De Novo Helix Discovery Engine Enables Near-Universal Druggability

FogPharma’s unique stapled phage display platform enables the De Novo discovery of helically constrained (Helicons) peptides, including Trimerizer (molecular glue) Helicons. Helicons are a new drug modality capable of targeting intracellular protein targets that are undruggable by conventional therapies. We describe here our unique phage-based screening approach for discovering helical binders to targets with no prior knowledge of their structure or of existing binders, and demonstrate its broad applicability by reporting hits to a diverse panel of E3 ligases. We also describe the use of this platform to discover Trimerizer Helicons that form ternary complexes between an E3 ligase and the oncoprotein β-Catenin. Finally, we show how phage hits discovered with this platform can be rapidly advanced into molecules with in pharmacodynamic activity using our multiplexed hit-to-lead synthetic screening platform.