XTEN: A Protein-Based, Biodegradable PEG Alternative with a Controlled Chemical Composition
Volker Schellenberger
Chief Scientific Officer, Amunix
Amunix has developed XTEN, a protein-based polymer that mimics the
biophysical properties of PEG, to extend the serum half-lives of attached
therapeutics. Peptides and other molecules can be conjugated to XTEN
through amino and/or thiol groups included in the XTEN sequence. XTEN is
produced in large quantities by microbial fermentation, and subsequent
purification yields homogenous polymer. Whereas reagent PEG is provided as
a heterogeneous mixture, XTEN and its conjugates are distinct molecular
species observable by ESI-MS, permitting the efficient monitoring of
coupling reactions. This monodisperse nature of XTEN also facilitates the
purification and analysis of XTEN peptide conjugates by HPLC.
XTEN has been fused to multiple approved biopharmaceuticals to extend serum
half-life while retaining in vivo potency. The XTEN polypeptide is stable
in serum but, unlike PEG, does not accumulate in cells, eliminating the
risk of kidney vacuolation. Multiple preclinical studies have yielded no
evidence of XTEN immunogenicity, and clinical evaluation of two XTENylated
products is in progress.