From the end of last year to the start of this year, the boom of small nucleic acid drugs has been initially fueled by a string of encouraging drug approvals and clinical trial data. These therapeutics are proving that they are not only a lifeline for rare diseases but also a powerful weapon against prevalent chronic conditions.

The cardiovascular sector has led the charge.

On January 6th, Sanofi announced the domestic approval of its first-in-class drug Inclisiran Sodium Injection. Indicated for reducing triglyceride levels in adult patients with Familial Chylomicronemia Syndrome (FCS) alongside dietary management, it has become China’s first approved effective treatment for FCS.

As a first-in-class liver-targeted siRNA therapy administered quarterly, Inclisiran Sodium works by potently and durably silencing the mRNA expression of Apolipoprotein C-III (APOC3). This mechanism downregulates APOC3 protein production, thereby effectively lowering serum triglyceride (TG) levels, as well as the concentrations of TG-rich lipoproteins and their degradation remnants.

Originally developed by Arrowhead Pharmaceuticals—a leader in the small nucleic acid space—the drug was licensed in China by Viva Biotech. Ultimately, Sanofi secured Greater China rights through business development (BD) initiatives. Its approval journey epitomizes the scramble among multinational pharmaceutical giants to secure a foothold in the small nucleic acid cardiovascular market.

Hot on its heels, a glimmer of hope has emerged for the functional cure of hepatitis B.

On January 7th, GSK announced positive results from two pivotal Phase III clinical trials (B-Well 1 and B-Well 2) of its investigational antisense oligonucleotide (ASO) therapy Bepirovirsen, designed for the treatment of chronic hepatitis B (CHB).

As the first small nucleic acid drug to complete Phase III studies in the chronic hepatitis B field, Bepirovirsen’s progress marks a critical step toward the ultimate goal of functional cure for CHB. GSK plans to submit marketing authorization applications to regulatory authorities worldwide in the first quarter of this year.

The ambition of small nucleic acid drugs extends far beyond this—they are even making inroads into the highly competitive weight management space, precisely redefining obesity treatment paradigms with the promise of "fat loss without muscle mass reduction".

On January 6th, Arrowhead Pharmaceuticals released Phase I/II clinical trial data demonstrating robust performance of two RNAi pipeline candidates (ARO-INHBE and ARO-ALK7) in reducing visceral fat and improving body composition. Notably, the combination of ARO-INHBE with Eli Lilly’s Tirzepatide delivered multi-fold improvements in weight loss and fat reduction efficacy among obese patients with diabetes, showcasing its potential to address the limitations of existing GLP-1 therapies.

Coincidentally, in December of last year, data released by Wave Life Sciences—another small nucleic acid drug developer—further ignited enthusiasm for the application of small nucleic acid therapeutics in weight management.

Wave’s GalNAc-conjugated siRNA candidate WVE-007, which targets INHBE, demonstrated impressive data in the world’s first Phase I human trial: a single subcutaneous injection of 240 mg led to a 9.4% reduction in visceral fat and a 4.5% decrease in total body fat at the three-month mark, while lean body mass (non-fat tissue such as muscle) increased by 3.2%.

Small nucleic acid drugs can target a vast array of targets that were previously considered "undruggable" by traditional small-molecule and antibody-based therapies—an advantage that has earned them the reputation as "the key to undruggable targets".

As their therapeutic potential is fully unleashed, the notion that "theoretically, every drug is worth redeveloping with small nucleic acid technology" is being increasingly validated.

The market frenzy is also reflected vividly in transactions involving real capital inflows.

In 2025, the potential total transaction volume in the small nucleic acid sector soared to USD 36.473 billion, and the "arms race" spearheaded by multinational pharmaceutical companies has already reached a fever pitch.

From a market landscape perspective, three companies—Alnylam, Ionis, and Sarepta—have long maintained industry dominance by virtue of their technological barriers and commercialization advantages. To date, the majority of approved small nucleic acid drugs globally have originated from these three players.

Leveraging their first-mover technological accumulations, mature delivery platforms, and extensive clinical expertise, they have built insurmountable competitive moats, profoundly steering the R&D trajectory and commercialization progress of global small nucleic acid therapeutics.

Multinational pharmaceutical corporations (MNCs) initially entered the space primarily through collaborations with these three giants to steadily accumulate industry experience. However, as the global market scale continues to expand and the commercial potential of the track accelerates, MNCs have begun ramping up investments aggressively via intensive business development (BD) deals, driving a rapid restructuring of the industry’s competitive landscape.

Novartis, Eli Lilly, Sanofi, and Roche are among the early and most intensive layout players in the small nucleic acid track. Over the decade spanning 2016 to 2025, they have established their presence through multiple strategies, including pipeline BD transactions, technology platform licensing agreements, and mergers and acquisitions.

