Gene drugs have significant advantages, capable of overcoming the limitations of traditional drug regulation of protein levels. They have become an important means to tackle difficult diseases and their application value in the fields of genetic and non-genetic diseases is becoming increasingly prominent. As of December 8, 2023, six gene therapy products have been approved for marketing. With the rapid development of gene editing technologies such as CRISPR, Base Editing (BE), and Pilot Editing (PE), as well as delivery technologies like AAV vectors, Lipid Nanoparticles (LNP), and Viral-like Particles (VLP), the research and development of gene drugs has accelerated and has received continuous attention from the capital market. Many domestic gene therapy companies have increased their investment in the gene drug sector, with research pipelines covering rare diseases, ophthalmology, central nervous system diseases, and other disease areas, marking a rapid development stage for gene therapy.

On December 18th, Frost & Sullivan (hereinafter referred to as 'Frost & Sullivan') officially released the 'Blue Book on the Current Situation and Development Trends of the Gene Drug Industry' (hereinafter referred to as the 'Blue Book'). The report analyzes the current situation of the gene drug industry, tracks the development context of the industry and technology, explores the huge potential for industry development, and examines the driving factors behind market development, aiming to provide a reference for participants and observers in the gene drug sector.

1

Overview of the Gene Drug Industry

Gene drugs refer to a method that uses vectors to transduce normal or therapeutic exogenous genes into target cells, replacing or correcting pathogenic genes. The target gene can integrate with the target cell's chromosomes or be located extrachromatically, but both can be transcribed and translated within the cell, altering the original gene expression pattern and achieving the purpose of treating diseases.

In the nearly 20 years since the advent of gene drugs for self-reporting, a total of 12 gene drugs have been approved for marketing worldwide. The rapid development of genetic engineering and drug delivery technologies has accelerated the research and development of gene drugs, with applications extending beyond genetic diseases to include malignant tumors, chronic diseases, and infectious diseases.

The 'Blue Book' sorts out the definition and classification of gene therapy, the mechanisms and advantages of gene drug treatment, the development history of gene drugs, and the application fields of gene drugs. For more detailed content, please refer to the full report.

2

Relevant technologies for the preparation of gene drugs

Gene drugs use viral or non-viral vectors to deliver the target gene into the patient's body to achieve the purpose of treating diseases. Gene drug-related technologies mainly include gene editing technologies (such as CRISPR/Cas9) and delivery system technologies (viral vectors, non-viral vectors). Gene editing technologies can edit gene sequences, serving to replace, silence, or augment genes; delivery systems can carry therapeutic genes or gene editing tools and introduce them into target cells.

Source: Frost & Sullivan research

CRISPR/Cas technology

CRISPR/Cas technology is a third-generation gene editing technique developed based on the adaptive immune system of prokaryotes to resist foreign viruses and plasmid DNA. It achieves the purpose of modifying genomic DNA by artificially designing sgRNA (guide RNA) to recognize the target genomic sequence, guiding Cas proteases to effectively cut the DNA double helix. Among them, Cas9 protein and Cpf1 protein are the most commonly used proteases. As the most widely used gene editing technology today, the CRISPR/Cas platform has advantages over ZFNs and TALENs such as lower cost, higher flexibility, and multi-targeting capabilities, facilitating rapid transformation from research to clinical applications. Currently, CRISPR/Cas technology is widely applied in fields such as in vitro molecular diagnosis, genetic marking, and single-base editing. In November 2023, the world's first CRISPR gene-editing hematopoietic stem cell drug, Casgevy, was approved for conditional marketing authorization in the UK, with indications for sickle cell anemia with recurrent vascular occlusion crisis and transfusion-dependent β-thalassemia.

Source: Frost & Sullivan research

Viral delivery system

After infecting host cells, viruses introduce their own genetic material into the host cells, where these gene sequences are used to express proteins. Based on this principle, by modifying natural viruses and placing target genes into the viral gene sequence, it is possible to use the virus to transfer target genes to target cells. Common viral vectors include retroviruses (Retrovirus), lentiviruses (Lentivirus), adenoviruses (adenovirusAdeno-associated viruses (AAVs), Herpes simplex virus (HSV), and others, among which AAVs have become a popular viral vector in recent years due to their low immunogenicity and mature production process.

