Explore the Agenda
8:00 am Check-In & Registration
8:45 am Chair’s Opening Remarks
Advancing Orphan GPCR Drug Discovery with Emerging Technologies to Transform Undruggable Targets into Therapeutic Opportunities
9:00 am Engineering GPCR Targets via Directed Evolution to Discover Pharmacologically Active Antibodies & Small-Molecule Modulators
- Enabling the discovery of inverse agonist antibodies with the EMP directed evolution platform: shifting the paradigm for CCR8 therapeutics
- Unlocking orphan receptors: discovery of inverse agonist small molecules to support target validation and therapeutic development
- Evolving conformationally biased receptor antigens for the discovery of agonistic antibodies
9:30 am Pan-Variant GPCR Correction: Engineering an Orthosteric Small Molecule to Reverse Rhodopsin Misfolding and ER Stress in adRP
- A first-in-disease small-molecule orthosteric corrector of Rhodopsin that restores folding, trafficking, and reduces toxic ER stress across diverse adRP variants
- Using deep mutational scanning to map variant-level misfolding and define a pan-variant correction profile that enables quantitative, mechanism-based patient stratification
- Establishing a genetics-driven precision ophthalmology framework that integrates variant-resolved pharmacology, structural biomarkers, and PK/PD modeling to guide clinical development
10:00 am Active, Monomeric GPCRs in 72h: Cell-Free GPCR Synthesis via Multiplexed Nanodisc Screening
- Producing active GPCRs by co‑translating receptors directly into MSP–lipid nanodiscs, avoiding detergents and preserving native-like stability
- Multiplexing 11 constructs across 8 lipid environments via automated CFPS–nanodisc screening to rapidly identify optimal biophysical conditions
- Delivering assay‑ready GPCRs in 48 hours, enabling high‑yield, functional β1AR and FFAR1 production for drug discovery and structural studies
10:30 am Morning Break & Networking
Expanding GPCR Therapeutics Beyond Small Molecules with Antibody & Peptide Platforms for Greater Selectivity, Functional Precision & Access to Previously Unreachable Receptors
11:00 am Unlocking the Potential of GPCRs for ADC-Based Oncology Therapies
- Revisiting GPCRs as viable oncology targets through the lens of mature ADC technologies, combining deep biological insight with innovative antibody design
- ADC optimization tailored to GPCR biology by balancing antigen density, expression heterogeneity, and internalization for maximal efficacy and selectivity
- Implementing a holistic design framework to match antibody properties, linker– payload chemistry, and target features to create next-generation, GPCR-directed ADC therapeutics
11:30 am Functional Screening of AI-Designed Peptide Library Identifies Novel Opioid GPCR Agonists
- The description of a Functional Screening platform that combines high-throughput microfluidics with ultra-large DNA-encoded peptide libraries to generate rich activity datasets at scale
- The application of the platform to an AI-designed peptide library targeting μOpioid Receptor 1: rapidly identifying novel agonists with strong specificity and potency
- We present our screening approach, assay methodologies, and cell-based validation to demonstrate how Orbit’s platform efficiently translates computational designs into experimentally verified therapeutic hits
11:40 am Advancing Antibody Discovery for GPCR Targets Through In Vivo Validation of an Agonistic Antibody
- Describing the discovery strategy used to generate an agonistic antibody, including target selection and screening approaches
- Demonstrating in vivo validation of the agonistic antibody and the pharmacological activity observed across relevant models
- Detailing key translational learnings from the program and how these insights inform broader GPCR-directed antibody discovery efforts
12:10 pm Lunch Break & Networking
1:10 pm Engineering Agonism: A New Frontier in GPCR Antibody Discovery
- Unlocking state-specific GPCR conformations to move beyond binding-only generative models
- Leveraging antibody agonists to precisely tune signaling bias in Class B GPCRs
- Integrating epitope selection with full-molecule engineering for PK, delivery, and developability
Advancing GPCR Translation with Predictive Models & Human-Relevant Systems to Improve Safety & Therapeutic Precision
1:40 pm Engineering of a Long-Acting Relaxin for the Treatment of Pulmonary Hypertension
- Using a biophysics-based approach to engineer a long-acting relaxin molecule for chronic therapy
- Showing that TX45 is effective in a rat model of severe pulmonary hypertension
- In parallel we used the well-established effects of relaxin on renal plasma flow in both rats in healthy volunteers to demonstrate the high degree of in vitro to in vivo correlation and the translatability of these effects for our optimized molecule
2:10 pm Interrogating GPCR Biology Across the Signaling Cascade: NanoLuc-Based Tools for Drug Discovery
- Deploying HiBiT/NanoBRET Target Engagement assays at endogenous receptor expression levels to quantify ligand binding and competitive displacement without the overexpression artifacts that confound pharmacological interpretation
- Resolving transient versus stable receptor–β-arrestin complexes in real time using NanoBiT complementation, enabling kinetic discrimination of Class A versus Class B GPCR trafficking behavior relevant to biased agonism studies
- Profiling internalization and arrestin recruitment of incretin receptors (GLP-1R, GIPR, GCGR) with semaglutide, tirzepatide, and retatrutide to demonstrate how a unified bioluminescent platform captures polypharmacology across next-generation GPCR-targeted therapeutics
- Integrating real-time and endpoint cAMP assays with broad dynamic range to link upstream receptor engagement to downstream G-protein signaling outputs in a single, scalable workflow compatible with HTS
2:20 pm Pharmacological Characterization of Novel 5-HT2A Receptor Agonists with Non-Hallucinogenic Potential Using Translationally-Relevant Models & Neural Circuit Evaluation
- Characterization of 5-HT2A/2C agonists using functional assays capture the pharmacological effects that relate to behavioral modification and translationallyrelevant antidepressive effects
- Embracing concept of “targeted polypharmacology” rather than single-target approaches may allow neural circuit modulation which may be important in depression and substance use disorders
- Integrating circuit-level and behavioral insights into lead optimization strategies of 5-HT2A/2C agonists may help fine-tune polypharmacological modulation of dynamic neural systems
2:50 pm Afternoon Break & Networking
3:30 pm Harnessing Long Residence Time to Overcome Hormone Fluctuations in Advancing MC2R Antagonists Toward the Clinic
- Optimizing a long-residence MC2R antagonist that maintains efficacy despite large hormone surges, benefiting patients where fast-off antagonists lose effect
- Building an HPA-axis systems biology and PBPK framework allowing confident prediction of human responses before first-in-human studies
- Recreating human-challenge paradigms in aligned in vivo models demonstrating clear advantages of long-residence compounds and benefiting clinical translation
Highlighting Clinical Successes of GPCRs: Driving Mechanism-Based Programs Forward with Predictive & Regulatory Clarity
4:00 pm Targeting EP4 Receptor in Cancer to Overcome Immunosuppression: DT-9081 an Oral Small Molecule Phase 2 Ready Therapeutic For Solid Tumors
- Presenting Phase 1 outcomes, including safety data, dose-escalation results and the establishment of the Phase 2 dosing regimen
- Highlighting our translational biomarker strategy, including target-engagement readouts and how these biomarkers support Phase 2 readiness
- Outlining the Phase 2 clinical plan in sarcoma, detailing study rationale and how PK/PD and exposure–response insights inform the development approach
4:30 pm From Discovery to First-in-Class: Pioneering an Orphan GPCR for Unmet Medical Needs
- Leveraging advanced computational methods to discover and verify a high-potential orphan GPCR linked to our disease of interest
- Pursuing the project against investor and industry skepticism, supported by strong clinical evidence and a differentiated indication strategy
- Presenting early clinical results from Phase 1 trial