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: 2:10-2:40 PM; part b: 2:40-3:10 pm
Display of Antibodies
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?
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
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
TABLE 4: Combination Therapies and the Tumor Microenvironment
Moderator: Allison Betof Warner, MD, PhD, Assistant Attending Physician, Melanoma Service, Memorial Sloan Kettering Cancer Center
- What are recent combination trials telling us about the mechanism of action of combinations in the microenvironment?
- What role does the microbiome play and how do we harness this to improve outcomes?
- Strategies for immune system priming and activation
- Control of immune-related adverse events
TABLE 5: 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
TABLE 6: 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)
TABLE 7: 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
TABLE 8: 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?
TABLE 9: 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
TABLE 10: 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)?
TABLE 11: 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
TABLE 12: 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 13: 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?
TABLE 14: 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, septemeber 2 | part a: 3:50-4:15 PM; part b: 4:15-4:40 pm
TABLE 15: 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 16: 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
TABLE 17: 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
TABLE 18: 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
TABLE 19: Pros and Cons of Assays to Predict the Half-Life of Antibodies in Primates
Moderator: Gundo Diedrich, PhD, Director, Antibody Engineering, MacroGenics, Inc.
- FcRn affinity chromatography
- Cell-based assays with FcRn-expressing cell lines (transcytosis assays, recycling assays)
- In vitro plasma stability assays
CAR-Ts, TCRs and TILs
TABLE 20: 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?
TABLE 21: 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)?
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?
TABLE 23: 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 24: 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?
Optimizing Protein Expression
TABLE 25: 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 26: 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?
TABLE 27: 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
Immunogenicity Assessment and Regulatory Approval of Biologics
TABLE 28: Strategies and Considerations for Developing Immunogenicity Assays for Novel Modalities
Moderator: Hao Jiang, PhD, Principal Scientist, Bioanalytical Sciences, Bristol-Myers Squibb
- Novel modalities such as bispecific Abs, probodies and lipid nanoparticle siRNA pose lots of challenges in clinical immunogenicity assay development
- What are the major considerations for developing ADA and NAb assays, such as assay formats and cell lines?
- What are the potential risks from regulatory perspective?
TABLE 29: 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
TABLE 30: 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?
TABLE 31: 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
TABLE 32: Cell and Gene Therapy Development in Europe: Navigating the Regulatory Framework
Moderator: Alex Bloom, PhD, Vice President, Regulatory Affairs and Quality Assurance, Gyroscope Therapeutics
- Clinical trial and GMO applications in the EU
- Opportunities for accelerating ATMP development
- Interacting with regulators in the EU and optimising scientific advice
TABLE 33: CQA Identification and Assessment in Gene Therapy Products
Moderator: Lin Liu, PhD, Principal Scientist, Biologics Development, Sanofi
- Identification of pCQAs for AAV based gene therapy products
- Design structure-functional study specific to gene therapy CQA assessment
- Role of forced degradation study in CQA assessment
- Potency assay used for structure-function studies