Source of this article: Times Business School Author: Lei Ying
Source | Times Business School
Author | Lei Ying
Edit | Sun Yiming
Market performance
Last month (March 1 to March 31), the CSI 300 Index fell by 7.84%, and the A-share Pharmaceutical and Biological Industry Index (Shenwan Level 1) rose by 0.87%, outperforming the CSI 300 Index by 8.71 percentage points. Among them, the six Shenwan secondary sub-industries of pharmaceutical commerce, traditional Chinese medicine, medical services, chemical pharmaceuticals, biomedicine, and medical devices increased by 11.28%, 4.75%, 1.1%, 0.66%, -0, 73%, -3.75%, respectively, although the large market with CSI 300 as the indicator continued to fall deeply due to the impact of the macro situation at home and abroad, capital sentiment, etc., the pharmaceutical sector continued to rebound weakly after the Spring Festival, in addition to the deep decline in medical devices, with pharmaceutical commerce, Chinese medicine and other low-value sectors leading the industry index , driving the pharmaceutical and biological sector to rise slightly in March.
As of March 31, 2022, the annual decline of the pharmaceutical and biological industry index was 10.79%, outperforming the CSI 300 index by 3.74 percentage points, from the perspective of secondary sub-industries, the annual increase of the six sub-industries of pharmaceutical commerce, traditional Chinese medicine, chemical pharmaceuticals, medical devices, biomedicine and medical services was -0.02%, -7.49%, -9.38%, -12.79%, -12.8%, -14.13%, ranking 16th and 36th in the 124 Shenwan secondary industries, respectively. 43、58、59、64。
In March 2022, in the A-share biomedical industry, excluding new stocks, the top three gains were Rhein Bio (59.14%), Fosun Pharma (25.78%), and Junshi Bio-U (21.1%); the top three decliners were Palin Bio (-25.02%), Kanghua Bio (-24.85%), and Hualan Bio (-20.97%).
Policy and industry highlights
On March 11, the official website of the National Health Commission issued the "Notice on Printing and Distributing the Application Plan for The Detection of New Coronavirus Antigens (Trial)" (hereinafter referred to as the "Plan") and the supporting "Basic Operating Procedures for The Detection of New Coronavirus Antigens in Primary Medical and Health Institutions" and "Basic Requirements and Procedures for Self-Testing of New Coronavirus Antigens in Primary Medical and Health Institutions". The "Plan" proposes that according to the needs of epidemic prevention and control, in order to further optimize the detection strategy of the new crown virus, antigen detection will be added as a supplement on the basis of nucleic acid detection. Community residents who have self-testing needs can purchase antigen detection reagents for self-testing through retail pharmacies, online sales platforms and other channels.
According to the Plan, the people who apply the new crown antigen test mainly include those who go to primary medical and health institutions for treatment, accompanied by respiratory tract, fever and other symptoms and have symptoms within 5 days; isolation and observation personnel, including home isolation observation, close and sub-close connection, entry isolation observation, sealing and control areas and control areas; community residents with antigen self-testing needs. People in home isolation who are mandatory users of COVID-19 antigen testing are required to undergo antigen self-testing once a day for the first 5 days of the isolation period. (Official website of the Health Commission)
On March 16, the National Health Commission and the State Administration of Traditional Chinese Medicine organized experts to revise the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Eighth Revised Edition)" to form the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9)". The new version of the diagnosis and treatment plan is formed on the basis of careful study of the transmission characteristics and case characteristics of mutated strains such as Delta and Omicron, and in-depth analysis of relevant research results, aiming to guide the medical treatment of new crown pneumonia and effectively improve the level of standardized and homogeneous diagnosis and treatment. This revision of the standard also includes two specific anti-coronavirus drugs, namely PF-07321332/ritonavir tablets (Paxlovid) and domestic monoclonal antibodies (amphavir monoclonal antibody/romimavir monoclonal injection). (Official website of the Health Commission)
