Pre-Conference Workshop Day
Tuesday, October 25
Our workshops are streamed so you are able to attend 3 out of 9 workshops. You can choose A, B or C followed by D, E or F, followed by G, H or I. Do you want to attend all of our workshops? Check out our group booking discounts so you can bring your colleagues!
Workshop A - 9:15 am
Structural Biology in Protein Degrader Discovery: Technology & 3D Atomic Insights
Structure-based drug discovery (SBDD) has proven to be faster, more efficient and cost-effective. 3D atomic
structures of drug targets and their complexes are essential to understand drug mechanism and to establish SAR for lead optimization. This is also true for protein degrader discovery. However, solving those 3D structures has been difficult and slow until atomic-resolution cryoEM (cryoelectron microscopy) came along.
Join this workshop to find out:
• How structural biology can help understand mechanisms
of protein degraders
• How 3D atomic details of interaction can help lead optimization
• What are the techniques to solve 3D atomic structures?
• Why cryoEM is the method of choice?
• What are the steps in cryoEM?
• How to get started and what to expect from cryoEM structures
• Case studies
Taosheng Chen, Director of High Throughput, Bioscience Center, St. Jude Children’s Research Hospital
Jack Yan, VP of cryoEM, Biortus
Larry Jin, Chief Operating Officer, Biortus
Workshop B - 9:15 am
Exploring Tissue Specific Protein Degradation
TPD approaches offer a wide array of opportunities for the tissue or cell-specific targeting of disease-causing proteins. Tissue-specific disease intervention could greatly broaden the number of proteins that can be targeted safely and efficaciously across many different therapeutic areas. This workshop will seek to highlight and discuss how different types of TPD approaches, such as Glues, PROTACs and LYTACs could each offer their own angles on cell or tissue specific protein targeting. We will also interrogate the specific advantages that may be presented within certain therapeutic areas such as degradation of targets specifically within the CNS and cancer essential E3 ligases that may offer opportunities for breaking resistance mechanism.
Join us to discuss:
• How could tissue specific E3 ligases help to broaden cancer target scope?
• What opportunities are there for CNS specific TPD?
• What opportunities are there for tissue specific protein degradation beyond E3 ligase recruitment?
William Farnaby, Principal Investigator, University of Dundee
Workshop C - 9:15 am
Targeting Pediatrics Cancer Dependent Proteins Through Small Molecule Degraders
In this workshop, we will explore the challenges as well as perspectives of using degraders as a novel therapeutic strategy for pediatric cancers.
Join us to discuss:
• How to identify the unique dependent genes in pediatric cancer to reduce the toxicity of degrader
• What are the mechanistic findings behind the target degradation in pediatric cancer?
• What is the advantages and challenges of using degraders for pediatric cancer?
• Key learnings on how toxicity is reduced in paediatric patients that could be translated to adults
• Understanding and addressing key challenges with treating paediatric brain tumours and revealing the why and how protein degradation could be a promising treatment option for this subset of patients
Jun Qi, Assistant Professor, Dana-Farber Cancer Institute
Mariella Filbin, Assistant Professor, Dana-Farber Cancer Institute, Harvard Medical School
11:15 am Morning Break & Refreshments
Workshop D - 12:15pm
Opportunistic Findings & Rational Discovery of Molecular Glues
Molecular glues, monovalent targeted protein degraders have historically been serendipitous in discovery. However, with the influx of more data and new technologies, rational drug discovery of MGDs is now a more achievable goal. In this workshop we will discuss the strategies of how to move from serendipity to rational design.
Join us to discuss the following topics and more:
• Historical overview and current state of the art of MGD discovery
• Principles underlying MGD mechanism of action
• Key technologies to identify MGDs and when/how to employ them
• Characterizing the neosubstrates of MGDs
Shanique Alabi, Scientist I, Monte Rosa Therapeutics
Helen Trinh Pham, Senior Scientist II, Monte Rosa Therapeutics
Workshop E - 12:15 pm
Optimizing Mechanistic Drivers of Potent Degraders
Join this workshop to discuss:
• How to optimize degraders in forward looking matter?
