Anti-KRAS Antibody Prodrug, Protease Activated (VS-1025-YC25)

The Anti-KRAS Antibody Prodrug, Protease Activated (VS-1025-YC25) is an antibody prodrug comprised of a recombinant human antibody targeting human KRAS, linked to a masking peptide that conceals the active antigen-binding site via a protease-cleavable linker. The mask peptide is recombinantly attached to the amino terminus of either the light or heavy chain of the antibody, designed to block access to the antigen-binding site and physically prevent the antibody from binding to KRAS protein. Once the masking peptide is cleaved by matrix metalloproteinases (MMPs), the prodrug is activated, allowing the unmasked monoclonal antibody component to bind to KRAS effectively. KRAS is the most frequently mutated member of the RAS family and a dominant oncogene in many solid tumors, including over 90% of pancreatic cancers, 45% of colorectal cancers, and 30% of lung adenocarcinomas. Point mutations (e.g., G12C, G12V) lock KRAS in its active signaling state, promoting uncontrolled growth. Recent drug developments have successfully introduced inhibitors for specific KRAS mutants, overcoming its previous status as "undruggable."