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Detecting and managing immune response from biological therapies can be challenging, especially as new constructs and immunotherapy products continue to be developed. This meeting will review case studies and latest understanding in the causes of immunogenicity for a variety of products by focusing on the development, optimization, and validation of immunogenicity assays for traditional and challenging products such as bispecifics, ADCs, immunotherapies and combination therapies.

Final Agenda

Recommended Conference Short Course*

SC14: Overcoming the Challenges of Immunogenicity Assays, Risk Assessment and Regulatory Requirements - Detailed Agenda

*Separate registration required

WEDNESDAY, MAY 3

7:30 am Registration and Morning Coffee

Immunogenicity Assessment of Multi-Domain Therapies

8:30 Chairperson’s Remarks

Wendy White, Ph.D., Fellow and Scientific Director, Translational Sciences, MedImmune, LLC

8:40 Immunogenicity Assay Strategies for Multi-Domain Products

Seema KumarSeema Kumar, Ph.D., Associate Director, EMD Serono

Many biotherapeutics currently in development have complex mechanisms of action and contain more than one domain, each with a specific role or function. In general, the presence of a domain with high immunogenicity risk or presence of a domain with high endogenous protein homology may result in an overall high immunogenicity risk level for the entire multi-domain biotherapeutic. Depending on the specific risk factors, the tiered immunogenicity assay strategy may benefit from additional characterization such as domain specificity of immune response, as discussed in this presentation.

9:10 Development and Characterization of Neutralizing Anti-Idiotype Antibodies Directed against Mirvetuximab Soravtansine

Sven LoebrichSven Loebrich, Ph.D., Development Scientist III, Immunogen

The antibody-drug conjugate Mirvetuximab soravtansine represents a potential new treatment for ovarian cancer patients. Anti-idiotypic antibodies are powerful tools in the development of sensitive and specific bioassays for monitoring patient immune responses. Here, we report the generation and characterization of highly specific anti-idiotypic antibodies against Mirvetuximab soravtansine, and assess their utility in proof-of-concept studies of a simulated anti-drug-antibody (ADA) assay.

Interpreting ADA Data

9:40 Strategies of Dealing with Pre-existing Antibodies during the Assay Validation and the Impact on Data Interpretation

Cheikh Kane, Ph.D., Principal Scientist, DMPK, Boehringer Ingelheim

Pre-existing ADA can be a challenge for method development and validation of ADA assays due to the impact on assay baseline and data interpretation. This presentation will discuss approaches to deal with pre-existing ADA and data interpretation, including a case study.

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

10:55 Setting Targets for Relative ADA Assay Performance

Theo_RispensTheo Rispens, Ph.D., Senior Scientist, Department of Immunopathology, Sanquin

One factor that hampers our understanding of immunogenicity is the difficulty in unambiguously generating and interpreting ADA data. This presentation will address comparability of ADA assays, the use of standards in determining assay performance and pitfalls in doing so, as well as the relationship between technical and clinical performance.

11:25 KEYNOTE PRESENTATION: The Use of Population Specific ADA Assay Cut Points

Albert_TorriAlbert Torri, Ph.D., Executive Director, Bioanalytical Sciences, Regeneron

In various disease populations, patient background responses in an ADA assay can vary significantly. This variability in the background response may require the establishment of population specific assay cut points. This presentation will discuss case studies where baseline samples from different clinical studies were evaluated to determine the appropriateness of the established assay cut points, and when necessary, how alternative cut points were established.

11:55 Strategies for Mitigating the Impact of Pre-Existing Antibodies and Interfering Substances on Anti-Drug Antibody Screening Assay Cutpoints

Jason_DelCarpiniJason DelCarpini, Ph.D., Manager, Clinical Assays, Celldex Therapeutics

Pre-existing antibodies and other interfering matrix components can confound anti-drug antibody screening assay cutpoint calculations and increase the risk of false negative results for patients. Strategies for mitigating the impact of these factors on the assay cutpoint are dependent on both the nature and prevalence of the interfering substance. A variety of approaches exist that can be employed pre-study to reduce the risk of false-negative responses in-study.

12:25 pm Sponsored Presentation (Opportunity Available)

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

1:55 Session Break

Interpreting ADA Data (Cont.)

2:10 Chairperson’s Remarks

Wendy White, Ph.D., Fellow and Scientific Director, Translational Sciences, MedImmune, LLC

2:15 Storage Conditions of Conjugated Reagents Can Impact Results of Immunogenicity Assays: Lessons Learned

Robert_KubiakRobert Kubiak, Ph.D., Senior Manager, Clinical Immunology and Bioanalytics Group, MedImmune LLC

Integrity of conjugated reagents used for measurement of anti-drug antibody (ADA) in study samples is critical for generation of reliable immunogenicity data. Small amounts of aggregates present in preparations of conjugated reagents may lead to a spurious increase of ADA positive classifications creating an appearance of immune response developing in certain individuals. Methods for maintenance of critical reagents and ensuring consistent long-term performance of ADA methods will be discussed.

2:45 New Technology on Multiplex ADA Isotyping

Shuangping_ShiShuangping Shi, Ph.D., Director, Biologics and Vaccines Bioanalytics, Merck Research Laboratories

Biotherapeutic drugs such as monoclonal antibodies (mAbs) have the potential to induce immunogenicity; therefore, it is critical to perform an immunogenicity assessment to ensure drug efficacy and patient safety. In general, an immunogenicity assessment is performed in a multi-tiered approach: screening of anti-drug antibodies (ADA), confirmatory test, titer assessment, characterization of ADA for neutralizing drug activity and isotyping. The goal of our work is to develop multiplex approaches on various platforms including Meso Scale Discovery (MSD), Luminex and Delfia for ADA characterization.

