This article comes from the official account "Zhongjin finishing Point" on Wechat.

The domestic neural intervention industry is still in the early stage of development. with the increase of treatment penetration and the release of grass-roots demand, we believe that the industry will usher in a period of rapid development, and estimate that China's potential market space is about 27 billion yuan. At the same time, the R & D of domestic enterprises is gradually promoted, and the gap between domestic enterprises and foreign capital is constantly narrowing. We think that the improvement of the localization rate is worth looking forward to.

Abstract

The latest research affirms the efficacy of mechanical thrombectomy and the development of nerve intervention to welcome new students. Neurological intervention, also known as cerebrovascular intervention, is mainly used for the prevention and treatment of stroke. Stroke is mainly caused by cerebral vascular obstruction or rupture and bleeding, which is divided into ischemic and hemorrhagic. Nerve intervention was performed by intravascular catheter and treated by thrombectomy, dilatation, embolization and so on. Acute ischemia accounts for a large proportion of stroke patients, the proportion of ischemia to bleeding is about 80% and 20%, and the ratio of acute to chronic is about 80-90% and 10-20%. The traditional method of intravenous thrombolysis in the treatment of acute ischemia has the advantages of short time window, low recanalization rate and obvious defects. mechanical thrombectomy has become a new trend. The positive results of MR CLEAN and other five major experiments from 2014 to 2015 confirmed the effectiveness of mechanical thrombectomy, the treatment guidelines were adjusted accordingly, and the industry began to develop rapidly. The release of the DIRECT-MT results in May this year affirms that the results of mechanical thrombectomy are not inferior to those of intravenous thrombolysis combined with intravascular thrombectomy, which we believe will become a new milestone and push the industry into a high boom.

China's neural intervention in the potential market is about 27 billion yuan, and the industry is still in the early stage of development with a rapid growth rate. Neurointerventional instruments can be divided into: 1) Ischemia (10.7 billion yuan): thrombectomy or vasodilation is used to treat ischemic stroke caused by cerebral blood thrombus, cerebral embolism, vascular stenosis and so on. The core products include thrombectomy stents, suction catheters and dilatation stents. Mechanical thrombectomy is the main development direction of ischemic stroke treatment in recent years, and it has great potential for development. 2) Hemorrhage (6.5 billion yuan): cerebral hemorrhage caused by aneurysms is prevented and treated by coil embolization or vascular reconstruction. the main products include coils, coil auxiliary stents, dense mesh stents, etc., according to the size and complexity of the tumor, coil embolization or dense mesh stent can be selected for blood guidance. The price of raw materials for spring coils is high, so there is little room for price reduction. 3) Pathway (10.6 billion yuan): it is mainly used for establishing pathway, transmitting equipment, blocking compression and so on in nerve interventional operation. Among the high-value consumables, the barriers to R & D and production process of microguide wire are the highest, and the loyalty of doctors is the highest, because we think that it is the most difficult for domestic enterprises to break through this subdivision. The intermediate catheter is often used as a simple substitute for suction catheter.

The timeliness of treatment determines that the grass-roots market has great potential, and domestic enterprises have a bright future. The golden rescue time for acute ischemic stroke is 3 hours, which makes territorial treatment inevitable. Under the graded diagnosis and treatment, the primary health care resources are increasingly rich; the new rural cooperative medical insurance coverage greatly reduces the medical burden of residents; the construction of first aid map of stroke in China can improve the awareness rate and treatment rate of grass-roots patients. The demand for treatment in the domestic grass-roots market is constantly released, opening up space for the development of neural intervention. We believe that, compared with foreign-funded enterprises, local enterprises have natural advantages in grass-roots market expansion. With the research and development of domestic enterprises, the technological gap between domestic and foreign products continues to narrow, superimposing a strong terminal coverage capacity, we believe that in the next few years, the share of local enterprises of neural interventional devices is expected to increase significantly. Domestic leaders will usher in a golden period of development. Local enterprises have more products on the market, and in 2020, domestic core products have been approved to be listed intensively.

