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

  • Cesare Orlandi Assistant Professor, University of Rochester Medical Center

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 tackle orphan receptors with little known pharmacology with innovative strategies to discover their functional roles
  • How to biochemically and biophysically characterize and validate orphan GPCRs?
  • Identifying the signaling pathways, downstream activities, and mechanisms of action of orphan GPCRs to understand their therapeutic relevance

10:15 am Morning Networking Break

Achieving Success with the Development of Therapeutics for Metabolic Diseases Targeting GLP-1 & Beyond

11:15 am Design and Development of QMD Driven Physiological Biomolecular GPCR Small Molecule Agonist Complexes

Synopsis

  • Peptides physiological confirmation, binding mode, design of peptidomimetics & to constraining peptidomimetics into peptides utilizing unnatural amino acids, we can develop orally agents. Further profiling against several GPCRs as targets for selective and stable peptides treating metabolic diseases
  • Generate natural peptide sequence stable conformer, search for amidic back-bone, alpha C, acid and amine mimetic functional groups in to peptidomimetics. Covert peptidomimetics scaffolds region constrains to serve as small molecules for oral delivery
  • Biolexis MolecuLern methodology employed in design of selective, oral, small, molecule agonists of GLP-1R, a class of GPCR agonists will be discussed

11:45 am Roundtable Discussion: Maximizing the Effectiveness of GLP-1 Targeted Therapies

Synopsis

  • Designing drugs that promote fat loss while preserving muscle mass to ensure improved therapeutic outcomes and metabolic health
  • Identifying new obesity targets within BiTE and class B GPCRs to broaden scope of potential therapeutic interventions
  • Optimizing small molecules with enhanced specificity for GLP targets to avoid unintended toxicity and improve patient compliance

12:15 pm Networking Lunch

Overcoming Translational Challenges in Targeting GPCRs in Diseases for Seamless Clinical Transition

1:15 pm Leveraging Effective Models for Anti-CCR8 Antibody to Inform First In- Human Clinical Trials

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

1:45 pm Successfully Translate a Non-Hallucinogenic Seretonergic Receptor Space from Discovery to the Clinic

  • Glenn Short Chief Scientific Officer, ATAI Life Sciences

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

2:15 pm Afternoon Networking Break

Diving into the Clinical Story of GPCR-Targeted Drugs Showcasing Challenges & How to Overcome Them

3:00 pm Roundtable Discussion: Navigating Challenges in Translational Models for GPCR-Targeted Drugs to Achieve Clinical Success

Synopsis

  • How to develop strategies that align preclinical models with human physiology to improve translational accuracy
  • Evaluating the strengths and limitations of cell-based, animal, and disease models for GPCR-targeted drugs
  • What has been learned from GPCR clinical trials to drive therapeutics success and inform better trial designs?

3:30 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

4:00 pm Chair’s Closing Remarks

4:15 pm End of the 4th GPCRs-Targeted Drug Discovery Summit