Pipeline Overview of 22 Chinese Companies Developing AAV Gene Therapies

AAV vectors have become one of the popular carriers in the field of gene therapy due to their high safety, good tissue targeting, stable and continuous expression of exogenous genes, and low immunogenicity. In recent years, AAV gene therapy has shown promising application prospects in the field of rare diseases, including age-related macular degeneration (AMD).Hemophilia, spinal muscular atrophy, frontotemporal dementia, glycogen storage disease, Huntington's disease and other indications have all made certain progress in clinical settings.

As a research hotspot in the field of gene therapy, the AAV gene therapy sector has already attracted a large number of pharmaceutical companies, including Spark, Regenxbio, uniQure, BioMarin, Belief BioMed, and ZhiShan WeiXin. This article will review 22 companies in China that are involved in AAV gene therapy (feel free to leave comments for additions), and provide an overview of their pipelines for reference.

Source: Frontier of Cell and Gene Therapy

Neurophth was founded in 2016 as the result of over a decade of exploration and accumulation in ophthalmic gene therapy technology by Professor Li Bin's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, starting from 2008. The company has established operations in Wuhan, Suzhou, Shanghai, and the United States. Professor Li led the team to successfully complete translational research from the laboratory to clinical application, confirming the application value of adeno-associated virus (AAV) vector technology in ophthalmic gene therapy through a series of clinical trials both in China and internationally.

With the help of a mature AAV gene therapy technology platform, Neurophth has established a rich product pipeline, including more than 10 research projects targeting optic nerve injury diseases, vascular retinopathy, and various other ophthalmic conditions.

Core ProductsNFS-01 (NR082, Trade Name: Nuweijia®), aimed at treating ND4-mediated Leber’s Hereditary Optic Neuropathy (ND4-LHON), has been granted Orphan Drug Designation (ODD) by the U.S. FDA and the European Medicines Agency (EMA). It is the first gene therapy new drug developed in China to receive both clinical trial IND approval from China's NMPA and the U.S. FDA. Patient enrollment and dosing have been completed for the Phase III clinical trial in China, as well as for the Phase I/II trials in the United States.

The second U.S. ODD drug of the company, NFS-02, has completed the dosing of the first patient in the China-U.S. international multicenter Phase I/II clinical trial. The company's third gene therapy drug, NFS-05 for ADOA, has been approved for clinical trials in Australia. The company’s pipeline also includes preclinical candidates for optic neuroprotection and vascular retinopathy.

CHIGENOVO Co., Ltd. is a national high-tech enterprise specializing in clinical genetic diagnosis and gene therapy drug research and development for hereditary eye diseases. It is one of the first companies in China to engage in the research and development of ophthalmic gene therapy drugs. The company has established a clinical genetic diagnosis platform for hereditary eye diseases and a gene therapy drug research and development platform, dedicated to providing precise gene testing and gene therapy "one-stop" services for patients with hereditary eye diseases.

ZVS203e Injection, developed by CHIGENOVO, is a gene-editing therapeutic drug that utilizes the third-generation artificial nuclease CRISPR/Cas9 to perform targeted editing on the mutation hotspot of the RHO gene, achieving a single-dose lifelong cure.This product is the first in vivo AAV gene editing therapeutic product accepted in China.。On February 7, 2024, CHIGENOVO Co., Ltd.'s first ophthalmic gene-editing Class 1 innovative drug - ZVS203e Injection - received the CDE clinical trial (IND) implied permission. This is another landmark event following the product's receipt of U.S. FDA clinical trial (IND) implied permission in December 2023. Phase I/II trials are currently underway.

The company mainly develops two types of products:One type is gene replacement therapy.The main strategy is to use rAAV viruses to deliver normal copies of the mutated gene into patients' retinal cells for gene expression supplementation, serving a therapeutic role. This treatment approach primarily targets genetic diseases caused by mutations leading to insufficient gene expression, such as autosomal recessive genetic disorders and X-linked recessive genetic diseases; additionallyOne category is gene editing therapy.The main strategy is to use rAAV viruses to deliver repair sequences capable of fixing gene mutation sites into patients' retinal cells, performing targeted repair of the gene mutation sites to restore normal gene function. This treatment method mainly targets autosomal dominant genetic diseases.

