Figure 1.
Figure 1. Effects of in vivo administration of AMG 191 on CD34+ HSPCs and peripheral blood of cynomolgus macaques. (A) AMG 191 is cleared in the serum of NHPs in a dose-dependent manner. The highest levels of AMG 191 in serum of all animals were observed at the first time point collection (5 minutes after dose administration on day 1). Antibody levels measured on day 4 in the 0.1 mg/kg group fell below the assay detection limit of 50 ng/mL. The level of AMG 191 in serum was analyzed and terminal elimination half-life (t1/2) was determined. The averages of half-life (t1/2) obtained from 2 animals of each group are presented. (B) Representative fluorescence-activated cell sorter (FACS) plot showing CD34+ cells in BM of NHP #4 on days 0 (before AMG 191 treatment), 10, and 42 postadministration of 1.0 mg/kg AMG 191. CD34+ cells were gated from live cells. (C) Frequency of CD34+ cells among live cells in BM aspirates obtained from each NHP. BM aspirates were collected from individual NHPs (2 animals for each dose group) prior to the administration of AMG 191 (baseline, designated as day 0), and on days 4, 7, 10, 21, and 42 postadministration. AMG 191 was infused into animals on day 1. *Note: There was a technical inconsistency with the staining of the baseline cell samples collected from NHPs #5 to #8 (day 0). Red cell lysis was performed after the cells were stained, leading to a lower baseline of the CD34+ frequency of the stained populations. In all subsequent analyses, red cell lysis was performed before staining with the marker antibodies. Colors correspond to days relative to infusion. Animal identification (#1-#8) and dose level are shown on the x-axis. (D) RBC parameters affected by AMG 191 treatment. Hemoglobin and absolute reticulocyte count from individual NHPs taken before treatment (day 0) and postinfusion of AMG 191. Colored lines correspond to individual NHPs with doses as shown in the legend on the right. NHPs #3 to #8 had statistically significant decreases in hemoglobin from baseline compared with day 21 (P = .001; paired Student t test).

Effects of in vivo administration of AMG 191 on CD34+ HSPCs and peripheral blood of cynomolgus macaques. (A) AMG 191 is cleared in the serum of NHPs in a dose-dependent manner. The highest levels of AMG 191 in serum of all animals were observed at the first time point collection (5 minutes after dose administration on day 1). Antibody levels measured on day 4 in the 0.1 mg/kg group fell below the assay detection limit of 50 ng/mL. The level of AMG 191 in serum was analyzed and terminal elimination half-life (t1/2) was determined. The averages of half-life (t1/2) obtained from 2 animals of each group are presented. (B) Representative fluorescence-activated cell sorter (FACS) plot showing CD34+ cells in BM of NHP #4 on days 0 (before AMG 191 treatment), 10, and 42 postadministration of 1.0 mg/kg AMG 191. CD34+ cells were gated from live cells. (C) Frequency of CD34+ cells among live cells in BM aspirates obtained from each NHP. BM aspirates were collected from individual NHPs (2 animals for each dose group) prior to the administration of AMG 191 (baseline, designated as day 0), and on days 4, 7, 10, 21, and 42 postadministration. AMG 191 was infused into animals on day 1. *Note: There was a technical inconsistency with the staining of the baseline cell samples collected from NHPs #5 to #8 (day 0). Red cell lysis was performed after the cells were stained, leading to a lower baseline of the CD34+ frequency of the stained populations. In all subsequent analyses, red cell lysis was performed before staining with the marker antibodies. Colors correspond to days relative to infusion. Animal identification (#1-#8) and dose level are shown on the x-axis. (D) RBC parameters affected by AMG 191 treatment. Hemoglobin and absolute reticulocyte count from individual NHPs taken before treatment (day 0) and postinfusion of AMG 191. Colored lines correspond to individual NHPs with doses as shown in the legend on the right. NHPs #3 to #8 had statistically significant decreases in hemoglobin from baseline compared with day 21 (P = .001; paired Student t test).

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