Cambridge Healthtech Institute’s 12th Annual

Immunogenicity Assessment & Clinical Relevance

Assay Strategy for Meaningful Evaluation

October 20 - 21, 2021 ALL TIMES EDT

This year's Immunogenicity Summit brings the FDA together with leading industry and academic experts to discuss the development, application and validation of immunogenicity assays. Learn how to manage drug and target interference and tolerance, understand the impact of pre-existing antibodies and interpret the clinical significance of assay data. Novel modalities including cell and gene therapies are posing new challenges to the industry, all of which will be discussed in-depth at this meeting.

Wednesday, October 20

7:30 am Registration and Morning Coffee


8:25 am

Chairperson's Opening Remarks

Eric Wakshull, PhD, CEO, Eric Wakshull Consulting

Circumventing the Immune Responses to Protein Therapeutics: De-Immunization Strategies

Wojciech Jankowski, PhD, Commissioner’s Fellow, CBER, FDA

The immune response to protein-therapeutics (immunogenicity) is an important safety and efficacy concern during drug development and regulation. The potential consequences of immunogenicity range from loss in quality life to a life-threatening situation. Because most protein-therapeutics address serious medical conditions many are approved even if some fraction of the population elicits an immune response. One strategy to circumvent immunogenicity is de-immunization. My presentation will highlight the most recent advances and remaining challenges for de-immunization of protein therapeutics, with a special focus on T cell epitope identification and deletion.


9:00 am

Regeneron’s Rapid Response to COVID-19

Susan Irvin, PhD, Staff Scientist, Bioanalytical Strategy, Regeneron

Regeneron developed 2 non-competing, anti-SARS-CoV-2 neutralizing monoclonal antibodies, casirivimab and imdevimab, as a therapeutic for COVID-19. Our bioanalytical teams navigated multiple hurdles to support development of this cocktail (REGEN-COV): multiple drug concentration and immunogenicity assays were developed, logistical issues were overcome throughout, and a non-standard immunogenicity package was used for the BLA submission. In this presentation, I will describe the clinical bioanalytical strategy and submissions for this important therapy.



The Role of Clinical Pharmacology and Clinical Relevance of Immunogenicity – A Regulatory Perspective

Yow-Ming Wang, PhD, Associate Director for Biosimilars and Therapeutic Biologics, CDER, FDA

Immunogenicity developed against therapeutic biologics is undesirable and can have serious clinical consequences. While it remains challenging in assessing immune-related adverse reactions, advances in leveraging clinical pharmacology data have offered an option for evaluating clinical impacts, particularly for potential secondary treatment failures, and more emerging methodologies are becoming available. This presentation will discuss the successes, the remaining challenges, and potential future directions through the lens of a regulatory scientist.

James Sharkey, Field Application Scientist, Gyros Protein Technologies

Immunoassays are routinely used for anti-drug antibody (ADA) assessments in clinical studies, with a drive towards improvements in assay performance and bioanalytical laboratory productivity. Moreover, assay performance between sites or institutions can facilitate assay transfer during outsourcing. Here we present results for a pembrolizumab ADA bridging assay using Gyrolab microfluidic CD-based platform developed at two different companies with both assays showing high precision and drug tolerance, improving productivity and assay transfer. 

10:30 am Exhibit Hall with Poster Viewing
11:10 am

Evaluating the Potential Role of CQAs in Inducing Anti-Drug Antibodies and Possible Clinical Relevance

Marisa Joubert, PhD, Scientific Director and Group Leader, Amgen

The role of critical quality attributes (CQAs) in inducing clinically relevant immune responses is largely unknown. Here, data will be presented that explores the potential impact of subvisible particles and silicone oil droplets in pre-filled syringes on inducing anti-drug antibodies and possible clinical relevance.

11:40 am

To What Extent Do We See Clinical Impact of Different Types of Immunogenicity in Real-Life and How Do Clinicians and Physicians Respond to This?

Theo Rispens, PhD, Head of Lab/PI, Sanquin

Therapeutic monoclonal antibodies in use in the clinic differ widely in their ability to elicit unwanted antidrug antibodies, and includes fairly immunogenic examples such as infliximab and adalimumab. Routine diagnostic testing service for PK and ADA has been available and is being used to variable degrees by clinicians to make informed treatment decisions for these drugs. Which role does immunogenicity of these therapeutic monoclonal antibodies play in clinical practice?

