2013 Archived Content
 

Safety Stream

Inaugural
Immunogenicity Prediction & Mitigation

Predictive Tools & Risk Assessment - How Far Have We Come?

May 1-2, 2013

Immunogenicity Prediction & Mitigation will focus on predictive tools and mitigation strategies that are being used in immunogenicity today. There are more and more innovative protein products being produced, and the less human they are, the higher the risk and the need for mitigation. New predictive tools are creating improved cost effectiveness, whether in silico, in vivo, or ex vivo. This conference will explore the questions on most minds today: What can we get out of these predictive tools? What really works and what doesn’t? How can current methods be refined so they are more useful?

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 Tuesday, April 30 from 4:15 - 5:30 PLENARY KEYNOTE PANEL 

Conventional vs. Non-Conventional Formats 

 Janice ReichertModerator: Janice Reichert, Ph.D., Editor-in-Chief, mAbs; Managing Director, Reichert Biotechnology Consulting LLC
With the explosion in the number of formats available, what are the potential benefits and risks to patients? This panel will discuss the realistic outlook and uncertainties with developing a diverse array of non-canonical antibodies in terms of immunogenicity, safety, competitive marketplace, commercial development, business strategies, regulatory approval, target validation and clinical development.
 

Panelists: 

David Meininger David Meininger, Ph.D., MBA, Executive Director, Molecular Discovery, Merck



 

Tillman GerngrossTillman Gerngross, Ph.D., CEO and Co-Founder, Adimab LLC; Professor, Bioengineering, Thayer School of Engineering, Dartmouth College


 

Trudi VeldmanTrudi Veldman, Ph.D., Senior Director, Biologics Generation, AbbVie



 


WEDNESDAY, MAY 1

7:00 am Conference Registration and Morning Coffee


Predictive Tools & Risk Assessment 

8:30 Chairperson’s Opening Remarks

Bonnie Rup, Ph.D., Research Fellow, Immunogenicity Sciences Lead, Pfizer    

8:40 Immunogenicity Risk Prediction: An Overview of Current Tools and Approaches

Theresa GoletzTheresa J. Goletz, Ph.D., Director, Clinical Immunology, Amgen

Therapeutic proteins are a growing class of drugs, yet most elicit immune responses, such as antidrug antibodies (ADAs) when administered to patients. ADAs can range from weak, non-neutralizing antibodies to neutralizing antibodies (nAbs), all of which have the potential to reduce efficacy and potency or alter safety.  A clearer understanding of immunogenic risk throughout the drug development process could reduce development time and cost while helping to ensure lead candidates with more favorable immunogenic profiles. This presentation will provide an overview of the current tools available for immunogenicity risk prediction and management.  Examples will be provided illustrating the use of these tools at various stages of drug development.

9:10 Aiming for Improved Biotherapeutic Immunogenicity Risk Profiles through Implementation of New Risk Assessment Tools

Bonnie Rup, Ph.D., Research Fellow, Immunogenicity Sciences Lead, Pfizer

Currently the most effective strategy for evaluating immunogenicity risk of a biotherapeutic is active monitoring of clinical trial subjects for development of anti-drug antibodies and evaluating clinical outcomes.  In addition, methods to characterize  functional potential of the ADA (e.g. measuring in vitro neutralizing antibody activity, isotype or epitope specificity), may be applied, again combined with observations of clinical outcomes, to further define the immunogenicity risk. These ADA measurement and characterization tools are therefore highly valuable in assessing the immunogenicity potential of the developed biotherapeutic and determining long term immunogenicity risk management strategies.  Yet these tools and observations are applied long after decisions are made about selection of candidate molecules, formulations, and dosing regimens and therefore are not useful in making early critical decisions that could reduce immunogenicity potential of a biotherapeutic product.  This presentation will overview risk assessment tools that are being applied earlier, will provide examples of the tool application in decision making, and will discuss limitations that should be addressed to increase their reliability. 

9:40 An Overview of the ABIRISK Initiative

Dan SikkemaDan Sikkema, Ph.D., Head, BioPharma Clinical Immunology, GlaxoSmithKline

ABIRISK is a €35M Public Private partnership (35 partners in 13 countries) receiving support from the Innovative Medicines Initiative and EFPIA.  The program will investigate mechanisms of anti-drug immune response, technologies for predicting immunogenicity, and establish an immunogenicity databank to identify common and disease-specific/drug-specific variables.

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

11:10 Prediction of Clinical Immunogenicity of Adnectins: Guiding Lead Optimization

Daron Forman Ph.D., Senior Scientist, Adnexus a Bristol Myers Squibb, R&D Co

Immunogencity assessment with in silico tools and in vitro T cell-based assays open the possibility to change the human immune response to therapeutic proteins by protein engineering. Here we will discuss the use of these tools in discovering Adnectins with low immunogenicity.

