Conference Day Two

* Please note that the following agenda timings are EDT *

For PDT, please download the full event guide here

08:00 am | Morning Networking Coffee

8:20 am Chair’s Opening Remarks

  • Ingrid E. Wertz Scientific Executive Director, Protein Homeostasis Center of Excellence, Bristol Myers Squibb

8:30 am Targeted Protein Degraders: Design, Optimization & Chemistry Innovation

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

Synopsis

  • Optimizing PROTACs by stabilizing the ternary complex
  • Optimizing PROTACs by improving cell permeability
  • Trivalent PROTACs expand the chemical degrader space beyond molecular glues and bifunctional molecules, and can act as “super-glues”

9:00 am Discovery & Characterization of Molecular Glue Degraders

Synopsis

  • Identification of molecular glues via different phenotypic assays
  • Integration with multi-omics target-identification platform
  • Predicting and overcoming resistance mechanisms

9:30 am Panel Discussion: Expanding Diversity & Inclusion in Targeted Protein Degradation Field

Synopsis

This panel discussion is designed to bring value to all leaders in healthcare looking to unlock the potential of their team, career and business. Through tapping into multiple diverse perspectives and experiences we can accelerate innovation and drive progress in the field. Join this conversation to support gender equality and diversity in the TPD field.

Tech Slam: Hear An Exclusive Update of the Latest Technology Available to You to Support Your Efforts in 2021 & Beyond

10:15 am

Refeyn (002)

10:25 am

MERCK_MSIG_RRed_RGB-1

10:35 am

Life-Sensors

10:45 am

Untitled design (3)

10:55 am

Bio-Techne-Logo

11:05 am | Morning Networking Break

Accelerating Discovery & Emerging Strategies

Optimizing AI & Computational Modelling to Find Novel Ligases

Chairperson:

11:30 am Utilizing Covalent Chemistry to Validate New E3 Ligases for Targeted Degradation

Synopsis

  • Overview of Vividion’s chemoproteomic platform for the discovery of new drug targets
  • Our approach for targeted protein degradation and the discovery of covalent ligands for enabling new E3 ligases
  • In vitro and in vivo data supporting the use of a covalent Cullin-based degrader against AR

12:00 pm Large-Scale Chemoproteomic Profiling Surveys the Degradable Proteome for Accelerated Degrader Development

Synopsis

  • Comprehensive top-down degrader synthesis strategy and chemoproteomic profiling provides target mapping and unique chemical leads for new proteins.
  • Quantified cellular and chemical variables that impact TPD
  • Built a growing open access resource for chemoproteomics data

Optimizing Drug Design & Pre-Clinical Validation

Analyzing Resistance Mechanisms to Inform Next Generation Drug Design

11:30 am Tumor-Targeted Protein Degradation Mediated by Cellular Chaperones

  • Kevin Foley Chief Scientific Officer, Ranok Therapeutics

Synopsis

  • Chaperones can direct not only the correct folding of proteins, but also their degradation via the ubiquitinproteasome system
  • Chemically inducing proximity between a drug target and the cellular chaperone machinery results in its degradation, which is mediated by the numerous E3 ligases associated with chaperone complexes
  • Chaperone-mediated protein degradation (CHAMP™) has a number of advantages over other TPD approaches, including the evasion of mechanisms of drug resistance and an improved safety margin due to selective drug accumulation in tumor tissues

12:00 pm New Opportunities in Targeting Cancer Resistance Mechanisms with TPD

Synopsis

  • Different mechanisms of cancer resistance
  • Intervention in cancer resistance with TPD
  • Case study

Alternative Approaches & Applications of Degradation

Future Directions of PROTACs & Novel Degrading Mechanisms

Chairperson:

11:30 am SARS-CoV-2 Pandemic will be Overcome by PROTAC Drugs

Synopsis

  • Potent and selective PROTAC drugs block viral growth. Can SARS-CoV-2 targeted PROTACs be successful in clinic?
  • Traditional mono-antiviral therapy has not been successful due to poor efficacy and emergence of resistance. Drugs that targeted viral protein for ubiquitin E3 ligase mediated degradation can eliminate the viral protein and prove to be highly efficacious
  • Progenra has targeted SARS-CoV-2 viral proteins with PROTAC drugs. Potent and selective PROTACs degrade viral proteins in cells and block viral growth. Discovery and development of PROTAC drugs that target SARS-CoV-2 will be discussed

12:00 pm Discovery & Development of Targeted Protein Degraders for DDR Therapeutics by Screening Compound Libraries to Obtain Empirical 3D Information

Synopsis

  • TPD warhead discovery and development with a novel approach
  • Quick conversion of hits to leads
  • Application of the approach for novel oncology therapeutics

12:30 pm Rising Stars of Targeted Protein Degradation | In Exclusive Partnership with Kymera Therapeutics

Synopsis

Do you know a Post-Doc that is working on ground-breaking science?
Supporting the next generation of scientific and business leaders, we are inviting 3 budding pioneers of TPD to join the community to be exposed to the trail blazing developments in this space! With an opportunity to present a poster and meet with the TPD leaders, take advantage of this opportunity to drive the progress of the next generation of leaders.

