8:15 am Light Breakfast & Check-In
9:00 am Chair’s Opening Remarks
Tackling Toxicity, Bioavailability, Dosing & Patient Selection Challenges in Bifunctional Molecule Clinical Trials to Enhance Patient Outcomes
9:15 am Targeted Protein Degradation & the Chromatin Regulatory System
Synopsis
- Expanding delivering optionality for degrader programmes
- Recent developments from Foghorn’s degrader pipeline
9:45 am Targeting ‘Undruggable’ Targets: Pioneering Novel Applications of Heterobifunctional Degrade
Synopsis
- Astellas’ long-term innovation strategy in Targeted Protein Degradation
- Learnings from the discovery and development of ASP3082
- Accelerating progress through an integrated R&D approach and strategic collaborations
10:15 am Morning Break & Speed Networking
Synopsis
This networking session is your opportunity to get face-to-face with many of the brightest minds working in TPD and induced proximity therapies to establish meaningful relationships to pursue for the rest of the conference
Discovery Track
Advancing Glue Design: Profiling Selectivity, Target Engagement, & Mechanism of Action to Create Tailored Molecules with Enhanced Therapeutic Effects
Synopsis
Chair: Ian Storer, Head of Hit Discovery, AstraZeneca
11:15 am Engineering of Selectivity Between Closely Related Paralogs Via a Novel Molecular Glue Degrader of a Highprofile Epigenetic Target
Synopsis
- Monovalent molecular glue degraders for a high-profile epigenetic target were identified using our ligase-agnostic screening platform
- Degrader treatment recapitulates genetic dependencies and affects downstream signalling pathways.
- Molecular dynamics modelling and biochemical validation enabled us to rationalise the determinants of selectivity over closely related proteins and inform chemical optimisation of the molecules
11:45 am From Sequence to Glue: A Multi-Dimension Journey in the Embedding Space
Synopsis
- Leveraging advanced machine learning algorithms and data augmentation techniques to integrate diverse datasets, creating a unified and actionable embedding space for drug discovery
- Streamlining the identification of optimal E3 ligases for targeted protein degradation by utilizing predictive models to enhance ligand-ligase pairing accuracy
- Enabling the rational design of molecular glues through computational insights, accelerating the development of highly specific and effective degraders for challenging therapeutic targets
Pre-Clinical & Translation Track
Leveraging Novel MoAs to Unlock New Disease Targets & Realise the Full Therapeutic Potential of Degraders
Synopsis
Chair: William McEwan, Sir Henry Dale Fellow, Cambridge University
11:15 am Bridging Pharmacokinetics & Pharmacodynamics to Enhance the Pre-Clinical Efficacy of Degrader-Loaded ADCs Targeting SMARCA &CDK9 for Drug Development Optimisation
Synopsis
- Exploring the pharmacokinetic and pharmacodynamic challenges unique to SMARCA and CDK9 targets, focusing on degradation thresholds required to maximise therapeutic efficacy
- Examining the role of linker stability and release mechanisms in ADCs carrying degrader payloads, aiming to achieve controlled, targeted delivery of degraders to tumour cells
- Assessing how linker and payload characteristics influence absorption, distribution, metabolism, and excretion (ADME) profiles, and fine-tuning bioavailability to ensure a balanced therapeutic index and enhanced safety profile
11:45 am Developing Optimised Folding Interfering Degraders Targeting Cyclin D1
Synopsis
- Providing an overview of folding interference as a new modality to induce the degradation of a target protein
- Demonstrating that folding interfering degraders (FIDs) can be optimised to achieve high potency and desirable ADME properties
- Showing in vitro and in vivo characterisation of FIDs acting on Cyclin D1
12:15 pm Lunch Break & Networking
Accelerating Molecular Glue Discovery & Development to Unleash the Next- Generation of Induced Proximity Therapeutics
Synopsis
Chair: Ian Storer, Head of Hit Discovery, AstraZeneca
1:15 pm From Ligases to Molecular Glues – Strategies to Discover Novel Molecular Glues
Synopsis
- Advancing E3 ligase ligand discovery through cutting-edge techniques to identify high-affinity, selective ligands that serve as the foundation for novel degraders
- Transforming ligase ligands into functional molecular glues, engineering them to precisely target and modulate protein-protein interactions for therapeutic benefit
- Pioneering new approaches to develop molecular glue degraders, unlocking unique pharmacological effects to address previously undruggable targets and expand therapeutic possibilities
