2022 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, May 2, 2022 12:45 PM EST

DISPLAY OF BIOLOGICS

TABLE 1: Breaking Away from Nature: Using de novo Designed Proteins as Therapeutics
Moderator: Chris Bahl, PhD, CSO and Co-Founder, AI Proteins

Problems that can only be solved using de novo designed proteins
Computational de novo design methods: past, present and future. How and when will machine learning replace the current way that we design proteins de novo?
De novo designed proteins are an unprecedented modality. What are the challenges of implementing them and how will the unique properties of these proteins help us to we solve them (e.g. immunogenicity, manufacturing, administration)?

ANTIBODIES FOR CANCER THERAPY

TABLE 2: Engineering Better CARs for Solid Tumors
Moderator: Mitchell Ho, PhD, Senior Investigator; Deputy Chief, Laboratory of Molecular Biology; Director, Antibody Engineering Program, National Cancer Institute (NCI), NIH

Targets in the tumor microenvironment: tumor cells vs myeloid cells
CAR design for better efficacy and safety: bispecific, hinge, costimulatory
CAR T vs CAR NK

TABLE 3: Beyond Cell Engagers: What More Can Bispecific Antibodies Contribute to the Fight Against Cancer?
Moderator: Jonathan H. Davis, PhD, Vice President of Innovation and Strategy, Invenra, Inc.

What are the most promising uses of bispecifics as next generation antibodies against cancer?
Discuss and compare approaches: Dual targeting for increased specificity, Dual targeting to activate receptors for agonism, Biparatopics for clustering, Generation of novel biologic activity, Cis vs Trans binding, others
What mechanisms are most promising? ADCs, Direct killing, Immune system modulation, others
How much does format matter? IgG-like vs. linked binders? Monovalent vs. bi- or multi-valent? More critical for some approaches than others?

TABLE 4: Targeting Intracelllular Antigens - Challenges and Opportunities
Moderator: Cheng Liu, PhD, Founder & CEO, Eureka Therapeutics, Inc.

Intracellular antigens as new pool of tumor-specific targets
TCR mimic antibody vs TCR: affinity and specificity
Can ADCC and ADC be viable MOA in addition to anti-CD3 bispecific approach?
HLA-restriction of targeting Intracellular antigens

IMPROVING IMMUNOTHERAPY EFFICACY AND SAFETY

TABLE 5: Understanding and Overcoming Resistance for Immunotherapies
Moderator: Michelle Krogsgaard, PhD, Associate Professor, Pathology, New York School of Medicine

Increasing sensitivity of T cells
Protein-to-protein Interactions
Signaling pathways

TABLE 6: Immunotherapy Safety and Managing Toxicity
Moderator: Saad Kenderian, PhD, Assistant Professor, Medicine and Oncology, Mayo Clinic College of Medicine

Improving safety via engineering and monitoring
Impact of tumor microenvironment, co-stimulants
Emerging trends

DIFFICULT-TO-EXPRESS PROTIENS

TABLE 7: Challenges in Finding/Training/Retaining Technical Staff Post-pandemic
Moderator: Anne Skaja Robinson, PhD, Professor & Head, Chemical Engineering, Carnegie Mellon University

Best practices in remote recruiting and onboarding?
Job flexibility as a retention incentive?
How do we train or retrain entry-level scientists with limited hands-on experience?
What skills are missing in entry-level or more experienced scientific staff?

TABLE 8: Challenges in Working with Protein Complexes
Moderator: Oleg Brodsky, Senior Principal Scientist, Structural Biology & Protein Sciences, Pfizer Inc.

Protein expression and purification strategies
Biochemical/biophysical/structural characterization
Opportunities and pitfalls – what works and what doesn’t

CHARACTERIZATION FOR NOVEL BIOTHERAPEUTICS

TABLE 9: Characterization Challenges for New Biotherapeutic Modalities
Moderator: Ming Huang, PhD, Scientist, Regeneron Pharmaceuticals, Inc.

