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Registration & Coffee


Chair’s Opening Remarks 

Adam Gilbert
Senior Director, Discovery Sciences,
Design & Synthesis Sciences


Pre-Recorded Welcome Video by Aaron Cjechanover

• Distinguished Research Professor- Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
• Laureate, the 2004 Nobel Prize in Chemistry for discovery of the ubiquitin-proteasome system (shared with Avram Hershko &
Irwin A. Rose

Adam Gilbert
Senior Director, Discovery Sciences,
Design & Synthesis Sciences

Keynote Plenary: Delivering the New PROTAC Paradigm


PROTAC-Mediated Protein Degradation: Chemical Biology Comes of Age

• History of PROTACs
• Exploring PROTAC substrate specificity
• Future of induced protein degradation

Craig Crews
American Cancer Society Professor of MCDB, Chemistry & Pharmacology
Yale University




Molecular Recognition Principles of How PROTACs Work

• PROTACs are a new paradigm in targeted molecular therapeutics
• PROTACs function by bringing a target protein to an E3 ubiquitin ligase for ubiquitination and proteasomal degradation
• Structural and biophysical studies of ternary complexes illuminate important molecular recognition principles and understanding of how PROTACs work

Alessio Ciulli
Professor of Chemical & Structural
University of Dundee


Monitoring Dynamics of Protein Degradation in Living Cells

• Three case studies of PROTAC mechanism of action in different systems
• The Degradogram: live cell kinetic degradation profile for quantitative rank ordering of compounds
• Relationship of cellular ternary complex formation and ubiquitination to degradation rate
• Rapid entry for HTS screening of compounds in cellular assays

Kristin Riching
Senior Research Scientist, R&D


Speed Networking and Morning Refreshments

Target Identification
& Mechanism of Action
Confirmed Chair:
Paola Castaldi, Associate Director & Head of Chemical
Biology, AstraZeneca

Optimizing Emerging TPD Strategies
Confirmed Chair:
Charu Chaudhry, Senior Research Investigator, Lead
Discovery and Optimization, Bristol-Myers Squibb

Translation & Early Clinical
Confirmed Chair:
Darryl McConnell, Vice President and Research Site Head
Austria, Boehringer Ingelheim

Reimagining Novel Target Discovery by Leveraging Versatile Tools in the Toolbox

Tackling the Chemical Challenges of Emerging TPD Strategies

Addressing Key Translational Challenges Towards Accelerated & Robust Clinical Development 


Reimagining Druggability using Chemoproteomic Platforms

• Chemoproteomics-enabled covalent ligand discovery platforms can be used to access the undruggable proteome
• Chemoproteomics can be used to discover new E3 ligase recruiters
• Chemoproteomics can be used to assess proteome-wide selectivity of covalent ligands

Daniel Nomura, Professor, University of California, Berkeley


Harnessing Monofunctional and Heterobifunctional Cereblon-Mediated Protein Degradation for Therapeutic Benefit

• New insights into cereblon mechanisms of Action
• Toward a biased toolkit for heterobifunctional degraders
• Progressing degraders into clinical proof-of concept

Joshua Hansen, Director, Chemistry, Celgene


Moving PROTAC® Protein Degraders from the Laboratory to the Clinic

• Insights gained from our two lead programs, ARV-110 and ARV-471: Preclinical data
• IND enabling studies
• Initial clinical experience

Ian Taylor, Chief Scientific Officer, Arvinas



Computational Modeling of PROTAC-Mediated Ternary Complexes: Applications and Insight

• Multiple computational procedures have been developed for generating ensembles of ligasePROTAC-target ternary complexes
• Comparison of these conformational ensembles to existing X-ray crystal structures has enabled the identification of properties that can be used to a priori to identify ternary complex structures that are more likely to be similar to experimental structures
• These computational modeling tools and filtering criteria have been applied to numerous experimentally-characterized protein degradation systems, across different targets, PROTACs, and ligases, with significant agreement with experiment

Michael Drummond, Scientific Applications Manager, Chemical Computing Group



Hinova's PROTAC Approach Towards Cancers

• Introduction of Hinova: our mission and focus
• Optimization of PROTAC degrader for cancers
• Degradation approach to overcome drug resistance

Wu Du, Senior Vice President, Hinova Pharmaceuticals



Evolution of Cereblon Modulating Drugs in the Clinic: From Phenotypic Observations to Molecular Mechanism Driving Clinical Development

• Targeted protein degradation has had tremendous clinical success in oncology
• Preclinical understanding of substrates and downstream biology are key to drive future clinical development
• These insights can lead to rational selection of dose/ schedule, patient populations, tumor types and combinations

Michael Pourdehnad, Executive Director Translational Medicine, Celgene



Principles of Small Molecule Mediated Ubiquitin Ligase Targeting

• Computational methods to predict small molecule mediated ubiquitin ligase targeting
• Large scale proteomics approaches to protein degradation therapeutics
• Structural principles of small molecule mediated ubiquitin ligase targeting

