Figure 3.
PK profiles of constructs 3 and 4. PK profiles were evaluated using methods described in Figure 2. (A) The PK of construct 3 was compared with rFVIIIFc and rFVIII in HemA mice. The PK of rFVIII (B), rFVIIIFc (C), and construct 3 (D) were compared in HemA, VWF heterozygous (VWF Het), and FVIII/VWF DKO mice. Doses from 125 to 200 IU/kg were used for IV injection, and plasma FVIII activity was normalized to the dose of factor administered and was plotted against time. Half-life (t1/2) was calculated by noncompartmental modeling using WinNonLin, version 5.2 (Pharsight Corp, Mountain View, CA). Data are means ± SD; n = 3 to 4 animals per group for all mouse studies. (E) The PK of BIVV001 (construct 4; 100 and 300 IU/kg IV) was evaluated in cynomolgus monkeys. FVIII activity was measured with a capture chromogenic assay (Act) or enzyme-linked immunosorbent assay (ELISA) (Ag). For capture chromogenic assay, a biotinylated anti-XTEN monoclonal antibody was used to capture BIVV001 and prevent interference from endogenous FVIII. For ELISA, antihuman FVIII (GMA-8023) was used to capture BIVV001 and prevent interference from endogenous FVIII. Data are means ± SD; n = 4 per group with 4 animals per time point.

PK profiles of constructs 3 and 4. PK profiles were evaluated using methods described in Figure 2. (A) The PK of construct 3 was compared with rFVIIIFc and rFVIII in HemA mice. The PK of rFVIII (B), rFVIIIFc (C), and construct 3 (D) were compared in HemA, VWF heterozygous (VWF Het), and FVIII/VWF DKO mice. Doses from 125 to 200 IU/kg were used for IV injection, and plasma FVIII activity was normalized to the dose of factor administered and was plotted against time. Half-life (t1/2) was calculated by noncompartmental modeling using WinNonLin, version 5.2 (Pharsight Corp, Mountain View, CA). Data are means ± SD; n = 3 to 4 animals per group for all mouse studies. (E) The PK of BIVV001 (construct 4; 100 and 300 IU/kg IV) was evaluated in cynomolgus monkeys. FVIII activity was measured with a capture chromogenic assay (Act) or enzyme-linked immunosorbent assay (ELISA) (Ag). For capture chromogenic assay, a biotinylated anti-XTEN monoclonal antibody was used to capture BIVV001 and prevent interference from endogenous FVIII. For ELISA, antihuman FVIII (GMA-8023) was used to capture BIVV001 and prevent interference from endogenous FVIII. Data are means ± SD; n = 4 per group with 4 animals per time point.

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