By: congratulations
From the successful development of biotechnology to the head of biopharmaceuticals (Cinda and Junshi), the two biopharmaceutical companies from all the way to the very interesting, the following personal insights on the two companies.
1, the development of the enterprise
Cinda Biological
In August 2011, Cinda Biological was founded in Suzhou; in October 2018, Cinda Biological was listed on the main board of the Hong Kong Stock Exchange; in December 2018, Cinda Biological PD-1 Sindolizumab (trade name: Dabersu) was launched as a 3L classical Hodgkin's lymphoma was officially approved, becoming the second domestic PD-1 monoclonal antibody approved; at present, we have established a product chain including 23 new drug varieties, covering a variety of disease areas such as oncology, metabolic diseases, autoimmunity, etc., of which 6 varieties have been selected for the national special project of "creation and manufacture of new drugs of major importance", and 4 products have been listed (Sindilizumab Among them, 6 products have been selected for the National New Drug Innovation and Manufacturing Special Project, 4 products have been listed on the market (Sindilizumab Injection (trade name: Dabexu, English trademark: TYVYT), Bevacizumab Injection (trade name: DanyuTong, English trademark: BYVASDA), Adalimumab Injection (trade name: Sulindacin, English trademark: SULINNO), and Dabvar (rituximab injection), which has obtained the approval of the NMPA for marketing and sale, and 4 products have entered into the phase III or pivotal clinical study, and 15 products have entered into or are currently in the phase III or pivotal clinical study. An additional 15 products have entered or will soon enter clinical studies.
Cinda Bio has become the only pharmaceutical company in China with 4 monoclonal antibody drugs on the market.
Junshi Bio
2, business development and performance
Both currently on the market commercialized products are PD1.
Cinda Bio
In 2017-2019, the revenue was 0.19, 0.095 and 1.048 billion yuan. 2019 revenue increased significantly due to the listing of PD-1 monoclonal antibody, and Sindelizumab sold 1.016 billion yuan in 2019. R&D expenses in the past three years were $612 million, $1.222 billion and $1.295 billion, respectively.The company's revenue in the first half of 2020 was $980 million, a year-on-year jump of 185%, of which the revenue was mainly contributed by Dabexu ($920 million). Gross profit margin of 81.2% in the first half of the year, compared with last year's 88.1% gross profit decline is mainly due to product price cuts. R&D investment in the first half of the year increased by 20.4% year-on-year to 810 million, while selling expenses increased by 67.5% year-on-year to 447 million. Adjusted net profit was -454 million, a 32% year-on-year loss reduction.
The manufacturing site is currently operating five 1,000-liter bioreactors to support the production needs of Dabexol, Dyauto and other product candidates in the pipeline. An additional six 3,000 liter stainless steel bioreactors have completed GMP commissioning and process validation, expanding the Company's total capacity to 23,000 liters.
Junshi Bio
From 2017-2019, revenues will be $0.54, $0.03 and $775 million, with a compound annual growth rate of 278.8%, and net income attributable to the mother of the company will be -$317, -$723, and -$747 million, respectively.R&D expenses will be $122 million, $275 million, $538 million, respectively, from 2016-2019 and 946 million yuan. total revenue of RMB575 million in the last quarter of 2020, an increase of 86% year-on-year. R&D expenses amounted to RMB709 million, representing a significant increase of 92% over the same period last year.
Production bases currently have 3,000L fermentation capacity (6*500L) in addition to Suzhou Wujiang, which is currently GMP certified, and a 30,000-liter scale antibody production base (5*3*2,000L disposable fermenters) in Lingang, which is in the first phase of construction and commissioning.
3. Corporate Core Team
Cinda Biotech: Cinda Biotech has increased from approximately 2,000 employees as of December 31, 2019 to 2,600 employees as of June 30, 2020 in the first half of 2020, of which more than 750 are in charge of R&D, more than 1,100 are in charge of commercialization, and more than 500 are in charge of CMC. The Company will have over 750 employees for R&D, over 1,100 employees for commercialization, over 500 employees for CMC, and over 200 employees for general and administrative functions.
Cinda Bio's core personnel include Yu Dechao (founder), Liu Xiaolin (former VP, left in 2018 to found Pumice, has filed 2 double antibiotics), Kan Hong (VP, R&D, QC and registration filing), Zhou Qinwei (coo), Liu Junjian (VP, core R&D), Xu Wei (VP, manufacturing and process development), Ronnie Ede (cfo), also includes core personnel Hu Guojian (VP, R&D and process development), and also includes core personnel Hu Guoguo (VP, commercialization). ), also including core personnel Hu Guoqiang, Sun Zuoyu, and Yu Cailin ......
