CT-001 is a rapid clearing factor VIIa with enhanced clearance and hemostatic activity for the treatment of acute bleeding in non-hemophilia settings.

Acute bleeding leads to significant morbidity and mortality. Recombinant wildtype Factor VIIa (WT FVIIa) had been reported to have some therapeutic effects in some clinical trials, however, its use was associated with thromboembolic events. We sought to develop a novel FVIIa molecule (CT-001) with enhanced activity and lowered thrombogenicity risk. CT-001 has 4 N-glycans (T106N/N145/V253N/N322) with terminal sialic acid residues removed to promote active clearance via the asialoglycoprotein receptor, and P10Q/K32E substitutions introduced to its gamma-carboxyglutamic acid (Gla) domain for enhanced phospholipid affinity and activity. In mice, CT-001 had a half-life of 5 min and a clearance of 467 mL/h/kg at 3 mg/kg, significantly faster than WT FVIIa (t The data on CT-001 demonstrate that a short duration of highly active FVIIa procoagulant activity has the potential to be an optimal paradigm for the treatment of acute bleeds.

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