Biophysical Methods

Biophysical analytical methods are now playing an increasingly important role in the discovery and development of next-generation biotherapeutics, and these tools are applied for developability evaluation, structural characterization, understanding aggregation, and as important inputs at different stages of R&D. New informatics and instruments are increasingly allowing these methods to be used in a quantitative, rather than qualitative way – and biophysical studies now play a key role in regulatory filings. The PEGS Biophysical Methods conference brings together an international audience of protein scientists and analytical specialists to explore the latest technologies and methods for problem-solving in this dynamic field.

Final Agenda


Recommended Short Course*

SC9: Introduction to Biophysical Analysis for Biotherapeutics: Development Applications

*Separate registration required.


7:15 am Registration and Morning Coffee

7:25 Women in Science Panel Discussion with Continental Breakfast

Rochard_LucieLucie Rochard, PhD, Liaison, Scientific & Entrepreneurial Initiatives; Director, Innovation Services, Massachusetts Biotechnology Council

Nora MinevaNora Mineva, PhD, CSO, Adecto Pharmaceuticals

Liu_TinaTina Liu, MBA, Co-Founder and CEO, Ally Therapeutics

Chadwich_JenniferJennifer Chadwich, PhD, Vice President, Biologic Development, BioAnalytix, Inc.



8:40 Chairperson’s Opening Remarks

Gabriel Rocklin, PhD, Assistant Professor, Pharmacology, Northwestern University

8:50 Discovery Developability Workflow to Utilize Machine Learning Algorithms for Biologics Optimization

Marc Bailly, PhD, Associate Principal Scientist, Merck

The current race to develop better drugs faster has led biopharmaceutical companies into optimizing all drug discovery and development processes. As part of this effort, machine learning algorithms are being developed to identify correlations between amino acid sequences and physicochemical properties observed during drug development. Here, we describe our ongoing efforts aiming at benchmarking such machine learning algorithms to facilitate our drug discovery process.

9:20 Modeling and Experimental Investigation of Avidity-Driven Bispecific Antibody-Antigen Binding Interactions

John Rhoden, PhD, Senior Research Scientist, Drug Disposition, Eli Lilly and Company

Multivalent binding of antibodies and bispecifics to cell surface targets can be strongly modulated by leveraging avidity to affect target antigen binding. Avidity-driven target engagement can be exploited to improve properties, such as drug potency and target-cell or tissue selectivity. We demonstrate examples utilizing mathematical modeling as a powerful tool to make mechanistically driven predictions and guide experiments to optimize multivalent proteins, guide dosing, and select desirable targets.

9:50 KEYNOTE PRESENTATION: Machine Learning Applications for Analysis of Process-Induced Protein Aggregates

Theodore Randolph, PhD, Professor, Chemical and Biological Engineering, University of Colorado

Protein aggregates can be produced in almost any processing step and should be carefully monitored and controlled. Recent advances in flow imaging microscopy provide rich data sets of images of particles produced within protein formulations. Machine learning techniques can be exploited to analyze large collections of flow microscope images of aggregates in order to detect process upsets and perform root-cause analyses of process-induced aggregate populations.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Women in Science Speed Networking in the Exhibit Hall

11:05 Machine Learning for Sub-Visible Particle Classification

Björn Boll, PhD, Head, Particle Lab and Higher Order Structure Protein Analytics, Physical Chemical Analytics, Novartis Pharma AG, Switzerland

Sub-visible particles, inherently present in all protein drugs, are considered an important safety-related quality attribute of biopharmaceuticals due to their potential immunogenicity. Flow image microscopy techniques allows counting and also discrimination between potentially harmful protein aggregates and harmless pharmaceutical components, e.g. silicone oil. This talk will present a novel application of image analysis via nonparametric Bayesian density estimator to identify silicone oil particles, and a comparison to current benchmarks.

11:35 High-Throughput Investigation of Protein Energy Landscapes in Non-Antibody Scaffolds

Gabriel Rocklin, PhD, Assistant Professor, Pharmacology, Northwestern University

An ideal therapeutic scaffold should possess both high folding stability and minimal conformational fluctuations, but to date it has not been possible to measure conformational fluctuations on a large scale. We developed a multiplexed hydrogen-deuterium exchange mass spectrometry-based approach for measuring stability and conformational fluctuations for thousands of designed protein scaffolds in parallel. These data should reveal the structural determinants of conformational fluctuations and enable the design of optimized scaffolds.

