Who can win the hot mitral valve market, attracting more than 4 billion yuan in gold?

There are many participants in the mitral valve, which is about to attract an IPO boom

Interventional treatment of heart valve disease has been one of the hottest directions of cardiovascular intervention in recent years, and it is also one of the most popular tracks for capital investment. Globally, heart valve intervention has spawned Edward Life Sciences, which has a market value of nearly US$50 billion. In China, only the field of transcatheter aortic valve replacement (TAVR) has spawned three listed companies with a market value of tens of billions, namely, Minimally Invasive Cardiac, Qiming Medical, and Peijia Medical. According to predictions from multiple institutions, mitral regurgitation is considered to be the biggest hot spot for cardiovascular intervention after TAVR, and it is currently the track with the most bets. The domestic mitral regurgitation circuit is also extremely hot, with dozens of companies participating in the competition. This article makes an analysis of the situation of domestic companies on this track.

Mrshave

The fiery mitral valve market in the primary market, how high is the ceiling

Mitral regurgitation (MR) is the most common heart valve disease. According to an authoritative large-scale epidemiological survey in the United States, the incidence of MR in patients over 75 years old is as high as 9.3%. In China, the team of Academician Ge Junbo of Shanghai Zhongshan Hospital estimated that there are 7.5 million MRs in my country that require intervention (moderate to severe). According to Frost & Sullivan’s prediction, the market for mitral regurgitation interventional therapy will reach US$2 billion by 2024, and will eventually grow 3-4 times the TAVR market to tens of billions of US dollars (Figure 1). In recent years, international giants (Edward, Medtronic, Abbott, Poco, etc.) have invested in the layout of this track, or developed their own products, or invested heavily in the acquisition of the products of start-up companies. In the primary market, valuations in the mitral valve field have skyrocketed, and there has been serious competition for projects. According to the domestic mitral valve track financing data, the field of mitral valve interventional therapy has attracted more than 4 billion yuan from 2020 to 2021 (Table 1). In addition, a number of companies have recently started the IPO process and will soon enter the secondary market.

Multiple technical routes are parallel, who will win in the end?

Surgical thoracotomy is the only effective treatment method for MR in the past, but it has the disadvantages of large trauma, high risk, and slow recovery. Only 2% of patients receive surgical treatment. Transcatheter therapy has the advantages of minimal invasiveness, low risk, and quick recovery, which can bring new treatment options for these patients. This procedure is also one of the most popular research directions in international cardiovascular interventions. In the past ten years, people have also developed dozens of devices for transcatheter interventional treatment of MR. The technology is basically derived from the principle of surgical valve repair.

Transcatheter mitral valve intervention can be divided into the following categories according to technical principles: (1) Transcatheter mitral valve "edge-to-edge" repair (TEER); (2) Transcatheter mitral annuloplasty, including direct Annuloplasty and indirect annuloplasty; (3) implantation of transcatheter mitral valve artificial chordae; (4) ventricular annulus reconstruction; (5) transcatheter mitral valve replacement (TMVR). The internationally approved products for mitral valve regurgitation interventional therapy are shown in Table 1. At present, 7 products of 5 companies have been approved (CE) to go on the market. Among them, Carillion is the route of indirect annulus through the jugular vein coronary vein, MPAS (Mitrailgn) is the indirect annuloplasty through the femoral artery, Cardioband is the direct annuloplasty through the femoral vein, NeoChord is the transapical chordal implantation, MitraClip PASCAL and PASCAL are transfemoral mitral valve edge-to-edge repair (TEER) devices, and Tendyne is transapical mitral valve replacement.

Although there are many technical routes for transcatheter interventional treatment of mitral valve, due to technical defects or other reasons, only Abbott’s MitraClip products based on "edge-to-edge" repair have been approved by the U.S. Food and Drug Administration (FDA). , Has been widely used in clinical practice, and was approved for marketing by the National Medical Products Administration (NMPA) in 2020. The widespread use of MitraClip (more than 100,000 cases) also proves the feasibility of the "fate-to-fate" repair technology . Transcatheter edge-to-edge repair (TEER) is currently the only mitral valve interventional regurgitation technical route recommended by European and American guidelines. Many industry experts believe that this technical direction is currently the only mature technical direction and will continue to lead the second in the short to medium term. Interventional treatment of cusp regurgitation.

There are many participants in the mitral valve, which is about to attract an IPO boom

There are many participants in domestic interventional valve companies. There are three giants in the TAVR field: Qiming, Beijing, and Minimally Invasive Cardiac. The main players in the mitral valve include Dejin, Hanyu, Jianshi, Niumai, and Xintai Medical. Many companies are preparing or undertaking listings, among which Hanyu, Jianshi, and Xintai have already submitted their listings.

Hangzhou Qiming Medical Devices Co., Ltd. was established in 2009 and listed on the Main Board of The Stock Exchange of Hong Kong Limited (The Stock Exchange of Hong Kong) (02500.HK) in December 2019. The company developed China's first TAVR device Venus-A, which was approved for sale in May 2007, and China's first interventional pulmonary valve Venus-P. Qiming Medical entered into a cooperation with Opus Medical Therapies in May 2020 to jointly develop, produce and sell original transcatheter mitral valve replacement and transcatheter tricuspid valve replacement products. The products are currently in the stage of animal experiment exploration.