1:45 pm Unveiling Basal Protein-Protein Interactions to Drive Molecular Glue Discovery Across 200 Therapeutic Targets
Synopsis
- Mapping over 500 basal protein-protein interactions between therapeutic targets and a diverse range of ligases and chaperone proteins to uncover novel degradation opportunities
- Employing site-directed mutagenesis to characterize protein-protein interaction interfaces, enabling a deeper understanding of structural determinants for affinity modulation
- Prioritizing key interactions to inform small molecule discovery campaigns, accelerating the identification of molecular glues with high therapeutic potential
2:15 pm Revolutionizing Molecular Glue Discovery Through High-Throughput Neomorphic Remodelling of Effector Proteins
Synopsis
- Addressing the bottleneck in induced degradation therapeutics by introducing systematic tools to uncover critical design principles for molecular glue discovery
- Showcasing GlueSEEKER®, a cutting-edge intramolecular editing-based screening platform to precisely remodel E3 ligase surface landscapes for therapeutic innovation
- Demonstrating how re-engineered effector proteins with neomorphic activity expand substrate repertoires, unlocking ideal induced pharmacophores to guide the design of next-generation molecular glues
Optimising Drug Development Through Case Studies on Molecular Design & Predictive PK-PD Studies to Ensure Successful Translation into the Clinic
1:15 pm Optimising Pre-Clinical PROTAC Development: Predicting Bioavailability, Enhancing ADME Assays, & Overcoming DMPK Challenges for Clinical Translation
Synopsis
- Predicting bioavailability of pre-clinical PROTACS for effective translation from cellular to animal models and finally clinic
- Advancing assay design to accurately measure ADME properties including metabolic stability, PD and more
- Tackling critical challenges during DMPK characterisation of your PROTACs to enable accurate profiling and prediction for clinical performance
1:45 pm Targeting KRAS Mutations Beyond G12C: Advancing ACBI3 for Comprehensive KRAS Degradation and Tumour Regression
Synopsis
- Addressing the challenge of undruggable KRAS mutants and secondary mutations by developing ACBI3 as a next-generation therapeutic targeting a broader range of KRAS variants
- Leveraging a fragment-first approach and structure-guided optimization to refine ACBI3 (a compound developed collaboratively by Boehringer Ingelheim and Prof. Alessio Ciulli’s group) to enhance its biophysical properties and therapeutic potential
- Demonstrating the ability of ACBI3 to selectively degrade prevalent oncogenic KRAS variants, sparing H- and NRAS, resulting in a potent reduction of KRAS signalling and tumour regression in preclinical models
2:15 pm Pioneering a Differentiated Approach to Targeted Protein Degradation Using the Ubiquitin Conjugating Enzyme (E2) Family
Synopsis
- Overcoming the challenge of modulating ubiquitin-conjugating enzymes with small molecules by identifying novel strategies to address the lack of druggable pockets
- Leveraging Fragment-Based Drug Design for PTM-E2 complexes to enable the discovery of first-in-class ligands that open new therapeutic avenues
- Developing efficacious bi-functional degraders through E2 ligand extension and molecular design to target multiple high-value proteins of interest
2:15 pm Afternoon Networking Break & Poster Session
Harnessing Innovative Approaches for the Discovery of Effectors Beyond Cereblon & VHL to Develop Safer & Selective Degraders
Synopsis
Chair: Andreas Mantoulidis, Head of Medicinal Chemistry Lab, Boehringer Ingelheim
3:45 pm Advancing PROTAC Discovery Through SLIP: Identifying Degradation Effector Sites for Targeted Therapeutics
Synopsis
- Addressing the need for more TPD effectors and their ligands to expand the therapeutic potential of protein degradation
- Introducing SLIP, a cutting-edge platform that enables the creation of proximity in live cells, enhancing the discovery of new degradation pathways
- Demonstrating how SLIP has successfully identified PROTAC-able sites on key TPD effectors, paving the way for the development of next-generation targeted therapies
4:15 pm Reserved for NEOsphere Biotechnologies GmbH
4:45 pm Novel E3 Ligase-Based Targeted Protein Degradation: Potential Applications Within & Beyond Cancer Therapy
Synopsis
- Somatic mutation of some E3 ligases create novel E3 ligase that do not exist in normal tissues
- Targeted protein degradation using the mutated E3 ligases are very specific and only happen with the presence of the mutated E3 ligase
- Novel E3-based TPD and potential applications are discussed with an example