Cinda Bio Patent Reserve:
Junshi Bio
Junshi Bio had about 200 employees in 2017***, and as of the end of 2019, the company*** had 1,421 employees, of which there were 415 technology research and development personnel and 360 sales personnel, accounting for 29.2% and 25.28%, respectively. Today Junshi has over 2,000 people, of which 30% are R&D staff and about 700 are commercialization operations staff.
Junshi Bio's core people include: Junshi core team members Dr. Sheng Yao (Vice President), Dr. Xin Duan (Vice President, Clinical Research) Dr. Hai Wu (Chief Scientist), Dr. Hui Feng (COO), Zhuo-Bing Zhang (Vice President) and Ning Li (CEO) are y involved in the company's research and development work. Jun Xiong (founding partner), Gang Wang (VP, QC), Net Han (VP, marketing) Bo Chen (founding partner, who has left in 2016 to found Konoa Biopharmaceuticals in Chengdu)
Junshi Bio Patent Reserve:
4. Antibody Platform
Cinda Biologics
(The above image is sourced from Armstring Biologics)
Junshi Bio
5. Similarities and Differences in Target Layout
R&D Pipeline:
Cinda Bio
Junshi Bio
Same Target Layout:
PD1: Junshi Bio (more than 30 clinical trials are being conducted in parallel, of which 15 key registration clinics are targeting a number of expanded indications such as non-small cell lung cancer, esophageal cancer, triple-negative breast cancer, melanoma, etc.).
Cinda Bio (layout indications more than 25 clinical trials, including, non-small cell lung cancer, hepatocellular carcinoma, advanced gastric cancer and esophageal cancer, etc. is the largest market size of the indications)
PDL1: Jun Chen R&D Project Progress Phase 2, Cinda does not have a single-target layout, Cinda Bio in 2017 applied for a patent on PD-L1 nano antibody CN201710657665, the first inventor of the patent is Shen Xiaoning. In order to carry out a number of PDL1 double antibody (PD-L1/TGF-β, PDL1/CD47, PDL1/OX40, PDI1/LAG-3)
Bevacizumab: the original drug is Roche's "Anvitin" 2019 sales of up to 7.494 billion U.S. dollars.2019 On December 6, Qilu Pharmaceutical's bevacizumab (trade name "Ankoda") was approved for listing, successfully taking the first generic. 2020, since April 2020, Green Leaf Pharmaceuticals / Boan Biologicals, Beda Pharmaceuticals / Hai Zheng Biologicals, Hengrui Pharmaceutical's Shengdia Biologicals, Biotek Biologicals, Dongyao Pharmaceuticals, have submitted bevacizumab biosimilar new drug listing application. New Drug Listing Application (NDLA) for bevacizumab biosimilars. There are at least 20 companies in the pipeline for bevacizumab biosimilars. In addition to the above listed or declared for listing, Hualan Gene, Fuhong Hanlin, Shenzhou Cell, Kangning Jieri, Huahai Pharmaceuticals, Trix Pharmaceuticals, Zhengda Tianqing and many other companies of bevacizumab biosimilars have also entered the phase III clinical trials.
Cinda Bio has been approved for marketing, and Junshi is still in phase II clinicals.
Adalimumab injection: Cinda Bio's anti-TNF-α monoclonal antibody, supported by the National Special Project for the Creation and Manufacture of Major New Drugs (NSPMND), was officially approved for marketing by the National Drug Administration (NMPA) on September 3, 2020, for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis. Junshi has submitted an application for marketing. Adalimumab (Xumeler) is the first fully humanized anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody developed by Abbvie. At the end of 2019, the adalimumab of BIOTEK and Haizheng were approved successively, with the lowest winning price of RMB 1,150 in the collective procurement. Domestic adalimumab began to release volume. Biotest's 2020 half-year report showed that its adalimumab injection domestic sales reached 48,786,400 yuan. Among them, the similar drugs of Fuhong Hanlin and Zhengda Tianqing are also being listed for review and approval.
TIGIT: Junshi preclinical research, Cinda Biological in phase 1 (faster progress has Baiji Shenzhou, the layout of the same target companies are Fuhong Hanlin, Biotest, Kangfang Biological, Hengrui Medicine, Shenzhou Cell .........)
PCSK9 target: Cinda (7 companies in the layout, including Hengrui phase 2, Xinlitai phase 1), Junshi is introduced through Zhidao biology
CTLA-4: Junshi is in preclinical research, Cinda biology in phase 1. (The rest of the research companies include Hengrui Medicine, Keystone Pharmaceuticals, Kangning Jieri, Kangfang Bio "sold to Merck Sharp & Dohme for $200 million in 2015")
IL-2: Cinda Bio is the first Follow in China for independent research and development, while Junshi is introducing two through capital. The introduction of Anwita's IL-21 fusion protein and the introduction of Zhidao Bio's IL-2 drug LTC002.
