Cambridge Healthtech Institute’s 5th Annual
Characterization of Biotherapeutics
Prediction, Screening And Characterization Of New Biologics
January 14-15, 2019
The popular 5th Annual Characterization of Biotherapeutics conference will bring together leading scientists from biopharmaceutical industry, academia and government to discuss case studies, new technologies, assays on analytical development and characterization
of mAbs, ADCs, bispecifics, and other novel protein formats, biosimilar. Some of the hot topics for discussion this year will include discuss regulatory expectations and developability of new product formats, cell and gene therapy products, biosimilars,
high-throughput analytics, multi-attribute methods, glycosylation/post-translational modifications and biophysical assays more.
SUNDAY, JANUARY 13
4:00 - 6:00 pm Pre-Conference Registration (Sapphire West Foyer)
MONDAY, JANUARY 14
7:00 am Registration and Morning Coffee (Sapphire West Foyer)
9:00 Welcome by Conference Organizer
Nandini Kashyap, Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Kelly Loyet, PhD, Senior Scientist, Biochemical and Cellular Pharmacology, Genentech
9:10 Antibody Therapy: From Substitution to Immunomodulation and Monoclonal Immunotherapy
Paul Imbach, MD, Professor, Ped. Oncology/Hematology, University of Basel, Switzerland
Polyvalent antibody concentrate substitutes patients with immune deficiency and severe infection and synergistically immunomodulates the disturbed immune system with no or mild adverse effects in patients with autoimmune disease. While monoclonal immunotherapy
may evoke severe adverse effects such as immune deficiency, infection, autoimmune or oncologic diseases and others, the question arises whether to combine monoclonal with polyvalent antibody therapy for avoidance of severe adverse effects and for
treatment of the loss of tolerance – the common cause of autoimmunity and cancer.
9:50 Structure and Function Relationships: Link Control Strategy to CQAs
Jane (Xiaoyao) Xiao, PhD, President, BioPeak Solutions
Structure and function relationships are essential to a risk assessment for ranking and prioritizing quality attributes. The development of a robust control strategy in manufacturing process can be challenging due to the structural and functional complexity
of therapeutic proteins. The presentation will focus on the approaches in establishing structure-function relationships to manage CQAs and to develop a control strategy, including aggregation, oxidation and glycan structures relationship with FcRn
binding potency, proliferation potency and cytotoxicity bioactivity.
10:20 Networking Coffee Break (Sapph8ire & Aqua West Foyer)
10:45 Approaches to Understanding the Manufacturability of Monoclonal Antibodies
Michael Anyadiegwu, PhD, Senior Scientist, Downstream
Processing, Centre for Process Innovation Ltd., National Biologics Manufacturing Centre
A short list of 50 monoclonal antibody sequences was selected based on experimental data from 200 monoclonal antibodies sequences. These 50 molecules covered a range of titres and quality attributes. Using a standard CHO USP and DSP platforms, the 50
molecules were manufactured and purified to provide material for measurement of biochemical, biophysical and immunological information. This presentation provides an update on the project outputs and progress to linking biochemical and quality data
to sequence and structural liabilities.
11:15 LabChip Electrophoresis: A Robust, Sensitive & Intelligent Platform for Bio-therapeutics Characterization and Analysis
James White, Senior Application Scientist, PerkinElmer
To succeed in today’s competitive environment, significant efforts are being made by biopharmaceutical companies to produce recombinant protein products with high yield and more critically high quality to ensure therapeutic protein product safety
and efficacy. For protein purity analysis, microfluidic molecular separation offers distinct advantages over traditional capillary electrophoresis in sample consumption, ease of use, and speed of analysis. We use a smart microfluidic platform for
high throughput quantitation and quality screening of protein products.
11:45 Glycan Characterization Strategies to Guide Early Biotherapeutic Development
Nathan Brown, PhD, Senior Scientist III, Global Biologics, AbbVie,
Post translation modifications (PTMs) can significantly alter protein function and disposition and, therefore, necessitate detailed analytical characterization of protein therapeutics as well as the targeted proteins. One category of PTMs of interest,
importance and complexity is protein glycosylation. Here, we present strategies utilizing multiple, orthogonal approaches, to characterize glycan micro- and macro-heterogeneity, guiding early development and providing increased understanding of novel
biologics and their protein targets.
