TABLE 2

In vivo pharmacokinetic parameters following 2-mg/kg intravenous administration of aDNP or conjugate 4 to wild-type mice and receptor knockout mouse models

Mouse Strain	T1/2	AUC_0–168	Cl	Vss	AUC_KO/AUC_WT	Cl_KO/Cl_WT
	h	μM h*	l/h/kg	l/kg
aDNP
WT	191	11.4	0.0006	0.150	—	—
FcRn KO	4.98	1.36	0.0092	0.063	0.12	15.3
LDL KO	183	8.45	0.0007	0.199	0.74	1.16
MR KO	240	12.3	0.0005	0.150	1.08	0.83
ASGR1 KO	333	14.2	0.0009	0.142	1.24	1.50
Conjugate 4 (total)
WT	164	2.79	0.0027	0.544	—	—
FcRn KO	1.19	0.096	0.133	0.237	0.03	49.3
LDL KO	118	4.67	0.0028	0.376	1.67	1.04
MR KO	104	1.55	0.0059	0.759	0.56	2.18
ASGR1 KO	197	3.57	0.0036	0.456	1.28	1.33
Conjugate 4 (intact)
WT	26.3	0.943	0.0131	0.277	—	—
FcRn KO	1.27	0.149	0.0892	0.164	0.16	6.81
LDL KO	38.4	1.30	0.0103	0.286	1.38	0.79
MR KO	24.7	1.12	0.0117	0.418	1.19	0.89
ASGR1 KO	19.9	1.32	0.0092	0.174	1.39	0.70

Cl, clearance; KO, knockout; MR, mannose receptor; WT, wild-type.