Industries that are not too market-oriented are about to become market-oriented.

For most people, “nuclear medicine” is strange and mysterious, but it is closely related to everyone’s lives. For example, to check whether a person is infected with Helicobacter pylori in a daily physical examination, doctors will mostly use carbon 14 (C14) breath kits. C14 is an isotope. It belongs to the category of nuclear medicine.

Nuclear medicine, in one sentence, is the non-invasive, precise and targeted application of radionuclide tracing technology in medical diagnosis and treatment. Tumor screening, metastasis search, preoperative staging, postoperative evaluation, efficacy monitoring, targeted therapy… Nuclear medicine plays a huge role in clinical diagnosis and treatment.

The field of nuclear medicine is mainly divided into diagnosis and treatment, including nuclear medicine equipment and nuclear medicine. However, because nuclear medicine equipment has always been a game for industry giants such as “GPS” and relies on imports; in addition, the threshold of “nuclear medicine” is not low, and the subordinate enterprises of the relevant national nuclear research institutes are basically responsible for R&D and production.< /span>.

According to the information given in the prospectus of China Tongfu, the current global scale of the nuclide drug market alone has exceeded US$10 billion, and the compound growth rate in the next 10 years will exceed 11 %. ChangeIn other words, the nuclear medicine Not too market-oriented.

But the situation has started to change in recent years. Because of the large-scale medical equipment deployment policy supported by the state, the number of PET-CT instruments has soared several times; the implementation of the radiopharmaceutical MAH system, and a batch of innovative radiation The rise of pharmaceutical companies; superimposing the industry’s unique high-barrier attribute of “the stronger the stronger”, The nuclear medicine industry is generally considered to be “warm spring”.

In addition, nuclear medicine in the “14th Five-Year Plan” has also risen to the national strategic level, and “one county, one nuclear medicine department” has been officially included in the plan. Official data show that in 2017, my countryThere are a total of 853 nuclear medicine departments (including separate PET/SPECT centers), and there are 2,340 tertiary hospitals in my country. There is huge room for growth. It is expected that my country’s nuclear medicine departments will enter a period of rapid construction in the next 10 years strong>.

At the same time, not long ago, eight ministries and commissions including the National Defense Science and Industry Bureau, the Medical Insurance Bureau, the Health Commission, and the Food and Drug Administration jointly issued the “Medicine Isotope Medium and Long-term Development Plan (2021-2035)”. The development, production, radiopharmaceutical research and development, medical insurance policy, industrial layout and other important aspects have been deployed. The policy spring breeze further promotes the acceleration of nuclear medicine.

So, where are the industry opportunities? In view of the long-term monopoly of giants (including equipment and nuclear drugs), how should new entrants get stuck? What are the challenges? Observation research found:

  • In recent years, targeted therapy has opened a window of precision treatment to nuclear medicine. Policy deregulation and capital injection will promote the rapid development of nuclear medicine diagnostic imaging and nuclear medicine market; p>

  • Nuclear medicine has high barriers to entry but high gross profit, industry development continues to exceed expectations, and a high degree of commercial certainty is added. There are many “entrants” who want a piece of the pie, mainly focusing on PET-CT Equipment and radiopharmaceutical fields;

  • The development of China’s nuclear medicine market is still in its early stage. Although breakthroughs have been made in the PET field, the development of nuclear medicine and SPECT is still in its early stages. New entrants face greater difficulties in breaking the game, and “integration of diagnosis and treatment” It is the inevitable development.

Nuclear medicine: “imaging pathology” + targeted “radiotherapy”

The so-called nuclear medicine is a science that uses drugs labeled with radionuclides to diagnose and treat diseases. It is radioisotopes, beams of rays and radioisotopes produced by accelerators. Medical applications of the generated nuclear radiation.

Nuclear medicine has a long history. In 1898, Madame Curie discovered the element of radium, which laid the foundation for nuclear medicine theory; in 1874, pharmacist Morten Nyegaard discovered nuclide; in 1935, Nobel Prize winner Von Hevesy proposed isotope tracing The principle and technology have promoted the medical application of nuclide drugs; in the late 1950s, China began to explore related applications.

As mentioned above, nuclear medicine application scenarios are divided into two categories: diagnosis and treatment. The entire format includes nuclear medicine equipment and nuclide drugs, which complement each other.

