Preventive effects of ACE910 on spontaneous joint bleeds in a long-term primate model of acquired hemophilia A. (A) Experimental protocol used for evaluating preventive effects of ACE910 in a long-term hemophilia A model induced by the weekly IV doses of 10 mg/kg cyVIII-2236. The 8 cynomolgus monkeys received weekly IV injections of cyVIII-2236 on days 0, 7, 14, 21, 28, 35, 42, and 49. ACE910 was administered as an initial 3.97 mg/kg SC dose 2 hours after cyVIII-2236 injection on day 0, and thereafter as a weekly 1 mg/kg SC dose on days 7, 14, 21, 28, 35, 42, and 49. Citrated blood was collected on days 0, 4, 7, 11, 14, 18, 21, 25, 28, 32, 35, 39, 42, 46, 49, 53, and 56 (before and 2 hours after cyVIII-2236 injection on day 0; just before cyVIII-2236, vehicle, and ACE910 injections on days 7, 14, 21, 28, 35, 42, and 49). (B) The time courses of APTT are shown as individual values for respective cynomolgus monkeys (#1-4) of the vehicle and ACE910 groups. The APTT of the vehicle #3 monkey on day 46 was not determined due to a handling failure. (C) The days in which limping was observed are shown in red for the individual cynomolgus monkeys. The gray boxes indicate that no data are available because the ACE910 #4 monkey was killed for humane reasons on day 28 (See “Results”). The number of days with limping (C) and the number of bleeding joints at necropsy (D) are shown as individual values (#1-4) and as means ± SD in the vehicle group (n = 4) and the ACE910 group (n = 3). **P < .01 indicates significant differences from the vehicle group (2-tailed Student t test). (E) Representative macroscopic findings of the joints at necropsy. Left hip joint with limping in the vehicle #1 monkey; dark-red area in the Af (i) and Hf (ii) is detected. Left hip joint without limping in the ACE910 #3 monkey; no abnormalities are noted in the Af (iii) and Hf (iv). Ac, acetabulum; Af, acetabular fossa; Hf, head of femur.