FronGenes Bio was founded in September 2019, bringing together professionals from both China and the U.S. with extensive experience in innovative gene drug research and development, production, registration, and clinical study management. Focusing on rare diseases and chronic conditions, the company is committed to developing and manufacturing high-quality, affordable recombinant adeno-associated virus (rAAV) vector gene therapy products to meet the significant unmet clinical treatment needs of patients with genetic disorders and chronic diseases worldwide.

FronGeno is striving to achieve the goal of developing rAAV gene therapy products across a broader range of fields. Its pipeline not only covers rare diseases but also includes chronic conditions in ophthalmology, hematology, neurology, cardiovascular, and metabolic areas.

FT-001 Injection is a recombinant adeno-associated virus (AAV) gene therapy drug targeting RPE65 biallelic variants-related inherited retinal degeneration, which has been granted clinical trial approval by both the U.S. Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA).

Sichuan Zhishan Weixin Biotechnology Co., Ltd. is a leading gene therapy company in China that focuses on the research and development of rAAV gene drugs and disruptive production. It is the first innovative pharmaceutical company in China to have both original gene drugs for types A and B hemophilia approved for clinical trials.

Relying on cutting-edge technology, ZSWX has laid out multiple pipelines, covering treatment areas such as blood diseases, rare diseases, and more. It has successfully advanced two rAAV gene therapy products to receive clinical approval, becoming the first Chinese pharmaceutical company to obtain dual clinical certificates for new gene drugs for both type A and B hemophilia. Since its establishment in 2018, ZSWX has completed three rounds of financing—angel round, Series A, and Series A+—empowering the high-quality development of ZSWX.

• ZS802 Injection is an rAAV gene drug with clinical indications for Hemophilia A, classified as a Class 1 new drug in China.June 28, 2023, "ZS802 InjectionIND Approved by CDE to Initiate Phase I/II Clinical Trials.

• On August 30, 2022, the gene therapy product independently developed by the companyZS801 InjectionClinical trial application receives tacit approval from CDE,Indications: For the control and prevention of bleeding in male patients aged 18 years and above with severe or moderately severe Hemophilia B (congenital Factor IX deficiency, Factor IX < 2%).

• On April 20, 2022, the clinical trial application for VGB-R04 injection was approved by the CDE, with the indication being Hemophilia B caused by congenital deficiency of coagulation factor IX.VGB-R04 is the first AAV gene therapy product independently developed by Tianzeyun Therapeutics.

• On November 1, 2022, the Investigational New Drug (IND) application for VGR-R01 injection was granted tacit approval by the CDE. VGR-R01 is a gene therapy product independently developed by Tianze CloudTech for patients with crystalline retinal dystrophy (BCD) caused by CYP4V2 gene mutations. It is also the world's first therapeutic drug targeting BCD to apply for clinical trials for a new drug, with the mechanism of action being gene replacement.

• 2023On March 1, the first clinical study of the AAV gene therapy product VGN-R08b injection — "An Exploratory Clinical Study to Evaluate the Tolerance and Safety of Intracerebroventricular Injection of VGN-R08b in Patients with Type II Gaucher Disease" — was successfully initiated at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine.

• On July 13, 2023, VGM-R02b was approved by the CDE to conduct clinical trials for the treatment of Glutaric Acidemia Type I.

• On April 19, 2024, VGN-R09b, independently developed and produced by Tianze CloudTech and its wholly-owned subsidiary Shanghai Taichang, was approved by the CDE to conduct clinical trials for the treatment of Parkinson's disease (PD) and aromatic L-amino acid decarboxylase deficiency (AADCD).VGN-R09b is the first gene therapy in China to be approved for clinical registration using an AAV-mediated dual-gene strategy.

  
  

Langxin Bio was founded in 2020, focusing on the research, development, and manufacturing of innovative gene therapy drugs. Since its establishment, the company has built a GMP-compliant, scalable platform process for AAV production, with the capability to develop high-yield, high-quality gene therapy products at a controllable cost.June 11,Longxin Bio Completes B+ Round Financing to Advance Gene Therapy Drug R&D and Industrialization.

