Over 20 Small Nucleic Acid Therapeutics Poised to Revolutionize Cardiovascular Disease Treatment: RiboBio Files for Hong Kong IPO

Recently, Suzhou Ribo Life Science Co., Ltd. submitted its prospectus to the Hong Kong Stock Exchange, officially embarking on its IPO journey. This news has caused quite a stir in the pharmaceutical industry. As a pioneer in China’s small nucleic acid drug research and development, this push for an IPO represents not only a significant milestone in Ribo Life Science's own development but also offers an excellent window for observing the progress of small nucleic acid drug research in metabolic fields such as cardiovascular diseases.

Cardiovascular diseases have long been the "number one killer" threatening human health worldwide. Traditional treatment methods have many limitations in dealing with complex cardiovascular conditions. The emergence of small nucleic acid drugs has brought new hope for the treatment of cardiovascular diseases, relying on RNA interference.（RNAi）Technology that can precisely target specific genes, effectively silence pathogenic genes, and thus intervene in disease progression at its root.

Traditional drugs typically only target sites on the cell surface and are often powerless against disease-causing proteins inside the cell. However, small nucleic acid drugs can directly enter the interior of cells and act on previously "undruggable" disease pathways, significantly expanding the scope of drug development. Moreover, small nucleic acid drugs exhibit higher specificity, reducing the impact on non-target genes and minimizing drug side effects.

In the treatment of cardiovascular diseases, small nucleic acid drugs have achieved remarkable results.Small Interfering RNA Targeting PCSK9（siRNA）Inclisiran（Inclisiran）It is a successful example. Inclisiran reduces the production of PCSK9 by inhibiting the mRNA translation of PCSK9 in hepatocytes, thereby lowering low-density lipoprotein cholesterol.（LDL-C）Level.

Clinical data shows that the dosing regimen for Inclisiran is one dose on the first day and another dose three months later, followed byAdministered once every six months, it can continuously reduce LDL-C for up to 240 days., and can also significantly reduce major adverse cardiovascular events（MACE）The incidence rate is as high as 25%. This long-acting and highly effective lipid-lowering effect brings new hope to patients with cardiovascular diseases.

Ribo Life Science has built a rich and highly promising R&D pipeline after many years of intensive efforts in the field of small nucleic acid drug development, with extensive layouts particularly in the cardiovascular and metabolic disease areas.

RBD4059 is one of the core product pipelines of Ribo Life Science, andThe world's first and fastest-progressing anti-thrombotic siRNA candidate drug targeting FXI in clinical development. Coagulation Factor XI（FXI）It is a key molecule in the endogenous coagulation pathway. Inhibition of FXI can block the intrinsic coagulation pathway, providing a new antithrombotic method with low bleeding risk for clinical use.

RBD4059 specifically targets the messenger RNA of FXI（mRNA）, inhibiting its protein expression and activity, thereby effectively blocking the activation of the endogenous coagulation pathway, achieving anticoagulant and antithrombotic effects. Compared with traditional anticoagulants, the biggest advantage of RBD4059 is that it reduces the risk of thrombosis without significantly increasing the risk of bleeding. This feature addresses a major challenge in traditional anticoagulation therapy and is expected to provide patients with thrombotic diseases a safer and more effective treatment option.

Moreover, RBD4059 is expected to have long-lasting efficacy in clinical settings, producing a prolonged effect with low-frequency dosing, which will greatly enhance patient compliance and reduce the treatment burden. Currently, RBD4059 has been approved for Phase II clinical trials in the EU, and its clinical research results are highly anticipated.

Hypertriglyceridemia is a type of dyslipidemia that can cause endothelial dysfunction, accelerate the occurrence and development of atherosclerosis, and increase the risk of acute pancreatitis. RBD5044 from Ribo Life Science isThe second siRNA targeting APOC3 to enter clinical development globally.

APOC3 plays a key role in lipid metabolism, and targeting APOC3 through the RNAi mechanism is considered to effectively and sustainably reduce plasma triglycerides and ApoB-containing lipoproteins in patients, thereby lowering the risk of cardiovascular diseases.

Non-clinical safety and efficacy studies of RBD5044 have shown that it has the potential for Best-in-Class efficacy and a prolonged duration of action, which means RBD5044 is expected to become a powerful tool for treating hypertriglyceridemia. Currently, RBD5044 is in Phase I clinical trials, and as the research progresses, it is expected to bring good news to a wide range of patients.

In addition to RBD4059 and RBD5044, Ribo Life Science has multiple products in its pipeline focusing on the cardiovascular and metabolic disease fields. For example, targeting angiotensinogen.（AGT）The GalNAc-siRNA molecule R0797070 has shown in preclinical efficacy data that it can efficiently inhibit liver AGT expression, continuously reduce blood pressure, and significantly improve left ventricular hypertrophy. The efficacy data for improving ventricular hypertrophy, when compared to Captopril, suggests a mechanism not entirely dependent on blood pressure. This candidate product is about to initiate IND-enabling studies and will explore new indications beyond hypertension in future clinical trials.

In the global race for small nucleic acid drug development, numerous companies have engaged in fierce competition around cardiovascular disease targets, presenting a situation of both competition and breakthroughs.

Source: Public information

In the research and development of antithrombotic drugs,In addition to RBD4059 from Ribo Life Science, companies such as Bayer/Ionis Pharmaceuticals and Jingyin Pharma are also actively exploring. Among them, SRSD107, a next-generation FXI-targeted siRNA therapy developed by Jingyin Pharma, submitted an application to the European Medicines Agency for Phase II clinical trials in March 2025. Preclinical trial data showed that a single subcutaneous injection of SRSD107 reduced peripheral blood FXI concentration by nearly 100%, with effects lasting up to half a year without any observed bleeding. Moreover, SRSD107 demonstrated excellent safety and is expected to become a potential First-in-Class and Best-in-Class next-generation anticoagulant with enhanced safety.

