Editor's note: Through the continuous cultivation of new phage presentation antibody library technology, Zhixiang Jintai has overcome the important bottleneck of antibody drug research and development, and has quickly established core advantages in the field of monoclonal antibody and bispecific antibody innovative drug research and development. With strong core technology advantages, a number of blockbuster products under development by Zhixiang Jintai have been in the final clinical stage or are about to be launched, becoming a leader in similar domestic drugs. Zhixiang Jintai(688443. SH) won the title of "China's Science and Technology Innovation Force" in the 2023 China Business Network's "Science and Technology Innovation Industry Atlas".
Zhixiang Jintai(688443. SH) is an innovation-driven biopharmaceutical company with a focus on therapeutic areas such as autoimmune diseases, infectious diseases, and oncology. Up to now, the company has complete antibody drug R&D and production capabilities from molecule discovery, process development and quality research, clinical research to commercial production.
In terms of source innovation, the company has established two major technology platforms: a monoclonal antibody drug discovery technology platform based on a novel phage presentation system and a bispecific antibody drug discovery technology platform. Based on an efficient and reliable technology platform, the company has greatly shortened the discovery cycle of antibody drug candidates, improved the efficiency of drug research and development, and become its important core competitiveness.
Up to now, Zhixiang Jintai has 8 products with 15 indications that have entered the clinical trial stage. Among them, GR1501 for the indication of psoriasis has applied for NDA, GR1802 for the indication of moderate to severe atopic dermatitis has entered the phase III clinical trial stage, which is expected to help the company open up a huge blue ocean market for autoimmune drugs, GR1801 for the passive immunity indication of rabies virus has completed the III clinical trial enrollment, and GR2001 for the passive immunity indication of tetanus has entered the phase II clinical trial, which will help the company achieve a leading layout in the field of infectious diseases. Relying on its technological advantages, the company plans to achieve 1-2 new products entering the clinical trial stage every year in the next few years.
Two major technology platforms build core competitiveness
Zhixiang Jintai is an innovation-driven biopharmaceutical company, based on independent research and development, the company has established a monoclonal antibody drug discovery technology platform and a bispecific antibody drug discovery technology platform based on a novel phage presentation system, and has quickly achieved core advantages in the field of monoclonal and bispecific antibody drugs.
Compared with other antibody discovery methods, phage presentation antibody library technology is a high-throughput technology, which has many advantages such as simple and easy control, fast screening speed, and easy production, and can be used to screen almost any target on the cell surface or within cells, which is one of the mainstream technologies for antibody discovery. At present, among the nearly 30 monoclonal antibody drugs approved for clinical use by the FDA, 7 are isolated by phage presentation technology.
In view of the problems faced in practical application, such as low preparation efficiency and difficulty in the optimization of lead molecules, Zhixiang Jintai has built a new phage presentation antibody library technology platform with independent intellectual property rights: phage presentation technology based on dual vector and antibody library construction technology based on lambda recombinant system. Through the combined use of the above two technologies, the company has successfully shortened the discovery cycle of novel monoclonal antibody drug candidates to 6-9 months, greatly improving the efficiency of drug development.
At present, the new phage presentation antibody library technology has become the underlying core technology of Zhixiang Jintai, and has been successfully applied to the pre-development and research of multiple monoclonal antibody drugs in a variety of antibody drug pipelines. On this basis, the company has also developed single-domain antibody drug discovery technology and new structural recombinant protein drug discovery technology in the field of structural expansion of antibody drugs, and TCRm drug discovery technology in the expansion of antibody drug targets, which has become an important technology accumulation for the company's rapid development in the field of antibody drugs in the future.
In addition to monoclonal antibody drugs, Zhixiang Jintai's exploration of bispecific antibody drugs is also at the forefront of China.
Bispecific antibodies (BsAbs) can bind to two different antigens or two different epitopes of the same antigen at the same time, achieving better results than can be achieved by combining two monoclonal antibodies. However, due to the bottlenecks in preparation technology and the lack of suitable clinical application scenarios, this technology has not received attention for a long time. With the breakthrough of bottlenecks in the field of recombinant antibody expression and purification technology, the clinical value of BsAb has been recognized, and in the decade after 2010, the technology has ushered in a round of development climax, with more than 70 structures developed so far, and four typical clinical application scenarios have been identified.
