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Biophysical analysis is now playing a significant role in the research and early development for a new generation of complex protein therapeutics. As protein engineers and analytical scientists increase their reliance on biophysical analysis, they are driving a move to instruments with higher throughput and resolution – and working to quantify analytical results previously used only for qualitative assessments. The Biophysical Analysis meeting at PEGS will bring together an international audience of protein scientists and analytical specialists to explore the latest technologies and techniques used for problem solving in this dynamic field.

Final Agenda

Recommended Short Courses*

SC12: Study Design and Statistical Data Analysis of Flow Cytometry Assays - Detailed Agenda

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

8:30 Chairperson’s Remarks

David D. Weis, Ph.D., Associate Professor, Pharmaceutical Chemistry, University of Kansas

8:40 KEYNOTE PRESENTATION: Criticality of Biologics Quality Attributes and Integrated Analytical Control

Tapan_DasTapan Das, Ph.D., Director, Biologics Characterization & Analytical Development,

Bristol-Myers Squibb

Increasing emphasis is placed for in-depth understanding of critical quality attribute and associated control strategy in biologics development and production. Link of CQAs to robust development, manufacturing, and pre-clinical and clinical outcomes is paramount to modern biologics development strategies. This session will cover phase-appropriate CQA assessments and establishing advanced analytical control.

Methods and Instruments

9:10 Understanding and Overcoming Trade-Offs between Antibody Affinity, Specificity, Solubility and Stability

Peter_TessierPeter M. Tessier, Ph.D., Richard Baruch M.D. Career Development Professor, Chemical & Biological Engineering, Rensselaer Polytechnic Institute

Antibodies initially identified via immunization or in vitro display methods are often further engineered for therapeutic applications. The process of engineering antibodies for improved properties – such as increased affinity, effector functions and/or bispecificity – often involves trade-offs between improvements in some properties and defects in other ones. We will discuss our work in identifying the causes for these trade-offs as well as our development of new methods for overcoming such trade-offs.

9:40 Forced Degradation Strategies for Biotherapeutics Development

Robert_ChouYite Robert Chou, Ph.D., Principal Scientist, Merck

Forced degradation studies are often used in biotherapeutics development to determine possible biologic product degradation pathways under various stress conditions. Forced degradation also plays an important role in the development of analytical methods, setting specifications, and design of formulations under the quality by design (QbD) paradigm. Different strategies on applying force degradation at different stages and on increasing the workflow of biotherapeutics development will be presented. 10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Stable Formulation Development of Peptides - Interpretation of Ordered Peptide Aggregation

Adrian_PodmoreAdrian Podmore, Ph.D., Formulation Scientist, Medimmune

The current understanding of ordered peptide aggregation will be discussed with respect to formulation development strategies. The presentation will review the application of techniques such as field flow fractionation with light scattering, batch method dynamic light scattering, and nanoparticle tracking analysis to investigate ordered aggregation in the context of defining a ‘stable’ formulation. A new suggested strategy of stable peptide formulation development will be provided.

11:25 Biophysical Mechanism of Captisol-Induced Solubility of Protein Biologicals

Murali_BilikallahalliMurali Bilikallahalli, Ph.D., Senior Director, Ultragenyx Pharmaceuticals

Captisol has been historically used to solubilize small hydrophobic drug molecules. This study for the first time establishes the mechanism of Captisol as a protein solubilizer at high concentrations. Results illustrate why and why not this works with all kinds of proteins that differ in their physic-chemical properties.

11:55 An Innovative Method That Provides Direct Molecular Evidence Used to Decipher the Mechanism and Extent of Aggregation under Stress Conditions

Belinda_PastranaBelinda Pastrana, Ph.D., Professor, Chemistry, University of Puerto Rico Mayaguez, Puerto Rico

The technology presented is transformative for the biopharma industry, because it is capable of determining mechanism and extent of aggregation, as well as the stability of the candidate in one experiment. The method is a label free method, and is independent of the protein therapeutic molecular weight or modification. Because the results are based on first principle, they can be analyzed in a quantitative manner providing the much needed information to decision makers.

