Amunix Operating Inc. presented unpublished data from its XTEN half-life extension technology development programs during two sessions at IBC’s 9th Annual Next Generation Protein Therapeutics Summit in San Francisco, CA. Amunix is a biotechnology company developing hydrophilic, unstructured polypeptides which can be recombinantly fused or chemically conjugated to other peptides, proteins and small molecules.
Vladimir N. Podust, PhD, Director of Analytical Chemistry, Amunix Operating Inc., presented “Extension of in vivo Half-Life of Biologically Active Molecules via Chemical Conjugation to XTEN Protein Polymer” during the section titled “Alternative Scaffolds and Delivery Strategies.”
XTEN (unstructured biodegradable polypeptides) have been used to extend the half-life of genetically fused therapeutic proteins and peptides. To expand the applications of XTEN technology to half-life extension of other classes of molecules, XTEN protein polymers and methods for chemical XTENylation were developed. Monovalent, multivalent and bispecific XTEN conjugates with various payloads have been synthesized and tested for their biological activities.
The presentation will show an efficient method of synthesis of targeted XTEN-drug conjugates, exemplified by folate as a targeting moiety and DM1 as a chemical toxin. The modular synthetic approach allows investigation of the effects of valency and polymer length, as well as the nature of the toxic payload to select the most potent product format for each indication.
Volker Schellenberger, PhD, Amunix President and Chief Executive Officer, presented “XTEN – A Biodegradable Alternative to PEG Enabling Biopharmaceuticals with Precisely Controlled Structure and Valency” during the section titled “Alternatives to PEG for Plasma Half-Life Extension.”
Amunix has developed XTEN, a protein-based polymer that mimics the biophysical properties of PEG. XTEN is easily metabolized, thereby eliminating the risk of tissue accumulation. Single or multiple payloads can be conjugated or genetically fused to XTEN which allows the generation of monospecific, bispecific, as well as multivalent biopharmaceuticals.
This presentation focused on the ability to customize XTEN for each application to enable discovery of long-acting biologics with best-in-class product attributes. Amunix’s technology allows one to include multiple XTEN polymers into a single product while maintaining precise positional control of each insertion site. Each insertion site and the length of inserted XTEN can be optimized to maintain or enhance biological activity while achieving increased duration of action of the resulting product. Examples of XTENylated biologics with class-leading duration of action will be shown.