In terms of equipment, nuclear medicine imaging diagnostic equipment is currently the most widely used clinically. The more mature applications include positron imaging equipment (PET-CT as the Main) and single photoelectron imaging (SPECT) equipment. These two devices need to be used in combination with nuclide drugs (isotopic imaging agents), and patients need to inject specific imaging agents before going through the equipment for examination: the former generally uses positron imaging agents such as F18-FDG, and the latter is labeled with Tc99m A variety of developers.

In terms of medicines, it is mainly divided into two types: diagnostic and therapeutic. Diagnostic nuclear drugs are mainly auxiliary nuclear medicine imaging equipment, the most important of which are single-photon drugs and positron drugs, relying on SPECT and PET-CT detection respectively. Therapeutic nuclear drugs are of various types, and they are mostly used in the treatment of tumors, alleviating bone pain and other fields.

Classification of nuclear medicine industry (picture source: Alpha Factory Research Institute)

When it comes to diagnosis, one has to talk about the “magic effect” of nuclear medicine.

In layman’s terms, itis functional visualization, it is to inject the tracer into the human body to participate in the metabolism, by selectively measuring the radiation emitted by the ingested radionuclide, it can reveal the body’s Metabolism and function information can also be used to detect differences in cell activity for early diagnosis of diseases;Other imaging methods are structural imaging , like taking a picture, if a visible mass is taken, it may be a malignant tumor, but it may also be an inflammation or benign tumor.

Take the diagnosis of angina pectoris as an example. Traditional coronary CT can see whether there is stenosis in the coronary arteries, but it cannot reflect the loss of function. Nuclide myocardial perfusion imaging requires the injection of a radionuclide tracer. If the blood vessel is unobstructed, it will enter and exit very smoothly; if it is not unobstructed, this radioisotope is lacking in some part of myocardial tissue, reflecting the supply of myocardial blood flow.

Look at tumors again. Generally, the gold standard for pathological examination is puncture + immunohistochemistry. However, considering the technical principle itself, the immunohistochemical response is a single point of static information. This method cannot reflect the heterogeneity of the tumor and has certain limitations; and radiography combined with whole-body PET/CT can obtain all tumors in the whole body. The expression level of specific antigens in primary and metastatic foci is equivalent to systemic immunohistochemistry. Doctors can obtain more real-time and comprehensive dynamic information for guiding medication and follow-up after medication.

For this,Zhang Xiangsong, Director of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou An example: “the tumor is unevenly distributed in the bodyThe tumor is uniform, and the tumor can spread-the original location may be different from the metastatic location, and the tumor is also changing at different time points, including before and after treatment; but pathological examinations cannot be repeated, and it is not It is possible to collect materials for every part. If it is this kind of liquid test, of course the cells can be checked in the blood, but it is not possible to know where its source is and how it is distributed throughout the body. The advantage of nuclear medicine imaging is that after the marked markers are injected into the body, the whole body can be seen through the whole body tomography, even the unevenness inside the tumor, that is, the heterogeneity of the tumor can be reflected. . “

In addition, nuclear medicine also has irreplaceable significance in the nervous system and cardiovascular system. Even Parkinson’s Field alternative to pathological examination.

Take the neurodegenerative disease-Alzheimer’s disease or Parkinson’s disease as an example. After the clinical symptoms appear, there is a lot of difficulty in differential diagnosis on the one hand. On the other hand, treatment was relatively late. The imaging method of nuclear medicine can be diagnosed several years before the appearance of clinical symptoms of similar diseases, or even more than ten years before, so that clinical intervention can be carried out earlier.

According to him, the pathogenesis of Parkinson’s disease is the damage to the substantia nigra-striatal dopamine nerve pathway of the central nervous system. Nuclear medicine can detect dopamine nerve function. The probe can detect whether the patient’s dopamine nerve function is damaged by nuclear medicine imaging 10-20 years before the onset of motor symptoms in Parkinson’s disease, and then diagnose it. “

Professor Zhang Xiangsong believes that the development trend of nuclear medicine may be towards the development of “imaging pathology.” Advantages, imaging may partially replace the role of pathological examination in the future.”