12:05 pm Automating Protein A through Tryptic Digest LC-MS/MS for Looking at Post-Translational Modifications on mAbs and Multi-Specifics

Stephen D'Eri, Scientist, Sanofi

Rapid technological growth in analytical instrumentation and data processing has enabled researchers to develop powerful new methods for use in the biopharmaceutical industry. Unfortunately, sample preparation methods have progressed at a much slower rate, leading to a bottleneck in high-throughput analytics. By incorporating automation into our sample preparation and data analysis methods, we address the bottleneck issue while supporting harmonization of workflows across multiple sites.

12:35 Presentation to be Announced

1:05 Session Break

1:10 Luncheon Presentation I to be Announced

1:40 Luncheon Presentation II to be Announced

2:10 Session Break


2:25 Chairperson’s Remarks

Björn Boll, PhD, Head, Particle Lab and Higher Order Structure Protein Analytics, Physical Chemical Analytics, Novartis Pharma AG, Switzerland

2:30 Emerging Applications for Rapid Surface Plasmon Resonance (SPR) Analysis

Diana Pippig, PhD, Senior Scientist and Team Lead, Functional Characterization, Roche, Germany

While therapeutic antibody and protein formats gain in complexity, it is key to warrant fast- and high-quality target interaction analysis. Cutting-edge SPR analysis allows in-depth characterization and selection of distinct binding modes already in early lead identification. Further, we constantly improve SPR-based QC assay setups and data evaluation in support of process development with a focus on structure-function relationship and physiological context of the compounds.

3:00 Utilizing High-Throughput Differential Scanning Fluorimetry (DSF) to Inform Protein Engineering Decisions

Andrew Urick, PhD, Senior Scientist, AbbVie

As the initial stages of biologics discovery become geared toward generating large numbers of small quantities of material, there is increasing need for sensitive and high-throughput structural assays. Thermostability is an important property for therapeutic proteins, particularly for new biologics formats of increasing complexity. We will describe our implementation of differential scanning fluorimetry to interrogate thermostability in both our protein production and protein engineering workflows.

3:30 Developability Assessment and Property Prediction by pH-Dependent Conformational Sampling

Thorsteinson_NelsNels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group

mAb candidates identified from high-throughput screening or binding affinity optimization often present liabilities for developability; aggregation-prone regions or poor solution behavior. We developed a method for modeling proteins and performing pH-dependent conformational sampling, which enhance property calculations such as hydrophobic patches, charge and pI. Retrospective data analysis demonstrates that these 3D descriptors, averaged over conformational sampling and stochastic titration, accurately predict pI values, screen candidates and enrich libraries with favorable developability properties. The clinical landscape of antibodies is analyzed and its property profile and insights thereof are presented.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

TABLE: The Role of Denaturing and Native-MS in Pharma: From mAbs to Membrane Proteins and Beyond

Moderators: Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen

Wendy Sandoval, Principal Scientist, Genentech

  • LCMS in pharmaceutical research: can it be improved upon?
  • Native-MS in pharma: is it established or still niche? What needs to improve?
  • Required improvements for native-MS to become main-stream in pharma
  • LC-MS and native-MS in membrane protein analysis: what role does it have?

TABLE: High Throughput (HT) Analytical Data Management to Enable Machine Learning

Moderator: Marc Bailly, PhD, Associate Principal Scientist, Merck

  • Enabling HT data generation through efficient data capture, processing, storage and streaming
  • Identifying meaningful data related to the specific project/question asked to the machine learning algorithm
  • Building a relevant and accurate training data set to enable machine learning (identify test and validation data sets)

TABLE: Biophysical Methods to Drive Protein Decisions: What Matters and How Do We Measure It?

Moderator: Andrew Urick, PhD, Senior Scientist, AbbVie

  • Assessing different types of protein stability
  • Informing biophysical techniques with computational modeling
  • How do we leverage biophysical methods for increasingly complex therapeutic formats?
  • What new assays do we need?

