The number of listings in a year exceeded the sum of ten years, and the double resistance finally waited for the golden age

There is no shortage of breakthroughs

From the concept of dual antibodies first proposed in 1960 to the end of 2021, in the field of dual antibodies for more than 60 years, only four products in the field of dual antibodies have been listed, namely ketosomumab, Bonatutusab, Emesizumab, and Rybrevant, of which Catasoxalumab has been delisted

Compared with the hundreds of competitions on popular tracks such as single-resonance, ADC, and CAR-T, the double-resistance track seems to be much

On August 24, Johnson & Johnson's dual antibody drug Tecvayli was approved for marketing in the European Union, which is the world's first dual antibody drug targeting BCMA/CD3, and the fifth dual antibody

With only one year's data, the number of approvals for double resistance has exceeded the previous total

/ 01 /

BCMA/CD3 dual antibody,

A new hope for patients with multiple myeloma

In recent years, although innovative drugs have been frequently released, there is still a long way to go before we can truly conquer tumors

For example, in the field of hematomas, which is relatively easy to overcome, effective treatments for multiple myeloma are still scarce

But overall, advances in oncology drugs are there for all to see

On August 24, Johnson & Johnson's Tecvayli was approved as the first dual antibody to be used to treat adult patients with relapsed/refractory multiple myeloma

The targets of action of the Tecvayli dual antibody are BCMA and CD3

In simple terms, Tecvayli has two hands, one targeting the BCMA is responsible for grabbing the cancer cells, and the other hand is responsible for dragging CD3-positive T cells near the cancer cells, so that they can kill

In actual clinics, Tecvayli's performance is remarkable

It is worth mentioning that 58.

The emergence of Tecvayli not only means a new hope for patients with blood tumors, but also means the heat and hope

/ 02 /

2022 Double Resistance Outbreak Year:

In 1 year, the approved listed products exceeded the previous total

In fact, Tecvayli is already the fifth dual antibody drug

In January this year, Kimmmtrak Dual Antibody, which was approved for marketing in the United States, ignited the first fire

Kimmtrak is both the first novel T cell receptor (TCR) dual antibody therapy to target gp100/CD3 and the first to receive FDA approval for the treatment of unresectable or metastatic uveal melanoma
.

Also in January, the FDA approved Vabysmo, a roche-targeted Ang-2/VEGF-A dual antibody drug for the treatment of neovascular or wet age-related macular degeneration and diabetic macular edema
.

Vabysmo is also the first bispecific antibody
approved for eye treatment.
For the field of dual antibodies, this also means that dual antibody indications are no longer limited to blood tumors and solid tumors
.

It seems that these two double antibodies are already very powerful, but this is not the end
.

In June, Roche's CD20/CD3 diantine Lunsumio was launched in Europe, becoming the world's first CD20/CD3 monoclonal antibody
.
In clinical trials, Lunsumio has also demonstrated its ability
to become a strong competitor to CAR-T therapy.

For domestic dual antibody players, it is more meaningful that Kangfang Bio's dual antibody products have been approved
.

On June 29, Kangfang Bio's PD-1/CTLA-4 dual anti-KN046 was approved for the terminal treatment of cervical cancer
.
This is the world's first PD-1/CTLA-4 dual antibody
.

In the past, the combination of PD-1 and CTLA-4 had a good effect on many cancer types, but the disadvantage of the combination was that it had more serious adverse effects
.

Compared with combination therapy, PD-1/CTLA-4 dual antibodies are more effective and safer
.
Kang Fang also became the first person to eat crabs, opening up a feasible path
for later domestic players.

It can be said that the double antibody that came out this year is refreshing the ceiling of the double antibody field, and also brings more imagination space for the future of the double antibody
.

If you extend the cycle, the number of approved and listed dual antibodies worldwide since 2022 has created a record high
.

As shown in the figure above, before this year, the approved double antibody was also 4.

/ 03 /

Behind the double resistance explosion,

The technical bottleneck was broken

Seeing this, do you also have such a question, from the starting time, the start of the double antibody field is not too late, so why in the past ten years, the double antibody has developed slowly, but this year it suddenly broke out?

The answer, perhaps, is thick and thin
.

Although the concept of dual antibodies seems simple, it seems that as long as the two antibodies are randomly put together, a stronger and innovative drug
can be obtained.
However, in the actual research and development process, it faces many constraints, and every step forward in technology is extremely difficult
.

Specifically, the previous constraints in the field of dual antibodies mainly lie in two aspects, one is the low efficiency of proprietary drugs and industrialization, and the other is the short
half-life of drugs.

We know that diantine drugs can be divided into IgG-like dual antibodies in the Fc region (crystallizable region) and non-IgG-like double antibodies without the Fc region according to the structure
.

For the IgG-like dual antibody in the Fc region, what needs to be solved in the research and development process is the problem of antibody structure mismatch, which is the chain exchange problem
.
It is also therefore the resulting in low industrialization efficiency of dual antibodies and more impurity proteins
.

For this problem, many large pharmaceutical companies around the world have launched their own dual antibody technology platforms, such as KiH, Crossmab, DuoBody and other platforms, through which the problem of double anti-light and heavy chain mismatch has been gradually solved
.

For non-IgG-like dual antibodies without the Fc region, the problem is that the half-life is shorter
.
Non-IgG-like dual antibodies without the Fc region have a small molecular weight and are susceptible to degradation by target cell lysosomes, resulting in a half-life of usually only two hours
.
Blincyto is like this, with a half-life of two hours and patients need to take the drug
frequently.
This has also become one of the factors restricting Blincyto's
sales.

In view of this drawback of dual antibodies, pharmaceutical companies are currently designing different platforms to improve the half-life of dual antibodies to solve
.
The bottlenecks that were once in the field of dual antibody research and development have been broken
one by one.
It is precisely because of this that the double resistance ushered in a bumper harvest period
.

/ 04 /

summary

All in all, it is precisely because of the continuous efforts of the medical community in the past few decades that the shackles of the dual antibody have been broken layer by layer, and now we can see the explosive success of the double antibody
.

However, there are still many places that can be improved in the future, such as the exploration
of solid tumors.
Since hematology tumor drugs are less difficult to develop, most of the current achievements of dual antibodies are based on blood tumors
.

However, only by breaking through the indications for solid tumors can we bring exponential growth to the imagination space of the double antibody
.
It's like the DS-8201 breaking through the ceiling of an ADC
.

But there is no doubt that in the field of double resistance, the same story may be staged
.
With the influx of more pharmaceutical companies in the field of dual antibody, the ceiling is bound to continue to be raised
.

Only in China, many pharmaceutical companies, including Kangfang Biologics, Corning Jereh Pharmaceutical, BeiGene, Xinda Biologics, Hengrui Pharmaceutical, Yiming Onke, Wamai Biologics, Youzhiyou and so on, have entered the game
.

In the golden age of double antibody that is about to open, it is inevitable that the figure
of domestic pharmaceutical companies will be indispensable.