On March 14, the State Food and Drug Administration held a meeting to promote the evaluation of the World Health Organization's national vaccine regulatory system (NRA), summarizing the preliminary work, in-depth analysis of the current situation, and deploying the work related to the formal assessment. The meeting pointed out that in 2021, the preparations for the vaccine NRA assessment will be in full swing and achieve good results. Under the unified command of the State Food and Drug Administration, all departments and provincial bureaus have steadily promoted relevant preparatory work and successfully completed the WHO remote mid-term assessment. The meeting requested that we should continue to improve the vaccine inspection quality management system to ensure the consistency of the vaccine regulatory system; pay attention to cross-departmental and cross-regional common collaboration; continue to strengthen information disclosure; and do a good job in the coordination of related sub-indicators of various sectors. In view of the problems and challenges existing in the current work, it is necessary to carefully analyze the reasons and promote rectification and improvement, not only to ensure the smooth passage of formal assessment, but also to base on the long term, so as to continuously promote the modernization of the mainland's vaccine regulatory system and regulatory capacity. (Chinese Medicine News)
On March 2, the FDA approved the chimeric antigen receptor T cell (CAR-T) therapy Sidakiolensay (trade name: Carvykti), a chimeric antigen receptor T cell (CAR-T) therapy independently developed by Legendary Biologics. This drug is used to treat patients with relapsed or refractory multiple myeloma who have previously received 4 or more treatments. Carvykti is a CAR-T cell therapy with two kinds of single-domain antibodies targeting B cell maturation antigens, which is the first cell therapy independently developed in China and approved for overseas marketing, and the second CAR-T therapy approved for the treatment of blood cancer in the world. In 2021, Bristol-Myers Squibb's multiple myeloma CAR-T cell therapy Abecma was approved by the FDA. (Biological latitude and longitude)
On March 8, the U.S. Securities and Exchange Commission (SEC) included five companies on the provisional list of the Foreign Companies Accountability Act (HFCAA), including BeiGene, Zaiding Pharmaceutical, Hehuang Pharmaceutical, Yum China, and Shengmei Semiconductor. However, by March 29, the five companies could provide evidence to apply for removal from the list.
According to the SEC's official website, on December 18, 2020, the Foreign Company Accountability Act ("HFCAA") officially became law. The bill imposes additional disclosure requirements for foreign companies listed in the U.S. and applies to all foreign companies listed in the U.S., but most believe it is primarily aimed at U.S.-listed Chinese companies. Trade frictions have extended to the pharmaceutical field, and the future internationalization of China's innovative drugs may face various problems. At present, these five companies are only on the tentative list, and it is still expected that they will be able to provide evidence to apply for removal from the list by March 29. (Biopharmaceutical Era)
On March 24, Eli Lilly announced that the US FDA is currently unable to approve the application of Sindec and Eli Lilly Pharmaceuticals' PD-1 inhibitor Sindili maclizumab. In February, when the ODAC meeting reviewed Sindec and Eli Lilly's PD-1 inhibitor, Sindili Maclizumab, the expert committee voted 14:1 that Sindili maclizumab should be supplemented with clinical trials to be approved. In its reply, the FDA recommended that the combination chemotherapy of Xindi case monoclonal antibody and the standard therapy of first-line metastatic NSCLC should be conducted in multi-regional non-inferior efficacy clinical trials with overall survival as the endpoint. Currently, Innovent Bio is conducting more than 20 clinical studies on sinilimab to evaluate its safety and efficacy in a variety of cancer treatments. (Biopharmaceutical Era)
On March 17, 2022, the official website of the Drug Evaluation Center (CDE) of the State Food and Drug Administration showed that the CTA101 UCAR-T cell injection product (acceptance number: CXSL2101509) independently developed by Nanjing Beiheng Biotechnology Co., Ltd. (hereinafter referred to as "Beiheng Biotechnology") was officially authorized for clinical trials by the State Drug Administration (NMPA). CTA101 is the first "spot" UCAR-T cell therapy product approved by cde for the treatment of adult relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).
