On April 14, Shanghai Hanyu Medical Technology Co., Ltd. (referred to as Hanyu Medical) submitted an application for listing to the Hong Kong Stock Exchange and launched an IPO to Hong Kong, with China International Capital Corporation and Citigroup as its co-sponsors. Nearly five months later, on September 13, 2021, Hanyu Medical listed its prospectus after being heard by the Hong Kong Stock Exchange.

Hanyu Medical was founded in 2016 and has completed six rounds of financing from 2017 to March 2021. Investors include Yunfeng Fund, Oriental Securities, CITIC Industrial Fund, Zhejiang Merchants Innovation Capital and other institutions.

As a medical technology company, Hanyu Medical is mainly engaged in the research, development and commercialization of innovative medical devices for structural heart disease. ValveClamp, a self-developed device for minimally invasive interventional treatment of mitral regurgitation, is its first product.

The core R & D team of Hanyu Medical has reached 38 people, most of which come from first-tier medical device companies at home and abroad, with an average experience of more than 5 years, of which 42% have master's degree or above. Mr. Dai Yufeng, founder and CEO, graduated from the Medical College of Suzhou University, and has successively worked as an orthopedic surgeon, medical device sales, real estate project operation, secondary market investment and so on. He has rich experience in medicine, enterprise management and capital operation. Mr. Tang Yushi, CTO, graduated from Shanghai Jiaotong University with a master's degree, engaged in medical device research and development and product upstream development for more than ten years, and successively engaged in electrophysiology and neurostimulation product development in Boston Science and minimally invasive Medicine.

Hundreds of billions of mitral valve interventional therapy market

Whether in the world or in China, mitral valve interventional therapy is a promising market, but it has not yet been fully developed.

The human heart is divided into four chambers: the left atrium, the left ventricle and the right atrium, the two atriums are connected to two ventricles, and the two ventricles are connected to two great arteries. The heart valve grows between the atrium and the ventricle, and between the ventricle and the aorta, which acts as an one-way valve to ensure the one-way movement of blood flow and plays an important role in ensuring the normal function of the heart. The four valves in the human body are called mitral valve, tricuspid valve, aortic valve and pulmonary valve.

Over the past 20 years, heart disease has been the "number one killer", accounting for 16% of all deaths. Among the patients with heart disease, the scale of patients with valvular heart disease continues to expand, especially mitral regurgitation and tricuspid regurgitation account for the highest proportion and the fastest growth rate. According to the China Cardiovascular Health and Disease report (2019), the number of patients with valvular heart disease in China reached 36.3 million in 2019. Among them, patients with aortic stenosis, mitral regurgitation and tricuspid regurgitation accounted for 11.8%, 29.2% and 25.1% of patients with valvular heart disease, respectively.

Based on the results of current literature research, GE Junbo, academician of the Chinese Academy of Sciences, director of the Department of Cardiology of Zhongshan Hospital affiliated to Fudan University, and director of Shanghai Institute of Cardiovascular Diseases, estimated that in people over 80 years old, the incidence of heart valvular disease is at least 20%. Mitral regurgitation is the most common disease, followed by aortic stenosis (the former is about 3-4 times that of the latter).

According to the Hanyu Medical prospectus, the number of patients with moderate and severe mitral regurgitation worldwide was 96.7 million in 2019, and it is expected that there will be 122 million patients worldwide by 2030. In terms of the number of minimally invasive interventional procedures, the number of transcatheter mitral valve repair tables worldwide is 22000 in 2019, and is expected to increase to 144000 in 2030. According to Frost Sullivan, the number of mitral regurgitation patients in China increased from 9.4 million in 2014 to 10.3 million in 2018 and is expected to increase to 12.1 million by 2025.

However, less than 1% of patients with mitral regurgitation underwent surgery. "in clinical practice, the patient base of mitral and tricuspid valves is more than that of aortic valves, but the development of interventional therapy of mitral and tricuspid valves lags behind. Academician GE Junbo said.

Frost Sullivan also pointed out that the entire mitral valve intervention market is in its early stage and has great potential for growth. by 2030, the global mitral valve intervention market is expected to reach US $17.4 billion (or 117 billion yuan). It will eventually increase to three to four times the market for transcatheter aortic interventional therapy.

Heart valvular disease is a kind of physical structural change, which is difficult to be corrected by drugs, so it needs physical methods (such as surgical treatment) to carry out fundamental correction. At present, there is no clear and effective drug to prevent valvular disease. With the aging of the population, the incidence of valvular disease in the whole population is gradually increasing.

Academician GE Junbo pointed out that traditional surgery requires thoracotomy and cardiac arrest, which has the disadvantages of great trauma, high risk, and slow recovery, and is not very suitable for the elderly. With the emergence of transcatheter valve repair or replacement technology, minimally invasive interventional therapy of heart valve in the elderly has become a reality. In the past 10 years, this technology has developed by leaps and bounds and has become one of the most popular medical technologies. For example, minimally invasive transcatheter mitral valvuloplasty was listed as one of the top ten medical innovations by Cleveland Medical Center for two consecutive years from 2018 to 2019, on a par with cancer immunotherapy, AI medical therapy, and genomic prevention.

For the field of interventional devices for structural heart disease, the research report of Southwest Securities believes that this field is expected to achieve more than 10 times the space in China for 10 years in the future.

It is expected to be the first commercial domestic TMV product.

According to the prospectus, the core product of Hanyu Medical is the mitral interventional device ValveClamp, which was independently developed by Hanyu Medical and Academician GE Junbo. The product is mainly used for minimally invasive interventional treatment of mitral regurgitation disease. 12 exploratory human clinical trials have been completed in October 2018, with a success rate of 100%. Pre-market clinical trials were officially launched in February 2019.

