Targeted Protein Degradation Europe Summit Day 2 Agenda

8:30 am Morning Coffee

8:50 am Chair’s Opening Remarks

Spotlighting the Progression of Molecular Glue Degraders & Novel DUB Inhibitors

9:00 am Novel DUB Inhibitor Platform Addressing Protein Homeostasis

Synopsis

  • Mission has developed a world-leading potent and selective DUB inhibitor library
  • Selective tools provide best method for elucidating DUB enzyme regulation of disease pathophysiology
  • USP30 inhibitors exemplify progression from hit to candidate, with more DUB target programs to follow

9:30 am Unlocking Molecular Glues Potential- From Serendipity to Rational Design

  • Amine Sadok Director, Head of Biology, Monte Rosa Therapeutics

Synopsis

  • Introducing Monte Rosa QuEEN™ discovery platform
  • Identification of NEK7 as a novel CRBN neo-substrate
  • Discovery of potent and selective NEK7-directed Molecular Glue Degraders

10:00 am Introduction of X-Synergy & Molecular Glue Development Platform of Kangpu Biopharmaceuticals

  • David Wang VP Business Development, Kangpu Biopharmaceuticals

Synopsis

  • What are the scientific challenges in developing molecular glues?
  • Thoughts on maximizing potential clinical benefits of molecular glues
  • Early evidence of immunomodulatory molecular glues in treating solid tumor

10:30 am Morning Coffee Break

Advancing Discovery & Development

Assessing Technologies that Fast Track the Rational Discovery, Characterisation & Design of Molecular Glues

11:00 am Functional Screening for Glue Degraders Hijacking E3 Ligases of Interest

Synopsis

  • Functional screening for neo-substrate recruitment enables E3 ligase-centric discovery of glue degraders
  • Identified glue degraders can serve as recruiting moieties for PROTACs harnessing E3 ligases with favourable expression profiles

11:30 am Novel Molecular Glues in the Treatment of Cancer

Synopsis

Details to be revealed

Optimising Pre-Clinical Validation & Translation

Improving Drug-Like Properties of the Next Wave of Degraders

11:00 am Amide-to-Ester Substitution as a Strategy for Optimising PROTAC Permeability & Cellular Activity

  • Adam Bond PhD Student Centre for Targeted Protein Degradation (CeTPD), University of Dundee

Synopsis

  • Bifunctional PROTAC degraders belong to “beyond Rule of 5” chemical space, and criteria for predicting their drug-like properties are underdeveloped
  • A simple, yet unconventional, amide-to-ester substitution in BET degraders leads to increased cellular activity
  • Increases in PROTAC activity is due to increases in cellular permeability and not due to enhancement of ternary complex formation

11:30 am Target Protein Degradation & Drug Discovery: Lessons Learnt

Synopsis

  • Tumor cell dependence on SMARCA2 in SMARCA4 mutant tumours: an opportunity for PROTAC drug discovery
  • Steep structure property relationships in working towards bioavailability
  • Discovery of the first selective and orally bioavailable SMARCA2 degrader BI-0284

12:00 pm Networking Lunch

Applying Artificial Intelligence Based Approaches

1:00 pm Data-Driven Design Of Small Molecule Protein Degraders – Utilising Deep Learning To Streamline Drug Development

  • Oskar Hoff Head of Medicinal Chemistry, Celeris Therapeutics

Synopsis

  • Heterobifunctional degraders to hijack E3 ligases
  • Machine learning models leading to ternary complex prediction
  • Synthesis and in vitro screening of selected candidates

1:30 pm Relating Perturbations to Patients for Protein Degraders

  • Matthew Trotter Vice President, Predictive Sciences, Bristol Myers Squibb

Synopsis

  • Outlining the aim of relating complex chemical space and protein degradation to benefit increasingly precise patient populations
  • How the R&D landscape is changing to enable and empower predictive approaches towards this aim
  • Highlighting multiple roles for machine learning and inter-disciplinary research across this evolving landscape

Strategies to Achieve Successful Brain Penetration to Meet the Unmet Need of Neurodegenerative Diseases

1:00 pm Leveraging Protein Manipulation in CNS disorders

Synopsis

  • The challenges and opportunities in CNS disorders
  • A validated method in crossing the BBB
  • Case study of our alpha-synuclein degradation peptide for Parkinson’s disease

1:30 pm Round Table Discussion: Examples of Degraders Entering the CNS

Synopsis

  • What E3 ligase was utilised?
  • What does the structure of the PROTAC look like?
  • What are the main challenges of delivering protein degraders across the blood brain barrier and how is this overcome?
  • What are the druggable and undruggable targets within neurodegenerative disease that could be targeted with protein degradation strategies?

2:00 pm Scientific Poster Session

3:00 pm Protein Manipulation using Peptides: Opportunities & Challenges

Synopsis

  • Protein manipulation refers to the ability to degrade proteins using either proteasomal or lysosomal pathways, to relocate proteins within the cell, and to modulate the interactions of the target protein with other proteins
  • Short peptides can be effective agents to manipulate intracellular proteins
  • Strengthening or weakening of protein/protein interactions using rational design can be achieved to hit therapeutic targets

3:30 pm Panel Discussion: What Makes a Good Degrader?

  • Kevin Moreau Associate Director, PROTAC Safety Science AstraZeneca
  • Cornelia Wilson Senior Lecturer and Academic Laboratory Director, Canterbury Christ Church University

Synopsis

There is a current lack of protocols for making a successful degrader with good chemical matter. Being able to determine the parameters for what good look like and establishing common determinants will help the fast track development of the next generation of degraders. During the panel these key topics will be discussed:

  • Understanding why early degraders failed and what can be learned from these experiences
  • What makes a good product?
  • What are the minimum binding affinity requirements to produce a successful degraders?
  • What are the key chemical entity requirements?
  • How to degrade novel undruggable targets

4:15 pm Chairs Closing Remarks & End of 2nd TPD Europe Summit