Author: Congratulations on the New Year

From the successful development of biotechnology to the leading biopharmaceutical companies (Innovent and Junshi), these two biopharmaceutical companies have been very successful all the way. It’s interesting. Let’s talk about my personal views on these two companies.

1. Enterprise development history

Innovent Biologics

In August 2011, Innovent Biologics was established in Suzhou; Listed on the main board of the Hong Kong Stock Exchange; in December 2018, Innovent Biologics' PD-1 sintilimab (trade name: Tyvyt) was officially approved for 3L classic Hodgkin lymphoma, becoming the second approved drug Domestic PD-1 monoclonal antibody; currently has established a product chain including 23 new drug varieties, covering multiple disease fields such as tumors, metabolic diseases, autoimmunity, etc., of which 6 varieties have been selected into the national "Major New Drug Creation" special project, and 4 products Obtained the market (sintilimab injection, trade name: Tyvyt, English trademark: TYVYT; bevacizumab injection, trade name: Dayutong, English trademark: BYVASDA; adalimumab injection, Trade name: Su Lixin, English trademark: SULINNO), Dabohua (Rituximab Injection), has been approved for marketing by NMPA, 4 products have entered Phase III or critical clinical studies, and 15 other products have been Entering or about to enter clinical research.

Innovent Biologics has become the only pharmaceutical company in China with four monoclonal antibody drugs on the market.

Junshi Biotech

2. Business development and performance

Both of the two currently commercialized products on the market are PD1.

Innovent Biologics

From 2017 to 2019, the revenue was 0.19, 0.095 and 1.048 billion yuan respectively. The reason for the significant increase in revenue in 2019 is due to the launch of PD-1 monoclonal antibody. Sintilimab sold for 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. In the first half of 2020, the company's revenue was 980 million, a year-on-year increase of 185%, of which revenue was mainly contributed by Tybushu (920 million). The gross profit margin in the first half of the year was 81.2%. The decline in gross profit from last year's 88.1% was mainly due to product price reductions. In the first half of the year, R&D investment increased by 20.4% year-on-year to 810 million, and sales expenses increased by 67.5% year-on-year to 447 million. Adjusted net profit was -454 million, a year-on-year loss reduction of 32%.

The production base is currently operating five 1,000-liter bioreactors to support the production needs of Tyvyt, Davytong and other product candidates in the pipeline. Another six 3,000-liter stainless steel bioreactors have completed GMP debugging and process verification, expanding the company's total production capacity to 23,000 liters.

Junshi Biotechnology

From 2017 to 2019, 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 parent was -3.17 , -723 and -747 million yuan. R&D expenses from 2016 to 2019 were 122 million yuan, 275 million yuan, 538 million yuan and 946 million yuan respectively. Total revenue in the first quarter of 2020 was RMB 575 million, a year-on-year increase of 86%. R&D expenses were RMB 709 million, a significant increase of 92% compared with the same period last year.

In addition to Suzhou Wujiang, the production base currently has a fermentation capacity of 3,000L (6*500L). At present, the Suzhou Wujiang production base has obtained GMP certification. There is also a 30,000-liter antibody production base built and put into operation in Lingang. Production base (5*3*2000L disposable fermentation tank).

3. Corporate core team

Innovent Biologics: In the first half of 2020, Innovent Biologics increased from approximately 2,000 employees as of December 31, 2019 to 6,000 employees as of June 2020. As of March 30, we had 2,600 employees, of which more than 750 employees were responsible for R&D, more than 1,100 employees were responsible for commercialization, more than 500 employees were responsible for CMC, and approximately 200 employees were responsible for general and administrative functions.

The core figures of Innovent Biologics include: Yu Dechao (founder), Liu Xiaolin (former vice president, left to found Pumis in 2018, and has applied for 2 dual antibodies), Kan Hong (vice president, R&D, quality control and registration application), Zhou Qinwei (coo), Liu Junjian (vice president, core R&D personnel), Xu Wei (vice president, production and process development), Ronnie Ede (cfo), and also core figures Hu Guoqiang, Sun Zuoyu, Yu Cailing... < /p>

Innovent Biologics’ patent reserves:

Junshi Biologics

Junshi Biologics had about 200 employees in 2017***. As of the end of 2019, the company** *There are 1,421 employees, including 415 technical R&D personnel and 360 sales personnel, accounting for 29.2% and 25.28% respectively. Today, Junshi has more than 2,000 employees, 30% of whom are R&D personnel, and about 700 are commercial operation personnel.

