DAY TWO

Thursday | January 18, 2024

8:00 am Morning Refreshments

8:55 am Chair’s Opening Remarks

  • Beth Hoffman Chief Executive Officer, Origami Therapeutics

OPTIMIZING PROTEIN DEGRADER PHYSICOCHEMICAL PROPERTIES TO IMPROVE DELIVERY ACROSS THE BLOOD BRAIN BARRIER

9:00 am Explaining Blood−Brain Barrier Permeability of Small Molecules by Integrated Analysis of Different Transport Mechanisms

Synopsis

  • Constructing a model to determine small molecule feasibility to cross the BBB via different transport mechanisms
  • Breaking down small molecule ability to cross the BBB via diffusion, influx and efflux mechanisms
  • Predicting impacts on adding chemical moieties on small molecule BBB penetration

DISCOVERING TARGET PROTEINS & MAXIMIZING SCREENING STRATEGIES TO ENSURE PROTEIN DEGRADER SPECIFICITY TO CNS INDICATIONS

9:30 am Roundtable Discussion: Starting From Scratch: Investigating CNS Targets Without Binding Inhibition Knowledge to Identify Brain & Pathology-Specific Target Proteins

Synopsis

  • Tackling difficult to drug targets across CNS disease pathologies
  • What are the clinically effective targets for CNS protein degraders?
  • Outlining best practices to screen and develop ligands specifically targeting toxic CNS aggregates

10:15 am Exploring High-Throughput Target Screens to CNS-Specific Protein Degraders

Synopsis

  • Adapting Plexium’s high-throughput screening for degraders of CNS-relevant diseases
  • Setting expectations for optimal library size when screening for CNS protein degraders
  • Exploring high-throughput screening in iPSC-derived neuronal cells to search for protein degradation characteristics

10:45 am Morning Break & Networking

11:15 am Identifying & Advancing Hits from CNS Protein Degrader Library Screens

Synopsis

  • Investigating the promise of phenotypic screens to identify protein degraders
  • Detailing a strategy for rapidly translating from degrader hits to in vivo efficacy
  • Outlining leading indications for degraders targeting autophagy in CNS disorders

OVERCOMING THE BARRIERS TO TRANSLATON TO UNLOCK CLINICAL SUCCESS IN CNS PROTEIN DEGRADATION

11:45 am Panel Discussion: Breaking Down the Pitfalls in Protein Degrader Assays & Brainstorming CNS-Specific Considerations

  • Robert Blake Senior Principal Scientist, Biochemical & Cellular Pharmacology, Genentech
  • Beth Hoffman Chief Executive Officer, Origami Therapeutics

Synopsis

  • Streamlining PROTAC sample handling to foster standardized degrader assay development and analysis
  • Evaluating PROTAC behavior as small molecules to understand mechanism of action
  • Spotlighting additional PK and in vitro cost and time burdens in non-optimized assay conditions

12:15 pm Lunch & Networking

1:15 pm Re-Evaluating Pharmacokinetic Profiles, Brain Penetration & Off-Target Effects of PROTAC-Like Compounds Targeting Tau

  • Robert Blake Senior Principal Scientist, Biochemical & Cellular Pharmacology, Genentech

Synopsis

  • Exploring pharmacokinetic profiles of CNS protein degraders
  • Evaluating small molecule measurements of brain penetration against previously reported data
  • Analyzing understanding of off target-effects misleading target engagement

1:45 pm Fireside Chat: Navigating the Future Development of Protein Degraders for CNS & Making the Most of Early Industry Collaboration

  • Beth Hoffman Chief Executive Officer, Origami Therapeutics
  • Eric Masson Senior Vice President - Early Clinical Development, Arvinas

Synopsis

  • To what extent are gaps in biological understanding hampering development of CNS protein degraders?
  • What are the short to medium term barriers to overcome to accelerate CNS degrader development on par with oncology?
  • How can the drug development community collaborate and mutually benefit in exploring TPD applications to CNS?

2:15 pm Chair’s Closing Remarks

  • Beth Hoffman Chief Executive Officer, Origami Therapeutics

2:30 pm End of Conference

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Targeted Protein Degradation for CNS Event Guide
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