According to Frost Sullivan, ValveClamp is the first TMV treatment product in China to enter a confirmatory clinical trial (transcatheter mitral valve therapy). ValveClamp is expected to be registered and listed in the first quarter of 2023, becoming the first commercial domestic TMV product in China.

Compared with similar instruments at home and abroad, ValveClamp has obvious advantages.

In the field of innovative medical devices, there is a commonly used general formula-the degree of subversion of medical device innovation, which is directly proportional to the benefits of patient treatment, the resolution of technical pain points, and the doctor's self-realization, and inversely proportional to the cost of clinical application and the net expenditure of the payer.

Because ValveClamp products use the "classic" edge-to-edge repair technique in the field of mitral valve treatment, the mitral valve is intervened through the apical approach. Compared with other transfemoral TMVr instruments, the intervention path is shorter and easier to operate, and requires less surgical aids. Cardiac physicians and surgeons can perform surgery. This not only shortens the learning curve of doctors, especially young doctors, but also reduces the difficulty of clinical large-scale application, and brings help for the realization of doctors' value and the reduction of clinical application cost.

At the same time, from the perspective of patients' treatment benefits and technical pain point resolution, it is difficult to bend the delivery system due to factors such as vascular stenosis, thickening of septum, presence of foreign body or too small left atrium, and patients are not suitable for transfemoral approach. At this time, transcardiac apical interventional therapy with ValveClamp products will become the only clinical solution.

In clinical application, ValveClamp consists of three major components: delivery system, straddle device and clamp. Through apical intervention, and using a special closed loop design, it produces a "curling effect" on the valve and is easier to clamp. And its product structure and transportation system design is simple and compact, and can be manufactured in a cost-effective way. Once commercialized, the production capacity can climb quickly, and the products can be introduced to the market more quickly. User costs, payers' net expenses and other aspects have also been greatly reduced. Effectively reduce the burden of patients and society.

Generally speaking, ValveClamp is not only more competitive in the market, but also greatly reduces clinical application and patient expenditure, creating huge commercial value while taking into account social value.

Huge patient demand and market space, excellent product and technical strength, for ValveClamp, once commercialized, it undoubtedly means broad prospects for development. With the help of the core product of ValveClamp, Hanyu Medical has established a cooperative relationship with dozens of top third-class hospitals across the country to jointly promote the development of TMV treatment in the Chinese market.

Moreover, Hanyu Medical also uses the successful development experience of ValveClamp to rapidly promote its own advantages of transcatheter heart repair products, including 5 transcatheter heart repair products, 3 transcatheter valve replacement products and 2 electrophysiological products, covering the treatment and detection of structural heart disease, which can provide more comprehensive medical solutions.

For the most common adult congenital heart disease, atrial septal defect, Hanyu Medical strategic layout of the world's first punctuable occluder ReAces. On July 19th, 2021, the early scientific research clinical trial of ReAces was concluded, and the success rate of operation was 100%.

In addition, the 10,000-square-meter Xinzhuang production base, which Hanyu Medical has put into development, is expected to start construction by the end of 2021 and put into production by the end of 2023. The initial design of the base has an annual production capacity of 100000 sets, laying a solid foundation for the commercial mass production of ValveClamp and subsequent products.

Global patent layout

Because of its excellent product innovation and R & D capability, Hanyu Medical continues to win patents at home and abroad. So far, it has 30 patents in China, including 8 invention patents and 22 utility models, as well as 26 patent applications to be approved, including 20 invention patents and 6 utility models.

At the same time, Hanyu Medical has also applied for three PCT patents, and its core ValveClamp-based patents have been granted by Japan, the European Union and other countries and regions, thoroughly eliminating the risk of patent infringement for products going to sea.

In the second half of 2021, Hanyu Medical launched an European application for CE certification to assess ValveClamp's business opportunities and plans to further promote overseas product registration in other countries, such as Japan, the United States, Australia and Israel.

Hanyu Medical also plans to submit an application for the CE logo within 2021 and is expected to be approved within 2023, while using the CE logo to develop and enter the Southeast Asian market.

The global patent layout of "people without me" has also laid a good foundation for defending the global business expansion of Yu Medical. In the future, the stage for Hanyu Healthcare will be not only the Chinese mainland market, but also the global market.

Enter the pet medical market

Not only for "people", Hanyu Medical has also expanded its product line to the field of pet heart intervention medical devices and entered the global pet medical market.

Yuanyu Medical, the holding subsidiary of Hanyu Medical, is the company's platform for the research and development and commercialization of veterinary medical devices, and it is also the first company in the world to carry out the research and development and successful commercialization of medical devices for pet (dog) interventional mitral regurgitation.

With the help of Hanyu Medical's rich clinical research and development experience, Yuanyu Medical has launched a variety of product portfolios for the treatment of pet structural heart disease, and has successively reached cooperation with multinational pet medical teams in the United States, Japan, the United Kingdom, Israel and other countries.

Data show that the size of China's pet medical market will increase to 267 billion yuan in 2021. If you look at the world, the pet medical market will undoubtedly be larger. For Hanyu Medical, this is also a subdivided track with long slopes and thick snow.

Conclusion

On the whole, with the continuous improvement of China's per capita income, the further awakening of health awareness, the evolution of aging and the deepening of market education, the structural heart intervention medical device track is about to usher in a huge explosive growth. And Hanyu medical R & D innovation strength, obvious product advantages, high competitive barriers, few competitors, coupled with global patents and multi-track layout firmly stuck in a strong position, the future will also usher in broad prospects for development.