12:40 pm Enjoy Lunch on Your Own
2:00 pm

Clinical Characterization Methods and ex vivo Activity Measures Both Inform Our Understanding of Complement during an Assessment of Immunogenicity Clinical Impact

Ben Hock, PhD, Director of Immunogenicity, BioMarin Pharmaceutical

Complement can be a meaningful immunogenicity effector. I will discuss specific data that were required for a comprehensive understanding of Pegvaliase immunogenicity: characterization of both the maturation of the anti-therapeutic immune response (specificity and isotypes over time) as well as complement (circulating immune complex and complement levels). In addition, I’ll discuss how nonclinical assessments of complement activation by oligonucleotide therapeutic candidates can inform our clinical immunogenicity risk-assessment.

2:30 pm

Enabling Clinical Immunogenicity Impact Assessment with Standardized Data Tabulation Models

Joleen White, PhD, Bioassay Development Lead (PK, ADA, Biomarker); Clinical Development, Bill & Melinda Gates Medical Research Institute

While all biotherapeutics have immunogenic potential, clinical outcomes such as safety and efficacy drive clinical development. Incorporating immunogenicity data into the clinical database will facilitates future analyses of potential impact on these outcomes. In November 2021, the Standardized Data Tabulation Model (SDTM) update to the Immunogenicity Specimens Assessments domain (IS) will provide structure to consistently capture immunogenicity data while maintaining flexibility to represent different tiered testing schemes. 


3:00 pm Interactive Discussions

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. For in-person events, the facilitator will lead from the front of the room while attendees remain seated to promote social distancing. For virtual attendees, the format will be in a Zoom room. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussion page for a complete listing of topics and descriptions. 

VIRTUAL INTERACTIVE DISCUSSION: Drug Interference in Immunogenicity Assays: Strategies to Improve Drug Tolerance

Eric Wakshull, PhD, CEO, Eric Wakshull Consulting
  • Evaluating the need for drug tolerance: How much drug, what is your molecule risk assessment?
  • Regulatory guidance and expectations
  • Acid dissociation is not the only approach
3:40 pm Exhibit Hall with Poster Viewing
4:20 pm

Signal-to-Negative Control (S/NC) Ratio as an Alternative to Titer for Characterizing the Magnitude and Stratification of Anti-Drug Antibody (ADA) Response: Bococizumab as a Case Study

Frederick McCush, Director, Clinical Assay Lead, Clinical Assay Group, Pfizer

Reporting levels of antibodies in terms of titer is generally understood and accepted by regulatory and medical communities. A strong correlation between signal-to-negative control (S/NC) and titer has been observed across multiple Pfizer programs. Retrospective analysis of anti-bococizumab ADA response and correlation of impact on pharmacokinetic (PK) and pharmacodynamic (PD) endpoints illustrates S/NC is a valid alternative to titer for characterizing the magnitude and stratification of clinically relevant ADA response.


Assessing the Clinical Relevance of ADA

Panel Moderator:
Mohamed Hassanein, PhD, Associate Director, Clinical Assay Lead (Biologics), Pfizer
  • Cost of developing assays and new techniques
  • Optimal methods for collecting good data 
  • Effectively detecting ADA 
  • Interaction and feedback from the FDA
Yow-Ming Wang, PhD, Associate Director for Biosimilars and Therapeutic Biologics, CDER, FDA
Theo Rispens, PhD, Head of Lab/PI, Sanquin
Ben Hock, PhD, Director of Immunogenicity, BioMarin Pharmaceutical
Joleen White, PhD, Bioassay Development Lead (PK, ADA, Biomarker); Clinical Development, Bill & Melinda Gates Medical Research Institute


Michael Partridge, PhD, Associate Director, Bioanalytical Sciences, Regeneron Pharmaceuticals

Pre-existing responses to an IgG4 mAb therapeutic were detected in ~20% of patients using a bridging assay, hindering detection of treatment-emergent ADA. This presentation describes the extensive characterization of the pre-existing response to identify the specific binding region in the molecule. A novel mitigation strategy used a modified version of the drug as an assay reagent. This approach enabled straightforward assessment of drug-specific treatment-emergent immunogenicity for the therapeutic.

