Yuanxin Medical Pioneers Global Iron-Based Bioresorbable Vascular Scaffold to Capture Multi-Billion-Dollar Stent Market

Coronary heart disease is one of the major diseases threatening human health. In the treatment of this disease, coronary intervention has undergone iterations over the past 40 years, including balloon angioplasty, bare-metal stents, and drug-eluting stents. However, drug-eluting stents have disadvantages such as chronic vascular inflammation, delayed vascular healing, and in-stent thrombosis after implantation, which make them less than the optimal choice for cardiac stent placement.

With continuous investment and innovation in the field of coronary stent development, bioresorbable scaffolds are triggering the fourth revolution in the interventional cardiology space, and a group of pioneering bioresorbable scaffold companies have emerged in China.

Distinguished by the world's first iron-based bioabsorbable vascular scaffoldBiotyx Medical (Shenzhen) Co., Ltd.(hereinafter referred to as "Biotyx Medical), is a typical representative.

Biotyx Medical (Shenzhen) Co., Ltd., spun off from Hong Kong-listed LifeTech Scientific Corporation (01302.HK), was established in May 2019. From its inception, the company has been committed to the mission of providing safe and innovative cardiovascular medical devices to doctors and patients worldwide, focusing on the research and development of absorbable materials and devices. In 2020, it receivedIDG Capital, Cornerstone Capital $160 Million Series A Financing。

Its self-developed, globally pioneering iron-based bioabsorbable material has broad application space and expansion potential in the medical field, and has been successfully developed.Multiple Fully Degradable Iron-Based Bioabsorbable Stent Products, applied toCoronary Heart Disease, Pediatric Pulmonary Artery StenosisAndInfrapopliteal Artery StenosisIn multiple mainstream business fields.

According to material classification, absorbable stents are mainly divided into two categories: absorbable polymer scaffolds and absorbable metal stents. The former is primarily composed of poly-L-lactic acid (PLLA), while the latter includes magnesium alloy, iron alloy, and zinc alloy.

Absorbable polymer stents were the first to be commercialized, which is why many companies in and outside of China have chosen this route. However, the mechanical properties of polylactic acid are far lower than those of metal materials. To maintain sufficient support, the stent must be thicker, with wider struts and higher vascular coverage, which hinders endothelialization, activates platelets, promotes thrombosis, offers fewer specifications, and is inconvenient to operate.

Among absorbable metal stents, only iron alloy materials have mechanical properties comparable to those of permanent stent materials. Currently, only magnesium stents and iron stents have entered clinical trials globally. According to Zhang Deyuan, founder of Biotyx Medical, the currently approved degradable stents can be used for young patients with simple lesions, but the benefits to patients and market potential are limited.

Iron stents, due to their mechanical properties being identical to those of permanent materials, do not require any compromise in stent performance and can cover all existing markets for permanent stents.Moreover, its excellent mechanical properties, combined with degradability and biosafety, significantly broaden the range of product applications.Can be used for many indications where permanent stents are currently not applicable.Such as vascular malformations in children, infrapopliteal artery stenosis, etc. MeanwhileIron materials have good technical ductility.It can also be used in many other non-vascular stent applications, such as cavity stents, orthopedics, valves, etc.

From the perspective of degradation cycles, the degradation period of polylactic acid scaffolds exceeds three years, requiring at least three years of DAPT (dual antiplatelet therapy). Iron-based scaffolds degrade by 34% within six months in human coronary arteries, relieving vascular constraints, and are mostly degraded within two years. Complete endothelial coverage occurs within six months, with a DAPT duration similar to permanent scaffolds. The three-year clinical results of the IBS scaffold FIM indicate no safety events such as death, myocardial infarction, or thrombosis. Six months later, LLL (late lumen loss) stabilizes with no additional TLF (target lesion failure).

The biggest challenge for using iron-based materials in vascular stents is the slow degradation of iron in the human body environment and the slow absorption of its degradation products. Biotyx Medical has found a unique technical solution to this problem—encapsulating the iron stent with a special polylactic acid, which, as the coating degrades, creates an acidic microenvironment that allows iron to quickly degrade into soluble iron ions. Additionally, by infusing nitrogen into the iron, the mechanical properties of the iron are significantly enhanced, allowing sufficient support with much less material. For instance, the amount of iron in a typical Biotyx Medical stent is equivalent to less than a week's worth of an individual’s iron intake, ensuring MR safety.

Biotyx MedicalThe first batchThere are three products——Absorbable Drug-Eluting Coronary Stent (IBS), Iron-Based Absorbable Pediatric Pulmonary Vascular Stent (IBS Angel)AndAbsorbable Drug-Eluting Peripheral Stent (IBS Titan),Both have been granted the qualification of innovative medical device by the Drug Administration.IBS is used to treat coronary artery stenosis, targeting elderly, middle-aged, and young patients; IBS Angel is used to treat pulmonary artery stenosis, targeting infants, children, and adolescent patients, with a maximum diameter of 16mm; IBS Titan is used to treat infrapopliteal artery stenosis, targeting elderly, middle-aged, and young patients, with a maximum length of 118mm.

Biotyx Medical's 3 Iron-Based Stent Products

Among them, the main advantages of the IBS iron-based absorbable drug-eluting coronary stent are that its clinical maneuverability, mechanical properties, storage and transportation methods, and range of indications show no differences from currently mainstream permanent DES, while also having the advantage of being absorbable. Therefore,It is the only absorbable stent that can comprehensively replace permanent DES.Strut thickness is an independent factor affecting clinical outcomes. The total strut thickness (strut plus coating) of this stent is only 70μm, which is slightly thinner than mainstream permanent stents.It is currently the thinnest and slimmest stent available on the market.

