Table 2.
Status of NADs-based therapeutics clinical trials
| Drug (alternate name) | Company | Classification | Indication (Phase) | Target | Modification & Delivery | Clinical Trail Number | Ref(s) |
|---|---|---|---|---|---|---|---|
| Rare genetic disorders | |||||||
| NTLA-2001 | Intellia Therapeutics | CRISPR-Cas9 | ATTR-CM (III) | TTR | LNP | NCT06128629 | 296,588 |
| Zilganersen (ION-373) | Ionis | ASO | Alexander disease (III) | GFAP mRNA | 2’-MOE | NCT04849741 | 589 |
| Fitusiran (ALN-AT3) | Sanofi | siRNA | Hemophilia A/B (III) | Serpin C1 | GalNAc | 590 | |
| Donidalorsen (IONIS-PKK-LRx) | Ionis | ASO | HAE (III) | PKK | GalNAc, 2’-MOE | NCT05392114 | 591,592 |
| Ulefnersen (ION-363) | Ionis | ASO | ALS (III) | FUS | PS, 2’-MOE | NCT04768972 | 506 |
| Cemdisiran (ALN-CC5) | Alnylam & Regeneron | siRNA | PNH, Myasthenia gravis (III), IgAN, (II) | Complement C5 | 2ʹ-OME,2’-OF & GalNAc | 593,594 | |
| Vesleteplirsen (SRP-5051) | Sarepta Therapeutics | ASO | DMD (II) | Exon 51 of DMD | PMO/ PPMO | NCT04004065 | 500 |
| PGN-EDO51 | PepGen | ASO | DMD (II) | Exon 51 of DMD | EDO | NCT06079736 | 501 |
| ATL-1102 (ISIS-107248) | Antisense Therapeutics | ASO | DMD (II) | ITGA4 | 2’-MOE | NCT05938023 | 595 |
| Zorevunersen (STK-001) | Stoke Therapeutics | ASO | Dravet Syndrome (II) | SCN1A | 2’-MOE | 596 | |
| IONIS-MAPTRx (BIIB-080) | Ionis & Biogen | ASO | Mild Alzheimer’s Disease (II) | MAPT | 2’-MOE, PS | / | |
| SQY51 | Sqy Therapeutics | ASO | DMD (I/II) | Exon 51 of DMD | tricyclo-DNA | NCT05753462 | / |
| NTLA-2002 | Intellia Therapeutics | CRISPR-Cas9 | HAE(I/II) | KLKB1 | LNP | NCT05120830 | 597 |
| mRNA-3705 | Moderna | mRNA | MMA (I/II) | MUT | LNP | 598 | |
| Cancer | |||||||
| mRNA-4157 (V-940) | Merck & Moderna | mRNA | NSCLC, Melanoma (III) | / | LNP | 599 | |
| Autogene Cevumeran (BNT-122) | BioNTech | mRNA | Colorectal, PDAC (II) | unspecified TAAs | LNP | 600 | |
| IGV-001 | Imvax | ASO | GBM (II) | IGF type 1 receptor | PS, Goldspire™ | NCT04485949 | 520 |
| Cotsiranib (STP-705) | Sirnaomics | siRNA | Keloid, BCC, hypertrophic scars, isSCC (II) | TGF-β1、COX-2 | PNP | NCT04669808 | 482 |
| QN-165 (AS1411) | Qualigen Therapeutics | Aptamer | RCC, glioma and AML (II) | Nucleolin | / | 183,184 | |
| Cobomarsen (MRG-106) | miRagen Therapeutics | miRNA | MF, CTCL, DLBCL, CLL, ATLL (I/II) | miR-155 inhibitor | LNA | 125,126 | |
| olaptesed pegol | TME Pharma | Aptamer | Tumor, GBM (I/II) | CXCL12 | / | 601 | |
| TTX-MC138 | TransCode | miRNA | advanced solid tumors (I/II) | miRNA-10b inhibitor | iron oxide nanocarrier | 127 | |
| STP-707 | Sirnaomics | siRNA | solid tumors (I) | TGF-β1、COX-2 | PNP | NCT05037149 | / |
| MTL-CEBPA | MiNA Therapeutics | saRNA | HCC (I) | CEBPA | / | NCT02716012 | 142–144 |
| RAG-01 | Ractigen Therapeutics | saRNA | NMIBC (IND) | CDKN1A | / | / | 122 |
| Ophthalmic diseases | |||||||
| Tivanisiran (SYL1001) | Sylentis, S.A. | siRNA | DED (III) | TRPV1 | / | 528 | |
| Sepofarsen (QR-110) | ProQR Therapeutics | ASO | LCA10 (III) | CEP290 | 2’-OME | NCT03913143 | 602 |