Bispecific Antibodies: Junshi was introduced through Revitope and utilized the latter's TEAC technology to construct five bispecific antibodies. Currently in preclinical studies targets have not been announced, but from the platform technology TEAC is actually a tri-specific (2 TAA antibodies and 1 CD3 antibody), with the basic target being cd3.
Cinda Biotech constructed several bispecific antibodies using PD-L1 nanobodies. Cinda Bio's PD-L1 nanoantibodies come from the same technology platform (Xiaoning Shen and Yakun Wan) as Centsen Pharmaceuticals' KN-035. In addition to a series of bispecific antibodies built around PD-L1 nanoantibodies, Cinda Bio has also introduced the bispecific antibody technology platforms of Kishimai Bio, Hanmi Pharmaceutical, and Roche. Kishimai Bio's FTI-Ig is a tandem Fab double antibody technology, and there are currently no double antibodies based on this collaboration between the two companies. Cinda Bio's dual antibody introduced to Hanmi Pharmaceutical is the PD-1/HER2 dual antibody IBI315. Hanmi Pharmaceutical's dual antibody technology platform is Pentambody, and Cinda Bio's collaboration with Eli Lilly is the Azymetris dual antibody technology introduced by Lilly from Zymeworks, which develops the PD-1/PD-L1 bispecific antibody IBI318. in addition, Cinda's most significant was another important collaboration with Roche's 2:1 TCB dual antibody.
6. Layout of different targets
Junshi Bio: IL-21 (introduced from Anwita); BLyS antibody (introduced from Huaxin Kangyuan); Trop-2 ADC (introduced by Doshi Biotech); Neutralizing antibody (cooperation with Chinese Academy of Sciences); IL-17A monoclonal antibody; CGRP target; CDK inhibitor (introduced by Runjia Pharmaceuticals); BTLA monoclonal antibody (introduced by Ruijia). Pharmaceuticals introduced), BTLA monoclonal antibody (independent research and development of the world's first)
Cinda Biotechnology: VEGF fusion protein (Taiwan Yuanxiang cooperation) CAR-T (reindeer health care, Roche generic CAR-T) inhibitor OXM3 (introduced from Lilly GLP-1/GcG dual target), CD47, OX40, RANKL, LIG3.
7, Cinda Biotechnology Vs.
Cinda in the target layout is basically "borrowed chicken to lay eggs", or cooperation to use other people's or the introduction of other people's technology platform to build their own products. Borrowing someone else's beautiful chicken to lay big, round eggs. For example, the earliest PD1 was introduced from adimab, and even a series of immune-checkpoint antibodies were introduced from adimab, including target CD47, OX40, TIGIT, LAG-3, and PCSK9 antibodies. In the later stage, we used BIOCTU's RenMab TM mice with proprietary intellectual property rights to develop fully human monoclonal antibodies and antibody-related drugs. Even today's nano-double antibody is from Vanya Kun's technology platform. Other dual antibodies are HER2 antibodies from Roche, Hanmi, zymeworks, Eli Lilly and the University of Zurich.
Junshi's target layout is basically a "chicken and egg" model, raising beautiful chickens and laying eggs that belong to their own interests. For example, the self-developed PD1, BTLA, IL-17A monoclonal antibody. Junshi Biological has a superb "chicken" antibody integration technology platform, from the initial antibody development and industrialization technology platform, to carry out protein expression, pharmacological research, preparation screening, antibody engineering transformation, cell line construction, test method establishment, large-scale production and testing have the industry's first-class high-efficiency and advanced foundation. This is Guo Jia, one of the reasons why the team fund in the neutralization of antibody cooperation in the Junshi Biological.
And now Junshi is also learning from Cinda Biologicals' "borrowed chicken to lay eggs" model to quickly layout new targets, because "raising chickens to lay eggs" in the layout of cutting-edge targets is slower, so we have to copy the model of Cinda, borrowing other people's chickens to lay eggs, for example, and Revitope reached a cooperation, the two sides have reached a cooperation with Revitope. For example, the two companies reached a cooperation with Revitope, the two sides will use Revitope's protein engineering patent platform and the new antibody developed by Junshi Biologicals, **** with the research and development of dual-antigen targeted "global new" T-cell chimeric activation of cancer therapies. We have also introduced small molecule targeting drugs from Microcosmos and monoclonal antibodies from Zhidao.
