*All times shown in EDT*

8:00 am Online Registration

8:50 am Chair’s Opening Remarks

  • James Tonra Chief Scientific Officer, BeyondSpring Pharmaceuticals

Keynote Plenary Session

9:00 am PROTACS: Entering the Third Decade of Targeted Protein Degradatio

  • Craig Crews John C. Malone Professor of MCDB, Chemistry & Pharmacology, Yale University

Synopsis

  • Historical perspective of the TPD field
  • Current challenges in the TPD field
  • Current efforts to address the ‘undrugged’ proteome

9:30 am Inducing Protein Degradation with Bifunctional Small Molecul

  • Alessio Ciulli Professor of Chemical & Structural Biology, University of Dundee

Synopsis

  • Recent years have seen a resurgence of interest in designing bifunctional molecules that serve as bridging agents to bring proteins together
  • Recruitment of target proteins to E3 ubiquitin ligases to induce protein degradation promises to significantly expand the range of tractable targets for chemical biology and therapeutic intervention
  • Pioneering structural and biophysical studies of the ternary complexes formed by these molecules highlight that proximity-induced de novo formation of protein–protein interactions is a general feature

10:00 am Cellular Mechanistic Profiling of Degradation Compounds

Synopsis

  • Several case studies to understand PROTAC mechanism of action in different systems
  • Correlation of real-time kinetic degradation profiles to ternary complex formation and ubiquitination
  • Cell-based assay strategies for rank ordering compound potency and efficacy

10:30 am Virtual Speed Networking

11:30 am The Promise of PROTAC® Protein Degraders: What’s Next for Arvinas’ Pipeline & Platform

Synopsis

  • Twenty years in: how far the field of protein degradation has come
  • The potential for protein degradation in neuroscience
  • Update on Arvinas’ clinical stage programs

12:00 pm Targeted Protein Degradation: Chemical Biology to Therapeutics

  • Jay Bradner President, Novartis Institutes for Biomedical Research

Synopsis

  • The increasingly atomic resolution of human biology presents an unprecedented opportunity for the innovation of definitive medicines for life-threatening diseases. Still, many well-defined, high-value protein targets remain “undruggable” – beyond the limits of historical efforts in ligand discovery
  • Discussing progress in the field of targeted protein degradation (TPD), inspired by natural products and advances in chemical-induced dimerization
  • Highlighting both foundational research as well as our recent, first all-chemical approach that establishes design principles for new ligands, demonstrates extensibility to numerous cellular targets, and informs mechanistic target validation and cellular biology
  • Lead optimization of chemical probes brings extraordinary (sub-nanomolar) potency, reveals catalyst-like activity, and now emanates first-in-class therapeutics
  • Discussing learnings from our TPD Initiative, including curious challenges, around which our ongoing research organizes

12:30 pm Lunch & Virtual Networking

Accelerating Discovery & Emerging Strategies

Optimizing Drug Design & Pre-Clinical Validation

Validation Robust Translation Towards Clinical Development

Enabling High-Affinity Targeting of E3 Ligases to Induce Selective Degradation

Chairperson: Kevin Foley, Chief Scientific Officer, Ranok Therapeutics

Ensuring Selectivity & Target Engagement of PROTAC-based Approaches

Chairperson: Matthias Wittwer, DMPK/PD Project Leader, Roche

Advancing the Protein Degradation Landscape Towards Clinical Success

Chairperson: Stephanos Ioannidis, Vice President & Head of Chemistry, H3 Biomedicine

13:30 Drugging the Undruggables with PROTACs

  • In addition to achieving exceedingly high potency and selectivity, the PROTAC approach can be used to drug those traditionally undruggable or difficult to drug proteins, including transcriptional factors
  • Presenting our research in employing the PROTAC strategy to drug those undruggable targets

Shaomeng Wang, Warner-Lambert/Parke-Davis Professor in Medicine; Director of Michigan Center for Therapeutic Innovation, University of Michigan

