Can Shimai Pharmaceutical get hundreds of millions of financing again to stir up the tens of billions of anti-dumping rivers and lakes?

Recently, Shimai Pharmaceutical announced the completion of several hundred million yuan in Series C financing
.

This round of funds raised will be used for the domestic and overseas clinical trials of the company's new dual-antibody drug SMET12 (solid tumors with high EGFR expression), class I new drugs DNV3, CMD003 and other core innovative drugs, accelerating the global R&D process

It is reported that Shimai Pharmaceutical Co.
, Ltd.
is located in Hangzhou and was established in 2017.
It is an innovative tumor and immune disease antibody drug developer.
Its marketing model includes completely innovative drug development, terminal product development and phased mid-term product transfer and technology platform application authorization.
etc.
in combination
.

Table.
Shimai Pharmaceutical's previous financing

Source: Tianyancha

The highlight of Shimai Pharmaceuticals is also one of the reasons why it is favored by capital, that is, it has independently built two HBiBody and proBibody bispecific antibody platforms with completely independent intellectual property rights
.

Compared with other top double antibody platforms, HBiBody/proBibody can overcome the two major obstacles of poor drugability and large toxic and side effects of double antibody products.

The double resistance of the attack, the breaking point is coming

The double resistance of the attack, the breaking point is coming

The reason why double antibodies can become Shimai's secret weapon is that antibody drugs have become one of the fastest-growing and most promising fields in the global pharmaceutical industry, which is obvious to all
.

From the outbreak of antibody-drug conjugated ADCs in 2021, it can be expected that the next flashpoint in the world will be more challenging dual-antibody drugs
.

According to Frost & Sullivan, the market size of dual-antibody drugs will reach US$8 billion by 2025, and the growth rate of its research and development pipeline will be three times that of monoclonal antibody drugs

In fact, the research and development of double-antibody drugs has accumulated for decades
.

With the continuous improvement of gene recombination and protein engineering technologies, therapeutic strategies based on double antibodies are also being introduced.

From the analysis of the mechanism of action, the double antibody (BsAb) has two different binding sites for the antigen or two different epitopes that can recognize an antigen, and the functional path is relatively flexible
.

Some BsAbs play the role of immune cell connector, which can connect immune cells to tumor cells to exert cellular immunity and kill tumors

Compared with monoclonal antibody, the research and development of double antibody is more challenging and the process is more complex.
It is not a simple "1+1=2", but also considers functionality, affinity, titer (number of antigen-binding sites), antigenic characteristics, Antibody size, Fc structure, chain related and many other issues
.

Since double antibody requires artificial recombinant DNA or cell fusion technology, molecular structure design has become a key element.

The global double antibody platform can be roughly divided into two categories: Fc region (similar in structure to IgG), and Fc region-free (composed of the Fab region of an IgG single chain)
.

Fig.
Classic BsAb platform and representative antibodies

Source: frontiers in Immunology

Fc region-containing platforms and their characteristics are as follows: knobs-into-holes (change the local spatial structure of Fc), SEED (use complementary sequences to promote heterodimer assembly), DEKK (use mutation to form salt bridges), Orthogonal Fab (use electrostatically to generate mutual effect), ART-Ig (using electrostatic interaction), FAST-Ig (using electrostatic interaction), DuoBody (controlling Fab dynamic recombination exchange), DVD-Ig (symmetric structure), FIT-Ig (symmetric structure), DAF (which relies on phage display technology), as well as Crossmab and Wuxibody can resolve light chain mismatches
.

Platforms without an Fc region include BiTE (using a linker to connect two ScFvs), DART (containing VL, VH domains and coiled heterodimers), TandAbs (tetravalent antiparallel structure), Bi-Nanobody (only including VH structure)
.

Generally, non-IgG-like antibodies do not contain an Fc region, so the design is relatively simple, and the molecular weight is small and has high permeability, which can penetrate tumor tissue, but the disadvantage is that multiple administrations are required

Figure.
Representative BsAb platforms and companies

Source: Baiaogu

Only four models are on the market, and the clinical stage is "rich in stock"

Only four models are on the market, and the clinical stage is "rich in stock"

From the perspective of the global double-antibody R&D pattern, as of February 21, 2022, the Cortellis database has included a total of 1,061 double-antibody data, 785 drugs under development, involving 394 companies
.

