Breakout Discussions - Drug Discovery Chemistry

2019 Archived Content

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, APRIL 10, 7:30 AM

Protein-Protein Interactions

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

Topic: Degradation-Inducing Therapeutics

Moderator: Philip Chamberlain, DPhil, Director, Structural and Chemical Biology, Celgene

Various ‘molecular glues’ for ubiquitin-mediated protein degradation strategies: SNIPER, cereblon, PROTACS, degronomid
Which technique to try first?
Hurdles to their therapeutic potential
Any stories or difficulties to share?

Topic: RNA Complexes as Drug Targets

Moderator: Hasane Ratni, PhD, Expert Scientist, Medicinal Chemistry, F. Hoffmann-La Roche, Basel, Switzerland

Different types of RNA-based processes to target
Screens and other approaches for RNA-targeted inhibitor discovery
State of the field

Topic: Performing Internal Research vs. Insourcing/Outsourcing Strategies for Primary, Secondary and Safety Pharmacology

Moderators: Daniel Di Sepio, Business Line Leader, Eurofins Pharma Discovery Services

Approaches
Best practices
Areas of weakness in current paradigms

Small Molecules for Cancer Immunotherapy

Topic: Use of Targeted Protein Degradation Strategies for Oncology

Moderators: Peter Ettmayer, PhD, Scientific Director, Cancer Research, Boehringer Ingelheim RCV GmbH & Co KG

Markus Queisser, PhD, Scientific Leader, Protein Degradation DPU, R&D Future Pipelines Discovery, GlaxoSmithKline

Exploring use of PROTACs and other protein degraders for oncology treatments
Pursuing previously undruggable protein targets
Issues surrounding PK/PD, biotransformation and in vivo delivery

Topic: Exploring Diverse Target Classes for Cancer Immunotherapy

Moderator: David Wustrow, PhD, Vice President, Drug Discovery, FLX Bio

Discussion on new target classes and next-generation checkpoint inhibitors
Targeting the tumor micro-environment
Challenges developing assays and models for target identification and validation

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

Kinase Inhibitor Chemistry

Topic: Artificial Intelligence in Kinase Drug Discovery and Development

Moderator: Avner Schlessinger, PhD, Assistant Professor, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai

Use of AI in kinase inhibitor drug design and optimization
Can we design kinase inhibitor with conformational selectivity?
What is a novel kinase inhibitor and how can we expand the chemical space of kinase inhibitors?

Topic: Kinase Inhibitors and Immune Oncology

Moderator: Nicholas Kwiatkowski, PhD, Lead Scientist, Nathanael Gray Lab, Cancer Biology, Dana-Farber Cancer Institute

Sensitizing cancers to immune cells with kinase inhibitors
Activating the immune system with kinase inhibitors

Topic: Kinases as Tumor Suppressors – Therapies to Enhance Activity?

Moderator: Tim Baffi, Graduate Student, UC San Diego Biomedical Sciences Graduate Program, Department of Pharmacology, UCSD

Protein Kinase C activity in cancer
New therapeutic strategies to enhance activity

Fragment-Based Drug Discovery

Topic: Integrating Fragment, HTS and DEL Hit-Finding Approaches

Moderator: Robert D. Mazzola, PhD, Director, Chemical Research, Merck Research Labs

Fragment screens v. HTS v. DNA-Encoded Libraries (DEL)? Or combos?
Prosecuting hits: Use separate teams of chemists? Collect data simultaneously?
Sharing examples/lessons learned

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: FBDD without Crystallography

Moderator: Ben Davis, PhD, Research Fellow, Biology, Vernalis Research

Strategies for evolving fragment hits in the absence of protein-fragment x-ray structures
Structural techniques: NMR, molecular modeling
Chemical approaches

Topic: Emerging Technologies and Applications for Biophysics in Drug Discovery

Moderator: Delphine Collin, PhD, HarkerBio

New technologies, including SHG, Switchsense
Applications in lead identification
Virtual screening combined with insight for understanding mechanism of action

Directed Evolution-Based Drug Discovery

Topic: Genetically/DNA Encoded Libraries of Macrocyclic Peptides

Moderator: Rudi Fasan, PhD, Professor, Department of Chemistry, University of Rochester

Current and emerging strategies for generation and screening of genetically encoded macrocyclic peptides
Applications/target classes: When to use which platform?
Challenges and opportunities for future development