We suggest that we should pay attention to the neural intervention equipment track which is in the early stage of development, the rapid growth of the industry and the layout of many high-quality domestic enterprises.

Risk

The product research and development is not up to expectation, the product declaration progress is not as expected, and the risk of iterative update of technology upgrade.

Text

Nerve intervention: another breakthrough in mechanical thrombectomy, the industry welcomes the opportunity for development

Neural intervention: a New trend in Prevention and treatment of Stroke

Stroke is caused by blockage or rupture of cerebral vessels. Stroke, commonly known as "stroke", is a disease caused by the blockage or rupture of blood vessels in the brain, which can not smoothly flow into the brain and cause brain tissue damage. According to the etiology, the former is called ischemic stroke and the latter is called hemorrhagic stroke.

Nerve intervention is a minimally invasive operation to dredge and repair cerebrovascular pathways. Nerve intervention means that with the support of digital subtraction angiography DSA (Digital subtraction angiography), through femoral artery puncture, the treatment instruments are delivered to the diseased vessels by catheters and other auxiliary instruments, and endovascular treatment is carried out by means of thrombectomy, dilatation, embolization and so on.

According to different causes and scenarios, nerve interventional devices can be divided into ischemia, bleeding and pathway types.

Ischemia (including acute and chronic): acute ischemic nerve interventional devices include mechanical thrombectomy instruments such as thrombectomy stents and suction catheters, which are mainly used to remove thrombus or emboli to dredge vascular pathways; chronic ischemic neurointerventional devices include intracranial dilatation stents, balloon dilatation catheters and other instruments, mainly used to open narrow vascular pathways.

Bleeding type: ruptured aneurysm can cause hemorrhagic stroke. Nerve interventional instruments include spring coils and dense mesh stents (blood flow guiding devices), the former is used for filling to embolize aneurysms, and the latter is used for vascular reconstruction to divert blood to isolate the aneurysm lumen, both of which can also be used together.

Pathway type: pathway type nerve interventional instruments are mainly used in interventional surgery to establish pathways, transfer instruments, block compression and other scenes, high-value consumables include nerve microcatheters, nerve microwires, guide catheters and so on. In the process of practical application, it is also often used in cross-field applications, such as distal access catheter (also known as intermediate catheter) can also be used to aspirate thrombus.

Stroke patients: ischemia (80%) > hemorrhage (20%). In 2017, according to the proportion of new cases, the proportion of ischemic and hemorrhagic stroke patients was 71. 5% respectively. 6% and 28.4%; from the proportion of patients with disease stock, the proportion of ischemic and hemorrhagic stroke patients in China is 82.4% and 17.6%, respectively. The incidence of ischemic stroke was higher than that of hemorrhagic stroke, and the proportion was on the rise. From 2005 to 2017, the proportion of ischemic stroke increased from 51.6% to 69.0% (this data takes into account stroke caused by other unknown factors).

The new incidence of ischemic stroke was acute (80-90%) > chronic (10-20%). According to the China Stroke Prevention and treatment report in 2017-2018H1, the incidence of acute stroke in China accounted for 80% and 90%, which was much higher than that of chronic ischemic stroke. According to Frost Sullivan data, the number of acute ischemic stroke cases in China increased from 2.6 million in 2014 to 3.3 million in 2018, with a 4-year CAGR of 6.14%.

Academic trend: the advantages of neural intervention appear to promote the development of the device market.

Ischemic treatment: at present, the mainstream method is intravenous thrombolysis. In the early stage, bloodletting was the core of Chinese and Western therapy. After 1950, with the popularization of cerebral angiography, carotid endarterectomy and anticoagulation therapy began to be used. In 1983, 3 cases of arterial thrombolysis were reported in Germany. In 1992, an American hematologist led the trial of intravenous alteplase in the treatment of acute ischemic stroke. since then, intravenous thrombolysis has been the mainstream treatment.