| Ultevursen (QR-421a) | ProQR Therapeutics | ASO | Usher syndrome and nsRP (II/III) | USH2A | 2’-OME | NCT05158296 | 533 |
| SYL1801 | Sylentis | siRNA | AMD (II) | NRARP | / | NCT05637255 | 526 |
| RBM-007 (APT-F2) | Ribomic | Aptamer | wet AMD (II) | FGF2 | / | 525 | |
| IONIS-FB-LRx (RO7434656) | Roche & Ionis | ASO | GA (II) | Complement Factor B | 2’-MOE & GalNAc | NCT03815825 | 603 |
| Cardiovascular diseases | |||||||
| Pelacarsen (AKCEA-APO(a)-LRx) | Novartis AG | ASO | CVD (III) | ApoA | 2’-MOE & GalNAc | 542,604 | |
| Lepodisiran | Lilly | siRNA | ASCVD (III) | ApoA | 2’-MOE, 2’-F & GalNAc | NCT06292013 | 546 |
| Olpasiran (AMG 890) | Amgen Biopharmaceuticals | siRNA | ASCVD (III) | ApoA | 2’-MOE & GalNAc | 547,548 | |
| IONIS-FB-LRx (RO7434656) | Roche & Ionis | ASO | Primary IgA Nephropathy (III) | Complement Factor B | 2’-MOE & GalNAc | NCT05797610 | / |
| Olezarsen (IONIS-APOCIII-LRx) | Akcea Therapeutics & Ionis | ASO | SHTG & FCS (III) | ApoC-III | GalNAc | 605,606 | |
| Zodasiran (ARO-ANG3) | Arrowhead Pharmaceuticals | siRNA | HoFH (II) | ANGPTL3 | 2’-OME, 2’-F & GalNAc | NCT05217667 | 607 |
| Zilebesiran (ALN-AGT01) | Alnylam | siRNA | Hypertension (II) | Angiotensinogen | 2’-MOE, 2’-F & GalNAc | 608 | |
| MRG-110 (S-95010) | miRagen Therapeutics | miRNA | Chronic heart failure (I) | miR-92a Inhibitors | LNA | NCT03603431 | 125 |
| Infection diseases | |||||||
| mRNA-1345 | Moderna | mRNA | Respiratory syncytial virus infection (III) | RSV fusion | LNP | NCT06067230 | 609 |
| mRNA-1647 | Moderna | mRNA | Cytomegalovirus infection (III) | HCMVgB & HCMVgH | LNP | NCT05085366 | 610 |
| Bepirovirsen (GSK-3228836) | GSK & Ionis | ASO | HBV (III) | HBV RNA | 2’-MOE | 559 | |
| GSK-5637608 (JNJ-73763989) | GSK | siRNA | HBV (II) | HBV RNA | GalNAc |
NCT0512359 |
560 |
| ALN-HBV02 (VIR-2218) | Alnylam & Brii Biosciences Ltd & Vir Biotechnology | siRNA | HBV (II) | HBV RNA | 2’-OME, 2’-F & GalNAc | NCT05612581 | 561 |
| Imdusiran (ARB-270729) | Arbutus Biopharma | siRNA | HBV (II) | hepatitis B surface antigen | 2’-F & GalNAc | 562 | |
| mRNA-1944 | Moderna | mRNA | Chikungunya Virus (I) | CHKV-24 | LNP | NCT03829384 | 295 |
| Other diseases | |||||||
| Sapablursen (IONIS-TMPRSS6-LRx) | Ionis | ASO | PV (II) | TMPRSS6 | 2’-MOE & GalNAc | NCT05143957 | 611 |
| CWT001 (TenoMiR) | Causeway Therapeutics | miRNA | Lateral epicondylitis (II) | microRNA-29a mimic | 2’-OME, 2’-F | NCT06192927 | / |
| ION224 | Ionis | ASO | MASH (II) | DGAT2 | 2’-MOE & GalNAc | NCT04932512 | 612 |
| Rapirosiran (ALN-HSD) | Alnylam | siRNA | NASH (II) | HSD17B13 | 2ʹ-MOE, 2’-F & GalNAc | NCT05519475 | / |
| ALN-KHK | Alnylam | siRNA | T2DM (I/II) | KHK | GalNAC | NCT05761301 | / |
| OLX10010 (BMT-101) | Olix Pharmaceuticals | siRNA | Hypertrophic scars (II) | CTGF | 2’-MOE | / | |
| Remlarsen (MRG-201) | miRagen Therapeutics | miRNA | Keloid disorder (II) | microRNA-29 mimic | / | NCT03601052 | 124 |
| AON-D21 | Aptarion Biotech | Aptamer | Community-acquired pneumonia (II) | C5a | / | NCT05962606 | 613 |