XTEN-Drug Conjugates

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

Fig 1 XDC
Fig 2 XDC

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.

Fig 3 XDC

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

Fig 4 XDC