At present, intravenous thrombolysis is the first choice in the guidelines, and the defect is obvious. At present, the preferred method of Chinese treatment guidelines is intravenous thrombolysis, but it has the advantages of short time window, many contraindications, low recanalization rate and obvious defects. According to the latest guidelines, treatment follows the priority principle of intravenous atypase thrombolysis, even if the patient conforms to intravascular mechanical thrombectomy, if the patient also meets the indication of intravenous thrombolysis, then should first receive atiplase intravenous thrombolysis therapy (Ⅰ recommendation, class An evidence), but the doctor should be prepared before operation and should not wait to observe the efficacy of alteplase intravenous therapy and then delay mechanical thrombectomy (Ⅰ recommendation, class B evidence).

At present, mechanical thrombectomy is mainly performed by stent, and direct thrombectomy has developed rapidly in recent years. In 2004, FDA approved the first mechanical thrombectomy device, MERCI. Since then, mechanical thrombectomy has undergone four generations of changes. The core principle is to remove intravascular thrombus in time to restore blood flow to ischemic brain tissue, which can be divided into two categories: stent thrombectomy and aspiration thrombus.

The milestone of direct stent thrombectomy in the treatment of acute ischemic stroke in 2015. Since the end of 2014, the positive results of MR CLEAN and other five studies have been published one after another, confirming the improvement of the curative effect of intravascular mechanical thrombectomy. Since then, in 2015, China, Europe and the United States have updated guidelines and expert consensus to improve the recommendation level of mechanical thrombectomy for the treatment of acute ischemic stroke, and the industry has entered a stage of rapid development. In May 2020, the results of the DIRECT-MT study were released, indicating that the functional outcome of intravascular thrombectomy alone is not inferior to that of intravenous thrombolysis combined with intravascular thrombectomy, which has become a new milestone of direct mechanical thrombectomy in the treatment of stroke.

The breakthrough of stent thrombectomy has led to the great development of acute ischemic nerve interventional devices. Penumbra, an American penumbra company, was founded in the United States in 2004 and listed on the New York Stock Exchange on September 18, 2015. Mainly engaged in nerve intervention and other vascular intervention equipment business, the core products include thrombus aspiration equipment ACE, JET and coil system and so on. After reviewing the historical changes of the company's market capitalization, we believe that the increase in the tendency of treatment guidelines for mechanical thrombectomy and the release of positive results of major mechanical thrombectomy studies are important catalysts for the rise of stock prices.

We expect that the penetration rate of mechanical thrombectomy in China will increase significantly. The US guidelines for early treatment of Acute Ischemic Stroke in 2019 have listed mechanical thrombectomy as the best choice for endovascular treatment, and the penetration rate of mechanical thrombectomy has exceeded 20% in 2017. In 2019, the penetration rate of mechanical thrombectomy in the treatment of acute ischemic stroke in China is only about 1.18%. We expect that mechanical thrombectomy will also be widely used in the Chinese market, and the permeability is expected to increase significantly.

Bleeding treatment: endovascular intervention is the main method for the treatment of hemorrhagic stroke caused by aneurysms. The traditional method for the treatment of intracranial aneurysms is surgical clipping. Vascular intervention has undergone four stages: thrombosis in intracranial aneurysms caused by electrocoagulation, balloon embolization, coil embolization and blood flow guiding device. At present, the mainstream use of equipment in the market is the latter two.

The scale of the global market for neural interventional devices is growing faster than ever. From 2014 to 2018, the global medical device market grew from $375.2 billion to $425.3 billion, a compound growth rate of 3.2 per cent, and Frost Sullivan predicts 5.4 per cent growth from 2018 to 2023. In 2018, the global market for neural interventional devices reached US $2.26 billion, and Fortune Business Insights expects to maintain a compound growth rate of 8.3% from 2018 to 2026, exceeding the average growth rate of medical devices.

