Fig. 4. REGN5381 reduces systolic BP and CVP in a temporally dose-dependent manner.

a,b, Beagle canines were surgically implanted with a radiotelemetry transmitter. A cross-over design was used and animals each received a single intravenous bolus of saline (control) (n = 2; black circles) or REGN5381 25 mg per kg (n = 2; red circles). BP measurements were collected pre-dose (baseline measurements) and during a 48 h post-dose monitoring period. Post-dose systolic BP assessment after administration of REGN5381 (red circles) or control (saline, black circles) (a) and urinary cGMP concentration (b). PK, pharmacokinetics. c,d, Anaesthetized beagle canines were instrumented with venous and arterial catheters. Each canine received a single intravenous bolus of saline (control, n = 6) or 25 mg per kg REGN5381 (n = 6) and was monitored for acute haemodynamic changes. Post-dose CVP (c) and heart rate (d) change from baseline (subscripted ‘Δbaseline’) is shown. bpm, beats per minute. e–h, Cynomolgus monkeys were surgically implanted with a radiotelemetry transmitter. The animals each received a single intravenous bolus of saline/vehicle (n = 4; black circles) or REGN5381 subcutaneously (s.c.; n = 4, 1 mg per kg, pink line; n = 5, 5 mg per kg, pale yellow line; n = 5, 25 mg per kg, red line) or intravenously (n = 5, 5 mg per kg, light blue line; n = 5, 25 mg per kg, dark blue line). BP measurements were collected for each animal before dosing (baseline measurements) and until study day 56. The change from baseline over time was determined for each individual non-human primate (NHP) for systolic BP (e), heart rate (f) and pulse pressure (g). h, The baseline and 24 h post-dose cGMP levels in the urine of non-human primates. Each symbol represents one individual animal. Data are mean ± s.e.m. *P = 0.0178 (light blue group), **P = 0.0081 (dark blue group), ****P < 0.0001 (red group).