Nucleic Acid Medicine Industry Trends: First Half of July 2026
Simultaneous 'advancement and selection' in late-stage clinical trials: RNA editing, CNS/cardiac delivery, and DDS/manufacturing platforms emerge as the next axes of competition
In the first half of July 2026, the nucleic acid medicine industry saw significant progress across a wide range of modalities, including ASOs, siRNAs, RNA editing, mRNA, and aptamers.
Of particular note was the steady progress of Phase 3 trials for ASOs targeting rare neurological diseases, while the challenges of late-stage clinical development were once again highlighted in ATTR cardiac amyloidosis and Huntington's disease. Furthermore, progress was seen in technical foundations that expand the scope of nucleic acid medicines, such as proof-of-concept for RNA editing in humans, siRNA delivery to the heart and central nervous system, and LNP targeting utilizing aptamers.
The second half of June saw notable progress in the approval and filing of siRNA drugs, ASOs targeting neurological and muscular diseases, next-generation artificial nucleic acids, and manufacturing technologies. The first half of July saw these trends accelerate, reinforcing the impression that nucleic acid medicine has entered a stage of competing on 'how far clinical efficacy can be proven' and 'how delivery to difficult-to-target tissues and commercial supply can be achieved.'
RNA editing demonstrates target binding in humans: Toward clinical validation of new therapeutic principles
ProQR Therapeutics announced that it has obtained positive data demonstrating target binding in a Phase 1 trial of AX-0810, a therapeutic candidate using its proprietary Axiomer™ RNA editing platform. Biomarker changes supporting pharmacological action, such as an increase in total bile acid levels of up to approximately 8-fold, were confirmed, and the company states that it has achieved proof-of-concept for cholestatic liver diseases, including biliary atresia.
Axiomer™ is a technology that uses ADAR present within cells to edit RNA at the single-nucleotide level. It is characterized by its ability to regulate the expression or function of target proteins at the RNA level without permanently altering DNA.
While there has been a succession of excellent preclinical data in RNA editing, a major challenge has been whether the intended editing and pharmacological effects can be reproduced in humans. Although this result is at an early stage, it is an important milestone indicating that RNA editing has begun to move from platform technical validation to clinical value verification.
Rare neurological disease ASOs move to Phase 3 one after another
Stoke Therapeutics has completed enrollment of the planned 162 patients in the Phase 3 EMPEROR trial of the ASO zorevunersen for Dravet syndrome. Zorevunersen is a therapeutic agent that aims to intervene in the fundamental pathology of the disease by increasing the production of NaV1.1 protein from the normal SCN1A gene. The company plans to begin a rolling NDA to the U.S. FDA in the first quarter of 2027.
Ionis Pharmaceuticals also announced the completion of enrollment for the pediatric pivotal cohort in the Phase 3 REVEAL trial of obudanersen (ION582) for Angelman syndrome. Obudanersen aims to suppress UBE3A-ATS and restore protein production from the paternal UBE3A gene. Top-line data is scheduled to be released in the second half of 2027.
Furthermore, Ionis has initiated dosing of the first subject in the Phase 1/2 ASCEND trial of ION337 for Dravet syndrome. ION337 is an ASO that uses next-generation NMA modification technology to control SCN1A splicing and increase the expression level of NaV1.1 protein.
It is also noteworthy that Stoke and Ionis are developing different ASO technologies for the same Dravet syndrome. Moving forward, a comprehensive comparison will be conducted, including the degree of protein expression recovery, effects on clinical symptoms, dosing frequency, safety, and patient age.
Personalized ASOs as a treatment option for ultra-rare diseases
Vanda Pharmaceuticals has received Rare Pediatric Disease Designation from the U.S. FDA for VCA-894A, which targets Charcot-Marie-Tooth disease type 2S (CMT2S).
VCA-894A is a personalized ASO that targets a cryptic splice site mutation in the IGHMBP2 gene. It aims to correct abnormal splicing for a limited number of patients with specific mutations.
Unlike standardized drugs targeting diseases with large patient populations, N-of-1 or N-of-1+ nucleic acid medicines designed according to individual genetic mutations have the potential to open new paths for ultra-rare diseases that were difficult to treat with conventional drug discovery models.
Late-stage clinical trials highlight the severity of nucleic acid medicine development
The first half of July saw not only progress in development but also a series of harsh results in late-stage clinical trials.
AstraZeneca and Ionis announced that the Phase 3 CARDIO-TTRansform trial of Wainua (eplontersen) for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary endpoint of evaluating cardiovascular death and recurrent cardiovascular events.
Safety was consistent with previous results, and nominal significance was confirmed in the monotherapy subgroup. However, subgroup analysis is exploratory in nature and does not replace the failure to meet the primary endpoint of the overall study.