The market of neural interventional devices in China is in the early stage of development, with a rapid growth rate. From 2014 to 2018, the size of China's medical device market increased from 255.6 billion yuan to 528.4 billion yuan, with a compound growth rate of 19.9%. The market size of nerve interventional devices increased from 953 million yuan to 1.77 billion yuan, with a compound growth rate of 16.7%, which is still in its infancy.

Nerve intervention is one of the most growing domestic innovative equipment subdivision tracks. In 2018, implanted device occluders and coronary stents were subdivided tracks with a high domestic rate, with a market share of 93.0%, followed by coronary stents and aortic stents. The localization rates of spring coils and mechanical thrombectomy devices in nerve interventional devices are only 6.1% and 5.4%, respectively, and there is still a large market space for domestic use.

The permeable space of nerve interventional equipment market is about 27 billion yuan.

Taking the relevant parameters of market capacity in 2018 as the core hypothesis base, we calculate the permeable market space scale of each subdivided core equipment in 2030, and come to the conclusion that the overall permeable space is 27.75 billion yuan.

We estimate that the market scale of nerve interventional ischemia, bleeding and pathway devices in 2030 is 10.68 billion yuan / 6.51 billion yuan / 10.56 billion yuan, accounting for 38.5%, 23.4% and 38.0%, respectively. Among the secondary segments, the market scale of thrombectomy stent is the largest, 5.06 billion yuan, accounting for 18.2%; the second is intermediate catheter, the market size is 4.23 billion yuan, accounting for 15.3%; the third is suction catheter, the market scale is 3.89 billion yuan, accounting for 14.0%.

Acute ischemic stroke: the main products of mechanical thrombectomy are thrombectomy stents and suction catheters. The treatment of acute stroke is to remove the intravascular thrombus in time and restore the blood flow of the ischemic brain tissue, which can be divided into: 1) stent thrombectomy: the thrombus is embedded after the stent is implanted into the blood vessel and pulled out of the body at the end of the treatment; 2) thrombus aspiration: the thrombus is extracted by negative pressure.

Compared with thrombectomy stent, direct aspiration thrombus operation time is shorter, and can avoid secondary thrombus shedding. The recanalization rate and neurological function recovery degree of direct suction first pass technique (ADAPT,a direct aspiration first-pass technique), alone and auxiliary stent thrombectomy (SRFL,stent retriever first line) are similar to those of using stent alone, and the opening time is short, the operation is simple, economic cost can be saved, and there are certain advantages.

We expect that suction catheters will become more and more popular in the future. At present, aspiration suppository is still lack of high-level evidence-based medicine, and the caliber of the catheter extending into the distal vessels is narrow, so it is necessary to sacrifice a certain suction force to affect the curative effect. At the same time, the curative effect of old thrombus is not as good as that of thrombectomy stent. In the United States, under the marketing promotion of Penumbra, there are a little more applications, but it is still not the mainstream solution. At present, it has not been widely used in China. Domestic enterprises are in the stage of research and development, and imported products are more expensive. Doctors can also use access products for simple substitution, which limits the popularity of products. Considering the advantages of short suction time and simple operation, we think that this method will begin to be widely used in the future.

The stent technology of Chinese enterprises is mature, and the layout potential of thrombectomy stent is great. China's coronary stent market is mature, with the use of 1.385 million stents in 2010 and a year-on-year growth rate of more than 10 per cent from 2018 to 2018. Domestic enterprises have rich experience in coronary stent research and development and production. After minimally invasive and Lepu entered the bureau in 2004, the domestic market share reached 60% in 2006, and domestic enterprises took about 2-3 years to occupy the market. We believe that local enterprises have great potential in the layout of intracranial stents.

China's mechanical thrombectomy has a low base and great potential for development. At present, mechanical thrombectomy is not popular in Chinese market, and the scope of application is small. We expect that the increase of mechanical thrombectomy permeability in the future will lead to an increase in the demand for related equipment. According to the data of CINS in 2019, there were 40, 000 mechanical thrombectomy operations in China in 2019.