CTA101 uses the "off-the-shelf" CAR-T cell therapy developed by Beiheng Bio's universal CAR-T technology platform, using CRISPR gene editing technology, knocking out the TRAC gene to avoid graft-versus host disease (GvHD), while knocking out the CD52 gene and using anti-CD52 monoclonal antibody to avoid rejection response (HvGR) of patients to CAR-T cells, prolonging the body duration of UGAR-T cells. UCAR-T is prepared using T cells from healthy people, compared with autologous CAR-T, UCAR-T has the advantages of high anti-tumor activity, low cost and high accessibility. General-purpose immune cell therapy does not require matching, "spot" storage, immediate use, significantly reducing the patient's treatment cycle, a healthy donor can prepare hundreds of thousands of "spot", which can significantly reduce the cost of cell therapy. (Biological latitude and longitude)
On March 7, The Team of Wei Yanchang of Shanghai Jiao Tong University published a research paper titled "Viable offspring derived from single unfertilized mammalian oocytes" in PNAS, which studies live mammal offspring from a single unfertilized oocyte, which studies live mammal offspring from a single unfertilized oocyte, which is targeted DNA through seven imprint control regions Methylation rewriting is achieved. The data suggest that parthenogenesis can be achieved by targeting epigenetic rewrites in multiple key imprint control regions. (Biological latitude and longitude)
Business Highlights
【Departure of core technical personnel of BeiGene】On March 4, BeiGene (688235. SH) announced that Dr. Jane Huang, a senior executive and core technical officer of the company, will officially resign as chief medical officer of hematology on April 3, 2022 due to personal planning. Thereafter, Dr. Huang Weijuan will continue to serve BeiGene in her capacity as a consultant, and the service period is expected to be until November 14, 2022 or other dates to be negotiated by the two parties to ensure the smooth progress and smooth transition of related R&D work. Less than a month before Dr. Huang Weijuan's official announcement of her departure, on February 12, 2022, BeiGene issued an announcement that Yong Ben, the company's core technical personnel, had applied to the company in August 2021 to leave the company, and that he would no longer serve as the company's chief medical officer of immuno-oncology from February 9, 2022, local time in the United States.
On March 11, according to the official website of the State Food and Drug Administration, a new indication for BeiGene PD-1 tirelizumab was approved for the treatment of patients with previously treated, locally advanced unresectable or metastatic highly microsatellite unstable (MSI-H) or mismatch repair defect type (dMMR) solid tumors. (Announcement of Listed Companies)
【Salem Biology listed on the Science and Technology Innovation Board】Salem Biologics (688163. SH) recently announced that the company has been officially listed on the Science and Technology Innovation Board of the Shanghai Stock Exchange on March 11. Founded in 1999, Cylon Biotech is a biomedical company focused on the field of antiserum antitoxin, dedicated to the research and development of preventive and therapeutic drugs for the field of biotoxins and biosafety. According to the prospectus, the funds raised from this IPO will be mainly used for special effects new drugs and innovative technology research and development projects, plant expansion projects, etc. According to the Cylon Biotech prospectus, the company's existing products focus on the field of antiserum antitoxin treatment, including antivenom series, equine immunoglobulin, and anti-rabies serum. (Announcement of Listed Companies)
On March 31, Rongchang Biology, the "dark horse" of the bio-innovative drug industry, Rongchang Biologics (688331. SH) listed on the Science and Technology Innovation Board, Rongchang Bio is an innovative biopharmaceutical enterprise with a global vision, focusing on the discovery, development and commercialization of therapeutic antibody drugs such as antibody drug conjugates (ADCs), antibody fusion proteins, monoclonal antibodies and bispecific antibodies. The company provides safe, effective and accessible clinical solutions around major disease areas such as autoimmune diseases, oncological diseases, and ophthalmic diseases to meet a large number of unmet clinical needs. As early as November 2020, Rongchang Bio was listed on the Hong Kong Stock Exchange, attracting a lineup of nearly 20 luxury investment institutions including BlackRock, Aobo Capital, and Hillhouse Capital, and won the highest record for global biotech IPO fundraising in 2020. Since then, Rongchang Biology has taken advantage of the victory to pursue and then go to the science and technology innovation version for listing, and has now become an "A + H" dual-share listed company. Rongchang Bio's ADC drug, vidicetizumab, was approved for marketing in China on June 8, 2021. According to the 2021 financial report, it sold 84 million yuan in about half a year, entering the top 10 queue of global ADC drug sales. (Announcement of Listed Companies)
