Conference Day Two | Thursday, May 22
8:00 am Morning Coffee
8:55 am Chair’s Opening Remarks
Transforming the GPCR Landscape with Effective Tools & Strategies to Develop Drugs Targeting Orphan GPCRs
9:00 am Unlocking Strategies to Identify Ligands that Activate Orphan GPCRs to Develop Agonists
Synopsis
- Developing and optimizing novel methods to identify endogenous and synthetic ligands acting on GPCRs to allow for the design of targeted GPCR therapies
- Application of the novel Gz-Enhanced Signal Transduction assaY (GzESTY) for identifying orphan GPCR ligands in complex tissue extracts and compound libraries
- Development of novel screening assays for the rapid identification of inverse agonists targeting GPCRs and orphan GPCRs
9:30 am Fireside Chat: Uncovering Tools to Discover Synthetic Ligands for Orphan GPCRs to Advance the Development of Effective Therapies
Synopsis
- How to begin tackling orphan receptors with little known pharmacology to discover their functional roles?
- What tools do we have to identify the signaling pathways, downstream effects, and mechanisms of action of orphan GPCRs to understand their therapeutic relevance?
- Is there a need to always discover a ligand against an orphan GPCR and can we work off signatures in the data instead?
- How to biochemically and biophysically characterize and validate orphan GPCRs for drug discovery?
10:15 am Morning Networking Break
Decoding GPCR Pharmacology Through Mechanisms of Action to Enhance Drug Design & Targeting
11:00 am Structural & Functional Basis of Ligand Multispecificity at Human Chemokine Receptors
Synopsis
- How to define and relate structure and pharmacology
- How to elucidate the mechanisms of action by which endogenous ligands can differentially recognize and activate the same receptor
- How can these findings potentially guide discovery of targeted therapeutics
11:30 am Pharmacogenetics of the Human Hydroxycarboxylic Acid Receptor 2 (HCAR2)
Synopsis
- Uncovering GPCR mutations in mouse models that match the human phenotype
- Reviewing how pathway-specific targeting has led to distinct drug properties highlights the ability to fine-tune drug effects
- Determining what is physiologically relevant by assessing the functional context of signaling pathways to ensure that drug effects align with natural biological processes
12:00 pm Pharmacogenetics of the Human Hydroxycarboxylic Acid Receptor 2 (HCAR2)
Synopsis
- Synaptic adhesion molecules interface with GPCRs and allosterically modulate their pharmacological properties
- Disruption of these molecules lead to neuropsychiatric and neurodevelopmental consequences in animal models and humans
- Targeting these GPCRs, or the interface between GPCRs and synaptic adhesion molecules, may represent a new direction in pharmacological strategies
12:30 pm Networking Lunch
Overcoming Translational Challenges in Targeting GPCRs in Diseases for Seamless Clinical Transition
1:30 pm CCR8: Great Expectations
Synopsis
- CCR8 is emerging as the next hot immuno-oncology target
- DT-7012: discovery of a highly differentiated anti-CCR8 depleting antibody
- DT-7012 is about to enter the clinic
2:00 pm Successfully Translate a Non-Hallucinogenic Seretonergic Receptor Space from Discovery to the Clinic
Synopsis
- Harnessing AI and medicinal chemistry to identify a highly selective lead candidate
- Utilizing non-traditional models, including EEG parameters, with strong translational validity to streamline preclinical testing
2:30 pm Afternoon Networking Break
Diving into the Clinical Story of GPCR-Targeted Drugs Showcasing Challenges & How to Overcome Them
3:30 pm Progressing a GPR65-Targeted Drug to the Clinic to Treat Cancer
Synopsis
- Advancing to phase I/II clinical trials with a novel immune-oncology therapy
- What has been learned from GPCR clinical trials to drive therapeutic success and inform better trail designs?
- Addressing challenges in clinical trials through molecular-level discoveries to enable more precise targeting
4:00 pm Clinical Development of Urcosimod, a Drug Candidate Targeting CMKLR1 (ChemR23), to Treat Eye Disease & Neuropathic Corneal Pain
Synopsis
- Spotlighting results from randomized Phase 2b clinical trials of the lipidated peptide urcosimod to treat dry eye disease (DED) and neuropathic corneal disease (NCP)
- Covering in vitro and animal model data on urcosimod, an agonist of the ChemR23 receptor, that led to the decision to develop urcosimod to treat NCP and DED
- Providing advice for those developing drugs