The research and development pipeline of Chinese antibody pharmaceuticals includes CD22 antibody SM03, SM06, IL-17BR antibody SM17 and the like. The fastest progress is SM03, covering NHL, RA, SLE and other indications. SM17 was originally developed by British scientists and is not highlighted here.
The antibody research and development of China's antibody pharmaceuticals is mainly completed by its subsidiaries Shenzhen Sailein and Shenzhen Longrui Pharmaceutical. Since 2005, Longrui Pharmaceutical has applied for CD22 antibody for the first time. It has been 14 years since it was one of the early pharmaceutical companies in China.
The SM03 and SM06 projects are long-standing. One of the important reasons is that the CD22 target is quite special, which has caused many international twists and turns in the clinical development of the CD22 target. The first company to develop CD22 antibodies was ImmunoMedics, and Dr. Liang Ruian worked in this company in the early years. ImmunoMedics has developed the CD22 humanized antibody Epratuzumab, which was first used to treat NL and ALL. However, due to the limited function of Epratuzumab killing B cells, it was not successful. Considering that it can not effectively kill B cells, it can still regulate B cell activation and down-regulate inflammatory cytokines. Epratuzumab is used to treat autoimmune diseases such as RA, SLE, etc., but the SLE phase III clinical trial still failed.
After follow-up research, the scientists found that CD22 is special and easily endocytosed after binding to antibodies. Therefore, the development direction of CD22 target is converted to ADC, which becomes an ideal target for ADC. Epratuzumab tried the ADC with SN-38, but the first to be approved was Pfizer's Besponsa (inotuzumab ozogamicin) and AstraZeneca's Lumoxiti (moxetumomab pasudotox). Besponsa was approved by the FDA for the treatment of ALL in 2017. Lumoxiti was approved by the FDA in 2018 for the treatment of hairy cell leukemia. The Epratuzumab binding epitope is a D2\D3 non-ligand binding region and is also thought to be associated with poor efficacy.
Returning to SM03 and SM06 of China's antibody pharmaceuticals, SM03 was previously reported as a Class 2 biological product, that is, imitation, because SM03 is derived from the mouse maternal antibody of Epratuzumab and is fused with human constant region to be a chimeric antibody. SM06 is a humanized transformation of the variable region framework sequence FR based on SM03, a conventional humanization technique.
In summary, SM03 and SM06 of Chinese antibody pharmaceuticals are chimeric antibodies and humanized antibodies derived from Epratuzumab mouse maternal antibody RFB4. This is why SM03 is declared as a Class 2 biological product. More than a decade ago, there were only a handful of domestic antibody drugs, mainly imitation. This kind of research and development is also understandable, and Oriental Baitai has also applied for a patent for humanizing RFB4 antibodies.
