2020 Archived Content

Breakout Discussions

Engage in in-depth discussions with industry experts and your peers about the progress, trends and challenges you face in your research!
Interactive discussion groups play an integral role in networking with potential collaborators. They provide an opportunity to share examples from your work, vet ideas with peers, and be part of a group problem-solving endeavor.

MONDAY, AUGUST 31 | part a: 2:30-3:00 PM; part b: 3:20-3:50 pm

Display of Antibodies

PART A

TABLE 1: Can Mammalian Display Compete with Yeast and Phage? Challenges and Benefits of Mammalian Selection Systems for Protein Engineering

Moderator: Jennifer Maynard, PhD, Henry Beckman Professor, McKetta Department of Chemical Engineering, Cockrell School of Engineering, The University of Texas at Austin

What are the trade-offs among reported mammalian systems?
What proteins are right for mammalian display? (GPCR, transport proteins and intramembrane proteases)
How can we design selections based on protein activity?
How to introduce and maintain a library – retroviral elements, CRISPR or others?
Can we simultaneously engineer glycosylation and proteins for desired functions?
How can we maximize library size, ensure just one variant per cell and maximize the dynamic range to separate populations of interest?

PART B

TABLE 2: Enabling Technologies to Enhance Selections Based on Immune Function

Moderator: Jamie Spangler, PhD, Assistant Professor, Biomedical and Chemical & Biomolecular Engineering, Johns Hopkins University

Interfacing new flow cytometry tools with directed evolution to facilitate functional selections
Yeast biopanning techniques to improve recognition of active signaling proteins
Choosing readouts to couple with selection process
Designing selection strategies to evolve proteins that enact therapeutic mechanisms of interest

Antibodies for Cancer Therapy

PART A

TABLE 3: What is the Best?

Moderator: Daniel Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center

Best target for solid tumors
Best route of delivery
Best way of minimizing adverse reactions
Best way of prolonging half-life of therapeutics

Improving Immunotherapy Efficacy and Safety

PART A

TABLE 4: CAR T Safety

Moderator: Saad Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine

CART cell therapy efficacy and safety balance
CART cell engineering
CART cell application

Characterization of Novel Biotherapeutics

PART A

TABLE 5: Co-formulation of Therapeutic Proteins

Moderator: Dennis Krieg, PhD, Researcher, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilians-University Munich, Germany

Analytical challenges (deconvolution of chromatographic and spectroscopic data, systematic and efficient method development
Formulation challenges (DoE approaches, setup of stability studies for co-formulations)
Regulatory challenges (demands for co-formulation characterization by the regulatory authorities, use of single formulation stability data for co-formulations)
Clinical challenges (setup of PK studies for flexible or fixed dosing ratios, extrapolation of clinical data from single to co-formulations)

PART B

TABLE 6: Challenges Associated with Analytical Method Development for the Characterization of AAV-Based Therapeutics

Moderator: George Bou-Assaf, PhD, Scientist, Analytical Development, Product & Technology Development Biogen

Similarities and differences between AAV and protein-based challenges
Transferability of methods from proteins to AAV-based molecules
Sample limitations and design of experiments to take into account this limitation
Simplified and streamlined approaches to method development that still meets ICH guidelines and regulatory expectations
New tools and instrumentations that enable analytical method development of AAV based therapeutics

Difficult-to-Express Proteins

PART A

TABLE 7: Experiences with Using Different Binder Types as Crystallization Chaperones or Cryo-EM Handles

Moderator: Susanne Gräslund, PhD, Principal Investigator, Structural Genomics Consortium, Karolinska Institute

What binder types/scaffolds have the participants worked with?
Has any comparisons of different binder types have been made?
What type of antigens, soluble proteins, complexes, integral membrane proteins?
Different methods of immobilizing the antigens during selections?

PART B

TABLE 8: Cell-Free Approaches to Difficult Proteins

Moderator: Matthew Coleman, PhD, Senior Scientist & Group Leader, Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory

Eukaryotic versus prokaryotic cell-free expression systems
Variants of cell free expression (batch versus dialysis)
Additives for screening and producing membrane bound proteins

Immunogenicity Case Studies and Clinical Management

PART A

TABLE 9: Immunogenicity of PEG: Impact and Analysis

Co-Moderators: Johanna Abend, PhD, Senior Scientist I, Immunogenicity Assessment, Translational Sciences, BioMarin Pharmaceutical Inc.
Madhukar Aryal, MS, Senior Research Associate, BioAnalytical Sciences, BioMarin Pharmaceutical Inc.