Currently, the company has advanced 5 candidate molecules into clinical trials, taking the lead in conducting gene therapy clinical research in three blinding eye disease indications and obtaining 3 INDs. The first pipeline, LX101 for treating RPE65 mutation-associated inherited retinal dystrophy (IRD), has entered Phase III clinical trials; the second pipeline, LX102 for treating wet age-related macular degeneration, has entered Phase II clinical trials; the third pipeline, LX103 for treating X-linked retinoschisis, has completed an IIT trial with 6 patients, showing significant safety and efficacy.

Beijing Jinlan Gene Technology Co., Ltd. was established in 2018 as a biotechnology platform company focused on the innovative research and development of gene therapy drugs.

Relying on the AAV gene delivery technology platform of Jinlan Gene, Jinlan Gene has developed multiple gene therapy drug pipelines, including treatments for Spinal Muscular Atrophy (SMA), Hypertriglyceridemia, Pompe Disease, and Familial LCAT Deficiency. The selection of these gene therapy research directions is guided by an inherent logic and represents key areas within their respective fields.

• On April 6, 2023, the IND application for "GC101 Adeno-Associated Virus Injection," an AAV gene therapy drug for treating Spinal Muscular Atrophy (SMA), received clinical trial approval from the CDE. The approved indication this time is Type 3 Spinal Muscular Atrophy (Type 3 SMA). This marks the third new indication for GC101 Injection following the approval of clinical trials for Type 1 and Type 2 SMA.

• On March 29, 2023, the IND application for "GC301 Adeno-Associated Virus Injection," an AAV gene therapy drug used to treat Pompe disease, was officially approved by the CDE, with the indication being late-onset Pompe disease (LOPD). This is another new indication for GC301 Injection following the approval of its clinical trial (IND) for infantile Pompe disease.

• On November 15, 2022, the IND for GC304 Adeno-Associated Virus Injection ("GC304 Injection") was approved by the CDE, indicated for hypertriglyceridemia with recurrent acute pancreatitis.

Belief BioMed Inc., founded in May 2018,The company is committed to providing more effective innovative gene therapies for severe genetic diseases and chronic diseases through safe and efficient viral vector technology.

Currently, the product pipeline of Belief BioMed covers multiple disease areas, including hemophilia B/A, Parkinson's disease, arthritis, cancer, ophthalmic diseases, muscular dystrophy, hereditary muscle diseases, and lysosomal storage disorders. Several products have already entered the clinical trial stage.

BBM-H901 Injection is the first AAV gene therapy drug for hemophilia administered intravenously to enter the registration clinical trial in China, and also the first gene therapy drug for rare diseases administered intravenously in China. Currently, globally, there are no AAV gene therapy drugs approved for the prevention of bleeding in adult male patients with hemophilia B. The US company Biomarin, which has the fastest R&D progress, is currently conducting Phase III clinical trials.

Dingxin Gene, established in July 2020, completed its angel round in October and the Pre-A round in 2021. Its main core technology is derived from the AAV viral vector, with indications primarily focusing on rare diseases in ophthalmology and otology. Currently, the company has two main pipelines targeting deafness caused by OTOF gene mutations and neovascular age-related macular degeneration (nAMD). Additionally, it has developed a non-viral siRNA-GalNAc liver-targeted delivery technology platform.

Developed independently by Dingxin GeneRecombinant Adeno-Associated Virus (rAAV) Gene Therapy ProductsRRG001 Intravitreal Injection, the data from investigator-initiated clinical studies (IIT) conducted in the early stage has preliminarily revealed sustained clinical efficacy at a lower single-dose level. Subjects in the three ongoing dose-exploration studies are safe and tolerant, with no SAEs reported.

Following the CDE clinical trial approval for RRG001 intravitreal injection in November 2023, a Phase I/IIa multicenter clinical study targeting patients with neovascular age-related macular degeneration (nAMD) was initiated on December 28, 2023, at Tianjin Medical University Eye Hospital, the leading institution. Under the leadership of Professor Xiaorong Li, the hospital's president, the first patient dosing was successfully completed, with the participant showing good postoperative ocular and systemic conditions.

