Table 2.
Selected oligonucleotide therapeutics that have entered development
| Company | Drug (partner) | Modality/delivery technology | Target/organ | Indication | Clinical trial stage |
|---|---|---|---|---|---|
| Ionis Pharmaceuticals | IONIS-HTTRx/RG6042 (Roche) | ASO/none | HTT/brain | Huntington disease | Phase III |
| Tofersen (Biogen) | ASO/none | SOD1/brain and spinal cord | ALS | Phase III | |
| IONIS-C9Rx | ASO/none | C9ORF72/brain and spinal cord | ALS | Phase II | |
| IONIS-MAPTRx | ASO/none | MAPT/brain | Alzheimer disease/FTD | Phase II | |
| IONIS-DNM2-2.5Rx (Dynacure) | ASO/none | DNM2/muscle | Centronuclear myopathy | Phase I | |
| Undisclosed | ASO/none | Various targets/heart and tumours | Various rare diseases, cardiometabolic disorders and cancers | Phase II | |
| Sarepta Therapeutics | Casimersen | PMO ASO/none | DMD exon 45/muscle | DMD | Phase III |
| SRP-5051 | PPMO ASO/peptide platform | DMD exon 51/muscle | DMD | Phase I | |
| Nippon Shinyaku Pharma | Viltolarsen | ASO/none | DMD exon 53/muscle | DMD | Phase II (approved in Japan) |
| Alnylam Pharmaceuticals | Fitusiran/ALN-AT3 (Sanofi Genzyme) | siRNA/GalNAc platform | SERPINC1/liver | Haemophilia A and B | Phase III |
| Lumasiran/ALN-GO1 | siRNA/GalNAc platform | HAO1/liver | Primary hyperoxaluria type 1 | Phase III | |
| Vutrisiran/ALN-TTRsc02 | siRNA/GalNAc platform | TTR/liver | Hereditary amyloidosis | Phase III | |
| Revusiran/ALN-TTRSC | siRNA/GalNAc platform | TTR/liver | Hereditary amyloidosis | Phase III — discontinued | |
| Inclisiran (Medicines Company and Novartis) | siRNA/GalNAc platform | PCSK9/liver | Hypercholesterolaemia | Phase III | |
| Wave Life Sciences | Suvodirsen | ASO/stereopure | DMD exon 51/muscle | DMD | Phase III — discontinued |
| WVE-120101; WVE-120102 (Takeda) | ASO/stereopure | Mutant HTT/brain and spinal cord | Huntingdon disease | Phase I | |
| Quark Pharmaceuticals | QPI-1002 | siRNA/none | TP53/kidney | Kidney delayed graft function/acute kidney injury | Phase III |
| Sylentis | Tivanisiran | siRNA/none | TRPV1/eye | Dry eye syndrome | Phase III |
| Moderna | AZD8601 (AstraZeneca) | mRNA/none | VEGFA/heart | Cardiac regeneration | Phase II |
| Santaris/Roche | Miravirsen | Anti-miRNA/none | miR-122/liver | Hepatitis C infection | Phase II — discontinued |
| Regulus Therapeutics | RG-012 (Sanofi Genzyme) | Anti-miRNA/none | miR-21/kidney | Alport syndrome | Phase II |
| RGLS4326 | Anti-miRNA/none | miR-17/kidney | Autosomal dominant polycystic kidney disease | Phase I | |
| RG-101 | Anti-miRNA/GalNAc platform | miR-122/liver | Hepatitis C infection | Phase II — discontinued | |
| Mirage Therapeutics | Cobomarsen/MRG-106 | Anti-miRNA/none | miR-155/lymphomas | Cutaneous T cell lymphoma | Phase II |
| Remlarsen/MRG-201 | miRNA mimic/none | miR-29/skin | Cutaneous fibrosis | Phase II | |
| Arbutus Biopharma | AB-729 | Anti-miRNA/GalNAc platform | Hepatitis B virus HBsAg/liver | Hepatitis B infection | Phase I |
| Arrowhead Pharmaceuticals | ARO-AAT | siRNA/TRiM platform — GalNAc-related | AAT/liver | α1-Antitrypsin deficiency | Phase II |
| Silence Therapeutics | SLN124 | siRNA/GalNAc platform | TMPRSS6/liver | β-Thalassaemia | Phase I |
| Dicerna Pharmaceuticals | DCR-PHXC | siRNA/GalXC platform — GalNAc-related | LDHA/liver | Primary hyperoxaluria | Phase I |
| MiNA Therapeutics | MTL-CEPBA | saRNA/LNP (SMARTICLES) | CEBPA/liver | Hepatocellular carcinoma | Phase I/II |
| Avidity Biosciences | Undisclosed | siRNA or ASO/antibody platform | DMPK/muscle | Myotonic dystrophy I | Preclinical |
| PepGen Ltd | Undisclosed | siRNA or ASO/peptide platform | Undisclosed target/muscle and central nervous system | Neuromuscular disease | Preclinical |
| Stoke Therapeutics | Undisclosed | ASO/none | SCN1A/brain | Dravet syndrome | Preclinical |
ALS, amyotrophic lateral sclerosis; ASO, antisense oligonucleotide; DMD, Duchenne muscular dystrophy; FTD, frontotemporal dementia; GalNAc, N-acetylgalactosamine; LNP, lipid nanoparticle; miRNA, microRNA; PMO, phosphorodiamidate morpholino oligonucleotide; PPMO, peptide–PMO; saRNA, small activating RNA; siRNA, small interfering RNA.