【The first share of domestic RNA detection landed on the Science and Technology Innovation Board】On March 30, Rendu Bio (688193. SH) was listed on the Science and Technology Innovation Board, becoming the first domestic RNA testing stock, with an issue price of 72.65 yuan per share, issuing 10 million shares, and a total share capital of 40 million shares. Founded in 2007, Rendu Biologics is a high-tech enterprise focusing on RNA molecular diagnostic technology and products in China, and is committed to developing and promoting RNA molecular diagnostic products based on real-time fluorescence constant temperature amplification detection technology (SAT technology). Rendu Bio has a complete set of core technologies with independent intellectual property rights from diagnostic reagents to the research and development and production of automatic supporting instruments. At present, the company has successfully established the SAT technology platform, 42 related patents have been authorized, and 20 products have obtained NMPA registration certificates and are listed for sale. (Announcement of Listed Companies)
【Gloria Ying invested 3 billion yuan to build a biological drug CDMO project】On March 4, Gloria Ying (002821. SZ) announced that in order to promote the strategic layout of the company's overall industrial development and further enhance the service capabilities of the company's emerging business segments, Gloria Ying Pharmaceutical Group (Tianjin) Co., Ltd. (hereinafter referred to as the "Company") and Shanghai Industrial Comprehensive Development Zone Co., Ltd. signed an investment agreement on March 4, 2022, in which the company invested in a newly established wholly-owned subsidiary to invest in the construction of a biopharmaceutical CDMO R&D and commercialization production base in Fengxian, Shanghai with its own or self-financing funds of 3 billion yuan.
The company invested in the construction of biopharmaceutical CDMO R&D and commercialization production base in Shanghai Fengxian, and will further improve the construction of the biopharmaceutical CDMO service platform with the help of the technical accumulation and talent advantages of Shanghai Jinshan Biomacromolecule R&D Center, and accelerate the expansion of antibody-coupled drugs (ADCs) by building an international quality system, actively expanding overseas orders, strengthening the driving force of head customers, ensuring order delivery capabilities, and accelerating the expansion of antibody-coupled drugs (ADCs). The new antibody drug CDMO market strategy and new business layout represented by the new antibody drug are more involved in and shared with the market space spawned by the rapid development of biological drugs at home and abroad. The construction of the project is in line with the company's overall "two-wheel drive" strategy of strengthening the small molecule CDMO business and accelerating the rapid development of strategic emerging businesses. (Announcement of Listed Companies)
【Junshi Biology plans to raise 4 billion yuan to invest in innovative drug projects】On March 7, Junshi Biology (688180. SH) announced that the company intends to issue no more than 70 million shares (including the number of shares) to specific targets, and the total amount of funds raised will not exceed 3.980 billion yuan (including the number), and the net proceeds after deducting the issuance expenses will be used for the innovative drug research and development project, Shanghai Junshi Biotechnology Headquarters and research and development base project. Innovative drug projects include PD-1, BTLA, TIGIT, CD112R, XPO1, EGFR, CTLA-4, etc.
On March 3, the latest announcement on the official website of NMPA showed that the listing application of adalimumab biosimilar (UBP1211) submitted by Junshi Bio has been approved. According to the announcement of Junshi Bio, the indications for the approval of this product are: rheumatoid arthritis, ankylosing spondylitis and psoriasis. Adalimumab is a fully human anti-tumor necrosis factor α (TNF-α) monoclonal antibody. (Announcement of Listed Companies)
【Baike Bio's 2021 revenue and net profit double decline, nasal spray flu vaccination is less than expected】 On March 17, Baike Biotech (688276. SH) released its 2021 annual report: In 2021, the company's total operating income was 1,202.0266 million yuan, down 16.6% year-on-year; the deducted non-net profit attributable to shareholders of listed companies was 233.6257 million yuan, a decrease of 41.87%. The Company attributed the main reasons affecting revenue to: the impact of the COVID-19 pandemic and the concentrated vaccination of COVID-19 vaccines on non-immunization programmes and the increasing impact of the competition pattern in the product market (Listed Company Announcement)
