After Bowave's $4.165B Out-Licensing Deal, Which Chinese Oligonucleotide Therapeutics Companies Are Worth Watching? — A Comprehensive Review of 40+ Firms and 60+ Drug Programs

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Argo Biopharma was founded in April 2021 as a biotechnology company focused on the development of siRNA drugs. The company now has over 50 employees, with core members coming from Arrowhead, a siRNA drug company, and multinational pharmaceutical companies such as Merck.

Information from Argo's official website shows that this company, established just over two years ago, has already developed 27 pipelines. Among them, nine are for cardiovascular diseases alone, while others cover disease areas such as rare diseases, metabolism, neurology, and antivirals. Currently, four projects have entered the clinical stage, and a fifth project has submitted a clinical application. The rapid pace of siRNA product development and patent applications targeting different pathways like ANGPTL3, AGT, HBV, and PKK reflects strong screening and optimization capabilities. This level of efficiency is highly impressive in the small nucleic acid field.

In less than three years since its establishment, the company has advanced four projects into clinical trials, with a fifth project already submitted for clinical application. The therapeutic areas cover cardiovascular diseases, rare diseases, hepatitis B, autoimmune conditions, and neurological disorders. Some projects are expected to enter Phase 2 clinical trials by early 2024.Among them, BW-01 and BW-02 in the cardiovascular field have entered the clinical stage.

As one of the earliest active small nucleic acid drug research and development companies, Suzhou Ribo Biotech wasFounded in 2007, the main business is the development of small nucleic acid drugs, forming a pipeline of products under research and development that includes several small nucleic acid drugs for lowering blood sugar, anti-prostate cancer, anti-optic nerve injury, anti-hepatitis B, and anti-high cholesterol. Ribo Biotech has established internationally leading small nucleic acid technology R&D capabilities, a complete small nucleic acid drug R&D platform, and the largest variety chain of small nucleic acid drugs in Asia. It is the main pioneer and leader in China's small nucleic acid technology and small nucleic acid pharmaceuticals, achieving multiple zero breakthroughs in China's small nucleic acid pharmaceutical industry.

RBD7022: As based on RiboRBD7022 is a GalNAc-conjugated siRNA drug developed using RIBO-GalSTAR® liver-targeting delivery technology aimed at treating hyperlipidemia. RBD7022 inhibits the expression of PCSK9 (proprotein convertase subtilisin/kexin type 9), reduces lysosomal degradation of LDL-R (low-density lipoprotein receptor), and increases the number of LDL-R on the surface of hepatocytes, thereby achieving the goal of lowering LDL-C (low-density lipoprotein cholesterol) levels in the blood. RBD7022 has entered its first-in-human clinical trial in China.

RBD5044: As Ribo-basedRIBO-GalSTAR® is a liver-targeted delivery technology developed for the treatment of hypertriglyceridemia using GalNAc-conjugated siRNA drugs. RBD5044 can inhibit the expression of APOC3 (apolipoprotein C3) in hepatocytes, upregulate lipoprotein lipase and receptor-mediated remnant particle uptake in hepatocytes, promote the hydrolysis of triglycerides (TGs) on triglyceride-rich lipoproteins (TRLs), and achieve the goal of reducing TG levels in the blood. It has entered the first-in-human clinical trial in Australia.

RBD1016: A treatment for hepatitis BGalNAc-conjugated siRNA drugs can cover the majority of hepatitis B patients with genotypes A-E in China, Europe, and the United States. Non-clinical studies have shown that it can efficiently and sustainably reduce HBsAg in serum and liver tissue, with a single dose suppressing HBsAg for nearly six months. It is currently the world's only drug to achieve seroconversion in preclinical animal models as a monotherapy, indicating that RBD1016 has Best-In-Class potential. If confirmed in clinical trials, it is expected to functionally cure hepatitis B patients. Phase Ia clinical trials have been completed in Australia, and Phase Ib clinical trials are currently underway in Hong Kong, China. Phase II clinical trials are in preparation.

As a self-developed product by Ribo BiotechThe good safety and expected pharmacokinetic characteristics of RBD1016, a GalNAc-siRNA innovative drug, in clinical research, strongly validate the GalNAc-siRNA liver-targeted delivery technology and small nucleic acid drug development platform established by Argo Biopharma. Argo Biopharma anticipates that more GalNAc-siRNA products will enter the clinical development stage.

SR061YessiRNA (small interfering RNA) new drug, a type of optic nerve protective medication that targets caspase 2, with the first clinical indication developed being non-arteritic anterior ischemic optic neuropathy (NAION). This drug was developed by Quark and the company obtained rights for certain Asian regions. Notably, interim data from a randomized, double-blind, international multicenter Phase II/III pivotal clinical trial of SR061 showed that the efficacy data for the primary endpoint was insufficient to support continued enrollment, and the enrollment and visits for this clinical trial have been terminated. However, Ribo Bio plans to complete the analysis of the Phase II/III clinical data and will design a clinical protocol based on the analysis results, applying for and initiating a confirmatory Phase III clinical trial in China.

RBD1007: A targetedCaspasesAn siRNA drug for optic nerve protection that inhibits the expression of target genes through RNAi, preventing retinal ganglion cell (RGC) apoptosis and subsequent neurite degeneration, thereby halting further deterioration of vision and visual field, achieving a therapeutic effect of vision protection. The first clinical indication under development is non-arteritic anterior ischemic optic neuropathy (NAION), which currently lacks a standard clinical treatment. RBD1007 has the potential to become a First-In-Class drug for optic nerve protection. Globally, one Phase I clinical study and one Phase II/III international multicenter clinical trial (including 34 Chinese subjects) have been completed. Analysis of the clinical trial data supports conducting a Phase III confirmatory clinical study in NAION subgroups with significant unmet clinical needs. An IND application is currently being prepared. Future plans include conducting clinical studies for open-angle glaucoma and other ophthalmic diseases involving optic neuropathy requiring optic nerve protection.

