Immunogenicity Assay Assessment

Newly developed biologics, including biosimilars, bispecifics, and antibody drug conjugates, have unique features and require a specific skill set. To continue pushing safe and efficacious products to patients, researchers must adapt. At the Ninth Annual Strategies for Immunogenicity Assay Assessment, industry experts will deliver case studies and critical insight into development, optimization, and validation of immunogenicity assays. This event will address proactive strategies for managing off-target toxicity and mitigating risks from concept to product.

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7:00 am Registration and Morning Coffee


8:00 Chairperson’s Remarks

Yao Zhuang, Ph.D., Principal Scientist, PKDM Bioanalytical Sciences, Amgen

8:10 Strategies to Determine Assay Format for the Assessment of Neutralizing Antibody Responses to Biotherapeutics

Bonnie_WuBonnie Wu, Ph.D., Principal Scientist, Bioanalytical Sciences, Janssen R&D, LLC

A white paper has currently been developed that provides recommendations on how to select a suitable NAb assay format (cell-based or non cell-based) to detect clinically relevant NAbs for biotherapeutics with varying MoAs and diverse complexity. This talk will provide an overview of the white paper and discuss the practical considerations for NAb assay format selection strategies. The utility of correlating NAb response with pharmacodynamic data will also be presented.

8:40 Cell-Based Assays for the Detection of Neutralizing Antibodies against BiTe Molecules and ADCC-Based Therapeutic Monoclonal Antibodies

Yao_ZhuangYao Zhuang, Ph.D., Principal Scientist, PKDM Bioanalytical Sciences, Amgen

Recruiting effector cells for target cell destruction is an important strategy to provide the therapeutic interventions in the oncology or auto-immune diseases. Molecules like Rituxan leverage on the mechanism of ADCC, others like Blincyto® are Bispecific T cell Engager (BiTE®) molecules. Due to their complex mechanisms, developing assays for detecting neutralizing antibodies (NAbs) poses significant challenges. Successful approaches in developing robust cell-based assays for NAb detection will be described.

9:10 A Neutralizing Antibody Assay Based on a Reporter of Antibody Dependent Cell-Mediated Cytotoxicity

Yuling_WuYuling Wu, Ph.D., Principal Scientist, Clinical Pharmacology & DMPK, Translational Sciences, MedImmune

Immunogenicity assessment is an essential component of safety evaluation in biopharmaceuticals clinical development. Benralizumab 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) assays to detect NAb against benrulizumab in human serum. This study presents the development, optimization and characterization of an ADCC cell-based NAb assay.

9:40 Optimizing Reporter-Gene Assays for the Quantification of Neutralizing Anti-Drug Antibodies

Michael_ToveyMichael Tovey, Ph.D., INSERM Director, Research, Laboratory of Biotechnology & Applied Pharmacology, Ecole Normale Supérieure de Cachan

Regulatory authorities recommend cell-based assays for the detection of neutralizing anti-drug antibodies (NADAs). Fully validated reporter-gene assays for numerous biopharmaceuticals including novel insulins, FGF21 peptides, Herceptin, and Avastatin based on innovative engineered reporter-gene cell lines will be described that quantify both functional drug levels and NADAs with a high degree of precision within 2 to 4 hours in the same sample without drug interference or serum matrix effects.

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


10:55 Anatomy of an Anti-Drug Antibody Assay

Dharmesh_DesaiDharmesh Desai, Ph.D., Group Leader, Bristol-Meyers Squibb

Protein therapeutics can come in various sizes and shapes ranging from small hormones to monoclonal antibodies to even larger antibody fusion proteins. All of these biologic therapeutics have the potential to generate an immune response against the drug. I will discuss current strategies for designing a robust method for detecting anti-drug antibody. I will cover selection and characterization of the positive control, assay formats and assay optimization (e.g., improving drug tolerance) using design of experiments. 

11:25 PandA: A Novel Method Effective at Reducing or Eliminating the Drug and Target Interferences in Immunogenicity Assays

Jad_ZoghbiJad Zoghbi, Senior Scientist, Sanofi (Genzyme)

Biological matrix interference in immunoassays remains a major challenge in the field of bioanalysis. Circulating drug may interfere with the detection of anti-drug antibodies (ADA) and drug target, or ADA may interfere in drug quantitation assays. Various approaches have been used to improve drug tolerance in ADA analysis but limited success was observed. Our novel method uses Precipitation and Acid (PandA) to overcome drug or target interference in immunogenicity assays.

11:55 PANEL DISCUSSION: Immunogenicity Testing Strategy: Assay Format Selection, Validation Challenges and Data Impact

Moderator: Jim McNally, Ph.D., Associate Director, QPD Program Representative and Immunogenicity Expert at EMD Serono, Inc.

