Activity of Mim8 in HA plasma and whole blood. (A-B) Peak thrombin generation (mean ± standard deviation, n = 5-8) in FXIa-triggered (1 mU/mL) platelet-poor severe congenital HA plasma supplemented with FVIII (A) or Mim8, emicizumab SIA, or Mim8 in combination with 100 U/dL FVIII (B). Using a variable slope 4-parameter model, 50% effective concentration of 12 ± 2 nM (Mim8) and 153 ± 29 nM (emicizumab SIA) were estimated. (C) Peak thrombin generation of Mim8 or emicizumab SIA in platelet-rich plasma (250 000-320 000 platelets/µL) from healthy volunteers supplemented with neutralizing anti-FVIII polyclonal antibody and triggered with 1 pM TF. (D) Effect of Mim8 or emicizumab SIA on the time to clot (R-time; mean ± standard deviation, n = 6) in whole blood from healthy volunteers supplemented with neutralizing anti-FVIII polyclonal antibody. Clot formation was triggered with TF (∼30 fM) and monitored by using thromboelastography (TEG). Using the same model as in panels A and B, 50% effective concentrations of 0.18 ± 0.02 nM (Mim8) and 6.2 ± 0.9 nM (emicizumab SIA) were estimated. Ranges obtained under normal or HA conditions are highlighted in light blue.