In ATTR-CM, existing treatments have become widespread, and patient backgrounds and concomitant medications have become more complex. Therefore, it is required not only to sufficiently reduce target proteins but also to clearly demonstrate improvements in clinical outcomes such as cardiovascular death and hospitalization. Even if the pharmacological action of nucleic acid therapeutics can be confirmed, the hurdle to linking it to patient value has become even higher.
Roche also announced the discontinuation of development for the Phase 2 GENERATION HD2 study of the ASO tominersen for Huntington's disease and the Phase 1 POINT-HD study of RG6496. Although tominersen showed a reduction in mutant huntingtin protein, it did not reach its efficacy goals. For RG6496, the decision to discontinue development was made based on the results of animal studies.
In central nervous system diseases, a reduction in target molecules does not necessarily lead directly to an improvement in clinical symptoms. The necessity of integrally designing the timing of intervention, patient selection, dosage, brain distribution, and the degree of target reduction has been demonstrated once again.
Tau-targeting ASO looks toward Phase 3 despite missing primary endpoint
Biogen presented data from the Phase 2 CELIA study of the tau-targeting ASO diranersen for early Alzheimer's disease at AAIC 2026.
Although the primary endpoint was not met in the overall study, the 60mg dose group showed a trend toward suppressing clinical deterioration at 18 months, and tau in the cerebrospinal fluid and brain was also significantly reduced. Biogen is planning to transition to Phase 3 development.
These results illustrate a challenge common to central nervous system nucleic acid therapeutics: how to interpret the relationship between biomarker-based target suppression and clinical efficacy and reflect it in the next study design. Whether appropriate dosage, treatment initiation timing, and patient populations can be selected is considered to determine the success or failure of Phase 3 studies.
siRNA moves toward reduced dosing frequency and expanded target organs
Progress in siRNA development by Chinese companies was also notable.
Argo Biopharmaceutical presented Phase 2 study data for the prekallikrein-targeting siRNA BW-20805 for hereditary angioedema (HAE) at EAACI 2026. Sustained seizure suppression effects and a favorable safety profile were demonstrated with twice-yearly dosing, results that show the value of siRNA in reducing the treatment burden for chronic diseases.
Suzhou Ribo Life Science achieved its first development candidate selection milestone in its siRNA program for MASH in partnership with Madrigal Pharmaceuticals. The company plans to begin preclinical studies for an IND application in the future.
The company also revealed plans to present Phase 2a study data for the FXI-targeting siRNA vortosiran (RBD4059) for coronary artery disease at CPIC. It aims for a sustained effect of up to 6 months using RiboGalSTAR™ technology.
siRNA is maturing as a modality that can significantly extend dosing intervals, primarily in the liver. Going forward, it will be important to see if dosing once every six months to once a year can be achieved and if clear clinical superiority over existing drugs can be demonstrated.
Heart and central nervous system become new frontiers for RNAi
Atrium Therapeutics has received IND clearance from the US FDA for the heart-targeting siRNA ATR 1072 for PRKAG2 syndrome. ATR 1072 is a therapeutic agent that aims to knock down mutant PRKAG2 mRNA and normalize abnormal AMPK activity. The first patient enrollment for the Phase 1/2 Corventis™ study is scheduled by the end of 2026.
The heart is an organ where nucleic acid therapeutics are more difficult to deliver compared to the liver. The entry of ATR 1072 into clinical trials will be an important opportunity to verify whether effective siRNA delivery to the myocardium can be replicated in patients.
Alnylam Pharmaceuticals also announced progress in its central nervous system RNAi pipeline. In addition to starting the Phase 2 APPlauDS study of mivelsiran for Alzheimer's disease and cerebral amyloid angiopathy, it is advancing a Phase 1 study of ALN-5288, which targets tau.
Whether RNAi, which has succeeded in the liver, can be expanded to the central nervous system and heart is an important theme that will determine the next growth of the nucleic acid therapeutics industry. Beyond target selection, the entire delivery technology, including tissue distribution, cellular uptake, duration of action, and safety, will be the source of competitiveness.
mRNA therapeutics reach the stage of looking toward commercial manufacturing
Arcturus Therapeutics has announced a strategic partnership with Thermo Fisher Scientific for clinical supply and commercial manufacturing support for ARCT-032, an inhaled mRNA therapeutic targeting cystic fibrosis.
In the field of nucleic acid medicine, the manufacturing systems required for small-scale production in early clinical stages differ significantly from those needed for stable supply in late-stage clinical and commercial phases. For mRNA therapeutics in particular, it is necessary to integrate mRNA drug substance production, formulation, filling, quality control, and scale-up.