SineuGene (Beijing) Biotechnology Co., Ltd. (English name "SineuGene," abbreviated as "SineuGene") was established at the end of 2021. It is a biopharmaceutical enterprise focusing on gene therapy for neurological diseases. Its core pipeline originates from over a decade of fundamental research achievements in the field of neuroscience by Professor Yichang Jia's laboratory at the School of Medicine, Tsinghua University.

By integrating technologies such as AAV-mediated gene expression and editing, as well as small nucleic acid-mediated gene expression regulation, the company has developed multiple product pipelines aimed at addressing neurological disorders including Amyotrophic Lateral Sclerosis (ALS), Stroke, Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), and Autism Spectrum Disorder (ASD).

On May 22, 2023, the first compassionate use of SNUG01 in a single-arm, open-label exploratory clinical study assessing a single intrathecal injection for treating patients with Amyotrophic Lateral Sclerosis (ALS) was completed. This marks the first clinical dosing attempt in China using AAV gene therapy for ALS.As of today, the subjects have been dosed with SNUG01 for a full year. In terms of safety assessment, indicators such as vital signs, hematology, and imaging examinations show that the drug has good safety and tolerability, with no serious adverse events (SAE) or any drug-related adverse events (AE) occurring.

Jinweike Bio is a company dedicated to the development of AAV gene therapies for ophthalmic diseases, neuromuscular diseases, and genetic metabolic disorders. Currently, several of its AAV gene therapy products in the pipeline have entered the IIT clinical research stage.

Currently, the company has multiple products under research, with a focus on ophthalmic diseases, neuromuscular diseases, and genetic metabolic disorders. Among them, JWK001 for treating wet age-related macular degeneration (wAMD) and JWK002 for treating X-linked retinoschisis (XLRS) are the leading pipelines with the fastest progress.

On February 22, 2024, the Investigational New Drug (IND) application for "JWK001 Injection," a Class I innovative gene therapy independently developed by Jinweike for neovascular age-related macular degeneration (nAMD), was successfully approved by the National Medical Products Administration (NMPA).JWK001 Injection is the first AAV gene therapy new drug to adopt a "two-plasmid packaging system."

Based on the regulatory mechanisms of protein phase separation within biological systems, Regeneron has developed a series of innovative drug pipelines. In addition to ALS, its product pipeline also covers diseases such as Parkinson's disease, Alzheimer's disease, cataracts, dry age-related macular degeneration, and cardiovascular plaque deposition.

On May 9, Ruijikang's Class 1 new drug RJK002 injection received clinical trial tacit permission from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), with the indication for Amyotrophic Lateral Sclerosis.This is the first ALS AAV gene therapy drug approved for clinical use in China,It is also the world's first AAV gene therapy drug for ALS targeting abnormal protein aggregation.

RJK002 demonstrated significant neuroprotective effects and extended survival in preclinical ALS model animal studies. It was granted Orphan Drug Designation by the U.S. FDA in October last year. Currently, the multi-center IIT study (investigator-initiated clinical research) for RJK002 is proceeding in an orderly manner in China, with Phase I clinical trials about to commence. In addition, Regigene is actively preparing for the U.S. IND application for RJK002, gradually advancing its global strategic layout.

Skyline Therapeutics is an innovation-driven global clinical-stage gene therapy company dedicated to researching, developing, and producing breakthrough new therapies to address unmet medical needs of patients in serious disease areas.Skyline Therapeutics has established a robust R&D pipeline covering disease areas such as ophthalmology, neurology, cardiovascular, and metabolism. Multiple innovative gene therapy projects have received regulatory approval from China and the U.S. to conduct clinical trials or have entered the IND application stage.

• In October 2023, Skyline Therapeutics announced its AAV ophthalmic gene therapy drug under research.SKG0106 Intravitreal InjectionThe Investigational New Drug (IND) application has been approved by the National Medical Products Administration (NMPA) to conduct clinical trials for a new drug to treat neovascular age-related macular degeneration (nAMD). SKG0106 received FDA approval in June this year to initiate global Phase I/IIa clinical trials for treating nAMD, and the global clinical trial program has now been launched.

