Conference Day One

   **All times in EDT**

8:30 am Registration & Chair’s Opening Remarks

  • Jeff McKenna Associate Director, Global Discovery Chemistry, Novartis Institutes for BioMedical Research

Optimizing Discovery, Selection & Validation of E3 Ubiquitin Ligases

9:00 am Reimagining Druggability Using Chemoproteomic Platform

  • Daniel Nomura Professor of Chemistry, University of California, Berkeley

Synopsis

  • Using chemoproteomic platforms to expand the scope of targeted protein degradation
  • Using chemoproteomic platforms to develop next-generation induced proximity-based therapeutic modalities

9:25 am Drugging Tissue selective E3 ligases

9:50 am Arvinas’ PROTAC® Discovery Engine: Selecting & Employing E3s for PROTACs

  • Miklos Bekes Senior Research Investigator & Group Leader in Platform Biology, Arvinas

Synopsis

  • Overview of Arvinas’ PROTAC portfolio
  • Overview of Arvinas’ PROTAC Discovery Engine platform
  • Employing E3 ligases at Arvinas

10:15 am A Best In-Class Method to Quantify Target Engagement and Cellular Entry for PROTACs

Synopsis

  • Target engagement and cellular entry are potential limiters to efficacy for E3 Ligase ligands and PROTACs
  • We will present a NanoBRET™ Target Engagement based workflow to quantitatively assess cellular entry for un-derivatized E3 ligase ligands and PROTACs
  • We will present applications of this workflow to the study of model ligands and PROTACs and demonstrate its utility within the broader degradation toolbox

10:40 am Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Jeff McKenna Associate Director, Global Discovery Chemistry, Novartis Institutes for BioMedical Research
  • Daniel Nomura Professor of Chemistry, University of California, Berkeley
  • Chris De Savi Vice President, Head of Drug Discovery, Kymera
  • Miklos Bekes Senior Research Investigator & Group Leader in Platform Biology, Arvinas

11:00 am

Morning Break & Speed Networking

Revealing Powerful Tools & Strategies for the Discovery of Novel E3’s & Effective Ligands

12:00 pm Unlocking the Ligandable Space with Ligase-centric PROTEINi Screening

Synopsis

  • E3 ligases are a rich and under-exploited space for therapeutic ligand development
  • We use our proprietary PROTEINi approach in an ultra-high throughput pooled phenotypic screening platform, exploiting high-diversity programmable drug mimetics
  • Systematic application of these tools to ligand discovery has yielded a substantial cache of novel E3 ligase binders and peptide-based degraders which have been deployed to degrade key therapeutic targets

12:25 pm Discovery of Novel Ligands & Probes for E3 Ligases

Synopsis

  • Chemical tools facilitate a better understanding of basic biology and therapeutic utility of E3 ligases
  • Discussing new opportunities in understudied E3 complexes from novel E3 ligands

12:50 pm A Strategy to Assess the Cellular Activity of E3 Ligases Against Neo-Substrates Using Electrophilic Probes

  • Benika Pinch Principal Scientist, Novartis Institutes for Biomed Research, Inc

Synopsis

  • Chemical biology method to evaluate E3 ligases in cells for neosubstrate degradation
  • Maleimide-thiol chemistry for Covalent Functionalization Followed by E3 Electroporation into live cells (COFFEE)
  • Discovery of new E3 ligases amenable for targeted protein degradation

1:15 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Jeff McKenna Associate Director, Global Discovery Chemistry, Novartis Institutes for BioMedical Research
  • Benedict Cross Chief Technology Officer, PhoreMost Ltd
  • Benika Pinch Principal Scientist, Novartis Institutes for Biomed Research, Inc
  • Alex Bullock Associate Professor, University of Oxford, Centre for Medicines Discovery
  • Dalia Barsyte-Lovejoy Principal Investigator, Structural Genomics Consortium

1:30 pm

Lunch Break & Networking

Reviewing & Characterizing E3’s to Harness the Full Potential of Effective & Selective Degradation

2:30 pm Computational Methods for Degrader Ternary Complex Prediction using HDX Data