12:25 pm An Automated Platform to Predict and Characterize the Colloidal and Conformational Stability of Biologics

Dennis_BreitsprecherDennis Breitspecher, Ph.D., Head of Research and Development – Biochemistry, NanoTemper Technologies, GmbH

Biopharmaceutical development projects become increasingly complex, which calls for straightforward and precise analytical tools to increase research efficiency. Automated stability prediction and characterization by nanoDSF can help to significantly streamline development processes from early discovery to formulation development, resulting in better informed decisions and eventually reduced time to market.

12:40 Sponsored Presentation (Opportunity Available)

 ProteinSimple Large12:55 Luncheon Presentation: Optimizing the Speed and Efficiency of Vaccine Analytical Development Using Automated Simple Western Technology

John_LoughneyJohn Loughney, MSc, Senior Scientist, Vaccine Analytical Development, Merck & Co.

Simple Western is a technology that separates, immunoprobes and detects proteins, all steps taking place in a capillary. We have used the size based assay to replace both traditional qualitative and quantitative Westerns. Traditionally, theses assays are performed using either an ELISA or manual Westerns, which are tedious, laborious, and they can be difficult to transfer. We illustrate how Simple Western allows for reproducible and quantitative results that are also fully automated.

1:55 Session Break

Methods and Instruments (Cont.)

2:10 Chairperson’s Remarks

Anacelia Ríos Quiroz, Ph.D., Group Leader, Particle Lab, Pharma Technical Development Europe (Biologics) Analytics, F. Hoffmann-La Roche Ltd.

2:15 Enabling Structural Biology In Situ – Ribosome Biogenesis in C. Reinhardtii

Philipp_StawskiPhilipp S. Stawski, Ph.D., Scientist, Molecular Structural Biology, Max Planck Institute of Biochemistry, Germany

Cryo focused ion beam (FIB) milling has opened new avenues to explore the biology of cells in their native state. Here we showcase the process of sample preparation and data processing in the green alga C. Reinhardtii by following its path of ribosome biogenesis. Specifically, we focus on the role of the nucleolus and the precursor of the small ribosomal subunit, the pre 90s particle.

2:45 New USP Initiatives for Biophysical Characterization of Biologics

Maura_KibbeyMaura Kibbey, Ph.D., Director, Science & Standards, Global Biologics, United States Pharmacopeial Convention

The USP is an independent scientific organization that protects public health through standards for medicines and their ingredients. As biological science contributes to more advanced therapies, standards continue to play a critical role in drug development and manufacturing. This talk will preview a USP Stimuli Article resulting from USP’s recently convened roundtable of recognized experts on higher order structure characterization of biologics. These best practices may lead to a new USP General Chapter.

 Malvern Instruments3:15 Recent Advancements in Differential Scanning Calorimetry for Stability Profiling of Biotherapeutics

Verna Frasca, Ph.D., Product Marketing Manager, Sales and Marketing, Malvern Instruments

Microcalorimetry is the gold standard technique for thermal stability characterization of protein drugs. DSC measures the protein’s thermal transition temperature (TM), and heat (ΔH) of unfolding. DSC data are used to optimize formulations, choose “developable” candidates, and comparability and biosimilarity studies. The new MicroCal PEAQ-DSC introduces advancements in DSC function, speed, and accessibility, including tools to support regulatory requirements. Protein stability characterization by DSC complements data from Dynamic Light Scattering and Taylor Dispersion Analysis.

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.

Protein Aggregates and Particles

Moderator: Tapan Das, Ph.D., Director, Biologics Characterization & Analytical Development
Bristol-Myers Squibb

Developability Assessment of Protein Therapeutics

Moderator: Shantanu Sule, Ph.D., Senior Research Scientist, Eli Lilly & Company

  • What is developability in context of antibodies, bispecifics, ADCs, non-mAb proteins?
  • Which assays or analytical techniques suit developability assessment?
  • Stability engineering of mAbs – what have we learnt?
  • What are the risks that need to be captured after developability profiling?
  • What are emerging assays or methods can be incorporated in such activities?