13:30 Computational Workflows for Bifunctional Degrader Design 

  • Presenting ongoing efforts at Schrödinger to develop computational workflows to address different design challenges of bifunctional degraders
  • Workflows include the conformational sampling of the isolated bifunctional degrader, the determination of the degrader exit vector, the prediction of the target-degrader-ligase ternary complexes and linker enumeration strategies
  • Preliminary method validation using available public crystal structures and highlights of their limitations

Agustina Rodriguez-Granillo, Principal Scientist II, Schrödinger

13:30 Targeted Protein Degraders: From Discovery to the Clinic

  • Quantitative SAR elements required for lead degrader optimization
  • Understanding the linkage of PKPD and efficacy
  • Molecular properties required for drug-like profiles

Rhamy Zeid, Director of Target Biology, C4 Therapeutics

13:50 Development of a Phenotypic Screen to Identify New E3 Ligases for Targeted Protein Degradation

  • Using HaloPROTACs to test E3 ligases
  • Establishing high throughput chemistry
  • Validation of a high throughput phenotypic screen

Markus Queisser, Scientific Leader, GlaxoSmithKline

13:50 Teaching an Old Dog New Tricks: Traditional Small Molecule Drug Discovery & Targeted Protein Degradation  

  • Introducing the industry to targeted protein degradation
  • Selected highlights from in-house projects
  • Exploring PROTAC selectivity – lessons learned from chemical proteomics

Phillip Cromm, Discovery Chemist, Bayer

13:50 Targeted Protein Modulation: Harnessing or Inhibiting E3 Ligases to Decrease or Increase Protein Levels

  • Advancing BTK degraders to the clinic for B cell malignancies
  • Advancing CBL-B E3 Ligase inhibitors to the clinic for immuno-oncology
  • Combining targeted protein modulation with adoptive cell therapy for cancer

Arthur Sands, Chief Executive Officer, Nurix Therapeutics

14:10 Overcoming Bottlenecks in PROTAC Drug Discovery

  • LifeSensors offers high-throughput screens for E3 ligases and PROTAC libraries. Services are customized for the scale and scope of your specific project. Our assays accelerate the discovery process of your next breakthrough
  • Hits are confirmed in selectivity panels as well as in high-throughput cell-based assays. The ubiquitylation of the target protein is the key step, we are equipped to monitor this dynamic process
  • Biomarkers are identified by TUBE-based mass spectrometry for preclinical and clinical studies

Karteek Kadimisetty, Assistant Director of Research & Development, LifeSensors

14:10 Degradation Sensation: A Life Science Perspective on the TPD Market

  • An emergent field in drug discovery yields an evolving commercial landscape
  • Outlook on the future degradation toolbox in life science research

Kaelyn Wilke, Senior Product Manager - Emerging Chemical Synthesis, MilliporeSigma

14:10 Exploring New Tools for Remote Collaborative Structure-Based Design

  • Session details to be confirmed

Steve McCloskey, Chief Executive Officer, Nanome

 

14:20 Toward Universal Druggability and Tissue-Selective Targeting Using TED-Helicons

  • Helicons make it possible to target ~60% of single-domain proteins and ~80% of all multidomain proteins with high-affinity, high-specificity drugs
  • Helicons make it possible to drug nearly all E3 ligases, and to obtain allosteric activators, null binders and substrate antagonists
  • Universal druggability and tissue-selective targeted degradation of ubiquitous targets are readily within sight using TED-Helicons

Greg Verdine, Chairman, President & Chief Executive Officer, Fog Pharma

 

14:20 Enhancing Intracellular Concentration and Target Engagement of PROTACs with Reversible Covalent Chemistry

  • How different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, may affect the degradation of a model protein Bruton’s Tyrosine Kinase (BTK)
  • Cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular concentration and target engagement of BTK PROTACs
  • This reversible covalent strategy can be generalized and applied to improve other PROTACs 

