This article is based on publicly available materials and is for informational purposes only and does not constitute any investment advice.
There are not many medical techniques that have been touched by the Pope, and "regenerative medicine" counts as one.
In 1955, Pope Pius XII of Rome made the Swiss physician Paul Niehans a member of the Vatican Academy of Papal Sciences in recognition of the "living cell therapy" he gave to the pope.
Twenty years after Paul Nihans' death, "live cell therapy" was falsified and put into the Cold Palace,[1] until 1992, when Leland Kaiser dusted off the dust of "live cell therapy" and proposed "regenerative medicine", arguing that regenerative medicine technology "will become a new branch of medicine".
From being denied to being regarded as an advanced technology today, what has "regenerative medicine" experienced? Can we live forever on it? Now, how hot is this market?
Since its inception, the concept of regenerative medicine has undergone many refinements. Nowadays, small cells, tissues, and large glands and organs have become the object of regeneration research. Through regenerative medicine technology, medical scientists systematically improve the level of human life expectancy and quality of life by replacing aging and damaged body structures. [3]
01
When the organ becomes a consumable
Simply put, regenerative medicine treats humans as modular "big Legos" that replace wherever something goes wrong.
According to the type of "parts" that need to be replaced, regenerative medicine can be divided into two technical routes: stem cell therapy that directly replaces stem cells and tissue engineering that replaces differentiated tissues and organs.
Stem cell therapy
Stem cells are a type of cell with the ability to proliferate and differentiate, and every piece of flesh and blood in the human body is ultimately a masterpiece of stem cells.
Stem cell therapy is the transplantation of healthy stem cells into the patient's body to repair diseased cells or rebuild normal cells and tissues. The bone marrow transplant mentioned above is the use of healthy hematopoietic stem cells from others to rebuild the patient's hematopoietic and immune systems.
In addition to hematopoietic stem cells, mesenchymal stem cells, neural stem cells, skin stem cells, and islet stem cells can be used for transplantation and treatment of diseases at the corresponding sites.
According to the U.S. Clinical Trials Registry, as of March 24, 2022, there were 6,136 clinical trials of stem cells in the United States, of which 2,624 had been completed.
Among them, mesenchymal stem cells have the most clinical applications due to their strong topotent type. According to the statistics of the national and local laboratories of adult stem cells, at least 18 mesenchymal stem cell therapies have been listed worldwide. [4]
The fastest-moving of these treatments is Osteocle, a bone regeneration product that repairs and replaces damaged bones. According to Newarso's official website, since it was approved for marketing in 2005, more than 300,000 patients have been treated with Osteocle. [5]
According to the data of the Drug Evaluation Center of the State Drug Administration, 19 stem cell therapies in the mainland have obtained clinical approvals, including 18 various types of mesenchymal stem cell therapies and 1 epithelial stem cell therapy. [6]
Organizational engineering
If stem cell therapy is the "skeleton of Lego", then tissue engineering is "flesh and blood".
Tissue engineering refers to the cultivation of biologically active tissues and organs in vitro for the maintenance, replacement or repair of original diseased or damaged tissues and organs.
In vitro culture uses "seed cells", and these "seed cells" are mostly one or more stem cells, so tissue engineering is often used in conjunction with stem cell technology.
There are three technical challenges in growing tissues and organs in vitro:
How to induce the directed differentiation of stem cells, form a tight physiological structure, and perform corresponding physiological functions;
How to prescribe that cells grow according to the shape of the organ and form a three-dimensional structure;
How to address unstable factors in the process of organ cloning, such as cell mutations, culture media, and cytokines.
With the development of biomaterials and in vitro culture and amplification technology, the laboratory has successfully cultivated some simple structures and organs, and even transplanted patients.
