SC1: Clinical Assessment of Immunogenicity of New Modalities: Focus on Bispecific Antibodies, Gene Therapy and Oligonucleotides
SUNDAY, August 30 | 10:00 AM – 1:00 PM
ABOUT THIS COURSE:
The course will discuss immunoassays and ELISPOT, binding antibody assays, neutralizing antibody assays, and best practices in assay development and validation, as well as reagent challenges.
COURSE AGENDA:
10:00 Chairperson’s Opening Remarks
Darshana Jani, MS, Associate Director, Pfizer, Inc.
10:10 Immunogenicity of Oligonucleotides – Practical Considerations
Ramakrishna Boyanapalli, PhD, Associate Director, Bioanalytical and Biomarker Development, Wave Life Sciences
The course is for researchers in the field of oligonucleotide drug development. Topics included in the course are innate and humoral immune responses to oligonucleotide drugs, practical considerations during assay development, and highlights of immunogenicity assessment for oligonucleotide-based drugs.
10:45 Coffee Break
11:15 Immunogenicity Assessment in Support of Gene Therapy Program-Use of ELISPOT Technology
Magdalena Tary-Lehmann, MD, PhD, CSO, Cellular Technology Limited (CTL); Adjunct Associate Professor of Pathology, Case Western Reserve University (CWRU)
Assessing immunogenicity in support of gene therapy programs can be a challenge in the biopharmaceutical industry, as reliable measurements of antigen-specific T cell responses remain seemingly problematic. Typically, T cells occur in very low frequencies. Focusing on the T cell response evaluation using the ELISPOT readout we have assessed the recall responses to different antigens including AAV capsids in the human outbred population. Examples of such T cell monitoring by ELISPOT will be presented.
11:50 Challenges and Mitigation Strategies for Immunogenicity Assessment of Bispecific Antibody-Based Biotherapeutics
Seema Kumar, PhD, Associate Director, Quantitative Pharmacology & Drug Disposition (QPD), R&D Global Early Development (GED), EMD Serono
Bispecific Ab generation often involves extensive protein engineering that may render them more immunogenic than conventional mAb therapeutics. A robust immunogenicity monitoring and testing strategies driven by thorough immunogenicity risk assessment is thus needed for the development of bispecific Ab-based biotherapeutics. The presentation will highlight the immunogenicity risk assessment strategies, the challenges associated with immunogenicity assays and the mitigation strategies that could be used to address such challenges for bispecific antibodies and bispecific antibody conjugates.
12:25 pm Hybrid LC-MS Approach to Overcome Drug Interference in Immunogenicity Assays
Linzhi Chen, PhD, Senior Research Fellow & Bioanalytical Group Leader, Boehringer Ingelheim Pharmaceuticals
Very recently, immunocapture-LC/MS has been developed for ADA analysis in support of immunogenicity assessment. This novel approach enables simultaneous ADA isotyping and semi-quantitation. One of its attractive features is that immunocapture-LC/MS could be used as an alternative ADA assay platform in cases where traditional ligand binding ADA assays suffers from drug or target interference. This talk presents immunocapture-LC/MS ADA assay development and a real-world application to overcome drug interference in monkey ADA analysis.
1:00 Close of Course
INSTRUCTOR BIOGRAPHIES:
Ramakrishna Boyanapalli, PhD, Associate Director, Bioanalytical and Biomarker Development, Wave Life Sciences
Rama has a PhD in Biology from Bowling Green State University, Bowling Green, Ohio and Postdoctoral fellowship in immunology and Biochemistry, University of Colorado, Boulder, Colorado. Currently working in department of Bioanalytical and Biomarker Development at Wave Life Sciences, Rama leads a group assessing immunogenicity of oligonucleotides. Before joining Wave, Rama worked for three years at Shire Pharmaceuticals, Lexington, Massachusetts, seven years at Nivalis Therapeutics, and three additional years at RoMonics and Boulder Diagnostics, Boulder, Colorado. He held various positions of increasing responsibilities working on immunogenicity, immunogenicity impact assessment, PK and PD assay development.