Analytical challenges faced with characterization of multi-specific proteins
Determining CQAs for next-gen alternative antibody formats
Utility of LC/MS vs. sequencing techniques in characterization of nucleic acid therapeutics
Bridging antibody therapeutics and nucleic acid therapeutics, antibody-ASO conjugates and antibody-siRNA conjugates analytical challenges

TABLE 10: Analytical Challenges in the Characterization of Biotherapeutics: Sample Preparation, Analysis and Data Processing
Moderator: Ross Yang, Scientist, Merck Research Labs

ADC, Bioconjugates, bi-specific, multi-specific, etc.
Excipients and their interaction with drug substances.
RNA/DNA (as drug substance or impurities)
HCPs (mammal, bacteria, insect, yeast, etc.)
PTMs – glycosylation, deamidation, oxidation, SVA, etc.

Wednesday, May 4, 2022 1:35 PM EST

ENGINEERING ANTIBODIES

TABLE 1: Emerging Immunizations in Antibody Discovery
Moderator: Wei-Ching Liang, Senior Principal Scientific Researcher, Antibody Engineering, Genentech, Inc.

Emerging systems: rabbits, chickens, llamas, cows, sharks
Broad applications in research and development
Best practices for antibody discovery with these technologies
Areas for improvement in humanization

TABLE 2: Developing an Antibody Discovery Pipeline from the Ground Up
Moderator: Kathryn M. Hastie, PhD, Instructor, La Jolla Institute for Immunology

Sample source: hybridoma vs plasma or memory cells
Hit identification: antigen selection is key
NGS vs sanger sequencing
Screening and characterization of antibodies at the same time – single clones or bulk expressions?
Triaging hits: affinity measurements, epitope binning and cell-based assays from crude or purified samples
Rapid structural characterization from small scale expression

EMERGING TARGETS AND NOVEL APPROACHES FOR ONCOLOGY & BEYOND

TABLE 3: Emerging Strategies to Discover Therapeutic Antibodies and Novel Targets
Moderator: Jorge Dias, PhD, Principal Scientist, Alchemab Therapeutics Ltd

Identifying antibodies with therapeutic potential from polyclonal pools / libraries / immune repertoires
Strategies to identify, express and characterize novel targets
Engineering and formats for non-antibody protein therapeutics

TABLE 4: Challenges and Opportunities in Precision Medicine for CNS Diseases
Moderator: Miroslaw Janowski, MD, Associate Professor, Diagnostic Radiology, University of Maryland Baltimore

Precision medicine enables the ability to see how much drug gets into the brain and if the amount is sufficient - a more expensive way but enables scientists to finally understand where the problem lies
Closing the gap in drug delivery by capturing biodistribution dynamics of biologics for 3D pharmacokinetics
Obstacles - slow disease progression; animal data not relevant to clinical settings

ADVANCING BISPECIFIC ANTIBODIES AND COMBINATION THERAPY TO THE CLINIC

TABLE 5: Challenges and Solutions to Engineering Multispecific Antibodies
Moderator: Carole Estoppey, PhD, Senior Principal Scientist & Project Leader, Ichnos Sciences Biotherapeutics SA

What are the most useful assays in predicting developability of bispecific and trispecific antibodies? Is this different than for mAbs?
In your experience, what are some of the most effective in silico tools to guide the engineering of multispecific antibodies? How can they be improved?
What are the best tools to guide optimal format and spatial arrangement of the targets for bispecific and trispecific antibodies, without resorting to combinatorial screening? What about compatibility of binders for trispecific formats?
What are optimal antibody discovery workflows and data packages to help assess the ideal balance across desirable properties of the candidates (extended half-life, tuned effector functions, optimal linkers) and closeness to native human sequences?
What is the value of in silico immunogenicity prediction at early discovery stages?

CELL-BASED IMMUNOTHERAPIES

TABLE 6: Beyond First-Generation CAR T Therapies
Moderator: Adrian Bot, MD, PhD, CSO, Executive Vice President, R&D, Capstan Therapeutics

What have we learned from first-generation CAR Ts
Emerging modalities, latest engineering strategies
Autologous vs. off-the-shelf models

OPTIMIZING PROTEIN EXPRESSION

TABLE 7: Operating in the Inter-space Between Academia and Industry
Moderator: Bjørn Voldborg, MSc, Head, National Biologics Facility, DTU Bioengineering, Technical University of Denmark

What are the advantages/pitfalls?
What is needed?
When to do what? Collaboration, Partnering or Fee-for-Service?
Which infrastructures, technologies, competences are relevant?
Funding, Pricing, Priorities & Quality
Staff: Students? PostDocs? Staff Scientists?