Back in 2006, Anthony Atala, a surgeon at Vic Forest College in North Carolina, isolated and amplified specific cells of bladder tissue in the lab and placed them on a bladder mold made of collagen-polyglycolic acid material. The cells continued to grow on the mold and eventually became "artificial bladders" that were transplanted to 7 children with birth defects. [7]
The team of Paolo Macchiarini of the University of Barcelona in Spain successfully completed the world's first reincarnated tube transplant in 2008. Paul first extracted adult stem cells from the patient's bone marrow, and after inducing differentiation into chondrocytes, inoculated into biomaterials to grow a new trachea. [8]
The reason why regenerating bladders and reinvigorating tubes can be successful is that their structure and function are relatively simple, and the regeneration technology has matured. Similarly, cartilage, mucous membranes, blood vessels, teeth, etc., have emerged in these product areas.
Although researchers from various countries are also trying to cultivate the heart and kidneys, most of them are still in the laboratory stage, which is difficult to scale and commercialize.
At present, only two companies in China, Huayuan Regenerative Medicine and Gemmerrison, are engaged in the development of regenerative organs, but the former's fastest-moving regenerative pancreas project is still in the animal experiment stage; the latter's lung regeneration project and kidney regeneration project have only one clinical completion of Phase I clinical, which is still far from being listed.
But even so, capital has never dampened its enthusiasm for regenerative medicine.
02
A market of 500 billion is awaiting clinical trials
Existing regenerative medicine therapies have supported a huge market.
According to Polaris Market Research, the regenerative medicine market was only $14.76 billion in 2017, but by 2026 this figure will reach $79.23 billion (about 504.47 billion yuan), and the growth rate is still increasing. [9]
In addition, regenerative medicine technology will also penetrate into the existing traditional medicine, medical equipment and other mature industries.
Take the insulin industry, for example.
In October 2021, Forte Pharmaceuticals successfully restored islet function in a type 1 diabetic patient using a stem cell therapy called VX-880. Next, Forte Will also try to develop stem cell therapy for type 2 diabetes. If the regenerative islets are successfully commercialized, it is expected to replace the existing insulin products.
This is a fairly large market. According to the World Diabetes Alliance, there are about 537 million adult diabetics worldwide by 2021, bringing more than $20 billion to the market for human insulin. [10]
Regenerative teeth are also highly anticipated by researchers.
In 2021, the team of Wang Songling, an academician of the Chinese Academy of Sciences, developed a new drug called "pulp mesenchymal stem cells", which can allow alveolar bone to grow again. The team of Mao Jian, a tenured professor at Columbia University in the United States, has also developed stem cell regeneration tooth technology, which only takes 9 weeks to cultivate new teeth.
The implant tooth has to go through the steps of implant implantation, healing cap, denture repair, etc., and the implant cycle is between 3 months and 6 months, which is cumbersome and painful.
"2020 China Oral Medical Industry Report" shows that the total number of teeth missing in the mainland population is 2.642 billion, of which the potential demand for implants is 18.88 million, if the price of each implant is estimated at 10,000 yuan, it is a market of nearly 200 billion yuan, and the potential for regenerative teeth is huge. [22]
In addition, bones, blood vessels, and kidneys manufactured using regenerative medicine also have the opportunity to replace the market for artificial joints, artificial blood vessels, and hemodialysis products.
Source: [13][14][15]
Under the optimistic prospects, pharmaceutical giants have announced the development of regenerative medicine research. CAR-T of Novartis, Fosun and other companies, Pfizer, Roche cell therapy, are typical regenerative medicine products, and even the domestic Chinese medicine company Jiuzhitang also invested in the American stem cell company Systemedica in 2019 to get involved in the field of regenerative medicine.
Startups won't be absent either. According to the American Alliance for Regenerative Medicine (ARM), since 2019, the regenerative medicine industry has set funding records for three consecutive years, from $9.8 billion in 2019 to $19.9 billion in 2020, while the first three quarters of 2021 alone have tied the full year of 2020. [16]
In the past 7 years, the financing/listing of foreign regenerative medicine companies | Hard technology watchmaking of fruit shells
The wind of regenerative medicine blew from Europe and the United States to Asia. There are also many regenerative medicine startups in China, and financing events are numerous and dense.
In the past 7 years, the financing/listing of domestic regenerative medicine companies | Hard technology watchmaking of fruit shells
As shown in the table, the financing peak of domestic regenerative medicine companies is 2021, and there are signs of continuing until 2022, although these projects are in the early stages, but the A round of financing can easily reach hundreds of millions, and the amount is generally high.
