Day One

Wednesday, March 23 2022 | 8.00 AM - 5.30 PM

8:00 am Registration & Morning Coffee

8:50 am Chair’s Opening Remarks

Emerging Screening & Modelling Tools to Accelerate Hit-to-Lead Identification & Optimization of GPCR Drugs

9:00 am Discovery of Functional Antibody Drugs for GPCRs


  • Functional GPCR antibodies, such as agonist and modulator antibodies, tap the hidden therapeutic potential of the body’s biological activities
  • Abalone Bio’s Functional Antibody Selection Technology (FAST) platform couples a massively parallel in vivo search with data-powered selection to discover these ultra-rare antibodies
  • Using the FAST platform, we have identified a highly specific CB2 agonist antibody that has shown efficacy in in vivo models

9:30 am Developing Highly Signaling-Pathway Selective Molecules Using Mebias’ 19Fluid Platform


  • 19F NMR of native GPCRs in solution
  • Conformation driven drug discovery to determine pathway selectivity
  • Integrating pathway selectivity into drug discovery

10:00 am Applying Multiplex Strategies to Solve Multimodal Drug Discovery Problems


  • Deploying our deep scanning mutagenesis approach to identify misfolded and mistrafficked variants that are amenable to small molecule chaperone therapy
  • Multiplex assays at massive scale allow for comprehensive functional profiling of every possible missense mutation across a given target
  • This Deep Mutational Scanning allows us to better address the genotype – phenotype problem, identify drug-responsive patient cohorts and map SARs from the target side

10:30 am Morning Break & Structured Networking

Advancing GPCR Structure-Based Drug Discovery & Design to Improve Ligand-Receptor Affinity

11:30 am Cryo-EM in GPCR Structure-Based Drug Discovery


  • Cryo-EM is a valuable method adding to the repertoire of biophysical and structural techniques for GPCR structure based drug discovery
  • Exploitation of cryo-EM is now providing additional opportunities to solve structures of GPCRs for which limited tool ligands are available, which we will exemplify with cryo-EM enabled GPCR SBDD case studies
  • Cryo-EM has improved accessibility of challenging receptors to SBDD and has revealed novel modes of binding opening up new opportunities for modulating receptor function in disease

12:00 pm Uncovering Structural Insights into GPCR Activation & Drug Design with Cryo-EM

  • John McCorvy Assistant Professor, Medical College of Wisconsin


  • How to successfully capture ligand-receptor structural affinity complexes with higher resolution for structure-based drug discovery and design
  • How to detect a dynamic range of GPCR activation and conformation with protein binding transitions using Cryo-EM technology for lead optimization
  • Deciphering the homology of ligand binding pocket structures to improve drug fusion characteristics

12:30 pm Application of Structural Mass Spectrometry to GPCR Drug Discovery


  • Introduction to OMass therapeutics
  • Introduction to OMass structural MS platform
  • Application of the platform to gain insight in receptor biology and drug discovery

1:00 pm Delineating the Conformational Landscape of the Target Receptor by NMR – Insights into Activation Mechanisms & Opportunities for Drug Discovery

  • Scott Prosser Professor of Biophysical Chemistry, University of Toronto


  • The utility of HDL- Nanodiscs for functional assays and NMR studies of functional states and dynamics
  • Relating the conformational landscape to pharmacology
  • Enhancing GPCR pharmacology with NMR spectroscopy to achieve region specific site and motif detection

1:30 pm Networking Lunch

2:30 pm Panel Discussion: Leveraging Human Genetics for Hit-to-Lead Optimization & Effective GPCRTarget Discovery


Creating target discovery platforms based on genetic human data for better hit-to-lead optimization is at the forefront of early drug discovery pipelines across biotech and pharma industries. We will explore the learnings from Regeneron’s key candidate GPR75 and how to inform, develop and expedite the drug discovery process for clinical success.

  • Leveraging the UK Biobank databases to assist in genetic validation of GPCR target– the case of GPR75
  • How best to select a leading candidate for optimisation and taken through for translation and clinical development?
  • How to expedite the drug discovery process for clinical efficacy?

3:30 pm Afternoon Networking Break & Poster Session

Successfully Validating & Drugging the Undrugged Orphan GPCRs

4:00 pm Optimizing Novel Tools to Validate Orphan GPCR Targets


  • Novel ligands and animal models to validate GPR35 and GPR84 as therapeutic targets
  • Use of ‘human specific’ ligands
  • Activation state biomarkers for poorly characterized GPCRs

4:30 pm Discovery & Pharmacological Targeting of an Orphan GPCR with “AntiOpioid” Activity


  • Unbiased forward genetic screening for regulators of opioid signaling using in vivo behavioral platform identifying GPR139 – a conserved orphan receptor antagonizing mu-opioid receptor actions
  • Biology of GPR139, its role in controlling function of brain circuits and animal behavior
  • Developing an assay to monitor GPR139 activity and performing HTS campaign to identify selective antagonists of GPR139

5:00 pm Targeting Brain Enriched Orphan GPCRs

  • Cesare Orlandi Assistant Professor , University of Rochester Medical Center


  • Orphan GPCR landscape in the central nervous system
  • Measurement of constitutive activity to identify G protein coupling of orphan GPCRs
  • Development of improved G protein chimeras for screening purposes

5:30 pm Chair’s Closing Remarks & End of Conference Day One