assay to detect NAbs against benrulizumab in human serum. This study presents the development, optimization and characterization of an ADCC cell-based NAb assay.

9:05 Evaluation of Pre-Existing Antibodies: How Meaningful is the Investigation?Lakshmi Amaravadi, Ph.D., Senior Director, Translational Medicine, Biogen Idec, Inc.Pre-existing antibodies have been detected in many clinical programs and have been receiving increased attention in the last decade. It is important to appropriately characterize the pre-existing antibody reactivity in the immunogenicity program in order to identify treatment emergent anti-drug antibodies appropriately, to quantify the titer response, and more importantly to understand if there is any clinical risk associated with such pre-existing antibodies. In order to further our understanding of this key aspect of immunogenicity evaluation an AAPS sub-committee has been assembled. The presentation will discuss some key findings from this committee. Some case studies will also be discussed.

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9:35 Experiences with Confirmatory Assays, False Positives and Negatives, and Cutpoint DeterminationAmy Loercher, Ph.D., Manager, Clinical Immunology, GlaxoSmithKlineThis presentation will focus on difficulties that may be encountered with confirmatory assays, false positive and false negative assay signals and various approaches to cutpoint determinations. Case studies will be presented that examine strategies for immunogenicity assessments of biopharmaceuticals for both soluble and membrane-bound cellular targets.

10:05 Presentation to be Announced Sponsored by


CLINICAL CASE STUDIES ON SPECIFIC BIOTHERAPEUTICS

FEATURED PRESENTATION: 11:10 Immunogenicity Testing in Patients Treated with Anti-TNF: What is the Best Measure of Clinical Response?

Theo Rispens, Ph.D., Senior Scientist, Immunopathology, SanquinAnti-drug antibody (ADA) formation to therapeutic monoclonal antibodies such as adalimumab and infliximab (anti-TNF) is associated with lower drug levels and clinical non-response. Controversy exists about the clinical consequences of ADA formation, which partly

arises from the use of different assays and testing strategies. This presentation will focus on the relationship between concentrations of the drug (PK), anti-drug antibodies and clinical response, as well as the characteristics of ADA responses to these drugs.

11:40 Immunogenicity and Clinical Relevance Assessment Enabling the Approval of a Subcutaneous Formulation of HerceptinRebecca Elliott, MSc, Manager, BioAnalytical Sciences, Genentech, Inc.The assessment of immunogenicity (antibodies against Herceptin® or recombinant human hyaluronidase) was one of the secondary objectives of a randomized, multi-center, open-label Phase III study. This demonstrated non-inferiority of a fixed-dose subcutaneous formulation of Herceptin® when compared with an intravenous formulation based on pharmacokinetics and efficacy in patients with HER2-positive early breast cancer. Exploratory analyses were performed to investigate any potential correlation of immunogenicity to pharmacokinetics, efficacy, and safety.

12:10 pm Rapid ADA Response against a C5a Receptor Antagonist Impacting PK and PDPer Holse Mygind, Ph.D., Senior Scientist, Immunogenicity Assessment, Novo Nordisk A first generation antibody therapeutic against the C5a receptor was developed to treat patients with chronic autoimmune diseases. A rapid and significant ADA response was detected in a large number of patients. These discoveries contributed to the development of a second generation antibody against the C5aR receptor. The presentation will provide details on the analytical strategies, assays applied and ADA characterizations, as well as the impact on clinical measures of pharmacokinetics and pharmacodynamics.

12:40 End of Immunogenicity Assessment & Clinical Relevance

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Immunogenicity Prediction & MitigationIdentification of Risk Factors and Tolerogenic Approaches November 18-19, 2015


1:00 pm Conference Registration

2:00 Chairperson’s Opening Remarks Stephan Kontos, Ph.D., Co-Founder, Director, Research, Anokion

RISK ASSESSMENT

2:05 Evaluating Relative Risk of Immunogenicity of Biotherapeutics with Chemical Modifications and ImpuritiesMarisa Joubert, Ph.D., Senior Scientist, Process Development, Amgen, Inc.We have investigated the potential biological impact of different product quality attributes, including oxidation of amino acid residues and the level of host cell impurities, in an in vitro comparative immunogenicity assessment (IVCIA) assay. The results highlight the relative risk of immunogenicity of product specific factors and point to a dependency on multiple parameters including the type of attribute, amount of attribute, the presence of multiple attributes, and the immune status and medication regimen of the individual.

