Using PASylation®, a proprietary process of XL-protein GmbH, XL-protein has modified nomacopan by adding a 600 amino acid proline/alanine/ serine (PAS) N-terminal fusion tag to generate PAS-nomacopan (68kDa). The unstructured and uncharged PAS polypeptide increases the apparent molecular size to approximately 700kDa, slowing kidney clearance and extending the half-life.
Data from animal studies of PAS-nomacopan demonstrated that the expected terminal half-life in humans should be approximately 4 days. Based on these data, PK modelling supports that a once-weekly dosing regimen is feasible.