10:00 am – 1:00 pm
(SC 4) ESSENTIAL CONSIDERATIONS FOR DEVELOPMENT OF ANTIBODY-BASED THERAPEUTICS FROM DISCOVERY TO THE CLINIC
The biologics market continues to witness an impressive rate of growth, and the Antibody-Based Therapeutics (ABTs) market in particular has contributed remarkably to the expansion of this segment within the pharmaceutical industry. ABTs exhibit exclusive specificity for the target antigen they recognize. This unique characteristic discriminates ABTs from other therapeutic modalities such as small molecule drugs. Successful strategies for development of ABTs require integration of relevant knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, pharmacokinetic (PK)-pharmacodynamic (PD) properties, biophysical characterization and antibody cross-reactivity across species from the early stages of antibody development. This introductory course will evaluate critical considerations necessary for effective development of ABTs.
- This introductory course will evaluate critical considerations necessary for effective development of ABTs
- Integration of relevant knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, pharmacokinetic (PK)-pharmacodynamic (PD) properties, biophysical characterization and antibody cross-reactivity across species from the early stages of antibody development
- Key learnings will include: Considerations for target selection, screening and preclinical development; Affinity and biophysical characterization; Translational Considerations
Course Instructors:
Mohammad Tabrizi, Ph.D., Vice President, Preclinical Development, AnaptysBio, Inc.
Gadi Bornstein, Ph.D., Principal Scientist, AstraZeneca R&D
Scott Klakamp, Ph.D., Research Fellow, Biophysical Chemistry and Bioinformatics, Takeda
AGENDA
10:00 - 10:05 Introduction
Mohammad Tabrizi, Ph.D., Vice President, Preclinical Development, AnaptysBio, Inc.
10:05 - 10:55 Considerations for Target Selection, Screening and Preclinical Development
Gadi Bornstein, Ph.D., Principal Scientist, AstraZeneca R&D
10:55 - 11:05 Networking Coffee Break
11:05 - 12:00 Affinity and Biophysical Characterization
Scott Klakamp, Ph.D., Research Fellow, Biophysical Chemistry and Bioinformatics, Takeda
12:00 - 12:50 Translational Considerations
Mohammad Tabrizi, Ph.D., Vice President, Preclinical Development, AnaptysBio, Inc.
12:50 - 1:00 Q&A
ABOUT THE INSTRUCTORS:
 Mohammad Tabrizi, Ph.D., Vice President, Preclinical Development, AnaptysBio, Inc.
Mohammad Tabrizi PhD is a leader in translational sciences as related to development of antibody-based therapeutics. His product development experience spans many therapeutic areas including oncology and inflammatory disease, and his technical expertise includes preclinical pharmacology and safety, preclinical and clinical pharmacokinetics, pharmacodynamics, GLP-compliant bioanalytics, and clinical pharmacology of therapeutic monoclonal antibodies. He is currently the Vice President of Preclinical Development at Anaptysbio Inc., a privately held biotechnology company in San Diego CA, USA, the leader in Somatic HyperMutation (SHM) technology for development of therapeutic antibodies.
 Gadi Bornstein, Ph.D., Principal Scientist, AstraZeneca R&D
Dr. Bornstein has experience in research and development with an emphasis in development of biologics and monoclonal antibodies. Dr. Bornstein is a Principal Scientist at AstraZeneca, where he currently leads several antibody programs within the Preclinical oncology portfolio. Dr. Bornstein is author or co-author of more than 25 scientific publications, abstracts, and patents.
 Scott Klakamp, Ph.D., Research Fellow, Biophysical Chemistry and Bioinformatics, Takeda
Dr. Scott Klakamp is a Research Fellow at Takeda San Francisco. He leads the Biophysical Chemistry and Research Informatics Groups and has extensive experience in research and development involving the biophysical and analytical characterization of biologics and monoclonal antibodies. Dr. Klakamp is one of the leading scientists in utilizing Biacore®, KinExA®, and FACS techniques to measure the binding kinetics and equilibrium constants of human monoclonal antibody/antigen complexes.
