From the successful development of biotechnology to the head enterprises of biopharmaceuticals (Xinda and Junshi), these two biopharmaceuticals have been very interesting all the way. Let me talk about my personal views on these two companies.
1, enterprise development process
Xinda biology
2011August, Cinda Bio was established in Suzhou; On 20 18, 10, Cinda Bio was listed on the main board of the Hong Kong Stock Exchange. 20 18 12 and cinda bio-PD- 1 Cindilizumab (trade name: daboshu) were officially approved for 3L classic Hodgkin's lymphoma, becoming the second approved domestic PD- 1 monoclonal antibody; At present, a product chain including 23 new drug varieties has been established, covering tumors, metabolic diseases, autoimmune diseases, etc., among which 6 varieties have been selected into the national "major new drug creation" project, and 4 products have been listed (Cindilizumab injection, trade name: Daboshu, English trade name: TYVYT；; Bevacizumab injection, trade name: Dayutong, English trade name: BYVASDA；; Adalimumab injection (trade name: Sulinox) and Dabohua (rituximab injection) have been approved for marketing by NMPA, 4 products have entered phase III or key clinical research, and 15 products have entered or will enter clinical research soon.
Cinda Bio has become the only pharmaceutical company with monoclonal antibody drugs listed in China.
Junshi biological science
2. Business development and performance
Two commercial products are PD 1.
Xinda biology
From 20 17 to 20 19, the revenue was 0. 19, 0.095 and10.48 million yuan respectively. The reason why the income of 20 19 increased greatly was that PD- 1 monoclonal antibody went on the market, and 20101600 million yuan was sold by Suntory monoclonal antibody. In recent three years, the R&D expenditure was 6 1.2 million,1.222 million and1.295 million respectively. In the first half of 2020, the company's revenue was 980 million, up 185% year-on-year, of which revenue was mainly contributed by Daboshu (920 million). The gross profit margin in the first half of the year was 865,438+0.2%, which was lower than last year's 88.65,438+0%, mainly due to the price reduction of products. In the first half of the year, R&D investment increased by 20.4% year-on-year to 86,543.8+billion, and sales expenses increased by 67.5% year-on-year to 447 million. The adjusted net profit was-454 million, a year-on-year decrease of 32%.
At present, the production base is running five 1 1,000-liter bioreactors to support the production needs of cypress, Dayoutong and other candidate products under study. Another 6 3000-liter stainless steel bioreactors completed GMP debugging and process verification, which expanded the company's total production capacity to 23000 liters.
Junshi biological science
From 20 17 to 20 19, the revenue was 0.54, 0.03 and 775 million yuan respectively, with a compound annual growth rate of 278.8%, and the net profit attributable to the mother was -3. 17, -7.23 and-747 million yuan respectively. From 20 16 to 20 19, the R&D expenditure was 654.38+22 million yuan, 275 million yuan, 538 million yuan and 946 million yuan respectively. In the last quarter of 2020, the total revenue was RMB 575 million, an increase of 86%. R&D expenditure was 709 million yuan, a substantial increase of 92% over the same period last year.
At present, the production base in Wujiang, Suzhou has a fermentation capacity of 3000 l(6 * 500 l). At present, the production base in Wujiang, Suzhou has obtained GMP certification, and there is also a 30,000-liter antibody production base (5*3*2000L disposable fermentor) in Lingang.
3, the core team of the enterprise
Cinda Bio: In the first half of 2020, Cinda Bio increased from about 2,000 employees in February 2065,438+0,2065,438+09 to 2,600 employees on June 30, 2020, of which more than 750 employees were responsible for research and development, and more than 1 100 employees were responsible for commercialization.
The core figures of Cinda Bio include: Yu Dechao (founder), (former vice president, who left his job on 20 18 to start Pumis, and has applied for double antibodies twice), Kan Hong (vice president, quality control and registration declaration), Zhou (coo), Liu Junjian (vice president, core personnel) and Wei Xu (vice president, production).
Cinda Bio-patent Reserve:
Junshi biological science
Junshi Bio 20 17 * * has about 200 employees. By the end of 20 19, the company had employees 142 1 person, including 4 15 technicians and 360 salesmen, accounting for 29.2% and 25.5% respectively. Today, Junshi has more than 2,000 employees, 30% of whom are R&D personnel and about 700 are commercial operators.
