DAY TWO - Thursday May 9, 2024

8:00 am Morning Networking Coffee

8:50 am Chair’s Opening Remarks

Streamlining Ligase Ligand Discovery & Optimization through Advanced Screening Platforms to Accelerate Hit Generation

9:00 am Utilizing DEL-ML & ASMS Screening Platforms for Small-Molecule Hit Identification Targeting E3 Ligases

  • Levon Halabelian Principal Investigator & Assistant Professor, University of Toronto & Structural Genomics Consortium

Synopsis

  • Employing affinity-based screening technologies to discover novel E3 ligase handles
  • Leveraging structural biology and biophysical tools to validate and optimize the identified hits
  • Designing heterobifunctional degraders with the identified hits and assessing their activities in cells

9:30 am Panel Discussion: Addressing Current Challenges in Ligand Screening & Strategizing the Next- Generation of Discovery Platforms to Overcome Data & Capacity Constrains

  • Oscar Huang Associate Director, Biophysics, Lyterian Therapeutics
  • Peter Gareiss Research Investigator, Arvinas, Inc.
  • Marc Scanio Principal Research Scientist, Abbvie
  • Dalia Barsyte-Lovejoy Principal Investigator & Professor, University of Toronto & Structural Genomics Consortium

Synopsis

  • How to face ligand screening in the absence of an active construct after purification?
  • What are the next generation of ligand discovery platforms? Biochemical versus cell-based assays
  • What challenges do we need to overcome to de-risk these?
  • Should we pursue covalent or non-covalent interactors?

10:30 am Discovery & Optimization of Ligands for a Tissue-Restricted Ligase

Synopsis

  • How to identify suitable chemical matter starting points from screens for ligase binders?
  • What are the desired chemical features for ligase binding and activity?
  • How to streamline the iterative synthesis and testing of ligand analogs?

11:00 am Building a DEL-Driven Discovery Pipeline for More Efficient Access to E3 Ligase Binders for Degrader Development

Synopsis

  • Using a ligand-first approach to speed access to more ligase binders
  • Employing multiple orthoganol methods to survey and confirm novel ligase ligands
  • High-throughput degrader discovery platform enables identification of multiple novel E3 ligase effectors

11:30 am Morning Networking Break & Scientific Poster Session

Expanding the Therapeutic Utility of CRBN, VHL & KLHDC2 to Overcome the Validation Bottlenecks of Alternative Ligases

12:30 pm Discovery of KLHDC2-Based PROTAC® Degraders

Synopsis

  • Development of KLHDC2 small molecule ligands
  • Investigation of KLHDC2 structure and mechanism
  • Utilization of KLHDC2 ligands for PROTAC mediated degradation

1:00 pm Pioneering the Developing of a Novel VHL Recruiter Displaying Improved Safety & Efficacy Using the PRISM™ Platform

  • Bradlee Heckmann Scientific Co-founder & Chief Scientific Officer, ASHA therapeutics

Synopsis

  • Leveraging breakthrough drug design technology in the PRISM™ Platform to rapidly design novel chemical technologies and clinic-ready medicines.
  • Development of a novel VHL recruiter for TPD
  • Expansion of the ligase recruiter landscape with novel tissue, cell, and cell compartment specific E3 recruiters

1:30 pm Networking Lunch Break

Exploring the Versatility of E3 Ligases in Mediating Non-Degrading & Degrading Functions to Offer Novel Opportunities for Therapeutic Intervention

2:30 pm Roundtable Discussion: Discussing the Utility of Activating or Inactivating Ligases to Strategize a Novel Class of Modulating Drugs

Synopsis

What is the current progress in identifying inactivating/activating ligases?

What are biggest bottlenecks preventing the progression of inactivating/activating ligases?

What is the clinical perspective on the development of activating or inactivating ligases?

3:30 pm Understand the Antagonism & Synergism Between Ligases & Deubiquitinases to Tackle Challenging Ligase Indications

  • Yongli Shan Associate Director- Discovery Biology, Vicinitas Therapeutics

Synopsis

  • How do E3 ligases and ubiquitinates achieve a balance between degradation and stabilization?
  • Apart from PROTAC, what are the other modalities of induced proximity in the ligasetarget-DUB complex?
  • Further strategies for tackling challenging ligase indications and for what diseases or therapeutic modalities?

4:00 pm Chair’s Closing Remarks & End of 4th Ligase Targeting Drug Development Summit 2024