2:00 pm – 6:00 pm
(SC 6) ANALYTICAL TOOLS AND METHODS USED IN BIOPHARMACEUTICAL CHARACTERIZATION TO DRIVE THERAPEUTIC DRUG DESIGN
- Overview of the common analytical techniques used to for performing a structural assessment of biopharmaceuticals, with real-life examples highlighting how they are applied
- Speakers are leaders in structural characterization for biopharmaceutical drug development, and bring a wide breath of experience to the forum
- Discussion will span a range of topics from protein profiling for isoform detection and percent population to peptide mapping for detecting low-level changes to drug product and the identification of post-translational modifications
- Additionally, methods for looking at solvent accessibility and epitope mapping will be presented
Course Instructors:
Jennifer F. Nemeth, Ph.D., Head, Discovery Mass Spectrometry, Centocor R&D, Inc.
Steve Pomerantz, Ph.D., Senior Research Scientist, Centocor R&D, Inc.
Jason C. Rouse, Ph.D., Director - Mass Spectrometry, Analytical Research and Development, Pfizer, Inc.
Sharon Gao, Ph.D., Principal Scientist, Analytical Biochemistry, Biogen Idec
Paul Schnier, Ph.D., Molecular Structure & Design, Amgen, Inc.
AGENDA
2:00 Introduction, Clarification of Goals, Understanding the Audience
Chair: Jennifer F. Nemeth, Ph.D., Head, Discovery Mass Spectrometry, Centocor R&D Inc.
2:15 Introductory Presentation
An Overview of the Analytical Techniques Used for Structural Characterization of Biopharmaceutical Drug Candidates
Jennifer F. Nemeth, Ph.D., Head, Discovery Mass Spectrometry, Centocor R&D Inc.
There are a wide range of biopharmaceutical drugs, which range in molecular type including peptides, proteins, and antibodies. The biopharmaceutical arena presents a unique set of challenges, compared to the small molecule field, for structural analysis; and therefore, a unique set of analytical techniques are needed to characterize these molecules. Some of the most common techniques include SDS-PAGE and size-exclusion chromatography for general protein size, aggregation, and purity assessment, to N-terminal sequencing for purity and terminal assessment, to mass spectrometry for mass assessment, isoform heterogeneity, and post-translational modification identification and localization. An overview of these techniques, and how they might be applied to characterize biopharmaceuticals, is presented
2:45 Enhanced Utility of the Advion Triversa Ion Source for Protein Characterization in the Biopharmaceutical Industry
Steve Pomerantz, Ph.D., Senior Research Scientist, Centocor R&D Inc.
Since its introduction, the Advion Nanomate chip-based ESI source has been principally marketed to the pharmaceutical industry as a means of obtaining high-throughput and high-sensitivity analyses with minimal cross-talk. However, the instrument has several very desirable features for the Drug Discovery researcher. Specifically, the ability to disentangle complex mixtures by effectively lengthening the chromatographic time-scale is invaluable for the identification of low-level post-translational modifications (PTMs) of both target and biopharmaceutical drug product. The use of the Triversa ion source in all of its operating (LC/MS, fraction collector, infusion MS(/MS)) modes for the in-depth PTM characterization of complex mixtures will be presented.
3:15 Profiling Intact Proteins by High-resolution Mass Spectrometry: Key Applications in the Discovery, Development, Commercialization, and Manufacturing of Biopharmaceuticals
Jason C. Rouse, Ph.D., Director - Mass Spectrometry, Analytical Research and Development, Pfizer, Inc.
3:45 Interactive Panel with All Faculty
4:15 Break
4:30 Structural Fingerprinting of Intact Heterogeneous Proteins Using Traveling Wave Ion Mobility Tandem Mass Spectrometry
Paul Schnier, Ph.D., Molecular Structure & Design, Amgen Inc.