The core figures of Junshi Bio include: Dr. Yao Sheng (vice president), Dr. Duan Xin (vice president, clinical research), Dr. Wu Hai (chief scientist), Dr. Feng Hui (chief operating officer), Dr. Zhang Zhuobing (vice president) and Li Ning (CEO), all of whom are deeply involved in the company's research and development work. Xiong Jun (founding partner), Wang Gang (vice president, quality control), Han Jing (vice president, marketing) and Chen Bo (founding partner, who left on October 6th to establish Kangnuo Biomedical in Chengdu).
Junshi Bio-patent Reserve:
4. Antibody platform
Xinda biology
(The above picture is from Armstring biopharmaceutical information)
Junshi biological science
5. Similarities and differences of enterprise target layout.
R&D pipeline:
Xinda biology
Junshi biological science
On the same target layout:
PD 1: Junshi Bio (more than 30 clinical trials are being carried out at the same time, among which 15 key registered clinical trials are aimed at non-small cell lung cancer, esophageal cancer, triple negative breast cancer, melanoma and other expanded indications. )
Cinda Bio (there are more than 25 clinical trials with indications, including non-small cell lung cancer, hepatocellular carcinoma, advanced gastric cancer and esophageal cancer, which are the most indications on the market at present).
PDL 1: In the second phase of Junshi Research Project, Cinda has no single target layout. In 20 17, Cinda Bio applied for the patent of PD-L 1 nano-antibody CN20 17 10657665, and the first inventor of this patent was Shen. Carry out a number of PDL 1 double antibodies (PD-L 1/TGF-β, PDL 1/CD47, PDL 1/OX40, PDI 1/LAG-3).
Bevacizumab: From 2065438 to 2009, the sales of Avastin originally developed by Roche reached 7.494 billion US dollars. On 20 19 12.6, bevacizumab (trade name "Ankeda") of Qilu Pharmaceutical was approved for marketing and successfully obtained the first imitation. Since April 2020, Luye Pharmaceutical/Boan Bio, Beida Pharmaceutical/Haizheng Bio, Hengrui Pharma's Shengdiya Bio, Baiaotai Bio, and Dongyao Pharmaceutical have all submitted applications for the listing of new bevacizumab analogues. At least 20 companies are developing biological analogues of bevacizumab. In addition to the listed companies mentioned above, bevacizumab biological drugs from Hualan Gene, Fu Honghanlin, Shenzhou Cell, Corning Jerry, Huahai Pharmaceutical, Tracy Pharmaceutical, Zheng Da Tianqing and other companies have also entered the phase III clinical trials.
Cinda Bio has been approved for listing, and Junshi is still in Phase II clinical practice.
Adalimumab injection: Cinda biological anti-TNF-α monoclonal antibody supported by the national major new drug creation project. It was officially approved for marketing by the State Pharmaceutical Products Supervision and Administration (NMPA) on September 3, 2020, and is used to treat rheumatoid arthritis, ankylosing spondylitis and psoriasis. Shi Jun has submitted an application for listing. Adalimumab (Hummel) is the first fully humanized monoclonal antibody against tumor necrosis factor -α (TNF-α) developed by AbbVie. At the end of 20 19, adalimumab of Baiaotai and Haizheng were successively approved to purchase the lowest quotation 1 150 yuan. Domestic adalimumab began to increase its volume. Baiaotai's semi-annual report in 2020 showed that its domestic sales of adalimumab injection reached 48,786,400 yuan. Among them, Fu Honghanlin, Zheng Da Tianqing and other similar drugs are also under review and approval.
TIGIT: Pre-clinical research in Shi Jun, Cinda Bio is in the 1 stage (Baekje Shenzhou is progressing faster, and companies with the same target layout include Fu Honghanlin, Baiaotai, Kangfang Bio, Hengrui Pharma, Shenzhou Cell ...).
PCSK9 target: Cinda and Junshi have entered the third phase with the fastest clinical progress (7 companies are in the layout, Hengrui Phase II, Xinlitai 1 phase), and Junshi has been introduced through Zhi Zhi Bio.
CTLA-4: Preclinical Study of Junshi Biology, Cinda Biology 1 period. (Other enterprises under research include Hengrui Pharma, Cornerstone Pharmaceutical, Corning Jerry and Kangfang Bio "20 15 sold to Merck for $200 million").
IL-2: Cinda Bio independently developed the first Follow in China, and you actually introduced two models through capital. The IL-2 1 fusion protein of Anvita and the biological IL-2 drug LTC002 were introduced.