RBD4988: A treatment forAn antisense nucleic acid drug for type 2 diabetes, which is expected to become the first drug targeting the glucagon receptor (GCGR), with no similar targeted drugs currently on the market. This product can exert its glucose-lowering effect through a dual mechanism of action, reducing hepatic glucose production while increasing GLP-1 to provide pancreatic protection. The drug is expected to meet the clinical needs of patients who respond poorly to interventions solely via the insulin pathway. Globally, one Phase I clinical trial and three Phase II clinical trials have been completed. In China, two Phase II clinical trials for type 2 diabetes were recently successfully completed.

RBD2018: A targeted von Willebrand factor (An aptamer for vWF, the intended indication under development is Hemophilia A. The drug molecule specifically binds to vWF, preventing the clearance of vWF and its carried FVIII, extending the half-life of FVIII, and simultaneously enhancing FVIII activity. The foreign partner has completed Phase I and Phase IIa clinical trials, showing good safety and efficacy. Ribo owns the rights to develop, manufacture, and commercialize the product in Greater China and plans to initiate clinical trials for Hemophilia A.

As an outstanding representative of small nucleic acid enterprises in China, SirnaomicsOn July 15, Argo Biopharma officially submitted the prospectus application for a main board listing to the Hong Kong Stock Exchange. Following the termination of Ribo Biotech's STAR Market IPO, Sirnaomics could become the first China-based small nucleic acid drug stock.

Sirnaomics was founded inFounded in 2007, it is a biotechnology company focused on applying RNA interference technology (RNAi) for new drug creation. It possesses a nucleic acid drug delivery technology and a platform for new drug development and industrialization, with a deep focus on therapeutic areas such as cancer, fibrotic diseases, and viral infections. It has established a rich pipeline with more than ten products currently under research and development.

Source: Sirnaomics Prospectus

STP705Is the company's core candidate drug, based onRNAi reaction and utilizing the company's proprietary peptide nanoparticle (PNP) delivery platform, it is a dual inhibitor of TGF-ß1 and COX-2 that can be applied for local administration.

CurrentlySTP705 has three prioritized product pipelines: a late-stage clinical trial for in situ squamous cell carcinoma (isSCC), a completed Phase II clinical trial for basal cell carcinoma (BCC), and a Phase I clinical trial for fat remodeling. Additionally, STP705 has received orphan drug designations for the treatment of cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC) in other indications.

STP707By targeting transforming growth factorSTP707 consists of two siRNA oligonucleotides targeting β (TGF-β) and cyclooxygenase-2 (COX-2) mRNA, formulated into nanoparticles by binding to a histidine-lysine copolymer (HKP+H) carrier. Each individual siRNA has the ability to inhibit the expression of the corresponding target mRNA. STP707 can simultaneously suppress the expression of TGF-β1 and COX-2, thereby producing a synergistic effect to reduce inflammatory responses. In a preclinical study, intravenous administration of STP707 demonstrated knockdown of TGF-β1 and COX-2 gene expression in organs such as the liver, lungs, and xenograft tumors. In multiple preclinical models, STP707 exhibited potent anti-tumor activity against various solid tumor types. In a mouse orthotopic hepatocellular carcinoma model, the combination of STP707 with immune checkpoint antibodies showed synergistic anti-tumor activity.

RV-1730It is currently in the early stage of development and utilizes lipid nanoparticles (LNP) delivery technology formulated mRNA vaccine of the full-length spike protein of the Delta variant SARS-CoV-2. RV-1730 will be administered subcutaneously to prevent COVID-19.

Haichang Bio focuses on the development of mRNA vaccines, small nucleic acid drugs, and other nucleic acid innovative drugs as well as high-end complex injectables. Its subsidiary, the "Nucleic Acid Innovation Research Institute (NAMIC)," is dedicated to the research and development of nucleic acid innovative drugs, fully leveraging the core technological advantages of its proprietary nucleic acid drug delivery system, QTsome™. Based on this, the platform has been extended and expanded to create a first-class mRNA delivery system technology platform in China. Currently, there are more than 6 small nucleic acid drugs under research and development.

HC0201It is an antisense nucleic acid for primary renal cell carcinoma (RCC). The original administration method required continuous infusion for 14 days, but after the improvement of the delivery system, it only needs to be injected once a week. In addition, with the continuous improvement of RCC treatment regimens, HaiChuang Bio has begun to develop the optimal drug combination therapy for HC0201 to enhance efficacy. Moreover, using the QTsome™ platform, HaiChuang Bio has developed HC0201 into lipid nanoparticles, which are currently in Phase I clinical trials in the United States, with existing clinical data showing good safety.

HC0301It is a new generation of antisense nucleic acid AKT-1 inhibitor encapsulated by QTsomeTM nucleic acid delivery technology. The AKT-1 target acts on the PI3K/AKT/mTOR signaling pathway, playing a key role in cancer cell proliferation, survival, angiogenesis, metastasis, and drug resistance, and is overexpressed in various cancers, including liver cancer, kidney cancer, breast cancer, colorectal cancer, gastric cancer, and pancreatic cancer. It is currently under clinical development for primary liver cancer in the United States.

HC2101The target is Anti-miR-21, and its potential for treating non-small cell lung cancer is currently being explored.

HC009It is a COVID-19 mRNA vaccine developed based on the QTsome™ delivery technology platform, which is owned by Highchem Bio and has global independent intellectual property rights. The booster product of this vaccine will be used to prevent infections caused by various variants, including Omicron, and is suitable for people who have been vaccinated against COVID-19 as well as those who have not been vaccinated.