Cinda Biotechnology in the core product PD1 is a heavy attack, favoring large indications for clinical development. In the target layout only the popular ADC has not yet involved. From the monoclonal antibody, double antibiotic, fusion protein, CAR-T, small molecules, a full range, and Junshi target difference is VEGF fusion protein (Kanghong's "Longmu" core product), the current generation of VEGF fusion proteins have Novartis, Friends and Rongcang Biological for the strongest rivals, which Rongcang Biological founder that is The founder of Rongcang Bio is the inventor of Kanghong Pharmaceutical's core product "Longmu", and the founder of Xinda, Dr. Gui, is the successor of the research and development, and these two can be said to be the most certain of the success rate of the research and development of VEGF fusion proteins of the double antibiotic companies.
VEGF fusion protein double antibiotic is evaluated by industry insiders as "having the most perfect design", cracking the fatal defect of the current international similar drugs treating the symptoms but not the root cause (that's why I said in the early stage that Kanghong Pharmaceutical's core product can't make up for the fact that it has already become a laggard product by opening up even more indications); CD47, OX40, and Junshi are also the most important products in the industry. OX40, Junshi has not yet layout, the best clinical data of OX40 is Baizi, clinical data show that it is possible to have a wide range of efficacy beyond the PD1. IL-23 antibody using hybridoma humanized antibody, this is the first time that the yeast demonstration library to return to the hybridoma (after the departure of the core character Liu Xiaolin), dual-antibody layout is far more than Junshi Biotechnology, the current declaration of the PD-L1/CD47 nano-antibody IBI322, and PD-L1/CD47 nano-antibody IBI322, and PD-L1/CD47 nano-antibody IBI322. antibody IBI322, and PD-L1/LAG-3 dual antibody IBI323, PD-L1/OX40 dual antibody IBI327, PD-1/PD-L1 bispecific antibody IBI318 is Azymetris dual antibody technology introduced by Eli Lilly from Zymeworks. PD-1/HER2 dual antibody IBI315 was introduced to Hanmi Pharmaceutical. The dual-antibody technology platform with Kishimai has not found the corresponding product structure for the time being. CAR-T Junshi has no layout, and Xinda layout is introduced through Reindeer Medical and Roche General CAR-T.
GLP-1/GcG dual-target inhibitors from Eli Lilly cooperation in research and development, the current optimal diabetes dual-target agonists, mainly to balance the role of each target glucose, weight loss.
The core product PD1 is prioritized in the layout of the characteristics of the "small indications", to obtain the absolute market share, the accumulation of a small amount into a large number. The strategy adopted is orphan drug certification or even breakthrough therapies "rapid listing", "small indications + large indications" market expansion strategy. TIGIT and JS009 monoclonal antibody is the same. BTLA monoclonal antibody is the world's first anti-tumor drugs into the clinic. entered the NDA stage, Junshi Bio's UBP-1213 is in clinical phase I. TIGIT inhibitors currently have the fastest clinical progress of Baiji and Xinda, and Baiji is currently the world's best product.
Xin Guan neutralizing antibody is the first domestic drug to enter clinical phase II, and the offshore interest is commercialized by Eli Lilly, while the neutralizing antibody of Baizi Shenzhou and Daxun is in phase I, including the cooperation between Tsinghua University and Shengbo is also in phase 1, and Fuhong, which is following the popular targets, has started to lay out, and in fact, Baizi Shenzhou's neutralizing antibody has more value space for the offshore interest.
In the core of the enterprise Cinda is subdivided hierarchical management system, each person is responsible for the management of their own position system. And Junshi's core person is basically all involved in the enterprise project research and development. Cow.
Through the above comparison we see Cinda Biological and Junshi Biological core product PD1 revenue growth and market situation, Cinda's release is greater, the layout of the indications Cinda is also more heavyweight, Junshi to small indications first, and then heavyweight for ladder access.
On biosimilars Cinda has three listed products, Junshi has only the same Adalmu is about to be listed.
In the research pipeline in the same target layout on the Cinda R & D progress faster, different target layout on the layout of the Cinda layout is also more cutting-edge, but also more than Junshi product prospects. For example, in the new generation of biopharmaceutical double antibiotic, Cinda now declared six double antibiotic, while Junshi is not, Junshi introduction of double antibiotic technology platform basically centered around the cd3 target to carry out the layout. Cinda biology even includes cell therapy Junshi is not.
Cinda's in-development products and in-market products even if and Lilly equal share of the market value of the product program is greater than Junshi, Junshi also has most of the products to be shared equally with the partner commercial interests (such as cdk, p13k, tnf-a, Blys, vegf ......), Junshi's biggest highlights are with Cinda The biggest highlight of Junshi is the neutralizing antibody, BLyS antibody, ADC, BTLA monoclonal antibody that it doesn't have, but the value is far less than the new generation of biological targets of Cinda Biologicals that are more commercially valuable.
So the final conclusion is that Cinda biological market value is greater than Junshi is the normal value, I think the current greater than 50% of the market value of Junshi are very normal value.