Denecimig (Mim8) is a bispecific and humanized IgG4κ antibody mimicking activated coagulation factor VIII with anti-FIXa and anti-FX arms, which is used for the treatment of hemophilia A and coagulation disorders primarily by facilitating the assembly of activated coagulation factors IXa (FIXa) and X (FX) on platelet membranes, stimulating activation of FX, and arresting bleeding.

In a study of hemostatic activity in blood samples from hemophilia patients, both Thrombin Generation Assay (TGA) and Thromboelastography (TEG) were used for evaluation. TGA was performed using PPP-low reagent and PRP reagent. Whole blood samples were analyzed with the ROTEMdelta device for NATEM analysis, providing a comprehensive assessment of the coagulation status. The study also evaluated the effects of Denecimig when used in combination with recombinant FVIII (100 IU/dL), recombinant FVIIa (25 mM), and APCC (20 and 30 U/kg). The in vitro Results showed that Denecimig significantly enhanced thrombin generation in severe hemophilia A patients, with its procoagulant effect comparable to 100 IU/dL of FVIII. Further research found that when Denecimig was used in combination with rFVIIa (90 µg/kg), it did not induce a hypercoagulable state. However, when Denecimig was combined with APCC, it could significantly increase the risk of hypercoagulation [1].

In the toxicity study of Denecimig using monkeys as subjects, intravenous or subcutaneous administration (0.3–60 mg/kg/week) was employed. The Results showed that Denecimig (0.3–3 mg/kg/week, subcutaneous injection) did not induce significant clinical symptoms, excessive coagulation, or pathological changes. However, when the dose was increased to 6–20 mg/kg/week, 16% of the animals exhibited thrombosis-related pathological changes[2].