8:00 am Registration & Morning Networking Coffee
8:50 am Chair’s Opening Remarks
Deconvoluting Human Genetics to Understand Untapped GPCR Families & Expose the Relevance of GPCRs in Previously Unidentified Disease Indications
9:00 am Human Genetics-SAR: A Novel Approach to Decipher the Biology & Therapeutic Potential of Human GPCRs
Synopsis
- How to approach the large-scale multiparametric profiling of naturally occurring human GPCR missense variations
- How to leverage the power of human genetics by linking the molecular, cellular, and clinical consequences of rare GPCR missense variations to accelerate the discovery of disease relevant pathways
9:30 am Examining Commercial & Investor Perspectives to Fulfil the Future Opportunities of Next-Generation GPCRs
Synopsis
- What is investible when considering the GPCR landscape?
- What do investors look for when investing in GPCR pipelines?
- How to secure interest from collaboration partners?
- What is the scope for other types of funding partners?
10:30 am Morning Break & Speed Networking
Synopsis
Our speed networking is the ideal opportunity to get face-to-face time with many of the brightest minds working in the field & introduce yourself to the attendees that you would like to have more in-depth conversations with. Benchmark against industry leaders & establish meaningful business relationships to pursue for the rest of the conference & beyond.
TRACK A: Target ID & Validation
Reinvigorating Biophysical Assays with Dynamic Confirmation Insights to Improve Candidate Selection
11:30 am Fireside Chat: Overcoming Diversity in Therapeutic Outcomes by Elevating Bias Signaling
Synopsis
- How to leverage bias in candidate selection? How to identify the best signalling profile, and correlate cell signalling with efficacy?
- What are the methods for revealing signaling bias for different G proteins? Understanding the preferential activation and recruitment of G protein and beta-arresting, respectively
- Can we design biased ligands rationally?
- How to leverage AI to interpret data and inform drug design?
12:00 pm Chemogenetic Activation of Specific GPCR Signaling Pathways to Identify Novel Targets for Antidiabetic Drugs
Synopsis
- Leveraging designer GPCRs known as DREADDs (Designer Receptors Exclusively Activated by a Designer Drug) to selectively activate distinct classes of heterotrimeric G proteins
- Using DREADDs to identify novel cellular targets for the treatment of major metabolic disorders
- Optimizing DREADD technology to identify distinct GPCR signaling pathways involved in type 2 diabetes and obesity in vivo
TRACK B: Hit ID & Optimization
Pioneering Rational GPCR Drug Discovery with Structure-Based Design
11:30 am Pros & Cons of Positive Allosteric Modulation in GPCR Drug Discovery – Case Studies from Lilly Research Labs
Synopsis
- Discussing the attributes of a target that make allosteric modulation a desirable MOA for drug discovery
- Importance of profiling and understanding the key parameters of allosteric modulation (affinity, alpha, and beta) and their impact on target product profile
- Emerging importance of GPCR structural biology in the design and optimization of allosteric modulators
12:00 pm Enabling Structure-Based Drug Discovery on GPCRs
Synopsis
- Protein engineering strategies for enhancement of expression and stability
- Biophysical methods to characterize small-molecule ligand binding
- Selecting EM and/or X-ray for structure research to investigate ligand interaction
- Time resolved X-ray crystallography to investigate receptor dynamics
12:30 pm Networking Lunch Break
Reinvigorating Biophysical assays with Dynamic Confirmation Insights to Improve Candidate Selection
1:30 pm Understanding the Role of GPCRs in the Tumor Microenvironment: Identification & Validation of Novel Immuno-oncology Targets
Synopsis
- Identifying immunosuppressive GPCRs in the TME
- Further validation of immuno-oncology targets ex vivo and in vivo
- Illustration of Domain’s R&D efforts and GPCR pipeline
2:00 pm Adopting NMR Spectroscopy to Address the Dynamic Aspects of Receptor-Drug Complexes
Synopsis
- How is NMR spectroscopy addressing conformational and dynamic changes?
- What data packages are associated with NMR and how are these analyzed?
- Uncovering kinetics of the GPCR landscape and how these motions govern receptor activation?
Streamlining Hit ID & Optimization with Advanced Screen Platforms to Accelerate Lead Generation
1:30 pm The Salipro® Platform Enables Discovery of Novel Therapeutics Against GPCRs
Synopsis
- How to reconstitute wildtype GPCRs into Salipro® nanomembrane particles
- DEL screening using purified wildtype GPCRs
- Hit verification using SPR and CryoEM
2:00 pm Assay Development & High-Throughput Screening of the pH-Activated GPR65 & GPR68 Receptors
Synopsis
- • Development of recombinant cell lines expressing the pHactivated GPR65 and GPR68 receptors
- Validation of cAMP and IPOne HTRF functional assays for GPR65 and GPR68 receptors for HT
- HTS of a 260k compounds library for antagonist activity at the GPR65 and GPR68 receptors, and identification of validated hits
2:10 pm Advancing the Optimization of Lead Biologic Candidates using New Screening Platforms
Synopsis
- What is the workflow to screening for highly specific biologics
- How to enhance binding affinity of anti-GPCR antibodies with chemical optimization?
- How to exploit the druggability of antibodies to target previously undrugged GPCRs?
2:30 pm Afternoon Networking Break
Addressing Complex Unknowns to Unlock Previously Undrugged Targets & Finally Spearhead the Revolution of GPCR Deorphanization
3:30 pm Roundtable Discussion: Leading Deorphanization with the Identification of Endogenous Ligands as a Compound to Advance Rationale Drug Development
Synopsis
- How to validate proposed true orphan GPCR-ligand pairs and with what suite of assays?
- What are the emerging methods for accomplishing deorphanization? Structural characterization, Mass spec etc
- How to reveal the therapeutically relevant signaling pathways activated by orphan GPCRs?
4:00 pm Leveraging Structure Based Insights to Inform Novel Roles for Orphan GPCRs & Lead Cognate Ligand Identification
Synopsis
- How to structural characterize orphan GPCRs using AlphaFold2?
- How to use structural insights to inform the development of orphan GPCR ligands?
- How to elucidate novel mechanisms with these insights?
4:30 pm Validation of GPR65 as a Novel Immuno-oncology Target using Advanced In Vitro & In Vivo Models
Synopsis
- Identification of GPR65 as a novel immuno-oncology target as well as potent GPR65 inhibitors
- Provide additional validation using primary tumorhistocultures and genetically engineered mice
- Advancing biomarker development to accelerate clinical development