FEATURED PRESENTATION 2:35 Development of Mechanistic Models for the Prediction of Immunogenicity Outcomes in the Clinic

Tim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.This presentation will describe a mathematical approach to quantitatively forecasting the outcome of immunogenicity in clinical trials. A generic model will be described that incorporates

immunogenicity risk assessment data, e.g. Epitopes, patient HLA-type, ADA assay characteristics (Sensitivity/Drug-tolerance). A case study will be presented with fitted clinical data to demonstrate predictive capability. Application of this approach in the context of inflammatory disease and to other therapeutic areas will be discussed.

3:05 Relevance of Animal Models for Immunogenicity PredictionJack Ragheb, Ph.D., Principal Investigator, Therapeutic Proteins, CDER/FDAThe immunogenicity of therapeutic proteins in humans cannot be assessed by testing these drug products in non-human species as the immune system can distinguish orthologous proteins as foreign and will mount an immune response. The recent advent of humanized mice may represent a relevant preclinical model for in vivo testing of the human immunogenicity of a therapeutic protein. The qualification of such a model should lead to identification of critical attributes responsible for immunogenicity, permitting the design of suitable control strategies that ensure product quality and mitigate risk.

3:35 Sponsored Presentation (Opportunity Available)

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

FACTORS CONTRIBUTING TO IMMUNOGENICITY

4:30 Innate Immune Response Modulating Impurities in Therapeutic Proteins Daniela Verthelyi, M.D., Ph.D., Chief, Immunology Lab, CDER/OBP/FDATherapeutic proteins can contain impurities derived from the cell substrate and the manufacturing process that have the potential to activate innate immune cells fostering product immunogenicity. This talk will describe different approaches for the detection of innate immune response modifying impurities in therapeutic proteins and discuss how that may inform immunogenicity risk assessments, particularly in the context of comparability exercises.

5:00 Immunogenicity of Therapeutic Proteins: Impact of Aggregates, Glycosylation and Other Post-Translational Modifications.Naren Chirmule, Ph.D., Vice President, Scientific Research, Biocon During the manufacturing of protein therapeutics several post translational modifications occur, the majority of which have been attributed to immunogenicity risk potential. A systematic analysis of various critical quality attributes such as aggregation, glycosylation etc. has been studied. This presentation will focus on comparing the impact of different types of aggregates on immune activation. These observations may inform the monitoring approaches of these aggregates during process development.

5:30 Immunogenicity of Sub-Visible Particles: Are We Barking Up the Wrong Tree?Atanas Koulov, Ph.D., Group Head, Pharma Technical Development Europe (Biologics), Analytics, F. Hoffmann-La Roche Ltd.This presentation will discuss our recent findings using an IgG1 transgenic mouse model and newly developed methods for particle fractionation and selective particle modification. Using chemically characterized and well-defined size-fractions of subvisible particles afforded interrogation of the factors governing potential break of immune tolerance. Our findings demonstrate that only particles that are heavily modified chemically (oxidized) can break immune tolerance in this transgenic mouse model, whereas unmodified particles cannot.

6:00 End of Day One of Immunogenicity Prediction & Mitigation

6:00 Dinner Short Course Registration

6:30 – 9:30 Dinner Short Courses*

SC3: Immunogenicity Risk Assessment and Regulatory Strategy

SC4: Strategic Bioassay Design and Analysis*Separate registration required. See page 3 for details.

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THURSDAY, NOVEMBER 19

TOLERANCE INDUCTION


8:00 am Chairperson’s RemarksMarisa Joubert, Ph.D., Senior Scientist, Process Development, Amgen, Inc.

