8:00 am
Registration & Morning Coffee

8:50 am Chair’s Opening Remarks

  • Nan Ji CEO, PAQ Therapeutics

Shining a Spotlight on Induced Proximity Strategies for ‘Undruggable’ Targets

9:00 am Keynote Presentation | The Quest for Universal Druggability: Lessons from Evolution

9:30 am Chemically Induced Proximity for Investigative & Therapeutic Purposes

  • Jerry Crabtree David Korn Professor, Stanford University Medical School

10:00 am Exclusive Update from Promega

10:30 am
Structured Networking

11:30 am Panel Discussion: Advancing the Discovery & Development of Induced Proximity Molecules

Synopsis

  • How to optimize the drug like properties of induced proximity molecules
  • Understanding and overcoming PKPD challenges
  • What ADME properties are desirable and how does this differ between targets?
  • What should the pharmaceutical profile look like?
  • Covalent interactions vs non-covalent interactions
  • Proximity is target and enzyme dependent so what is the best way of going about the rational discovery and design?
  • Is it best to use purified proteins and enzymes or is it more efficient to do it in cells first and then optimize?
  • Expanding therapies beyond oncology

Revealing Different Mechanistic Approaches to Induced Proximity

12:15 pm Chemically Controlling Chromatin

  • Nate Hathaway Associate Professor, The University of North Carolina at Chapel Hill

Synopsis

  • Chemical Epigenetic Modifiers allow for dose dependent control of gene expression
  • Bifunctional small molecules bridge gene targeting proteins with host gene activators
  • Applying chemically controlled catalytically inactive dCas9 to human disease

12:45 pm Chemical Approaches to Examine the Function & Druggability of Essential ATPases

  • Tommaso Cupido Assistant Faculty, St Jude Children’s Research Hospital

Synopsis

  • An approach that uses silent mutations to develop selective and potent ATPase inhibitors
  • Insight into the druggability of Nucleic Acid-dependent ATPases
  • Inducing proximity using allosteric ATPase ligands

1:15 pm
Networking Lunch

2:15 pm Translating Frontier Oncology Targets to Outsmart Cancer™

Synopsis

  • Revolution Medicines (RevMed) has developed a series of Tri-Complex inhibitors targeting RAS(ON)
  • RevMed RAS(ON) inhibitors work by sequestering Cyclophilin A to form an inhibitory complex with RAS mutant proteins, preventing pathway signalling
  • Covalent RAS(ON) Tri-Complexes display sustained stability in biochemical and in vitro assays, and drive impressive regression in tumor xenografts

Analyzing Non-Traditional Proximity Inducing Approaches Targeting Intra-& Extra-Cellular Proteins & RNA for Therapeutic Benefit

2:45 pm Exploring the Use of Induced Proximity Medicines for Targeted Degradation of RNA

  • Ryan Potts Head of Induced Proximity Platform, Amgen

Synopsis

  • Current opportunity areas in Induced Proximity Medicines
  • Expanding the druggable genome through targeting RNA
  • Overview and updates on targeted RNA degradation by hetero-bifunctional small molecules

3:15 pm Sequence Based Design of Small Molecule RNA Degraders

Synopsis

  • Understanding the design and optimization of compounds that bind RNA targets and trigger their interaction with quality control machinery
  • Data will be presented from cells to mouse models

3:45 pm
Afternoon Networking Break

4:15 pm 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 ubiquitin-proteasome 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, including an improved safety margin due to selective drug accumulation in tumor tissues

4:45 pm Strategies for Dynamic Protein Control in Cancer

  • Behnam Nabet Assistant Professor, Fred Hutchinson Cancer Research Center

Synopsis

  • Development of the tag-based technology platforms for protein control
  • Case studies highlighting functional evaluation and drug target validation of cancer vulnerabilities using the dTAG system
  • Recent advances in protein control using tag-based technology platforms

5:15 pm Targeted Degradation of Extracellular Proteins Using Antibody-Based Biologics

  • Katarina Pance PhD Candidate (Jim Wells Lab), University of California, San Francisco

Synopsis

  • Targeted protein degradation is an established new modality for drug discovery for intracellular proteins, yet most small molecule and biologics engage extracellular targets
  • We have recently shown it possible to degrade therapeutically relevant membrane proteins by recruiting transmembrane E3 ligases to proteins of interest using bi-specific antibodies, a biologics technology akin to small molecule PROTACs, we call AbTACs (Cotton et al. JACS 2021)
  • This talk will describe recent optimization and expansion of this modality for degrading surface proteins

5:45 pm
Chair’s Closing Remarks & End of Conference Day One