BREAKOUT DISCUSSIONS

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

Protein-Protein Interactions

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