Join a breakout discussion group. These are informal, moderated discussions with brainstorming and
interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and
experiences and develop future collaborations around a focused topic.
WEDNESDAY, SEPTEMBER 26 | 5:05 - 6:05 PM
Small Molecules for Cancer Immunotherapy
Exploring Diverse Target Classes for Cancer Immunotherapy
Moderators: Paul Kassner, PhD, Vice President, Quantitative Biology, FLX Bio Inc.
Buvana Ravishankar, PhD, Scientist, Discovery Biology, FLX Bio Inc.
- Enzyme targets vs. protein-protein interactions and approaches to target them
- Immuno-metabolism targets
- Kinase inhibitors for immunotherapy
The Chemistry of Small Molecule Immunomodulators in the Clinic
Moderator: David Ferguson, PhD, Professor, Medicinal Chemistry, University of Minnesota
- Single agents
- Vaccine adjuvants
- Combination therapies
- Drug delivery and formulation
NK Cell-Based Cancer Immunotherapy
Targeting Solid Tumors with NK Cells
Moderator: Dan Kaufman, MD, PhD, Professor, Director, Cell Therapy Program, University of California, San Diego
- What antigen(s) are best to target?
- CAR vs. antibody vs. NK cell engager strategies against solid tumors
- How best to combine NK cells with other agents in clinical trials?
Addressing NK Cell Complexity in Clinical Trials
Moderator: Karl-Johan Malmberg, MD, PhD, Professor, Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway
- Which subsets predict response?
- Which phenotypes are generated by selection or expansion methods?
- How to implement the emerging insights into the regulatory role of NK cells as a bridge to adaptive immunity?
- How to address these questions systematically and consistently in clinical trials?
Targeting the Ubiquitin-Proteasome System
Novel Targets for Cancer in the Proteostasis Space
Moderator: Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston
- Biological insights into the Ubiquitin-Proteasome System pathway
- Target validation approaches for novel proteostasis targets
- Emerging proteostasis targets
Screening Tools to Identify PROTACS, Kinases and Other Molecules
Moderator: Davide Gianni, PhD, Team Leader, Discovery Sciences, AstraZeneca
- Biochemical, biophysical and cellular based approaches to monitor ternary complex formation
- Approaches to identify novel E3 ligases and E3 ligase ligands
CNS and Neurodegenerative Targets
The Use of Precision Medicine in Drug Development for CNS Disorders
Moderator: Daniel Klamer, PhD, MBA, Vice President, Business Development & Scientific Strategy, Anavex Life Sciences Corp.
- What questions should be asked before adding a new biomarker to your clinical trial?
- What lessons can we learn from oncology?
- Pros and cons using biomarkers as surrogate endpoints
Machine Learning Models in CNS Drug Discovery
Moderators: Istvan Enyedy, PhD, Principal Scientist, Biogen
Jane Yu, Technical Pre-Sales, Life Sciences, IBM Watson Health
- Pros and cons of AI in drug discovery
- Implementing AI in drug development – when and how
- Methods and building models
Constrained Peptides and Macrocyclics
Conformational Searching and Macrocycles
Moderator: Maxwell D. Cummings, PhD, Senior Principal Scientist, Computational Chemistry, Discovery Sciences, Janssen R&D
- Is the binding mode known, suspected or unknown?
- Selection of conformers and conformer sets: energy, RMSD, properties, etc.
- Aspects of computational search methods relevant to macrocycles
Lead ID Using Macrocycle Libraries
Moderator: Adrian Whitty, PhD, Associate Professor of Chemistry, Boston University
- What properties define a good macrocycle screening hit?
- What represents good potency, and does this depend on library chemistry?