How is our understanding of anti-PEG responses evolving (eg, pre-existing PEG antibodies, drug-induced anti-PEG responses)?
Can dosing regimens affect the anti-PEG response (eg, is desensitization / tolerance possible)?
Can other strategies be used to overcome the effect of anti-PEG response (eg, administration of free PEG)?

PART B

TABLE 10: How to Optimize Sample Pretreatment Methods

Moderator: Lynn Kamen, PhD, Senior Scientist, BioAnalytical Sciences, Genentech Inc.

ACE vs BEAD vs SPEAD
How much positive control antibody recovery is sufficient?
How to optimize assay sensitivity while maintaining drug tolerance?
What is the best sample pretreatment method for cellular assays?

Emerging Indications for Therapeutic Antibodies

PART A

TABLE 11: Biotherapeutics for Respiratory Indications

Moderator: Bas van der Woning, PhD, Research Fellow, arGEN-X, Belgium

What are the biggest unmet medical needs in respiratory diseases (asthma, cystic fibrosis, COPD, idiopathic pulmonary fibrosis, etc.)
Systemic versus local administration of biotherapeutics
Challenges of local administration of biotherapeutics
Methods to measure an effect on lung function (spirometry, CT, 3He MRI, airway resistance, ect.)
Biomarkers (eosinophils, neutrophils, IgE, FeNO, ..any new biomarkers?)

TABLE 12: Antibody Targeting and Delivery Strategies for CNS Indications

Moderator: Charles Glabe, PhD, Professor, Molecular Biology and Biochemistry, University of California, Irvine

Do antibodies that modulate inflammation or complement activity have potential therapeutic activity in CNS diseases?
Does immunotherapy hold promise for other amyloid related neurodegenerative diseases? If so, is it possible to have a broad spectrum or universal antibody for neurodegenerative diseases?
What parameters are important for making immunotherapy more effective?
Does amyloid structural polymorphism mean that immunotherapy needs to be personalized according to specific conformational strain?

PART B

TABLE 13: Strategies for Modulating, Targeting and Directing T Cell Activity for Therapeutic Gain

Moderator: Elissa Leonard, PhD, Postdoctoral Fellow, Biomedical Engineering, Johns Hopkins University

What are the most viable emerging or established strategies for directing T cell specificity? Engineered TCRs? Expansion of endogenous populations? CARs?
Other stimulatory signals that can direct lineage and suppressive/inflammatory activity
Engineering or controlling persistence
Therapeutic viability in terms of cost and scale

Wednesday, september 2 | part a: 4:10-4:40 PM; part b: 5:00-5:30 pm

Engineering Antibodies

PART A

TABLE 14: Mammalian Cell Display for High-Throughput Engineering of Immune Receptors

Moderator: Rodrigo Vazquez-Lombardi, PhD, Postdoctoral Fellow, Biosystems Science and Engineering, ETH Zurich, Switzerland

Advantages and limitations of mammalian cell display platforms relative to traditional display methods

Design and development of mammalian display platforms using CRISPR-Cas9 genome editing
Deep mutational scanning as a key method for the design of highly focused combinatorial libraries

Orthotopic introduction of immune receptor libraries into the genome of mammalian cells using CRISPR-Cas9
Selection of desired variants using flow cytometry coupled with deep sequencing and enrichment analysis

TABLE 15: Modulating the Dynamic and Subcellular Trafficking Behavior of Antibodies for Therapy

Moderator: Sally Ward, PhD, Professor, Molecular Immunology, University of Southampton, United Kingdom

How can microscopy inform the design of therapeutics?
Targeting FcRn to clear pathogenic antibodies
Half-life extension technology
Modulating endosomal trafficking of ADCs to enhance drug delivery to lysosomes

PART B

TABLE 16: Big Data Challenges in Protein Engineering

Moderator: David Gifford, PhD, Professor, Computer Science and Biological Engineering, MIT

The role of machine learning in the discovery and optimization of biologics
What quantity of data is required to build effective machine learning models
What experimental designs are necessary to get optimum machine learning performance
Error correction and processing of data for machine learning

Advancing Bispecific Antibodies and Combination Therapy to the Clinic

PART B

TABLE 17: Pre-Clinical Mouse Models to Examine Immunotherapeutics

Moderator: Alison Crawford, PhD, Senior Staff Scientist, Oncology & Angiogenesis, Regeneron Pharmaceuticals

Xenogenic versus syngeneic models
Read-outs examining T cell activation
Combination therapy in pre-clinical models

CAR-Ts, TCRs and TILs

PART A

TABLE 18: Mirror, Mirror on the Wall, Who is the Finest CAR T Phenotype of Them All?