Therapeutic proteins produced by recombinant DNA technologies are often heterogeneous due to a variety of modifications. Monitoring these molecules for alterations in either primary sequence or post-translational modifications from cell culture to final product is important as mutations and chemical modifications can compromise product quality and efficacy. Here we demonstrate how ion mobility and tandem mass spectrometry can be used to simplify the spectra of large protein ions and enable top down characterization of intact glycoproteins and monoclonal antibodies.
5:00 Assessment of Oxidation/Deamidation/other PTMs in Biopharmaceuticals
Sharon Gao, Ph.D., Principal Scientist, Analytical Biochemistry, Biogen Idec
Deamidation, oxidation and fragmentation are major degradation pathways for biopharmaceuticals. These modifications can significantly alter drug product quality and efficacy. Here we present methods that accurately determine these critical attributes and discuss the impact of deamidation on binding kinetics.
5:30 Interactive Panel with All Faculty
6:00 Close of Short Course
ABOUT THE INSTRUCTORS:
 Sharon Gao, Ph.D., Principal Scientist, Analytical Biochemistry, Biogen Idec
Sharon Gao received her PhD in Analytical Chemistry at UC San Diego in 1992. Her work experience includes staff scientist in Scripps Research institute, Senior Scientist at Ei Lilly, San Diego and a group leader in Analytical Biochemistry at Biogen Idec Corp.
 Jennifer F. Nemeth, Ph.D., Head, Discovery Mass Spectrometry, Centocor R&D Inc.
Dr. Nemeth heads up the mass spectrometry group focusing on the characterization of molecules from inception through pre-clinical. The principal role of the group is structural characterization of biopharmaceuticals, and the antigens and receptors used during drug development. The Discovery Mass Spectrometry group is also involved in numerous collaborations both outside the Department, as well as within the Johnson & Johnson family of companies. Her publications include detailed protein characterizations, as well as new methods for protein analysis using mass spectrometry.
 Steve Pomerantz, Ph.D., Senior Research Scientist, Centocor R&D Inc.
Dr. Pomerantz obtained his B.S. in Biomedical and Chemical Engineering from the University of Pennsylvania and a Ph.D. in Medicinal Chemistry from the University of Utah under the tutelage of Dr. James McCloskey. He has co-authored numerous articles and several book chapters on the structure elucidation of post-transcriptional modifications and unique RNA moieties, and the HPLC-MS based method developments in support of that research. He entered the biopharmaceutical industry in 2004, joining Centocor to lead the Advanced Technologies efforts in the newly formed Discovery Mass Spectrometry group, with responsibilities for structural characterization of biopharmaceuticals, and the antigens and receptors used during drug discovery and early development, from inception through pre-clinical.
 Jason C. Rouse, Ph.D., Director - Mass Spectrometry, Analytical Research and Development, Pfizer, Inc.
Jason Rouse is a Director of Mass Spectrometry at Pfizer in Andover, MA (formerly Wyeth BioPharma and Genetics Institute). At present, he manages a core mass spectrometry laboratory in the BioTherapeutics Development organization, which supports early- and late-stage product characterization, commercial product comparability assessments, and commercial manufacturing investigations. Jason received his Ph.D. degree in Analytical Chemistry from Michigan State University in 1993 and joined Genetics Institute as a post-doctoral research fellow.
 Paul Schnier, Ph.D., Molecular Structure & Design, Amgen Inc.
Paul Schnier received his Ph.D. in Physical Chemistry from the University of California, Berkeley, in 1998, followed a by post-doctoral fellowship at the Oak Ridge National Laboratory. He has worked in the biopharmaceutical industry for the last eight years, and is currently Principal Scientist in the Department of Molecular Structure at Amgen. His current research interests are focused on the application of novel mass spectrometric, NMR, and biophysical methodologies to drug discovery.
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