- Specialized/biased versus general purpose libraries
- Applications of machine learning
Drug Development Challenges of Stapled Peptides and Synthetic Macrocyclics
Moderator: Vincent Guerlavais, PhD, Director, Medicinal Chemistry, Aileron Therapeutics
- Lead op challenges unique to stapled peptides or macrocyclics
- Planning ahead: making it easier for formulation/scale-up
- Converting a drug candidate into a macrocyclic
Target Identification and Validation – Part 1
Exploiting CRISPR, RNAi and Single-Cell Analysis: What You Need to Know Before and After
Moderators: Sarah Boswell, PhD, Director of Sequencing Technologies, Laboratory of Systems Pharmacology and Director, Single-Cell Sequencing Core, Harvard Medical School
Roderick Beijersbergen, PhD, Group Leader, Netherlands Cancer Institute and Head, NKI Robotics and Screening Center
- Understanding inherent limitations and need for using complementary techniques
- Examples of how multiple techniques have been put to good use for addressing biological questions
- Evaluating and testing the reagents and tools
- Insights on inherent challenges and ways to overcome it
- Tackling data analysis
Exploring Artificial Intelligence for Improving Drug Discovery and Healthcare
Moderators: Arvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, University of Michigan
Nicholas P. Tatonetti, PhD, Herbert Irving Assistant Professor of Biomedical Informatics and Director of Clinical Informatics, Herbert Irving Comprehensive Cancer Center, Columbia University
- In silico modeling of complex cellular phenotypes and disease models: paradigms to bridge the computational-experimental gap
- Deconvolution of preclinical data and translating into clinical space: integrative modeling, generalizability, transportability and data harmonization
- Why ML/AI in healthcare data will never work; bias, missingness, and confounding in secondary data use
- Why ML/AI is our only hope to solve healthcare’s biggest problems; the power of scale, the complexity of medicine, and where the opportunities lie
Growing Use of 3D Spheroids and PDX Models in Drug Discovery
Moderators: Madhu Lal-Nag, PhD, Group Leader, Trans-NIH RNAi Facility, National Center for Advancing Translational Sciences, National Institutes of Health
Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Developing multi-cellular 3D cell culture models for high-throughput screening
- Specific 3D models for target identification and validation screens
- Challenges with high-throughput screens utilizing 3D spheroid models
- Patient-derived xenograft ex vivo (PDXEx) models as a screening platform
Antibacterial Discovery and Development
Alternative Approaches to Treatment of Antibiotic-Resistant Pathogens
Moderator: Neeraj (Neil) Surana, MD, PhD, Assistant Professor of Pediatrics, Molecular Genetics and Microbiology, Duke University
- Microbiota-based therapies
- Phage-based therapies
- Vaccines-based therapies
Considerations for the Discovery Scientist
Moderator: James Levin, PhD, Director of Preclinical Development, Cidara Therapeutics
- What makes a good hit? What makes a good lead?
- How do you build a screening paradigm?
- How important is a target product profile? When should it be developed?
- What clinical development aspects should be considered in the discovery process? When should they be incorporated?
NASH and Fibrosis
Non-Invasive Assessment of Liver Fibrosis
Moderator: Bryan C. Fuchs, PhD, Assistant Professor of Surgery, Harvard Medical School
- Serum tests: Will omic analyses hold the key?
- Which imaging technologies have the most promise?
- Are tools that assess dynamic changes needed for early assessment of anti-fibrotics?
NASH Drug Development Challenges
Moderator: Rebecca Taub, MD, CMO & Executive Vice President, Research & Development, Madrigal Pharmaceuticals
- Role of biomarkers
- FDA guidance
- Defining target population
- Animal models
Cirrhosis and NASH
Moderator: Peter Traber, MD, Partner, Alacrita Consulting; Adjunct Professor of Medicine, University of Pennsylvania School of Medicine
- Challenges in treating cirrhosis and NASH
- Common and unique targets between cirrhosis and NASH
- Designing clinical trials for cirrhosis NASH
Antibody Discovery Forum – Part 1
How Can NGS Support Library Production, Selection and Screening?
Moderator: Andrew Bradbury, PhD, MB BS (MD), CSO, Specifica, Inc.
- Different NGS platforms
- NGS traps
- NGS in estimating library diversity
- NGS in screening analysis
Tools for Enhancing Antibody Discovery
Moderator: Colby Souders, PhD, Chief Technology Officer, Abveris Antibody
- Design and production of quality antigens and reagents required for discovery
- Integration of next-generation sequencing in the discovery and engineering platform
- Naïve discovery: library, hybridoma or B cell sorting?
- Transitioning from low-throughput to high-throughput to full automation
Synthetic Single-Domain Antibody Libraries and the Future of Antibody Discovery
Moderator: Conor McMahon, PhD, Postdoctoral Fellow, Biological Chemistry and Molecular
Pharmacology, Harvard Medical School
- Library design and discovery of binders
- What makes a synthetic antibody library good?
- Measuring library quality: Can we learn something from structural biologists?
- Phage and yeast…is that the best we can do?
- Pushing the limit: Interfacing with computer scientists to design ‘smart’ libraries
- Will synthetic libraries ever be as good as animal derived?
Antibodies Against Membrane Protein Targets – Part 1
How Will We Accomplish Future Progress in Generating Therapeutic Biologics to Challenging Membrane Targets?
Moderator: Catherine Hutchings, PhD, Independent Consultant, United Kingdom
- GPCRs, ion channels, transporters, tetraspanins, etc.
- Target selection and validation of emerging targets
- Biology of disease, e.g., is there temporal and tissue ligand bias in disease?
- Biology of function, e.g., active, inactive or allosterism, antibody-based formats
- What has been an enablement (and what has been a distraction)?