The core figures of Junshi Biotech include: Junshi core team members Dr. Yao Sheng (Vice President), Dr. Duan Xin (Vice President, Clinical Research), Dr. Wu Hai (Chief Scientist), Dr. Feng Hui (Chief Operating Officer) Officer), Zhang Zhuobing (Vice President) and Li Ning (CEO) are deeply involved in the company's R&D work. Xiong Jun (founding partner), Wang Gang (vice president, quality control), Han Jing (vice president, marketing) and Chen Bo (founding partner, left to found Connoya Biomedicine in Chengdu in 2016)

Junshi Biologics’ patent reserves:

4. Antibody platform

Innovent Biologics

(The above picture is from Armstring Biopharmaceutical Information)

Junshi Biologics

5. Similarities and differences in corporate target layout

R&D pipeline:

Innovent Biologics

Junshi Biologics

On the same target layout:

PD1: Junshi Biologics (is simultaneously conducting more than 30 clinical trials, including 15 key registered clinical trials) Multiple expanded indications such as non-small cell lung cancer, esophageal cancer, triple-negative breast cancer, melanoma, etc.)

Innovent Biologics (more than 25 clinical trials for indications, including non-small cell). Lung cancer, hepatocellular carcinoma, advanced gastric cancer and esophageal cancer are the indications with the largest market size)

PDL1: Junshi’s research project is in phase 2, Innovent does not have a single target layout, Innovent Biologics 2017 Applied for PD-L1 nanobody patent CN201710657665. The first inventor of this patent is Shen Xiaoning. A number of PDL1 double antibodies (PD-L1/TGF-β, PDL1/CD47, PDL1/OX40, PDI1/LAG-3) have been developed.

Bevacizumab: The original drug is Roche’s “ Avastin's sales in 2019 reached US$7.494 billion. On December 6, 2019, Qilu Pharmaceutical’s bevacizumab (trade name “Anchor”) was approved for marketing and successfully obtained the first generic version. Since April 2020, Luye Pharmaceuticals/Boan Biologics, Beida Pharmaceuticals/Haizheng Biologics, Hengrui Pharmaceutical's Shengdia Biologics, Biotech Biologics, and Dongyao Pharmaceutical have all submitted bevacizumab biopharmaceuticals. New drug marketing applications for similar drugs. Subsequently, at least 20 companies are developing bevacizumab biosimilars. In addition to the above-mentioned companies that have been listed or have applied for listing, the bevacizumab monotherapy of Hualan Gene, Henlius, China Cell, Alphamab, Huahai Pharmaceuticals, Terex Pharmaceuticals, Chia Tai Tianqing and many other companies Antibiosimilars have also entered phase III clinical trials.

Innovent Biologics has approved marketing, and Junshi is still in phase II clinical trials.

Adalimumab injection: Innovent's anti-TNF-α monoclonal antibody received special support from the National Major New Drug Creation Project and was officially approved by the National Medical Products Administration (NMPA) on September 3, 2020. ) for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis. Junshi has submitted an application for listing.

Adalimumab (Humira) is the first fully humanized anti-tumor necrosis factor-α (TNF-α) monoclonal antibody developed by Abbvie. At the end of 2019, Biotech and Hisun Adalimumab has been approved successively, with the lowest winning bid price in centralized procurement being 1,150 yuan. Domestic adalimumab has begun to increase in volume. Biotech's 2020 semi-annual report shows that its domestic sales of adalimumab injection reached 48.7864 million yuan. Among them, similar drugs from Henlius and Chia Tai Tianqing are also undergoing review and approval for marketing.

TIGIT: Junshi is in preclinical research, Innovent Biologics is in phase 1 (BeiGene is progressing faster, and companies with the same target layout include Henlius, Biotech, and Kangfang Biologics) , Hengrui Medicine, China Cell...)

PCSK9 target: Innovent and Junshi have made the fastest progress and have entered Phase III clinical trials (7 companies are in the process of layout, including Hengrui Phase 2, Xinli CTLA-4: Junshi Biologics is in preclinical research, and Innovent Biologics is in Phase 1. (Other companies under research include Hengrui Pharmaceuticals, CStone Pharmaceuticals, Alphamab, and Kangfang Biologics, which were sold to Merck for US$200 million in 2015.)

IL-2: Innovent Biologics is independent Developing the first Follow in China, Junshi introduced two models through capital. Introduced Anwita's IL-21 fusion protein and Zhidao Biological's IL-2 drug LTC002.

Bispecific antibodies: Junshi introduced it through Revitope and used the latter's TEAC technology to construct 5 bispecific antibodies. The target of preclinical research has not yet been announced, but from the perspective of platform technology, TEAC is actually a trispecific (2 TAA antibodies and 1 CD3 antibody), and the basic target is cd3.