12:15 pm NEW: Small Molecule Inhibitor Screening Utilizing Capillary Electrophoresis
Senior Associate Scientist, Gilead
Simple Western is a capillary-based immunoassay platform for protein characterization. We use the platform to determine the EC50 of small molecule inhibitors in tissue culture cells. Compared to a traditional Westerns that is a time consuming semi-quantitative
process that is fraught with the potential inconsistencies of protein transfer to a membrane, Simple Western is a membrane free system that can be set up in under an hour and runs autonomously overnight.
12:45 Session Break
12:55 Luncheon Presentation I: N-Glycan Sample Preparation and Analysis Workflows for Screening and Characterization of Biotherapeutics
Aled Jones, PhD, Senior Product & Applications Manager, Marketing, ProZyme
The structure of N-glycans on biotherapeutics can potentially affect immunogenicity, pharmacokinetics and pharmacodynamics, making the characterization of N-glycans an essential part of the development process. We present N-glycan sample preparation and
analysis workflows for biotherapeutics, including labeling of released glycans for characterization by liquid chromatography and mass spectrometry, and Gly-Q for rapid screening using an integrated system with capillary electrophoresis.
1:25 Luncheon Presentation II (Sponsorship Opportunity Available)
2:00 Chairperson’s Remarks
Alexey Rak, PhD, Head of Bio-Structure and Biophysics, Integrated Drug Discovery, Sanofi R&D
2:05 Deamidation and Isomerization Liability Analysis of 131 Clinical Stage Antibodies
R. Paul Nobrega, PhD, Scientist, Protein Analytics, Adimab, LLC
The deamidation and isomerization liabilities of 131 mAbs were evaluated under high and low pH accelerated stress conditions. Tryptic peptide mapping was used to identify the modified residues and quantitate the modifications. Comparison across all of
the mAbs in our dataset reveals that specific positions within the CDRs have elevated frequencies of modifications under our stress conditions.
2:35 Novel Concert of Biophysical Methods for Multi-Specific Biologics Characterization
Alexey Rak, PhD, Head of Bio-Structure and Biophysics, Integrated Drug
Discovery, Sanofi R&D
Modern drug discovery requires characterization of biomolecular interactions to be time- and cost-effective, highly precise and reproducible. New multispecific biologics formats require new approaches to assess their developability. Here we report applications
of novel biophysical methods Second Harmonics Generation, nano-Differential Scanning Fluorimetry, MicroScale Thermophoresis and thermal stability kinetics experiments that we are applying in our biologics discovery for multi-specific drugs as well
as for mAbs and ADCs. The effectiveness of the novel integrated biophysical methods will be presented and discussed.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments (Sapphire & Aqua Foyer)
Join your peers and colleagues for interactive roundtable discussions.
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4:30 Bioanalytical Challenges for Ocular Therapeutics
Kelly Loyet, PhD, Senior Scientist, Biochemical and Cellular Pharmacology,
There is a need for long-acting delivery (LAD) modalities for back of the eye ocular biologics to reduce the injection burden and achieve better outcomes. Many proposed LAD modalities that rely on half-life extension pose challenges for bioanalysis due
to molecular complexity, immunogenicity, and in vitro to in vivo translation. Here we present new strategies for overcoming bioanalytical challenges in order to better understand and evaluate
potential LAD modalities.
5:00 Particle Size Characterization of a mRNA-Containing Lipid Nanoparticle Formulations
Jessica Banks, PhD, Scientist, Moderna Therapeutics
Understanding and controlling the size distribution of therapeutic lipid nanoparticles is essential to the development of a well-defined and stable drug product. Both sub-micron and micron-sized subvisible particles are relevant, highlighting the need
for selective and orthogonal techniques applicable to a broad particle size range. This presentation will describe studies on a panel of biophysical techniques to characterize particle size attributes of an mRNA lipid nanoparticle drug product.
5:30 Early Stage Evaluation of Excipient Effects on the Stability of ADCs
Brittney J. Mills, PhD, Senior Scientist II, Drug Product
Development, AbbVie, Inc.