Radoslaw Nowak, Scientist, Fischer Lab, Dana-Farber Cancer Institute



Degrading ‘Undruggable’ Proteins with Molecular-Glues

  • We describe a method to screen for small-molecule degraders in cell-based assays using DNA-encoded libraries
  • We describe high-throughput, phenotypic assays to monitor functional consequences of target degradation
  • We describe a path to automated evolution of hits to lead-like compounds using examples

Kandaswamy Vijayan, Chief Executive Officer, Plexium



Transforming Kinase Enzymatic Inhibition to Degradation: The Quest to Bring Novel AML Therapies into the Clinic

• Brief summary of BTX-A51, BioTheryX’s most advanced clinical compound that targets leukemic stem cells and transcriptional enhancers of leukemic oncogenes currently in Phase I clinical trial for AML
• The development of PROTACs using BTX-A51 linked to BioTheryX’s novel cereblon binding small molecules
• The unique protein degradation profiles of these PROTACs with potentially different therapeutic window and novel clinical opportunities will be discussed

Kyle Chan, Chief Technology Officer, BioTheryx


Networking Lunch

Exploring the Ubiquitin & Lysosomal Systems for Novel Ligase Targeting

The Horizon Beyond PROTAC Induced Degradation & Potential Therapeutic Benefits

From Pre-Clinical to Clinical Development: The Quest to Unlock the Full Therapeutic Potential of TPD



Targeting the Ubiquitin System for Therapeutic Benefit

• Overview of the ubiquitin system and its key enzymes
• Identification of new enzymes suitable for PROTAC development
• Prospective development of molecular glues targeting new E3 ligases

Michael Rape, Investigator, HHMI and Dr. K. Peter Hirth Chair of Cancer Biology, University of California at Berkeley



SNIPERs: Hijacking IAP Ubiquitin Ligases for Targeted Protein Degradation

• SNIPERs recruit IAP family proteins for degradation of target protein
• SNIPERs simultaneously degrade IAPs overexpressed in cancer cells
• Advantages of IAP degradation for anti-cancer therapy

Mikihiko Naito, Chief, Division of Molecular Target and Gene Therapy Products, Japan National Institute of Health Sciences



Co-Opting the Ubiquitin System for Therapeutic Benefit

• The MCL-1 oncoprotein is a resistance factor for the BCL2 inhibitor venetoclax in Non-Hodgkin’s Lymphoma
• We describe a combination treatment regimen, including a non-PROTAC targeted agent that promotes MCL-1 degradation, that promotes tumor growth inhibition in pre-clinical models of Non-Hodgkin’s Lymphoma
• This treatment regimen is showing clinical benefit in a Phase 1 Trial with relapsed/refractory Non-Hodgkin’s Lymphoma patients

Ingrid Wertz, Senior Scientist and Project Team Leader, Genentech



Degraders Induce Specific MHC Peptides on the Cell Surface

• The cell surface MHC immunopeptidome can be modulated through enhanced intracellular protein degradation via degrader treatment
• Mass spectrometry is a versatile tool for monitoring changes in the immunopeptidome upon increased intracellular protein degradation
• Results from the analysis of immunopeptides after degrader treatment have the potential to reveal
novel cell surface targeting strategies as well as deeper understanding of on-target, off-target, direct, and indirect cell biology effects

Melanie Patterson, Principal Research Scientist, Abbvie



Target Intrinsic Approaches to Protein Degradation

• Precedent for target-intrinsic protein degradation
• Direct ligand induced degradation
• Baselining proteome-wide protein half lives

Brian Jones, Chief Scientific Officer, Cedilla Therapeutics



Oral Degraders of IRAK4 in Myddosome Driven Diseases

• Target rationale and clinical promise
• Properties optimization to orally active degraders
• Activity in translational models in oncology and autoimmune disease

Nello Mainolfi, Founder and Chief Scientific Officer, Kymera Therapeutics



Landscaping Different E3 Ligases and Lysosomal Pathway as a Platform of Protein Degradation Therapeutics

• Proximity-based protein degradation therapeutics
• Protein-protein interaction domain
• Clinical consideration in protein degradation therapeutics

Hyunsun Jo, Founder and Chief Executive Officer, Pin Therapeutics



Target Class Approach Accelerates Development of DUB Inhibitors

• Our lab has established a platform for discovery and validation of DUB inhibitors
• The platform has enabled structure-guided design of both covalent and noncovalent DUB inhibitory probes
• Use of novel DUB-targeting libraries in phenotypic screens has led to discovery of novel DUB functions

Sara Buhrlage, Assistant Professor, Dana-Farber Cancer Institute



Targeted Protein Degradation: From Cells to In Vivo Pharmacology

• Quantifying kinetic parameters from Cellular degradation data
• Optimizating PK profiles for efficacy
• Degrader PKPD relationships

Stewart Fisher, Chief Scientific Officer, C4 Therapeutics



Overcoming Bottlenecks in PROTAC Drug Discovery

• LifeSensors offers high-throughput screens for E3 ligases and PROTAC libraries. Services are customized for the scale and scope of your specific project. Our assays accelerate the discovery process of your next breakthrough
• Hits are confirmed in selectivity panels as well as in high-throughput cell-based assays. The ubiquitylation of the target protein is the key step, we are equipped to monitor this dynamic process
• Biomarkers are identified by TUBE-based mass spectrometry for preclinical and clinical studies