8:05 Anti-Drug Antibody – A Challenge in the Field of Therapeutic Proteins, Lessons Learned from Pompe Disease; Immune Tolerance Induction in ERTZoheb Kazi, MBBS, Postdoctoral Research Associate, Pediatrics/Medical Genetics, Duke University Medical CenterCross-Reactive Immunological Material (CRIM) -negative (CN) and a subset of CRIM-positive (CP) Infantile Pompe disease (IPD) mount an immune response against enzyme replacement therapy (ERT) resulting in clinical decline. Prophylactic immune tolerance induction (ITI) protocol has prevented immune responses in CN patients treated with ERT. We will present data on the safety and efficacy of ITI approaches for CP and CN IPD receiving ERT.

KEYNOTE PRESENTATION:8:35 Addressing Immunologic Sabotage of Dystrophin Replacement Therapies in Duchenne Muscular Dystrophy

Amy S. Rosenberg, M.D., Division Director, Office of Biotechnology Products, FDAClinical investigation for more definitive treatment of Duchenne Muscular Dystrophy (DMD), will only meet with success by addressing key immunologic features of the

disease: the profound inflammatory response in DMD muscle mediated by innate immune system elements and the preexisting or potential cellular immune response to dystrophin, mediated by CD8+ and CD4+ T cells. Thus, taming inflammation is essential not only to reducing muscle cell loss and fibrosis per se, but as well to facilitate induction of immune tolerance to dystrophin by facilitating the conversion to, recruitment of, and function of regulatory T cells (Tregs).

9:05 Tools and Technologies for Comprehensive Sponsored by Immunogenicity Risk ManagementEmilee Knowlton, D.Phil., Immunology Sales Specialist, ProImmuneImmunogenicity is a very complex issue to address in drug design and development. An overview of the best tools for immunogenicity risk mitigation will be provided, including Mass Spectrometry antigen presentation assays, DC-T cell assays to measure responses to fully formulated biologics, HLA-peptide Binding Assays, and naïve T cell Proliferation Assays to characterize individual epitopes. How the potential risk of first infusion reactions can be mitigated using whole-blood cytokine release assays will also be described.


Table 1: Potential Immunogenic Risk of Drug Product FormulationsModerator: Marisa Joubert, Ph.D., Senior Scientist, Process Development, Amgen, Inc.

Table 2: Current and Emerging Tools: Selecting Candidates and Predicting Clinical OutcomeModerator: Tim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.

Table 3: Protein Design Tools for Biotherapeutic DeimmunizationModerator: Karl Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth

Table 4: Progress towards Inducing Immunological Tolerance to BiotherapeuticsModerator: Stephan Kontos, Ph.D., Co-Founder, Director, Research, Anokion


ROLE OF B AND T CELL EPITOPES

11:15 Decreasing Immunogenicity of Recombinant Immunotoxins by Identifying and Modifying B and T Cell EpitopesIra Pastan, M.D., Co-Chief, Molecular Biology, National Cancer Institute, National Institutes of HealthRecombinant Immunotoxins are chimeric proteins designed to kill cancer cells. They consist of an Fv or Fab that binds to the cancer cell and a portion of pseudomonas exotoxin A that kills the cell. RITs have shown anti-tumor activity in some leukemias and in mesothelioma, but antibody formation limits the amount that can be given. We have developed experimental approaches to identify and remove T and B cells while maintaining high cytotoxic activity. Clinical trials with one of these have recently opened.

11:45 Design and Development of Deimmunized Lysostaphin for Treatment of Drug-Resistant Staphylococcus aureus InfectionsKarl Griswold, Ph.D., Associate Professor, Thayer School of Engineering, DartmouthUsing advanced protein design algorithms, predicted T cell epitopes were depleted from lysostaphin, a potent antibacterial drug candidate that exhibits undesirable immunogenicity. Aggressively deimmunized variants rescued humanized mice from recurrent infection by methicillin-resistant Staphylococcus aureus, whereas wild type lysostaphin failed due to high anti-drug antibody titers. These controlled experiments in a clinically relevant, immunocompetent disease model demonstrate for the first time that T cell epitope depletion enhances therapeutic efficacy.

