8:00 am Morning Coffee & Virtual Networking
8:55 am Chair’s Opening Remarks
Keynote Plenary Session
9:00 am Targeted Protein Degradation Beyond Oncology
Synopsis
- Advancing understanding and impact of TPD beyond existing E3 ligases
- What is needed to build programs beyond oncology
- IRAK4 degrader programs in immunology
9:30 am New Approaches to Degradation – Beyond the Usual Suspects
Synopsis
- First public disclosure of the Amphista platform using a completely novel range of mechanisms to degrade a wide range of disease-relevant proteins
- Mechanisms go beyond the usual E3 ligases utilized by most in the field and instead use other UPS proteins which offer new opportunities to expand the scope and utility of TPD strategies
- We will discuss how novel mechanisms have the potential to overcome current limitations with TPD strategies
10:00 am Efficient Degradation with Reversible Covalent PROTACs
Synopsis
• Demonstrating a proof-of-concept for reversible covalent cyanoacrylamide PROTACs
• Showing that for irreversible covalent PROTACS the interplay between covalent bond formation and degradation kinetics
determine degradation efficiency
• Presenting a new computational protocol for PROTAC ternary complex modelling that can enable more efficient design of PROTACs
10:30 am Virtual Speed Networking
Accelerating Discovery & Emerging Strategies
Optimizing Drug Design & Pre-Clinical Validation
Beyond UPS-mediated Degradation Strategies
Novel Discovery of E3 Ligases & Recruiters to Advance Molecular Glue Applications
Chairperson: Yonghao Yu, Associate Professor of Biochemistry, UT Southwestern Medical Center
Advancing Medicinal Chemistry Properties of Degraders to Optimize PKPD
Chairperson: Didier Berthelot, Principal Scientist, Janssen
Discovering the Capability of Autophagy as a Novel Path to Targeted Protein Degradation
Chairperson: Amine Sadok, Director of Biology, Monte Rosa Therapeutics
11:00 Reimagining Druggability Using Chemoproteomic Platforms
- Covalent ligand discovery against undruggable targets
- Discovery of new E3 ligase recruiters
- Discovery of new molecular glue scaffolds
Daniel Nomura, Professor of Chemistry, University of California, Berkeley
11:00 DMPK Optimization of Targeted Protein Degraders - Challenges & Strategies to Success
- Properties of targeted protein degraders fall outside the traditional small molecule property space and pose complex DMPK optimization challenges
- Presenting fundamental aspects of DMPK optimization of degraders
- Optimization challenges of degraders as well as methodologies and strategies to overcome these hurdles will be presented
Matthias Wittwer, DMPK/PD Project Leader, Roche
11:00 AUTACs: Autophagy-Mediated Degraders
- AUTACs regulate autophagy-mediated clearance of disease-related debris
- S-Guanylation is a standalone tag that destines substrate for selective autophagy
- Mito-AUTAC enhances mitochondria quality via removal of fragmented mitochondria
Hirokazu Arimoto, Professor, Tohoku University
11:20 Leveraging a Cereblon-Directed ‘Molecular Glue’ Library to Deliver on the Therapeutic Promise of TPD - from Immune Suppression to Immune-Oncology
- 'Phenotypic observation-to-target profile' platform utilized to discover novel immunosuppressive 'Molecular Glue' Protein Homeostatic Modulators (PHM-MGs)
- Development of first-in-class 'dual' PHM-MGs that possess both cytotoxic and immune-inducing activities
- Strategic integration of novel PHM-MGs into PROTAC design: optimization of the PROTAC’s target profile to further improve therapeutic efficacy
Frank Mercurio, Chief Scientific Officer, BioTheryx
11:20 Rapid PROTAC Development for Undruggable Targets
- Despite numerous efforts from industry and academia, PROTAC based drug development remains challenging
- The complex chemistry and molecular mechanism associated with PROTAC design and function pose additional challenges and demand innovative approaches
- Providing approaches to the development, optimization, and characterization of novel E3 ligand based PROTACs for degrading undruggable targets
Suresh Kumar, Senior Director of Research & Development, Progenra
11:20 Leveraging Chemoproteomics to Create a Novel AutoTAC Degrader Platform
- Chemoproteomics can be used to create ligands for key degrader targets
- Autophagic adaptors can be targeted to create AutoTACs
- AutoTACs may provide a novel path to targeted degradation
James Winkler, Head of Degrader Technology, Frontier Medicines
11:40 Discovery & Profiling of Molecular Glues to New E3 Ligases
- One approach to identification and verification of molecular glues to new E3 ligases illustrated with an example
- Method to map the full span of biology modulable by E3 ligase modulators illustrated with an example
- Advancing drug discovery programs from novel E3 molecular glues
Kandaswamy Vijayan, Chief Executive Officer, Plexium
11:40 Thalidomide Analogues and PROTACs for Hematologic Diseases
- Application of thalidomide analogues and PROTACs in multiple myeloma and other hematologic diseases
- Resistance mechanisms to thalidomide analogues and PROTACs
- Mouse models for thalidomide analogues and CRBN based PROTACs
Jan Krönke, Professor, Charité Berlin
11:40 Harnessing the Cell’s Degradation Machineries Nature’s Way to Manipulate Protein Stability
- The common underpinning basis of the cell’s proteostasis network is molecular recognition involving the specific interactions of proteins with one another
