List of the fastest-growing biological drug pipelines in China!

Under the wave of innovation, domestic pharmaceutical companies are shifting from imitation to fast-follow, and then moving towards a truly global initiative

Entering 2021, this point is clearly reflected in the data: whether it is clinical application, clinical start, or new drug application and approval, all have broken the original record, especially domestic Class 1 new drugs in the first half of 2021.

What are the new domestic drugs that are worth looking forward to next? Based on the Insight database, we have compiled a total of 31 bio-innovative drug projects that domestic companies are currently in phase 3 clinical trials (including phase 2/3 clinical trials and phase 1b/3 clinical trials) but have not yet been reported for production.

23 monoclonal antibodies ready to go

In recent years, the innovation and transformation of domestic companies has mostly focused on the active deployment of innovative biological drugs; while in the research and development of biological drugs, monoclonal antibodies should be the mainstream

Immune checkpoint inhibitors account for the majority,

A new ``innovation leader'' was also born in the inner scroll

Counting from the dimensions of the target, PD-1/L1 is the most "volume" monoclonal antibody target in China , which must not be unexpected by everyone

Why do we have to continue to develop PD-1/L1 after it has been internalized so far? On the one hand, the sales of the top four domestically produced companies are really envy everyone.

On the other hand, PD-1 shows excellent potential for joint use
.
Because immune checkpoint inhibitors are widely used in various cancers, major companies are currently exploring the combination of PD-1 with a variety of chemical and biological drugs with different mechanisms to treat different cancers
.
Therefore, PD-1 may be an indispensable part in the construction of new anti-cancer drug pipelines for various companies in the future
.

The competition for the PD-L1 target is actually much milder than that of PD-1
.
Although PD-1 and PD-L1 are usually placed in the same category when discussing, there are certain differences in their mechanism of action and cancer types
.
At present, only two imported drugs of PD-L1 in China have been approved, and two domestic drugs have been approved for production.
The next production application is likely to appear among Hengrui, Zhaoke, Tianqing and Zhixiang Jintai, as the first domestic echelon.
, The future potential is still considerable
.

Immunization checkpoints other than PD-1/L1 are also very popular recently , such as TIGIT, CD47, LAG-3, TIM-3, etc.
, which have also attracted domestic companies to get together, but most of them are still relatively early
.
The two well-known Biotechs in China, BeiGene and Cinda Biotech, dominate the crowd
.
BeiGene has Phase 3 TIGIT monoclonal antibody Ociperlimab, and Cinda has Phase 3 CD47 monoclonal antibody Letaplimab.
It is worth noting that no product has been approved for these two targets globally, and BeiGene and Cinda are in the forefront of the world.
, To be proud of
.
Click here to enter the Insight applet to query specific target research and development details

   3 new drugs for hematoma have entered 3 phases,

   Self-immune IL17, metabolize PCSK9, who will be the first domestic product?

For the development of monoclonal antibodies for hematomas , Tianguangshi's MIL62 and Zebetuzumab, which is authorized to be transferred to Hisun, are both CD20 monoclonal antibodies.
They are currently in phase III clinical registration, but the specific indications are different
.
Tianjing Biotechnology has a CD38 monoclonal antibody fezetuzumab in phase III clinical trials.
In 2019, it initiated phase 3 clinical trials for multiple myeloma
.

MIL62 is the core product of Tianguangshi Biology.
It belongs to the third-generation anti-CD20 antibody .
Compared with the existing first-generation CD20 monoclonal antibody rituximab and other related analogues on the market, it has a unique competitive advantage
.
In phase 3 clinical trials, MIL62 combined with lenalidomide was used to treat rituximab refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL).
This clinical trial was first announced in March 2021
.
MIL62 project details

Hisun Borui’s Zebetuzumab is a new and differentiated human-mouse chimeric anti-CD20 monoclonal antibody .
Its Phase 3 clinical trial aims to compare Hi-CHOP ( zebetuzumab) in the first-line treatment environment.
, Cyclophosphamide, doxorubicin, vincristine and prednisone ) and R-CHOP ( rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone ) in the treatment of DLBCL And safety
.
Zebetuzumab project details

