New biotherapeutics formats are flooding the discovery and development pipelines and with this comes an increasing need for better and faster characterization tools and strategies, improved biomolecular and biophysical assays for the new biotherapeutics.
The Fourth Annual Characterization of Biotherapeutics conference will present new tools, strategies and case studies on analytical development and characterization of mAbs, ADCs, bispecifics, and other novel protein formats, biosimilars,
HOS, and developability. We invite you to present a poster and attend to join with colleagues in this discussion of the key challenges and solutions improving predication, screening and characterization of new biologics.
Final Agenda
SUNDAY, JANUARY 7
4:00 - 6:00 pm Pre-Conference Registration
MONDAY, JANUARY 8
7:00 am Registration and Morning Coffee
9:00 Welcome by Conference Organizer
Nandini Kashyap, Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Alexey Rak, Ph.D., Head of Bio Structure and Biophysics, Integrated Drug Discovery, Sanofi R&D
9:10 Novel Low-Protein Consuming High Throughput Biophysical Methods for mAbs, ADCs and Multi-Specific Biologics Characterization
Alexey Rak, Ph.D., Head of Bio Structure and Biophysics, Integrated Drug Discovery, Sanofi R&D 
Modern drug discovery operations require characterization of biomolecular interactions to be both time- and cost-effective as well as to be highly precise and reproducible. Here we report applications of novel biophysical methods nano-Diffrential
Scanning Fluorimetry (nanoDSF), MicroScale Thermophoresis (MST) and kinetic stability experiments that we are applying in our biologics discovery and development for mAbs, ADCs and multi-specific biologics. The examples of the demonstrated effectiveness
of the novel integrated biophysical methods will be presented and discussed.
9:50 Analytical Characterization of Next-Generation Antibody-Based Therapeutics
Tasneem Bahrainwala, PhD, Analytical Sciences Mass Spectrometry
Group Leader, MacroGenics, Inc.
DART® molecules are bispecific antibody-based proteins developed for a variety of indications including immune-oncology, and are designed to simultaneously bind to two targets.
These versatile molecules have the potential for improved efficacy and safety profile through enhanced selectivity and recruitment of specialized effector cells. This presentation will discuss analytical characterization strategies using this
novel class of molecules and other antibody molecules as case studies.
10:20 Networking Coffee Break
10:45 Effects of Chemical Degradation on Higher Order Structure, Conformational Stability, Physical Instabilities, and Biological Properties of an IgG1 mAb
Dinen Shah, Department of Pharmaceutical Sciences (Krishna Mallela Lab), University of Colorado
Denver Health Sciences Center
Oxidation is a critical challenge during the life cycle of any therapeutic protein. In this study, we probed the effect of oxidation on the structure, stability, aggregation, and function of a therapeutic IgG1 monoclonal antibody (mAb-8). In particular,
we examined whether the extent of protein destabilization, aggregate formation, and loss of specific protein activity can be correlated with the site and extent of oxidation.
11:15 Composition and Thermal Stability of Adsorbed Vaccines
Marina Kirkitadze, Ph.D., Deputy Director, Head of Biophysics and Conformation
Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada
The focus of this presentation is a characterization of adsorbed vaccine consisting of several protein antigens and new adjuvant. The applicability of several biophysical methods (FTIR, Raman, DSF) to characterize vaccine components in the final
drug product without desorption.
11:45 Analytical QbD Applied to the Development of a Robust Reversed Phase Separation Method to Monitor Free Drug Related Impurities in an ADC
Kevin Strozyk, Sr. Research Associate, Analytical Sciences, Seattle Genetics
Quality by Design (QbD) allows for a systematic approach to method development with predefined objectives while leveraging prior method understanding. Here we present a case study for the development of a robust reversed phase UPLC separation
to accurately and precisely quantify free drug related impurities (FDRI) in an ADC using components of analytical QbD including the use of an Analytical Target Profile (ATP), prior knowledge, and Design of Experiment (DoE).
12:15
pm Expanding the Role of Circular Dichroism (CD) in Higher Order Structure (HOS) Characterization of Biotherapeutics – Forced Degradation Studies of mAbs
Helen Wu, Ph.D., Senior Scientist, Boehringer Ingelheim Pharmaceuticals Inc
This presentation includes case studies highlighting the role of CD in Higher Order Structure (HOS) comparisons of potential biotherapeutics. Detection of even minor changes in secondary and tertiary structure and generation statistically-validatable
data for critical quality attributes contributes to informed decision-making and strengthens totality of evidence in regulatory submissions.
12:45 Session Break
1:00 Luncheon Presentation: Glycans before Lunch: Rapid N-Glycan Sample Preparation Workflows for Screening and Characterization of Biotherapeutics
Aled Jones, Senior Product and Applications Manager, ProZyme
The structure of N-linked glycans can play a critical role in the pharmacology of therapeutic proteins, potentially affecting immunogenicity, pharmacokinetics and pharmacodynamics. This makes the characterization of N-glycans an essential part
of the biotherapeutic development process. We present 3 rapid N-glycan sample preparation and analysis workflows: Gly-X with InstantPC or 2-AB Express labeling for glycan characterization by liquid chromatography, and Gly-Q for rapid screening
using an integrated system with capillary electrophoresis.