In 2018, the localization rate of mechanical thrombectomy is only 5.4%, and the localization of thrombectomy stents has a bright future. The mainstream product of mechanical thrombectomy in China is thrombectomy stent, with Medtronic PLC (MDT.US) and Stryker Corp (SYK.US) taking the lead in the share of products. So far, the products of three domestic enterprises have been approved for listing, and their central Wei Medical and Gui Chuang Tongqiao were approved in August and September this year. According to the company's website and announcement, we expect at least three companies to be approved new products in the next 2 years. Only Penumbra products have been certified by NMPA in Chinese market, and domestic manufacturers have products under research.

The core evaluation criteria of thrombectomy stent are recanalization rate and recanalization time, and the performance of domestic products is excellent. The criteria for evaluating the advantages and disadvantages of thrombectomy stents include: (1) vascular recanalization rate: high stent capture rate (thrombus clamping), firm fixation in the process of thrombectomy, and low risk of thrombus shedding; (2) recanalization time: it is a race against time to treat stroke. Shorter recanalization time will improve the curative effect. (3) Safety: little damage to blood vessel wall and surrounding vessels. Approved in 2020, Xinwei Medical Captor thrombectomy stent and Tongqiao Medical Jiaolong thrombectomy stent, the clinical trial results are excellent in all aspects, showing the strong strength of domestic products.

Chronic ischemic stroke caused by vascular stenosis: at present, most of them are treated with drugs, and the main products of interventional dilatation instruments are arterial stents. SAMMPRIS study compared the efficacy of drugs and stents in the treatment of intracranial arterial stenosis, and published negative results in 2011, suggesting that drug treatment is superior to stents. Since then, the treatment guidelines have been based on drugs. However, this study has defects in experimental design, technical operation and result analysis, and the follow-up research is expected to change the torsion results and promote the development of expansion instruments.

At present, the leading domestic enterprises are minimally invasive avatar, Saino Medical and Xinwei Medical. Compared with Europe and the United States, the prevalence rate of intracranial vascular stenosis caused by atherosclerosis in Asian people is higher and the demand space is larger, so the research on domestic related therapeutic devices has been relatively leading, and there are fewer foreign brand layout products. therefore, the subdivision of domestic manufacturers has a better prospect. The APOLLO system of minimally invasive Avatar was launched in 2005. In terms of balloon dilatation catheter, Saino Medical has a new generation of products on the market in 2020, and Xinwei Medical is expected to be approved by the end of 2020.

We believe that the switching barrier of vasodilator is low and the synergistic effect is strong. As the mainstream of coronary intervention is dilatation devices, we think that other interventional device manufacturers can change the competition pattern of intracranial dilatation stent market with synergistic effect in the future. However, the research and development of intracranial devices is difficult, and the technical strength of related enterprises is more abundant, and high-quality nerve intervention manufacturers can also switch markets and seize share.

Evaluation criteria of dilatation instruments: the incidence of restenosis, there was no significant difference between domestic imports. At present, the most widely used products are Stryker Corp Wingspan and Johnson & Johnson (JNJ.US) Enterprise intracranial stents, and the domestic expansion instruments have minimally invasive avatar APOLLO system. Stryker Corp Wingspan safety and short-term efficacy is better, minimally invasive APOLLO operation is simple, accurate location, low price, each has its own advantages, but both have the problem of postoperative restenosis, there is no significant statistical difference in clinical data.

Product development trend: intervention does not implant new ideas, with medicine balloon. Compared with intracranial dilatation stent, balloon dilatation catheter can be treated for many times, which can alleviate the problem of high restenosis rate after stent operation and is more safe. The newly upgraded product comes with a drug balloon and uses a safe and effective rapamycin coating for better efficacy. Both Xinwei Medical and Saino Medical have product layout.

Bleeding (6.5 billion yuan): when the domestic development of spring coils is right, dense mesh brackets are a new trend.

