In this weekly report, we discuss the supply and demand analysis of adeno-associated virus AAV vector for gene therapy.
Virus vector titer is affected by many factors
Virus vector titer is affected by many factors. In addition to the difference of production process, the difference of cell line and culture volume affect the cell density, and the difference of transfection reagent affects the transfection efficiency. According to literature data, most upstream production processes (USP) can obtain 1 × 104 -5 × The carrier titer of 105vg / cell, combined with the cell culture density, corresponds to the unit volume titer in the crude harvest solution at 1 × 1013- 2 × Between 1014vg / L.
AAV carrier demand analysis - commercialization demand
On the demand side, it is assumed that the indications are divided into rare diseases and epidemics, different doses are corresponding to different administration sites, and the local delivery dose is assumed to be 1 × 1012vg / person, the system delivery dose is assumed to be 1 × 1015vg / person; Assuming that the number of patients with rare diseases and epidemic diseases treated each year under each administration mode is 1000 and 100000 respectively, the maximum annual demand of AAV carrier can reach the order of 1020.
The titer of the upstream process of suspension culture was 2 × 1013vg / L (the volume of a single reactor is 2000L) and the titer of adherent culture is 4 × 1013vg / L (volume of a single reactor is 1000L), the downstream process yield is 30%, and the annual production is 20 batches; the dosage supplied by the reactor varies greatly according to different patient doses, 1 × The dosage of 1015vg / person corresponds to only 240 people. In order to meet the needs of indications with a relatively large number of patients such as hemophilia and frostbite, it is expected that there will be a large capacity gap.
Analysis of clinical research needs of AAV carrier
Assuming that the growth rate of the number of clinical projects in the field of CGT in 22-26 years is 25% and that in 27-31 years is 20%, the number of clinical projects in 31 years is 3964 based on 522 clinical projects in 21 years. Assuming that viral vector delivery accounts for 90% and AAV vector accounts for 42% of the total viral vector, the number of AAV vector related clinical projects is about 1500.
According to the statistical registered clinical information of nature research, among the 152 registered clinical trials of AAV vector gene therapy, ophthalmic indications accounted for 25%, nervous system accounted for 19%, blood diseases accounted for 14%, muscle system accounted for 12%, and metabolic system and other rare diseases accounted for 30%. Assuming that the proportion of phase I / II / III projects is 10:5:2, the corresponding number of patients is 10 / 15 / 50 respectively. According to the model calculation, it is estimated that 76 2000L suspension or 1000L wall attached reactors are required for the clinical research demand of AAV carrier. Therefore, in the long run, the production capacity of AAV carrier will still mainly meet the needs of a large number of potential adaptive people after commercialization. However, considering the occupation of reactor resources by clinical projects and project development and conversion costs, it is expected that the shortage of existing capacity will continue for a long time.
Related companies
Wuxi Apptec Co.Ltd(603259) , Kingsley biotechnology, Porton Pharma Solutions Ltd(300363) , and metabiology.
Market review: driven by the market consumption track, the trend of the pharmaceutical sector was low before and high after this week, and the traditional Chinese medicine sector and the oversold pharmacy and service sector rebounded in the early stage. The biomedical sector rose 1.34% this week, underperforming the CSI 300 index by 1.80pct and outperforming the gem index by 1.68pct, ranking in the middle of 30 CITIC first-class industries. Most sectors of CITIC medicine rose this week, among which the sub sectors of traditional Chinese medicine, medicine circulation and medical devices increased significantly, rising 5.23%, 4.62% and 3.06% respectively, and only the chemical API sector fell.
Investment suggestions:
In case of plate shock, two ideas are recommended in the short term: no game policy, and on the premise of relative immunity of the policy, it is preferred:
Vaccines: Beijing Wantai Biological Pharmacy Enterprise Co.Ltd(603392) , Chongqing Zhifei Biological Products Co.Ltd(300122) and Shenzhen Kangtai Biological Products Co.Ltd(300601) ; Oral consumables: Yantai Zhenghai Bio-Tech Co.Ltd(300653) (active biological bone will be approved soon); upstream: Jenkem Technology Co.Ltd(688356) (PEG derivative), Nanjing Vazyme Biotech Co.Ltd(688105) (molecular enzyme).
2. Downside risk is limited, waiting for Fundamentals to catalyze. Blood products sector (leading enterprises are expected to benefit from the 14th five year plan of pulp stations in many provinces, and the growth of pulp volume will be further opened, including Beijing Tiantan Biological Products Corporation Limited(600161) and Hualan Biological Engineering Inc(002007) ); pharmacy sector ( Yifeng Pharmacy Chain Co.Ltd(603939) , Yixintang Pharmaceutical Group Co.Ltd(002727) ), Shenzhen Mindray Bio-Medical Electronics Co.Ltd(300760) (short-term policy disturbance does not change the long-term development logic), China's sublingual desensitization leader Zhejiang Wolwo Bio-Pharmaceutical Co.Ltd(300357) ; China's leading pharmaceutical glass enterprise Shandong Pharmaceutical Glass Co.Ltd(600529) .
Long term view: Based on the demand improvement such as aging and the improvement of disposable income, as well as the increase of supply capacity driven by technological innovation, some excellent head enterprises are always strong, and the pharmaceutical sector has the same long-term investment value. The essence of investment is to share the growth value of enterprises. Plates and companies with long-term sustainable high rate of return are scarce.