Innovent Biologics has constructed multiple bispecific antibodies using PD-L1 nanobodies. Innovent Biologics' PD-L1 nanobody and Simcere Pharmaceuticals' KN-035 come from the same technology platform (Shen Xiaoning and Wan Yakun). In addition to a series of dual-antibodies built around PD-L1 nanobodies, Innovent has also introduced dual-antibody technology platforms from ApMatic, Hanmi Pharmaceuticals, and Roche. Imaging's FTI-Ig is a tandem Fab double-antibody technology. Currently, there are no two double-antibodies based on this cooperation. The dual antibody introduced by Innovent Biologics from Hanmi Pharmaceutical is the PD-1/HER2 dual antibody IBI315. Hanmi Pharmaceutical's dual-antibody technology platform is Pentambody. The collaboration between Innovent Biologics and Eli Lilly is the Azymetris dual-antibody technology introduced by Eli Lilly from Zymeworks to develop the PD-1/PD-L1 bispecific antibody IBI318. In addition, the most important thing for Innovent is that it has reached another important cooperation with Roche’s 2:1 TCB dual antibody.

6. Different target layouts

Junshi Biological: IL-21 (introduced from Anwita); BLyS antibody (introduced from Huaxin Kangyuan) Trop-2 ADC (Duoxi) Biological introduction) Neutralizing antibodies (in cooperation with the Chinese Academy of Sciences), IL-17A monoclonal antibodies, CGRP targets, CDK inhibitors (introduced by Runjia Pharmaceuticals), BTLA monoclonal antibodies (independently developed, the first in the world)

Innovent Biologics : VEGF fusion protein (cooperated by Taiwan Yuanxiang) CAR-T (Reindeer Medical, Roche Universal CAR-T) inhibitor OXM3 (GLP-1/GcG dual target introduced from Eli Lilly), CD47, OX40, RANKL, LIG3.

7. Summary of Innovent Biologics VS Junshi Biologics

Junshi Biologics and Innovent Biologics have similar layouts. Immune checkpoints are the focus of development, and they also develop autoimmune diseases through cooperation. , diabetes and many other treatment areas.

Cinda's target layout is basically "borrowing chickens to lay eggs", and it cooperates to use other people's or introduce other people's technology platforms to build its own products. Borrow other people's beautiful chickens to lay big, round eggs. For example, the earliest PD1 was introduced from adimab, and a series of immune checkpoint antibodies including target CD47, OX40, TIGIT, LAG-3, and PCSK9 antibodies were even introduced from adimab. This includes the later use of Biocytogen’s RenMab TM mice with independent intellectual property rights to develop fully human monoclonal antibodies and antibody-related drugs. Even today’s nano-double antibodies come from Wanyakun’s technology platform.

Other double antibodies are HER2 antibodies from Roche, Hanmi, Zymeworks, Eli Lilly and the University of Zurich.

Junshi’s early target layout is basically a “chicken-laying and egg-laying” model, raising beautiful chickens and laying eggs that belong to their own rights. For example, independently developed PD1, BTLA, IL-17A monoclonal antibodies and other antibodies. Junshi Biotech has a first-class "chicken-raising" antibody integrated technology platform. From the initial antibody development and industrialization technology platform, it carries out protein expression, pharmaceutical research, preparation screening, antibody engineering, cell line construction, test method establishment, Large-scale production and inspection have the industry's first-class, efficient and advanced foundation. This is one of the reasons why the Guo Jia Team Fund is interested in Junshi Biotech in its neutralizing antibody cooperation.

Today, Junshi is also learning from Innovent Biologics' "borrowing chickens and laying eggs" model to quickly deploy new targets, because "raising chickens and laying eggs" is slower in the layout of cutting-edge targets, so We have no choice but to copy Innovent's model and borrow other people's chickens to lay eggs. For example, we have reached a cooperation with Revitope. The two parties will use Revitope's protein engineering patent platform and the new antibodies developed by Junshi Biologics to jointly develop dual-antigen targets. A "global new" T-cell chimeric activation cancer therapy. We also introduced small molecule targeted drugs from MicroBio and monoclonal antibodies from Zhidao Biology.

Innovent Biologics has launched a major attack on its core product PD1, which is being developed for clinical trials in major indications. In the target layout, only the popular ADC has not yet been involved. It has everything from monoclonal antibodies, double antibodies, fusion proteins, CAR-T, and small molecules. The target difference from Junshi is VEGF fusion protein (Zikanghong's "Langmu" core product), the current new generation of VEGF fusion protein Novartis, Friends of Friends and Rongcang Biotech are the strongest competitors. Among them, the founder of Rongcang Biotech is the inventor of "Langmu", the core product of Kanghong Pharmaceutical, and Dr. Yu, the founder of Innovent, is a successful researcher. It can be said that the company with the greatest certainty of research and development success rate is the dual antibody for VEGF fusion protein.