Beijing Medical was established in 2012 (9996.HK), headquartered in Suzhou, Jiangsu, and listed on the Hong Kong Stock Exchange in May 2020. The company has two major business segments, interventional valve business, and neuro intervention business. Among them, the R&D interventional aortic valve product Taurus one and the second-generation recyclable product Taurus Elite were approved for listing in China in April and June 2021, respectively. In December 2020, Peijia and HighLife signed a license and technology transfer agreement for transarterial septal mitral valve replacement products. Pursuant to this agreement, Highlife will grant Peijia Medical an exclusive license for the TMVR patented products it is developing, and Peijia Medical has the right to produce, develop and sell these products in Greater China. The TMVR technology developed by HighLife uses a transarterial septal approach to treat patients with mitral regurgitation and is currently undergoing international exploratory clinical trials.

MicroPort Xintong Medical Technology Co., Ltd. (02160.HK) is a subsidiary of MicroPort Medical Science Co., Ltd., which was successfully listed on the main board of the Hong Kong Stock Exchange in February 2021. It has developed China's second TAVR valve VitaFlow, which was approved for listing in China in July 2019 and is now widely sold in the market. MicroPort Xintong’s strategy in the mitral valve market is a combination of independent R&D and overseas mergers and acquisitions. In terms of overseas cooperation, MicroPort Xintong has invested in 4C Medical and ValCare. Both companies focus on mitral and tricuspid valves. Medical device research and development. The transcatheter mitral valve replacement system (AltaValve) developed by 4C Medical is fully recaptured and retrievable. ValCare has developed the transapical annulus system (Amend), which has completed some clinical cases.

Hangzhou Dejin Medical and Qiming Medical belong to the Deno Medical platform. They were established in 2015 and are currently in preparation for listing. Dejin Medical has developed China's first transapical mitral valve repair product, MitralStitch, in the mitral valve field. It entered exploratory clinical trials in May 2018 and is currently undergoing pre-marketing confirmatory clinical trials. Judging from the completed cases, the main principle of the device is the implantation of the mitral valve chordae. In July 2020, Dejin Medical launched DragonFlyTM, China's first transfemoral TEER product, and successfully completed the first human clinical application. From May 2021, the product will begin pre-market clinical trials.

Shanghai Hanyu Medical was established in 2016 and has submitted a listing application to the Hong Kong Stock Exchange in April 2021. In July 2018, it launched the world's first transapical TEER device, ValveClamp, and completed its first implantation. This product completed pre-market clinical trials in March 2021 and is currently the fastest-growing product in China. According to the prospectus of Hanyu Medical, its developed transfemoral TEER device ValveClasp has completed long-term animal experiment evaluation and plans to enter clinical trials in the third quarter of 2021.

Shanghai Numai Medical was established in 2015 and is currently in preparation for listing. In May 2019, Numai Medical launched Asia's first transapical mitral valve replacement system (Mithos) and completed the first implantation in Shanghai Zhongshan Hospital. In February 2021, the company announced that Mithos entered the pre-market registration clinical study, but there is no news report on clinical entry. The company's femoral vein TEER device is also under development and is expected to enter clinical trials this year. The company has also developed China's first balloon-expandable TAVR valve, PrizeValve, which is currently in exploratory clinical trials and is expected to enter pre-market clinical trials this year.

Ningbo Jianshi Technology was established in 2011 and submitted a listing application to the Hong Kong Stock Exchange in June 2021. In September 2018, the company launched Asia's first transcatheter tricuspid valve replacement product (Lux-valve) with originality. In June 2020, the product entered pre-market clinical trials, and clinical trials are currently underway. The company has also developed the Ken-valve transapical TAVR system, which has now entered pre-market clinical trials. The TEER device developed by the company is in the stage of animal testing.

Lepu Xintai Medical Technology (Shanghai) Co., Ltd. (hereinafter referred to as "Xintai Medical"), a subsidiary of Lepu Corporation, raised nearly US$100 million at the end of May and submitted it to the Hong Kong Stock Exchange on June 25. For the listing application, the company is mainly engaged in the research and development and sales of structural heart disease products, and its mitral valve products are in the sample development stage.

Mitral valve interventional therapy devices have become the golden track after TAVR in China, and it is expected to give birth to several listed companies. As far as the technical route is concerned, TEER is currently the most mature technical route, and it will become the focus of competition among various enterprises. Many domestic companies have invested heavily in research and development in this direction.

At present, domestic companies currently have three routes in the research and development of TEER equipment. The first is to imitate MitraClip, the second is to improve and innovate on the basis of MitraClip (such as Dejin’s DragonFly), and the third is to imitate PASCAL. In China, the protection period of invention patents is 20 years. MitraClip's patent application was filed around 2000, and the PASCAL patent application was filed in 2019. In terms of patent protection, the second route has the lowest risk of patent infringement, followed by the first route, while the third route has greater potential legal risks. China has made rapid progress in the research and development of interventional devices for mitral regurgitation, and it is expected that the market will explode in a few years and some companies with a certain global influence