Topic: Phage Display

Moderator: Sepideh Afshar, PhD, Principal Research Scientist, Department of Protein Engineering, Eli Lilly and Company

What is next for phage display platforms?
Using phage display to identify peptides that cross biological barriers
Integrating phage display with other display platforms to overcome its limitations

Topic: DNA-Encoded Library Technology

Moderator: Brian Paegel, PhD, Associate Professor, Department of Chemistry, Department of Molecular Medicine, Scripps Research

DNA-compatible reaction development
Scaffold design
Screening strategies

WEDNESDAY, APRIL 10, 5:30 PM

Modulating the Ubiquitin-Proteasome System

Topic: 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

Topic: Development of Small Molecule Protein Degraders as New Therapeutic Modalities

Moderators: Michal Walczak, PhD, CSO, Captor Therapeutics

Nan Ji, PhD, Director of Chemistry, Kymera Therapeutics

Stewart Fisher, PhD, CSO, C4 Therapeutics

Applying enzymology concepts to the optimization of targeted protein degraders
Protein degradation beyond bi-functional degraders

Topic: Use of Targeted Protein Degradation Strategies for Oncology

Moderators: Peter Ettmayer, PhD, Scientific Director, Cancer Research, Boehringer Ingelheim RCV GmbH & Co KG

Markus Queisser, PhD, Scientific Leader, Protein Degradation DPU, R&D Future Pipelines Discovery, GlaxoSmithKline

Exploring use of PROTACs and other protein degraders for oncology treatments
Pursuing previously undruggable protein targets
Issues surrounding PK/PD, biotransformation and in vivo delivery

Topic: Emerging Ubiquitin Targets and Modulators for Drug Discovery

Moderators: Tauseef Butt, PhD, CEO, Progenra

Sachdev Sidhu, PhD, Professor, Donnelly Centre and Department of Molecular Genetics, University of Toronto

Inflammation Inhibitors

Topic: Developing Kinase Inhibitors for Chronic Indications

Moderator: Andrew Fensome, PhD, Associate Research Fellow, Medicines Design, Pfizer

Utility of kinase selectivity profiling data
Safety assessment as an experiment rather than a progression gateway
Integrating PK/PD to predict safety margins

Topic: Targeting Innate Immunity

Moderators: Daniel Dairaghi, PhD, Senior Research Advisor, Medicinal Chemistry, Eli Lilly & Co.
Chip Lugar, Senior Research Scientist, Discovery Chemistry Research, Eli Lilly & Co.

Challenges targeting RORg
Other promising targets in IL17 pathway
Safety concerns
Animal models

Topic: Targeting Protein-Protein Interactions in Inflammation

Moderator: Derek Cole, PhD, Senior Director, GI Medicinal Chemistry, Gastroenterology Drug Discovery Unit, Takeda Pharmaceuticals

Promising PPI targets
Strategies for druggability assessment of PPI targets
Biophysical approaches for PPI screening

Macrocyclics & Constrained Peptides

Topic: Macrocyclic Lead Optimization

Moderators: Petr Jansa, PhD, Senior Research Scientist II, Medicinal Chemistry, Gilead Sciences

Vicky Steadman, PhD, Business Line Leader, Integrated Drug Discovery, Eurofins Discovery (formerly Eurofins Pharma Discovery Services)

Challenging ADME properties
Drug design challenges (conformational sampling of macrocycles,IMHB incorporation...)
Advances in macrocyclization strategies
Natural products as starting points

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: Modelling or empirical property-based selection?
What is missing? What technologies could rapidly enhance macrocycle discovery and development? Better modelling, more efficient synthesis, more diverse hits...?

GPCRs & Membrane Proteins

Topic: Hit-Finding and Medicinal Chemistry Strategies for GPCRs

Moderator: Dean G. Brown, PhD, Director, External Chemistry, Hit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca

Cell-based screens, affinity-based screens (DEL, fragments, others) to drive hit-finding
HTS evaluation and lead generation on GPCRs
Integrating results from orthogonal approaches
Medicinal chemistry challenges for GPCRs

Topic: Opioid Alternatives and GPCRs

Moderator: Susruta Majumdar, PhD, Associate Professor of Pharmacology, Center for Clinical Pharmacology, St. Louis College of Pharmacy/Washington University