Jin Wang, Associate Professor, Baylor College of Medicine

14:20 Targeting the Ubiquitin System for Therapeutic Benefit

  • Presenting examples of heterobifunctional degraders in which both the ligase ligand and target ligand
    contribute to a therapeutic response having maximal efficacy
  • The intrinsic tumor cell biology, target degradation, and activation of tumor immunity all drive the therapeutic
    response
  • The basic science elucidating the interplay between these cellular effects will be discussed

Ingrid Wertz, Principal Scientist & Project Team Lead, Genentech

14:40 Discussion/Q&A

Moderator: Kevin Foley, Chief Scientific Officer, Ranok Therapeutics

  • Shaomeng Wang, Warner-Lambert/Parke-Davis Professor in Medicine; Director of Michigan Center for Therapeutic Innovation, University of Michigan
  • Markus Queisser, Scientific Leader, GlaxoSmithKline
  • Karteek Kadimisetty, Assistant Director of Research & Development, LifeSensors
  • Greg Verdine, Chairman, President & Chief Executive Officer, Fog Pharma

14:40 Discussion/Q&A

Moderator: Matthias Wittwer, DMPK/PD Project Leader, Roche

  • Agustina Rodriguez-Granillo, Principal Scientist II, Schrödinger
  • Philipp Cromm, Discovery Chemist, Bayer
  • Kaelyn Wilke, Senior Product Manager of Emerging Chemical Synthesis, Millipore Sigma
  • Jin Wang, Associate Professor, Baylor College of Medicine

14:40 Discussion/Q&A

Moderator: Stephanos Ioannidis, Vice President & Head of Chemistry, H3 Biomedicine

  • Rhamy Zeid, Director of Target Biology, C4 Therapeutics
  • Arthur Sands, Chief Executive Officer, Nurix Therapeutics
  • Ingrid Wertz, Principal Scientist and Project Team Lead, Genentech
  • Steve McCloskey, Chief Executive Officer, Nanome

3:10 pm Virtual Poster Session

Harnessing Novel Platforms to Discover Identify New Targets & Ligands

Enabling Orally Bioavailable, Potent & Selective Protein Degrader Design

Overcoming Pre-Clinical & Translational Hurdles to Advance Degrader Development

16:00 Targeting the Ubiquitin Pathway through Tissue-Specific Regulators

  • Ubiquitin ligases can be redirected to target new substrates for ubiquitination by endogenous, tissue-specific
    protein regulators, akin to small-molecule PROTACs
  • MAGE proteins are testis-specific ubiquitin ligase regulators that are upregulated in cancer and reprogram ligases towards new substrates to drive tumorigenesis
  • Discovery of small molecule regulators of MAGEs enable targeting the ubiquitin pathway specifically in cancer

Ryan Potts, Executive Director & Head of Induced Proximity Platform, Amgen

16:00 What Makes a Good PROTAC Target: Lessons Learned

  • PROTACs have the potential to inhibit previously intractable targets but also offer differentiated biology
    over traditional catalytic inhibitors
  • Showing examples of potent, selective degraders from our internal PROTAC projects, including BCL6 and MALT1
  • Presenting some of the challenges in achieving a differentiated phenotype over the small molecule inhibitor

Claire Crafter, Oncology Team Leader & Biology PROTAC Lead, AstraZeneca

 

16:00 PKPD Relationship of Targeted Protein Degradation: Connected or Disconnected?