In recent years, Boehringer Ingelheim (BI), GSK, and AbbVie have also stepped up their activities in the small nucleic acid field. Notably, all four of BI’s transactions in this space are associated with indications for Nonalcoholic Steatohepatitis/Metabolic Dysfunction-Associated Steatotic Liver Disease (NASH/MASH).

Among these giants, Novartis launched the most aggressive initiatives in the just-concluded 2025, executing a series of small nucleic acid deployments centered on two core directions: expanding therapeutic indications and advancing delivery system optimization.

It not only acquired Avidity Biosciences for USD 12 billion to secure its Antibody-Oligonucleotide Conjugate (AOC) platform and neuromuscular disease pipeline but also inked deals worth USD 5.2 billion, USD 2.2 billion, and USD 1.7 billion respectively to in-license multiple pipelines from Epirium Bio, Arrowhead, and Regulus. These pipelines cover a broad spectrum of therapeutic areas, including cardiovascular diseases, neurodegenerative disorders, and renal diseases.

Eli Lilly, on the other hand, has focused on deepening its strengths in the metabolic disease domain. Over the past year, it has secured multiple partnerships with companies such as OliX Pharmaceuticals and Synermore Biotech, totaling more than USD 3 billion in value. Additionally, it has joined forces with Creyon Bio to explore AI-enabled next-generation drug design.

Overall, a global arms race is underway in the small nucleic acid drug sector. Enterprises represented by Alnylam, Ionis, Sarepta, and Arrowhead hold first-mover advantages rooted in their proprietary technology platforms, while MNC giants are leveraging their capital strength to aggressively bolster their portfolios, reshaping the industry landscape.

Against the backdrop of a globally evolving landscape, China’s innovative forces—armed with proprietary delivery technologies, differentiated pipeline layouts, and cost advantages—are surging forward as a formidable and unignorable variable, acting as a "catfish" to galvanize the entire sector.

Among these developments, the successful IPO of Ribo Bio stands as a landmark event marking the rise of China’s small nucleic acid drug R&D capabilities.

As one of the first domestic enterprises to delve deep into the small nucleic acid space, Ribo Bio has established a platform-driven development model centered on "deep liver targeting and extrahepatic expansion". It has advanced 7 drug candidates to clinical stages and built a pipeline of over 20 preclinical assets. This platform-based advantage translates to significantly reduced development risks and timelines for subsequent products once the underlying core technologies are validated.

From a pipeline perspective, three mid-to-late clinical-stage candidates derived from this platform are strategically positioned in three high-value therapeutic markets: thrombosis, dyslipidemia, and hepatitis B. Notably, its lead candidate RBD4059 is the world’s most advanced siRNA drug targeting Factor XI (FXI). With its ultra-long-acting efficacy and low bleeding risk, it addresses the key limitations of traditional anticoagulant therapies. Meanwhile, RBD5044 follows the approved development pathway of Arrowhead’s analogous drug, thereby minimizing R&D risks substantially.

A string of consecutive BD deals also fully demonstrates the company’s commercialization potential. Its collaboration with Boehringer Ingelheim (BI) in the MASH field serves as compelling evidence that its technology platform has gained recognition from top-tier multinational pharmaceutical companies. Additionally, licensing the Greater China rights of RBD7022 to Qilu Pharmaceutical represents an optimal allocation to maximize commercialization efficiency, showcasing a sophisticated pipeline operation strategy.

Beyond Ribo Bio, a cohort of innovative Chinese biotechs—represented by Sirnaomics, Epirium Bio, and Synermore Biotech—are also emerging onto the global stage. Their frequent overseas licensing deals have earned international recognition for China’s R&D prowess in the small nucleic acid domain.

As noted in a research report by Kaiyuan Securities: In the siRNA drug space, Chinese companies have gradually broken through the overseas-monopolized core underlying technologies and secured licensing deals with multinational corporations (MNCs). Leveraging their increasingly sophisticated pharmaceutical capabilities, these enterprises are poised to achieve further breakthroughs in siRNA therapeutics, bringing more China-originated pipelines to the global market and emerging as new hotspots in BD transactions.

Chinese biotechs have not only gained recognition from MNCs through outward licensing; they have also advanced multiple candidates to Phase III clinical trials in hyperlipidemia and chronic hepatitis B—the two fastest-expanding therapeutic areas for small nucleic acid drugs.

These include VSA-003, a siRNA drug developed by Viva Biotech, which effectively reduces LDL-C levels in HoFH patients via dual lipid-lowering mechanisms (both LDLR-dependent and LDLR-independent); RBD1007 by Ribo Bio, indicated for non-arteritic anterior ischemic optic neuropathy (NAION); and AHB-137, an unconjugated ASO drug developed by Habo Biopharma targeting the functional cure of chronic hepatitis B.

