*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 in Oncology & Neuroscience

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

13:30 Enabling High-Affinity Targeting of E3 Ligases to Induce Selective Degradation

Chairperson: Kevin Foley, Chief Scientific Officer, Ranok Therapeutics

13:30 Ensuring Selectivity & Target Engagement of PROTAC-based Approaches

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

13:30 Advancing the Protein Degradation Landscape Towards Clinical Success

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

The Potential of BioNMR to Assist Discovery and Optimization of Targeted Protein Degraders

  • Structural information on the interactions among the target protein, TPD, and E3 is valuable for guiding optimization of the affinity and selectivity
  • BioNMR can provide this structural information, and is complementary to x-ray crystallography
  • Using 15N- and 13C-labeling of components, NMR can determine regions of contact
  • NMR can also yield the conformation of the linker segment of the bound TPD

David Fry, Distinguished Research Leader, NJ Biopharmaceuticals

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

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

Stewart Fisher, Chief Scientific Officer, C4 Therapeutics

14:00 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

14:00 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

14:00 Session Details to be Confirmed

Arthur Sands, Chief Executive Officer, Nurix Therapeutics

14:30 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 Researcg & Development, LifeSensors

14:30 Reserved for Sponsored Talk 

Please get in touch with sponsor@hansonwade.com to enquire about speaking opportunities.

14:30 Reserved for Sponsored Talk 

Please get in touch with sponsor@hansonwade.com to enquire about speaking opportunities.

14:45 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

 

14:45 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

14:45 Targeting the Ubiquitin System for Therapeutic Benefit

  • Presenting examples of two novel degraders
  • Both degraders have demonstrated in vivo tumor growth inhibition - one of which is in clinical trials
  • The basic science elucidating the cellular mechanisms that lead to target inactivation and degradation will be discussed

Ingrid Wertz, Principal Scientist & Project Team Lead, Genentech

3:15 pm Virtual Poster Session

16:00 Harnessing Novel Platforms to Discover Identify New Targets & Ligands

16:00 Enabling Orally Bioavailable, Potent & Selective Protein Degrader Design

16:00 Overcoming Pre-Clinical & Translational Hurdles to Advance Degrader Development

Computational Evaluation of PROTAC-Mediated Protein Degradation: Recent Developments and Case Studies

  • Recent improvements to our computational methodologies for predicting ternary complex structures will be discussed
  • In addition to methodological improvements, particular attention is given to clustering generated ensembles of ternary complexes, affording more accurate predictions when validated against known crystal structures
  • The improved success of these new in silico approaches will be demonstrated via multiple retrospective case studies, encompassing different protein targets, E3 ligases, and PROTAC characteristics

Michael Drummond, Scientific Applications Manager, Chemical Computing Group

Design of Oral Bifunctional Degraders: Lessons Learned and Future Considerations

  • One key challenge with PROTACs is oral absorption as these molecules typically exhibit molecular weights and other properties well beyond typical rule-of-5 (Ro5) compliant drug-like chemical space
  • Presenting an analysis of a range of orally bioavailable PROTACs and discuss some key design guidelines that can be applied to overcome the challenge of oral absorption in this unique chemical space
  • These analyses and guiding principles will enhance and accelerate the development of orally bioavailable PROTACs and other heterobifunctional molecules

Scott Edmondson, Director & Head of Boston Oncology Chemistry, AstraZeneca

 

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

16:30 Session Details to be Confirmed

Gwenn Hansen, Senior Vice President of Research, Nurix Therapeutics

16:30 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

16:30 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

17:00 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

 

17:00 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

17:00 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, Assistant Professor of Biochemistry, UT Southwestern Medical Center

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