Our Approach: Leveraging
Our aim is to inhibit the function of pathogenic proteins by degrading them to treat disease. The mannose-6-phosphate receptor (M6PR) is a cell-surface glycoprotein that acts as a lysosomal trafficking shuttle.
As shown in this graphic to the left, M6PR ligands bind M6PR and are internalized and shuttled through the endosome-lysosome pathway into the degradation compartments.
Central to our approach, we hijack this naturally occurring lysosomal trafficking shuttle process by linking an extracellular target binder to an M6PR ligand. The M6PR then drags the ligand with its linked extracellular target into lysosomes for degradation. The platform extends beyond M6PR, and we have established LYTACs with multiple receptor systems for both broad-based and tissue-specific targeting.
While the graphic to the left shows an antibody target binder, the original modality explored with this method, we have expanded target binders to include low molecular weight/small molecules and bispecific antibodies.
To date, we have generated hundreds of LYTACs across multiple modalities.