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.

Wednesday, September 2

AUTOMATION, MODELING AND HIGH-THROUGHPUT ANALYSIS

9:05 am

Discovery Developability Workflow to Utilize Machine Learning Algorithms for Biologics Optimization

Marc Bailly, PhD, Principal Scientist, Merck Research Labs

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.

9:25 am 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.

Kevin Lance, PhD, Marketing Manager, Marketing, Unchained Labs

Choosing one protein quantification tool that spans upstream and downstream workflows means that sample volume, throughput, and accuracy are all critical. Stunner delivers fast, automation-compatible protein quantification to within 2% accuracy and 1% precision on 2 µL of sample. And when moving downstream, Stunner will ace the USP and Ph. Eur. standards for UV/Vis.

10:10 am

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

John J. Rhoden, PhD, Director, Preclinical Development, Fusion Pharmaceuticals Inc.

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.

10:30 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
John J. Rhoden, PhD, Director, Preclinical Development, Fusion Pharmaceuticals Inc.
Panelists:
Marc Bailly, PhD, Principal Scientist, Merck Research Labs
Theodore Randolph, PhD, Professor, Chemical and Biological Engineering, University of Colorado
Kevin Lance, PhD, Marketing Manager, Marketing, Unchained Labs
10:55 am

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

Peter M. Tessier, PhD, Albert M. Mattocks Professor, Pharmaceutical Sciences & 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.

11:15 am

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

Andrew K. 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.

Charles Heffern, PhD, Product Manager, Research & Development, NanoTemper Technologies

Automated and high-throughput analysis of biologic stability spans the entire workflow of biologic development, from early stage developability assessments through protein engineering to formulation and manufacturing decisions. The necessity for high-quality data to inform modeling and pipeline decisions is pervasive. Here we discuss how Prometheus empowers organizations to improve their biologic development through the use of high-quality data to make better decisions.

12:00 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Andrew K. Urick, PhD, Senior Scientist, AbbVie
Panelists:
Peter M. Tessier, PhD, Albert M. Mattocks Professor, Pharmaceutical Sciences & Chemical Engineering, University of Michigan
Charles Heffern, PhD, Product Manager, Research & Development, NanoTemper Technologies
12:20 pm Lunch Break - View our Virtual Exhibit Hall

EMERGING METHODS AND INSTRUMENTS

1:05 pm

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

Gabriel J. 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.

12:45 pm

Membrane Mimetic FACS to Facilitate Antibody Screening

Christy A. Thomson, PhD, Senior Scientist, Amgen, Inc.

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.

Rony Nehmé, Dr, Application Scientist, Creoptix AG

In this presentation, we will discuss the benefits of early stage kinetic characterization from crude samples ranging from peptides to membrane proteins and relevant clinical samples.

Save time, work with suboptimal assay conditions and validate your ELISA data.

1:50 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Christy A. Thomson, PhD, Senior Scientist, Amgen, Inc.
Panelists:
Gabriel J. Rocklin, PhD, Assistant Professor, Pharmacology, Northwestern University
Rony Nehmé, Dr, Application Scientist, Creoptix AG
2:10 pm Session Break
3:50 pm Refresh Break - View Our Virtual Exhibit Hall
4:10 pm Problem-Solving Breakout Discussions Part A - View our Virtual Exhibit Hall

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

TABLE 20: High-Throughput (HT) Analytical Data Management to Enable Machine Learning

Marc Bailly, PhD, Principal Scientist, Merck Research Labs
  • 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 21: Biophysical Methods to Drive Protein Decisions: What Matters and How Do We Measure It?

Andrew K. 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?
4:40 pm Refresh Break - View Our Virtual Exhibit Hall
5:00 pm Problem-Solving Breakout Discussions Part B - View our Virtual Exhibit Hall

TABLE 22: The Role of Denaturing and Native-MS in Pharma: From mAbs to Membrane Proteins and Beyond

Wendy Sandoval, Principal Scientist, Genentech, Inc.
  • 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?
Iain Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen
5:30 pm Close of Day

Thursday, September 3

NEW APPLICATIONS FOR MASS SPECTROMETRY

9:05 am

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.

9:25 am

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.

Craig Magee, PhD, Director, Business Development, Life Sciences, DRS Daylight Solutions

We will introduce an entirely new class of high-sensitivity, inline mid-IR liquid analyzers. Based on ultra-high-brightness tunable quantum cascade lasers (QCL), this new platform technology offers fast scan rates, a large dynamic range and an ability to easily measure small sample volumes. We will present the physical operating principles of these new analyzers and provide several application examples including their use in fractionated HPLC measurements and chemical and biologic reactor monitoring.

10:10 am

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

Daniel D. Vallejo, Graduate Student Researcher, Chemistry, University of Michigan

The next generation of medicines depends upon our ability to quickly assess the structures and stabilities of protein and protein complexes, as well as protein-based biotherapeutics. Such endeavors are nearly insurmountable with current tools without exhaustive orthogonal experimentation. In this presentation, we will discuss recently developed ion mobility-mass spectrometry tools aimed at bridging this gap in basic technology to characterize novel biotherapeutics and their generic analogs (biosimilars).

Ryan Denomme, CEO, Nicoya

In-depth, quantitative characterization of protein interactions is crucial in engineering and optimizing new biologics that can act as effective therapeutics. Among the many biophysical techniques that have accelerated this process for scientists, surface plasmon resonance (SPR) is an industry standard that is both sensitive and powerful, enabling rapid and label-free detection of a wide range of molecular interactions. Yet, there has been minimal innovation in SPR platforms to date, considerably limiting their use and accessibility. Join us as we discuss how we’ve integrated digital microfluidics technology and AI-powered intelligence with SPR, and how this will eliminate challenges in efficiency and optimization to help you go-to-market faster with your biotherapeutics.

10:50 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
John Kelly, PhD, Senior Research Officer, Mass Spectrometry, National Research Council Canada
Panelists:
Stephen D'Eri, Scientist, Sanofi
Ryan Denomme, CEO, Nicoya
Craig Magee, PhD, Director, Business Development, Life Sciences, DRS Daylight Solutions
Daniel D. Vallejo, Graduate Student Researcher, Chemistry, University of Michigan
11:10 am Close of Biophysical Methods





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