2019 Archived Content

Interactive Breakout Discussion Groups

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.

This year’s breakouts with topics centered on each of the event’s 14 conference programs will take place on Tuesday evening, September 17 and – with breakfast – Thursday morning, September 19.

TUESDAY, SEPTEMBER 17 | 5:05 - 6:05 PM

TABLE 1: New Trends in Functional Genomics-Based Screening and Technologies

Moderator: Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute

Screen validation and follow-up with single well CRISPR technology
Large-scale screening with cell sensing and response reporters
CRISPR screening in primary cells using co-culture systems

TABLE 2: Chemical Biology in Drug Discovery

Moderators: Jaimeen Majmudar, PhD, Principal Scientist, Chemical Biology, Pfizer, Inc.

Jeff Martin, PhD, Scientist II, Chemical Biology & Proteomics, Biogen, 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?

TABLE 3: Use of Advanced Disease Models in Drug Discovery

Moderators: 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

Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration

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
Evaluation of microphysiological systems and models for efficacy, as well as safety studies

TABLE 4: Integrating FBLD with Other Screening Methods

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

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

TABLE 5: New Biophysical Technologies

Moderator: Anup Upadhyay, PhD, Senior Scientist III, Drug Discovery Science & Technology, AbbVie

Biophysical techniques for protein conformational plasticity and hydrodynamic properties, e.g., microscale thermophoresis (MST), second harmonic generation (SHG)
‘Toolbox’ biophysical techniques: Which are most popular? Which to use for which applications?
Correlating results from various biophysical approaches: Identifying and validating true hits

TABLE 6: DNA-Encoded Libraries

Moderator: Svetlana Belyanskaya, PhD, Scientific Leader, Encoded Library Technologies, R&D Platform Technology & Science, GlaxoSmithKline Boston

NEW: Chris Phelps, PhD, Manager, R&D Platform Technology & Science, GlaxoSmithKline 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

TABLE 7: New Technologies and Assays to Study Protein Degraders

Moderators: Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston

Carles Galdeano, PhD, Serra Hunter Professor, Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona

Yue Xiong, PhD, William R. Kenan Professor of the Biochemistry and Biophysics, University of North Carolina; Co-Founder, Cullgen

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?

TABLE 8: Novel Applications and Approaches for PROTAC-Based Protein Degradation

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 to develop “Me Too” PROTACs

TABLE 9: Challenges with Developed Targeted Protein Degrader Molecules

Moderators: Susanta Samajdar, PhD, Senior Vice President and Head of Discovery, Aurigene Discovery Technologies Limited

Upendra Dahal, PhD, Senior Scientist, Pharmacokinetics and Drug Metabolism, Amgen, Inc.

Differential activity in cells and preclinical models
PK/PD relationships
Bell-shaped dose response
Achieving oral bioavailability
BBB permeability
CMC challenges

TABLE 10: Animal Models for NASH

NEW: Moderator: Rebecca Taub, MD, CMO & President, R&D, Madrigal Pharmaceuticals

Re-evaluating NASH animal models in the context of the new FDA guidelines for NASH cirrhosis
Which noncirrhotic NASH animal models have the most representative histology?
Are there NASH cirrhosis animal models that develop complications?
Which biomarkers will be reflective of improvements in histology or predictive of complications?

TABLE 11: Efficacy of MOA in the Treatment of NASH

Moderator: Karin Conde-Knape, PhD, Corporate Vice President, Cardiovascular and Liver Disease Research, Novo Nordisk

What is decrease in liver fat telling us?
What will be the needed efficacy to make a difference to patients?
Are we any closer to having surrogate markers of efficacy?

TABLE 12: Cirrhosis and NASH

Moderator: Peter Traber, MD, Partner, Alacrita Consulting; Adjunct Professor of Medicine, University of Pennsylvania School of Medicine

Targets in common between chirrhosis and NASH
Challenges in treating cirrhotic NASH
Regulatory guidance for cirrhosis NASH trials

TABLE 13: STING: An IntereSTING IO Target

Moderators: Gottfried Schroeder, PhD, Senior Scientist, Department of Pharmacology, Merck Research Labs Boston

Charles A. Lesburg, PhD, Senior Principal Scientist, Computational and Structural Chemistry, Merck & Co., Inc.

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.

TABLE 14: Targeting the IDO/TDO-Kynurenine-Arylhydrocarbon Receptor Pathway and Beyond

Moderator: Thomas Hoffman, PhD, CFO, Phenex Pharmaceuticals

Pros and cons of IDO / TDO single / dual inhibitors vs. AHR antagonists?
Which tumor autonomous effects and which effects on the immune system can you expect?
For which cancers might such IDO / TDO / AHR inhibitors be applicable?