Bispecific antibody: Jun Shi was introduced through Revitope, and five bispecific antibodies were constructed by using the latter's TEAC technology. At present, the target of preclinical research has not been announced, but from the perspective of platform technology, TEAC is actually trispecific (2 TAA antibodies and 1 cd3 antibody), and the basic target is CD3.
Cinda Bio constructed several bispecific antibodies with PD-L 1 nano-antibody. Cinda Bio-PD-L 1 nano-antibody and KN-035 from the voice come from the same technology platform (Shen He Wan Yakun). In addition to a series of double antibodies built around PD-L 1 nano-antibody, Cinda Bio also introduced the double antibody technology platform of Anmai Bio, Hanmei Pharmaceutical and Roche. The FTI-Ig of Anmai Bio is a Fab series double antibody technology. At present, there are no two kinds of double antibodies based on this cooperation. The double antibody introduced into Hanmei Pharmaceutical by Cinda Bio is PD- 1/HER2 double antibody IBI3 15. The double antibody technology platform of Hanmei Pharmaceutical Co., Ltd. is the cooperation of Pentambody, Cinda Bio and Lilly Company, and the Azymetris double antibody technology introduced by Lilly Company from Zymeworks has developed bispecific antibody ibi3 1/PD-L 1. In addition, the most important thing for Cinda is to reach another important cooperation with Roche 2: 1 TCB double antibody.
6, different target layout
Junshi Bio: IL-2 1 (imported from Anvita); BLyS antibody (introduced by Huaxin Kangyuan) Trop-2 ADC (introduced by Duoxi Bio) neutralizing antibody (cooperated by Chinese Academy of Sciences), IL- 17A monoclonal antibody, CGRP targeting, CDK inhibitor (introduced by Runjia Medicine) and BTLA monoclonal antibody (independently developed for the first time in the world).
Cinda Bio: VEGF fusion protein (Taiwan Yuanxiang Cooperation) CAR-T (Reindeer Medical, Roche General CAR-T) inhibitor OXM3 (GLP- 1/GcG double targets introduced from Lilly), CD47, OX40, RANKL, LIG3.
7. Overview of Cinda Bio VS Junshi Bio
The layout of Junshi Biological and Cinda Biological are similar, and the immune detection point is the development focus. At the same time, through cooperation in the layout of autoimmune diseases, diabetes and other treatment areas.
Cinda's goal layout is basically to "borrow chickens and lay eggs", so cooperate with others or introduce other people's technology platforms to build their own products. Borrow someone else's beautiful chicken to make big round eggs. For example, the earliest PD 1 was introduced from adimab, and even a series of immune checkpoint antibodies including CD47, OX40, TIGIT, LAG-3 and PCSK9 antibodies were introduced from adimab. Including all human monoclonal antibodies and antibody-related drugs developed by RenMab TM mice with independent intellectual property rights in Biosaitu. Even today's nano-antibodies come from Wan Yakun's technical platform. Other double antibodies are HER2 antibodies from Roche, Han Mei, zymeworks, Lilly and the University of Zurich.
The goal layout of the military adviser in the early stage is basically to "raise chickens and lay eggs", raise beautiful chickens and lay their own eggs. For example, antibodies such as PD 1, BTLA, IL- 17A were independently developed. Junshi Bio has a super-class "chicken raising" antibody integration technology platform. From the initial antibody research and development and industrial technology platform to protein expression, drug research, preparation screening, antibody engineering transformation, cell line construction, detection method establishment, large-scale production and testing, it has a first-class efficient and advanced foundation. This is also one of the reasons why Guo Jia and the Team Fund have taken a fancy to Junshi in neutralizing antibody cooperation.
Nowadays, Junshi also draws lessons from Cinda Bio's "borrowing chickens to lay eggs" model and quickly lays out new targets. Because "raising chickens and laying eggs" is slow in the layout of frontier targets, we have to copy Cinda's model and borrow other people's chickens to lay eggs. For example, if we reach a cooperation with Revitope, the two parties will jointly develop "global new" T cells with double antigens by using the protein engineering patent platform of Revitope and the new antibody * * developed by Junshi Bio. Microbial small molecule targeted drugs and monoclonal antibodies of Zhi Dao were also introduced.