Panelists: Dharmesh Desai, Ph.D., Group Leader, Bristol-Meyers Squibb

Yuling Wu, Ph.D., Principal Scientist, Clinical Pharmacology & DMPK, Translational Sciences, MedImmune

Jad Zoghbi, Senior Scientist, Sanofi (Genzyme)

  • New technologies
  • How you deal with poor drug tolerance, lack of sensitivity and matrix interference
  • Challenges for validation
  • Interpretation of the results and implications for risk assessment

12:25 pm Presentation to be Announced

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:55 Session Break

2:10 Chairperson’s Remarks

Michael Tovey, Ph.D., INSERM Director, Research, Laboratory of Biotechnology & Applied Pharmacology, Ecole Normale Supérieure de Cachan

2:15 Method to Improve the Recovery of pH Labile Anti-Drug Antibodies during Acid Dissociation and Extraction

Weifeng_XuWeifeng Xu, Ph.D., Senior Research Investigator, BAS-Biologics, Bristol-Myers Squibb

When large amount of biotherapeutics drug is present in the clinical samples, these drugs has to be dissociated and removed from anti-drug antibodies (ADA) so that ADAs can be detected by either ligand-binding assay or cell-based bioassay. By screening a panel of more than 20 ADA positive control mAbs, we found that current widely used acid dissociation followed by biotinylated-drug extraction led to low recovery of more than 40% of these ADA PCs, due to sensitivity to low pH and denaturation. Here we discuss the alternative methods for ADA extraction so that both pH labile and pH resistant species can be maximally recovered.

2:45 Case Studies and Methods for Limiting Target Interference in Anti-Drug Antibody Assays

Jim_McNallyJim McNally, Ph.D., Associate Director, QPD Program Representative and Immunogenicity Expert, EMD Serono, Inc.

The presence of soluble target in study samples can present significant issues for anti-drug antibody (ADA) assays. In particular, multimers of the target create multiple binding sites for the biotherapeutic and may result in false positives in ADA assays using the bridging format. This presentation will focus on identifying these false positives and methods to either block or remove circulating target from samples to minimize false positives that occur due to this problem.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

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8:00 am Morning Coffee


8:30 Chairperson’s Remarks

Kyra J. Cowan, Ph.D., Scientist, Genentech/Roche

8:35 Immunogenicity Assessment of Bi-Specific Antibodies

Laura_Salazar-FontanaLaura I. Salazar-Fontana, Ph.D., Strategic Advisor for Immunology and Biomarkers, Sanofi R&D

Bi-specific antibodies represent a new class of biologics aimed to treat conditions such as cancer and autoimmunity. As for any other therapeutic protein, these molecules can elicit an immune response once administered into patients. An adequate immunogenicity risk assessment is extremely useful in guiding assay development and testing strategies since it is tailored to the associated risks identified for the bi-specific antibody therapy. The goal of this talk is to illustrate how this approach helps predict, collect, report and mitigate anti-drug antibody (ADA) data during the clinical development of this class of biologics.

9:05 Bioanalytical Strategy for a Bispecific Antibody in Cancer Immunotherapy

Kyra_CowanKyra J. Cowan, Ph.D., Scientist, Genentech/Roche

Designing appropriate bioanalytical strategies and approaches for new multi-domain protein therapeutic molecules requires specific considerations. This includes not only the selection of suitable nonclinical and clinical pharmacokinetic (PK) formats, but also the corresponding immunogenicity risk assessments and anti-therapeutic (ATA) assay formats for characterization. This presentation will provide the bioanalytical strategy for a new bispecific cancer immunotherapy molecule. The difference between this and a bioanalytical strategy for a typical IgG is summarized.

Lonza9:35 Presentation to be Announced

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

11:05 PANEL DISCUSSION: Assays for Novel Products

Moderator: Jack A. Ragheb, M.D., Ph.D.,Chief Medical Research Officer, Office of Biological Products, CDER/FDA; Attending Physician, Warren Grant Magnuson Clinical Center, NIH

Panelists: Kyra J. Cowan, Ph.D., Scientist, Genentech/Roche

Laura I. Salazar-Fontana, Strategic Advisor for Immunology and Biomarkers, Sanofi R&D

  • Applying risk factors and systems immunology
  • Designing bioanalytical strategies
  • Selecting PK formats

Immunogenicity from Animal Models and Beyond

11:35 Humanized Mouse Models: Applicability and Potential Use in Immunogenicity Studies

Jack A. Ragheb, M.D., Ph.D., Chief Medical Research Officer, Office of Biological Products, CDER/FDA; Attending Physician, Warren Grant Magnuson Clinical Center, NIH

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. 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 in safer and more efficacious therapeutic biologicals.

12:05 pm Historical Perspective on Immunogenicity: What Have We Learned and Where are We Headed

Melissa_WojcikMelissa Wojcik, Sr. Associate Scientist, Analytical Development, Histogenics Corp. (Contractor)

In 1985, the FDA approved the organ transplant rejection therapy, Muromonab-CD3, the first monoclonal antibody. Patients responded well; however, some experienced serious adverse events. The immunogenic hybridoma structure forced scrutiny on dosing strategy. Unlike small molecules, biologics don’t have the luxury of in vitro toxicity ADME modeling. In spite of these challenges, biologics improved to predict immune responses. This presentation walks through industry’s lessons learned and future path.

12:35 End of Strategies for Immunogenicity Assay Assessment

5:15 Registration for Dinner Short Courses

Recommended Dinner Short Course*

SC12: Strategic Bioassay Design and Analysis

*Separate registration required

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