HER2 ADC melee is coming!

In January 2021, Enhertu's gastric cancer indications are one step ahead and the first to be approved by the FDA for marketing
.
Compared with the irinotecan/paclitaxel group, Enhertu's efficacy data is eye-catching.
The EnhertuVS chemotherapy group has an OS of 12.
5 months VS 8.
4 months, and PFS of 5.
6 months VS 3.
5 months, making it the world's first approved treatment for HER2-positive gastric cancer The antibody conjugated to the drug
.

two

Domestic layout

At present, domestic enterprises, including the layout of HER2 ADC Rongchang biological, Zhejiang Medicine (new code bio), Dong Yao medicine, Cologne medicine, HRH medicine and so on
.
Among them, the top R&D companies include Rongchang Bio (Phase III, NDA), Zhejiang Pharmaceutical (Phase II/III), and Toyo Pharmaceutical (Phase III)
.

Rongchang Biological's RC48 uses a novel antibody disitamab that is highly selective for HER2
.
Compared with trastuzumab, disitamab has a higher affinity for HER2, with an EC50 of 6.
4pM, while trastuzumab has an EC50 of 20.
1
.
Due to the high affinity, the clinically qualified dose may be relatively lower, and the side effects may be smaller
.

In August 2020, RC48's HER-positive advanced or metastatic gastric cancer indication was declared for marketing, and it was included in the priority review and approval process, becoming the first HER2 ADC drug in China to declare the advanced gastric cancer indication for marketing
.

Zhejiang Medicine's ARX788 is formed by conjugated trastuzumab and AS269
.
AS269, the full name of Amberstatin, is Ambrx's proprietary and potent tubulin inhibitor, which can form highly stable covalent bonds with synthetic amino acids in antibodies
.
The core technology of ARX788 lies in the site-specific coupling technology of unnatural amino acids.
By introducing unnatural amino acid pAF, the site-specific coupling of the cytotoxic drug AS269 forms an oxime bond with high stability and good uniformity, which reduces the off-target toxicity of cytotoxic drugs in the body
.

From the perspective of competition, although only one HER2 ADC from Kadcyla has been approved for listing in China, the crowded R&D pipeline of HER2 ADC is worrying
.
The first mover advantage of Kadcyla and the excellent clinical data of DS-8201 are in the front, and there are many innovative drug companies catching up in the back, and there is no lack of pharmaceutical leaders such as Hengrui and Kelun.
Once their products are on the market, although they are too late, With strong marketing capabilities, it can also bring huge changes to the market
.

Therefore, pharmaceutical companies should start to reform from the ideas of accelerating R&D and deploying small indications
.
On the one hand, it is a kind of wisdom to race against time, accelerate research and development, and strive to obtain more positive clinical results.
It is also a kind of wisdom to choose "the strong man to break his wrist" when forced to do so.
Just like Biotech's BAT8001, which discontinues clinical practice and focuses precious resources on Trop-2 ADC On the other hand, choose an inaccessible road to avoid being crowded with breast cancer, gastric cancer and other indications.
Only in this way can we have the opportunity to market with Phase II data, reduce R&D costs and shorten the R&D cycle
.
Here, I have to boast the vision of Rongchang Biotech’s leader, early deployment of indications for gastric cancer, urothelial cancer, biliary tract cancer, non-small cell lung cancer, etc.
It is expected to bloom more in the future and become a waver in the domestic market of HER2 ADC
.