In 2016, Zhixiang Jintai launched the construction and optimization of the bispecific antibody drug technology platform. With its technical advantages, the company solves the problem of heavy chain mismatch in the expression process of bispecific antibodies, and solves the problem of light chain mismatch through two unique schemes. In particular, on the basis of the company's unique dual-vector phage presentation antibody library technology, a large-capacity human antibody light chain library resource has been constructed, which can screen and construct common light chain bispecific antibodies in a very short time, providing a practical solution for the company to rapidly promote the research and development of BsAb drugs.
Self-exempt blockbuster products hit the 10 billion market
Relying on the advantages of antibody drug R&D efficiency established by the two technology platforms, Zhixiang Jintai has rapidly promoted the clinical research of a number of drugs in recent years. Up to now, the company has developed a number of monoclonal antibody drugs and bispecific antibody drugs, and 15 indications of 8 products have entered the clinical trial stage, covering moderate to severe plaque psoriasis, axial spondyloarthritis, systemic lupus erythematosus, rabies passive immunity and other autoimmune diseases, infectious diseases and other therapeutic areas.
Among them, the marketing application of cerikimab (GR1501) for the indication of moderate to severe plaque psoriasis was submitted in March 2023, and it is the first anti-IL-17 monoclonal antibody drug in China to submit an NDA. At the same time, the drug has also completed phase III clinical trial enrollment for the indication of radiologically positive axial spondyloarthritis.
Autoimmune diseases are chronic diseases in which the immune system loses immune tolerance to autoantigens, which further induces tissue damage and inflammatory responses, and ultimately leads to damage to target organs. Psoriasis is an autoimmune disease in which genetic and environmental factors play a role, and the global prevalence has continued to increase in recent years. According to the Chinese Society of Dermatology and Venereology and the Frost & Sullivan report, the number of psoriasis patients in mainland China is expected to reach 6.85 million by 2030.
Since there is no complete cure, patients with autoimmune diseases such as psoriasis often need long-term medication, and the overall market space is very considerable. Judging from the sales of existing drugs, the market scale of psoriasis drugs in mainland China has expanded rapidly in recent years as biologics such as secukinumab and ixekizumab have been launched in China. According to Frost & Sullivan data, China's psoriasis drug market has grown rapidly from US$604 million in 2018 to US$1.436 billion in 2022, with a compound annual growth rate (CAGR) of 24.2%, and is expected to continue to increase to US$9.944 billion in 2030 at a CAGR of 27.4%.
Rabies passive immunization drugs are on the horizon
GR1801 is the first bispecific antibody against rabies virus G protein developed by the company in China, and the world's first bispecific antibody for passive rabies immunization. By blocking the binding of G protein to receptors, the drug blocks the infection of the virus on nerves and prevents rabies before the active immunization of the rabies vaccine fully exerts its protective effect. At present, the drug has entered phase III clinical trial and is expected to be approved for marketing in the fourth quarter of 2025.
According to the Technical Guidelines for Rabies Prevention and Control, there are more than 40 million suspected rabies virus exposure patients in China every year, of which more than 90% are grade II and III exposure. At present, there is no effective treatment for rabies virus, and "vaccine + immunoglobulin" is the most effective treatment method for rabies virus after exposure, and it cannot be replaced by each other.
At present, the passive immunization preparations for rabies virus that have been marketed in China are mainly human immunoglobulin, which has limited sources and supply due to its being a blood product. In contrast, GR1801 is not limited by biological raw materials while ensuring the blocking effect, and can achieve mass production while ensuring product uniformity, and has great potential for commercialization. According to the current domestic batch issuance of domestic batch issuance, Southwest Securities has a market space of about 2.1 billion yuan for the stock of rabies virus passive immunization preparations.
Commercial production capacity is expected to increase by more than 10 times
As the research and development of blockbuster drugs is approaching the clinical endpoint, the industrialization capacity building of Zhixiang Jintai is also accelerating. Up to now, the first phase of the construction of the company's antibody industrialization base has been completed, and the production scale of 4400L (2*2000L and 2*200L) antibody stock solution and two preparation production lines have been completed, and the "Drug Production License" has been obtained.
On this basis, the company remains committed to further consolidating its production capacity. According to the company's announcement, the first phase of the company's antibody industrialization base project has been started, and it is planned to add 20,000L of biological fermentation capacity, and the second phase of the antibody industrialization base construction project is also being planned, and the biological fermentation capacity will be further increased by 40,000L after completion.
With the successive commissioning of the industrialization base, the production capacity of Zhixiang Jintai antibody stock solution will increase by more than ten times, laying a solid foundation for the large-scale commercial production of blockbuster products such as GR1501 and GR1802 and quickly seizing the market.