The 'Blue Book' introduces gene editing technologies (ZFNs, TALENs, CRISPR, BE, PE, PASTE), delivery system technologies (viral delivery systems, LNP, VLP), and related technological advancements; sorts out the applications of gene editing technologies in in vitro cell therapy and marketed products; and summarizes the core key points of gene drug research and development. For more detailed content, please refer to the full report.

3

Regulatory Mechanism in the Field of Gene Therapies

Current situation of gene drug regulation in the United States

The United States Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), and National Institutes of Health (NIH) under the United States Department of Health and Human Services (HHS) are jointly responsible for the regulation of gene drugs in the United States. Among them, the Center for Biologics Evaluation and Research (CBER) and its subdepartmental organization, the Office of Tissues and Advanced Therapies (OTAT), under the FDA are responsible for the IND, NDA,BLAReview.

Current situation of gene drug regulation in the EU

The Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) is responsible for the approval of clinical trials for gene-drug products, marketing applications, product classification, and certification. Its main legal basis is the Medicinal Products 2001/83/EC and ATMP Medical Products Regulation (Regulation(EC) No 1394/2007), which are approved through a centralized review procedure. The final recommendation for a product that has passed the review is made by the Committee for Human Medicinal Products, which ultimately recommends that the EMA grant a certification after approval and continue to monitor the safety and effectiveness of the drug through testing.

Current situation of gene drug regulation in Japan

Japan has separated gene therapy, cell therapy, and tissue engineering products from drugs and medical devices into a separate category for regulatory oversight. It has revised the Pharmaceutical Affairs Law and introduced the Regenerative Medicine Promotion Law and the Regenerative Medicine Safety Law in succession from 2013 to 2014 as legal bases for the development of gene drug products. The main national regulatory departments in Japan's regenerative medicine field include the Ministry of Health, Labour and Welfare, the Ministry of Economy, Trade and Industry, the Ministry of Education, Culture, Sports, Science and Technology, and the Pharmaceuticals and Medical Devices Agency. The four agencies have different focuses and division of labor in specific matters such as research promotion, design and development, licensing and certification, quality evaluation, and procedure review. In addition, the Japanese Standards Association (JSA) is responsible for formulating industry standards such as safety evaluation.

Current situation of gene drug regulation in China

China started early in basic research and clinical trials in the field of gene drugs. The first clinical trial can be traced back to 1991 (a gene drug treatment clinical trial conducted on patients with hemophilia B). However, at that time, regulatory policies and laws regarding gene drugs were relatively lagging behind, and there were no detailed requirements or regulations for the specific content of multiple aspects of research and development, resulting in weak constraints. In 2003, the National Medical Products Administration issued the "Technical Guidelines for Human Gene Therapy Research and Dosage Form Quality Control," gradually strengthening the supervision of gene drugs. In 2018, China began to strengthen technical guidance and the formulation of laws and regulations in areas such as gene drugs and biosafety. In recent years, documents such as the "Technical Guidelines for Long-term Follow-up Clinical Research of Gene Therapy Products (Trial)," "Technical Guidelines for Non-clinical Research and Evaluation of Gene Therapy Products (Trial)," "Technical Guidelines for Non-clinical Research of Genetically Modified Cell Therapy Products (Trial)," and "Technical Guidelines for Pharmacological Research and Evaluation of In Vivo Gene Therapy Products (Trial)" have been successively issued, continuously optimizing China's gene drug regulatory system.

The 'Blue Book' details the regulatory situation and major policies regarding gene drugs in the United States, the European Union, Japan, and China. For more detailed content, please refer to the full report.

4

Research progress and market potential in the field of gene drugs

As of November 2023, there are 12 gene therapies approved for marketing globally. The therapeutic areas cover oncology, hematological diseases, neurological diseases, ophthalmology, musculoskeletal system, etc.

Source: Frost & Sullivan research

The 'Blue Book' analyzes the market launch of marketed gene therapies and their research and development pipelines. It sorts out the products on the market or in progress for indications such as congenital amaurosis, spinal muscular atrophy, bladder cancer, hemophilia B, crystalline retinitis pigmentosa, Huntington's disease, AIDS, etc., as well as the development trends in the pipeline. For more detailed content, please refer to the full report.

5

Capital market performance of companies in the gene drug field

The 'Blue Book' sorts out the financing situations of domestic and international companies in the gene drug sector, as well as industry cooperation in development and acquisition mergers and acquisitions events over recent years. For more detailed content, please refer to the full report.