Cinda's biological core product PD 1 made a heavy attack to develop large indications for clinical use. Only the popular ADC is not involved in the target layout. Monoantibodies, antibodies, fusion proteins, CAR-T and small molecules are available. The target difference from Junshi is VEGF fusion protein (the core product of Kanghong). At present, the new generation of VEGF fusion proteins include Novartis, Friends of Friends, and Rongcang Biological. Among them, the founder of Rongcang Bio is the inventor of Kanghong Pharmaceutical's core products, and the founder of Cinda, Dr. Yu, is a successful researcher.
The double antibody of VEGF fusion protein was evaluated as "the most perfect design" by the insiders, which solved the fatal defect of similar drugs in the world at present (which is why I said that the core products of Kanghong Pharmaceutical can't make up for the fact that they have become backward products no matter how many indications are given); CD47, OX40 and Junshi have not been laid out yet. At present, the best clinical data of OX40 is Baekje, and the clinical data show that it may have a wide range of curative effects beyond PD 1. The antibody of IL-23 is hybridoma humanized antibody, which is the first time that the yeast display library has returned to hybridoma (after the departure of Liu Xiaolin, the core figure), and the layout of double antibodies far exceeds that of Junshi. At present, there are PD-L 1/CD47 nano-antibodies IBI322, PD-L 1/LAG-3 double antibodies IBI323 and PD-L65438. PD- 1/PD-L 1 bispecific antibody IBI3 18 is the Azymetris double antibody technology introduced from Zymeworks by Lilly. Hanmei pharmaceutical introduced PD- 1/HER2 double antibody IBI3 15. For the time being, the double antibody technology platform cooperated with Shomai has not found the corresponding product architecture. CAR-T has no layout, but Cinda layout was introduced through Reindeer Medical and Roche GM CAR-T.
GLP- 1/GcG double-target inhibitor was jointly developed by Lilly Company. At present, the best dual-target agonist for diabetes is to balance the hypoglycemic and slimming effects of each target.
Shi Jun's core product PD 1 gives priority to "small indications" to gain absolute market share, and every little makes a mickle. Strategically, the market expansion strategies of orphan drug certification and even breakthrough therapy are "quick listing" and "small indications+large indications". TIGIT is the same as JS009 monoclonal antibody. BTLA monoclonal antibody is the first anti-tumor drug in the world. BLyS antibody (introduced from Huaxin Kangyuan) At present, Tatasip, the BLyS/APRIL double-target inhibitor of Rongchang Bio, has entered NDA stage, and UBP- 12 13 of Junshi Bio is in the first clinical stage. The clinical progress of TIGIT inhibitor is the fastest at present, and Baekje is the best product in the world.
COVID-19 neutralizing antibody is the first drug to enter the second phase of clinical practice in China, and its overseas rights and interests are commercialized by Lilly Company. Baekje Shenzhou and Danxun Neutralizing Antibody entered the first phase, including 1 cooperation between Tsinghua University and Shengbo, and followed the hot target of Fu Hong to start layout. In fact, Baekje Shenzhou Neutralizing Antibody has more valuable space for overseas rights and interests.
Among the core figures of the enterprise, Cinda subdivides the hierarchical management system, and everyone is responsible for managing their own post system. The core figures of Junshi are basically involved in enterprise project research and development. Cattle.
Through the above comparison, we can see the revenue growth and market situation of the core products PD 1 of Cinda Bio and Junshi Bio. Cinda has a larger volume, and its instruction layout is heavier. The military adviser takes the small indication first, and then the heavy indication is trapezoidal access.
Cinda has three products listed on biological drugs, and only the same Adamu will be listed soon.
In the research pipeline, Cinda's research and development progress is faster in the same target layout, and Cinda's layout in different target layouts is more cutting-edge than Junshi's products and has a broader prospect. For example, in the new generation of biopharmaceuticals, Cinda has now declared six kinds of double antibodies, but you have not. Junshi's double antibody technology platform is basically laid out around cd3 target. Cinda Bio even includes cell therapy, but it doesn't.
Cinda's research products and products on the market are more valuable than Junshi, even if they are equally divided with Lilly. Junshi also has most products that share commercial interests with its partners (such as cdk, p 13k, tnf-a, Blys, VEGF, etc.). ). The biggest highlight of Junshi is that there are no neutralizing antibodies, BLyS antibodies, ADC and BTLA monoclonal antibodies with Cinda, but its value is far less than Junshi's.
So the final conclusion is that the market value of Cinda Bio is greater than Junshi, which is a normal value. Personally, it is a very normal value embodiment that Junshi's current market value is greater than 50%.