Synopsis

  • Recent crystal structures of degraders in ternary complexes highlight the flexibility of a ligase to accommodate different targets
  • Computational modelling methods often struggle to identify the biologically relevant ternary complex
  • Experimental derived data can be used to constrain models and support rational optimisation of degraders

2:55 pm Mapping the Degradable Kinome

Synopsis

  • Provide unique chemical leads and chemo-proteomic data for over >200 protein kinases
  • Quantified cellular and chemical variables on TPD
  • Built a growing open access resource for chemo-proteomics data

3:20 pm Tissue-Specific Ubiquitin Ligases for Targeted Protein Degradation

  • Ryan Potts Executive Director & Head of IPP, Amgen

Synopsis

  • Targeted protein degradation (TPD) is an exciting new drug modality to unlock the undruggable genome
  • Degradation of target proteins of interest in select tissues will enable broader applications for TPD
  • Tissue-specific E3 ubiquitin ligases offer an opportunity for selective target degradation

3:45 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Jeff McKenna Associate Director, Global Discovery Chemistry, Novartis Institutes for BioMedical Research
  • Joe Patel Senior Director, C4 Therapeutics
  • Katherine Donovan Senior Scientist, Dana-Faber Cancer Institute
  • Ryan Potts Executive Director & Head of IPP, Amgen

4:00 pm

Afternoon Break & Networking

Characterizing Suitable Ligases for Rational Optimization of for PROTAC Degraders

4:30 pm Virtual Reality in SBDD: Exploring Complexes of the IMiDs and DDB1-CRBN E3 Ubiquitin Ligase in Nanome

Synopsis

  • Understanding Nanome’s intuitive, state-of-the-art Virtual Reality ((VR) platform for viewing, manipulating, and modifying chemical and macromolecular structures in a fully immersive and collaborative 3D environment
  • Examining the X-Ray structures (pdb ID’s: 4CI1, 4CI2, and 6H0F) of three related immunomodulatory drugs: thalidomide, lenalidomide, and pomalidomide in complex with DDB1-cereblon E3 ubiquitin ligase in VR
  • Allowing a team of drug discovery scientists to view and interact with the protein degrader complexes in real time, fostering novel collaboration, ideas, and discoveries

4:55 pm New Insights into PROTAC-based Target Validation Strategies

  • Rebecca Feltham Laboratory Head, The Walter and Eliza Hall Institute of Medical Research

Synopsis

  • Discussing new insights in target validation (dTAG technologies) to assess the therapeutic potential of targeting unwanted proteins for the
    treatment of disease
  • Exploring new dTAG strategies to target proteins using protein degrader technology
  • Sharing new insights into target validation by modelling the systems in vivo

5:20 pm Benchmarking Selection & Design of New E3 Ligases for PROTACS

  • Rick Davies Associate Director, AstraZeneca Pharmaceuticals

Synopsis

  • Discussing key attributes of E3 Ligases for PROTACS and potential selection studies
  • Exploring a cascade design for E3 selection and warhead identification
  • Elaborating on selective case studies

5:45 pm Effectively Harnessing E3’s for Rapid PROTAC Development

Synopsis

  • Discussing how Progenra’s UbiProTM platform has been employed to discover and characterize E3 ligands
  • Characterizing E3 ligands which are suitable for PROTAC applications
  • Elaborate on the unique approach to the discovery, optimization, and characterization of novel E3 ligands in vitro and in vivo.
  • Exploring specific examples of applying these novel ligands for generating PROTACs for degrading undruggable targets

6:10 pm Live Panel Q&A – Ask the Speakers Your Burning Questions!

  • Jeff McKenna Associate Director, Global Discovery Chemistry, Novartis Institutes for BioMedical Research
  • Rick Davies Associate Director, AstraZeneca Pharmaceuticals
  • Rebecca Feltham Laboratory Head, The Walter and Eliza Hall Institute of Medical Research
  • Kumar Suresh Senior Director R&D, Progenra Inc

6:30 pm Chair’s Closing Remarks & End of Day One