SPEARs™ (Stabilized Peptides Engineered Against Regulation) consist of a protein-protein interaction (PPI) disrupting domain and a cell penetrating domain. The PPI disrupting domain binds to one protein in a complex, which disrupts the interactions with other proteins and disables the complex, thereby blocking its function. The cell penetrating domain enables penetration into the cell’s cytoplasm or nucleus. Unlike conventional peptides, SPEARs are engineered to have several important properties:
Enhanced stability: constructed to be resistant to proteases, enabling SPEARs to remain intact in vivo
Not immunogenic: demonstrated non-immunogenic profile preclinically and in the clinic, with no ADAs observed against SPEARs in development
Long half-life: the half-life of SPEARs is measured in days, providing prolonged exposure per dose and enabling more favorable clinical regimens
Cell permeability: SPEARs are designed to enter the cell and are tunable for cytoplasmic vs. nuclear localization
Blood-brain barrier permeability: enables treatment of tumors within the brain and central nervous system
We discover SPEARs through our Assay for Discovery of Antagonist Peptides based on Transcription (ADAPT™), which is built on our team’s years of experience in peptide chemistry and molecular and cancer biology.
Our pipeline of SPEARs is progressing through various stages of clinical development and discovery.