Next Generation Protein Modulation Day
Thursday, October 31 2024
8:00 am Check-In & Morning Coffee
8:20 am Chair’s Opening Remarks
Innovating Techniques to Stabilize, Phosphorylate, & Degrade Intra & Extracellularly
8:30 am SureTACsTM: Beyond Blocking Membrane Proteins
Synopsis
- Membrane-bound E3 ligases can be repurposed for the targeted degradation of disease-driving cell surface proteins
- Laigo Bio’s TED-I screening platform is essential to identify optimal E3-target pairs with highest degrader potency
- SureTACsTM: bispecific antibodies that induce cell surface removal and target degradation in a tissue- and disease-specific manner
9:00 am CYpHER: Catalytic Extracellular TPD for Potent Durable Effect in Oncology & CNS Disease
Synopsis
- Engineering bispecific proteins that utilize transferrin receptor and pH-sensitive target binding to direct disease-driving proteins to the endolysosomal system
- Catalytic activity provides high potency and durability
- PD activity across mutational settings with superior activity and targeting versus traditional modalities
9:30 am Recent Progress in mRNA Based Targeted Protein Degrader Development
Synopsis
- Update of EPDegTM bioPROTAC development
- Proved differentiating points of bioPROTAC platform from others
- Current challenges and future directions
10:00 am Degradation of Key Intracellular Targets via the Cytosolic Delivery of Recombinant BioPROTACS
Synopsis
- Modification of antibodies and proteins with anionic polypeptides allows for complexation with cationic lipids and efficient intracellular delivery
- Recombinant BioPROTACS can be used to efficiently degrade “undruggable” intracellular targets
- Delivery of recombinant BioPROTACS may lead to significantly fewer differentially-regulated “off-target” proteins compared with mRNA encoded BioPROTACS
10:30 am Morning Break & Networking
Introducing New Approaches to Stabilization of Targets to Induced Therapeutic Benefit
11:30 am Advancing Oral RIPTACTM Therapeutics Towards the Clinic
Synopsis
- Novel heterobifunctional small molecule RIPTAC technology platform
- Leveraging protein-protein interactions and other mechanistic insights
- Halda’s Prostate Cancer RIPTAC Program
12:00 pm A Novel Approach to Targeted Protein Stabilization via E3 Ligase Inhibition
Synopsis
- E3 ligase inhibition to stabilize proteins otherwise degraded in disease is an untapped therapeutic modality
- Introducing a novel platform for identification of direct inhibitors of E3 ligases and novel E3 ligases
- Selective and potent small molecule inhibitors of E3 ligases have been identified that stabilize tumour suppressor proteins and induce cell death in target tumour cell populations
12:30 pm Networking Lunch Break
Novel Takes on Molecular Glue Discovery & Development
1:30 pm A Systematic Protein Editing Platform to Unlock Molecular Glue Discovery
Synopsis
- Describing the challenges of monovalent drug discovery for induced proximity
- Introducing GlueSEEKER™, a new platform to enable MGD drug discovery
- Demonstration that E3 effector protein engineering can deliver neomorphic activity
2:00 pm Non-Degrading Molecular Glues: A Platform for Finding Novel Chemical Matter for Inhibiting Intracellular & Transmembrane Proteins
Synopsis
- The described macrocycles form ternary complexes comprising a presenter protein (FKBP12), the molecular glue, and a target protein. Inhibition through formation of a ternary complex often results in potency, selectivity over homologous proteins and favorable drug like properties such as slow binding kinetics
- The construction of DEL and array libraries of molecular glues will be discussed as well as perspectives on topological diversity
- Screening of the platform has yielded chemical starting points have been discovered for several target classes. One program will described SAR leading to potent, cell permeable macrocycles for the inhibition of an oncology target. Another program will discuss the inhibition of a nucleoside transporter target that has yielded a development candidate
2:30 pm Afternoon Break & Networking
3:00 pm New Approach for TPD: Targeting the Secretory Translocon (Sec61) to Selectively Eliminate Extracellular Proteins
Synopsis
- Mother Nature pioneered targeting of Sec61 for secretory protein degradation
- Selectivity is enabled by virtue of the unique sequences of Signal Peptides across the secretome
- Synthetic small molecules are capable of selectively eliminating secreted and membrane proteins
3:30 pm PHOSTACs to Accelerate Targeted Protein Dephosphorylation
Synopsis
- PHOSTACs state of the art and current challenges
- Targets and phosphatases for PHOTAC design
- Targeted covalent ligands for small molecule PHOSTACs