Ruptured aneurysm is one of the causes of hemorrhagic stroke. A large proportion of hemorrhagic stroke is caused by hypertension and hyperlipidemia. Nerve intervention is aimed at cerebral hemorrhage caused by ruptured cerebral intravascular aneurysms (mostly subarachnoid hemorrhage), that is, patients with high-risk aneurysms. In 2018, the number of cases of cerebral aneurysms in China was 50.5 million, and the proportion of cerebral hemorrhage caused by ruptured cerebral aneurysms was 1%. We estimate that the proportion of high-risk patients is about 2%.

The treatment of aneurysms: 1) coil plus auxiliary stent embolization, 2) dense mesh stent to change the blood flow direction. Generally, the treatment products are judged according to the tumor size and the ratio of tumor body to neck. Coil embolization is the first choice for narrow-necked aneurysms, and auxiliary coil stents and dense mesh stents are selected for wide-necked aneurysms according to the shape of the tumor. All kinds of methods can be used in combination. Auxiliary stents can help to improve the density of embolization and reduce the possible risk of prolapse of pure coil embolization. At present, the new development direction is intraluminal spoiler (WEB).

At present, the main treatment in China is coils, and we expect the permeability to continue to increase. With the enhancement of patients' awareness of prevention and treatment and the improvement of financial affordability, we expect that the penetration rate of coil embolization in China will increase. In 2014, the permeability of coil embolization was 5.15%, and there were 52000 coil embolization operations, with a compound growth rate of 19.7% from 2018 to 2018.

The market demand for equipment related to coil embolization has maintained a high growth. In 2014, the market size of coil embolization equipment in China was 2.184 billion yuan, with a compound growth rate of 21.7% from 2018 to 2018. The sales revenue of core equipment spring coils accounts for more than 50% of all equipment. The size of China's spring coil market has maintained high growth, reaching 1.172 billion yuan in 2014, with a compound growth rate of 15.1% from 2018 to 2018.

In 2018, the domestic market localization rate of spring coils is only 6.1%, which is the right time for domestic development. At present, Peijia Medical (09996), Taijie Weiye and Weixin Medical have related products on the market, and the minimally invasive Avatar coils have also been approved in September this year. Wobbi Medical's products have been approved and commercialized in the United States, and we expect to enter the domestic market as soon as possible.

Core evaluation criteria of coil embolization: aneurysm filling rate. Coil-assisted stents can help to improve the density of embolization, increase the filling rate of aneurysms, and reduce the risk of prolapse of pure coil embolization. At present, the auxiliary stents on the market include Stryker Corp Neuroform stent, France Balter Leo stent, Johnson & Johnson Enterprise and so on.

The layout of the minimally invasive dense net stent is the leading, and the annual income of the core products is close to 10 million US dollars. At present, the imported dense net brackets include Kehui Pipeline, Stryker Surpass and so on. The layout of domestic minimally invasive Avatar products is early, and the Tubridge secret net support was approved to be listed in 2018. Minimally invasive Tubridge stents contributed $9.7 million in revenue in 2019, accounting for 35.1% of the neurointervention business.

Access (10.6 billion yuan): high demand for high-value consumables, work together to promote the volume of other involved products

Pathway instruments are widely used in nerve interventional therapy, and high-value consumables include microwire, microcatheter, guide catheter and so on. Pathway instruments are mainly used in nerve interventional surgery to establish pathways, transfer instruments, block compression and so on, and are widely used in all kinds of interventional surgery. This paper only discusses the nerve intermediate catheter, micro-guide wire and guide catheter of high-value consumables, in which the micro-guide wire technology is the most difficult and doctors use the highest stickiness.

The demand for high-value access equipment is strong, and the market maintains a high growth rate. As a widely used instrument in nerve intervention, the market demand for pathway devices continues to be strong. In 2014, the market size of neural microguide wire in China was 47.4 million yuan, with a compound growth rate of 38.0% in 2018-2018, a compound growth rate of 50.7 million yuan in 2014-2018, and a compound growth rate of 37.8% in 2018-2018. We believe that the access market has a qualitative impact on whether enterprises can provide integrated solutions for single disease, and the layout potential is greater.