TABLE 8: Cell-free Gene Expression
Moderator: Vincent Noireaux, PhD, Professor, Synthetic Biology and Biological Physics, University of Minnesota Twin Cities

Is poor reproducibility from lab-to-lab or systems-to-systems a big issue?
Can the preparation and utilization of CFE systems be standardized?
What are the current major CFE limitations?
What should the next major improvements to CFE systems be?

BIOPHYSICAL METHODS

TABLE 9: Characterization Methods and Technologies for Gene Therapies
Moderator: Borries Demeler, Canada 150 Research Chair for Biophysics, Professor, Chemistry & Biochemistry, University of Lethbridge, Canada

AUC for the characterization of solution composition
Bioassay challenges
Characterization of viral vector nucleic acid cargo loading
Emerging methods and instruments
Miniaturization and sample size reduction

IMMUNOGENICITY ASSESSMENT AND MANAGEMENT

TABLE 10: When Is ADA Assessment Needed?
Moderator: Seema Kumar, PhD, Director & Head, Clinical Bioanalytical Sciences, EMD Serono, Inc.

How sensitive does it need to be?
What’s the value of evaluating immunogenicity if you have good PKPD?
What does it mean when you pick up ADA activity?
How do you co-relate it with PKPD and clinical impact?

TABLE 11: Considerations of Immunogenicity Assessment for New Modalities
Moderator: Kate Peng, PhD, Director/Principle Scientist, BioAnalytical Sciences, Genentech

Considerations of immunogenicity assessment strategy for protein and cell therapeutics
Critical reagent generation
Data interpretation
Communication with health authorities

CELL-BASED IMMUNOTHERAPIES

TABLE 12: Understanding Resistance to CAR T Immunotherapy
Moderator: Marco Ruella, MD, Assistant Professor of Medicine, Scientific Director, Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, University of Pennsylvania
Moderator: Michael Hudecek, MD, Professor, Cellular Immunotherapy of Malignant Diseases, University of Wuerzburg

Mechanisms
Strategies to overcome resistance
TME
Combination therapies

Friday, May 6, 2022 7:30 AM EST

MACHINE LEARNING APPROACHES FOR PROTEIN ENGINEERING

TABLE 1: Best Practices for Using Machine Learning in NGS-Guided Antibody Discovery
Moderator: Andrew R.M. Bradbury, PhD, CSO, Specifica, Inc.
Moderator: M. Frank Erasmus, PhD, Head, Bioinformatics, Specifica, Inc.

How does unsupervised or supervised machine learning aid your discovery efforts (e.g., clustering, classification, inference)?
- If unsupervised – what approaches do you take (e.g., k-means, PCA, other)?
- If supervised, do shallow learning (logistic regression, naïve Bayes, etc.) approaches suffice or do you require deep learning (recurrent NN, 1D convnets, etc.) ?
What experimental and/or bioinformatics processing steps do you employ to ensure you have established an accurate ground truth for select population (e.g., binders / non-binders from FACS) and classification strategies do you employ as it pertains to antibody discovery?
What min/max read depth and/or fold coverage of the underlying region of interest (HCDR3) thresholds do you employ to dataset machine learning algorithm to avoid under / overfitting? Is this sufficient based on your accuracy assessment from your acc/loss curves? Do you utilize data augmentation or regularization techniques?
How do you typically allocate your training, validation, and test sets for NGS datasets from discovery campaigns?
What data encoding methods do you employ (e.g. one-hot encoding, tokenization) to represent your sequence data? Does 3D coordinate information enhance your dataset?

