TABLE 3

Summary of mean anti-PCSK9 antibody PK (±S.D.) and LDL-C PD (±S.E.M.) in monkeys

			Antibody Pharmacokinetics							LDL-C Pharmacodynamics
Antibody	Dose^{^a}	N	AUC_inf	AUC_last	CL	V_ss	CL/F	C_max	t_1/2,z	E_max	ECA	Duration
	mg/kg		μg×h/ml		ml/h per kg	ml/kg	ml/h per kg	μg/ml	h	mg/dl	mg × day/dl	day
mAb1	0.5	5	370 ± 52	364 ± 53	—	—	1.37 ± 0.17	4.84 ± 0.62	49 ± 18	41 ± 5	422 ± 97	6
	3	3	4410 ± 300	4400 ± 300	0.683 ± 0.047	44.1 ± 4.6	—	—	42 ± 4	44 ± 5	531 ± 109	10
mAb1_YTE	3	4	5460 ± 2590	5460 ± 2590	0.650 ± 0.307	53.1 ± 9.3	—	—	52 ± 9	52 ± 7	608 ± 178	10
mAb1_LS	3	4	4430 ± 910	4420 ± 450	0.684 ± 0.075	49.3 ± 4.8	—	—	43 ± 4	47 ± 6	508 ± 112	10
mAb2	0.5	5	4180 ± 700	3810 ± 490	—	—	0.123 ± 0.021	9.27 ± 0.27	340 ± 70	37 ± 7	1230 ± 280	51
	1^{^b}	4	6050 ± 450	5960 ± 830	0.168 ± 0.026	56.3 ± 3.7	—	—	270 ± 70	40 ± 5	1280 ± 250	35
	1^{^c}	4	4650 ± 850	4540 ± 790	0.222 ± 0.049	81.1 ± 14.4	—	—	250 ± 140	34 ± 6	1100 ± 280	36
mAb2_YTE	1	4	11,000 ± 1800	10,100 ± 1400	0.0931 ± 0.0164	61.1 ± 6.6	—	—	470 ± 110	38 ± 5	1490 ± 390	42
mAb2_LS	1	4	9200 ± 2560	8430 ± 2130	0.118 ± 0.044	67.7 ± 15.2	—	—	420 ± 230	44 ± 4	1970 ± 480	56
mAb2_8	1	4	7030 ± 1360	6500 ± 1070	0.147 ± 0.034	75.8 ± 18.8	—	—	430 ± 230	36 ± 4	1330 ± 290	43
mAb2_119	1	4	4950 ± 1530	4110 ± 1630	0.217 ± 0.068	59.4 ± 13.8	—	—	200 ± 130	40 ± 7	1450 ± 450	43
mAb3	0.5	5	1170 ± 120	1160 ± 120	—	—	0.432 ± 0.043	6.64 ± 0.68	150 ± 40	47 ± 5	925 ± 128	18
	1	4	1590 ± 190	1570 ± 170	0.634 ± 0.071	72.9 ± 17.2	—	—	150 ± 80	41 ± 5	470 ± 50	11
mAb3_8	1	4	2370 ± 150	2360 ± 150	0.422 ± 0.026	61.2 ± 9.5	—	—	140 ± 60	38 ± 6	718 ± 226	18
mAb3_119	1	4	2700 ± 510	2660 ± 520	0.381 ± 0.075	54.6 ± 5.3	—	—	120 ± 40	37 ± 6	370 ± 63	18
mAb4	0.5	5	2110 ± 500	2020 ± 490	—	—	0.249 ± 0.067	6.09 ± 0.71	250 ± 140	42 ± 5	1320 ± 240	39
IgG2 control	0.5	5	4030 ± 790	3390 ± 500	—	—	0.128 ± 0.028	6.92 ± 0.97	460 ± 90	—	—	—

AUC_inf, AUC from zero to infinite time; AUC_last, AUC from time zero to the time of last quantifiable concentration; C_max, maximum observed antibody concentration; V_ss, volume of distribution at steady state.
↵^a Doses of 0.5 mg/kg were administered s.c., and doses of 1 or 3 mg/kg were administered i.v.
↵^b Data from study 2.
↵^c Data from study 3; see Materials and Methods.