12:15 pm Designing Therapeutic Drugs with Reduced ImmunogenicityMark Fogg, Ph.D., Group Leader, Immunology, AbzenaThe importance of T cell help has been widely accepted as a significant risk factor in the development of anti-drug antibodies (immunogenicity). Case study data will be presented on the deimmunisation of naturally immunogenic non-human protein therapeutics.

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12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:15 Cupcakes and Coffee in the Exhibit Hall with Poster Viewing

DEIMMUNIZATION AND TOLERANCE MECHANISMS

2:00 Chairperson’s RemarksTim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.

2:05 Controlling Antibody Responses by Engaging CD22Matthew Macauley, Ph.D., Assistant Professor, Chemical Physiology, Scripps Research InstituteCD22 is an inhibitory B-cell co-receptor that recognizes glycans. We have shown that co-engaging it with the B-cell receptor (BCR) induces antigen-specific B-cell tolerance. This was first demonstrated using liposomes that co-present a high affinity CD22 and antigen. More recently, we have developed a cell-based platform that takes advantage of these same principles.

2:35 Creating Biologics Drugs with Improved Efficacy and Safety Profiles by Preventing Anti-Drug Antibodies with Tolerogenic NanoparticlesKei Kishimoto, Ph.D., CSO, Selecta BiosciencesAnti-drug antibodies (ADAs) can adversely affect the safety and efficacy of biologic drugs. We will describe the development of Synthetic Vaccine Particles (SVPs) for the induction of antigen-specific tolerance to prevent ADAs, using coagulation Factor VIII for the treatment of haemophilia A and pegylated uricase for the treatment of refractory gout as case examples.

3:05 Induction of Tolerance Using Engineered Regulatory T and Cytotoxic T Cells with Chimeric Antigen ReceptorsDavid W. Scott, Ph.D., Professor and Vice Chair for Research, Department of Medicine (MED), Uniformed Services University of Health SciencesHuman T cells engineered to express chimeric antigen receptors (CARs) have been utilized to successfully target cancer cells. We have adapted this approach to create specific T regulatory cells using both CARs and chimeric T-cell receptors from patients in two disease models. Application of engineered T cells to modulate adverse antibody responses in hemophilia and pathogenic responses to CNS proteins will be presented. Prospects with engineered cytotoxic cells will be discussed.

3:35 Inducing Immune Tolerance to Highly Foreign Therapeutics by Engineering for Erythrocyte BindingStephan Kontos, Ph.D., Co-Founder, Director, Research, AnokionWe sought to develop a recombinant, translational approach that exploits the tolerogenic potential of apoptotic cells without the need to manipulate cells themselves, with the goal of inducing antigen-specific tolerance to immunogenic therapeutics. In engineering erythrocyte-binding domains into the chemotherapeutic E. coli enzyme asparaginase, we show that in addition to greatly enhancing PK and PD profiles, erythrocyte-binding drives potent, long-lived antigen-specific humoral immune tolerance towards the therapeutic.

4:05 Close of Conference

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Optimizing Bioassays for BiologicsMerging Biology and Statistics for Successful Biological Assay Development

November 18-19, 2015


ADVANCES IN BIOASSAY TECHNOLOGIES

2:00 pm Chairperson’s Opening RemarksMax L. Tejada, Ph.D., Senior Research Scientist II, Analytical Operations, Gilead Sciences

2:05 Back to the Future, Envisioning the Next Generation Bioassay DevelopmentHan Li, Ph.D., Principal Scientist, Lead Discovery and Optimization, Bristol Myers SquibbBioassay development requires a unique combination of techniques, from cell line selection and generation, to assay design, validation and final testing. An ideal bioassay needs to reflect true MOA, robust, sensitive and reproducible. Our thoughts on a bioassay development incorporating advance technologies from in house and vendors will be presented. Our ultimate goal is to develop a system that will have broad and long lasting applications.