【The first in China, Sunshine Guojian PSGL-1 monoclonal antibody approved clinically】According to the official website of the Drug Evaluation Center (CDE) of the State Food and Drug Administration, on March 22, Sunshine Guojian (688336. SH) applied for an implied license for the clinical trial of "SSGJ-617 Injection" for advanced solid tumors. SSGJ-617 (VTX-0811) is a PSGL-1 targeted monoclonal antibody introduced by 3SBio from Versia Therapeutics, in 2019, Sunshine Guojian and Verseau reached a cooperation agreement to select VTX-0811 as the first authorized product, responsible for its development and commercialization in Chinese mainland, Hong Kong, Macau and Taiwan, it is worth mentioning that this is the first PSGL-1 monoclonal antibody approved for clinical trials in China. VTX-0811 has received IND approval from the FDA in the United States. (BioValley)
According to the latest public notice released by the official website of China's State Food and Drug Administration (NMPA), on March 24, Watson Bio (300142. Shanghai Zerun Biotechnology Co., Ltd. (hereinafter referred to as "Zerun Biotechnology"), a holding subsidiary of SZ), independently developed the "recombinant human papillomavirus bivalent (type 16/18) vaccine (yeast)" and has been approved for marketing. According to public information, the bivalent HPV vaccine is mainly used to prevent cervical cancer and precancerous lesions caused by HPV16/18 infection, including pre-filled syringes and vials. According to a press release issued earlier by Zerun Biologics, the divalent HPV vaccine developed by zerun is produced using the Pichi yeast expression system, which has many advantages. (BioValley)
【Biopharmaceutical upstream enterprise Nano Micro Technology 2021 High Performance Growth】On March 10, Nano Micro Technology (688690. SH) released its 2021 annual report, which showed that the company achieved revenue of 446 million yuan, an increase of 118% year-on-year, and net profit of 188 million yuan, an increase of 159% year-on-year; Achieved a non-net profit of 172 million yuan, an increase of 172% year-on-year. During the reporting period, the company's biomedical segment revenue continued to grow, of which the sales of affinity chromatography media, ion exchange chromatography media and other products increased significantly. In 2021, the revenue of Nano Micro Technology in the biomedical field was 390 million yuan, an increase of 34% year-on-year, accounting for 87% of revenue, an increase of 6 percentage points year-on-year.
Monthly observation: Legendary biology successfully broke through Europe and the United States, and domestic innovative drugs went to sea to meet milestones
As early as 2017, the former State Food and Drug Administration of the mainland joined the ICH (International Human Drug Registration Technical Coordination Council) as a member, officially integrating China's drug supervision and administration system with international standards. In this way, it will open up opportunities for local pharmaceutical companies to compete with international first-line innovative drug companies, and open up the passage for mainland innovative drugs to go overseas.
On the one hand, for Chinese innovative drugs going to sea, synchronous declaration can be achieved through global multi-center clinical studies; according to the ICCE5 (R1) guiding principle "ETHNIC FACTORS IN THE ACCEPTABILITY OF FOREIGN CLINICALDATA", Chinese clinical data can also be used, and the evaluation data meets the requirements of the regional regulations to be declared. At the same time, the evaluation of this data can be extrapolated to the area to be reported is not affected by ethnic factors (if necessary, supplementary bridging tests are required) and overseas registration and listing is sought.
On the other hand, the domestic market is subject to the double attack of the normalization of the medical insurance catalogue and the pressure of medical insurance negotiation and price reduction, although new drugs can quickly enter the medical insurance catalogue to achieve sales after the listing, but also face the sharp price reduction of products, the recovery cycle of early research and development investment is lengthened, which to a certain extent accelerates the journey of innovative drugs in the mainland.
Taking the four major domestic PD-1 production enterprises as an example, in 2020, Hengrui Pharmaceutical (600276. SH), BeiGene (688235.SH), Junshi Bio (688180.SH), Andia Bio (1801.HK) gathered at the medical insurance negotiating table, and all four domestic PD-1s entered the medical insurance, which means that in 2021, the era of PD-1 head-to-hand combat has begun. Judging from the PD-1 sales of the four enterprises in 2021, Hengrui Pharmaceutical's Carellizumab won the top spot with 3.8 billion yuan, Followed by Cinda Bio and BeiGene with 2.8 billion yuan and 1.65 billion yuan respectively, and Junshi Bio's Triprimumab was at the bottom with 410 million yuan.