Moderator: Peggy Sotiropoulou, PhD, Director, Research & Development, Celyad

What is the ideal memory phenotype for CAR T cells?
Is the ideal memory phenotype the same for autologous and allogeneic CAR T cells?
Does CD4/CD8 ratio matter?
Does the optimal CD4/CD8 ratio depend on the cancer type (heme vs solid – hot vs cold) and therapy type (autologous vs allogeneic)?

PART B

TABLE 19: Present and Future of Genetically Engineered T Cells in Oncology

Moderators: Adrian Bot, MD, PhD, Vice President, Translational Sciences, Kite, a Gilead Company

Current results and limitations of CAR-T therapy
Innovative receptor designs
Desired features of T cells: potency and controllability
Manufacturing optimizations to scale out, diminish cost, and fully utilize this platform technology
Beyond blood cancers and beyond cancer: what is next?

Biophysical Methods

PART A

TABLE 20: 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 21: 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?

PART B

TABLE 22: 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?

Optimizing Protein Expression

PART A

TABLE 23: Prepping Endogenous Protein Complexes for Downstream Analysis

Moderator: John LaCava, PhD, Group Leader, Laboratory of Macromolecules and Interactomes, European Research Institute for the Biology of Aging, University Medical Center Groningen

Quality assurance / quality control
Affinity capture, best practices
Intermediate readout - which tool for the job?
End game - routine structural analysis of endogenous complexes

PART B

TABLE 24: Non-Standard Amino Acid Incorporation in Recombinant Proteins

Moderator: Jesse Rinehart, PhD, Associate Professor, Cellular & Molecular Physiology, Systems Biology Institute, Yale University School of Medicine

Non-standard amino acids have been incorporated in a variety of protein expression systems
Each non-standard amino acid, the choice of cellular host, and incorporation strategy brings with it a host of unique challenges
From basic set up/trouble shooting to mass spectrometry/proteomics of non-standard amino acid containing proteins
Bacterial systems using non-standard amino acids and proteomics

TABLE 25: Challenges in Cell Therapy Manufacturing Development

Moderator: Zhimei Du, PhD, Director, Process Development, Merck and Co., Inc.

How to mitigate the variability during cell therapy manufacturing?
What are the practical strategies to reduce COGS of cell therapy manufacturing?
Is current the list of critical quality attributes sufficient to define product and process control?
What is the next generation manufacturing strategy for cell therapy?

Immunogenicity Assessment and Regulatory Approval of Biologics

PART B

TABLE 26: Fully Automated Cell-Based Binding Neutralizing Antibody Assay on MSD Platform

Moderator: Weifeng Xu, PhD, Principal Scientist, PPDM, Regulated Immunogenicity and Molecule, Merck

NAb assay development: when to have an assay, which format: cell or non-cell?
How to overcome drug interference;
Interpretation of new 2019 Jan FDA Immunogenicity guidance

Engineering Antibody-Drug Conjugates

PART A

TABLE 27: ADC Targets and Payloads: When Friends Become Foes

Moderator: Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen

Navigation of targets and payloads for ADCs
Wrong pairing of targets and payloads: turning friends into foes
Strategies for selection of targets and payload for improving the therapeutic index
Translational medicine strategies to maximize TI

PART B

TABLE 28: Antibody Engineering Approaches to Improve the Therapeutic Index of ADCs

Moderator: Dhaval K. Shah, PhD, Assoc Prof, Pharmaceutical Sciences, University of Buffalo

Is 150 kDa size of mAb the best to conjugate drug molecules, or fragment-drug conjugates may provide more/different benefits?
What are different antibody engineering approaches evaluated to improve ADCs (e.g. bi-specific etc.), and which one seems more superior.
Does the site of drug conjugation (e.g. specific amino acid, glycan etc.) matter dramatically for ADCs?
What are learnings from application of ADCs beyond oncology? Is it a viable targeted drug delivery approach for other disorders?

Gene Therapy

PART A

TABLE 29: CQA Identification and Assessment in Gene Therapy Products

Moderator: Lin Liu, PhD, Principal Scientist, Biologics Development, Sanofi