2:35 Development of Luminex as a Platform for the Detection of Anti-Drug Antibody IgE Isotypes in Human Serum LiNa Loo, Ph.D., Senior Scientist, Bioanalytical Development, MerckSince biotherapeutic drugs such as monoclonal antibodies (mAbs) have the potential to induce immunogenicity, it is critical to perform an immunogenicity assessment to ensure drug efficacy and patient safety. Here, Luminex and Mesoscale were evaluated as platforms for detection of anti-drug antibody IgE isotype in human serum. By using a mouse-human chimeric drug-specific monoclonal IgE antibody as the positive control, the assay characteristics were compared for the two platforms.

3:05 Presentation to be Announced

3:35 Sponsored Presentation (Opportunity Available)

3:50 Refreshment Break with Exhibit and Poster Viewing

POTENCY TESTING FOR GENE AND CELL THERAPIES

4:30 Challenges in Potency Assay Development for a Non-Replicating Lentiviral VectorBrenna Kelley-Clarke, Ph.D., Scientist II, Assay Development, Immune DesignImmune Design has developed an HIV-1-based integration-deficient lentiviral vector currently being evaluated in cancer immunotherapy (LV305). LV305 is designed to transduce human dendritic cells, triggering presentation of an encoded antigen via the MHC Class I pathway; this is proposed to elicit an effective CD8-T lymphocyte response towards malignancies that over-express that antigen. The biological complexity of LV305 and its proposed MOA pose unique challenges in developing a potency assay matrix.

KEYNOTE PRESENTATION 5:00 A Regulatory Perspective for Development of Potency Assay for Cellular and Gene Therapy Products: A Product Lifecycle Approach

Xiaobin (Victor) Lu, Ph.D., CMC Reviewer, Division of Cellular & Gene Therapies, OCTGT, CBER, FDAThe challenges of developing a potency assay for a CGT are multi-factorial including complexity of assay procedures, inherent variability due to use of living cells, tissues or live

organisms, and variable reagents. Furthermore, a bioassay based potency assay can be impacted by changes made in the product manufacturing processes. This presentation will outline a product life-cycle approach for developing potency assays for a CGT product from preclinical studies to the Biological License Application. It will conclude with general recommendations for addressing some of the challenges in potency assay development and implementation for CGT during product and clinical development programs.

ASSAY ACCEPTANCE CRITERIA

5:30 Assay Acceptance Criteria for Multiwell-Plate–Based Biological Potency AssaysC. Jane Robinson, Scientific Liaison, Biopharmaceutical Emerging Best Practices Association (BEBPA)Following preliminary consultation, a draft white paper “Assay Acceptance Criteria for Multiwell-Plate–Based Biological Potency Assays” was published in 2014. In the subsequent extensive consultation process, a variety of issues were raised and discussed, including a range of current practices. Some of these issues and the recommendations of the white paper, including the two-level sequential assessment of acceptance criteria and use of an assay control sample, will be presented.

6:00 End of Day One of Optimizing Bioassays for Biologics

6:00 Dinner Short Course Registration*

6:30-9:30 SHORT COURSE: Strategic Bioassay Development and DesignInstructor: Liming Shi, MS, MA, Senior Research Scientist, Bioassay Development, Eli Lilly and Company*Separate registration required. See page 3 for details.

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THURSDAY, NOVEMBER 19

DEVELOPING ASSAYS FOR MULTIPLE MODES OF ACTION


8:00 am Chairperson’s RemarksLiming Shi, MS, MA, Senior Research Scientist, Bioassay Development, Eli Lilly and Company

8:05 Bioassay Development for Bispecific Antibodies: A Different Ball GamePiyush M. Vyas, Ph.D., Research Scientist, Bioassay Development, Eli Lilly and CompanyBispecific Antibodies are evolving rapidly and are already in stages for clinical trials. Some of these Bispecific Antibodies have shown synergy in their biological activity as compared to the combination of their individual counterparts. Bioassay development and Data analyses for such Bispecific Antibodies to show the synergy, is a complex process. Traditional data analyses approaches might not be suitable enough in order to analyze such data. Data analyses of such Bispecific Antibodies need to be approached in a different way.