11:40 XTEN: A Protein-Based, Biodegradable PEG Alternative with Low Immunogenicity

Beth Pei-Yun ChangBeth Pei-Yun Chang, Ph.D., Associate Director, Cell Biology, Amunix, Inc.

XTEN represents a family of unstructured polypeptides that extends the half-life of an attached therapeutic. Biopharmaceuticals fused with XTEN displayed excellent serum half-life extension and good efficacy.  Preclinical and clinical studies on the immunogenicity of XTEN fusions will be discussed.


Lonza 12:10 pm Developability: Predicting, Avoiding and Reducing Immunogenicity and the Risk of Failure of Biotherapeutics

Yvette Stallwood, Ph.D., Head, Applied Protein Services, Lonza Biologics

Development risk, attrition and saftey remain some of the key challenges to a successful biopharmaceutical and vaccine pipeline. To help our customers streamline drug development, Lonza offers Applied Protein Services, a platform of in silico and in vitro tools for a multidisciplinary approach to risk assessment and product design. Our services incorporate immunogenicity, stability and aggregation assessment along with chemical and glycosylation assessment as well as small scale protein production services.

12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

1:40 Session Break


Protein Aggregates and Associated Immune Activation 

2:00 Chairperson’s Remarks

Theresa J. Goletz, Ph.D., Director, Clinical Immunology, Amgen

2:05 Preclinical Assessment of the Immunogenicity Potential of Protein Aggregates

Anja LangenkampAnja Langenkamp, Ph.D., Laboratory Head, Immunosafety, F. Hoffmann-La Roche Ltd.

Predictive tools for immunogenicity are currently under development but still need to demonstrate if they can provide valuable information about the occurrence and eventually clinical consequences of immunogenicity in a patient population. Nevertheless, they may help to better understand product characteristics and quality attributes and their relevance for immunogenicity and safety. Using artificially modified and/or stressed proteins as model antigens, in vitro and new in vivo models can provide informative data for risk assessments and help to support risk mitigation plans. A case study will be presented to show the benefit and limitations of pre-clinical tools for immunogenicity assessment.

2:35 Impact of Light and Chemical Degradation on Protein Therapeutics, and Cascade of Events that Can Result in Immunogenicity

Christian SchoneichChristian Schoneich, Ph.D., Takeru Higuchi Distinguished Professor and Chair, Pharmaceutical Chemistry, University of Kansas

This lecture describes the nature of light and reactive chemicals, which protein pharmaceuticals are exposed to during production, purification, formulation and storage, and delineates pathways by which these factors can impact drug substance and drug product. It will focus specifically on chemical pathways leading to aggregation, and summarize in vivo studies testing the immunogenicity of chemically modified proteins.

3:05 Panel Discussion - Predictive Tools and Risk Assessment: How Far Have We Come?

Moderator: Bonnie Rup, Ph.D., Research Fellow, Immunogenicity Sciences Lead, Pfizer
Jochem Gokemeijer, Associate Director, Preclinical Discovery & Development, Adnexus, a Bristol-Myers Squibb R&D Company

Theresa J. Goletz, Ph.D., Director, Clinical Immunology, Amgen

Bernard Maillere, Ph.D., Research Director, Head of Laboratory, Immunochemistry, CEA-Saclay

Dan Sikkema, Ph.D., Head, BioPharma Clinical Immunology, GlaxoSmithKline
 

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:20 Problem Solving Breakout Discussions

Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.

T Epitope Manipulation in Reducing Immmunogenicity

Moderator: Bernard Maillere, Ph.D., Research Director, Head of Laboratory, Immunochemistry, CEA-Saclay

  • Strategies for identification and elimination of T cell epitopes
  • Quantification of pre-existing T cells to predict immunogenicity

Product-Related Factors (Aggregates, Subvisible Particles)

Moderator: Anja Langenkamp, Ph.D., Laboratory Head Immunosafety, F. Hoffmann-La Roche Ltd.

  • Assessment of the immunogenicity potential of protein aggregates
  • Use of animal models and studies in uncovering effects of protein aggregates

Relevance of Animal Models for Predicting Immunogenicity

Moderator: Jochem Gokemeijer, Associate Director, Preclinical Discovery & Development, Adnexus

  • New in vivo models that can provide informative data for risk assessment
  • In vivo studies testing the immunogenicity of chemically modified proteins
  • Humanized mouse models
     

Blue Sky Bioservices5:20 Networking Reception in the Exhibit Hall with Poster Viewing
 


6:15 Poster Award

6:30 End of Day



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