In these sessions, attendees choose a specific roundtable discussion to join. Each group has a moderator to ensure focused conversations around key issues within the topic. The small group format allows participants to informally meet potential collaborators,
share examples from their work and discuss ideas with peers.
WEDNESDAY, AUGUST 26, 7:30 AM
Ubiquitin-Induced Targeted Protein Degradation
Topic: Designing and Optimizing Chemistry and Drug-Like Properties of Protein Degraders
Moderators: Chandrasekhar Abbineni, PhD, Senior Group Leader, Aurigene Discovery Technologies Limited
Upendra Dahal, PhD, Senior Scientist, Pharmacokinetics and Drug Metabolism, Amgen, Inc.
- Design of protein degraders, linkers
- Kinetics of binding and degradation
- Ternary complex formation
- Issues surrounding PK/PD, biotransformation, in vivo pharmacology and delivery
- Achieving oral bioavailability and BBB permeability
Topic: New Technologies and Assays to Target the Ubiquitin-Proteasome System
Moderator: Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston
- Key ubiquitination steps for inducing protein degradation
- Biochemical, biophysical and cellular-based approaches to monitor ternary complex formation
- How to identify novel E3 ligases and E3 ligase ligands: need and challenges
- How do PROTACs and IMIDs affect the normal UPS function?
Topic: PROTAC-Based Protein Degradation: Novel Applications and Approaches
Moderator: Tauseef R. Butt PhD, President and CEO, Progenra, Inc.
- Current limitations of PROTAC approaches – application of cereblon, cIAP, VHL, HDM2 ligases as degrader molecules ligase
- Big hurdles in therapeutic potential of PROTACs – toxicity for chronic diseases; oral bioavailability; IP issues
- Expanding therapeutic potential of PROTACs – developing novel ligases for membrane, cytosol or nuclear targets
- How to overcome the above hurdles and not develop “Me Too” PROTACs
Fragment-Based Drug Discovery
Topic: Orthogonal Biophysical Techniques for FBDD
Moderator: Charles Wartchow, PhD, Senior Investigator, Novartis Institutes for Biomedical Research
- When to use what: SHG, SPR, NMR, DSF
- Combining techniques: reconciling data
- The importance of biochemical assays in biophysical screening campaigns
- Applications to finding allosteric inhibitors
Topic: Covalent Fragments
Moderator: Daniel Erlanson, PhD, Vice President, Chemistry, Frontier Medicines
- Reversible vs. irreversible covalent fragments
- How to characterize covalent fragments
- Chemistries for cysteine and beyond
Topic: Early-Stage Development of Fragment Hits
Moderator: Martin Scanlon, PhD, Professor, Department of Medicinal Chemistry, Monash University
- Validation and ranking of hits from primary screens
- First stages of fragment elaboration (with/without structures)
- Selection criteria for progression to full chemistry program
Kinase Inhibitor Chemistry
Topic: Artificial Intelligence in Kinase Drug Discovery and Development
Moderator: Istvan J. Enyedy, PhD, Principal Scientist, Biogen
- Use of AI in kinase inhibitor drug design and optimization
- Pros and cons of AI in drug discovery
- What is a novel kinase inhibitor and how can we expand the chemical space of kinase inhibitors?
Topic: Kinase Inhibitors Moving beyond Cancer Therapy
Moderator: Carrow Wells, Research Associate, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill
- Chronic dosing
- CNS kinase targets
- BBB penetration and selectivity
Topic: The Future of Kinase Inhibitors
Moderator: Hatylas Azevedo, PhD, MBA, R&D Manager, Drug Discovery, Aché Laboratórios
- Allosteric inhibitors
- Artificial intelligence
- Different scaffolds (natural products, macrocycles, covalent inhibitors)
Macrocyclics & Constrained Peptides
Topic: 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
Topic: Technologies Driving Macrocycle Innovation
Moderator: Cameron Pye, PhD, CEO & Co-Founder, Unnatural Products
- Hit-finding strategies: DELs, mRNA display, phage, next-gen OBOC, biosynthesis. Where do they work, where do they struggle?
- Early prioritization: modeling or empirical property-based selection?
- What is missing? What technologies could rapidly enhance macrocycle discovery and development? Better modeling, more efficient synthesis, more diverse hits...?
