ARC19499 effect on clot formation in FVIII antibody–treated cynomolgus monkeys. (A) In vitro dose response of ARC19499 added to plasma from cynomolgus monkeys previously treated with a bolus of anti-FVIII antibody to eliminate FVIII activity. Lines represent activity of cynomolgus monkey plasma before (solid lines) and after (dashed lines) antibody treatment in the absence of aptamer, with shaded areas representing SEM. (B) Schematic of in vivo dosing and blood drawing schedule for the study. There were 4 distinct groups of monkeys treated with saline or with 100, 300, or 600 μg/kg of ARC19499. (C) Representative TEG tracings from plasma of cynomolgus monkeys treated with FVIII antibody followed by saline (left), 100 μg/kg of ARC19499 (middle), or 600 μg/kg of ARC19499 (right). Black line shows the baseline time point; green, 2.5 hours after antibody administration; pink, 0.25 hours after aptamer or saline treatment; red, 1 hour after treatment; and blue, 2 hours after treatment. (D) Effect of ARC19499 treatment on TEG parameters. Left panel shows the R value; right, angle. Monkeys were treated with anti-FVIII antibody, followed by saline (▵) or 100 (●), 300 (♦), or 600 (■) μg/kg of ARC19499. Results are represented as the means ± SEM; n = 3 for saline and the 100 μg/kg ARC19499 dose; n = 6 for the 300 μg/kg dose; and n = 2 for the 600 μg/kg dose.