6

Introduction to Some Companies in the Gene Drug Field

epistatic gene

Founded in 2018, the company focuses on developing gene innovation drugs. With the mission of "developing better gene therapy delivery technologies to treat more major diseases for which there are no available treatments," it has established an internationally leading innovative delivery technology platform BD-VLP and BDlenti, and is committed to "becoming a leading domestic and first-class high-tech biopharmaceutical enterprise and building a global multi-domain drug research and development platform." The company has already made progress in antiviral, Huntington's disease, glaucoma, thalassemia/sickle cell disease, and in vivoDC vaccineWe have laid out a core gene therapy R&D pipeline in areas such as

Kanglin Biology

Kanglin Biotech is a national-level specialized and innovative small giant enterprise founded by an elite team of returnees from overseas, aiming to develop first-in-class drugs and best-in-class innovative gene drugs. The company focuses on the research, development, and commercialization of innovative gene therapies. It has currently established three major innovation technology platforms: adeno-associated virus (AAV) vectors, lentiviral (LV) vectors, and hematopoietic stem cells (iHSC). The company has made leading progress in multiple therapeutic areas such as thalassemia, Parkinson's disease, AIDS, and hemophilia compared to international peers. With its unique innovation capabilities and professional level, the company has successively received multiple honors and titles, including national high-tech enterprise, Zhejiang Provincial Postdoctoral Workstation, Zhejiang Provincial R&D Center, and Hangzhou's quasi-unicorn enterprise.

Shenxi Biology

Shenxi BiologyNeuExcell) is a global leading innovative biotech company dedicated to applyingIn situ neural regeneration technologyTreats nerve injuries and degenerative diseases. Professor Chen Gong, the founder of NeuExcell, is an internationally renowned regenerative medicine expert. The management team consists of executives from several major international pharmaceutical companies, with rich experience in research and development, management, and operations. NeuExcell's mission is "Regenerate nerves for a better world," and they have developed an extensively applied in-situ neural regeneration technology platform. This platform can be used to treat various diseases such as stroke, Alzheimer's disease, Parkinson's disease, glioma, retinal diseases, and amyotrophic lateral sclerosis, opening up new avenues for the treatment of refractory neurological diseases. Currently, the company has more than 200 international patent applications and has been granted 55 international authorizations.

Tianze Yun Tai

Tianze CloudTech was established in 2020, dedicated to transforming cutting-edge gene therapy technologies into clinically accessible treatments for the benefit of more patients. Tianze CloudTech has assembled a team composed of top academic experts and experienced R&D personnel from the industry, covering all aspects of drug development from concept proposal to product launch. The company has established a series of core technology platforms with independent intellectual property rights, including the ViVec®AAV vector screening platform, ViLNP®lipid nanoparticle technology platform, ViCas®CRISPR gene editing technology platform, and ViHiYi®AAV high-yield technology platform. These platforms focus on developing innovative gene therapies to provide solutions for patients with genetic diseases and neurodegenerative diseases in China and around the world.

Zhongyin Technology

Zhongyin Technology was established in 2016 and is a national high-tech enterprise specializing in the development of gene therapy drugs for genetic eye diseases and clinical genetic diagnosis. It is one of the first enterprises in China to layout in this field. Zhongyin Technology is committed to leading genetic technology innovation, eliminating genetic eye diseases, and providing precise diagnosis and treatment “one-stop” services for patients with hereditary eye diseases. Through its clinical genetic diagnosis platform, Zhongyin Technology has established a database of genetic eye diseases and specialized disease cohorts, summarized the gene mutation frequency spectrum and hotspots among Chinese patients, and provided therapeutic targets for subsequent gene therapy drug research and development. On this basis, it develops drugs with independent intellectual property rights, including gene replacement therapy and gene editing therapy, striving to achieve a “zero-to-one” breakthrough. It has established a complete drug development system that includes target screening, basic research, animal experiment verification, stem cell verification, AAV virus research and production, clinical trial operation, and drug registration application. Zhongyin Technology's diagnostic platform owns the only ophthalmic professional medical laboratory in China that has obtained the “CAP (American Association for Pathologists) Quality System” certification. By transforming and applying cutting-edge life science technologies, it fully empowers the treatment and prevention and control of ophthalmic diseases.

The 'Blue Book' introduces some companies in the gene drug field, including company profiles, development history, technology platforms, research pipelines, core strengths, etc. For more detailed content, please refer to the full report.

A Glance at the Graph｜ The Emerging Asia-Pacific Hybrid Cloud Market Report, 2022

获取白皮书

联系我们