As domestic players "penetrate the core battlefield", it signals that in the near future, more China-developed innovative drugs will take center stage in the global competition for blockbuster therapeutics.

Beyond a cohort of aggressive, forward-looking biotechs that continue to forge ahead, established domestic pharmaceutical enterprises are also actively jumping on the bandwagon of this "third wave of modern pharmaceutical innovation".

Recently, China Biopharma made a blockbuster move: it acquired Hygia Bio for CNY 1.2 billion. Combined with its earlier investment in Synermore Biotech, this transaction marks another key strategic bet placed by China Biopharma in the small nucleic acid race.

Hygia Bio boasts a portfolio of cutting-edge technology platforms:

1. MVIP Liver-Targeting Platform: The world’s first clinically validated siRNA delivery platform enabling once-yearly dosing. Backed by U.S. patents, it breaks free from reliance on overseas technologies.
2. Dual Conjugation Platform (DDP): Capable of co-delivering siRNAs targeting two distinct molecular targets simultaneously, it achieves a synergistic therapeutic effect where the whole is greater than the sum of its parts, unlocking immense clinical potential.
3. Neuronal Delivery Platform (NSDP): A more pioneering initiative focused on extrahepatic targets, such as those implicated in brain and neurological disorders. It is anticipated that pipeline candidates leveraging this platform will enter clinical trials in 2026.

On the product pipeline front, Hygia Bio has 4 candidates already in clinical development. The standout asset is Kylo-11, a therapy targeting Lipoprotein(a) [Lp(a)]. As the world’s first investigational drug demonstrated in clinical settings to significantly reduce Lp(a) levels with a single annual injection, it holds the potential to become a Best-in-Class (BIC) product. Currently, Phase II clinical trials are underway both in China and the United States.

Additionally, over 20 preclinical programs are in the pipeline, covering high-profile therapeutic targets such as weight management (INHBE) and Alzheimer’s disease (APP).

In its official announcement, China Biopharma stated that this forward-looking strategic acquisition will accelerate the Group’s innovative layout and clinical advancement in the chronic disease space, spearhead the next generation of innovative therapeutics, and ultimately benefit patients worldwide.

In other words, what China Biopharma is acquiring is not merely a handful of drug candidates, but rather next-generation technologies that grant access to the vast chronic disease market—including cardiovascular and cerebrovascular disorders. This acquisition represents a precision strategic positioning maneuver ahead of the full-scale industrial boom of small nucleic acid drugs, securing a potentially high-value "entry ticket" for CNY 1.2 billion.

Beyond China Biopharma, other established pharmaceutical companies with strong expertise in chronic diseases—including Shenzhen Salubris Pharmaceuticals, Innovent Biologics, Qilu Pharmaceutical, and Huadong Medicine—are also accelerating their 布局 through in-licensing and co-development deals. For instance, Qilu Pharmaceutical in-licensed the PCSK9-targeting pipeline from Ribo Bio in a deal worth over CNY 700 million.

Furthermore, leading domestic pharmaceutical giants such as Jiangsu Hengrui Medicine, CSPC Pharmaceutical Group, and Chia Tai Tianqing are building proprietary technology platforms in-house, advancing domestically developed siRNA pipeline candidates into clinical stages.

Take CSPC Pharmaceutical Group as an example. Leveraging its proprietary siRNA innovation technology platform, the company currently has three siRNA drug candidates in clinical development:

• SYH2053, a PCSK9-targeting siRNA, has entered Phase II clinical trials;
• SYH2062 (an AGT-targeting siRNA) and SYH2068 (an Lp(a)-targeting siRNA) are in Phase I clinical trials.

Established pharmaceutical enterprises and biopharma companies boast broad and in-depth pipeline portfolios, with siRNA therapeutics positioned as a key component of their diversified pipelines. This strategic approach not only prevents them from falling behind in critical technological evolution but also enables them to steadily build comprehensive competitiveness for the next-generation pharmaceutical ecosystem through diversified deployment.

The boom of small nucleic acid drugs is no accident. It stems from the breakthroughs in key bottlenecks such as delivery technologies, the relentless drive to conquer "undruggable" targets, and above all, the urgent demand for a paradigm shift in chronic disease treatment.

The sector has now entered a competitive phase where success hinges on technology platforms, clinical data, and commercialization efficiency. Multinational giants are placing heavy bets with substantial capital, Chinese innovators are emerging prominently, and established pharmaceutical players are making aggressive inroads. The convergence of these diverse forces is destined to foster a more fiercely competitive yet infinitely promising golden era.

The year 2026 is merely the new starting point of this grand narrative.

Moving forward, the players who can take the lead in the next round of technological races—such as extrahepatic delivery—who can be the first to translate the promise of "ultra-long-acting efficacy" into therapies benefiting hundreds of millions of patients, will define the ultimate ceiling of small nucleic acid therapeutics and secure victory in the tide of medical innovation.