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. 

The study is recruiting patients under IND approved in USFDA, TGA (Australia) and DCGI (India).