Fizetomab (also known as TJ202/MOR202) is a highly differentiated CD38 human monoclonal antibody .
Compared with CD20 antibodies that target a wide range of B cells, Fizetomab (also known as TJ202/MOR202) is a highly differentiated human monoclonal antibody .
Anti-B cells have the core differentiation advantage of highly targeting pathological B cells
.
At present, according to the Insight database, Fizetomab has launched 2 clinical trials in China, and Phase 3 clinical trials are aimed at multiple myeloma
.
Fizetuzumab project details

In the field of oncology , there is also a HER2 monoclonal antibody Margetuximab introduced by Zai Lab
.
This product is one of three products that Zai Lab introduced from MacroGenics for a total of US$165 million in November 2018
.
Margetuximab has HER2 binding and anti-proliferative effects similar to trastuzumab.
It has also been engineered through Fc optimization technology to enhance the participation of its immune system and utilizes antibody-dependent cell-mediated cytotoxicity (ADCC ) Affect the lethality of cancer cells
.

In addition to tumors, self-immunity, ophthalmology, and metabolism are also key areas targeted by companies
.
Hengrui Medicine and Zhixiang Jintai have developed  IL17 monoclonal antibodies for plaque psoriasis and ankylosing spondylitis; Junshi, Hengrui and Xinda have all developed  PCSK9 monoclonal antibodies
.
These products have all entered Phase 3 clinical trials during 2019-2021
.
Click here to inquire about clinical trials

IL17 monoclonal antibody has been approved for the marketing of three imported drugs, cucciuzumab, ichizumab, and brolizumab in China, and PCSK9 monoclonal antibody also has two imported drugs, iloiumab and alixizumab.
Approved for listing, but who will get the first domestic product? Let us wait and see
.

Double antibody and ADC

It's time to take off

Compared with monoclonal antibodies, domestic companies have deployed ADCs and double antibodies a little later, so there are fewer projects entering phase 3 clinical trials, and the clustering of targets of leading companies is more significant
.
See the table below for details .
However, in the follow-up early R&D projects, differentiation has gradually begun to appear
.

   There are frequent large transactions in the ADC field,

   $2.
6 billion detonated ADC frenzy

Among the 4 ADC products that have entered phase 3 clinical trials in China, 2 target HER2
.
HER2 is a classic and old target in the ADC field.
The world’s first HER2 ADC, Roche enmetrastuzumab (T-DM1), was approved for marketing in 2013; however, this target is still old and strong.
Target ADC new projects are constantly being born
.
Recently, the first domestic ADC product Vidicuzumab developed by Rongchang Biotech broke the record of the authorized amount of a single product of domestically-made innovative drugs with a license-out transaction of US$2.
6 billion
.

Domestic companies are still attacking HER2 targets
.
According to the Insight database, there are currently 60 ADC projects (including imports) in China, and 19 of them all target HER2, accounting for almost one-third
.
Zhejiang Pharmaceutical's ARX788  and Toyao Pharmaceutical's TAA013  are closely following vedicitumumab, and both have entered phase 3 clinical trials
.
However, the success of the US$6.
9 billion Enhertu (DS-8201a) cooperation between Vidicuzumab and AstraZeneca/Dichimoto proves that old trees may still bloom new flowers.
As long as good products can be made, it is The first few paragraphs do not matter, and there is no need to blindly pursue First-in-class
.

List of domestic HER2 ADC original research drug projects

From the Insight database (http://db.
dxy.
cn/v5/home/)

Among the fast-developing ADCs
, those that target non-HER2 targets are imported products , such as the FRα ADC of East China Medicine/ImmunoGen and the EPCAM ADC of Qilu/Sessen .
Introduction is a good strategy.
With the help of foreign R&D capabilities and excellent projects, it can take the lead in using first-mover advantages to seize the domestic track in the same target/disease field
.
Yunding Xinyao’s TROP-2 ADC Gosartuzumab is an example.
This product has been reported for production in May this year, and domestic latecomers only progressed to phase 2 at the fastest
.

Huadong Medicine's IMGN853 (new code: HDM2002) is  the world's first ADC drug targeting FRα obtained from ImmunoGen of the United States with an initial payment of US$40 million + a milestone payment of up to US$265 million + sales commission in October 2020 
.
At present, the drug is conducting an international multi-center phase 3 clinical MIRASOL study in China for patients with platinum-resistant advanced high-grade epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer with high expression of folate receptor α
.