Phase I Clinical Research Data Published at 2024 ASH Showed that SRSD107 Had Good Safety and Tolerability, with Significant Changes in Pharmacodynamic Biomarkers Observed Compared to Baseline. At the Highest Dose, the Maximum Reduction in FXI Antigen and FXI Activity Exceeded 90%, and the Increase in aPTT Was Over 100%.(i.e., aPTT ratio > 2.0)The pharmacodynamic effect persists after a single dose, maintaining FXI antigen and FXI activity in a nearly 90% inhibited state for over 16 weeks.

Currently, no FXI-targeting small nucleic acid drugs have been approved for marketing, but with further research, more innovative therapies may emerge successively.

In the field of lipid-lowering drugs, the competition is equally fierce. Novartis' Inclisiran has been successfully approved for marketing, gaining a first-mover advantage in the market. However, Ribo Life Science's RBD7022, as a PCSK9-targeted siRNA for treating hypercholesterolemia, shows promise in preclinical andIIn the phase clinical trial research results, it demonstrated an LDL-C lowering effect comparable to Inclisiran, highlighting its potency and long-lasting efficacy, with the potential for dosing once every six months. This indicates that RBD7022 has promising prospects.Become a strong competitor in this field, breaking the market monopoly of Inclisiran.

In addition, Plozasiran, an siRNA drug targeting APOC3 developed by Arrowhead Pharmaceuticals/ViaGen.（VSA001）, in the treatment of familial chylomicronemia syndrome（FCS）In the treatment research of hypertriglyceridemia, it has also shown good efficacy. In March 2025, ViGeneron announced Plozasiran for Chinese familial chylomicronemia syndrome.（FCS）Phase III Clinical Trial of the Patient(CTR20231418/NCT05902598) Positive Topline Data Achieved, Successfully Meeting Primary Efficacy Endpoint and All Key Secondary Endpoints. Plozasiran’s sustained cholesterol-lowering properties simplify patient lipid management, offering a unique competitive advantage within its class.

In the field of hypertension treatmentAlthough there are currently fewer small nucleic acid drugs approved for marketing, the R&D enthusiasm continues to rise. Alnylam and Ionis target angiotensinogen.（AGT）All have been strategically positioned, with their developed Zilebesiran and IONIS-AGT-LRx currently entering Phase II clinical trials. Additionally, Ionis licensed the AGT-targeting ASO therapy Tonlamarsen to Kardigan, which also initiated Phase II clinical trials in March 2025.

Bowang Pharmaceutical, Shengyin Biotech/Innovent Biologics and other pharmaceutical companies in China are also actively developing AGT-targeted small nucleic acid drugs. Among them, SGB-3908, co-developed by Shengyin Biotech and Innovent Biologics, is an siRNA candidate drug based on Shengyin Biotech's proprietary small nucleic acid drug development platform LEAD™. Preclinical trial data shows that: SGB-3908 can reduce AGT protein and related biomarkers in the serum of hypertensive cynomolgus monkeys.（ANG I、ANG II）Significantly decreased, achieving a marked blood pressure-lowering effect with long-lasting results, and no safety issues such as hypotension were observed. In July 2024, SGB-3908 received clinical approval in China for the treatment of essential hypertension.

In addition, Bowang Pharmaceutical's BW-00163SYH2062 from CSPC Pharmaceutical Group, HRS-9563 from Shengdi Medicine (a subsidiary of Hengrui Medicine), LDR2402 from Chengdu Xiandao Biotech, ART101 from Antorna Biotech, SNK-2726 from Sinokang/Huadong Medicine, and RN1871 from Dazui Biotech, among other domestically produced antihypertensive small nucleic acid candidate pipelines in China, have all entered pivotal clinical trials.

Ribo Life Science's Push for HKEX Listing Undoubtedly Brings New Opportunities for Its Development. Meanwhile, It Will Also Increase Attention to the Small Nucleic Acid Drug Industry, Attracting More Capital and Talent Into the Field and Promoting the Development of the Entire Industry.

However, the development of small nucleic acid drugs is not smooth sailing, and they still face many challenges. First, the research and development of small nucleic acid drugs carry high risks and long cycles, requiring continuous investment of substantial funds. Second, issues such as the delivery system and immunogenicity of small nucleic acid drugs still need further resolution.How to improve the delivery efficiency and reduce the immunogenicity of drugs is one of the key challenges in the current development of small nucleic acid drugs.。

Overall, small nucleic acid drugs have shown great potential in the metabolic field, such as cardiovascular diseases. Although facing challenges, with the continuous advancement of technology and in-depth clinical research, small nucleic acid drugs are expected to bring more and effective treatment options for patients with cardiovascular diseases, opening a new chapter in the treatment of cardiovascular diseases.

Main References:

[1] IPO Early Notice. Ribo Life Science Charges at the Hong Kong Stock Exchange: siRNA Drug Targeting FXI for Antithrombotic in Phase II Clinical Trial [EB/OL]. (2025-04-28)[2025-04-29]. https://m.thepaper.cn/newsDetail_forward_29583493

[2] Frost & Sullivan. Global Small Nucleic Acid Therapeutics Market Report[R]. 2023.

[3] Ray KK, et al. Inclisiran and Cardiovascular Outcomes[J]. N Engl J Med, 2023, 388(13): 1175 - 1186.

[4] Ribo Life Science Prospectus [R]. 2025.

[5] Alnylam Pharmaceuticals Official Website. Research and Development Pipeline[EB/OL]. https://www.alnylam.com/research-development/pipeline/

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