Antishengshi was established in 2017 as the first company in China to develop antisense oligonucleotide (ASO) drugs targeting RNA splicing and RNA editing. It possesses several of the latest international ASO technologies, with multiple projects currently underway. Significant progress has been made in drug development for diseases such as DMD (Duchenne Muscular Dystrophy) and SCA3 (Spinocerebellar Ataxia Type 3). Building on its existing technology, Antishengshi has optimized and upgraded to invent a new generation of 5D-ASO for intervening in RNA splicing.Likon Life TechnologyNew drug R&D technologies centered on ASO, such as ANISPR for ASO-induced RNA editing.

The founder of the company, Hua Yimin, is a top scientist in the field of small nucleic acid drugs globally.Treatment for Spinal Muscular Atrophy drug Nusinersen (Nusinersen,Product NameSpinraza）The main inventor. The drug isThe world's top-selling small nucleic acid drug has saved the lives of tens of thousands of rare disease patients globally.。

Ractigen Therapeutics is an early-stage biotech company focused on developing first-in-class drugs through upregulating the expression of therapeutic genes in disease cells. Founded in 2017 by a team of original scientists in the field of RNA activation, the company has established a highly differentiated pipeline for treating various diseases caused by insufficient gene expression. Technically, the company owns RNA activation technology, which uses small activating RNA (saRNA) to target and "activate" the transcription of endogenous genes, thereby restoring the natural function of endogenous proteins.

saRNADrug development platform and multiple internationally leading small nucleic acid drug delivery platform technologies, including "SCAD." A drug pipeline with more than 10 projects has been established, prioritizing monogenic diseases as the primary indication and covering various disease areas such as the central nervous system (CNS), oncology, and liver diseases.

RAG-17Is aSOD1-Targeted Double-Stranded Small Interfering RNA (siRNA) for the Treatment of ALS Patients with SOD1 Mutations by Reducing SOD1 Protein Expression. RAG-17 Utilizes Argo Biopharma's Independently Developed SCAD (Smart Chemical-Assisted Delivery) Platform with Independent Intellectual Property Rights to Achieve Efficient Delivery to the Central Nervous System. Preclinical Efficacy Studies Conducted on ALS Mouse and Rat Models Have Demonstrated That RAG-17 Treatment Significantly Delays Disease Onset, Extends Survival Time, and Improves Motor Function in Animals.

R&D Pipeline

RAG-18 Is a method to increase by delivering to muscle tissueA saRNA drug that expresses the UTRN gene to compensate for DMD deficiency (not limited to the location of DMD gene mutations). RAG-18 utilizes Argo Biopharma's proprietary LiCO delivery platform technology, enabling effective saRNA delivery in muscles.

RAG-06ThroughThe RNA activation mechanism increases the expression of the SMN2 gene in neurons of the central nervous system, thereby raising the level of SMN protein expression to a level capable of compensating for the loss of SMN1 and maintaining the function of motor neurons in SMA patients.

RAG-01ThroughRNA Activation Mechanism Targets the Expression of a Tumor Suppressor Gene. This gene is typically underexpressed or not expressed in bladder cancer cells. RAG-01 represents a potential intravesical therapy for bladder cancer with low side effects and improved efficacy to reduce recurrence.

RAG-03To PassThe saRNA, which functions through the RNAa mechanism, stimulates the liver to produce and secrete THPO after being delivered to the liver, thereby restoring platelet counts to treat persistent thrombocytopenia.

RAG-05For targeted activationThe saRNA of the HMBS gene, after being delivered to the liver, restores the level of PBGD enzyme by activating HMBS expression in hepatocytes through the RNAa mechanism, thereby preventing acute attacks of AIP.

RAG-12Is a potential prevention and treatmentThe saRNA drug for Type I HAE increases the concentration of C1-Inh in patients' livers by targeting and activating the expression of the SERPING1 gene in liver cells.

RAG-20Is a utilization of Zhongmei Ruikang's proprietaryThe saRNA drug delivered to the liver using GLORY technology can promote the production of FVII in the liver. RAG-20 is under development for the treatment of hemophilia (including hemophilia with inhibitors), FVII deficiency, and Glanzmann's thrombasthenia, among other diseases.

RAG-1CA Potential Treatment via Intravitreal InjectionThe saRNA drug for PVR inhibits RPE cell proliferation by activating a negative cell cycle protein, thereby achieving the effect of treating or preventing the occurrence and development of PVR.

Brii Biosciences, founded in 2018, focuses on infectious diseases and central nervous system disorders and has built a pipeline comprising more than 10 innovative therapeutic candidates.

R&D Pipeline

In the product pipelineBRII-835BRII-835 is an investigational subcutaneously injected small interfering nucleic acid (siRNA) targeting HBV, with the potential to stimulate a potent immune response and direct antiviral activity against HBV. Under the licensing agreement with Vir Biotechnology, Brii Biosciences holds exclusive rights to develop and commercialize BRII-835 in Greater China.

Argo Biopharma, founded in April 2021, is committed to developing a new generation of siRNA drugs to provide better treatment options for patients worldwide. The team has extensive professional experience in all aspects of RNAi drug development, including nucleic acid sequence design, chemical modification, GalNAc delivery technology, extrahepatic delivery technology, oligonucleotide synthesis, and CMC.

News on November 1: Argo Biopharma has recently completed a 300 million RMB A+ round of financing. This round of financing will be used to further advance the global development of four clinical pipelines, the discovery of multiple preclinical candidate drug molecules, the iterative upgrading of modification technology platforms and extrahepatic delivery technology platforms, as well as the enhancement of the company's professional team building. Since its establishment, Argo Biopharma has been actively promoting multiple preclinical R&D pipelines. Currently, several pipelines are in the IND-enabling stage, and it is expected that there will be multiple Phase I clinical pipelines by 2023.