DRIVING CLINICAL SUCCESS IN ANTIBODY DRUG CONJUGATES

TABLE 2: The Linker in ADCs: Small but Important
Moderator: Philipp Spycher, PhD, CEO, Araris Biotech AG

Role of linker in ADC design and its key properties
Review of current and novel linker technologies
Cleavable and non-cleavable linkers

TABLE 3: Improving the Efficiency of the ADC Development Pipeline
Moderator: John M. Lambert, PhD, Consultant

There has been an explosion of ADC approvals in the past few years after long and hard fought gains. How do we continue from here to improve the efficiency of developing new agents?
Toxicity: ADCs are often given at the MTD, so toxicity is a major concern. Can we eliminate/reduce these toxicities, or do we learn to live with them?
Targets: Several ADC targets have had both clinical successes and failures (e.g. HER2 and TROP2). In light of this, should the field optimize previous targets with our new knowledge of design, or should the field focus on new targets?
Architecture (antibody, linkers, and payloads): The current agents use an IgG1 framework and cleavable linker, typically with microtubule inhibitors and topoisomerase for solid tumors and/or DNA damaging agents for hematological cancers. Is this the best format?

ENGINEERING BISPECIFIC ANITBODIES

TABLE 4: Making Bispecific Antibodies
Moderator: G. Jonah Rainey, PhD, Vice President, Antibody Engineering, AlivaMab Discovery Services

Right lead candidate inputs. Can I just use an off-patent sequence?
Platform selection: geometry, valency, and intellectual property
How many candidates need to be made and tested to find a good lead?

TABLE 5: Engineering Off-the-Shelf Bispecifics and CAR T Cells to Treat Cancer Harboring Intracellular Targets
Moderator: Sandra B. Gabelli, PhD, Assistant Professor, Biophysics & Biophysics Chemistry, Johns Hopkins University

Selection and engineering of the scfv partner for the bispecific antibodies
Expression of bispecifics (type of cells, stability, shelf life)
Structural based affinity maturation for bispecifics vs CART cell (tighter vs weaker binding vs specific)
Recognition of neoantigen-MHC with buried mutations

NEXT-GENERATION IMMUNOTHERAPIES

Table 6: Next-Generation Immunotherapies
Moderator: Jonathan Gilbert, PhD, Vice President, Exploratory Research, SQZ Biotech

Emerging modalities
Novel delivery methods - in vivo
Manufacturing considerations, developability

MAXIMIXING PROTEIN PRODUCTION WORKFLOWS

TABLE 7: Future Platforms for Future Modalities
Moderator: David Wood, PhD, Co-Founder, CSO, Protein Capture Science; Professor, Chemical & Biomolecular Engineering, The Ohio State University

Are columns here to stay, or is it time to reconsider other approaches?
What about cleavable tags? Is the risk justified by the need for platforms?
What kinds of products will be driving this innovation? What do those platforms need to look like in terms of scale, performance, and cost?
How open are companies to trying disruptive technologies? Are the innovations in the products enough for now, so we should play it safe on the methods?

TABLE 8: Common Issues with Transient Protein Production
Moderator: Richard Altman, Field Application Scientist, Life Science Solutions, Thermo Fisher Scientific
Moderator: Henry C. Chiou, PhD, Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific
Moderator: Dominic Esposito, PhD, Director, Protein Sciences, Frederick National Laboratory

What are the current challenges to transient protein production?
How has the COVID-19 pandemic affected your workflow and productivity?
How do we optimize the whole protein expression workflow process?
How can we maintain volumetric yields while scaling transient expression up or down?
What cell line(s) should we use and when?
What parameters can impact the quality or physical attributes of transiently produced proteins?

GENE THERAPY R&D ANALYTICS

TABLE 9: Towards Real-time Characterization of Viral Vectors During Biomanufacturing: Emerging Technologies and Challenges
Moderator: Georgios Katsikis, PhD, Postdoctoral Associate, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

Pushing the limits of established methods (e.g. PCR)
Integrating emerging methods in a production-line setting
Finding synergistic approaches between complementary methods
Identifying links between measurable critical quality attributes and potency

TABLE 10:Directions for Handling and Administration Studies for Gene Therapy Products
Moderator: Kruti Soni, PhD, Scientist, Technical Development, Biogen