Judging from the performance of Junshi Bio in 2021, the total revenue was 4.025 billion yuan, an increase of more than 150% year-on-year, and the main growth driver relied on espressiblizumab, which contributed at least 2 billion yuan of revenue, which greatly narrowed the company's net loss margin, and also made up for the shortcomings of its core product, triprimumab, in the domestic market sales growth. Ettexvirumab is a covid-19 neutralizing antibody developed by Junshi Bio in collaboration with Eli Lilly, which is mainly sold in the US market.
According to incomplete statistics, as of the beginning of 2022, of the 42 pharmaceutical companies in mainland China with clinical pipelines of innovative drugs above phase II, 30 of them have carried out overseas clinical research simultaneously, or have submitted listing applications to the United States, Europe, Japan and other countries. Among these overseas enterprises that have simultaneous clinical research or attempted to apply for listing, those that are expected to achieve the successful overseas development of related R&D varieties in the first half of 2022 include Legendary Biology (LEGN.O), Cinda Biologics, Junshi Biologics, and Huang Pharmaceutical (0013. HK), BIOTEC (688177. SH）。
On March 2, the FDA approved the chimeric antigen receptor T cell (CAR-T) therapy developed by Legendary Biologics, Siddha Kiolensay (trade name: Carvykti). This drug is used to treat patients with relapsed or refractory multiple myeloma who have previously received 4 or more treatments. Carvykti is a CAR-T cell therapy with two kinds of single-domain antibodies targeting B cell maturation antigens, which is the first cell therapy independently developed in China and approved for overseas marketing, and the second CAR-T therapy approved for the treatment of blood cancer in the world. Prior to this, Bristol-Myers Squibb's MULTIPLE MYELOMA CAR-T Cell Therapy (trade name: Abecma) was approved by the FDA in 2021.
As the first domestic CAR-T cell therapy approved by the FDA, the legendary biological Carvykti has a milestone significance at the level of domestic innovative drugs going to sea, and also injects another shot of tonic into the domestic innovative drug track. The company said it has established sales, physician education, academic promotion teams, and the drug is expected to sell for $465,000.
However, the sea of innovative drugs is not always smooth. On March 24, Eli Lilly announced that the US FDA is currently unable to approve the application of Innovent Biologics and Eli Lilly Pharmaceuticals' PD-1 inhibitor sindilizumab. As early as February 10, the FDA held an ODAC meeting to review the marketing application submitted by Cinda Biologics and Eli Lilly Pharmaceuticals for the treatment of the PD-1 inhibitor Sindilimab for first-line non-squamous non-small cell lung cancer (NSCLC), and the main concern raised by the expert committee was that ORIENT-11 was a single-country (China) clinical trial, and the clinical results obtained in the Chinese patient population were not necessarily applicable to PATIENTs in the United States, which was the most concerned issue for the FDA. Finally, the ODAC expert committee voted 14:1 to believe that sindilizumab should be supplemented with clinical trials to be approved.
On March 24, Eli Lilly disclosed that the FDA recommended in its reply that sindilizumab combined chemotherapy and standard therapy for first-line metastatic NSCLC should be conducted in multi-regional non-inferior efficacy clinical trials with overall survival as the endpoint. In the cooperation with Cinda Biologics, Lilai originally planned to open up sales in the US market with an aggressive pricing strategy after the product passed the FDA listing approval.
Looking back at the trend of innovative drugs in mainland China in contrast to the xindilizumab incident of Cinda Biologics, the FDA puts forward higher requirements for China's innovative drugs to be approved for listing in the United States, especially in the field of NSCLC, follow-up product listing applications, only providing Chinese clinical data may be difficult to succeed, and it is necessary to combine the first-line standard treatment program in the United States to carry out global multi-center clinical trials. However, the FDA also said that for nasopharyngeal carcinoma, hepatocellular carcinoma and other cancers with higher incidence in Asian populations, it is difficult to recruit patients in global multi-center clinical trials, and the FDA can give a certain degree of regulatory flexibility.
【This month's attention】
Global COVID-19 epidemic, COVID-19 diagnosis and treatment industry chain, and approval of COVID-19 special drugs
【Risk Warning】
Policy risks, medical anti-corruption, medical safety accidents
(Full text 7086 words)
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