The VEGF fusion protein dual antibody has been evaluated by industry insiders as "having the most perfect design" and has solved the fatal flaw of current international similar drugs that treat the symptoms but not the root cause (this is why I mentioned Kanghong Pharmaceutical's core product earlier) No matter how many indications it opens, it cannot make up for the fact that it has become a backward product); CD47, OX40, and Junshi have not yet laid out their plans. The best clinical data for OX40 currently is Baekje, and clinical data shows that it may have a broad spectrum beyond PD1. General efficacy. The IL-23 antibody uses a hybridoma humanized antibody. This is the first time that the yeast display library has returned to hybridoma (after the core figure Liu Xiaolin left). The dual antibody layout far surpasses Junshi Biological. Currently, PD-L1/CD47 nanoparticles have been applied for. Antibody IBI322, as well as PD-L1/LAG-3 dual antibody IBI323, PD-L1/OX40 dual antibody IBI327, and PD-1/PD-L1 bispecific antibody IBI318 are Azymetris dual antibody technology introduced by Eli Lilly from Zymeworks. The PD-1/HER2 dual antibody IBI315 was introduced to Hanmi Pharmaceutical. The dual-antibody technology platform cooperating with Amai has not yet found a corresponding product structure. CAR-T Junshi has no layout, and Innovent's layout is introduced through Reindeer Medical and Roche Universal CAR-T.

GLP-1/GcG dual-target inhibitors are jointly developed by Eli Lilly. Currently, the best dual-target agonists for diabetes mainly balance the hypoglycemic and weight-loss effects of each target.

Junshi’s core product PD1 gives priority to the layout of featured “small indications” to gain absolute market share and make up for the loss. Strategically, it adopts the market expansion strategy of orphan drug certification or even "quick launch" of breakthrough therapies, and "small indications + large indications". The same applies to TIGIT and JS009 monoclonal antibodies. BTLA monoclonal antibody is the world's first anti-tumor drug to enter clinical practice. The BLyS antibody (introduced from Huaxin Kangyuan) is currently in the domestic Rongchang Biotech's BLyS/APRIL dual-target inhibitor Tatacept, which has entered the NDA stage. Junshi Biotech's UBP-1213 is in clinical phase I, and the TIGIT inhibitor is currently in clinical progress. The fastest ones are Baekje and Cinda. Currently, Baekje is the best product in the world.

The new coronavirus neutralizing antibody is the first domestic drug to enter the second phase of clinical trials. The overseas rights are commercialized by Eli Lilly. The neutralizing antibodies of BeiGene and Danxun have entered the first phase, including Tsinghua University and Shengbo is also cooperating in the first phase, and Fuhong, which is following popular targets, has begun to make plans. In fact, BeiGene’s neutralizing antibodies have more value in overseas rights and interests.

Among the core figures of the company, Cinda has a subdivided and hierarchical management system, with each person responsible for managing their own position system. The core figures of Junshi are basically all involved in corporate project research and development. ox.

Through the above comparison, we can see the revenue growth and market conditions of the core product PD1 of Innovent Biologics and Junshi Biologics. Innovent Biologics has a larger volume, and its indication layout is also more important. Junshi Biologics In fact, we should focus on small indications first, and then focus on the most important ones in a trapezoidal manner.

In terms of biosimilar drugs, Innovent has three products on the market, while Junshi only has the same product, Adamu, which is about to be launched.

On the research and development pipeline, Innovent’s R&D progress is faster in the layout of the same target. In the layout of different targets, Innovent’s layout is also more cutting-edge and has a broader prospect than Junshi’s products. For example, in the new generation of biologic dual antibodies, Innovent has now applied for 6 dual antibodies, while Junshi has none. The dual antibody technology platform introduced by Junshi basically focuses on the CD3 target. Innovent Biologics even includes cell therapy, but Jun actually does not.

Even if Innovent’s products under development and products on the market share the market value of the product projects equally with Eli Lilly, the market value of the product projects is greater than that of Junshi. Junshi also has most of its products and has to share commercial rights equally with its partners (such as cdk , p13k, tnf-a, Blys, vegf...), the biggest highlight of Junshi is the neutralizing antibodies, BLyS antibodies, ADCs, and BTLA monoclonal antibodies that are not available in Innovent, but their value is far less than that of Innovent's new generation biological targets. points have more commercial value.

So the final conclusion is that it is normal value for Innovent Biologics to have a market value greater than Junshi. I personally think that the current market value of Junshi, which is greater than 50%, is a very normal manifestation of value.