3:15 Poster Presentation: Optimizing NBE PK/PD Assays Using the Gyrolab Affinity Software: Conveniently Within the Bioanalyst's Existing Workflow

Maria Myzithras, Ph.D., Scientist III, Boehringer Ingelheim

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


4:45 Problem-Solving Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.

ADA Data Generation and Interpretation

Wendy White, Ph.D., Fellow and Scientific Director, Translational Sciences, MedImmune, LLC
Zhandong Zhong, Ph.D., Senior Scientist, Amgen

  • Effect of removing "outliers" on setting of the cut point
  • Biological vs analytical variation
  • Is it really pre-existing antibody just because it confirms?
  • Do we have to use formal statistics to set cut points or can we go back to 1.5 or 2 times background (e.g. see the 2015 EMA guidance on Immunogenicity Assessment)

Focusing on Clinically Relevant ADA Analysis for Low Risk Molecules

Albert Torri, Ph.D., Executive Director, Bioanalytical Sciences, Regeneron

  • Are assay validation criteria such as sensitivity and drug tolerance resulting in less clinically relevant ADA data?
  • Does ADA data on early time points provide meaningful, long term information about overall immunogenicity and its potential clinical impact on the drug?
  • Should reporting of ADA be more focus on persistent higher titer or neutralizing responses to provide more relevant information to medical professionals and patients?

Assay Acceptance criteria for Multiwell-Plate-Based Biological Potency Assays

Ravish Patel, PhD., Scientist, Analytical Development Lab, Vitane

  • Why Multiwell-Plate-Based assays specifically
  • What type of assay?
  • AAC (assay Acceptance criteria) or System Suitability?
  • Commonly used AAC (assay Acceptance criteria) and Sample acceptance criteria (SAC).
  • Evolution of acceptance criteria during Development
  • Common practices that cause problems.
 

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

7:00 pm End of Day

THURSDAY, MAY 4

8:00 am Morning Coffee

Effect of ADA on PK Assays

8:30 Chairperson’s Remarks

Zhandong Zhong, Ph.D., Senior Scientist, Amgen

8:35 Evolving Methodologies for Measuring Immunogenicity: A Novel Automated all in one Cell-Based Ligand Binding Assay

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

Immunogenicity is a constant point of concern in the development in biotherapeutics both in terms of safety and efficacy. Understanding the potential impact on a project early in the life cycle is preferred. Thus we developed a method to better characterize the circulating immune complexes in preclinical species in terms of their size. The method can be applied to any humanized antibody or derivatives of such. 


 9:05 Predicting Clinical Immunogenicity for Biotherapeutics Using a Systems Model of the Immune Response

Abhinav_TiwariAbhinav Tiwari, Ph.D., Clinical Pharmacologist, Pfizer

Immunogenicity can be a key factor in strategic decisions regarding asset progression and competitive differentiation. Any unwanted immunogenicity can cause significant program delays and necessitates additional resources to manage and mitigate their consequences. While predicting immune responses and their consequences is not currently reliable, we have developed a multi-scale mechanistic mathematical model to forecast the incidence of anti-drug antibodies (ADA) and its impact on efficacy. Currently, we are evaluating this model by making quantitative comparisons between model predictions and observed ADA incidence for multiple biotherapeutics with substantially different incidences of immunogenicity.


9:35 Poster Presentation I: Human In Vitro Skin Explant Assays for Predicting Immunotoxicity of Drugs and Cellular Therapies

Shaheda Ahmed, Ph.D., Senior Scientist, Newcastle University

9:50Poster Presentation II: An Innovative Approach for Detecting Neutralizing Antibodies Directed to Antibody-Derived Therapeutics Based on the Conventional Bridging ADA Assay Format

Benedicte Brackeva, PhD, Associate Scientist Pharmacology, Ablynx

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

Managing Drug and Target Interference

11:05 Innovative Approaches to Overcome Matrix Interference for Anti-Drug Antibody Detection

Meina_LiangMeina Liang, Ph.D., Director, Clinical Pharmacology and DMPK, Translational Sciences, MedImmune

Immunogenicity assessment is a requirement for biopharmaceutics registration. It is often evaluated in clinical studies as a secondary endpoint. Matrix interference is a common challenge for immunogenicity testing. If not addressed during method development, the interference could lead to inaccuracy in immunogenicity reporting. In this presentation, we will use case examples to discuss innovative approaches to overcome various matrix interferences to ensure accurate immunogenicity assessment.

11:35 pm Drug Target Interference in Immunogenicity Assays

Zhandong-ZhongZhandong Zhong, Ph.D., Senior Scientist, Amgen

Soluble drug target in a sample can interfere with the accurate detection of anti-drug antibodies (ADA), confounding the assessment of the immunogenicity of a biotherapeutic. The outcome of such interference depends on the assay format and its susceptibility to other factors that may be present in the sample matrix. This presentation discusses approaches for the assessment and mitigation of the interference in immunogenicity testing, encompassing ADA and neutralizing activity assays.

12:05 Discussion Panel: Drug Interference in Immunogenicity Assessment

12:35 End of Strategies for Immunogenicity Assay Assessment


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