8:00 am Morning Networking Coffee

8:50 am Chair’s Opening Remarks

Addressing Hurdles in Pre-clinical Development to Fast-Track IND-filing & Overcome Bottlenecks in the Approach to the Clinic

9:00 am Showcasing the Pre-Clinical Development of AMG133, an Innovative Bispecific Molecule for the Treatment of Obesity

  • Shu-Chen Lu Scientific Associate Director, Amgen Inc.


  • Leveraging human genetics to understanding complex metabolic targets
  • Showcasing AMG133 and its mechanism of actions as a bispecific molecule targeting two GPCR pathways simultaneously
  • Demonstrating the efficacy of AMG133 in vitro and in pre-clinical models
  • Taking AMG133 from pre-clinical success to clinical promise

9:30 am Discovery of Clinical Candidate AZD5462, an Allosteric Oral Small Molecule Agonist for the Treatment of Heart Failure


  • Reviewing the optimization of small molecule agonists of the Relaxin Family Peptide Receptor (RXFP1) resulting in discovery of AZD5462
  • Exploring mechanism of action and signaling in vitro and in vivo
  • Demonstrating the efficacy of AZD5462 in non-human primates

10:00 am Revealing the Pre-Clinical Development of a Next Generation Biologic to Selectively Drug GPCR Targets & Address Diseases with Unmet Patient Needs


  • How to enhance efficacy and safety with advanced antibody formats?
  • What are the rate-limiting factors in biologic IND-filing?
  • What challenges need to be overcome to expand development of biologics for more complex cancers?

10:30 am Session Reserved for Wuxi Biortus Biosciences

11:00 am Morning Networking Break & Scientific Poster Session

TRACK A: Target ID & Validation

Spearheading the Development of Next-Generation Drugs in Oncology Indications & Beyond

12:00 pm Fireside Chat: Overcoming Diversity in Therapeutic Outcomes by Elevating Bias Signaling


  • How to illustrate bias in downstream pathways?
  • Understanding the preferential activation and recruitment of G protein and ꞵ-arresting, respectively
  • How to leverage bias in candidate selection?
  • Revealing signaling bias for different G proteins
  • Can we design biased ligands rationally?

12:30 pm Discovering & Bringing GPCR-targeting Drugs to Patients to Tackle Cancer


  • Identification of new GPCR Targets in I/O field
  • POC studies in animal models
  • Establishing emerging approaches to tackle identified GPCRs
  • Biomarkers to support Drug Discovery and Clinical trials Efforts

TRACK B: Hit ID & Optimization

  • Joshua Ziarek Associate Professor of Pharmacology, Northwestern University

Developing Highly Selective Drug Candidates to Reduce Off-Target Effects & Improve Candidate Safety

12:00 pm Focused & Thoughtful Discovery, a Comprehensive Approach to Anti-GPCR Biologics Discovery & Engineering


  • A comparison of antibody discovery methods, technologies and reagents for anti-GPCR biologics discovery
  • Development and engineering of anti-GPCR variable regions to achieve optimal biological activity
  • Molecular considerations for anti-GPCR containing multispecifics  

12:30 pm Discovery & Validation of a Highly Selective Agonistic VHH

  • Andreas Busch Senior Scientist - Protein Science, Confo Therapeutics


  • De novo discovery of potent, full agonistic and highly specific agonistic VHHs
  • VHH binding mode as compared to peptide agonists
  • Implications for drug discovery

1:00 pm Networking Lunch Break

Advancing Translational Models to Convey the Complex Microenvironments of Native GPCRs & Improve Physiological Relevance

2:00 pm Understanding Receptors for Metabolites Using Novel Transgenic Models


  • The development and use of transgenic mouse models that express epitope-tagged and otherwise-modified GPCRs for analysis of function
  • The use of phospho-site specific antisera that provide tissue level biomarkers of receptor activation
  • How such mouse models can be used in a disease-relevant manner

2:30 pm Validation of GPR65 as a Novel Immuno-oncology Target using Advanced In Vitro & In Vivo Models


  • Identification of GPR65 as a novel immuno-oncology target as well as potent GPR65 inhibitors
  • Provide additional validation using primary tumor-histocultures and genetically engineered mice
  • Advancing biomarker development to accelerate clinical development

Employing Chemistry Insights to Improve the Potency & Safety of Novel Drug Candidates

2:00 pm Discovery & Optimization of Novel GPCR Biologics for CV/Renal Disease


  • Development and optimization of the GEODe platform to overcome the structurally dynamic nature and biochemical instability of GPCRs
  • Discovery of a GPCR agonist biologic clinically developed in a CV/renal disease indication
  • Optimizing the potency, PK, and biophysical characteristics of lead biologic compounds

2:30 pm Peptide Agonists to Target GPCRs for Metabolic Disorders to Meet the Growing Patient Need


  • Why target GPCRs with peptide-based therapeutics?
  • Lead optimization of a novel peptide agonist to target Class B GPCRs
  • Understanding the functionality of a novel peptide agonist by revealing the mechanisms of action and downstream signalling
  • Using structure-based insights to design high affinity and potent drugs

3:00 pm Afternoon Networking Break

Learnings from the Clinic: Reviewing Clinical Proof of Concept Cases to Inform the Strategy for Progressing Newly IND Approved Compounds

3:30 pm Using Translational Techniques to Advance Next Generation 5-HT2A Agonists into the Clinic to Treat Depression

  • Zoë Hughes Vice President, Head of Biology, Gilgamesh Pharmaceutical


  • Developing an optimized small molecule agonist of 5-HT2A receptors
  • Utilization of biomarkers with high-translational value to guide dose selection for evaluating the safety and efficacy of small molecules targeting the CNS
  • Reviewing 5-HT2A receptor binding in vitro, in vivo and the markers of target engagement from the bench to Phase I clinical trials

4:00 pm Leveraging the Clinical Progression of GPC100, a small molecule inhibitor of CXCR4, in combination with Propranolol to Inform the Translation of Novel Candidates that Drive Clinical Decisions


  • Review GPCR Therapeutic’s heteromer hypothesis and rationale for selection of CXCR4 and ADRB2 targets.
  • Review the selection strategy for our small molecule, CXCR4 inhibitor, GPC100 and early clinical findings. Discuss pre-clinical and clinical findings of GPC100 combination to support targeting both ADRB2 and CXCR4.
  • Did the pre-clinical findings improve our probability of clinical success? Did previous clinical data relate to the new findings? How do we efficiently identify, and successfully address, challenges that arise in the clinic?

4:30 pm Chairs Closing Remarks & End of 3rd Annual GPCRs-Targeted Drug Discovery Summit 2024