BW-00112It is a siRNA new drug independently developed by the company, targeting the field of endocrinology and metabolic diseases, and has been approved for clinical trials in May this year. Previously, Argo Biopharma had two siRNA drugs approved for clinical trials in Australia.

Stellar KZ, founded in 2021, is an innovative drug developer in the field of liver disease treatment, primarily focusing on liver disease. It rapidly builds its product pipeline through a combination of self-research and License-in models.

HT-101The injection is a GalNAc-conjugated siRNA drug. According to publicly available information, HT-101 demonstrated the ability to reduce multiple key components of the hepatitis B virus and sustainably inhibit viral replication for over 70 days in preclinical pharmacodynamic studies. Notably, it showed exceptional performance in lowering hepatitis B surface antigen (S antigen) levels: in the AAV-HBV mouse model, the high-dose group achieved nearly a 1000-fold reduction in S antigen. Additionally, high levels of hepatitis B surface antigen antibodies were detected in the serum of mice in the high-dose group.

HT-102, a neutralizing antibody targeting the hepatitis B virus surface antigen (HBsAg), with its first indication being chronic hepatitis B (CHB). In subsequent clinical development, Argo Biopharma will explore the combination of siRNA and neutralizing antibodies for the functional cure of chronic hepatitis B. Argo Biopharma's "siRNA + neutralizing antibody" combination is a first in China.

Nucleic acid drugs are one of the important strategic layouts for Yuel Pharmaceutical's innovation and upgrading. In December 2020, Yuel Pharmaceutical was listed on the STAR Market of the Shanghai Stock Exchange. Two months after the listing, Yuel Pharmaceutical officially announced the full acquisition of Hangzhou Tianlong Pharmaceutical. Tianlong Pharmaceutical is one of the earliest companies in China to research nucleic acid drugs, and its Class 1 new drug CT102 is China's first completely self-developed antisense oligonucleotide (ASO) drug.

By acquiring 100% equity of Tianlong Pharmaceutical, Yooking Pharmaceuticals has aggressively entered the nucleic acid and mRNA innovative drug sector, becoming the first listed pharmaceutical company in China to obtain clinical approval for a nucleic acid drug.

In the third month after Yikang Pharmaceutical's IPO, the Phase I clinical trial of its nucleic acid drug "CT102 Injection" for the treatment of primary hepatocellular carcinoma was officially launched. On September 23 of the same year, Yikang Pharmaceutical announced that it would invest 180 million yuan of over-raised funds to establish a nucleic acid drug pilot and intermediate-scale platform project targeting small nucleic acid drugs and mRNA vaccines.

CT102CT102 is an ASO drug targeting the human insulin-like growth factor 1 receptor (IGF1R) gene, used for the treatment of primary hepatocellular carcinoma. Currently, CT102 is undergoing Phase IIa clinical trials. The results of the Phase I clinical trial showed that CT102 has good safety and tolerability, with no adverse reactions leading to drug discontinuation or participant withdrawal.

Staidson is committed to the research, production, and sales of therapeutic drugs for diseases with unmet clinical needs, primarily including protein-based drugs (containing therapeutic monoclonal antibody drugs) and gene therapy./ Cell therapy drugs, chemical drugs, and the three major drug categories. The therapeutic focus is on infectious diseases, autoimmune diseases, and neurological disorders. The company's mission is "Continuous innovation to provide safe and effective therapeutic drugs and contribute to human health," adhering to the core values of "Patient interests first, cooperative competition, and value creation."

STSG-0002For small nucleic acid gene drugs,STSG-0002 injection is a liver-targeting replication-defective recombinant adeno-associated virus carrying shRNA expression cassettes targeting the P and X regions of the HBV genome.

It uses recombinant adeno-associated virus (rAAV) as a delivery vector, the target gene sequence is introduced into cells to transcribe shRNA, which is cleaved into single-stranded siRNA in the cytoplasm. Subsequently, through the RNAi mechanism, it specifically silences pgRNA associated with HBV replication and sRNA related to HBV protein expression, blocking HBV viral replication and reducing the synthesis and secretion of HBsAg, HBeAg, and HBc proteins.

STSG-0002It has obvious hepatotropism, and a single intravenous administration can lead to long-term expression of siRNA in hepatocytes. A significant reduction in HBsAg is expected to promote HBsAg seroconversion, thereby achieving functional cure of HBV. The schematic diagram of its mechanism of action is as follows:

Xinhe Biotech is a company based onA high-tech enterprise that builds an RNA technology platform and develops innovative drugs using AI technology.

XH101Injection", developed by Shenzhen Xinhewave Biomedical Technology Co., Ltd.(Hereinafter referred to as: NeoX Biotech) independently developed the world's first (First in Class) therapeutic mRNA tumor vaccine targeting public neoantigens for gastric cancer. Current preclinical research data shows that XH101 injection can effectively stimulate patients' T-cell immune response and tumor cell killing effect, demonstrating significant clinical treatment potential.

Compared with traditional drugs, this vaccine has stronger immunogenicity and can induce the body's natural immune response. It not only shortens the vaccine preparation cycle and reduces the treatment cost for patients, but also generates long-lasting immune memory in patients, providing possibilities for preventing tumor recurrence and metastasis. Meanwhile,XH101 Injection can effectively suppress advanced tumors and metastatic tumors.

Stemirna is the first company in China to develop mRNA.An innovative pharmaceutical company that focuses on the R&D and production of novel vaccines and provides technical services for nano-liposome encapsulation and delivery. It is also one of the few companies in China that masters mRNA nucleic acid design, synthesis, and modification technologies, liposome encapsulation technology, large-scale production technology, and has achieved independent design and R&D of production-related equipment.