2:00 Chairperson’s Remarks
Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Biophysical Chemistry, AbbVie
2:05 Relationship between kinetic Stability and Structural Rigidity of IgG1 mAbs as Monitored by Resistance to SDS Induced Denaturation
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development,
Eli Lilly and Company
2:35 Deciphering the Root-Causes for Atypical PK of mAbs and Complex Biologics by Protein Engineering
Thomas E. Kraft, Ph.D., Postdoctoral Scientist, Large Molecule Research, Roche Diagnostics
GmbH
Therapeutic antibodies with nearly identical Fc domains show >10-fold differences in clearance. We systematically identified properties of the Fv domain that can cause atypical pharmacokinetic behavior. Using protein engineering, we created
Fab mutants with defined biophysical properties and tested them in biochemical PK prediction assays and for in vivo clearance. Our results are highly relevant for predicting and improving in vivo PK based on biophysical properties and biochemical assay data.
3:05 Transition to BuzZ Sessions
3:15 BuzZ Sessions with Refreshments
Join your peers and colleagues for interactive roundtable discussions.
4:30 Selection and Sensitivity of Biophysical Techniques in Characterization of Higher Order Structure of Proteins
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development,
Eli Lilly and Company
A strong correlation among higher order structure (HOS), conformational stability, and functional properties is generally observed for proteins. Characterization of HOS is primarily performed by different biophysical techniques. The selection
and sensitivity of these techniques is very important, and may depend on protein to protein. This presentation will discuss the sensitivity and limitations of different techniques used in the characterization of proteins of different sizes,
and the number of intrinsic chromophores under a variety of stress conditions.
5:00 Biologics Characterization and Comparability
Yemin Xu, Ph.D., Senior Regulatory Scientist, Regulatory Science, Regeneron
Biologics development is the fastest growing pharmaceutical market. Biologics development and licensing application require thorough physicochemical and biological characterization. Across development stages, analytical comparability exercises
are commonly required when changes are implemented into the manufacturing process. Analytical comparability plays a crucial role to demonstrate that pre- and post-change products are comparable and have no adverse impact on safety, identity,
purity, or efficacy of the product.
5:30 Biophysical Studies of Multivalent Antibody-Antigen Complexes
Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist,
Biophysical Chemistry, AbbVie
This presentation will describe electron microscopy studies of various complexes that are formed when TNF alpha interacts with anti-TNF monoclonal antibodies.
6:
00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing
7:15 Close of Day
TUESDAY, JANUARY 9
8:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company
8:35 Developability Assessment to Support Pre-Candidate Selection of Biotherapeutics
Jonathan S. Kingsbury, Ph.D., Principal Scientist, Global Pharmaceutical
Development Biologics, Sanofi
Developability/deviceability is a critical pipeline support activity, the results of which are used to focus the field of potential candidate molecules. Such assessments can be conducted in diverse ways, with different testing compositions
and timing. The benefits of a multi-checkpoint strategy for candidate credentialing completed at different stages throughout the early discovery/development timeline will be discussed. In addition, the defining qualities of a comprehensive,
process-relevant assessment strategy will be discussed and explained using examples. The use of the resulting data to enable decision making for pre-candidate selection using empirical benchmarks will be highlighted.
9:05 Case Study: Light-Induced Covalent Histidine Adducts on A IgG1 Molecule: Reaction Pathways and Influencing Factors
Ming Lei, Ph.D., Associate Scientist, Protein Analytical Chemistry, Genentech
Light is known to induce many reactions on protein residues such as tryptophan (Trp), cysteine (Cys) and histidine (His). In this work, light-induced His-adducts were found on a monoclonal antibody (mAb-1) formulated in His-containing buffer.
The reaction pathways and influencing factors such as solvent accessibility and the concentrations of common surfactants are thoroughly investigated.
9:35 Selected Poster Presentation: Detection of a Host-Cell Protein Impurity-Hamster Phospholipase B-Like 2 (PLBL2) in Therapeutic Monoclonal Antibodies
Sheetal Mehta, Research Scientist, Analytical Department, Bristol Myers Squibb Co.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Selected Poster Presentation: Structural Characterization of SDS-Solubilized Proteins by ESI-MS
Cheng Zhao, Ph.D., Principal Scientist, Abbott Laboratories
11:15 Selected Poster Presentation: Membrane-based Protein A Purification Device Offers High Dynamic Binding Capacity and Short Residence Time
Chao Zheng Ph.D., Senior Scientist, Department of Biotherapeutics Discovery, Boehringer Ingelheim
11:30 Rapid Development of Anti-Idiotypic Binders Using a Novel Affinity Scaffold
Matt Johnson, Ph.D., CSO, Avacta Life Sciences
Affimer® proteins are next-generation affinity scaffolds, offering highly specific and stable binders, with great potential for the generation of novel biotherapeutics and renewable research and diagnostics tools. We produced highly-specific
anti-idiotypic Affimers, for Trastuzumab, anti-CTLA4, anti-CD20 and anti-TNFa antibodies, via a 12-week development process. The resulting Affimer® binders can be used as reagents in pharmacokinetic and immune response assays, for
the characterisation of monoclonal biotherapeutics.
12:00 pm PANEL DISCUSSION: Application of New Analytical Tools and Mass Spectroscopy for Characterization of Biologics
Moderator:
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company
Panelists:
Jonathan S. Kingsbury, Ph.D., Principal Scientist, Global Pharmaceutical Development Biologics, Sanofi
Cheng Zhao, Ph.D., Principal Scientist, Abbott Laboratories
Ming Lei, Ph.D., Senior Research Associate, Protein Analytical Chemistry, Genentech
12:30 Close of Characterization of Biotherapeutics Conference