• Properties of optimal degrader and how to make optimization more rational?
• Theoretical framework for noncovalent and covalent degraders
• Assays to monitor target engagement and kinetics
• Assays to assess ternary complex formation
• Assays to quantify ubiquitination rates, and degradation kinetics
• What are the critical factors affecting catalytic efficiency and DC50, Dmax
Charu Chaudhry, Principal Scientist, Janssen R&D
Jin Wang, Professor, Baylor College of Medicine
Workshop F - 12:15 pm
Understanding preclinical species selection to accurately assess pharmacology and safety of targeted protein degraders
Choice of preclinical pharmacology or toxicology animal model is critical for successful translation of animal efficacy and safety data into the clinic. Species differences in pharmacological activity, selectivity and kinetics of PD effect of TPD molecules are all important components in the decision making.
Join this workshop to find out
• How pharmacological activity can look across species for molecular glues and PROTACs, and for different E3 ligases
• Methods for establishing selectivity of TPD molecules across species, and why does it matter?
• How does the rate of your favorite target degradation influences efficacy and safety, and how to probe it in preclinical studies?
• Case studies, examples of preclinical efficacy and safety programs for different types of TPD molecules
Natasa Zamurovic Ribrioux, Strategy & Portfolio Director - Pre-Clinical Safety & Translational Medicine, Novartis
Ammar Adam, Senior Director & Head of in-vivo Pharmacology, Foghorn Therapeutics
2:15 pm Lunch Break
Workshop G - 3:15 pm
Understanding E3 Ligase Biology to Find Novel E3 Ligase Ligands to Develop Novel Degraders
• What are the criteria for selecting E3s?
• What are the best linkers between the E3 Ligase and the warheads?
• Looking at the different screening strategies for E3s
• What has been learned so far when it comes to E3s?
• Understanding what stimuli turn on and off E3s?
• Predicting safety issues of new E3s
Jennifer Johnston, CEO, Nysbio
Workshop H - 3:15 pm
Novel Targeting of Cellular Machinery in Neurodegeneration
Asha’s PRISM™ platform of AI-driven discovery technology facilitates efficient drug design and development using computational assessment and ADMET characterization and correlation. PRISM™ uses novel physics-based computational methodology for accurate identification, assessment, and optimization of the most critical variables for UPS-directed protein degradation and has developed MITOPRISM™ technologies to safely and effectively drug mitochondrial targets.
Join us to discuss:
• What are the key challenges and opportunities of targeting mitochondria for degradation?
• How targeting mitochondria for degradation could be promising for neurodegenerative diseases
• What opportunities are there to target undruggable targets?
• What can be learnt from early degraders that can be applied to this technology?
• Assessing pre-clinical results of this exciting new modality
Sam Shrivastava, Founder & CEO, Asha Therapeutics
Workshop I - 3:15 pm
PROTACs in Clinical Oncology; Evaluating Protein Degraders in Hematologic Malignancies & Future Combination Considerations
• Degraders of pro-survival proteins BCL-XL and BCL-in hematologic malignancies.
• Pro-survival dependencies in different types of leukemia and lymphomas will be discussed; degraders vs small molecule inhibitors; safety vs efficacy
• BTK degraders in CLL
• Initial efficacy of single agent; degraders vs small molecule inhibitors; consideration of the future combination approaches
• BET protein PROTAC
• Promising pre-clinical activity in AML and T-ALL; targeting leukemia-initiating cells and tumor microenvironment; PROTACs vs BET inhibitors; future combinations
• PROTACS combined with standard chemotherapy and targeted therapy
• Multi-targeting PROTACs
• PROTACs conjugates: selective delivery to target cells
Marina Konopleva, Professor, Albert Einstein-Montefiore Cancer Center, NY