Linzhi Chen, PhD, Senior Research Fellow & Bioanalytical Group Leader, Boehringer Ingelheim Pharmaceuticals
Dr. Chen obtained his PhD degree in organic chemistry from the University of Mons, Belgium. After postdoctoral training, he joined 3M Pharmaceuticals and then Boehringer Ingelheim Pharmaceuticals and has worked primarily on metabolite profiling/ID and bioanalysis in support of small molecule drug development. In recent years at Boehringer Ingelheim, he has led a group to provide LC/MS-based bioanalytical support to biotherapeutic development programs, and developed a number of LC/MS assays for quantitation of various biotherapeutic proteins such as nanobodies, Fabs, bispecifics, mAbs, etc. His group also developed immunocapture-LC/MS methodology for simultaneous ADA isotyping and semi-quantitation. His recent research focuses on LC/MS determination of in vivo biomodifications of biotherapeutics and their impact on PK/PD. Dr. Chen has more than 30 publications in peer-reviewed journals.
Darshana Jani, MS, Associate Director, Pfizer, Inc.
Darshana Jani has nearly 25 years of practice in the academic and biotechnology field. Throughout her tenure at Genzyme, Medimmune, BiogenIdec until present employment as Senior Manager at Pfizer she has supported clinical and pre-clinical trials, in addition to post marketing studies inclusive of Safety, Immunogenicity, PK, Efficacy, and Biomarker analysis. Darshana has risen from the ranks, at the outset developing and applying boianalytical methods, while assuming numerous responsibilities germane to regulatory compliance of the validation and application of group procedure. She has guided bioanalytical lab groups, held responsible for overseeing all phases of drug recovery and development; a task which incorporated product characterization, potency determination, immunogenicity testing, as well as surrogate maker discovery.
Seema Kumar, PhD, Associate Director, Quantitative Pharmacology & Drug Disposition (QPD), R&D Global Early Development (GED), EMD Serono
Seema Kumar is currently an Associate Director and a DMPK senior project representative at EMD Serono Inc. (a business of Merck KGaA, Germany). In her role, Dr. Kumar is responsible for overall NBE drug disposition support including DMPK/ADME, Bioanalysis (BA) and Immunogenicity strategy for biotherapeutics from the concept generation through discovery and development stages. Previously, Dr. Kumar led regulated Bioanalytical group in BioMedicine Design (formerly PDM-NBE) department at Pfizer. The group provided regulated (GLP/GCP) BA support including assay development, validation and sample analysis for PK, ADA and Nab assessments for pre-clinical and clinical development of Pfizer’s large molecule portfolio. Dr. Kumar also managed Core Automation Team (CAT) engaged in automated large-molecule bioanalysis using Hamilton robotic liquid handlers. Prior to joining Pfizer, Dr. Kumar had served at roles of increasing responsibility as Director of Quality Control and Director of CLIA certified Clinical Bioanalytical Lab at XBiotech USA Inc. Dr. Kumar holds a PhD in Biophysical Chemistry from Johns Hopkins University and has published several publications in peer-reviewed journals and contributed to several book chapters. Dr. Kumar has also given numerous talks in various national and international scientific conferences and meetings. Dr. Kumar has a special interest in Pharmacokinetics and Drug Disposition of multidomain biotherapeutics.
Magdalena Tary-Lehmann, MD, PhD, CSO, Cellular Technology Limited (CTL); Adjunct Associate Professor of Pathology, Case Western Reserve University (CWRU)
Dr. Magdalena Tary-Lehmann is Co-Founding Scientist and CSO for Cellular Technology Limited (CTL). Dr. Tary-Lehmann received her MD and PhD, both from the University of Tübingen, Germany. Her postdoctoral training in Immunology was at the University of California, Los Angeles. She moved thereafter to Case Western Reserve University, where she was awarded tenure and appointed as Associate Professor in the Department of Pathology. As Chief Scientific Officer for CTL she oversees the performance of immunology assays in CTL’s GCP, GLP- and CLIA compliant contract laboratory for various pharmaceutical and biotechnology clients.