8:35 Regulated ADC Bioanalysis Using Ligand Binding Assays: Challenges and Strategies Seema Kumar, Ph.D., Principal Scientist, Pfizer, Inc.The complex multi-component structure in combination with heterogeneous and dynamically evolving behavior presents unique challenges in ADC bioanalysis. The challenges may vary depending on the objective of ADC bioanalysis. The case studies showcasing various bioanalytical strategies that could be employed in developing and validating successful ligand binding assays for ADC characterization will be presented.

9:05 Critical Success Factors for Cell-Based Assay Development and Transfer

Sponsored by

John Kamerud, Ph.D., Scientific Director, EurofinsMethod development or transfer must occur before a CRO validates an assay. The development / transfer of complex methods that involve the use of cell lines require specific criteria to be evaluated to ensure the success of the assay. In particular, the growth characteristics of the cell line, culture conditions, cell banking requirements, assay format, readout, reagents and data interpretation should be evaluated and controlled to ensure a robust path to validation.


Table 5: Incorporating New Technologies into Bioassay DevelopmentModerator: Han Li, Ph.D., Principal Scientist, Lead Discovery and Optimization, Bristol Myers Squibb

Table 6: Challenges in Assay BridgingModerator: Maura C. Kibbey, Ph.D., Senior Scientific Liaison, Biologics & Biotechnology, United States Pharmacopeia

Table 7: Method TransfersModerator: Max L. Tejada, Ph.D., Senior Research Scientist II, Analytical Operations, Gilead Sciences

10:35 Coffee Break with Poster Viewing

PROCESS COMPARABILITY AND CHARACTERIZATION

11:15 Use of a Tiered Approach to Develop Robust Potency Assays in Support of Monoclonal Antibody Product Development Laura Geagan, Principal Research Associate, Bioanalytical Development, GenzymeCell-based assays are often used for evaluating the potency of biological therapeutics during product development. The development of cell-based methods frequently coincides with the stage of development of the product they support. Early stage assays are often required to provide meaningful data to support process, purification and formulation development at a time when optimization of the method is not complete. As the drug progresses through the development paradigm, the performance of the cell-based potency assay improves as well. In this presentation we describe a tiered approach to develop a robust cell-based potency assay to support pre-clinical product development. The analysis paradigm was updated as the drug progressed into Phase I for consistency with guidance provided in USP chapters 1032-1034. The use of the assay to support process development will be discussed.

11:45 FTiH Support of an ADC: Stability, Assay Development, and Clinical ExperiencesJohn F. Kellie, Ph.D., Investigator, Bioanalytical Sciences and Toxicokinetics, GlaxoSmithKlineCharacterization of circulating ADC species (conjugated antibody, total antibody, and payload) is critical to understanding the safety and efficacy of ADC therapeutics. Current methodology requires development and validation of immunoassays and liquid chromatography-mass spectrometry assays. This presentation will share experiences from assay validation through first time in human bioanalytical study support along with an update and outlook for state-of-the-art technologies set to drive ADC method development in the future.

12:15 pm Sponsored Presentations (Opportunities Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:15 Cupcakes and Coffee in the Exhibit Hall with Poster Viewing

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BRIDGING STUDIES AND ASSAY TRANSFER

2:00 Chairperson’s Remarks

2:05 Transfer and Validation of a Cell-Based Neutralizing Antibody (NAb) Assay to a CROFlorence Guilhot, Ph.D., Head, Translational Pharmacology Lab, NovImmune SABiotherapeutics can lead to the production of anti-drug antibodies (ADA) in treated subjects which may result in loss of efficacy or elicit adverse events. Standard immunoassays can detect ADA, but cannot differentiate between neutralizing and non-neutralizing ADA. Development of a neutralizing antibody (NAb) assay is a key step to support clinical trials. This presentation will provide an overview of (i) assay characteristics of the functional reporter NAb cell-based assay (ii) challenges for the transfer and validation of a NAb assay to support the clinical trial.