Detergent-Free Production of Membrane Proteins
Moderator: Tim Dafforn, PhD, Professor, Biotechnology, University of Birmingham, United Kingdom
- Challenges of using detergent
- Variety of approaches to detergent free extraction
- Comparisons of each method
- Challenges of using detergent-free systems
- Use of detergent-free systems in drug discovery pipelines
The Role of MS in Pharma: From Small to Large Molecules and Beyond
Moderator: Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen
- Native-MS in pharma: Is it established or still niche?
- Required improvements for native-MS to become mainstream in pharma
- LC-MS and native-MS in membrane protein analysis: What role does it have?
- Specific MS improvements which would highly benefit pharmaceutical research
Structure and Function of Membrane Proteins for Ab Production and Drug Development
Moderator: Bonnie Ann Wallace, PhD, Professor, Institute of Structural and Molecular Biology, Birkbeck College, United Kingdom
- Expression of membrane proteins (eukaryotic and prokaryotic)
- Structure and modelling of membrane proteins
- Antibody production against membrane proteins
- Drug binding (in vitro and in silico) to channels and receptors
FRIDAY, SEPTEMBER 28 | 7:30 - 8:30 AM
Autoimmune and Inflammation Drug Targets
The Microbiome and Autoimmunity
Moderator: Ulrich Thienel, MD, PhD, CMO, Finch Therapeutics, Inc.
- Promising drug targets shared across platforms (microbiome/small molecules/biologics) in treating autoimmune disease
- Treating autoimmune disease with full microbiome spectrum vs. single strain
- Drug development challenges for microbiome-based treatments
Developing Kinase Inhibitors for Chronic Indications
Moderator: Philip A. Harris, PhD, Senior Director, Pattern Recognition Receptor DPU, GlaxoSmithKline
- Covalent vs. noncovalent
- Utility of kinase selectivity profiling data
- Integrating PK/PD to predict safety margins
Targeting the Microbiome
Standards for the Microbiome Therapeutics Industry: Navigating the Regulatory Landscape
Moderator: Scott A. Jackson, PhD, Leader, Complex Microbial Systems Group, Biosystems and Biomaterials Division, National Institute of Standards and Technology
- Validated analytical methods for demonstrating purity, identity, potency, stability of live biotherapeutic products
- The need for reference materials
- Leveraging current standards: e.g. USP
Targeting Tumor Myeloid Cells
Therapeutic Targeting of Myeloid Derived Suppressor Cells
Moderator: David A. Eavarone, PhD, Senior Scientist, Siamab Therapeutics
- In vitro assays
- Specific targeting of MDSC
- Effective payloads
Kinase Inhibitor Discovery
Challenges in Kinase Inhibitor Discovery
Moderator: Istvan Enyedy, PhD, Computational Chemistry, Biogen
- Selectivity for safety
- Blood-brain barrier permeability
Kinase Targets for Cancer Immunotherapy
Moderator: Guido Zaman, PhD, Managing Director & Head of Biology, Netherlands Translational Research Center B.V.
- What are the new and promising kinase targets for cancer immunotherapy?
- Lessons learned from combination studies with immune checkpoint modulators
- Technologies and approaches for target identification and validation
GPCR-Based Drug Discovery
New Ways to Screen GPCRs
Moderator: Samantha J. Allen, Ph.D., Senior Scientist, Lead Discovery - Screening, Janssen Research & Development
- Physiologically relevant cells and assays
- High-content screening
- Understanding signaling bias
New technologies for GPCR Structure-Function Insights and Drug Discovery Impact
Moderator: Matthew Eddy, PhD, Assistant Professor, Chemistry, University of Florida
- XFEL and other crystallography advances
- NMR applications for drug screening
- cryoEM: current applications and future directions
SMALP/Nanodisc Technology for Membrane Proteins
Moderator: Mahmoud l. Nasr, RPh, PhD, Instructor, Biological Chemistry and Molecular Pharmacology Department. Harvard Medical School
- Similarities and differences of lipid interactions with SMA (styrene-maleimide polymers) v. MSP (membrane scaffold proteins) nanodiscs
- Advantages and limitations of SMALP particles and MSP nanodiscs in solution
- Covalently Circularized Nanodiscs
- DNA-Corralled Nanodiscs
- Possible applications of small and large nanodiscs in biotechnology and medicine
- Future directions and problems
Lead Generation Strategies
Moderator: Joe Patel, PhD, Director, Structural Biology, C4 Therapeutics
- Ubiquitin-mediated protein degradation strategies
- Which technique to try first?
- Hurdles to their therapeutic potential
- Stories to share?
Co-moderators: Svetlana Belyanskaya, PhD, Scientific Leader, Encoded Library Technologies, R&D Platform Technology & Science, GSK Boston
Ghotas Evindar, PhD, Manager, ELT Chemistry, GSK Boston
- Different types/approaches (i.e., DNA recorded, DNA templated libraries)
- Current constraints on DNA-Encoded Libraries (DNA compatible chemistry, library diversity, selection methods)
- Applications/target classes
Moderator: Ashley Adams, PhD, Senior Scientist, Discovery Chemistry and Technology, AbbVie, Inc.