Karteek Kadimisetty, Assistant Director- R&D, LifeSensors



Targeted Protein Degradation – Dual Approaches:  ‘Hijacking’ or Direct Targeting PROTAC SAR Support & an Integrated DUB Drug Discovery Platform

• DUBs provide a rich seam of chemically tractable protein degradation regulation drug targets across many therapeutic areas
• Ubiquigent’s mission: To support and enable protein degradation focused drug discovery by the identification and characterization of novel DUB inhibitors across multiple therapeutic areas
• We will discuss Ubiquigent’s DUB targeting small molecule hit-to-lead platform and how it may be accessed via exclusive Collaborative Drug Discovery arrangements and our CRO access models

Jason Brown, Scientific & Business Development Director, Ubiquigent



Induced Proximity Inactivation

• Bispecific molecules of various formats and function are on the rise across different therapeutic areas
• Protacs (bispecific small molecule degraders) can be used to target proteins that are difficult to target by conventional approaches
• Directions that the field may evolve towards in the future (molecular glues, other types of induced proximity inactivation)

Raymond Deshaies, Senior Vice President for Global Research, Amgen


Networking Break & Poster Session

Advancing In Vitro & In Vivo Drug Target Validation for PROTAC Discovery

Enabling Immediate & Selective Protein Degradation Through Medicinal Chemistry Optimization

Unlocking the Full Therapeutic & Investment Potentials of TPD Through Successful Clinical Development



The Auxin-Inducible Degron System as a Tool for Target Validation

• Historical development of conditional degrons
• Recent improvements of the auxin-inducible degron (AID) technology
• Potential use of a conditional degron for PROTAC discovery

Masato Kanemaki, Professor, Japan National Institute of Genetics



Alternative Ways to Target Ubiquitin Specific Proteases

• Ubiquitin specific proteases and substrate-assisted catalysis
• Differences between ubiquitin specific protease paralogues
• Can ubiquitin specific protease S1’ regions be targeted

Ingrid Dreveny, Assistant Professor, University of Nottingham



Developing Ligase Inhibitor and Activators for Cancer Therapy

• Small molecule Inhibitors of the E3 ligase, Cbl-b, are potential novel, immuno-therapies
• Targeted degradation of resistance mutations in oncology
• Identification of candidate biomarkers to guide development of novel cancer therapies that modulate the UPS

Arthur Sands, Chief Executive Officer, Nurix



Leveraging the dTAG Platform to Degrade Cancer Dependencies

• Development of the dTAG system to enable immediate and selective protein degradation
• Case studies highlighting functional evaluation and drug target validation of cancer dependencies using the dTAG system
• Recent advances with the dTAG system including model system development and in vivo evaluation

Behnam Nabet, Research Fellow, Dana-Farber Cancer Institute



Targeted Degradation of the MTH1 Achilles-TAG: Medicinal Chemistry Optimization

• Structure based drug design concepts in the context of kinetically-driven targeted protein
• SAR navigation of off-target/on-mechanism pharmacology
• DMPK optimization of degraders

Christopher Nasveschuk, Vice President, Chemistry, C4 Therapeutics



Targeting the Undruggables by PROTAC for Clinical Development

• Highlighting the challenges and promise, as well as the remarkable potency, selectivity and efficacious achieved by PROTAC small-molecule degraders
• Showcase of our efforts to design highly potent & specific efficacious PROTAC small-molecules to drug those traditionally “undruggable” protein targets
• Clinical candidate development considerations

Shaomeng Wang, Warner-Lambert/Parke-Davis Professor in Medicine, University of Michigan



Target Identification and Therapeutic Potential of Cereblon Modulation

• Cereblon harnesses antigen-specific activation of CD8+ T cells
• Crbn loss or IMiD compounds promote a hypermetabolic T-effector cell phenotype orchestrated by cereblon control of Myc
• Crbn deficient T cells exacerbate graft-vs-host disease (GVHD) but promote superior anti-tumor reactivity

Pearlie Epling, Burnette, Professor, Senior Member Department of Immunology, Moffitt
Cancer Center & Research Institute



An Efficient Degrader Drug Discovery Focused on Rapidness and Diversity

• Don’t you need to optimize not only the linkers but also the E3 binders depending on the target of interest?
• Targeted IRAK-M degradation as a novel and efficacious cancer-immunotherapy
• Expansion of RaPPIDS (TM) platform to apply the next programs

Yusuke Tominari, Chief Executive Officer, FIMECS



Invite Only CEO Roundtable

• An invite only session that will unite the leaders of the protein degradation field to discuss the long term challenges, opportunities and trends that lie within this ever-growing field

Christopher O'Donnell, Executive Director, Worldwide Research and Development; Principal, Pfizer Ventures


Chair’s Closing Remarks & End of Day One