FIGURE 3.

Pharmacodynamics of MEDI1814 in cynomolgus monkeys. Intravenous weekly administration of MEDI1814 over 13 weeks in cynomolgus monkey: (A), free CSF Aβ₄₂; (B) total plasma Aβ₄₂; (C) total CSF Aβ₄₂; (D) total CSF Aβ₄₀. A dose‐dependent increase in total Aβ₄₂ in both plasma and CSF was observed at the end of the treatment phase in the 10 mg/kg IV, 100 mg/kg IV, and 75 mg/kg SC groups. The majority of free Aβ₄₂ (> 95%) was suppressed in CSF at all dose levels at the end of the treatment phase (A). At the end of a 9‐week treatment‐free period, total Aβ₄₂ levels in plasma increased in the 100 mg/kg IV dose group compared to the vehicle group (B); compared to the vehicle group, total CSF Aβ₄₂ was higher, though not significant (C), and free CSF Aβ₄₂ was suppressed. The specificity of MEDI1814 binding to Aβ₄₂ over Aβ₄₀ was confirmed by lack of effect on total CSF Aβ₄₀ at all tested doses (D). Washout denotes a period of 9 weeks after dosing had stopped. Aβ, amyloid beta; CSF, cerebrospinal fluid; ELISA, enzyme‐linked immunosorbent assay; IV, intravenous; LOQ, limit of quantification; SC, subcutaneous.