5:50 pm

Taming a Tough Positive Control mAb for Neutralization Ab Assay by Utilizing a Surface Plasmon Resonance Tool

Tatyana Yun, PhD, Senior Scientist, Merck
6:20 pm Welcome Reception in the Exhibit Hall with Poster Viewing
7:20 pm Close of Day

Thursday, October 21

7:30 am Registration and Morning Coffee


Soumi Gupta, PhD, Senior Director, Head of Immunogenicity Assessment, BioMarin Pharmaceutical

I will discuss the potential impact of pre-existing immunity on the efficacy of AAV-based gene therapy and provide a brief overview of mitigation strategies. Additionally, I will present preliminary non-clinical data from a few approaches we have evaluated aiming to remove existing antibodies or prevent the development of treatment-induced antibodies.

8:30 am

Bioanalytical Strategies for Cellular and Humoral Immunogenicity in CAR T Cell Therapies

Britta Zehnpfennig, PhD, Senior Principal Scientist/Team Lead, Novartis Institutes for BioMedical Research (NIBR)

CAR T cell immunotherapy has become one of the most promising approaches for treatment of hematological malignancies. While both cellular and humoral immunogenicity of CAR T products could affect efficacy and may be monitored, most published assessments have so far failed to indicate direct clinical correlations with in vitro testing. This presentation will provide an overview of concepts, strategies, and methodologies for assessing cellular and humoral immunogenicity of CAR T cell therapies. 

9:00 am

Precipitation, Acid Dissociation, and Biotin-Drug as Assay Drug (PABAD), a Novel Approach to Improve the Drug Tolerance of Neutralizing Antibody (NAb) Assays while Preserving the Sensitive NAb Species by Dramatically Reducing Acid Treatment

Dilki Wickramarachchi, PhD, Associate Principal Scientist, PPDM, Merck & Co

Drug interference is a major challenge in clinical immunogenicity assessment, especially assaying for neutralizing antibodies (NAb), which could lead to erroneous results. Herein, we are excited to share our new approach to increase the drug tolerance of NAb assay while preserving the sensitive NAb species in serum. In addition, our new approach offers several advantages towards cost-effectiveness with minimal use of biotin-drug and unnecessity to use streptavidin-coated magnetic beads.

9:30 am Exhibit Hall with Poster Viewing
10:40 am

Key Considerations for Development of Immunogenicity Assays for Cellular Therapies

Lynn Kamen, PhD, Senior Scientist, BioAnalytical Sciences, Genentech, Inc.

Cellular therapies where patient T cells are engineered to attack tumors have been shown to be an effective cancer treatment; however, persistence of the infused T cell product is critical for clinical efficacy. Depletion of the infused T cell product can occur through several mechanisms, but one critical pathway is through the host immune response. Therefore, it is critical to develop robust cellular immunogenicity assays to detect the patient immune reactivity.


11:00 am

Impact of Acid Treatment on Anti-Drug Antibodies in Serum Samples

Uma Kavita, PhD, Immunogenicity Assay Leader, Spark Therapeutics, Inc.

Anti-drug antibody (ADA) assessment is a critical component of the safety and efficacy evaluation of protein therapeutics in the clinic since ADA can interfere with target engagement, eliminate the drug from the body and/or lead to serious adverse events. Serum samples are frequently treated with low pH solutions to dissociate the therapeutic from ADA prior to measurement. Such treatment may result in ADA denaturation and defeat the intended purpose. Using a domain antibody therapeutic and several ADA controls of varying affinities, we examine and report the differential impact of several acids/pH levels on assay drug tolerance and antibody sensitivity.


11:20 am

Changes in Clinical ADA Assays During Long-Term, Multi-Site Clinical Trials: Case Studies

Kyra Cowan, PhD, Senior Director, Global Head of New Biological Entities, Drug Metabolism and Pharmacokinetics, Merck

During clinical trials, immunogenicity assays can face impactful alterations due to new patient populations being enrolled, additional contract research organizations being used, or changes in assay format with the advent of new approaches and regulatory recommendations. This presentation will provide case studies of changes to immunogenicity assays, to support a program with several global clinical studies, for which team members had to incorporate appropriate measures to ensure high quality data.

11:40 am Close of Immunogenicity Assessment & Clinical Relevance