Table 1.

Summary of GalNAc-siRNA or GalNAc-ASO Conjugates in the Clinic from the Leading Oligonucleotide Platform Companies

Clinical Phase	Company	Modality	Drug Name	Target	Lead Indication
Registered	Alnylam	siRNA	Givlaari	d-aminolevulinate synthase 1	acute hepatic porphyria
Submitted for registration	Alnylam	siRNA	lumasiran	glycolate oxidase 1	hyperoxaluria type 1
Submitted for registration	Alnylam/ Novartis	siRNA	inclisiran	PCSK9	hypercholesterolemia
Phase 3	Akcea/Ionis	ASO	AKCEA-TTR-LRx	transthyretin	TTR amyloidosis
Phase 3	Akcea/Ionis/Novartis	ASO	AKCEA-APO(a)-LRx	apolipoprotein(a)	cardiovascular disease
Phase 3	Alnylam/ Sanofi	siRNA	fitusiran	antithrombin	hemophilia/bleeding disorders
Phase 3	Alnylam	siRNA	vutrisiran	transthyretin	TTR amyloidosis
Phase 3	Dicerna	siRNA	nedosiran	lactate dehydrogenase	primary hyperoxaluria
Phase 2	Alnylam	siRNA	cemdisiran	complement C5	complement-mediated diseases
Phase 2	Akcea/Ionis	ASO	AKCEA-AOPCIII-LRx	apoC-III	cardiovascular disease
Phase 2	Ionis	ASO	IONIS-GHR-LRx	growth hormone receptor	acromegaly
Phase 2	Ionis	ASO	IONIS-PKK-LRx	prekallikrein	hereditary angioedema
Phase 2	Ionis	ASO	IONIS-TMPRSS6- LRx	transmembrane protease, serine 6	β-thalassemia
Phase 2	Akcea/Pfizer/Ionis	ASO	AKCEA-ANGPTL3-LRx	angiopoietin-like 3 protein	multiple lipid disorders
Phase 2	Ionis	ASO	IONIS-AGT-LRx	angiotensinogen	resistant hypertension
Phase 2	Ionis/Roche	ASO	IONIS-FB-LRx	complement factor B	Immunoglobulin A (IgA) neuropathy/age-related macular degeneration
Phase 2	Ionis/GSK	ASO	IONIS-HBV-LRx	HBV viral proteins	hepatitis B infection
Phase 2	Arrowhead/JNJ	siRNA	JNJ-3989(ARO-HBV)	HNV viral proteins	hepatitis B infection
Phase 1/2	Alnylam	siRNA	ALN-AAT02	AAT	α1 liver disease
Phase 1/2	Alnylam	siRNA	ALN-HBV02	HBV viral proteins	hepatitis B virus infection
Phase 1	Arrowhead/Amgen	siRNA	AMG-890 (ARO-LPA)	lipoprotein(a)	cardiovascular disease
Phase 1	Alnylam	siRNA	ALN-AGT	AGT	hypertension
Phase 1	Dicerna/Roche	siRNA	DCR-HBVS(RG6346)	HNV viral proteins	hepatitis B virus
Phase 1	Dicerna	siRNA	DCR-A1AT	SERPINA1	α1 anti-trypsin deficiency liver disease
Phase 1	Ionis/Bayer	ASO	IONIS-FX1-LRx	factor X1	thrombosis
Phase 1	Ionis/AstraZeneca	ASO	IONIS-AZ4-2.5LRx	not reported	cardiovascular disease
Phase 1	Ionis/AstraZeneca	ASO	ION839	not reported	NASH
Phase 1	Arbutus	siRNA	AB-729	viral protein	hepatitis B infection
Phase 1	Silence	siRNA	SLN-124	TMPRSS6	β-thalassaemia and MDS

Source: Alnylam, Ionis, Dicerna, Arbutus, Silence, and Roche pipeline website data accessed March 2020. Arrowheads ARO-AAT, ARO-APOC3, ARO-ANG3, and ARO-HSD use their TRIM (targeted RNAi molecule) technology but are not included since the exact nature of the liver-targeting conjugates for these molecules are not yet published but are assumed to be GalNAc targeting.