Only 4 products have been listed so far, 5 registrations, 6 pre-registrations (pre-registered products are applications that have been submitted for marketing of the drug and are awaiting approval), 18 are in clinical phase III, and 18 are in clinical phase II.

Table.
Global marketed dual anti-drugs

Source: Compiled by Coretellis Shell Society

Among the global listed double antibodies, the TOP 1 blockbuster product in sales is Emicizumab, and its company is Chugai harmaceutical, a wholly-owned subsidiary of Roche.
Roche announced that the sales of Emicizumab (Hemlibra) in 2021 will be 3.
022 billion Swiss francs (3.
414 billion US dollars), compared with 2020.
A year-on-year increase of 41.
0%
.
Emicizumab, the third dual antibody approved for marketing in the world and the first dual antibody drug in the non-tumor field, can simulate coagulation factor VIIIa, providing a new option for hemophilia A patients with coagulation factor VIII inhibitors
.

Another double-antibody drug on the list, Polatuzumab vedotin, although its sales are far less than Emicizumab, is also from Roche and was developed by the company it acquired, Genentech
.
According to the data, polatuzumab (Polivy) sales in 2021 will be CHF 247 million (US$ 279.
1 million), an increase of 48% compared to 2020
.

It is worth noting that there is currently only one double antibody on the market in China - blinatumomab, which was jointly developed by Amgen and BeiGene, targeting CD13 and CD19 for the treatment of R/R pre-B Cellular acute lymphoblastic leukemia (ALL) in adult patients
.
On December 7, 2020, the NMPA issued an approval document to allow the double antibody to belintuomo injection.
After that, the commercialization of this variety in China will be handled by Baiji, with a time limit of 5 to 7 years, during which the two companies will share the profits equally
.
It is understood that bilintumab is developed based on Amgen's BiTE platform, and it is also the first dual antibody product born from Amgen's BiTE technology platform.
It can present CD19 protein on tumor cells to CD3 specifically expressed on T cells.
protein, and then activate the immune system to recognize and kill tumor cells
.
Sales of the drug in 2021 will be $472 million, up 25% from 2020
.

From the perspective of therapeutic areas, the therapeutic areas of double-antibody drugs are mainly divided into three categories: anti-tumor (including hematological tumors, solid tumors and various cancers), autoimmune diseases and other diseases.
Among them, anti-cancer products are the majority, with nearly 80% of The pipeline is concentrated in the field of cancer, and other inflammatory diseases as well as double-antibody drugs for diabetes, osteoporosis, and Alzheimer's disease are all actively developed
.

Figure.
Global dual-antibody indications

Source: Chinese Journal of Bioengineering

As the most potential pharmaceutical subdivision track in the future, major pharmaceutical companies around the world have already entered the game
.
Roche, Amgen, Johnson & Johnson, Regeneron Pharmaceuticals, MacroGenics, AstraZeneca, AbbVie, Xencor, etc.
are all representative giants; domestic representative pharmaceutical companies include BeiGene, Innovent, Animai, Corning & Jereh, Primis Bio, Youzhi Yousheng, Kangfang Bio, Fuhong Henlius, Sunshine Guojian, Sihuan Pharmaceutical, Shihuan Pharmaceutical Group, etc.
; there are also some companies such as Betta Pharmaceuticals (investing in Shimai Pharmaceuticals) Industry) and Kaineng Health (investing in Yuanqi Bio) are also expected to occupy a place in the domestic double antibody market through equity investment
.

Figure.
Global Representative Enterprises of Double Antibiotics

Source: Cortellis

It can be seen that under the background of the global wave of innovative dual-antibiotics, pharmaceutical companies have entered the market with various postures, or independent research and development or cross-border cooperation or investment and mergers and acquisitions
.
In any case, only the star products with beautiful clinical data and the first to stand out can get a fresh share of the tens of billions of dollars in blue ocean dividends
.

references

1.
Inventory of the representative double-antibody platform of Baiaogu 2021.
3.
21

2.
Haoyue's research on key transactions in the medical and health investment market 2022.
2.
13

3.
Bispecific Antibodies: From Research to Clinical Application, frontiers in Immunology 2021.
5.
Volume12

4.
Analysis of the global bispecific antibody drug R&D pattern China Biotechnology 2021.
8.
26