WEDNESDAY, AUGUST 26, 5:30 PM
Topic: Biophysical Hit Assessment for PPI Targets
Moderator: Mary Harner, PhD, Research Investigator II, Mechanistic Biochemistry, Bristol-Myers Squibb R&D
- Molecular properties: eliminating false positive hits
- Target engagement technology selection 101: TSA, NMR, MST, SPR, other
- Improving confidence by combining technologies
- Importance of controls: reference molecules, specificity targets
- Delineating hits: mechanism of binding, binding site elucidation
Topic: Degradation-Inducing Therapeutics
Moderator: Philip Chamberlain, DPhil, Director, Structural and Chemical Biology, Celgene
- Various ‘molecular glues’ for targeted protein degradation strategies: SNIPER, cereblon, PROTACS, degronomid
- Which technique to try first?
- Hurdles to their therapeutic potential
- Any stories or difficulties to share?
Topic: Methods to Identify PPI Modulators
Moderator: Samantha J. Allen, PhD, Principal Scientist, Screening, Janssen R&D LLC
- Biochemical, biophysical and cell-based screening approaches
- Library selection
- Understanding ligandability
Artificial Intelligence for Early Drug Discovery
Topic: AI-Driven Target Discovery and Therapies
Moderator: Ruben Abagyan, PhD, Professor, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego
- Types of AI models predicting individual target activities of small molecules
- May the docking be a useful intermediate step before the AI model is applied?
- How under-characterized is the set of activities of small molecule therapeutics and drug candidates?
Topic: Use of Modeling Tools and Strategies for Predicting ADME-Tox Properties
Moderator: Maria A. Miteva, PhD, Research Director at Inserm, Medicinal Chemistry and Translational Research
- Machine-learning and structure-based approaches for ADME-Tox prediction
- Deep learning for ADME-Tox prediction
- Precision medicine and ADME-Tox
Topic: Trends in AI for Accelerating Drug Discovery
Moderator: Amol Jadhav, PhD, Industry Consultant, Transformational Health, Frost & Sullivan
- Current trends for the application of AI towards preclinical drug discovery, status and challenges
- What measures should be taken to invest and apply AI at various stages of drug development?
- Industry-Academia partnerships, shared experience from startups, academia and impact assessment
Topic: Binding Datasets in AI for Drug Discovery
Moderator: Kaspar Cottier, PhD, CTO, Creoptix
- How can actual measurement data from binding studies contribute to the success of AI for drug discovery?
- How does data protection within the industry affects the development of AI for drug discovery? What role can academic institutions take for filling in data gaps?
- Which parameters (kinetics, affinity, thermodynamics…) are most important, and how can instrument manufacturers contribute to future developments?
Small Molecules for Immunology & Oncology
Topic: The Chemistry of Small Molecule Immunomodulators in the Clinic
Moderator: Murali Ramachandra, PhD, CSO, Aurigene Discovery Technologies Limited
- Single agents and combination therapies
- Challenges with potency and selectivity
- Drug delivery and formulation
Topic: Cryo-EM for Drug Discovery
Moderator: Seungil Han, PhD, Cryo-EM Lab Head, Structural & Molecular Sciences, Pfizer Global R&D
- What is the bottleneck in cryo-EM?
- Current applications
- Future directions
Topic: Modulating STING
Moderator: Gottfried Schroeder, PhD, Senior Scientist, Department of Quantitative Biosciences, Merck Research Labs Boston
- Distinct structural features of STING to design modulators against
- Biologics vs. small molecule approaches for modulating STING
- MOA and physiological considerations, possible side effects, etc.
Encoded Libraries for Small Molecule Discovery
Topic: DNA-Encoded Library Technology
Moderator: Brian Paegel, PhD, Professor, Department of Chemistry, University of California, Irvine
- DNA-compatible reaction development
- Scaffold design
- Screening strategies
Topic: Future Developments in DEL Technology
Moderator: Joerg Scheuermann, PhD, Senior Lecturer, Chemistry & Applied Biosciences, ETH Zurich
- How best to speed-up hit validation
- Ways to quickly identify false positives
- Single or multiple display of ligands
Additional Breakout Discussions to be Announced