• December 12, 2023，Skyline BioSelf-developedThe Investigational New Drug (IND) application for the AAV gene therapy drug SKG0201 injection has been approved by the National Medical Products Administration (NMPA).LaunchTreatment of Type I Spinal Muscular Atrophy (SMA)Phase I clinical trial.

On January 16, 2024, the clinical trial application for LY-M001 Injection, a Class I therapeutic biological product independently developed by Lingyi Bio, received tacit approval from the National Medical Products Administration (NMPA).LY-M001 Injection is the first self-developed AAV gene therapy drug in China targeting Type I or Type III Gaucher disease.

This product uses recombinant adeno-associated virus (rAAV) as a vector, and after a single intravenous infusion, it can express the glucocerebrosidase required by patients. The IIT clinical research project led by Dean Huang He of the First Affiliated Hospital of Zhejiang University School of Medicine has officially started and completed the first patient dosing. Preliminary IIT data shows that LY-M001 performs well in both efficacy and safety, with no adverse events occurring.

Founded in 2016, NeuExcell Therapeutics is one of the representative companies dedicated to developing gene therapies for the treatment of neurological diseases. On May 4, 2023, NeuExcell Therapeutics completed a Pre-A+ round of financing exceeding 100 million RMB.The technology platform can be applied to the treatment of numerous neurological diseases, such as stroke, glioma, Alzheimer's disease, Huntington's disease, ALS, Parkinson's disease, and ophthalmic diseases, among others.

NXL-004 is an innovative treatment developed based on Professor Chen Gong's team's groundbreaking in-situ transdifferentiation technology platform, and it is also the first to receive FDA orphan drug designation for malignancy.GliomaAAV Gene Therapy Product.In March this year, NXL-004, an AAV-NeuroD1 gene therapy product independently developed by Shenxi Biotechnology, successfully completed the first patient dosing. The procedure was led by Professor Huang Yulun, Director of the Neurosurgery Department at the Fourth Affiliated Hospital of Soochow University (Dushu Lake Hospital, Suzhou), who is also a Chief Physician and Doctoral Supervisor. Professor Huang Yulun stated that NXL-004 demonstrated favorable efficacy and safety data in preclinical glioma models and animal studies. Currently, the first clinical subject has shown good safety after dosing, which is a positive signal. Continuous observation will be carried out, with expectations for promising therapeutic outcomes.

Beijing Anlong Biopharmaceutical Co., Ltd. was founded in August 2019 by Dr. Chunlin Zhao, a seasoned expert in the field. The company focuses on the research and development of gene drugs utilizing breakthrough advancements in molecular biology, including new drug development applying technologies such as gene regulation, gene therapy, and gene editing.At the beginning of January 2024, Anlong Biotechnology successfully completed a multi-million A+ round of financing.This round of financing was jointly invested by Taikun Fund and Shunchuang Industry Investment Management Fund. The funds will be used to advance the clinical trials of AAV gene therapy product AL-001 and the research and development of small nucleic acid innovative drugs under Anlong Biotechnology.

AL-001 Ophthalmic Injection, an AAV gene therapy drug independently developed by the company, received clinical trial approval from the CDE in April 2023 and successfully completed the first dosing of a subject in September 2023. The product's indication is age-related macular degeneration (wet form). This is the first AAV gene therapy drug in China administered via suprachoroidal space injection (SCS), and also the world’s first gene therapy expressing aflibercept delivered through the suprachoroidal space.

Huigene's R&D pipeline covers multiple fields such as central nervous system, ophthalmology, and neuromuscular diseases, possessing several technical platforms at a globally leading level. These platforms encompass an integrated R&D capability ranging from drug target screening, drug optimization, and the construction of efficient animal models to preclinical research including efficacy and toxicology analysis, and further to drug process development, CMC production transformation, as well as clinical and regulatory submissions for pharmaceuticals.

In addition, the new generation gene technology R&D center laboratory of CANbridge is developing novel and potentially "curative" gene therapies for rare genetic diseases, including Pompe disease, Fabry disease, Spinal Muscular Atrophy (SMA), and other neuromuscular disorders, while collaborating with researchers and biotechnology companies worldwide.

(Image source: CANbridge Official WeChat)

Reference: Official websites of various companies

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