Traditional excipients used in standard biologic formulations may affect ADCs differently due to the unique nature of the molecule. The distinct properties of the toxins used in the preparation of novel ADCs require extensive excipient screening to determine
the formulation most suitable for the entire molecule. Performing this type of screening is difficult due to the limited material available at this stage in the development process. This presentation will focus on our miniaturized approach for evaluating
the effects of excipients on the stability of ADCs.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:15 Close of Day
TUESDAY, JANUARY 15
8:00 am Registration and Morning Coffee (Sapphire West Foyer)
8:45 Chairperson’s Remarks
Jichao (Jay) Kang, PhD, RAC, Director, Analytical Development, Amicus
8:50 Setting Specification for Biologics
Jichao (Jay) Kang, PhD, RAC, Director, Analytical
Setting appropriate specification is a key control strategy for consistently manufacturing quality biologics product. However, due to the complexity and heterogeneity nature of the biologic molecules, it is challenging to set appropriate specification
that can effectively control process variation. The presentation will review the key considerations in setting specification for biologics product in different stages of product development life cycles with case studies presented.
9:20 Automated Carbohydrate Sequencing of Recombinant Protein Therapeutics
Andras Guttman, PhD, DSc, Professor, Horvath Csaba Laboratory for Bioseparation Sciences, Research Centre for Molecular Medicine, University of Debrecen
In this talk, we describe an automated carbohydrate sequencing approach using the appropriate exoglycosidase enzymes in conjunction with the utilization of some of the features of a capillary electrophoresis (CE) instrument to speed up the process. The
enzymatic reactions were accomplished within the temperature-controlled sample storage compartment of a capillary electrophoresis unit and the separation capillary was also utilized for accurate delivery of the exoglycosidase enzymes. CE analysis
was conducted after each digestion step obtaining in this way the sequence information of N-glycans in 60 and 128 minutes using the semi- and the fully-automated methods respectively.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 Understanding the Charge Requirements for Hyaluronic Acid Binding for Drug Delivery
Shrenik Mehta, Postdoctoral Fellow, Genentech
In this work a Microscale Thermophoresis (MST) based hyaluronic acid (HA) binding assay was developed that enabled the measurement of peptide - HA binding interactions. This assay was used to interrogate the charge requirements for HA binding. This work
provides clues towards engineering peptides for drug delivery with different affinities for HA.
11:30 A Robust and Sensitive Workflow to Assess the in/ex vivo Fragmentation of Antibody Variants using Capillary Eletrophoresis SDS Laser Induced Fluorescence (CE-SDS LIF)
Cong Wu, PhD, Scientist, Biochemical and Cellular Pharmacology, Genentech
We report a highly sensitive and robust workflow to quantify the degraded products of multivalent antibodies using capillary electrophoresis-laser induced fluorescence (CE-LIF) after affinity capture of stressed samples and fluorescent labeling. The improved
sensitivity and the simplified quantitative workflow of CE-LIF provide complementary information to LC-MS intact analysis and enables a faster and more reliable data turnaround to trigger in-depth investigation and to gate or rank drug candidates.
12:00 pm Improving Biotherapeutic PK Assays Using Highly Specific Anti-Idiotypic Affimers
Matt Johnson, PhD, CTO, Avacta Life Sciences
The Affimer® scaffold is a versatile next-generation non-antibody platform that offers great potential for both novel biotherapeutics as well as research and diagnostics
tools. We have successfully developed anti-idiotypic binders to a range of therapeutic antibody targets to facilitate and improve assays to better facilitate the drug development pipeline. This approach uses only a single target-specific reagent
allowing for simpler, more robust and standardizable assay design.
12:30 Session Break
12:40 Luncheon Presentation: Better Protein Characterization Using Tycho to Reveal Protein Quality
Peter Fung, Senior Manager, Product Marketing, NanoTemper
Starting with samples of questionable quality only leads to irreproducible results. Yet, researchers continue to use unvalidated material assuming it’s fine or because they lack an easy test of sample quality. For the first time ever, quickly
and precisely determine protein quality in just 3 minutes by using TychoTM NT.6. Tycho fits into any step of a purification or characterization workflow to easily monitor protein quality and enabling researchers to get more consistent results.
1:10 Close of Characterization of Biotherapeutics Conference
5:45 - 8:45 Recommended Dinner Short Courses*
SC3: Protein Aggregation: Mechanism, Characterization and Consequences
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*Separate registration required