R&D Pipeline

Wisgen Bio is a Chinese company with core technology and independent intellectual property rights, focusing on mRNA.A biopharmaceutical company focused on the research and development of innovative drugs and adjuvants, founded by the academician team from West China Hospital of Sichuan University, located in Chengdu Tianfu International Bio City.

Currently, it has developed over20 pipelines under research, 4 of which have entered clinical trials at home and abroad. Two mRNA tumor therapeutic vaccines are the first domestic products to enter clinical trials, and the new nano-adjuvant pipeline is conducting clinical trials in China and Mexico.

R&D Pipeline (Source: WestGene Bio)

is a company focused on messenger ribonucleic acid (mRNA) clinical-stage innovative biopharmaceutical company specializing in drug development, possessing industry-leading proprietary intellectual property rights in mRNA and nanodelivery technology platforms. The company's self-developed Dynamic Precision Mixing technology generates uniformly distributed nanolipid spheres in a single reaction while encapsulating mRNA with an encapsulation efficiency of over 90%.

Abogen Biosciences' pipeline includes multiple fields such as infectious disease prevention and treatment, tumor immunology, and protein replacement therapy.mRNA Cancer VaccineDEV-2011Currently entering the investigator-initiated clinical stage.DEV-2009, for the treatment of cervical cancer, is about to complete pharmacokinetic and toxicological studies. The subsequent pipeline includes a bivalent COVID-19 vaccine, a trivalent vaccine, a pan-coronavirus vaccine, a rabies vaccine, a respiratory syncytial virus vaccine, a herpes zoster vaccine, and more.

R&D Pipeline

Jia Chen Xi Hai(Hangzhou/Shanghai) Biotechnology Co., Ltd. is an innovative biotech company focused on the development of self-replicating and conventional RNA-based drugs and vaccines. The company’s pipeline covers cancer immunotherapy, infectious disease vaccines, rare diseases, and medical aesthetics. Its cancer immunotherapy and infectious disease vaccine programs are rapidly advancing into clinical trials.

R&D Pipeline

JCXH-211Is a self-replicating-basedA novel drug encoding human interleukin-12 (hIL-12) RNA, it is the world's first self-replicating RNA expressing cytokines for the treatment of advanced solid tumors, and also the first mRNA biotechnology company in China to receive an IND approval from the U.S. FDA. Preclinical studies have shown that JCXH-211 demonstrated superior anti-tumor efficacy compared to similar research drugs using traditional non-replicating mRNA across multiple PDX disease models. In mouse models, it effectively killed tumor cells, eliminated distant tumors, and prevented tumor recurrence.

Youjia Biotech has built an intelligent platform for target selection and sequence design.The NDDS system, the third-generation CMS3 modification technology with chemical modification, and the diversified delivery systems of CPNP, PNAC, and LNP, which possess independent intellectual property rights and meet various administration methods and targeting needs, have resolved key technical issues affecting drugability such as stability, half-life, immunogenicity, and specificity of nucleic acid sequences. The current product pipeline has covered areas including fibrosis, metabolic diseases, ophthalmology, and oncology.

The company's fastest progressing pipeline has chosen the most mature liver delivery method to treat liver fibrosis, and it is expected to be submitted in the second half of this year.IND。

Cormorant Biopharma is a startup innovative drug research and development company. Leveraging the capital, technology, and talent advantages of Shanghai, Boston, and Singapore, and combining the team's in-depth understanding of novel biological targets with years of industry experience in nucleic acid drug chemistry, Cormorant Biopharma focuses on developing new nucleic acid drugs for liver and eye diseases.

ComaBiopharma is dedicated to developing innovative targets that restore liver regeneration capabilities for the first time globally, with candidates currently in the preclinical research stage.CG-LR1 candidate and a pipeline layout targeting a series of innovative liver regeneration targets.

Technology Platform

Daru Biopharma is a leading nucleic acid innovation drug platform company dedicated to discovering and developing modular and programmable nucleic acid drugs to benefit patients worldwide. It has developed its own intellectual property.RAZOR™ Platform: Research and development of differentiated siRNA drug molecules from next-generation chemical modifications and novel biological insights.

RN0191Originated from Daraigen BiosciencesGAIA Liver-Targeting Platform's Double-Stranded Small Interfering RNA (siRNA) Targeting PCSK9. The GAIA Liver-Targeting Platform of Argo Biopharma has proprietary intellectual property rights with superior N-acetylgalactosamine (GalNAc) conjugation in its class, a finely optimized fully chemically modified backbone structure, and chemical modifications that enhance activity and specificity to achieve deeper and longer-lasting gene silencing effects in liver targeting, helping RN0191 to have the potential to become the best-in-class PCSK9 siRNA inhibitor. RN0191 is the first project from the GAIA platform of Argo to enter clinical trials, which also fully validates the drugability of the GAIA liver-targeting platform.

Napptide is a company dedicated toBiotechnology company specializing in siRNA small nucleic acid drug developmentNapptide focuses on the in-depth development of platform technologies for small nucleic acid drug research and development, establishing a mature R&D system for small nucleic acid drugs encompassing sequence design, chemical modification, and delivery platforms. Guided by unmet clinical needs, the company is committed to differentiated siRNA.Argo Biopharma's R&D pipeline is focused on developing novel and highly efficient siRNA therapeutics for liver-derived diseases, ophthalmic diseases, and CNS disorders. The founder, Academician Chen Pu, is a member of the Canadian Academy of Engineering and an internationally renowned expert in small nucleic acid delivery.