2:35 Leveraging Automated Liquid Handlers, High-Density Plates, and Multi-Dimensional Assay Optimization to Accelerate the Delivery of Neutralizing Antibody Bioassay John M. Lehrach, Research Scientist II, Bristol-Meyers Squibb BMS Core BioAssay Group (CBG) leveraged the cellular assay repertoire, cell inventory, and the detection technology platforms in Leads Discovery and Optimization (LDO) Department to perform automation assisted multi-dimentional optimization for the development of a Nab Bioassay. BMS informatics tools enabled automated data analysis. The technology platform selected was a homogenous cAMP HTRF assay. CBG delivered a 96-well format Nab assay with excellent Nab sensitivity, assay reproducibility, and serum tolerance utilizing assay-ready cryo cells.

KEYNOTE PRESENTATION 3:05 Compendial Potency Assays and Associated Biological Reference Materials – Challenges in Assay Bridging

Maura C. Kibbey, Ph.D., Senior Scientific Liaison, Biologics & Biotechnology, United States PharmacopeiaUSP, regulators, and manufacturers share a common goal of reducing in vivo testing, yet replacing animal assays with suitable in vitro assays may be challenging. This presentation

will highlight USP’s current efforts to include modern bioassays in the USP-NF as well as bridging expectations for revision sponsors who would like to propose a modern assay for the compendium.

3:35 Global Bioassay TransfersCamille Dycke, Ph.D., F. Hoffmann-La Roche Ltd. / Genentech; Associate Director, Method Management and Technologies, Bioassay, Global Biologics QCTo support global product release, the bioassay used in the commercial control system of the product is transferred to multiple QC testing laboratories around the globe. In order to facilitate these global method transfers, the implementation of global processes, a global training plan and a solid method life cycle management program, are key elements to ensure success. A few case studies will be presented, illustrating product globalization.

4:05 Close of Conference

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Sponsorship, Exhibit, and Lead Generation Opportunities:CHI offers comprehensive packages that can be customized to your budget and objectives. Sponsorship allows you to achieve your goals before, during, and long after the event. Packages may include presentations, exhibit space and branding, as well as the use of delegate lists. Signing on early will maximize your exposure to qualified decision-makers and drive traffic to your website in the coming months.

Podium Presentations — Available within Main Agenda! Showcase your solutions to a guaranteed, targeted audience through a 15- or 30-minute presentation during a specific program, breakfast, lunch, or a pre-conference workshop. Package includes exhibit space, on-site branding, and access to cooperative marketing efforts by CHI. Lunches are delivered to attendees who are already seated in the main session room. Presentations will sell out quickly! Sign on early to secure your talk.

Invitation-Only VIP Dinner/Hospitality Suite Select specific delegates from the pre-registration list to attend a private function at an upscale restaurant or a reception at the hotel. From extending the invitations, to venue suggestions, CHI will deliver your prospects and help you make the most of this invaluable opportunity.

Focus Group CHI will gladly provide you the opportunity of running a focus group on-site. This exclusive gathering can be useful to conduct market research, collect feedback on a new product idea, and collect marketing intelligence from industry experts on a specific topic.

User Group Meeting/Custom Event Co-locate your user group meeting or custom event. CHI will help market the event, manage logistical operations, develop the agenda, and more. CHI can handle the entirety of the meeting or select aspects.

Exhibit Exhibitors will enjoy facilitated networking opportunities with qualified delegates, making it the perfect platform to launch a new product, collect feedback, and generate new leads. Exhibit space sells out quickly, so reserve yours today!

