Post-Conference Focus Day
Next Generation TPD | Thursday November 2, 2023
7:00 am Registration & Morning Coffee
8:15 am Chair’s Opening Remarks
Exploring Next Generation ‘TACs: A New Paradigm
8:30 am Harnessing Deubiquitinases (DUBs) as a Novel Therapeutic Modality
Synopsis
- Identifying high impact targets for targeted deubiquitination therapeutics (TDT)
- Deploying novel ligands for DUB recruitment
- Novel insights into TDT and RESTORAC development
9:00 am Development of Caspase Cleavage Targeting Chimeras (CACTACs) for Targeted Protein Cleavage
Synopsis
- Showcasing CAspase Cleavage TArgeting Chimeras (CACTACs), bivalent molecules that hijack a caspase to destroy the target protein
- Demonstrating how Caspases can act directly on the target protein and the cleaved protein will immediately and irreversibly lose its function before subsequent disposal by cells
- Developing CACTACs that target oncoproteins and could potentially serve as cancer therapies
9:30 am mRNA medicines for Protein Modulation – Targeted Protein Degradation
Synopsis
- Leveraging AI/ML for programmable, modular therapeutic design
- Ubiquibodies (otherwise known as bio-protacs) for targeted protein degradation
- Design for compartment specificity
10:00 am Morning Break & Networking
Expanding the Scope of TPD by Leveraging the Ability to Degrade Extracellularly
11:00 am Heterobifunctional Molecules That Induce Targeted Degradation of Extracellular Proteins Through the Cell-Surface Asialoglycoprotein Receptor
Synopsis
- Clinically validating targeted intracellular protein degradation using the ubiquitin-proteasome system (UPS) motivated us to expand degradation approaches to extracellular proteins using a non-UPS pathway
- Harnessing the natural ASGPR pathway to access the endolysosome of hepatocytes for protein degradation. Heterobifunctional molecules (ASGPR-Targeting Chimeras or ATACs) recruit target proteins of interest through their extracellular domain while interacting with ASGPR for internalization and lysosomal degradation
- Describing the functionality of novel ATAC degraders that leverage Avilar’s proprietary, high-affinity ASGPR-binding ligands
11:30 am Harnessing Extracellular Degradation to Defeat Disease
Synopsis
- Highlight EpiBiologics strategy and platform for degrading extracellular targets
- Discuss process for target selection and pairing of targets with optimal degraders
- Disclose proof of concept data demonstrating that EpiBiologics platforms can drive degradation of extracellular targets
12:00 pm Targeting circulating IgG for the Treatment of Autoimmune Disease
Synopsis
Introducing the concept of extracellular protein degradation and highlighting its idiosyncrasy and potential advantages over other approaches with the focus on Biohaven Pharmaceuticals’ ASGPR based degradation.
- Uncovering IgG degradation in discovery and preclinical studies – progression of a development candidate towards IND
- Considering what else can be done; Targets, indications, applications
12:30 pm Lunch & Networking
The Beyond Oncology Perspective: Targeted Protein Degradation in Agriculture & Virology
1:30 pm Opportunities to Apply Targeted Protein Degradation as an Antiviral Strategy
Synopsis
- Exploring a paradigm for successful antiviral therapy involves the use of direct-acting antivirals that generally suffer from narrow spectrum activity and rapid evolution of resistance when these agents are used as monotherapies
- Developing antivirals that may better address the genetic diversity across a viral species or multiple species and also more resilient to point mutations that reduce drug-binding
- For “undruggable” viral proteins, the development of bivalent degraders (PROTACs) may be a more tractable process than development of functional inhibitors
2:00 pm Towards a TPD for Thirsty Plants Through AI Intervention
Synopsis
- Achieving chemical control of drought tolerance with small molecules; why a TPD?
- Implementing an AI driven approach and outlining benefits from AI (in vitro and in vivo results)
- Exploring future steps for harnessing TPD to alter plant traits
2:30 pm Oerth Bio’s Attune™ Platform: Delivering on the Promise of TPD in Agriculture
Synopsis
- Realizing the promise of TPD in agriculture for crop protection and crop efficiency
- Showcasing the Oerth Bio’s Attune™ platform to unlock potency, selectivity, and tunability of TPD in agriculture
- Disclosing exciting recent results from the field
3:00 pm Afternoon Break
3:30 pm Development of Novel Therapeutics via Stabilization of 14-3-3: Client Protein Protein Interactions
Synopsis
- Regulating the activity of phosphorylated client proteins, many of which are “undruggable”, through 14-3-3, a ubiquitously expressed hub protein
- Binding exclusively to disordered regions of these clients creating an ordered binary complex which can be targeted by small molecule stabilizers
- Developing small molecule therapeutics that bind the composite 14-3-3:client protein surface to drug the undruggable
4:00 pm Protein Homeostasis by Dual Precision Approach: TPD2 – Dual Precision Targeted Protein Degradation
Synopsis
- Exploring how to harness conjugates in TPD
- Highlighting the relevant ADME characteristics for conjugates
- Pinpointing the indications where this modality could be best-in-class / first-in-class
4:30 pm Uncovering Cancer-Associated Epigenetic Events Using Novel Chemical Tools
Synopsis
- Developing and applying new chemical tools to uncover epigenetic events that regulate cell fate
- Identifying a new E3 ligase that regulates histone ubiquitination and chromatin state in colorectal cancer
- Revealing new epigenetic vulnerabilities in chromosomal instability events in cancer
5:00 pm Chair’s Closing Remarks & End of 6th Targeted Protein Degradation Summit 2023