RJ Biotech is a company with global leadershipA biotechnology company specializing in mRNA technology. The company owns global independent intellectual property rights for foundational mRNA-related technologies. Currently, Ruiji Bio has developed the capability to advance from drug target discovery to clinical research. The company's next phase of development aims to promote the industrialization capacity while advancing multiple pipeline clinical studies.

R-J Biopharma has developed dozens of pipelines across three major fields, covering infectious disease vaccines, cancer immunotherapy, and protein replacement therapy. Notably,Since June 2022, RH109, the world's first lyophilized COVID-19 mRNA vaccine (Omicron strain) independently developed by Ruiji Biotech, has been granted clinical trial approvals in the Philippines, New Zealand, and Hong Kong, China. Shortly after, this vaccine was selected to conduct a special clinical study in China.

RH109Developed independently by Ruiji BioLNP lyophilization technology can effectively maintain the physicochemical properties and biological activity of mRNA, and achieve long-term storage at 2-8°C, solving the industry-wide problem of low stability and difficult storage and transportation that has commonly plagued mRNA vaccines.

Qilu Pharmaceuticals in gene therapy, cell therapy, small nucleic acid drugs,Layout in multiple fields such as ADC, targeted drugs, novel antibodies, and new delivery systems.

Qilu Pharmaceutical at its highestArgo Biopharma has introduced a small nucleic acid drug for the treatment or prevention of hepatitis B from Arbutus, which holds the most core patent for RNA delivery (LNP), at a price of $285 million. Earlier in May this year, a clinical trial application for this drug has been submitted.

Shi Neng Kang (SynerK) is a biopharmaceutical company focused on developing RNA-targeted therapies, with research and development centers located in Boston, USA, and Suzhou and Beijing, China. The founder is an industry expert with extensive experience in the discovery and development of RNA therapies. SynerK aims to build a world-class RNA-targeted therapeutics company to treat diseases that are difficult to cure through conventional therapies.

Shinengkang has innovative delivery technologies targeting the liver and extrahepatic organs. The first candidate drug is expected toEntered the clinical stage in 2023.

Recently, Argo and Xianweida have established a partnership to jointly develop small RNA interference-based therapies.(siRNA) technology innovative therapy for the treatment of liver and metabolic diseases with urgent clinical needs.

Shuimu Star Biopharmaceutical (Shenzhen) Co., Ltd. was established in June 2019. Shuimu Star is a biopharmaceutical developer, mainly engaged in the research, production, and sales of RNA drugs targeting tumor metabolism reprogramming, and provides a series of products such as small nucleic acid drugs and small nucleic acid kits, committed to offering relevant pharmaceutical products and services to patients.

In response to the crowding in the mRNA field, Shuimu Xingchen Biopharmaceutical has chosen long non-coding RNA (lncRNA) in the small nucleic acid drug sector.

On March 21, 2023, Shuimu Xingchen received angel round funding, the amount of which was undisclosed. The investor was Lihexiaokun.

AusperBio is a clinical-stage innovative drug development company operating simultaneously in China and the United States, dedicated to researching and developing First-in-class and Best-in-class proprietary targeted delivery small nucleic acid drugs. AusperBio owns the proprietary intellectual property Med-Oligo™ ASO patent technology platform, focusing on functional cures for chronic hepatitis B (HBV) and highly efficient targeted treatments for liver diseases, while also exploring the vast potential of new targets beyond the liver. AusperBio’s strategy is to combine its leading Med-Oligo™ oligonucleotide technology with specific and highly efficient targeting technologies to address a wide range of currently unmet medical needs.

On November 1st, AusperBio announced the completion of a 100 million RMB Pre-A+ financing round. This round was led by the investors from the Pre-A round, with the funds completing USD settlement in the middle of this year. The proceeds will accelerate the global clinical trials of AHB-137 and the research and development of other Med-Oligo™ small nucleic acid innovative drugs utilizing targeted delivery technology under AusperBio.

Shanghai Jinzhong Nuomei Biomedical Technology Co., Ltd. is a company dedicated to the development of small nucleic acid drugs. The company's first product targets Lp(a) drug development and is currently in the IND-enabling stage of research. It has already demonstrated excellent results in reducing lipoprotein(a) in preclinical studies and is expected to enter clinical research this year.

Jinzhong Nuomei has launched a liver-targeted delivery molecule with fully independent intellectual property rights. This liver-targeted delivery molecule features a "comb" structure and, compared to the existing "three-cluster" structure technology, offers higher delivery efficiency and a simpler synthesis process, providing a more cost-effective advantage for scaled production.

Top: "Three-cluster" structure, Bottom: "Comb" structure

Relying on a differentiated technical platform, Argo Biopharma has taken the lead in launching an siRNA product that reduces lipoprotein(a) (Lp(a)) to address the urgent, unmet clinical drug needs.

Founded in 2021, Argo Biopharma is a biopharmaceutical company established by top global scientists. It has an experienced RNA drug research and development team and owns proprietary intellectual property rights for RNAi liver-targeting technology and lipid nanoparticle mRNA delivery technology. With the support of the local government, the company has built an advanced mRNA vaccine production line with an annual capacity of over 400 million doses. Centered on "RNAi and mRNA technology," the company is developing a series of RNA drugs and mRNA vaccines.

The company owns proprietary intellectual property rights to the GalPET liver-targeting RNAi and lipid nanoparticle (LNP) delivery core platform technology. In March 2022, the COVID-19 mRNA vaccine developed by Aglaia Bio and Ribo Biotech entered Phase II clinical trials.

Ima Biotech is committed to achieving breakthrough therapeutic technologies in disease areas with significant unmet clinical needs, such as central nervous system (CNS) diseases, to develop small nucleic acid drugs.

