7:45 am Light Breakfast & Check-In
8:30 am Chair’s Opening Remarks
Overcoming Clinical, Funding & Partnership Challenges in the Degrader Space to Trailblaze a Path Towards the Clinic & Beyond
8:45 am PANEL DISCUSSION Clear Skies or Stormy Seas: Sailing the European Markets in Search of Funding & Partnerships for Effective Degrader Development
Synopsis
- What are the trends in the current European investment environment, and how can emerging companies effectively demonstrate commercial viability in these conditions?
- What is the average European life sciences VC’s risk appetite, and how can biotechs navigate this to secure investment?
- How do the dynamics of biotech-to-biotech deals compare to pharma partnerships? Does Europe need to match the more active partnering practices seen in the U.S.?
- How can biotech companies balance internal development with external partnerships, and what active decision-making criteria can they use to manage risks?
9:45 am Roundtable Discussion: Discussing Critical Challenges Faced in Clinical Trials for Degraders
Synopsis
- How can we best use preclinical data to predict the right dose and dosing regimen?
- How can we best confirm PK/PD/Efficacy a clinical in clinical study?
10:00 am Morning Break & Networking
Discovery Track
Leveraging Techniques for Warhead Discovery & Biological Validation of Novel Disease Targets to Unlock the Therapeutic Potential of Induced Proximity
Synopsis
Chair: Andrea Unzue Lopez, Head of TPD Chemistry, Merck Group
11:00 am Multimodal Screening Strategy for Discovery of Novel Cereblon-Directing Molecular Glue Degraders & Neosubstrates
Synopsis
- Molecular Glue Degrader (MGD) discovery mostly relies on screening-based approaches, such as cell viability assays. However, one limitation of such screening methods is the risk of overlooking non-essential neosubstrates of potential therapeutic value
- To address this risk, we developed a high throughput deep proteomics screening platform utilising label-free, data-independent acquisition mass spectrometry for integrated proteomics and “ubiquitinomics” analysis
- Screening a diverse subset of our large CRBN-focused library uncovered multiple potent and selective degraders of previously unreported cereblon neosubstrates
11:30 am The Power of Positive Selection in an E. coli Based Drug Discovery Engine for Induced Proximity Therapeutics
Synopsis
- Benefits of positive selection in E.coli bacteria
- Examples for application to TPD
- Describing glues for other PTMs and PPIs
Pre-Clinical & Translation Track
New Frontiers in Targeted Degradation: Advancing Extracellular Matrix & Surface Protein Degraders for Expanding the Targetable Proteome & Curing Novel Diseases
Synopsis
Chair: William McEwan, Sir Henry Dale Fellow, Cambridge University
11:00 am Harnessing Lysosomal Pathways for Effective Targeted Protein Degradation of Novel Targets to Cure Untreated Diseases
Synopsis
- Validating the lysosomal degradation pathway to define its targetable space, similar to the ubiquitination pathway in intracellular degradation
- Designing warheads to engage lysosomal sorting receptors to select novel proteins for degradation and pharmacological benefit
- Expanding the application of lysosomal degradation to different types of extracellular proteins in complex systems and organs to enable tissue specificity
11:30 am SureTACsTM: Beyond Blocking Membrane Proteins
Synopsis
- Membrane-bound E3 ligases can be repurposed for the targeted degradation of disease-driving cell surface proteins
- Laigo Bio’s TED-I screening platform is essential to identify optimal E3-target pairs with highest degrader potency
- SureTACsTM: bispecific antibodies that induce cell surface removal and target degradation in a tissue- and disease-specific manner
12:00 pm Lunch Break & Networking
Enhancing Structure-Based Design: Predicting Folding & Ternary Complexes to Accelerate the Development of Induced Proximity Therapeutics
Synopsis
Chair: Andrea Unzue Lopez, Head of TPD Chemistry, Merck Group
1:00 pm Leveraging Computational Approaches for the Discovery and Optimisation of Molecular Glues
Synopsis
- Evaluating the strengths and limitations of machine learning and molecular dynamics simulations for modelling ternary complexes in drug discovery
- Demonstrating how advanced computational platforms can enhance the discovery and optimisation of molecular glues, enabling more efficient development of targeted therapies
- Exploring the future potential of integrating computational techniques with experimental approaches to accelerate the development of novel molecular glue degraders
1:30 pm Drugging the 14-3-3 Interactome – From Fragments to Cellular Function
Synopsis
- Finding starting points to (selectively) stabilise 14-3-3 protein interactions is strongly aided via dynamic covalent chemistry
- Cooperativity and selectivity are intertwined
- Cellular effects depend strongly on the 14-3-3 clients’ mode of action
Precision Protein Modulation: Promoting Diverse Pharmacologies to Expand the Therapeutic Potential of Induced Proximity Drugs
Synopsis
Chair: Luc Brunsveld, Professor of Chemical Biology, Eindhoven University of Technology & Co-Founder, Ambagon Therapeutics
1:00 pm Non-Degrading Molecular Glues: A Platform for Finding Novel Chemical Matter for Inhibiting Intracellular & Transmembrane Proteins
Synopsis
- The described macrocycles form ternary complexes comprising a presenter protein (FKBP12), the molecular glue, and a target protein. Inhibition through formation of a ternary complex often results in potency, selectivity over homologous proteins and favourable drug like properties such as slow binding kinetics
- The principles of constructing DEL libraries with Topological diversity is a key driver for broadly unlocking target classes
- The performance platform against a number of target classes will be presented
- SAR studies directed at optimising lead molecules against a target will be described
1:30 pm ROUNDTABLE DISCUSSION Discussing Non-Degrading Induced Proximity Therapeutics & Transferable Learnings to & From Degraders
Synopsis
- How can we measure and optimise cooperativity in induced proximity therapeutics, including PROTACs and non-degraders?
- What strategies are most effective for interrogating targets to determine their sensitivity and compatibility with your induced proximity platforms?
- In what ways do finding starting chemical matter differ for non-degrading induced proximity therapeutics from those for degraders?
2:00 pm Afternoon Break & Networking
Overcoming Challenges in the Development of Degraders Against Diseases Beyond Oncology to Benefit a Whole New Class of Patients
3:00 pm Elucidating the Discovery of TRIM21 & the Development of Targeted Degraders Against it to Cure Neurodegenerative Diseases
Synopsis
15:00:
- The story of the of TRIM21 as a viable therapeutic target against neurodegenerative diseases
15:30:
- Engineering antibodies and synthetic biologics to demonstrate the potential of targeted degradation against TRIM21
- Development of small-molecule degraders aimed at TRIM21 for the treatment of neurodegenerative diseases