TABLE: Structural Mass Spectrometry (SMS): Tools for the Future of Therapeutic Discovery and Development

Moderator: Brandon Ruotolo, PhD, Professor, Chemistry, University of Michigan

  • What are the options for SMS platforms, and what plans are there for adopting SMS technologies into future projects?
  • What are the main barriers for adopting SMS tools into existing projects?
  • What are the deficits in existing SMS capabilities that would add immediate value to current discovery/development efforts?
  • What targets are most amenable to SMS-based analysis and screening capabilities?

6:00 Taste of New England Networking Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day


8:00 am Registration and Morning Coffee


8:30 Chairperson’s Remarks

Iain Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen

8:35 Membrane Mimetic FACS to Facilitate Antibody Screening

Christy Thomson, PhD, Senior Scientist, Research, Amgen

The ability to identify and characterize therapeutic antibodies targeting multi-pass membrane proteins is hampered by the often difficult expression and purification of membrane proteins in their native conformation. We examined the utility of novel methods for membrane protein stabilization, including SMALPs, nanodiscs, and amphipols, to isolate a model multi-pass membrane protein. Following successful incorporation into the membrane mimetics, we evaluated their utility in FACS to facilitate lead identification.

9:05 Combining Experimental and Computational Methods to Identify Antibody Variants with Drug-Like Biophysical Properties

Peter Tessier, PhD, Professor, Pharmaceutical Sciences and Chemical Engineering, University of Michigan

Monoclonal antibodies display variable and difficult-to-predict levels of nonspecific and self-interactions that lead to various drug development challenges, including antibody aggregation, abnormally high viscosity, and fast antibody clearance. In this presentation, we will report experimental and computational methods for identifying, engineering, and predicting antibody variants with drug-like biophysical properties for diverse panels of preclinical and clinical antibodies.

9:35 Shear Rate-Dependent Viscosity as an Indicator of Protein-Protein Interactions and Cluster Formation

Stacy Elliot, PhD, Principal Scientist, R&D, RheoSense, Inc.

9:50 Talk to be Announced

Speaker to be Announced, DRS Daylight Solutions

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


11:05 Gas-Phase Structural Biology: New Tools for the Rapid Assessment of Protein Sequence, Structure and Stability

Brandon Ruotolo, PhD, Professor, Chemistry, University of Michigan

The next generation of medicines depends upon our ability to quickly assess the structures and stabilities of macromolecular protein complexes, the influences of large libraries of conformationally selective small molecule binders, and structures of protein-based biotherapeutics. Such endeavors are nearly insurmountable with current tools. In this presentation, I will discuss recently developed ion mobility-mass spectrometry tools aimed at bridging this gap in basic technology.

11:35 From Screening to Mechanism: Using Mass Spectrometry for Small Molecule Drug Discovery

Benjamin Walters, PhD, Scientist, Biochemistry and Cellular Pharmacology, Genentech

Finding chemical matter that can achieve specificity and adequate target occupancy for therapeutic effect drives early discovery research. Drugs that can covalently attach to their targets, in addition to high affinity binding, are an attractive strategy towards this end. This talk discusses recent case studies benefiting from MS approaches to profile covalent fragment libraries, drive SAR, and explore mechanism with hydrogen exchange.

12:05 pm Probing the Interactions of BBB-Crossing Antibodies with IGF1R Using HDX-MS

John Kelly, PhD, Senior Research Officer, Mass Spectrometry, National Research Council Canada

NRC has developed nanobodies that act as carriers to shuttle therapeutic payloads across the blood-brain barrier. The antibodies bind to IGF1R on the surface of brain endothelial cells and trigger transcytosis. HDX-MS, integrated with NMR and imaging based structural techniques, is being deployed to better understand the mechanisms by which these antibodies bind to IGF1R and how this differs from interactions with its endogenous ligand, IGF-1.

12:35 End of Biophysical Methods

Recommended Short Course*

SC15: Introduction to Gene Therapy Products Manufacturing and Analytics

*Separate registration required.

* The program is subject to change without notice, due to unforeseen reason.

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