The popularity is close to PD-1!

Today, the official website of CDE shows that CP TQB2928 has been applied for clinical application

The 19 domestic CD47 antibody drugs have accounted for half of the world's research and development of the same target drug.

CD47-SIRPα pathway, an immune checkpoint of macrophages

CD47 (leukocyte differentiation protein 47), also known as integrin-related protein, was discovered in the 1990s and belongs to the immunoglobulin superfamily.

CD47 is overexpressed in various types of cancer cells and can directly bind to SIRPα, which is mainly located on macrophages

However, CD47 is also expressed on the surface of red blood cells

Develop CD47 antibodies with IgG4 type at the Fc end, instead of IgG1 antibodies that can trigger strong ADCC and CDC effects;

By reducing the binding ability of CD47 drugs to red blood cells, thereby avoiding the killing effect on red blood cells;

Completely abandon the powerful ADCC effect of CD47 antibody, and only use the biological effect of CD47/SIRPα itself to release the anti-tumor potential of phagocytes, but it often requires a combination of drugs

In summary, the general purpose is to enhance the positive tumor targeting effect and reduce the impact on red blood cells and platelets

In 2017, Arch Oncdogy terminated a phase I/II clinical trial of CD47 monoclonal antibody Ti-061 in solid tumors in Europe; in 2018, Celgene discontinued the use of CD47 monoclonal antibody CC-90002 for the treatment of AML and high-risk myelodysplastic abnormalities Syndrome clinical trials.

Multinational pharmaceutical giants bet heavily on new ignited CD47

Multiple transactions in 2020 witnessed the return of CD47 to the throne

In March 2020, Gilead announced the acquisition of Forty Seven Biotech (represented by Magrolimab), which focuses on the development of CD47 pathway inhibitors, for a total value of US$4.

In July 2020, SciClone Pharmaceuticals and Epicent Rx announced that they have reached an exclusive license agreement for RRx-001 in Greater China, involving an amount of up to 120 million U.

In September 2020, Pfizer invested nearly US$25 million in Trillium Therapeutics, and Trillium Therapeutics’s key varieties are CD47 monoclonal antibodies TTI 621 and TTI 622.

In September 2020, AbbVie received the development and commercialization rights of TJC4, the CD47 monoclonal antibody lemzoparlimab (TJC4), with a down payment of US$180 million and a milestone payment of up to US$1.

In October 2020, the domestic pharmaceutical company Immune Onco completed a US$25 million Series B investment led by Eli Lilly Asia Fund.

Global CD47 clinical drug research progress map (partial)

* Due to space limitations, all 39 projects cannot be presented.
If you need to inquire about global CD47 projects, please log in to the Insight database (http://db.
dxy.
cn/v5/home/)

There are already 19 CD47 antibodies in China, Cinda, and Tianjing Biological progress can be expected

According to the Insight database, at present, including Tianqing, there are as many as 19 CD47 drugs entering the clinic in China, occupying half of the world's CD47 target drugs entering the clinical stage
.
Many companies such as Tianjing Biological, Cinda Biological, Immune Onco, Hansi Biological, Hengrui Pharmaceutical, Zai Lab, Kangfang Biological, etc.
have already deployed in this field, and even single and double antibodies have been developed simultaneously, covering a wide range
.

Specific to the category, including 9 monoclonal antibodies, 9 double antibodies and 1 antibody fusion protein, see the figure below for details:

Domestic CD47 antibody drug development pattern (Insight)

Among the monoclonal antibody varieties, the highest stage of domestic development is Cinda Biologics IBI188.
The international multi-center trial of IBI188 combined with azacitidine in the treatment of newly diagnosed high-risk MDS phase Ib/III is currently underway.
The first public announcement time is July 2020.
, The first domestic subject was enrolled in September 2020
.

The results of a phase 1a clinical study of IBI188 monotherapy for advanced malignant tumors have been announced
.
As of June 18, 2020, IBI188 has completed the climb of all preset doses, with the highest exploratory dose of 30 mg/kg QW.
No dose-limiting toxicity occurred in each dose group, and the overall tolerance was good
.
Most of the treatment-related adverse events were grade 1-2, no drug-related adverse reactions leading to permanent discontinuation of the drug, and no treatment-related deaths occurred
.
In addition, the overall incidence of anemia after IBI188 monotherapy was 15% (3/20), only one subject (5%) developed grade 3 transient anemia, which appeared on the day of the first administration and recovered on the second day
.
At the same time, IBI188 single agent also observed certain anti-tumor activity in this study, including several patients who obtained stable disease for a long time
.

Two monoclonal antibodies, AK117 and TJ011133 (lemzoparlimab, TJC4), have also entered phase II clinical trials, and the latter is exactly the product introduced by AbbVie
.

Among the dual antibodies, the PD-1/CD47 dual antibody HX009 developed by Hangzhou Hansi Biotechnology and the PD-L1/CD47 dual antibody IMM2505 developed by Shenghe Biotechnology are both the fastest-developing CD47 dual antibodies in China and have entered phase II clinical trials
.

Fusion protein, IMM001 of IMM001, which has attracted more attention.
It is SIRPα-IgG4 Fc fusion protein.
It is the first domestic Fc fusion protein drug that targets human CD47.
This product is based on the company’s "mAb-Trap" technology.
The new generation of immune checkpoint inhibitors developed by the platform with independent intellectual property rights have been approved for invention patents in China, Japan, and the United States
.

Summary

From the global layout of new drugs, it can be seen that China's new drug research and development capabilities have taken a qualitative leap and attracted the attention of a large amount of foreign investment
.
But at the same time, the current global competitive environment for innovative drug research and development has become increasingly fierce
.
The "faster" and "updated" of new drug research and development are of course important, and the ultimate clinical benefit is where the core competitiveness of the product lies, and it is also the original intention of drug research and development
.