1. Chain medical services: chain medical services (Ophthalmology, stomatology and assisted reproduction) that conform to the general trend of consumption upgrading on the demand side, and related targets: Aier Eye Hospital Group Co.Ltd(300015) , Topchoice Medical Co.Inc(600763) and Jinxin reproduction.
The improvement of the penetration rate of medical inspection outsourcing is the general trend under the background of medical insurance cost control, and the related target is Guangzhou Kingmed Diagnostics Group Co.Ltd(603882) .
2. Consumer goods: the terminal demand for consumer upgrading products is huge and usually far from being met. With the improvement of awareness and material level, it can maintain steady growth for a long time, with high uncertainty of valuation digestion. The leading enterprises of corneal shaping lens Autek China Inc(300595) and Eyebright Medical Technology(Beijing) Co.Ltd(688050) ; Chinese sublingual desensitization faucet Zhejiang Wolwo Bio-Pharmaceutical Co.Ltd(300357) . It is suggested to pay attention to the leading enterprises of growth hormone Changchun High And New Technology Industries (Group) Inc(000661) ; Invisible orthodontic faucet era angel.
3. Life science industry chain: biological research reagents have a broad track, and domestic brands still have great prospects. Compared with foreign brands of scientific research reagents, domestic reagents have the advantages of price and delivery time. In the future, the domestic substitution of China's scientific research reagent market is relatively uncertain and the substitution space is huge. At present, upstream enterprises have high enthusiasm for IPO fund-raising and production expansion, and the overall prosperity of the industry continues to rise. It is suggested to pay attention to: Shanghai Aladdin Biochemical Technology Co.Ltd(688179) , Shanghai Titan Scientific Co.Ltd(688133) , Jenkem Technology Co.Ltd(688356) , Shanghai Haoyuan Chemexpress Co.Ltd(688131) , Suzhou Nanomicro Technology Co.Ltd(688690) , Sino Biological Inc(301047) , Acrobiosystems Co.Ltd(301080) and Nanjing Vazyme Biotech Co.Ltd(688105) .
4. Blood products sector: with high barriers, leading enterprises are expected to benefit from the 14th five year plan of pulp stations in many provinces, and the growth of pulp volume is further opened. Beijing Tiantan Biological Products Corporation Limited(600161) and Hualan Biological Engineering Inc(002007) .
5. Pharmacy sector: stable growth in performance and constant long-term growth logic. The valuation is below the historical center and the safety margin is high. It is recommended to Yixintang Pharmaceutical Group Co.Ltd(002727) , Yifeng Pharmacy Chain Co.Ltd(603939) , Dashenlin Pharmaceutical Group Co.Ltd(603233) and Lbx Pharmacy Chain Joint Stock Company(603883) .
6. Medical devices: continue to recommend Shenzhen Mindray Bio-Medical Electronics Co.Ltd(300760) . Short term policy disturbance does not change the logic of long-term development. The next decade will be the stage of self owned technological innovation and upgrading of domestic medical devices, and also the stage of "import substitution" as the main theme of the development of domestic medical devices.
We continue to recommend Shenzhen Mindray Bio-Medical Electronics Co.Ltd(300760) . Its complete product layout and strong product and information technology solutions are expected to usher in great opportunities in public health weaknesses and new medical infrastructure.
7. Medical consumables: it is recommended to pay attention to China's leading pharmaceutical glass enterprise Shandong Pharmaceutical Glass Co.Ltd(600529) . From the demand side, the consistency evaluation of chemical drug injections is accelerated, and there is a strong demand for influenza vaccine and covid-19 vaccine packaging materials; From the supply side, the domestic borosilicate glass tube drawing technology is mature and is expected to significantly increase the gross profit.
8. Innovative drugs: under the policy background, we suggest paying attention to 1) bigpharma with abundant funds, high clinical transformation efficiency and strong sales ability; 2) Biotech with strong platform scalability, differentiated competitive advantage and international potential.
Related targets: it is recommended to focus on A-share Jiangsu Hengrui Medicine Co.Ltd(600276) (China's leading innovative drug enterprise), Betta Pharmaceuticals Co.Ltd(300558) (growing into biopharma with ektinib and focusing on lung cancer) and innovative drug enterprises related to Hong Kong stocks.
9. Innovative drug industry chain: R & D investment and investment and financing are booming, and the orders of "water sellers" continue to be strong
The R & D and production of innovative drugs are complicated. It is very difficult for a single enterprise to run through the whole industrial chain. Efficient platform R & D and production institutions are born. Cro, cdmo and other enterprises focus on a few links in the industrial chain, have more professional talents and R & D and production technology, and become a representative industry of division of labor, cooperation and globalization of new drug R & D.
Chinese CXO enterprises have scale advantages and "engineer bonus". They can not only participate in the competition of global new drug R & D outsourcing, but also benefit from the rapid rise of Chinese innovative drug R & D. they are located in a wide track. Most enterprises have differentiated technical platforms, high customer recognition, build strong competitive barriers, and will maintain a high outlook in the medium and long term.
It is suggested to pay attention to: Wuxi Apptec Co.Ltd(603259) , Asymchem Laboratories (Tianjin) Co.Ltd(002821) , Yaoming biology, etc.
Risk tips: policy risk, price risk, performance risk less than expected, product R & D risk, expansion progress risk less than expected, medical accident risk, uncertainty of overseas covid-19 virus epidemic, M & A integration risk less than expected, etc.
