SBO-154 is a novel MUC-1 SEA domain targeting antibody drug conjugate (ADC).
MUC-1 or mucin 1 is a heavily glycosylated transmembrane glycoprotein found in the glandular or luminal epithelial cells and to a lesser extent, in hematopoietic cells. It is translated as a single polypeptide which undergoes auto-cleavage into two subunits: MUC-1 N-terminal subunit (MUC-1-α) and MUC-1 C-terminal subunit (MUC-1-β) to form a stable non-covalent heterodimeric complex at the cell membrane. MUC-1-α and β chains remain tightly associated via a strong hydrophobic interaction and is presented extracellularly on the cell surface.
MUC-1 is overexpressed in the vast majority of human carcinomas and has gained remarkable attention as an oncogenic molecule. Interestingly, in normal epithelia MUC-1 is confined to the apical surface of the cells whereas in cancerous cells, their expression is distributed evenly across all the surface along with aberrant glycosylation.
MUC-1 is an internalizing target making it an ideal candidate for antibody drug conjugates. SBO-154 targets SEA domain of MUC-1, that too only when it’s intact with both α and β chain. SBO-154 has demonstrated potent in-vitro cytotoxicity as well as robust preclinical in-vivo tumor growth inhibition of various MUC-1 expressing of carcinomas including pancreatic, head and neck, and hormone refractory breast carcinomas.
SPARC is in process of generating GMP grade ADC for safety study and clinical evaluation. SPARC plans to file US IND in 2025.