Moolizumab (Vicineum) is an antibody conjugate drug targeting EpCAM introduced by Qilu from Sessen Bio in July 2020 for 35 million US dollars .
It is also the first domestic ADC targeting this target for non-muscle use.
Layer invasive bladder cancer
.
In March this year, Qilu launched Phase 3 clinical trials
.

   Double resistance: the leader still chases PD-1/L1

Domestically produced double antibodies will pursue PD-1/L1 to the end
.
Double-antibody leader Kangfang Biology and Kangning Jereh, their respective fastest-growing products coincidentally target PD-1(L1)/CTLA-4; Xinda and Hengrui each have a phase III bi-antibody/bispecific Sexual fusion protein products, respectively targeting PD-1/PD-L1 and PD-L1/TGFβ
.

The combination of PD-1 and CTLA-4 has been confirmed by a number of excellent data of O+Y immune combination therapy
.
However, the toxicity caused by the combination is still one of the problems faced by this combination
.
Double antibodies are expected to reduce this side effect
.

Cadonilimab (R&D code: AK104) is a new and potential next-generation first-in-class PD-1/CTLA-4 double antibody independently developed by Kangfang Bio .
It has shown PD-1 and CTLA-4 monoclonal antibody combination therapy The clinical efficacy of PD-1 and CTLA-4 monoclonal antibody combination therapy cannot provide good safety
.

According to the Insight database, Cadonilimab has currently launched 12 clinical trials, including two first-line phase 3 clinical trials, targeting non-resectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and recurrent or metastatic cervical cancer.

.
In addition, the types of tumors it explored include liver cancer, cervical cancer, lung cancer, esophageal squamous cell carcinoma and nasopharyngeal carcinoma
.

Cadonilimab (AK104) project details

From the Insight database (http://db.
dxy.
cn/v5/home/)

Corning Jerry’s KN046 is composed of a fusion  of CTLA-4 and PD-L1 single domain antibodies with different mechanisms , which can target the tumor microenvironment enriched in the high expression of PD-L1 and eliminate Tregs that inhibit tumor immunity
.
According to the Insight database, currently KN046 has launched 12 clinical trials in China, including one Phase 2/3 clinical trial and one Phase 3 clinical trial, all for NSCLC
.
In addition, KN046 has carried out clinical trials in different stages covering more than 10 types of tumors including non-small cell lung cancer , triple negative breast cancer, esophageal squamous cell carcinoma, thymic cancer, liver cancer, and pancreatic cancer in Australia, China and the United States
.

KN046 project details

From the Insight database (http://db.
dxy.
cn/v5/home/)

Cinda’s IBI318 is a recombinant fully human IgG1 bispecific antibody that targets  PD-1/L1 and aims to block PD-1 and PD-L1/PD-L2 signaling pathways and block PD-L1 Combined with CD80 signaling pathway, restore T cell activation and anti-tumor function
.
The drug launched its first clinical trial in 2019, and the fastest progress is currently a phase Ib/III clinical trial launched in November 2020  , evaluating IBI318 in combination with paclitaxel for small cell lung cancer patients who have failed standard first-line and above chemotherapy
.

Cinda is one of the companies with the largest number of double antibodies in China.
According to the Insight database, there are currently 7 double antibodies that have entered the clinic, and 6 of them all involve PD-(L)1
.

SHR-1701 injection is an anti-PD-L1/TGF-βRII bifunctional fusion protein independently developed by Hengrui .
It can promote the activation of effector T cells, and it can also effectively improve the immune regulation in the tumor microenvironment, and ultimately promote immune response.
The killing of tumor cells is currently being studied by Merck and Pumis Biosciences
.

At present, according to the Insight database, SHR-1701 has launched 12 clinical trials in China, and the fastest progressing is the indication for advanced/metastatic colorectal cancer, which has entered phase III clinical trials; in addition, it also targets NSCLC, SCLC, pancreatic cancer, and head and neck.
Some squamous cell carcinoma, nasopharyngeal carcinoma, renal cell carcinoma, gastric cancer and other types of cancer have undergone clinical development
.