  • PKPD disconnect has been associated with targeted protein degradation both in vitro and in vivo
  • Reviewing the key steps of targeted protein process in the cellular system as well as in vivo
  • Case study of translating PKPD from preclinical to clinical will be presented

Haojing Rong, Vice President of Pre-Clinical Development, Kymera Therapeutics

16:20 Next-Generation PROTAC Discovery with a Systematic Screening Engine

  • Small molecule PROTAC development is hampered by a low complexity matrix of E3 recruitment modules, and hindered by a high degree of substrate specificity
  • PhoreMost have developed SITESEEKER, an ultra-high throughput pooled phenotypic screening platform, exploiting high-diversity programmable drug mimetics
  • Systematic application of the SITESEEKER tools to PROTAC discovery has yielded a substantial cache of novel E3 ligase ligands and peptide-based PROTACs which have been deployed to degrade key therapeutic targets

Benedict Cross, Chief Technology Officer, PhoreMost

16:20 Targeted Protein Degradation for the Treatment of TRK Fusion-Driven Cancers

  • Development of potent and orally active TRK fusion protein degraders
  • Optimization of physico-chemical properties for DMPK
  • Efficacy studies in TRK-driven xenograft models

Michael Plewe, Vice President of Medicinal Chemistry, Cullgen

16:20 A First Glance at Resistance to Degraders

  • Resistance to BET degraders using CRBN or VHL ligands emerged from long term culture in the presence of these degraders
  • Resistance primarily caused by defect in the E3 complex
  • Cells resistant to CRBN degrader remained sensitive to VHL degraders and vice versa

Yu Shen, Director of Cancer Biology, AbbVie

16:40 Structural Characterization of BTK-PROTAC-cIAP Ternary Complexes - From Snapshots to Ensembles 

  • Presenting a crystal structure of a plastic ternary complex that reveals multiple achievable poses
  • Structure-based linker design generates a tightly formed ternary complex and a second novel crystal structure
  • Biophysical, biochemical, and computational techniques paint a picture of a dynamic E3-PROTAC-substrate ternary complex driven primarily the PROTAC linker

James Schiemer, Senior Scientist, Pfizer

 

16:40 Novel Small Molecule Degraders of Full Length and Splice Variant Androgen Receptors

  • Discovery and lead optimization of small molecule androgen receptor degraders
  • Identification of an alternate binding region in the N-terminus of the androgen receptor
  • Optimized molecules have unprecedented activity in animal models of advanced prostate cancer

Ramesh Narayanan, Associate Professor & Director of Center for Cancer Drug Discovery, University of Tennessee

16:40 Uncoupling of PARP1 trapping and Inhibition Using Selective PARP1 Degradation

  • Development of a highly potent and specific PARP1 degrader
  • Dissection of PARP1 trapping and PARP1 inhibition, and understanding their relative contribution in mediating the cytotoxic effects of PARP1 inhibitors
  • Utilization of the PARP1 degrader for the protection against cell death in various diseases beyond human malignancies

Yonghao Yu, Associate Professor of Biochemistry, UT Southwestern Medical Center

17:00 Discussion/Q&A

Moderator: Kevin Foley, Chief Scientific Officer, Ranok Therapeutics

  • Ryan Potts, Executive Director & Head of Induce Proximity Platform, Amgen
  • Benedict Cross, Chief Technology Officer, PhoreMost
  • James Schiemer, Senior Scientist, Pfizer

 

17:00 Discussion/Q&A

Moderator: Matthias Wittwer, DMPK/PD Project Leader, Roche

  • Claire Crafter, Oncology Team Leader & Biology PROTAC Lead, AstraZeneca
  • Michael Plewe, Vice President of Medicinal Chemistry, Cullgen
  • Ramesh Narayanan, Associate Professor & Director of Center for Cancer Drug Discovery, University of Tennessee

 

17:00 Discussion/Q&A

Moderator: Stephanos Ioannidis, Vice President & Head of Chemistry, H3 Biomedicine

  • Haojing Rong, Vice President of Pre-Clinical Development, Kymera Therapeutics
  • Yu Shen,Director of Cancer Biology, AbbVie
  • Yonghao Yu, Associate Professor of Biochemistry, UT Southwestern Medical Center

 

5:30 pm Chair’s Closing Remarks & End of Conference Day One