The import of high-value consumables in the intervention channel is still the main force. The localization rate of vascular access devices is high, but the technical barriers to cerebrovascular intervention are high, and they are still mainly imported products, in which microguide wire is the most difficult to develop and produce, and the probability of doctors replacing commonly used products is low. we believe that it is the most difficult area for local enterprises to break through. At present, domestic enterprises have more product layout. We believe that other interventional device manufacturers also have the ability to quickly layout this field.

The treatment time window opens the grass-roots market, and the local first start accelerates the acquisition of share.

The golden treatment time increases the grass-roots demand and is optimistic about the domestic brands with obvious advantages at the grass-roots level.

The treatment time window of stroke is short. Time is life for the treatment of stroke. The golden rescue time for acute ischemic stroke is 3 hours. When drug thrombolysis is carried out within this interval, the damaged neurons can be fully recovered, but only 21% of stroke patients can receive thrombolytic therapy within this time, and measures will be taken more than 6 hours later. The effect will be greatly reduced.

Gold treatment requires localized treatment, and the basic market has great potential. Compared with many other disease patients can go to the city and third-class hospitals to get better treatment, stroke patients get effective treatment as soon as possible after the onset of stroke is the key to rescue, so the medical institutions within their life radius is the main body of treatment. We believe that the urgency of stroke treatment determines the territoriality of grass-roots needs.

There are a large number of patients at the grass-roots level, and the market demand is large. The number of stroke patients in rural areas is large, and the standardized prevalence rate in rural areas is higher than that in urban areas, which are 2.43% and 1.97% respectively in 2018. The stroke mortality rate in rural areas was higher than that in urban areas and there was a large gap. In 2018, the stroke mortality rates in rural and urban areas were 160.16 / 100000 and 129.15 / 100000 respectively. We believe that this situation is related to the lack of rapid and effective treatment of stroke due to the limited strength of primary health care institutions.

Stroke grading diagnosis and treatment helps to improve patients' treatment awareness and doctors' diagnosis and treatment ability, and improve the rate of grass-roots treatment. In 2017, the State brain Defense Commission and the expert Committee launched the "Construction of China Stroke first Aid Map" to create a "regional golden hour stroke treatment circle" and actively promote stroke graded diagnosis and treatment. According to the data of this year's OCIN conference, there are 30 national stroke demonstration advanced centers, 436 advanced centers and 898 prevention and treatment centers. We believe that these efforts will help to improve the awareness rate and treatment rate of grass-roots patients, improve the diagnosis and treatment ability of grass-roots hospitals, and drive the increase of grass-roots market penetration.

The new rural cooperative medical insurance reform will improve the ability of grass-roots patients to pay. In 2016, the basic medical insurance for urban residents was integrated with the new rural cooperative medical insurance, which made it clear that it was necessary to increase the reimbursement ratio of NCMS hospitalization expenses and the pilot project of serious illness insurance, and allow some secondary hospitals to carry out cardiovascular interventional surgery, so that the growth rate of PCI surgery in medical institutions at and below the county level exceeded the national average. We expect that the grass-roots market capacity for stroke prevention and treatment will also benefit from this rapid growth.

China has inherent advantages in the grass-roots market and benefits from the development of the grass-roots market. Compared with imported products, domestic prices are lower, have a closer relationship with grass-roots medical and health institutions, and have inherent advantages in channel sinking. The demand for stroke treatment is urgent, the regional requirement is high, and the grass-roots market space is particularly broad. We believe that with better market sinking capacity, domestic manufacturers are expected to grasp the needs of grass-roots patients and gain a larger market share.

Doctors are the key to volume at the grass-roots level, and academic promotion at the grass-roots level will enhance the stickiness of domestic brands.

