bone-targeted ENPP1-Fc

bone-targeted ENPP1-Fc (also known as ERT 2000 or clone 2000) is a preclinical-stage recombinant fusion protein designed as an enzyme replacement therapy for disorders associated with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency, such as Ossification of the Posterior Longitudinal Ligament (OPLL) and Diffuse Idiopathic Skeletal Hyperostosis (DISH). It consists of the extracellular domain of the ENPP1 enzyme fused to an antibody Fc domain, modified with a C-terminal bone-targeting peptide (a 6-aspartic acid tag, or D6 tag). This targeting moiety directs the enzyme specifically to bone tissue, where it hydrolyzes extracellular adenosine triphosphate (ATP) to generate inorganic pyrophosphate (PPi) and adenosine monophosphate (AMP). By restoring local PPi levels, the therapy prevents ectopic calcification of ligaments and tendons, suppresses spinal hyperostosis, and improves bone mineralization and skeletal fragility. The asset was developed by researchers at Yale University and Inozyme Pharma (which was acquired by BioMarin Pharmaceutical in 2025).

Other names

bone-targeted ectonucleotide pyrophosphatase/phosphodiesterase 1-Fc fusion proteinbone-targeted ENPP1bone-targeted ENPP1-Fc fusion protein