Opening Plenary Session
7:00 am Morning Registration & Networking Coffee
8:10 am Chair’s Opening Remarks
From Serendipity to Late Stage Clinical Development: New Update Towards First-In-Class Approval
8:15 am From Serendipity to Rational Design: Taking Molecular Glue Degraders to New Heights
Synopsis
- ShowcasingQuEEN™, a proprietary molecular glue discovery engine generating therapeutics that selectively degrade disease-causing proteins
- Discussing Monte Rosa’s approach to accelerate Molecular Glue degrader discovery and validation
- Developing a potent and selective GSPT1-directed Molecular Glue degrader
8:45 am Discovery, Characterisation, & Optimisation of CBP Selective Degraders
Synopsis
- Identifying and optimizing potent, selective degraders of CBP to address mutant EP300 Cancers
- Spotlighting demonstrated, robust activity in preclinical pk/pd and efficacy models
- Demonstrating no observed thrombocytopenia in mice at pharmacologically relevant doses
9:15 am Enabling Discovery of Classical & Next-Generation Targeted Protein Degraders
Synopsis
- Design of a potent CK1a-selective degrader guided by cellular degradation and ternary complex studies
- Development of modular tools to investigate lysosomal-mediated extracellular TPD
- Strategies for characterizing MoA of novel degradation modalities in live cells
9:45 am Panel Discussion: Assessing Targeted Protein Degradation’s Ability to be Both Selective & Safe
Synopsis
- How much progress has been made in identifying and utilising tissue-sparing E3 ligases? Are there more ligases to find? How do we effectively identify them?
- What does existing off-target safety data tell us about degraders’ behaviour in clinic?
- Are Molecular Glues a ‘safer’ option? Are there other ‘TACs’ that have potential to be safer due to their MOA?
10:15 am Morning Break & Speed Networking
Synopsis
With an international gathering of TPD experts, this valuable session will ensure you can reconnect with your peers in the room to make new and lasting connections. All attendees will have the opportunity to meet and network with their academic and industry colleagues!
Track A: Discovery & Early-Stage Development
Novel Platforms & Screening for High Throughput Targets & E3 Hit Finding for PROTACs
11:15 am The Application of Computational Structural Biology Approaches to Support the Rational Design of Degraders
Synopsis
- An introduction to current state-of-the-art methods for ternary complex modelling
- Bayesian Optimisation and Physics-based approaches developed by CelerisTx
- Generative AI for bespoke linker design
- Prospective and Retrospective validation of the CelerisTx ternary complex prediction pipeline
11:45 am Deep Proteomic Screening for Systematic Discovery of Novel Degrader Targets
Synopsis
- High-throughput proteome-wide degrader characterization with unparalleled sensitivity, data completeness, and turnaround times
- Identification of novel degrader targets, monitoring of proteome-wide selectivity, and detection of molecules acting through new E3 ligases and emerging TPD mechanisms.
- Demonstration of degrader-induced modification by ubiquitinomics to a depth of up to 50.000 sites and detection of degrader-induced E3 ligase binding by interactomics
12:15 pm Development & Validation of PROTACs Using New E3 Ligands
Synopsis
- Accelerating the development of new E3 ligands
- Demonstrating a new workflow for validation of new E3 ligands for PROTAC development
- Harnessing the development of cell-based sensor systems
Track B: Preclinical, Translational & Clinical Considerations
Leveraging Robust Lead Optimisation to Enable Efficacious Translation for PROTACs
11:15 am Physicochemical Properties of Oral, Clinical-Stage PROTACs
Synopsis
- Demonstrating how oral PROTAC properties differ from Rule-of-5 drugs
- Highlighting key PROTAC properties for chemistry design
- Showing where PROTAC stereochemistry matters
11:45 am A Review of the Bivalent Degrader Landscape
Synopsis
- An overview of the current TPD landscape
- A deep dive into the current data for bivalent degraders, including PROTACs
- Insights into novel bivalent degraders & a look to the future
12:15 pm A Tricycle Journey to in-vivo Degraders of the Oncogenic Transcription Factor BCL6
Synopsis
- BCL6 is an oncogenic transcriptional repressor upregulated in a large fraction of diffuse large B cell lymphomas (DLBCL)
- We discovered potent BCL6 inhibitors. Some inhibitors triggered degradation of BCL6.
- We elucidated the structural requirements for degradation enabling the discovery of a potent in vivo degrader of BCL6
12:45 pm Lunch Break & Networking
Novel Platforms & Screening for High Throughput Targets & E3 Hit Finding for PROTACs
1:45 pm Lessons From in-solution Structural Dynamics for the Design of CRBN Ligands
Synopsis
- Harnessing solution NMR to reveal how ligand binding gradually induces the folding of the thalidomide binding domain (TBD)
- Highlighting key criteria for ligands to induce folding for efficient molecular glue (MG) activity
- Discussing potential differences in the design criteria of CRBN ligands for MGs and/or PROTACs
2:15 pm Discovery of New Targeted Protein Degraders using DNA-Encoded Chemistry
Synopsis
- Introduction to DNA-Encoded Chemical Library Technology (DEL)
- Application of DEL to the discovery of new bispecific degraders
- Case study showcasing the platform
Leveraging Robust Lead Optimisation to Enable Efficacious Translation for PROTACs
1:45 pm Discovery of Novel Molecular Glues by Degron-Ligase Interactions
Synopsis
- Rational screen for Molecular Glues
- Characterisation of Degron-Ligase interaction
- Identifying novel chemical matter for neomorphic interactions
2:15 pm Using Autophagy for Targeted Protein- & Organelle Degradation
Synopsis
- Expanding the target space of targeted protein degradation by using autophagy (A-TPD)
- An induced-proximity screen was used to identify entry-points to A-TPD for degradation of various cargo
- A heterobifunctional biodegrader was developed that degrades mitochondria by recruitment of an endogenous autophagy cargo receptor
2:45 pm Afternoon Break & Networking
Broadening the Horizon of TPD From Oncology via Alternative Pathways
3:45 pm Aurora Kinase A Degradation as a Novel Therapeutic Entry Point for Neuroblastoma
Synopsis
- Learn how Aurora Kinase A is a validated target in neuroblastoma
- Development of selective Aurora Kinase A PROTACs
- Discussion of an entry point for unique drug combination treatments
4:15 pm Small Molecules Inducing Targeted Degradation of Extracellular Proteins in Lysosomes
Synopsis
- Targeting extracellular proteins with small molecules and introduction to degradation technology
- Designing degraders inducing lysosomal-mediated degradation for a broad range of targets
- Showcasing preclinical data of degrader mechanism of action
4:45 pm Discovery of Novel Molecular Glues & Anti-Microbial PROTACs
Synopsis
- Developing assays to identify new CRBN-based molecular glues
- Tailoring molecular glue libraries for functional screens
- Identification and validation of new anti-microbial PROTACS