The market of nerve interventional devices in China is in its infancy. Nerve intervention is difficult and the technical barrier is high. Compared with other intervention devices, the market is still in its infancy. Compared with the number of patients, in 2018, stroke and coronary heart disease accounted for 5% and 4% of cardiovascular patients in China, respectively, with little difference. In terms of the proportion of the market size of vascular interventional devices, coronary intervention accounted for 9.7% of Prida in 2019, while nerve intervention accounted for only 3.3%.

The number of interventional doctors is one of the factors limiting the improvement of the permeability of neurointerventional therapy at present, and there is a great demand for early market education. At present, there is a shortage of neurointerventional doctors in China, the penetration rate of mechanical thrombectomy and coil embolization is low, and academic promotion and doctor training have just started. The operation of nerve interventional surgery is complex, and it involves the linkage of neurology, intervention department, imaging department and so on, which requires high professional strength of doctors and high market education demand in the early stage.

The early stage of market development is a good time to cultivate doctors' stickiness. We believe that the relationship with hospitals and other institutions in the early stage of market development has established the pattern of competition in the future to a certain extent. Doctors come into contact with relevant brand products at the stage of learning and training, better understand the use of equipment, and cultivate corresponding operation habits, which are likely to delay the use of products in the follow-up treatment operation. At the same time, better understanding means that doctors can also maximize the effectiveness of the device, and may even narrow the technological gap of the device itself to some extent.

Domestic products are on the market one after another, with volume procurement driving the improvement of the localization rate.

In terms of technical strength, there is no significant difference between domestic products and imports, which has great competitive potential. Take the thrombectomy stent as an example, the Tongqiao Jiaolong thrombectomy stent approved for listing in September this year has no significant difference in all aspects of animal test with Medtronic PLC Solitaire FR stent, and even has advantages in reducing intimal injury, which proves that domestic stents have competitive strength with imported ones in terms of technology and quality.

Domestic price advantage is obvious, with volume procurement will play a magnifying role. Domestic brands have lower prices and obvious advantages, and we believe that the expansion of health insurance coverage and volume procurement will magnify this advantage. The proportion of medical insurance reimbursement for nerve intervention surgery in each city is more than 50%. Jiangsu Province has carried out coronary stent volume procurement this year. As a result, imported brands are at a disadvantage in terms of price reduction and final negotiation price, and market share is easy to decline in volume collection. At present, imported brands are absolutely dominant in the nerve intervention market, local enterprises usher in the development opportunity.

The purchase of high-value consumables is a major trend. In October 2020, the National Organization High-value Medical consumables Joint Procurement Office issued the "National Organization Coronary Stent centralized Belt Purchasing document", and the first round of consumables collection at the national level officially kicked off. We believe that the future procurement of neural interventional devices with volume is a major trend, and domestic manufacturers are expected to seize more market share by virtue of price advantage under this policy.

The full-line product layout of domestic enterprises is expected, and the domestic core products have been approved to be listed in an intensive period in 2020. At the present stage, foreign-funded enterprises still dominate the domestic neural intervention market, and the product layout is more complete. Judging from the current layout progress of local enterprises, more products such as bolt removal brackets, coils and channels have been put on the market:

Thrombectomy stent: Nico layout is the earliest, and the product has been put on the market in 2018. In August and September this year, Xinwei Medical and Tongqiao Medical (later merged with Guichuang Medical) products were approved, and according to company websites and announcements, we expect at least three companies to be approved new products in the next 2 years.

Spring coil: the first spring coil was approved by Tianjin Huanhu Medical College in 2006. Subsequently, Jiaqi Biology (later acquired by Peijia Medical) (2009), Weixin Medical (2011) and Taijie Weiye (2015) were approved respectively. In September this year, the minimally invasive Avatar spring coil was approved, and Wobbie medical products have been approved by FDA in the United States and entered the commercial stage. At the same time, there are still a number of domestic enterprises in the research.