Horizon

Horizon (also known as PAS-uricase) is a PASylated recombinant uricase (urate oxidase) enzyme being developed for the treatment of gout. Developed by XL-protein in collaboration with Horizon Therapeutics (now part of Amgen), the drug utilizes XL-protein's proprietary PASylation technology. This technology involves the genetic fusion of the enzyme with a conformationally disordered polypeptide consisting of Proline, Alanine, and Serine (PAS) residues. This modification increases the hydrodynamic volume of the protein, significantly extending its plasma half-life and potentially reducing its immunogenicity compared to PEGylated alternatives like pegloticase. The uricase enzyme functions by catalyzing the oxidation of uric acid into allantoin, a more soluble metabolite that is easily excreted by the kidneys, thereby reducing serum uric acid levels in patients with chronic gout. The program is currently in Phase 1 clinical development.