Attributes that make XTEN an ideal drug linker
- Stable in circulation
- Rapid degradation by intracellular proteases
- Precisely-controlled chemical structure
- Drug conjugation with defined stoichiometry
- High drug-XTEN ratio achievable even for poorly-soluble drugs
- Compatible with RP-HPLC purification
XTEN that has been pre-loaded with drugs and purified to homogeneity can be conjugated to IgGs, antibody fragments, metabolites, and peptides
Drugs can be selectively linked to Cys residues in XTEN polymers using stable iodoacetamide chemistry. Subsequently, the N-terminal amino group can be functionalized for conjugation to IgGs or other tumor-binding moieties, such as folate or scFv.
The figure below shows that XTEN loaded with 9 drug molecules (drug-XTEN ratio, DXR = 9) can be effectively purified at preparative scale from a reaction mixture containing XTENs carrying 8 or fewer drug moieties.
The figure below shows that a single dose of an antibody fragment linked to XTEN-3xDrug has good in vivo activity and low toxicity in a mouse xenograft model