Capital is eager, but regenerative medicine is not a technology that can be done quickly.
03
Regenerative medicine is not the Golden Fleece
In the field of regenerative medicine, Europe and the United States have always been a lesson for all countries.
Professor Paulo Marciarini, mentioned above, after completing the world's first reinventive tube transplant, repeatedly instigated patients to undergo high-risk transplants under non-essential circumstances, resulting in the death of 6 patients. [17]
In May 2018, three patients in Florida, USA, went blind after receiving eye stem cell therapy, and the FDA directly issued a "permanent ban" to the clinic concerned. Six months later, 12 more people in the United States were hospitalized for receiving stem cell therapy, forcing the FDA to issue more than 20 warning letters. [18]
And Japan has clearly not learned its lesson from the rollover cases in Europe and the United States.
In October 2012, Shinya Yamanaka, a professor at Kyoto University, was awarded the Nobel Prize in Physiology or Medicine for his work on inducing pluripotent stem cells. Then-Japanese Prime Minister Shinzo Abe hit the iron while it was hot, announcing that he would invest 110 billion yen in the regenerative medicine industry and create a freer regulatory environment for the industry.
Under the impetus of the Abe government, Japan has introduced a series of laws and regulations that eliminate the requirements for clinical trials of regenerative medicine therapies, opening the door to convenience.
Loose regulation has brought a "commercial boom" to the Japanese regenerative medicine industry. As of 2020, more than 3,700 regenerative medicine therapies have been approved in hundreds of clinics in Japan. [19]
After the policy was relaxed, Japan's regenerative medical industry has not become Abe's "golden fleece".
The Nature article mentioned that a patient with dilated cardiomyopathy in Japan saw HeartSheet, a stem cell therapy that can "repair the heart muscle", on TV, but in the 9 months after receiving treatment, the patient's condition took a sharp turn for the worse - diagnosed with heart failure and had to undergo a heart transplant; in 2019, Japan approved a therapy for the treatment of spinal cord injury, but independent researchers warned that the therapy lacked long-term evaluation and could lead to pulmonary thrombosis. [20]
This made Nobuya Yamanaka himself unable to look down, and in an interview with Nature, he appealed, "Scientists should do their best to ensure the objectivity and safety of clinical trials." ”[19]
Fortunately, no country other than Japan dares to abolish the clinical system of regenerative medicine therapy.
04
The price of the ship of Theseus
Clinical is a long-term, cost-effective and risky link, and most of the regenerative medicine projects with faster progress in China are also stuck in the pre-clinical stage.
Among the 10 domestic regenerative medicine startups mentioned above, only 4 show the R&D pipeline on the official website.
The official website shows that the four companies have a total of 34 research and development pipelines, and the indications include the nervous system, blood system and heart, kidney, lung and eye diseases. However, except for Gemerison's autologous lung precursor cell therapy, which has two indications for entering the clinical phase I, the remaining pipelines remain preclinical.
Gemmerickson estimates that the two therapies for the treatment of obstructive pulmonary disease and pulmonary fibrosis, respectively, will be subject to new drug applications by the end of 2023. [21]
Although it is too early to talk about the price, they are not cheap.
We can look at foreign precedents -
The price of regenerated cartilage by Genzyme in the United States ranges from $15,000 to $35,000;
Hematopoietic stem cell products from Canadian company Osirisherapeutics, priced at about $200,000;
The British company GSK for the immunodeficiency disease Strimvelis costs $665,000 for a single injection.
And that's just the price of stem cell therapy. In the future, after the commercialization of complex regenerative glands and organ products such as islets, hearts, and kidneys, the price can also be imagined.
Take a long-term view. One day, developed medical technology can turn people into real "Lego", and we can also replace internal organs, bones, and even replace the brain like a "replacement machine" for a computer in some low-cost way.
Only then will we face the paradox of the "Ship of Theseus" - if we update all the plates and parts, will the ship still be the ship? If you replace your organs and tissues, will I still be the "me"?
The article comes from Fruit Shell Hard Technology, written by Yang Jingyi