Part Two: Immunogenicity Prediction and Mitigation
12:30-5:30 Combined Plenary Session: (Parts One & Two)
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Thursday, NOVEMBER 17
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Table 1: Sub-Visible Particles and Immunogenicity
Moderator: Nadine M. Ritter, Ph.D., Senior CMC Consultant, Biologics Consulting Group, Inc. - Biography
Table 2: How Predictive are the Methods to Analyze T Cell Epitopes?
Moderator: Matthew Baker, Ph.D., CSO, Antitope Ltd. - Biography
Table 3: Immune Tolerance Approaches
Moderator: David W. Scott, Ph.D., Professor and Vice Chair for Research, Department of Medicine, Uniformed Services University of Health Sciences, Bethesda - Biography
Table 4: What Does the FDA expect from an Immunogenicity Program
Moderators: Laura Salazar, CDER, FDA and Daniela Verthelyi, M.D., Ph.D., Chief, Laboratory of Immunology, Therapeutic Proteins, CDER, FDA
Table 5: Immunogenicity Lessons from the Literature
Moderator: Fiona A. Harding, Ph.D., Senior Principal Research Scientist, Biologics Technologies, Abbott Biotherapeutics Corp. - Biography
Table 6: Relevance of Animal Models for Predicting the Immunogenicity of Therapeutic Proteins
Moderator: Kristina Howard, D.V.M., Ph.D., FDA Commissioner’s Fellow, Therapeutic Proteins, Pharmaceutical Sciences, CDER, FDA
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5:45 – 7:00 Networking Reception in the Exhibit Hall
FRIDAY, NOVEMBER 18
8:30 am Chairperson’s Remarks
Matthew Baker, Ph.D., CSO, Antitope Ltd.
Immunogenicity, why, how and what?
Michel Awwad, Senior Director, PDM-NBE, Pfizer, Inc.
Multiple factors; those related to patients and those related to the drug itself, play a significant role in inducing the generation of immune response. Some of these factors and attributes can be modified relatively without much difficulty, however, others might require novel and innovative approaches and a lot of effort to mitigate their role in inducing immunogenicity. I will be discussing the different mechanisms involved in the generation of an immune response and the different approaches either currently used or being developed to predict and mitigate immunogenicity.
9:05 Tools, Tools, Tools and even more Tools!
How to Predict Immunogenicity in Silico, in Vitro and in Vivo – an Overview
Melody Sauerborn. Ph.D., Pharmaceutical Sciences, University of Utrecht, and CEO, ADA InVivo BV - Biography
New analytical tools have been implemented in drug development processes to detect and characterize drug aggregates. Besides analytical tools, the industry uses biological tools such as in silico, in vitro and in vivo to predict immunogenicity of protein drugs. This presentation gives an overview about the currently used biological tools and discusses their pro and cons.
9:35Coupling of Aggregation and Immunogenicity in Biotherapeutics: T- & B-Cell Immune Epitopes May Contain Aggregation Prone Regions
Sandeep Kumar, Ph.D., Principal Scientist, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc. - Biography
Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- & B-cell immune epitopes from protein sequence and structure have become available recently. In this talk I shall describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation prone regions. The details of biological mechanisms behind this observation remain to be understood. However, this observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on, biotherapeutics with reduced aggregation propensity.
10:05 Identifying Immunogenic Regions of Antibodies
Fiona A. Harding, Ph.D., Senior Principal Research Scientist, Biologics Technologies, Abbott Biotherapeutics Corp. - Biography
Humanized and fully human antibodies can induce unwanted immune responses in vivo. The identification and modification of epitope regions of antibodies to create risk-reduced candidates will be discussed.
10:35 Networking Coffee Break in the Exhibit Hall with Poster Viewing
11:10 Advances in Abrogating Immunogenicity with Fc Fusion Proteins
David W. Scott, Ph.D., Professor & Vice Chair, Research, Department of Medicine, Uniformed Services, University of Health Sciences, Bethesda - Biography
Therapeutic proteins have the potential to elicit immune responses that can limit their efficacy. Understanding how to reverse and/or prevent this immunogenicity will be the focus of this presentation. Tolerance induction using IgG and Fc conjugated fusion proteins has been studied for over three decades. This talk will explore the basis of this tolerogenicity and its application using different modes of presentation to the immune system. The mapping and recognition of potentially tolerogenic peptides in therapeutic proteins will be emphasized. Possible mechanisms for their success and applications for the future will be discussed.