Take the neuroendocrine tumors suffered by Jobs as an example. Generally, pathological grading (G1, G2, G3) based on Ki67 proliferation index, and imaging examination for clinical staging. From the perspective of nuclear medicine, the routine clinical “dual-nuclides scan” will do two imagings: glucose metabolism and somatostatin receptor expression. According to the results of the dual-nuclides scan, it can be more accurate.Secret tumor grade and clinical stage.

In the field of treatment, radionuclide drugs have also made many breakthroughs, and they have been commonly used in the treatment of hyperthyroidism, rheumatoid arthritis, bone pain caused by tumor bone metastasis and other fields. Take tumors as an example. Its main trend is targeted therapy, precise treatment, “precise guidance” to cancer cells, avoiding “injury to the innocent”, and reducing side effects while killing tumors.

In recent years, various radioisotopes such as lutetium-177 and yttrium-90 have been used in clinical treatment of intestinal endocrine tumors and primary liver cancer; in addition, new drug development and clinical treatment based on nuclides are also being widely used Applications.

Nuclear drugs for treatment

What are the emerging “three highs” industries power?

In summary, nuclear medicine has important clinical value. ButNuclear medicine is a typical high-tech barrier industry, with the “three highs” characteristics of high clinical profit, high barriers, and high growth rate.

Nuclear medicine industry chain (picture source: Everbright Securities)

So, what are the factors that make up the high-barrier ecology? It can be viewed in detail in conjunction with the industrial chain.

First of all, radioisotopes have very high requirements for environmental impact assessment in the production and transportation of radioactive isotopes. Enterprises need to strictly follow the “Radioactive Isotope and Radiation Device Radiation Protection Regulations” to register with relevant departments and do a good job in radiation protection management. And accept the radiological protection supervision of the relevant departments, the qualifications that need to be obtained include the “radiopharmaceutical production license”, the “radiopharmaceutical business license”, and the “radiation safety license”.

In addition, the source of isotope raw materials is special, and there are two main ways-from reactor preparation or accelerator production, which is difficult for ordinary enterprises to obtain. In addition, the supply of short half-life isotopes is also a difficult point. Many isotopes have a short half-life. For example, F18-FDG has a half-life of less than 2 hours, which requires use on the day of production.

Ye Yin, the chief analyst of Ping An Securities, pointed out, “The short half-life of diagnostic nuclide drugs determines the pre-production attributes. If a company has only one base, it is obviously not able to meet the national supply. Therefore, the clinical use of diagnostic nuclide drugs requires A complete’nuclear pharmacy’ network.”

Note: “Nuclear pharmacy” is not a pharmacy, but a production workshop. The construction of a single “nuclear pharmacy” has a large investment of about 50 million yuan; the cycle is long, about 5 years; and there are many approval procedures, which further hinders the entry of “new players”.

Because of this, the concentration of China’s nuclear medicine market has been very high for a long time, and two strong positions have been formed. 60% share.

In addition, the configuration and use of nuclear medicine imaging equipment are also restricted. Since 2005, the state has implemented configuration management for large-scale medical equipment according to the plan, and the large-scale medical equipment configuration management catalog is divided into two categories: A and B. Prior to this, the National Health Commission was responsible for the configuration and management of the large-scale medical equipment belonging to nuclear medicine equipment and was responsible for the issuance of configuration licenses. Even if the hospital had to purchase nuclear medicine equipment, it was strictly controlled.

Nowadays, the threshold of nuclear medicine still exists, but the loosening of policies, the increase of capital, and the growth of the talent team are all beginning to add vitality to the industry. According to statistics, the global nuclear medicine market is expected to reach 24 billion U.S. dollars in 2030, with a compound growth rate of over 16% in the future. By then, the nuclear medicine treatment market will account for about 65% and the nuclear medicine diagnostic market will account for about 35%.

At the same time,Nuclear medicine industryThe result of the high barrier feature is a good competitive landscape, good growth, and high profit margins. It is a fairly certain “good business”:There are a large number of exclusive varieties, and there are basically no more than 3 competitive varieties; the growth rate is good, and the income growth rate is faster than the overall growth of the chemical preparation and pharmaceutical industries The profit margin is high. For example, the net profit margin of Yunke Pharmaceutical in 2019 is about 45%, which is much higher than the 6% net profit margin of the A-share chemical preparation and pharmaceutical industries.

The development of the nuclear medicine industry is also continuing to exceed expectations. With a high degree of commercial certainty, there are many “entrants” who want to get a share.