The third-generation nucleic acid delivery technology platform developed by iMab Biologics ensures the safety of nucleic acid drug delivery and achieves a breakthrough in the "lack of effective non-liver nucleic acid drug delivery systems." At the same time, this technology platform completely avoids the high cost of exosome production in vitro, the difficulty in quality control, as well as its instability, susceptibility to degradation, and inability to meet demand.

In August this year, the siRNA liver delivery platform MVIP (Multi-valent Introduction Platform), independently developed by Argo, was granted a patent by the United States Patent and Trademark Office. This patent protects Argo's globally unique GalNAc conjugation method and basic structure.

Unlike the platform patents of major siRNA drug manufacturers internationally, the MVIP technology not only ensures the efficient delivery of the active ingredient siRNA to hepatocytes but also exhibits better stability in vivo, without the degradation of the antisense strand in plasma. After entering hepatocytes, the MVIP technology can further inhibit the binding of the sense strand to the RNA-induced silencing complex (RISC), enhancing RISC's selectivity for the antisense strand and reducing off-target effects.

Prior to this, based on the MVIP platform technology, Argo Biopharma had already been granted its first patent for a liver-targeting siRNA drug in 2020. This marked the first time a Chinese company utilized fully independent and innovative technology to construct an siRNA delivery platform patent, breaking through the patent barriers in this field held by leading foreign companies. Based on the MVIP platform technology, Argo also became the first company in China to receive NMPA's tacit approval to enter clinical research for an siRNA drug. Meanwhile, Argo has engaged in BD collaborations regarding the MVIP-siRNA platform technology with several well-known pharmaceutical companies, working together to address unmet needs and urgent clinical demands for innovative therapies in various disease areas.

SicaGene is a biotechnology company focusing on the research and development of a new generation of single-stranded oligonucleotide (ASO) drugs. The team brings together senior experts from internationally renowned biotechnology companies such as BeiGene and Ionis, possessing extensive experience in oligonucleotide drug R&D, clinical trials, and industrial transformation. It has obtained qualifications and certifications such as "Zhongguancun High-tech Enterprise" and "Science and Technology Small and Medium-sized Enterprise," and was awarded the Most Innovative Award at the 10th "Dongsheng Cup" International Entrepreneurship Competition.

The company has independently developed "bottleneck" technologies in the field of oligonucleotide drug development, including the SicaScreenTM high-efficiency screening platform, the SicaChemistryTM nucleic acid combination modification platform, and the SicaDeliveryTM innovative multi-tissue delivery system. Based on the company's original research foundation in antisense oligonucleotide (ASO) drug development, for different diseases, an ASO drug development strategy is adopted to either "upregulate" the expression of functional proteins or "downregulate" the production of disease-causing proteins, enabling efficient screening of druggable targets while reducing development difficulty and cost. The company is committed to drug research and development in the fields of the central nervous system, ophthalmology, and liver diseases, with leading products already entering the preclinical research stage.

Founded in early 2021, Saintarna Biopharma is a biopharmaceutical company dedicated to developing novel small nucleic acid drugs based on RNA interference (RNAi) technology, with research and development centers in both China and the United States. The founding team consists of seasoned experts in the field of nucleic acid drugs, possessing years of experience in nucleic acid drug development and cutting-edge technical expertise in the industry.

Since its establishment, Argo Biopharma has successfully built a globally leading nucleic acid drug chemical modification and intrahepatic/extrah hepatic delivery technology platform with independent intellectual property rights, accelerating the R&D process of RNAi drugs with differentiated advantages. Its first core product has entered clinical trials, and multiple pipelines are also underway, covering disease areas such as cardiovascular and cerebrovascular and metabolic diseases, immune-mediated diseases, and neurological disorders.

R&D Pipeline of Saint Biologics, Image from Official Website

MolecularAxiomMolecularAxiom was founded in San Diego in 2021, focusing on nucleic acid drug discovery, clinical development, and commercialization. Its core strengths encompass multi-platform RNA technologies, including ASO, RNAi, mRNA, and drug delivery technologies such as LNP. Axiom aims to create highly differentiated nucleic acid drugs targeting high-value biological targets to address significant unmet medical needs.

At the end of last year, Molecular Axiom announced the completion of its Series A financing. This round of financing was led by Shenzhen Oriental Fortune, with participation from GoldPu Health Fund and RuiHe Capital. It is reported that the funds from this round of financing will be used for preclinical development of multiple projects including cancer and neurodegenerative diseases, accelerating the entry into Phase I clinical trials.

Oli Biopharmaceuticals (Suzhou) Co., Ltd. is a professional pharmaceutical nucleic acid CDMO company that provides customers with "one-stop" services ranging from nucleic acid drug discovery, laboratory R&D, process and analytical development, CMC services, API production, to drug registration. The technical team of Oli Biopharmaceuticals comes from one of the earliest teams in China that started the process development and CMC research for nucleic acid drugs, possessing extensive experience in project development and product registration.

Currently, the company has built four major core technology platforms that lead within the industry: solid-phase nucleic acid synthesis, chemical modification and conjugation, process development and analysis, and CMC pharmaceutical research. It has also established in-depth collaborations with many pharmaceutical companies and biotechnology firms both in China and internationally.

Hongliang Biopharmaceuticals is a biomedicine service provider. The company mainly engages in the research, application, and promotion of RNA drugs and innovative drug delivery technologies. Its pharmaceutical products can treat various major diseases such as cancer, genetic disorders, hypertension, and hyperlipidemia. Earlier this year, Hongliang Biopharmaceuticals received strategic investment from Dingfu Investment, Baidu Ventures, and F&R Venture Capital.