IBS Technology Diagram

In terms of the team, the founder and main technical inventor of Biotyx MedicalDr. Zhang DeyuanMainly engaged in the research of cardiovascular implantation and interventional devices and materials. With 15 years of experience in new material and surface strengthening technology research at a government research institute, and holding the title of Researcher at the Chinese Academy of Sciences (CAS). In 2006, joined Lifetech Scientific (01302.HK) as Chief Technology Officer and President; during his tenure as President, led Lifetech Scientific to achieve rapid and healthy growth.

Dr. Zhang Deyuan

Dr. Zhang Deyuan, as the Project Leader, drafted the ISO 22679-2021 international standard for cardiac occluders, which was released last year. In the past five years, he has published nearly 20 SCI papers in journals such as Science Advances, Biomaterials, and Bioactive Materials. He has successively received the State Council Special Allowance, the Second Prize of the National Technology Invention Award, and the National Patent Gold Award. As a postdoctoral mentor, he has trained more than 10 postdoctoral fellows.

Dr. Zhang Deyuan is a rare comprehensive talent in the industry who possesses advanced degrees, government work experience, executive experience in listed companies, and university teaching experience. He has profound expertise in scientific research and technology, as well as systematic thinking in team management and corporate operations.

Unlike other startups, Biotyx Medical had a well-established R&D and production team from the very beginning.

Biotyx Medical's current core technology and management teams are primarily derived from the spin-off of Lifetech Scientific. The team is mature, stable, and highly efficient in collaboration. In the nearly 80-person team, R&D personnel account for more than half, including six Ph.D.s, and over ten individuals have been working on this project for more than seven years, forming a stable, reliable, and enduring core team.

With such a powerful team, Biotyx Medical stands out in terms of technical approach and research and development.

The ability to think independently is an essential skill in scientific research and creative invention. In the selection of R&D pathways, Biotyx Medical did not choose existing material technologies available on the market but, based on scientific theory, bravely scaled new heights in technology.

Biotyx Medical chose to take a different path by entering the "iron-based" field for three main reasons: First, the company believes that among the two key terms in "biodegradable stents," "stent" is the core term. Sacrificing the essential performance of the "stent" for the additional benefit of "biodegradability" is not strategically acceptable. Second, Biotyx Medical positions itself as a research-driven company, and following a different technological path is part of its mission. Moreover, from an industry-wide and technological perspective, only when companies spread out across different technological paths can the best solutions be found most quickly. Third, through a stroke of serendipity, Biotyx Medical discovered a solution to the slow degradation and absorption of iron materials in the human body.

"The 16-year R&D process was a journey from one failure to another. Ten years ago, we thought the product would enter clinical trials the next year, and ten years later, we still think it will be ready for clinical trials the next year." Zhang Deyuan expressed his feelings when talking about product development. Material and mechanical issues can be easily tested in vitro and iterated quickly, but biological evaluation and degradation cycle optimization must go through repeated trial and error in animal experiments. In other words, the long R&D cycle has built a strong technical barrier and moat for Biotyx Medical. Currently, the iron stent technology has been approved.More than 40 Chinese invention patents`, Approved`16 U.S. patents，12 EU patents, and developedAutomated Production Equipment。

Three Academicians Gather for IBS Clinical Trial

In terms of animal experiments, Biotyx MedicalAcademician Runlin Gao's team from Fuwai Hospital, Professor Zhiwei Zhang's team from Guangdong Provincial People's Hospital, and Professor Wei Guo's team from 301 Hospital(In chronological order of the start time of animal experiments) Maintain close cooperation, analyze reasons together after each experiment, improve products, optimize methods, and begin the next animal experiment.

At the same time, Biotyx Medical maintainsInternational Expert Advisors, Government Regulatory Agenciesthrough close communication, making full use of their authority and professionalism to avoid working in isolation. Zhang Deyuan joked, "An FDA official once quipped that we were using them as free consultants."

Biotyx Medical is currently collaborating with93 hospitals in 9 countries worldwideReached Clinical Collaboration, including Fuwai Hospital Beijing, Fuwai Hospital Yunnan, Zhongshan Hospital Affiliated to Fudan University, General Hospital of the Northern Theater Command of the PLA, PLA General Hospital, Guangdong Provincial People's Hospital, Anzhen Hospital Beijing, etc. in China; Children's Hospital of Wisconsin, PIMA Heart and Vascular in the United States; Hospital of University of Florence, University Hospital Leipzig in Europe, etc.

According to Zhang Deyuan, three products of Biotyx Medical have been approved for clinical trials and formal clinical trials are being conducted in China. Some doctors, out of academic interest, have also used iron stents to attempt other indications. As of the time of writing, the number of clinical trial cases for these three products in China has exceeded 200. The ethical review for the clinical trial of its below-the-knee arterial stent in the EU has been submitted, with plans to conduct a clinical study of 100 cases across 14 hospitals in Germany, France, Italy, Belgium, Greece, and Austria. The pediatric stent and below-the-knee stent have been granted compassionate use approval in the United States and have been clinically implanted.

After the product is approved, the global market for iron-based bioabsorbable coronary stents will exceed 10 billion US dollars, and the global market for iron-based bioabsorbable below-the-knee stents will surpass 3 billion US dollars, indicating a broad market prospect.

Currently, the clinical trials of Biotyx Medical are proceeding smoothly worldwide. We hope more doctors and patients will participate in the clinical trials. Meanwhile, the company plans to initiate Pre-IPO financing as it seeks to go public in the capital market within the next two years. In the future, we also hope to attract more outstanding marketing and sales talents to join us, allowing China's technological innovation to benefit patients globally.