At present, in the field of nuclear medicine equipment, domestic PET-CT equipment manufacturers have Neusoft Medical, United Imaging Medical, Mingfeng Medical, Sino United, Ruishikang, etc. A few, they are also the subject of much attention in the capital market. A typical example is Neusoft Medical, whose new NeuWise PET/CT products have been fully introduced into the market. United Imaging’s independent research and development of PET equipment has reached the international first-line level, and domestic brands are gradually occupying a place in the field of high-end molecular imaging.

Chinese companies deploying PET-CT and other nuclear medicine equipment

As for the field of nuclear medicine, the traditional In addition to radiopharmaceutical R&D and production enterprises, Tianjin Saide, Jiangsu Huayi, and Dongcheng Pharmaceutical have also begun to enter the field of radiopharmaceuticals, which has promoted the development of radiopharmaceuticals in China.

There are some new forces, such as Nuruite Medical, medicine Mingbo Rui,Xiantong Pharmaceutical,Intelligent BioWait to join, and become a newly sought after “fragrance” by capital; in addition, I have also heard from many sources that the world’s first scientist in nuclear medicine is also about to return to China to start a business, which has aroused the attention of industry professionals.

The market value of Dongcheng Pharmaceutical (002675.SZ) in the secondary market has now exceeded 15 billion, and the market has given a PE valuation multiple of 93 times.

Chinese companies focusing on the layout of nuclear medicine

Not only that, since 2018, nuclear medicine has also become a hot spot for mergers and acquisitions in the international market. Within a year, Novartis spent US$6 billion on two radioligand therapy companies, which is enough to see the international capital market’s “eye-catching eyes” of nuclear medicine.

20In January 2018, Novartis acquired French AAA for US$3.9 billion and obtained lutetium 177, which is the first approved peptide receptor radionuclide therapy for the treatment of rare neuroendocrine tumors; in October of the same year, Novartis It also acquired the biopharmaceutical company Endocyte for US$2.1 billion, mainly to obtain the latter’s drug candidate for the treatment of metastatic castrated prostate cancer.

Enter the eve of the cake grab< /p>

There is no doubt that nuclear medicine is a sunrise industry with strong demand and many opportunities. Capital’s pursuit of nuclear medicine has undoubtedly further contributed to the confidence of the industry.

ButUnexpectedly, many practitioners in the industry agree that , There is no time to chase and snatch the “big cake”. Investors who have studied and contacted Xitong Medicine many times but failed to inject capital told them, “Nuclear medicine may not develop into the mainstream In addition to the high cost, they are also worried that radiation will damage the human body.”

But experts point out that, in fact, radionuclides have a short half-life and cause relatively little damage to the human body. As for the price issue, as domestic equipment continues to be put into use, some Nuclide drugs are also being added to the medical insurance catalog, and expensive inspection prices can be further compressed.

However, Zhang Jinsong, a deputy director of the Nuclear Power Institute, also pointed out that at this stage, there is no time to talk about competition among the various players in the industry. “At present, my country is still in the follow-up stage in the field of medical isotope. The upstream and downstream of the industrial chain should be united to achieve the leap from following to parallel running or even leading.”

The overall slow progress of technology is also a reason for the lagging development of the industry. A typical example is Lu 177, currently it is a radionuclide drug developed for the imaging and treatment of metastatic castration-resistant prostate. ItIt is the first new technological breakthrough in the field of nuclide medicine since its revival with iodine-131 in 1940.

Professor Zhang Xiangsong told that currentlythe fastest progress is peptide receptor-mediated radionucleus Primitive therapy (PRRT), there are two most obvious:

  • One ​​is to target prostate cancer molecular marker prostate membrane antigen (PSMA), which is Lu177 labeled PSMA to treat advanced prostate cancer; p>

  • In addition, it is the molecular marker somatostatin receptor for neuroendocrine tumors. Lu177-labeled somatostatin is used to target neuroendocrine tumors. At present, the clinical effect is also very good.

In addition, nuclear medicine “entrants” in certain fields have formed high industry barriers. For new entrants, it is not easy to break this situation..

As mentioned in the previous article, it takes time for companies to obtain radiopharmaceutical production licenses and radiopharmaceutical business licenses. The deployment of “nuclear pharmacy” outlets across the country requires high time and capital costs. These are currently new Challenges faced by entrants.