Ontology Biotech, established in 2022, is a drug development company based on antisense nucleic acid technology. The company has built an internationally leading, unique, and highly efficient siRNA technology platform as well as an ASO technology platform that enables bidirectional regulation of protein expression, significantly expanding the range of treatable diseases.

Oncotarget Bio has multi-pipeline layouts in the fields of cardiovascular diseases, fatty liver, renal cysts, cancer, and Alagille syndrome, and is committed to the research and development of innovative drugs. Currently, multiple animal experimental data have demonstrated the high efficiency of the company's proprietary technology platform, and the development of various pipeline drugs is proceeding smoothly.

ViaGen is a small nucleic acid drug therapy company based in China with a global outlook, aiming to build a biopharmaceutical enterprise with comprehensive capabilities from research and development, production to commercialization. The company was founded in 2022 and has established a long-term strategic partnership with Arrowhead Pharmaceuticals (NASDAQ:ARWR), an internationally leading small nucleic acid drug company. Currently, the company's product pipeline includes three small nucleic acid drugs in clinical development targeting the cardiovascular and metabolic disease fields.

VSA006It is a small interfering RNA (siRNA) drug targeting hydroxysteroid 17β-dehydrogenase 13 (HSD17β13) in hepatocytes. This product has completed safety and pharmacokinetic evaluations in Phase 1/2 clinical trials involving healthy subjects and patients diagnosed with or clinically suspected of having NASH (including patients recruited from Hong Kong). In the upcoming randomized, double-blind, placebo-controlled Phase 2 clinical trial in China, the safety and efficacy of VSA006 will be evaluated in Chinese patients with NASH.

Cagen Bio is one of the first biotech companies in China to engage in the research and development of small nucleic acid conjugate drugs. It achieves extrahepatic delivery of small nucleic acids through conjugation, filling a domestic gap in this niche field. Recently, it completed an angel round of financing worth tens of millions of RMB, jointly led by Matrix Partners China and Frees Fund.

The Lead Product of Caribou BioCGB1001An antibody-siRNA conjugate drug for Type 1 Myotonic Dystrophy (DM1) will initiate the IND-related work this year.

Dinayuan Sheng, established in May 2022, focuses on the development of novel nucleic acid self-assembly technology to create nanomedicines with organ and cell targeting capabilities. The company has shown great potential in the delivery of small nucleic acid drugs, offering promising solutions to the industry-wide challenge of extrahepatic targeting delivery for such drugs.

Currently, Dinayuan Sheng has built a team for research and development, process development, and quality management, fully promoting the pipeline development. Leveraging the advantages of vector targeting technology, the company has launched a rich pipeline layout in the treatment areas of cancer, metabolic diseases, and vaccines, with core pipelines progressing to the PCC confirmation stage.

Xianyan Bio is a medical research and experimental development service provider, focusing on the project development of nucleic acid drugs and related technology research and development.As a shareholder company, HitGen transferred seven small nucleic acid drug projects in the early stage of research and development to Xianyan Bio for 14.73 million yuan last year. Meanwhile, the company granted Xianyan Bio an ordinary license to use its platform technology within a reasonably necessary scope for the subsequent research and development, clinical trials, registration, production, and commercialization of the aforementioned small nucleic acid drug projects at a price of 2.27 million yuan.

Hongxin Biotech, established in December 2021, is an RNA innovative drug research and development enterprise that focuses on nucleic acid drug delivery technology. It has built three core technology platforms: mRNA sequence design, efficient mRNA synthesis, and lipid nanoparticle (LNP) delivery, to achieve the rapid development and industrialization of RNA drugs. Regarding its core ionizable amino lipids, Hongxin Biotech has completed a global patent layout, laying the foundation for the development of its mRNA innovative drug pipeline and external licensing partnerships.

Argo Biopharma was founded in April 2021, focusing on the commercial development of RNA drugs. Its founder, Dr. Jianxin Chen, has extensive industrial experience in the field of nucleic acid drug delivery. He led the development of MC3, the key delivery technology for Patisiran, the world's first siRNA drug. Additionally, he is one of the core founders of Acuitas Therapeutics, a company specializing in Lipid Nano-Particle (LNP) delivery technology. It is reported that the LNP delivery carrier ALC-0315 used in BioNTech and CureVac's mRNA vaccines comes from Acuitas Therapeutics.

In May 2021, Chuanxin Biotech partnered with Acuitas Therapeutics to establish a collaborative development and licensing agreement for LNP delivery technology. By adopting clinically validated and mature LNP delivery technology, the company aims to accelerate the commercial development of mRNA vaccines. Currently, Chuanxin Biotech is focused on developing proprietary LNP delivery technology with immune cell targeting capabilities. The company has built four core technology platforms centered around mRNA/LNP, establishing comprehensive end-to-end mRNA vaccine development capabilities. These include mRNA sequence design and synthesis, LNP formulation screening and process development, LNP pilot production, and quality control.

The astronomical deal between Argo and Novartis demonstrates that, after years of accumulation, the quality of some innovative drugs produced in China has reached a level capable of competing internationally, thereby attracting significant investment from multinational pharmaceutical companies. Small nucleic acid drugs, which often originate from rare disease treatments, possess advantages such as abundant targets, shorter R&D cycles, long-lasting efficacy, and high clinical development success rates. These qualities allow them to quickly capture certain markets that traditional small-molecule drugs cannot penetrate, thus holding the potential to become "blockbuster" drugs.

With the in-depth research on pathogenic mechanisms and the iterative upgrading of delivery carriers, there are currently more and more small nucleic acid drugs in clinical research, targeting vast markets of chronic diseases such as hypertension, hepatitis B, type 2 diabetes, and central nervous system diseases, or severe disease markets like cancer. These markets often have significant unmet medical needs and may potentially trigger a wave of R&D transactions in the future.