PolyXen for Protein Drug Delivery
PolyXen is an enabling platform technology for protein and peptide drug delivery. It uses the biological polymer polysialic acid (PSA) to prolong the drug's half-life and potentially improve the stability of therapeutic peptides and proteins. Both the site of attachment and the length of the PSA chain can influence the properties of the therapeutic by changing the apparent hydrodynamic radius of the molecule, which in turn, can enhance a number of the biological characteristics of the therapeutic. It can also be used for small molecule drugs.
Benefits of PolyXen
Preclinical proof-of-concept studies and multiple human clinical studies have shown that the key benefits of PolyXen for protein drug delivery may include:
- Prolongation of functional half-life in circulation
- Improved in vivo stability and prolonged pharmacological action
- Reduced frequency and amount of dosage
- Reduced immunogenicity and antigenicity
PolyXen has been demonstrated in human clinical trials to confer extended half-life to biotherapeutics such as recombinant human erythropoietin (rhEPO) and recombinant Factor VIII (rFVIII).
Xenetic is leveraging PolyXen to partner with biotechnology and pharmaceutical companies. The Company receives royalty payments under an exclusive license arrangement in the field of blood coagulation disorders. In addition, Xenetic’s partner, PJSC Pharmsynthez ("Pharmsynthez"), is leveraging the Company’s PolyXen® technology to improve the pharmacological properties of its Epolong (erythropoietin and polysialic acid conjugate) product candidate pursuant to a royalty-bearing collaboration agreement between the Company's wholly owned subsidiary, Lipoxen Technologies Limited, and Pharmsynthez's wholly owned subsidiary, SynBio LLC. Pharmsynthez has reported that it has started the registration phase of Epolong by filing a registration dossier to obtain approval of Epolong in Russia for the treatment of anemia in patients with chronic kidney disease. The registration dossier is based on previously reported data from Pharmsynthez's Phase 3 clinical trials of Epolong in Russia, which reportedly demonstrated the efficacy of Epolong and its potential to reduce side effects.
What is polysialic acid?
Polysialic acid (PSA) is a polymer chain comprised of sialic acids linked together. Sialic acid is found on the external membrane of a number of cell types in the body. In addition, it is a natural component expressed on the external membrane on a number of bacterial types. When used for therapeutic protein and peptide drug delivery, PSA provides a protective microenvironment following conjugation to the active drug. This increases the active half-life of the therapeutic drug in the body and allows it to exist largely undetected by the immune system.
How does PSA work?
The PSA polymer is naturally found in the human body. However, PSA evolved initially as part of the coat on the external walls of certain bacteria, which are able to remain largely undetected by the immune system. Our partners are producing PSA from these bacteria in large quantities and with predetermined physical characteristics. Bacterial PSA is an ideal polymer for drug conjugation as it is biodegradable and non-immunogenic, even when coupled to proteins. This is particularly important when a polymer is being used to deliver therapeutics chronically or in large dosages.
How does PolyXen technology use PSA?
PolyXen uses proprietary techniques to conjugate PSA molecules of appropriate length to specific sites of the therapeutic molecule. The PSA molecules form a glycocalyx (a carbohydrate shield) around the therapeutic molecule, rendering it less exposed to the body's immune system, as well as less exposed to serum proteases and other clearance mechanisms, including renal clearance.
Review our key scientific publications/presentations featuring our PolyXen technology.