For example, from the perspective of market share, in 2018, my country’s nuclear drug market has the largest categories of Yunke, C13/C14, FDG, etc. Take the domestic F18-FDG as an example. At present, only 3 companies in China, namely, Atom Hi-Tech, Dongcheng Adike and Jiangsu Huayi have obtained production approvals.

In this regard, Gao Wei, general manager of ge Medical’s nuclear medicine division, said that for the development of nuclear medicine, the integration of diagnosis and treatment is the future development trend.

The investment team of the CICC Qide Fund also stated previously: Since 2018, long half-life radiopharmaceuticals have achieved milestone breakthroughs in the field of tumor treatment, making nuclear medicine Learning has once again become a hot spot for pharmaceutical giants and innovative pharmaceutical companies. “The’integration of diagnosis and treatment’ based on radiopharmaceuticals and related technologies has become an important part of the precision medical system and will open up the Chinese drug release market. Fission gushing.”

The so-called integration of diagnosis and treatment means first detection and second treatment, and the use of companion diagnostics to guide targeted therapy. Accurate detection results can bring better results to patients. It is a precise and individualized medical choice to enhance the effect of disease diagnosis and treatment. Diagnosis and treatment both use targeted drugs to bind different isotopes. First, use weak radioactive isotopes to bind to the targeted drugs for diagnosis. Use PET-CT diagnostic images to clarify the location, and then replace the therapeutic isotope after the companion diagnosis is completed. .

To be specific, traditional pharmaceutical companies should focus on the development of targeted drugs that are more targeted and have fewer side effects, and then cooperate with nuclear medicine companies Cooperation to enter the integrated field of diagnosis and treatment; nuclear drug companies should continue to improve the production system of nuclide drugs to produce more and better isotopes suitable for the integration of diagnosis and treatment;ForFor new entrants, they can start with innovative drugs, or choose drugs with relatively long half-lives, so there is no need to build a nationwide “nuclear pharmacy” network.

For example, The strategy for the development of “nuclear drugs” by the sapiens is mainly to use its nanobody platform to chelate radioisotopes, using nanobodies with small molecular weight and rapid detection. The characteristics of the company start with diagnostic products, and then develop in the direction of integrated diagnosis and treatment in the future to seize this relatively blank field.

Look at Xiantong Pharmaceutical again. Its product pipeline adopts the strategy of “independent development + external cooperation”. The combination of imitation and innovation can achieve a balance of risk and return; then through strategic financing, it will further open up the upstream and downstream resources of the domestic and even global radiopharmaceutical industry chain. Achieve faster development.

Zhang Jinsong, a deputy director of the Nuclear Power Research Institute, revealed, “At present, we are planning the technology during the 14th Five-Year Plan period. The goal is to aim at the frontiers, such as foreign countries. We will follow up on the newly reported Holmium-166 and Scandium-47, which are integrated in diagnosis and treatment, in time. As long as the market and medical research are needed and the reactor can be produced, we will do it.”

Some scientists once said that the overall understanding of human life sciences is still in the stage of enlightenment.

For nuclear medicine, it’s not an exaggeration to say that humans are “hugging outside the gates of the Temple of Nuclear Medicine and cannot enter.” People only speculate that the lights in the temple are occasionally exposed from the windows of the temple. Scenario, there are still too many special codes for nuclear medicine science waiting to be unlocked in the future. But now, we have already seen hope.

References

  1. “Nuclear Medicine under Targeted Therapy”, Bairong Capital

  2. 《High barriers create duopoly and light up the sea of ​​nuclear medicine and stars— —In-depth report on the nuclear medicine industry, Everbright Securities;

  3. “The market size exceeds tens of billions of dollars! Nuclear medicine examinationEssential Radiopharmaceuticals”, Siyu Medical Devices;

  4. “Tighten your waistband and engage in “nuclear drug” weapons”, Alpha Workshop Research Institute;

  5. “2020 China Nuclear Medicine Industry Overview”, Head Leopard Research Institute;

  6. “The Status Quo and Development Trend of Radiopharmaceuticals in China”, Chinese Journal of Food and Drug Administration;

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  7. “Nuclear Medicine Breaks the Problem from the Source”, China Journal of the Nuclear Industry.

  8. “What are the challenges for fully implementing the MAH system? “, R&D guest