8:50 am Chair’s Opening Remarks

New Technologies to Discover Novel E3 Ligases Continued

9:00 am Presenting a Chemoproteomic Platform for Identifying Covalent Small Molecule Ligands of Novel E3 Ligases

  • PING CAO CEO, BridGene Biosciences Inc.

Synopsis

  • Harnessing the unique advantages of covalent small molecule ligands of E3 ligases
  • Showcasing how IMTAC-screening can quickly identify covalent small molecule ligands of novel E3 ligases in a live cell screening
  • Demonstrating effective covalent ligand identified by IMTAC using an established ligase assay

9:30 am Measuring the Tractability of E3 Ligases for Informed Drug Discovery

Synopsis

  • Discussing the tractability of different ligase classes and how this will impact downstream drug development
  • Recruiting new substrates to ‘hijack’ an E3 ligase with a small molecule with views towards degradation
  • Weighing up whether a BRD4 model system is the best model system moving forward

Validation & Optimization

Diving Deeper Into the 600+ Known Ligases, Do We Need to Know More?

10:00 am PANEL DISCUSSION: Beyond CRBN – Enrichment of PK Optimized E3 Ligase Recruiters for TPD

Synopsis

  • Developing of targeted small molecule libraries against multiple high-value E3 ligases with Asha’s PRISM platform
  • Exploring the use of these novel E3 ligase recruiters in Asha drug discovery pipeline for beta Catenin, KRAS, and MEK
  • Spotlighting a novel, non-peptide, PK optimized, small molecule for VHL and uses beyond oncology

10:30 am Morning Break & Poster Session

11:30 am What More Can We Get Out of the Established Ligases, Cereblon & VHL

Synopsis

  • How do we propel VHL from an ‘academic’ ligase to a viable clinical alternative to CRBN?
  • Are there lessons to be learned from years of CRBN work that can be applied to future novel e3 ligase discovery and development?

12:00 pm Examining the Molecular Basis for Recognition of the Degrons by Novel E3 Ligases

  • Cheng Dong Principal Investigator, Tianjin Medical University General Hospital

Synopsis

  • Uncovering the E3 ligases that promote ubiquitin change and modifications that are not directing targets to the proteome
  • Characterizing the biology in non-integrative processes and E3s that do not direct localization of substrates

Utilizing the Role of Tissue-Tumor & Cell Type-Specific Ligases

12:30 pm PANEL DISCUSSION: Tissue & Cell Selectivity – Debating the Potential for Selective E3 Targeting

  • David Duda Senior Scientist, Janssen Global Services, LLC
  • Kwok-Ho Chan Senior Scientist, GlaxoSmithKline Plc
  • Suresh Kumar Senior Director & Head Of Drug Discovery, Progenra Inc

Synopsis

  • What is the hurdle to targeting E3s specifically in tumor cells and tissue types?
  • How can specific degradation be induced within a specific tissue type, limiting off-target effects?
  • What is the importance and use of expression data for our understanding and insight to develop tissue and cell-specific E3 therapeutic?

1:15 pm Networking Lunch

2:15 pm Showcasing a Rational Approach to Tissue-Specific E3 Ligase Discovery

  • Suresh Kumar Senior Director & Head Of Drug Discovery, Progenra Inc

Synopsis

  • Outlining the current limitations in available technologies to explore and identify tissue and cell-specific ligases
  • Presenting an example of useful omic data showing ligase tissue specificity
  • Selecting the correct ligand for cell-specific studies when little is known about the endogenous ligand

2:45 pm Identifying Novel E3 Ligases for Targeted Protein Degradation

Synopsis

  • Examining considerations of E3 ligase selection for targeted protein degradation
  • Using small molecule-induced proximity to assess E3 ligase activity
  • Debating the current limitations in technologies to explore tissue and cell-specific ligases

Investigating Rational Design & Exploring Future Potential of E3 Ligases

3:15 pm Highlighting an Approach to Uncovering a Novel E3 Ligase to Bolster your Ligase Discovery Pipeline

Synopsis

  • Reviewing the structural biology of the novel ligase
  • Elucidating the novel ligase mode of action
  • Outlining opportunities for translation to the clinic

3:45 pm Afternoon Networking Break

4:15 pm Mapping E3 – Leveraging Target Protein Interactions to Guide Molecular Glue Discovery

  • Randolph Lopez Co-Founder & Chief Technology Officer, A-Alpha Bio Inc.

Synopsis

  • Measuring interactions between E3 ubiquitin ligases and targets of interest in the absence of any small molecule to find pairs that bind weakly
  • Generating E3 ligase/target binding data with AlphaSeq, a synthetic biology platform that utilizes yeast display for high-throughput and highly sensitive measurements of up to millions of protein-protein interactions
  • Showcasing data that provide significant insights into the glueability of novel interactions between E3 ligases and high-value therapeutic targets

4:45 pm Chair’s Closing Remarks

5:00 pm End of Conference

All times in EDT