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8:30 am
Morning Coffee & Networking

8:55 am Chair’s Opening Remarks

  • Radosław Nowak Senior Scientist , Fischer Lab, Group Leader at the Center for Protein Degradation

Assessing Drug Delivery Systems for Better Targeting

9:00 am Entropically Leveraged Reactions for Targeted Drug Delivery

  • Binghe Wang Regents Professor and Georgia Research Alliance Eminent Scholar, Georgia State University

Synopsis

  • Enrichment-triggered prodrug activation
  • Targeted drug delivery
  • Receptor-mediated drug activation

Uncovering Bifunctional Molecules that Induce Post-translational Modifications

9:30 am Expanding the Scope of Induced Proximity

Synopsis

  • Induced Proximity has a multitude of potential applications for drug discovery
  • Post-translational modifications dominate cell signalling and are often misregulated in disease
  • Chemical biology technologies enable us to control PTMs for therapeutic benefit

10:00 am Writing & Erasing O-GlcNAc from Target Proteins in the Cell

Synopsis

  • Over 15% of the cellular proteome is modified by O-linked N-acetyl glucosamine (O-GlcNAc), a post-translational modification (PTM) that consists of a single sugar attached to serine or threonine residues of nuclear, cytosolic and mitochondrial proteins
  • Due to the ubiquitous nature of the modification, O-GlcNAc has been implicated in numerous biological processes, including immune response, cancer progression, neurodegenerative disease, and diabetes
  • We have now developed a cellular approach for writing and erasing O-GlcNAc from target proteins in the cell. The method uses a nanobody fused to an O-GlcNAc writer or eraser to control O-GlcNAc levels on the desired target protein

10:30 am
Scientific Poster Session & Morning Break

Synthetic & Biologic Approaches to Proximity Induction in Immune Oncology

11:30 am Remote Presentation: Covalent Immune Proximity Induction Strategies for Translational Chemical Biology

Synopsis

  • To explore the molecular requirements and physical properties governing immune function, we have developed new classes of proximity-inducing molecules
  • These molecules use covalent chemistry to enforce immune receptor binding interactions
  • Discussing current progress in the use of covalent immune recruiting molecules to modulate antibody-dependent eradication of cancer and mechanistic insights into key factors governing anti-tumor potency and efficacy

12:00 pm TNB-486: An anti-CD19xCD3 T-cell Engager with a Better Therapeutic Window

Synopsis

  • TNB-486 is a novel anti-CD19xCD3 bispecific T-cell engager for the treatment of B-NHL
  • Preclinical data shows targeted lysis of CD19+ cells with minimal cytokine release, dose dependent clearance of CD19+ tumor cells in vivo, and favorable pharmacokinetics
  • TNB-486 has a better therapeutic window than first generation TCEs targeting CD19

12:30 pm Selective Targeting of T Cells to Tumors using Precision TwoGATE™ (Guided Antibody Tumor Engagers)

Synopsis

  • Traditional T cell engagers bring T cells in close proximity of tumors and drive potent tumor cell killing. Despite the highly potent nature of these agents, their clinical utility is limited by off-target and on-target/off-tumor toxicities
  • Revitope’s two-component bi-specific TwoGATE ™ platform aims to address these key liabilities by incorporating several design features to more specifically focus T cell redirection to the tumor including requirements for dual antigen expression in the tumor, tumor protease driven cleavage and activation, and a built in PK switch to limit systemic exposure of GATE™ once activated in the tumor

1:00 pm
Networking Lunch

Predicting & Leveraging Protein-Protein Interactions for Novel Discovery of Proximity- Inducing Drugs

2:00 pm Exploiting Cell Surface Interactions in Drug Development

Synopsis

  • Nature’s cell surface PPI machine: ordered, structural, and functional
  • Cell surface protein interactions are much more than dimerization
  • What can complex multi-protein interactions at the cell’s surface tell us

2:30 pm Drugging the Undruggable: Lessons Learned from Protein Phosphatase 2A

  • Goutham Narla Professor of Internal Medicine and Human Genetics, Division Chief of Genetic Medicine, The University of Michigan

Synopsis

  • Small molecule mediated reactivation of tumor suppressor proteins
  • Allosteric approaches to promote reassembly of protein complexes
  • The role of serine/threonine phosphatases in human cancer

3:00 pm Combining Machine-Learning & Molecular Modeling in Predicting Protein-Protein Interface

Synopsis

  • Recent advancement in machine-learning provides new tools for predicting protein interface
  • Challenges still exist in accurately modeling weak protein-protein interactions from unbound, apo structures
  • Combination of machine learning and molecular modeling can potentially lead to a promising solution for interface modeling

3:30 pm
Afternoon Break

Revealing Therapeutic Opportunities offered by Novel Targeted Protein Stabilization Strategies

4:00 pm Creating Small Molecule Stabilizers of the 14-3-3 Phosphoprotein Regulators & Their Disease-Driving Client Proteins

Synopsis

  • The 14-3-3 family of adaptor proteins regulate thousands of phosphoprotein clients, many of which play critical roles in diseases of unmet medical need
  • The identification of molecular glues stabilizing protein-protein interactions is facilitated by a detailed structural, biochemical and biophysical understanding of the interaction
  • Ambagon Therapeutics is a leader in developing a modular approach to molecular glue discovery, utilizing a significant data set of the interactions between 14-3-3 adaptor proteins and their phosphoprotein clients

4:30 pm Ushering in the Novel Modality of Targeted Protein Stabilization (TPS)

Synopsis

  • Stablix mission and overview of TPS
  • Harnessing DUBs for RESTORAC development
  • What are the therapeutic applications and opportunity space in TPS?

5:00 pm Chair’s Closing Remarks & End of 2nd Induced Proximity-Based Drug Discovery Summit

  • Goutham Narla Professor of Internal Medicine and Human Genetics, Division Chief of Genetic Medicine, The University of Michigan