- Revamping libraries – what have we learned?
- When to use which type of library?
- Pros and cons of various commercial libraries
Target Identification and Validation – Part 2
Chemical Biology Approaches for Target ID and Target Discovery
Moderators: Doug Johnson, PhD, Director, Chemical Biology & Proteomics, Biogen
Jaimeen Majmudar, PhD, Senior Scientist, Chemical Biology, Pfizer, Inc.
- Chemical biology approaches as an avenue for new targets
- Chemo-proteomics approaches to understand protein degradation
- Covalent fragment screening for the coupled discovery of targets and leads
- How can chemical biology approaches complement CRISPR-based technologies?
Targeting Gram-Negative Pathogens
Building an Understanding of Porin-Permeation in Gram-Negative Pathogens
Moderator: Ram Iyer, PhD, Principal Scientist (Bacteriology), Entasis Therapeutics, Inc.
- Addressing the knowledge gap for gram-negative pathogens
- Specific approaches, ie, TOMAS
- Identifying compounds that will disrupt the outer membrane
Filling in the Gaps in the MDR Gram-Negative Pipeline
Moderator: Todd A. Black, PhD, Executive Director, Infectious Diseases, Basic Research, Merck Research Laboratories
- Narrow spectrum antibiotics
- Non-traditional / non-antibiotic approaches
- Challenges for clinical trial designs
- Diagnostic challenges of identifying the right patients and strategies
- Future steps
Antibody Discovery Forum – Part 2
Considerations in Selecting Bispecific Antibody Formats for Immunotherapies
Moderator: Gundo Diedrich, PhD, Director, Antibody Engineering, MacroGenics
- Target considerations in selection of bispecific pairs
- Criteria to select a format: valency, half-life, effector function
- Manufacturing challenges: byproducts, aggregation, titer
- Considerations to modulate the affinity to both targets: cis vs. trans-binding, target expression
- MOAs of bispecifics that cannot be addressed with combinations of monospecific antibodies
Considerations in Target Selection for Antibody-Drug Conjugates (ADCs)
Moderator: Jennifer J. Hill, PhD, Team Lead, MS & NMR Analytics, National Research Council Canada
- Characteristics of real-world ADC targets and how these compare to the ideal ADC target
- Prediction and screening methods to determine target suitability for ADC development
- ADC target expression in healthy tissues: what is acceptable?
- Matching targets with optimal drug-linkers
Going Beyond Dual Antibody Targets to Tackle the Complexity of Cancer and the Immune System
Moderator: Marc Mansour, PhD, Senior Consultant, Leidos Health
- Could single targets (e.g., PD-1/ PDL-1) and dual targets (e.g., PD-1 and CTLA4) be the exception rather than the rule for effective immune modulation of cancer?
- Combining antibody-based therapies with other modalities such as other biologics or small molecules/targeted therapies – can we do better than simply follow rational (but generally blind) development plan?
- How do we assess success in our search of a clinical signal when testing complex combinations?
Antibodies Against Membrane Protein Targets – Part 2
Characterization of Antibodies Against Membrane Proteins
Moderator: Joseph Rucker, PhD, Vice President, Research and Development, Integral Molecular, Inc.
- Affinity and Kinetics: Useful approaches for characterizing antibody binding
- Epitopes: Different techniques for epitope mapping; binning versus mapping; why do epitopes matter?
- Cell Function: Integrating functional assays into antibody discovery and development
How Can we Optimize Therapeutic Antibody Discovery for Multi-Spanning Membrane Proteins (GPCRs, Ion Channels and Transporters)?
Moderator: Trevor Wilkinson, PhD, Associate Director, Antibody Discovery and Protein Engineering, MedImmune Ltd., United Kingdom
- What are the most efficient methods to isolate antibodies that modulate function?
- What are the most efficient screening methods?
- What are the preferred formats for antigens?
- Can we establish rules for how to address specific target classes?
Production Challenges for Membrane Proteins
Moderator: Nicola Burgess-Brown, PhD, Principal Investigator, Structural Genomics Consortium, University of Oxford, United Kingdom
- Construct design: preferred tags, proteases, how many constructs to screen?
- Challenges of expressing integral membrane proteins: which expression host?
- Problems of scale of production for structural biology: resource and cost issues
- Strategies to improve purification and stability of membrane proteins: detergents, lipids, affinity reagents, liposomes, nanodiscs
Droplet Microfluidics for Antibody Discovery
Moderator: Christoph Merten, PhD, Group Leader, Microfluidics, European Molecular Biology Laboratory (EMBL), Germany
- What kind of screens can be done on primary plasma cells from mice and humans?
- What are the specific advantages compared to other screening formats?
- How to get access to the technology?