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
8:30 am Targeted Protein Degraders: Design, Optimization & Chemistry Innovation
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 Advanced Cellular Screens for Degrader Discovery
Synopsis
- Identification of new molecular glues and PROTACs that reprogram a new, not yet hijacked, E3 ligase
- 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
Mass Photometry – Weighing Molecules with Light
- Introduction to mass photometry
- Applications of mass photometry, including its use in PROTACS experiments and analysis of biomolecular complexes.
Gael Nicolas, Sales and Applications Specialist, Refeyn
10:25 am
Duolink® Proximity Ligation Assay to Monitor the Protein Degradation Pathway
- Our Duolink® proximity ligation assay measures protein:protein interactions with high specificity and sensitivity using endogenous protein expression levels. This can be applied to the targeted protein degradation discovery workflow to validate E3 ligase tertiary complex formation, target ubiquitination and trafficking to the proteasome.
Josh Brettmann, Senior Scientist, Molecular Assays, MilliporeSigma
10:35 am
PROTAC® Drug Discovery: Bottlenecks & Solutions
- PROteolytic TArgeting Chimeras (PROTACs) have emerged as a new class of protein degrader drug that can target the “undruggable” proteome for novel therapeutics. Currently, PROTAC discovery is hampered by large gap in understanding link between ubiquitination and degradation, and current methods to quantify this process are of limited utility in drug discovery. We addressed these gaps utilizing Tandem Ubiquitin Binding Entities (TUBEs) in high throughput biochemical and cell based assays.
Karteek Kadimisetty, Director R&D, LifeSensors
10:45 am
PSCK9 Ligand-Induced Protein Degradation in Virtual Reality
Daniel Gruffat, Application Scientist, Nanome
10:55 am
Workflow Solutions for Degrader Development Programs
- Differentiated modalities require a differentiated toolbox of reagents, assays and platform technologies.
- An overview of the Bio-Techne product portfolio for Targeted Protein Degradation is presented, covering: target exploration and validation for TPD; degrader design and synthesis; assays for TPD; and tools for E3 ligase and ubiquitin proteasome system biology.
11:05 am | Morning Networking Break
Accelerating Discovery & Emerging Strategies
Optimizing AI & Computational Modelling to Find Novel Ligases
Chairperson:
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
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:
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 Development of Photo-Lenalidomide for Cellular Target Identification
Synopsis
- Photo-affinity labeling gives direct view of targets within a cell
- Development of chemical probes by structure activity relationship studies
- Discovery of new targets by chemical proteomics
2:30 pm Redefining drug discovery via immerging targeted protein degradation approach: Understanding biology of Protacs and beyond
Synopsis
- The differential biology offered by PROTACs
- The critical role of linker towards degradation efficiency and physico-chemical properties
- Protein-Protein Interactions are better predictors than affinity
- The journey of PROTACs & assessing their potency
- Syngene, a valued partner to accelerate the PROTAC discovery
- The future of targeted degradation (x-TACS)
3:00 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 Considerations for E3 Ligase Pairing and Screening of Immune-Inflammation Targets
Synopsis
- The Pegasus™ TPD platform allows the matching of target protein with appropriate E3 ligase based on expression, distribution, and biology
Broad E3 expression is not sufficient for equal potency across different cell types - Multiplexed flow screening in primary immune cells identifies differential degradation profiles based on E3 pairing
3:00 pm Discovery of a Highly Selective, IKZF-sparing Bruton’s Tyrosine Kinase Degraders (BTK-Degrader)
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
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 Rapid Characterization of Biologics on the Labchip GXII Touch System
Synopsis
Utilizing capillary gel electrophoresis (CGE) and capillary zone electrophoresis (CZE), PerkinElmer’s LabChip® GXII Touch™ Protein Characterization System provides characterization of proteins and nucleic acids in as little as 42 seconds per sample, delivering data comparable to other methods of quantitation with as much as 70x increase in throughput. The system can quickly measure yield, purity, titer, charge variation, and glycosylation of proteins.
3:00 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
3:30 pm | Virtual Speed Networking
Expanding Protein Degradation Therapeutic Boundaries with Novel & Repurposed Targets
4:00 pm Discovery of IRAK4 & IRAK1 Degraders to Probe Scaffolding Functions in ABC DLBCL
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
4:30 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
5:00 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
5:30 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.