Additional branding and promotional opportunities are available, including:• Conference Tote Bags• Literature Distribution (Tote

Bag Insert or Chair Drop)

• Badge Lanyards• Program Guide Ad• Padfolios and More...

For additional information, please contact: Carolyn Benton Business Development Manager 781-972-5412 | [email protected]

Conference Hotel:Hilton Baltimore401 West Pratt St. Baltimore, MD 21201Tel: 443-573-8700

Discounted Room Rate: $194 s/d

Discounted Room Rate Cut-off Date: October 20, 2015

Please visit www.ImmunogenicitySummit.com or you may call the hotel directly to reserve your sleeping accommodations. You will need to identify yourself as a Cambridge Healthtech Institute conference attendee to receive the discounted room rate with the host hotel. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space- and rate-availability basis. Rooms are limited, so please book early.

Car Rental Discounts are Available:For details, visit www.ImmunogenicitySummit.com and click on the hotel & travel button.

Hotel & Travel

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ADDITIONAL REGISTRATION DETAILSEach registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link.Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted in writing to CHI at least 30 days prior to the start of the meeting.To view our Substitutions/Cancellations Policy, go to http://www.healthtech.com/regdetailsVideo and or audio recording of any kind is prohibited onsite at all CHI events.

A series of diverse reports designed to keep life science professionals informed of the salient trends in pharmaceutical technology, business, clinical development, and therapeutic disease markets.For a detailed list of reports, visit InsightPharmaReports.com, or contact Adriana Randall, [email protected], +1-781-972-5402.

Pricing and Registration InformationCONFERENCE PRICING

Commercial Academic, Government, Hospital-Affiliated

SUMMIT PRICING BEST VALUE! (Includes access to all conference days, Tuesday-Thursday, excludes short courses) Early registration discount until August 21, 2015 $2,549 $1,149Advance registration discount until October 16, 2015 $2,749 $1,249Registrations after October 16, 2015 and on-site $2,949 $1,349

SINGLE CONFERENCE PRICING (Includes access to Tues. – Wed. am conference or Wed. pm – Thurs. concurrent conferences, excludes short courses)

Early registration discount until August 21, 2015 $1,699 $879Advance registration discount until October 16, 2015 $1,849 $899Registrations after October 16, 2015 and on-site $2,049 $1,029

Tues. – Wed. am, November 17-18 Wed. pm – Thurs., November 18-19

C1: Immunogenicity Assessment & Clinical Relevance C2: Immunogenicity Prediction & Mitigation

C3: Optimizing Bioassays for Biologics

SHORT COURSES

One short course $699 $399Two short courses $999 $699Three short courses $1,299 $899

Pre-Conference Short Courses: Dinner Short Courses:

Monday, November 16 Wednesday, November 18

1:30-4:30 pm SC1: Basics of Immunogenicity Testing 6:30-9:30 pm SC3: Immunogenicity Risk Assessment and Regulatory Strategy

5:30-8:30 pm (Dinner Course) SC2: Challenges of Immunogenicity Assessment

6:30-9:30 pm SC4: Strategic Bioassay Design and Analysis

CONFERENCE DISCOUNTS

Poster Discount ($50 Off): Poster abstracts are due by October 16, 2015. Once your registration has been fully processed, we will send an email containing a unique link allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact [email protected]. * CHI reserves the right to publish your poster title and abstract in various marketing materials and products.REGISTER 3 - 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form together for discount to apply.Alumni Discount: Cambridge Healthtech Institute (CHI) appreciates your past participation at the Immunogenicity and Bioassay Summit. As a result of the great loyalty you have shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate. Group Discounts: Discounts are available for multiple attendees from the same organization. For more information on group rates contact Uma Patel at 781-972-5447.

If you are unable to attend but would like to purchase the Immunogenicity & Bioassay Summit 2015 CD for $495 (plus shipping), please visit ImmunogenicitySummit.com. Massachusetts delivery will include sales tax.

How to Register: [email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use keycode 1527F

when registering!

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