11:40 New Data on the Impact of T Epitope Removal on Immunogenicity and Aggregate Formation
Matthew Baker, Ph.D., CSO, Antitope Ltd. - Biography
The importance of T cell help in the development of anti-drug antibodies has been generally accepted and there are numerous in silico, in vitro and in vivo technologies that attempt to measure and quantify T cell epitopes. The focus of this presentation will be to provide case study examples of how some of these technologies can be applied to select protein therapeutics with a reduced risk of immunogenicity. Furthermore new data will be presented on how aggregates in some formulations can trigger innate responses that ultimately enhance T cell immunogenicity in vitro.
12:10 pm Lunch on Your Own
1:30 Chairperson’s Remarks
Nadine Ritter, Ph.D., Senior CMC Consultant, Biologics Consulting Group, Inc.
» KEYNOTE PRESENTATION
1:35 Innate Immune Response Modulating Impurities
 Daniela Verthelyi, M.D., Ph.D., Chief, Laboratory of Immunology, Therapeutic Proteins, CDER, FDA - Biography
Immune cells express numerous receptors that respond to conserved molecular patterns present in pathogens as well as in stressed tissues. This talk will review recent data, present a few cases, and discuss the role of trace levels of impurities in therapeutic proteins that stimulate the innate immune response in facilitating an immunogenic response to therapeutic proteins.
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2:05 Sub-Visible Particles Relating to Pre-Clinical Immunogenicity Risk Assessment and Clinical Outcome
Mary Cromwell, Ph.D., Senior Scientist & Associate Director, Protein Analytical Chemistry, Genentech, Inc. - Biography
2:35 Studies from Utrecht/Leiden University on Impact of Aggregates on Immunogenicity in Immune Tolerant Mice
Miranda van Beers, Ph.D., Research Scientist, Analytics, Bioprocessing Technology Institute, A*STAR - Biography
The clinical immunogenicity of therapeutic proteins is often associated with the presence of aggregates. However, insight in what types of aggregates cause immunogenicity is lacking. Immune tolerant mice help to understand the mechanism responsible for breaking tolerance. This talk will review data on the immunogenicity of aggregates with different physicochemical characteristics in immune tolerant mice. The immune response against oxidized protein and protein adsorbed on (sub)visible particles will be discussed.
3:05 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
3:30 Recommended Strategies for the Assessment of Protein Aggregates in Pharmaceutical Biotech Product Development
John den Engelsman, Ph.D., Analytical Development and Validation, Merck, Sharpe & Dohme - Biography
Within the European Immunogenicity Platform (EIP) (http://www.e-i-p.eu), the Protein Characterization Subcommittee (EIP-PCS) has been established to discuss and exchange experience of protein characterization in relation to immunogenicity. As representatives of EIP-PCS, we reviewed the current state of methods for analysis of protein aggregates. Moreover, we elaborate on why these methods should be used during product development and make recommendations to the biotech community with regard to strategies for their application during the development of protein therapeutics.
4:00 Recent Developments Concerning Sub Visible Particulate (SVP) Characterization for Biotech Products
Nadine M. Ritter, Ph.D., Senior CMC Consultant, Biologics Consulting Group, Inc. - Biography
Protein-based therapeutics require orthogonal analytical methods for product characterization and comparability, many of which focus on product- and process-related impurities. One evolving concern is the characterization and quantitation of SVPs. Current compendial methods and specification limits were designed for extraneous particulate matter. But the emergence of biotechnology products has shown that SVPs are often intrinsic product-related material, challenging the available technology. It also may require safety limits different from those for extrinsic SVPs. This talk will provide an overview of the current expectations for the characterization and quantitation of SVPs in biotechnology products.
4:30 End of Part Two
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