The domestically produced "three anti-" works!

On December 29, Zhejiang Borui Biopharmaceutical Co.
, Ltd.
(abbreviated as "bo Rui Bio") tri-specific antibody BR110 (CMG1A46) clinical trial application was approved by the National Medical Products Administration.
This is the world's first clinically approved CD3/ CD19/CD20 triple antibody product
.

The product was developed by Enmu Bio, with which Borui Bio has reached an exclusive cooperation and authorization to introduce the exclusive clinical development, production and commercialization rights of CMG1A46 in Greater China (including Mainland China, Hong Kong, Macau and Taiwan)

Major breakthrough in the development of domestic trispecific antibodies

Major breakthrough in the development of domestic trispecific antibodies

Public information shows that BR110 is the first-of-its-kind T cell Engager tri-specific antibody that targets CD3, CD19 and CD20.
It can simultaneously target CD3 on the surface of T cells and two different biomarkers CD20 and CD20 on tumor cells.
CD19, by shortening the spatial distance between tumor cells and T cells, activates T cells and kills tumor cells that express CD19 and/or CD20
.

The 62nd Annual Meeting of the American Society of Hematology (Source: ASH)

In December last year, at the ASH annual meeting, Enmu Bio announced the preclinical study data of BR110 (CMG1A46) for the treatment of non-Hodgkin's lymphoma (NHL)
.

According to the conference abstract, because BR110 (CMG1A46) has a high affinity with CD19 and CD20 on the surface of tumor cells, it can not only target CD19+/CD20+DLBCL cells, but also CD19-/CD20+DLBCL cells, and CD20 Low-expressing DLBCL cells

In in vitro studies, BR110 (CMG1A46) can mediate tumor cell lysis through human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner
.

Compared with the conventional "1:1" CD3xCD20 bispecific antibody based on the IgG format, CMG1A46 shows stronger efficacy and safety

In vivo studies have shown that in NOD mouse models transplanted with human PBMC, BR110 (CMG1A46) showed strong tumor suppressor activity and induced CD19+/CD20+Jeko-1 lymphoma and CD19+/CD20-A20-hCD19 tumors The fast faded
.

Pharmacokinetic studies in cynomolgus monkeys showed that the half-life of BR110 (CMG1A46) in serum exceeds 70 hours when administered at a dose of 1mpk (mg/kg)
.

The administration dose up to 10mpk (mg/kg) also did not cause significant adverse reactions

In summary, in in vitro and in vivo experiments, BR110 (CMG1A46) showed better efficacy and safety than other CD3xCD20 bispecific antibodies in the traditional "1:1" IgG format
.

Preliminary studies in cynomolgus monkeys have shown that BR110 (CMG1A46) has a natural IgG-like half-life in the serum and its toxicity is controllable

The approval of the IND application is not only a key milestone for BR110 to enter the clinical development stage, but also an important verification of the drug-readiness of Enmu's trispecific antibody TRIAD technology platform.
It also represents another breakthrough in the development of domestic trispecific antibodies.

.

The once immune rookie has become an anti-cancer "old gun"

The once immune rookie has become an anti-cancer "old gun"

Entering the stage of comprehensive treatment of tumors, immunotherapy has become the natural C position of the country
.

On the one hand, as a targeted drug to fight blood system tumors, on the other hand, as a neoadjuvant immunotherapy to allow solid tumors to shrink and downgrade, for a while, cancer immunotherapy has become the darling of tumor surgery

When PD-1 monoclonal antibody was sold globally, it dropped a "blockbuster" in the oncology treatment industry, drove the development of a number of cutting-edge treatment concepts such as targeted therapy, precision therapy, and individualized therapy, and also promoted oncology medicine to enter the comprehensive treatment stage
.

Since cancer immunotherapy was rated as one of the top ten scientific breakthroughs of the year by Science in 2013, the development of specific antibodies for single targets has been extremely hot, and various pharmaceutical companies have sought out drugs with great potential and potential targets for mining layout.

.

A long way to go: monoclonal antibodies do not make their debut

A long way to go: monoclonal antibodies do not make their debut

Non-specific cell proliferation caused by a series of immune and biochemical reactions after proto-oncogene activation is the cornerstone of cancer cell proliferation and proliferation
.

Monoclonal antibodies use key proteins in the biochemical reaction as specific antigens to kill tumor cells, cause tumor cell apoptosis, or inhibit cancer cell proliferation through immune response

The ideal is bright, but to achieve the therapeutic effect of polyclonal antibodies, the multi-antibody target of the same antibody must be used, which limits the space of activity of antibodies from the beginning
.

For hematological tumors, multi-antibodies have a broad space in the plasma.

PS: Double antibodies provide a platform for the combination of tumor cells and T lymphocytes

Among the four dual-antibody drugs that have been on the market, Roche's Hemlibra's global sales surpassed the tens of billions of yuan mark
.
As of November 2021, nearly 70 dual-antibody drugs have entered clinical trials in China, most of which are aimed at hematological tumors in a big way, hoping to rub cancer cells on the ground
.

Not to be left behind: the dawn of the three anti-dawn

Not to be left behind: the dawn of the three anti-dawn

With the continuous improvement of specific target research, antibody modification technology has gradually improved, and third-antibody drugs will soon be released
.
In 2019, Sanofi developed a trispecific antibody against CD38, CD3, and CD28 and applied it to a mouse model of myeloma
.
The research results were included in the Science sub-Journal Nature Cancer on November 18, 2019
.

Research results (Source: Nature Cancer)

Dr.
Carl June from the Perelman School of Medicine at the University of Pennsylvania made a special comment on the research in the Science journal, and believes that trispecific antibodies provide a third direction for anti-cancer immunotherapy
.

Research results (Source: Nature Cancer)

Double antibodies have highlighted the huge value of the medical industry.
Will the triple antibodies become another outstanding work in cancer immunotherapy? Major pharmaceutical companies have deployed one after another, and innovative pharmaceutical companies in the science and technology sector have also used this as a breakthrough in new drug research and development.
However, most of them are still stuck in the complex data of animal experiments, failing to submit double-quality answers for safety and effectiveness at the same time , This track is looking forward to breaking the game
.

The new drug research application (IND) for the trispecific antibody BR110 (CMG1A46) developed by Enmu Bio was approved by the State Food and Drug Administration, which means that the world’s first anti-CD3/CD19/CD20 product can enter clinical trials from animal experiments.
Another ray of light in a field came in time
.

Reference source:

[1]https://doi.
org/10.
1038/d41586-019-03495-3

[2]https://doi.
org/10.
1038/s43018-019-0004-z

[3]https://news.
medlive.
cn/all/info-progress/show-55752_53.
html

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