Akari is progressing development of several formulations and enhanced molecules to extend the half-life of Coversin in humans. The objective of these projects is to reduce the dosing frequency of Coversin from daily to weekly self-administered subcutaneous injection, thereby further enhancing patient convenience.
The most advanced long-acting Coversin development-stage product involves the use of PASylation®, a proprietary technology of XL-protein GmbH. PASylation® entails modifying Coversin by adding a 600 amino acid proline/alanine/ serine (PAS) N-terminal fusion tag to generate PASylated Coversin (68kDa). The resultant unstructured and uncharged PAS polypeptide increases the apparent molecular size of Coversin from 17kDa to approximately 720kDa, thus slowing kidney clearance and dramatically extending the half-life. In mouse models, subcutaneously delivered PAS-Coversin was 100% bioavailable with a 52-fold increase in half-life compared to unmodified Coversin. In vitro complement lytic and C5 binding assays indicate PASylated Coversin inhibits complement C5 as potently as unmodified Coversin.
Akari currently expects to test PASylated Coversin in a human trial beginning in 2018.