Formulation Development of Monoclonal Antibodies in High Concentrations

Moderator: Gayatri Ganeshan, Scientist, Biologics and Vaccines, Merck

  • Overall challenges encountered – from early to late phase development
  • Repertoire of tools available for analytical and physicochemical characterization
  • Viscosity vs concentration vs colloidal stability- the winner?
  • Manufacturability assessment- alternative to the liquid image
 

 

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

7:00 End of Day

THURSDAY, MAY 4

8:00 am Morning Coffee

Applications of Mass Spectrometry in Biophysical Analysis

8:30 Chairperson’s Remarks

Murali Bilikallahalli, Ph.D., Senior Director, Ultragenyx Pharmaceuticals

8:35 HX-MS in Formulation Development and Similarity Assessment

David_WeisDavid D. Weis, Ph.D., Associate Professor, Pharmaceutical Chemistry, University of Kansas

Hydrogen exchange mass spectrometry (HX-MS) is gaining acceptance for its ability to monitor higher order structure in proteins. This talk highlights two areas of recent work. First, developing a molecular-level understanding of how protein-excipient interactions alter physical stability. Second, exploring the limits of HX-MS to detect small changes in higher-order structure in similarity contexts.

9:05 Mass Spec Based Techniques for the Characterization of Protein Biopharmaceuticals

George_Bou-AssafGeorge Bou-Assaf, Ph.D., Scientist, Technical Development, Biogen

Characterization of PTMs is essential to understanding the structure-function relationship in a protein and in the successful development of biopharmaceuticals. Here, we elucidate the impact of methionine versus methionine and cysteine oxidation on the HOS and structural dynamics of IFNβ-1a. We selectively oxidize IFNβ-1a and characterize the products of each oxidation condition with various methods. MS-based techniques, especially HDX-MS, play a dominant role in revealing the differential oxidation effects.

9:35 Identification and Quantitation of DuoBody® Bispecific IgG1 Using Mass Spectrometry and Automated Data Processing and Analysis Workflow

Ewald Van den Bremer, Ph.D., Senior Scientist, Genmab

The characterization of bispecific antibodies (BsAbs) by mass spectrometry (MS) offers several advantages over traditional chromatographic techniques (e.g. HIC, CEX). MS provides unambiguous identification and relevant quantitative information, and combined with automated data processing and analysis, it can be employed in a high-throughput environment. We present a software solution and the related workflows that enabled us to accelerate BsAb batch characterization and release, achieving high quality results and significant time and cost savings.

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

Computational Methods

11:05 Computationally-Guided Protein and Formulation Engineering

Paul_DalbyPaul Dalby, Ph.D., Professor of Biochemical Engineering and Biotechnology, University College London

Protein stability is a critical factor for the successful development of non-aggregating biopharmaceuticals. Routes to predictably engineer protein stability are therefore crucial. We have used a wide range of biophysical analyses to characterize the aggregation landscape of proteins, and used this understanding to inform better formulation design strategies. The use of molecular dynamics to guide protein engineering and formulation for improved shelf-life will be discussed.

11:35 Interfacing Simulation and Experiment for Protein-Protein Interactions

Chris_RobertsChristopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware

This presentation will show an example of combining “minimal” experimental data with molecular models to predict non-ideal interactions of monoclonal antibodies at high concentrations. It will illustrate examples where “simple” models can reasonably capture the high-concentration behavior if one uses low-concentration behavior to adjust the model, as well as challenges for systems with strong attractions and phase separation.

12:05 pm Computational Design and High-Throughput Characterization to Predict and Repair Molecular Attributes

Randy_KetchemRandal Ketchem, Ph.D., Vice President, Molecular Design, Just Biotherapeutics

Antibodies undergo somatic hypermutation to obtain their high levels of both antigen specificity and affinity. Hypermutation also leads to molecular issues as therapeutic candidates. Early molecular analysis enables an integrated approach to therapeutic design encompassing in silico tools, high-throughput screening, and development of predictive tools coupled with large scale data capture. Pushing molecular design earlier in the therapeutic pathway increases the success and lowers the cost of therapeutics.

12:35 End of Biophysical Analysis of Biotherapeutics


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