1:00 pm | Networking Lunch & Scientific Poster Session

Leveraging Biochemical Properties of E3 Ligases & Linkerology to Improve Degrader Design

2:00 pm Discovery of a Degron for the Thalidomide Binding Domain of Cereblon

Synopsis

  • How can we use targeted protein degradation for biological discovery?
  • What are the implications of the degron on targeted protein degradation therapeutic strategies?
  • What can be learnt from cereblon biology that can be used to inform the selection of additional E3 ligases more effectively?

2:30 pm Rationally Designed New Linker Resulted in the Generation of the First BCL-XL & BCL-2 Dual Degrader

Synopsis

  • Computational modelling of the entire NEDD8-VHL Cullin RING E3 ubiquitin ligase (CRLVHL)/PROTAC/BCL-xL/UbcH5B(E2)-Ub/RBX1 complex defines the specific lysines on BCL-XL and BCL-2 accessible for ubiquitination by E2
  • Rationally designed new linker site on the warhead leads to the generation of the first BCL-XL and BCL-2 dual degrader by changing the accessibility of lysines on these proteins
  • The new BCL-XL and BCL-2 dual degrader has an improved anti-leukemic activity against leukemic cells that depend on both BCL-XL and BCL-2 for survival

Unveiling Preclinical Efficacy Data of Bifunctional Degraders

2:00 pm New Degrading Mechanisms to Move Beyond PROTACs

Synopsis

  • Highlighting the need for new degrading mechanisms to increase the reach of TPD approaches even further
  • Sharing new data on bifunctional degraders with improved profiles over PROTACs
  • Future directions for next generation TPD drug discovery

2:30 pm Discovery of a Highly Selective, IKZF-sparing Bruton’s Tyrosine Kinase Degraders (BTK-Degrader)

  • Christina Hebach Associate Director, ATI ; GPM (Autoimmune/Transplantation/Inflammation ; Global Project Management, Novartis Institute Biomedical Research

Synopsis

  • Discovery of a potent selective BTK degrader
  • Application of a novel CRBN binding motif sparing IKZF co-degradation
  • Striking in-vivo efficacy data in BTK dependent TMD8 xenograft model

Assessing New TACs & Artificial Proteins for Degradation

2:00 pm Optical Degradation of Proteins in Neuroscience

  • Dirk Trauner Professor of Chemistry and Neuroscience, New York University

Synopsis

  • PHOTACs are PROTACs with a light switch
  • They can be used to optically degrade key proteins in memory formation
  • PHOTACs extend the reach of Optogenetics, which has transformed neuroscience

2:30 pm Allosteric Inhibition of the 20S Proteasome

Synopsis

  • We show selective 20S proteasome regulation
  • Through allosteric regulation all three proteasome’s enzymatic activities are modulated
  • An artificial designed protein is capable of regulating the 20S proteasome

3:00 pm | Virtual Speed Networking

Expanding Protein Degradation Therapeutic Boundaries with Novel & Repurposed Targets

3:30 pm Discovery of IRAK4 & IRAK1 Degraders to Probe Scaffolding Functions in ABC DLBCL

  • Jennifer Venable Senior Scientific Director, Discovery Chemistry, Janssen Research & Development

Synopsis

  • Selective degraders of both IRAK4 and IRAK1 have been identified
  • Degraders of both IRAK isoforms were utilized to elucidate the kinase vs. scaffolding function roles in ABC DLBCL
  • IRAK1 degraders have therapeutical potential in treating ABC DLBCL and other malignancies driven by MYD88 mutations

4:00 pm TRKing Down an Old Oncogene in a New Era of Targeted Protein Degradation

Synopsis

  • What does the development of potent TRK fusion protein degraders look like?
  • How do you optimize physico-chemical properties for oral delivery?
  • Efficacy studies in TRK-driven xenograft models

4:30 pm Revisiting Old Targets with New Drug Discovery Modalities

Synopsis

  • In house case study on a previously abandoned oncology target
  • Introduce novel biology: Small molecule inhibitor vs PROTAC degrader
  • PROTAC PK evaluation in vitro and in vivo

5:00 pm Panel Discussion | What’s Next on the Horizon for Targeted Protein Degradation?

Synopsis

Over the last few years the TPD field has exploded. With more and more degraders heading into the clinic in 2021 than ever before, and with the significant rise of molecular glues, it is important to look at the big picture. During this final panel we will discuss: future directions, opportunities beyond inflammation, neurodegenerative and oncology, predicting future challenges, strategic decisions to progress the field towards the first approval, and the top priorities going into 2022 and beyond.

5:45 pm Chairs Closing Remarks & End of the 4th TPD Summit

  • Ingrid E. Wertz Scientific Executive Director, Protein Homeostasis Center of Excellence, Bristol Myers Squibb