- The Polyproxin™ platform exploits our understanding of these interactions to harness proteostasis networks and thereby manipulate protein stability and disease outcome
- The platform comprises libraries of target-engagement modules and degradation-inducing modules in a mix-and-match format to identify the best combination for effective knockdown of the target
- The platform can thereby be directed to diverse targets and disease states by coopting the broadest range of degradation machineries including, but not limited to, the ubiquitin-proteasome system
Laura Itzhaki, Professor & Chief Scientific Officer, University of Cambridge, PolpProx Therapeutics
12:00 Discussion/Q&A
Moderator: Yonghao Yu, Associate Professor of Biochemistry, UT Southwestern Medical Center
- Daniel Nomura, Professor of Chemistry, University of California, Berkeley
- Frank Mercurio, Chief Scientific Officer, BioTheryx
- Kandaswamy Vijayan, Chief Executive Officer, Plexium
12:00 Discussion/Q&A
Moderator: Didier Berthelot, Principal Scientist, Janssen Pharmaceuticals
- Matthias Wittwer, DMPK/PD Project Leader, Roche
- Suresh Kumar, Senior Director of Research & Development, Progenra
- Jan Krönke, Professor, Charité Berlin
12:00 Discussion/Q&A
Moderator: Amine Sadok, Director of Biology, Monte Rosa Therapeutics
- Hirokazu Arimoto, Professor, Tohoku University
- James Winkler, Head of Degrader Technology, Frontier Medicines
- Laura Itzhaki, Professor & Chief Scientific Officer, University of Cambridge, PolyProx Therapeutics
12:30 pm Lunch & Roundtable Discussion
Synopsis
Challenges in a World of Opportunity
Development of Emerging Strategies in Targeted Protein Degradation
Harnessing Lysosomal & Chaperone Mediated Degradation as a Novel Target-Selective Approach
13:30 PHOTACs Enable Optical Control of Protein Degradation
- PHOTACs promote the optical degradation of target proteins
- PHOTACs appear to be applicable to a wide variety of proteins, including BRD2-4, CDK4/6 and MDM2/p53
- PHOTACS could enable a new form of photodynamic therapy and precision medicine
Dirk Trauner, Professor of Chemistry & Neuroscience, New York University
13:30 Degradation of Extracellular and Membrane Targets using LYTACs
- Heterobifunctional reagents, called LYTACs, can bridge extracellular proteins to internalizing receptors, causing trafficking of the complex to the lysosome and degradation of the extracellular target
- LYTACs thus open new target space for pharmacological induction of protein degradation
- Differential activity of internalizing receptors across tissues and cell types further broadens the potential of the platform, by allowing for tissue-selective pharmacology
Richard Glynne, Chief Scientific Officer, Lycia Therapeutics
13:50 Emerging Strategy for Protein Degradation; Combining Data Science, Cancer Genomics & Chemical Modalities
- Our drug discovery research focuses on a target-centric approach where patientderived information is utilized to create a therapeutic hypothesis and investigate several different modalities for effective target modulation
- Utilizing information provided from H3B’s data science and cancer genomics, we are developing a protein degradation strategy that contrasts traditional approaches and enhances the likelihood of clinical introduction and success
- Describing our approach towards targets that can benefit from the protein degradation approach
Stephanos Ioannidis, Vice President & Head of Chemistry, H3 Biomedicine
13:50 Chaperone-Mediated Targeted Protein Degradation
- Chaperones mediate the folding of many important client proteins and mutated oncoproteins but can also direct misfolded proteins for degradation by the UPS
- Ranok is developing a novel approach in which inducing the proximity of target proteins and chaperones can direct degradation through the associated E3 ubiquitin ligases
- This technology has a number of potential advantages including an improved safety margin due to selective accumulation in tumor tissues
Kevin Foley, Chief Scientific Officer, Ranok Therapeutics
14:10 Discussion/Q&A
Moderator: Yonghao Yu, Associate Professor of Biochemistry, UT Southwestern Medical Center
- Dirk Trauner, Professor of Chemistry & Neuroscience, New York University
- Stephanos Ioannidis, Vice President & Head of Chemistry, H3 Biomedicine
14:10 Discussion/Q&A
Moderator: Amine Sadok, Director of Biology, Monte Rosa Therapeutics
- Richard Glynne, Chief Scientific Officer, Lycia Therapeutics
- Kevin Foley, Chief Scientific Officer, Ranok Therapeutics
2:30 pm Final Virtual Speed Networking Opportunity
3:00 pm Women in TPD
Synopsis
- This discussion session highlights pioneering women working in TPD drug discovery & development
- Shining a light on their experience and success, this expert female panel will discuss their backgrounds in becoming key opinion leaders, identifying themselves as business experts and breaking through the glass ceiling in the industry
- Join this conversation to support gender equality in the TPD field
3:30 pm PROTACs to Sustainably Feed the World
Synopsis
- Resistance to fungicide, insecticide and herbicide and pressures from NGOs and governmental regulators for existing agricultural chemistries create acute challenges for farmers
- New modality of PROTACs offers the possibility to create a safer and more sustainable solution for the entire food supply chain
- Oerth Bio is committed to leveraging data science, biology and chemistry to design PROTACs that will be safer for the environment and more potent to increase crop yield