This partnership indicates that ARCT-032 has entered a stage that looks beyond efficacy evaluation toward post-approval supply. This program, which delivers mRNA to the lungs via inhalation, is also attracting attention as a test case for whether mRNA therapeutics can expand beyond vaccines into chronic diseases.
In Japan, the 'Medical Drug Development using mRNA Cancer Vaccines' project by Meiji Seika Pharma and ARCALIS has been selected for Fukushima Prefecture's 2026 Regional Revitalization Practical Development Promotion Project. In collaboration with Minamisoma City, the project aims to create global pharmaceuticals originating from Fukushima and revitalize the local industry.
CancerVax has announced the completion of the design and in vitro validation of a single Polyepitope Smart mRNA version 2, which it claims covers 99.5% of the world's population. The concept involves selectively activating mRNA within cancer cells to present multiple viral epitopes, thereby directing existing T-cell immunity toward the cancer cells. Future focus will be on reproducing selectivity, safety, and anti-tumor effects in vivo.
Aptamers advance in both pharmaceuticals and DDS
Ribomic has completed the first subject enrollment in a domestic Phase 3 clinical trial for the anti-FGF2 aptamer umedaptanib pegol (RBM-007), targeting pediatric patients aged 2 to 14 with achondroplasia.
While aptamer drugs can bind to target molecules with high affinity like antibodies, they can also be manufactured through chemical synthesis. The advancement of RBM-007 to a domestic Phase 3 trial is a significant step toward the practical application of Japanese-developed aptamer drugs.
The company has also concluded a business alliance agreement with FUJIFILM Wako Pure Chemical Corporation regarding CDMO services for LNPs applying DDS aptamers. Ribomic will provide DDS aptamers on a non-exclusive basis, while FUJIFILM Wako Pure Chemical will handle LNP manufacturing and aptamer modification.
By attaching aptamers to the surface of LNPs, the goal is to achieve selective delivery to specific cells or tissues. This is positioned as an initiative to commercialize aptamers not only as therapeutic agents but also as targeting ligands for transporting nucleic acid medicines and mRNA.
DDS business centered on sugar chain ligands and LNPs is also expanding in Japan
KH Neochem and Hokkaido System Science have concluded a business alliance agreement to expand their contract synthesis services for sugar-chain-modified nucleic acids.
By combining KH Neochem's high-purity sugar chain technology, GlyMuch™, with Hokkaido System Science's nucleic acid contract synthesis and CRDMO functions, they will provide contract synthesis services for sugar-chain-modified nucleic acids aimed at selective delivery to specific tissues.
As demonstrated by the success of GalNAc-siRNA, sugar chain ligands significantly influence the tissue selectivity and pharmacokinetics of nucleic acid medicines. If sugar chain ligands that recognize tissues other than the liver are commercialized in the future, sugar-chain-modified nucleic acids could become a key technological foundation supporting extrahepatic delivery.
The aptamer-modified LNPs by Ribomic and FUJIFILM Wako Pure Chemical, and the sugar-chain-modified nucleic acids by KH Neochem and Hokkaido System Science, are both noteworthy as moves by Japanese companies to build new business foundations by combining DDS materials, nucleic acid synthesis, formulation, and CDMO capabilities.
Summary of the first half of July: Nucleic acid medicine moves from 'moving targets' to 'changing patient outcomes'
Three major trends can be identified from the developments in the first half of July 2026.
The first is that ASOs and RNA editing have entered a stage looking toward late-stage clinical trials and approval applications for rare neurological and genetic diseases. Therapeutic strategies that directly regulate RNA expression or splicing, which cause disease pathology, are becoming concrete for conditions such as Dravet syndrome, Angelman syndrome, and CMT2S.
The second is that there remains a significant gap between moving target molecules and improving clinical outcomes for patients. The results for eplontersen, tominersen, and diranersen have shown that even if clear pharmacological effects or biomarker changes are obtained, that alone does not guarantee the success of late-stage clinical trials.
The third is that the growth areas for nucleic acid medicine are expanding from the liver to the central nervous system, heart, and lungs. At the same time, the importance of targeted delivery technologies using aptamers, sugar chains, and LNPs, as well as the manufacturing systems that support late-stage clinical and commercialization efforts, is increasing further.
Competition in the nucleic acid drug industry has entered a stage where finding superior sequences or targets is no longer enough to win. Which disease to target, which modality to choose, which cells to deliver to, and via which route of administration? Furthermore, can the effect on the target be translated into clinically meaningful outcomes for patients, and can it be stably manufactured and supplied? The first half of July was a two-week period that clearly demonstrated how this 'implementation capability' determines corporate value.
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