TABLE 15: Targeting the Adenosine Pathway

Moderator: Alwin Schuller, PhD, Senior Principal Scientist/Team Lead, Oncology, IMED, Biotech Unit, AstraZeneca

Targeting A2AR vs. CD73 vs. Dual Inhibitors
Other ways to modulate adenosine levels
Promising ‘synergistic’ combinations

TABLE 16: R&D for Emerging Modalities

Moderator: Zhiqiang An, PhD, Professor, Chemistry; Director, Texas Therapeutics Institute, University of Texas Health Science Center at Houston

Consideration of alternative modalities for intended target
Technologies for selections in final format
Emerging technologies for antibody discovery; NGS, single cell analysis, CRISPR, AI
Integrating traditional display platforms with new technologies
Multispecific platforms

TABLE 17: Fit-for-Purpose Membrane Protein Generation in Biologics Development

Moderator: Leyu Wang, PhD, Senior Scientist and Project Leader, Protein Sciences, AbbVie

Best practices to decide approaches for membrane protein production
Strategy for expression analysis for a novel multipanner
Challenges to close gap between membrane protein supply and demand
How to tap the external research organization or company

TABLE 18: Structural Biology Challenges in R&D for Membrane Protein Targets

Moderator: Xinchao Yu, PhD, Senior Scientist, Cryo-EM, Amgen

Producing sufficient quantity of minimally engineered human membrane proteins
Crystallography vs. cryo-EM, pros and cons
Detergents, nanodiscs or SMALPs
High-throughput structural biology for membrane proteins

THURSDAY, SEPTEMBER 19 | 7:30 - 8:30 AM

TABLE 19: What Happens When You Get Off-Target Effects?

Moderator: Arthur A. Levin, PhD, Executive Vice President, R&D, Avidity Biosciences

How are off-target events for RNA-targeting drugs being avoided and assessed?
What approaches are being taken to broaden delivery, the major hurdle for RNA-targeting therapeutics?
After delivery what is the next challenge for RNA-targeting drugs?

TABLE 20: Predictiveness of Animal Models

Moderator: Marla Weetall, PhD, Vice President, Pharmacology, PTC Therapeutics

Discussion will revolve around using animal models to predict safety and efficacy as many splicing sites are not conserved across species

TABLE 21: What Are the Next Actionable Precision Oncology Approaches?

Moderator: Vijaya Tirunagaru, PhD, VP, Head of Biology and Non-Clinical Development, Research, Rain Therapeutics

Technologies to identify novel oncogenic drivers
Mapping of driver mutations to specific patient populations
Synthetic lethality approaches

TABLE 22: 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?

TABLE 23: Designing and Optimizing Chemistry and Drug-Like Properties of Protein Degraders

Moderators: Ye Che, PhD, Head of Computational Design, Discovery Sciences, Pfizer, Inc.

Michael Plewe, PhD, Vice President, Medicinal Chemistry, Cullgen, Inc.

Design of protein degraders, linkers
Kinetics of binding and degradation
Ternary complex formation

TABLE 24: Novel Strategies for Protein Degradation

Moderator: Stewart Fisher, PhD, CSO, C4 Therapeutics

Applying enzymology concepts to the optimization of targeted protein degraders
Developing biochemical and cell-based assays for studying protein degradation
Protein degradation beyond bi-functional degraders

TABLE 25: Overcoming Translation Challenges

Moderators: Peter Dragovich, PhD, Staff Scientist, Discovery Chemistry, Genentech

Shaomeng Wang, PhD, Warner-Lambert/Parke-Davis Professor of Medicine, Pharmacology and Medicinal Chemistry; Co-Director, Molecular Therapeutics Program and Director, Cancer Drug Discovery Program, University of Michigan

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

TABLE 26: Translational Tools for Studying Fibrosis

Moderator: Vanessa M. Morales-Tirado, PhD, Senior Scientist III, Translational Immunology, Immunology Discovery, AbbVie Bioresearch Center

Advanced physiological models in fibrosis (animal models for safety and efficacy)
Current and novel biomarkers in discovery
New in vitro/ex vivo assays (3D cellular and organotypic models)

TABLE 27: Promising New Fibrosis Targets

Moderator: Victor J. Thannickal, MD, Professor & Director, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham

Cross-over Immuno-Oncology targets
Senolytics
Inflammation/Immune system targets

TABLE 28: Establishin Proof of Concept in Fibrosis

Moderator: Karl Kossen, PhD, Senior Vice President, Translational Science, Indalo Therapeutics

Biomarkers and imaging techniques
Enabling preclinical studies: opportunities and limitations
Notable clinical programs

TABLE 29: Biased Signaling

Moderator: John Janetzko, PhD, Damon Runyon Postdoctoral Fellow, Kobilka Lab, Department of Molecular and Cellular Pharmacology, Stanford University

Structural determinants of ligand bias
The role of GRKs in biased signaling
Cryo-EM of GPCR complexes and its role in drug discovery
How can academic research help the development of new drugs?

TABLE 30: GPCR Targeted Lead-Development Challenges

Moderator: Phil Carpino, PhD, Scientific Director, Discovery Chemistry, Janssen Research & Development

Untangling biased signaling
Comparing various cell-based screens
Medicinal chemistry challenges

TABLE 31: GPCR-Ligand Binding Kinetics

Moderator: Sam Hoare, PhD, Founder, Pharmechanics LLC

Compound residence time vs. compound in vivo efficacy
Off rate and duration of action
Kinetic artifacts in SAR assays

TABLE 32: Structure-Based Antibody Discovery and Design

Moderator: Christopher Corbeil, PhD, Research Officer, Human Health Therapeutics, National Research Council Canada

De novo design of antibodies: Useful and feasible?
Computational predictions in real-life projects: Better integration needed?
Using computational tools to access difficult-to-target proteins
Structure-based antigen design

TABLE 33: Opportunities in Antibody Discovery for Membrane Proteins

Moderator: Christyne Kane, PhD, Senior Scientist, Biologics Generation, AbbVie Bioresearch Center

In vivo vs. in vitro Approaches: The pros and cons
Antibody Databases: Requirements for the ideal database
IHC Tool Antibodies: Best practices for generation

TABLE 34: 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