8:00 am Morning Registration & Networking Coffee
8:50 am Chair’s Opening Remarks
From AI & Predictive Tools to Proteome-Wide Screens: Exploring Screening Approaches for Effective Binder Discovery
9:00 am Leveraging AI & Cryo-EM for Discovery of Molecular Glues
Synopsis
- Harnessing revolutionary new tools in artificial intelligence and atomic resolution cryo-electron microscopy (cryo-EM) to discover novel druggable protein interfaces
- Showcasing how our platform enables us to design and discover potent interfacial glues and allosteric inhibitors that influence protein-protein interactions
- Presenting on our rapid processes for hit discovery and hit-to-lead optimization result in accelerated paths to development candidates for unmet patient needs
9:30 am Conducting Proteome-Scale Induced Proximity Screens to Discover Novel Hits
Synopsis
- Understanding how proteome-scale induced proximity screens can reveal novel effectors of central biochemical processes
- Utilizing unbiased screening to facilitate discovery of unexpected effectors
- Exploring the potential for drug discovery using the aforementioned techniques
10:00 am Utilizing DEL as a Primary Discovery Engine for Induced Proximity Approaches
Synopsis
- Designing a DEL collection that addresses both traditional and challenging target space
- Presenting DEL affinity screening of targets and ligases for bifunctional degrader discovery
- Showcasing a DEL to degrader case study
10:30 am Morning Break & Speed Networking
Synopsis
Our structured 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
11:30 am Simulating the Conformational Basis of Induced Proximity to Predict Event-driven Pharmacology for Enhanced Drug Discovery
Synopsis
- Learning structure-based representations from molecular dynamics simulations to predict and assess induced proximity mechanisms
- Evaluating lysine proximity to E2 ligase to inform degrader design and prioritization for synthesis
- Application of our Auto/dx platform to quantitatively predict and improve degradation profiles by integrating live-cell kinetic data
Improving Heterobifunctional Design & Testing To Increase Efficacy
12:00 pm Reimagining Druggability Using Chemoproteomic Platforms
Synopsis
- Understanding the rational discovery and design of molecular glues
- Developing novel induced proximity based therapeutic modalities
- Learning about DUBTACs for targeted protein stabilization
12:30 pm Expanding the Toolbox to Enable New Induced Proximity Mechanisms for TPD
Synopsis
- Importance of cellular kinetics for understanding event-driven pharmacology
- Hijacking luminescent reporter tags for inducible degradation of a target
- General lysosomal recruitment strategies coupled with detection methods for membrane protein TPD
1:00 pm Networking Lunch
2:00 pm Linking Structure to Function for Heterobifunctionals: Structural Considerations that Affect Function
Synopsis
- Utilizing steric considerations to promote the interaction between protein of interest and effector machinery
- Using linker size and chemistry to positively affect heterobifunctional design and function
- How to optimize heterobifunctional structure for increased membrane solubility and oral drug availability
2:30 pm PANEL DISCUSSION: Rational Design versus “Serendipity”: Deciding When to Solve the Mechanism of Action
Synopsis
- Navigating the latest advancements in the quest for rational design of heterobifunctional molecules and its advantages
- Should we focus on optimizing phenotypic screening approaches for discovering and testing novel molecules
- Comparing the two approaches and evaluating their pros & cons
3:15 pm Poster Session & Networking
3:45 pm Accurately Measuring Ternary Complexes to Better Elucidate Mechanisms of Action
Synopsis
- Examining common approaches to understanding protein-protein interactions through ternary complex measurement
- Understanding the challenges with elucidating ternary complexes
- Advancing predictive technology to visualise ternary complexes
4:15 pm Targeting Oncogenic RAS(ON) by Engaging Cyclophilin A & Inducing Inhibitory Tri-Complexes
Synopsis
- Design of natural product-inspired molecules that induce a tri-complex between Cyclophilin A and the active state of RAS
- Tri-complex inhibitors of RAS(ON) are potent, orally bioavailable, and active in vivo in preclinical models of RAS-driven cancers
- Formation of tri-complex enables novel bRo5 functionality, including covalent targeting of mutations beyond KRASG12C
Inducing Proximity to Drive Immune Interfaces on the Cell Surface to Alter Disease Relevant Biology
4:45 pm Proximity-based Discovery & Manipulation of Cell Surface Proteins to Influence Disease-Relevant Pathways
Synopsis
- Examining post-translational modifications and steric proximity paradigms to influence disease-relevant biology
- Using induced proximity tools to characterize immune synapses between cells
- Manipulating cell surface protein proximity to alter signal transduction
- Establishing bispecific screening paradigms to identify productive protein pairings
5:15 pm Using Modified Cytokines to Target Immune Receptors for Selective Response Towards Cancer
Synopsis
- Designing modified cytokines that have low affinity/activity towards their natural receptors
- How to use induced proximity to restore/drive interactions between the modified cytokine and its natural receptor(s)
- Optimizing selectivity/pharmacology of the modified cytokine by focusing on localizing activity to clinically relevant targets for alleviating disease