The market value of the front antibody technology pioneer is "zero" by the market value of $ 2.5 billion, and the counterattack story of the misunderstanding

The market value of the front antibody technology pioneer is "zero" by the market value of $ 2.5 billion, and the counterattack story of the misunderstanding

Source: amino observation/Fang Taozhi

The field of innovative drugs has always been lacking.

It can also be understood. Today, the medical world still knows very little about the mystery of the human body. Whether it is unknown or known fields, there is still much room for exploration.

In this context, once a Biotech finds the new continent, it may quickly become the focus of the market.

This is the case for American biotechnology company CytomX.

In 2013, CytomX officially debuted with precursor technology Probody. It seems that this technology can reduce the adverse reactions of antibody drugs and have a great imagination space:

Not only can the treatment windows of existing drugs be increased, but it can reduce the efficiency of drug reduction;

It is precisely because of this subversive innovation technology that CytomX has been sought after by many major pharmaceutical companies and is also favored by capital. The market value once reached 2.5 billion US dollars (17.7 billion yuan).

However, the ventilation not only needs "story" support, but also depends on the results. Innovative drug research and development of nine deaths are doomed to the sudden came from this field, and the "caught off guard".

In a blink of an eye, ten years have passed, and CytomX has not been to the mountains to open the mountains to the mountains and effects as the previous expectations.

Both pharmaceutical companies and capital gradually lose patience. Today, the market value of CytomX is only more than 90 million US dollars, and it has fallen to the point of cutting pipelines and layoffs.

After ten years of struggle, Cytomx returned to the starting point.

/ 01 /

Previous antibody technology, CytomX burst fire

Immunotherapy has always been a popular area for innovative drugs. However, severe immune -related adverse reactions are like a sword of Damoris, which is high on the head of immunotherapy.

Therefore, many pharmaceutical companies are committed to finding a feasible technology to minimize the side effects of immunotherapy. The same is true of CytomX.

In 2013, Cytomx proposed the concept of Probody, a front antibody technology platform based on the pre -medicine and antibody.

Everyone is familiar with antibodies, but many people may be confused when they are mentioned. In fact, pre -antibody drugs are also an antibody, but it requires protein hydrolytic enzyme activation to play a role.

So, how does protein hydraulin enzyme activate the activity of antibody drugs before?

This is to start with its structure. The front antibody drugs are composed of three parts: a blocking peptide peptide that combines with antibody light chains, a protease of a connected obstion peptide and antibody can cut the joint, and an antibody antibody.

The functions of connecting and antibodies are well understood, focusing on shielding peptides. The role of blocking peptides is similar to the shield, which can protect the activity of antibodies. Under the protection of the obstion peptide, antibodies cannot be combined with the antigen in normal tissues, and the off -target effect will not occur, bringing side effects.

However, after the tumor's micro -environment, things are different. Because the tumor microe environment contains many proteases, it can cut the oblivion peptide and the antibody "bridge" connection, thereby unloading the antibody "camouflage", which can combine the receptor on the tumor.

Theoretically, anterior antibody drugs will only play a role in the micro -environment of the tumor, and naturally can avoid the side effects of immune drugs to the greatest extent. This can not only empower the antibody of the medicine, but also bring the dawn to the target of the unparalleled medicine.

In the field of immunotherapy, the reason why individual targets are not padded is because the content in normal tissue is high, so the side effects and efficacy are difficult to balance. But with the pre -antibody technology, there is the possibility of adults.

For example, CD166, because it exists in both cancer cells and normal tissue, has not been regarded as an ideal target.

Today, borrowing pre -antibody technology can block CD166 in the normal tissue. Therefore, CD166 also has the possibility of patent medicine, and CytomX is aimed at CD166 before research and development of antibody ADC CX-2009.

What's more popular is that the pre-antibody drugs do not limit the types of drugs. From monethea to ADC or even CAR-T, this technology can be used, which can be called immunotherapy drugs.

This has attracted the attention of many international pharmaceutical companies. Although this technology is still in the early clinic, big pharmaceutical companies have submitted gold and accounting. In the past few years, Pfizer, Beltay Schimi Bao, Anjin, and Albervi are all partners of CytomX.

Many domestic pharmaceutical companies have followed up. For example, Tianyan Pharmaceutical and Zhangjiang Biological are engaged in the development of antibody drugs before.

Under the high attention, CytomX's market value rose and rose at a height of $ 2.5 billion in March 2018. Unfortunately, CytomX's highlights come quickly and go fast.

/ 02 /

From childhood to Mrs. Niu, why did Cytomx fall?

The development of innovative drugs has a "double ten" law: one billion US dollars, ten years. This is not only a huge amount of money, but also a long cycle.

However, if the cycle is long, it also needs to continue to release good information for pharmaceutical companies to let the market see hope. Cytomx failed to do this. This also made CytomX's partner began to withdraw from this gambling one after another.

The first exit was Pfizer. In March 2018, Pfizer canceled cooperation with CytomX. The reason may be that in the past four years, the projects of CytomX and Pfizer have not entered the clinical stage. Immediately after February 2019, Belky Schimi Bao announced his retreat and abandoned the three candidate drug projects previously traded with CytomX, and continued to develop CTLA-4 monoclonal anti-resistance.

Both the big pharmaceutical companies and CyotmX even broke up, making many people began to doubt the prospects of CytomX. After all, if CytomX's technology is bright, how can you see how well -informed big pharmaceutical companies are willing to let go. The same is true. After the news of Belief Shi Guibao announced the news, CytomX's stock price fell 31%.

Since then, the clinical data of the pre -antibody drug released by Cytomx seems to prove the "foresight" of these two major pharmaceutical companies.

In December 2021, CytomX announced the first clinical data of the front antibody ADC drug CX-2019 that targeted CD71, and the result could not bear to look directly.

Among the 16 patients with evaluation of advanced non -small cell lung cancer, the objective relief rate was 18.8%, which means that only about 20%of patients are effective. This number has no competitiveness in the face of K medicine single medicine.

Among the 25 patients with evaluated head and neck squamous cell carcinoma, only one patient was partially relieved, and the objective relief rate was 4%, which basically had no effect.

In terms of security, CX-2029 does not achieve the effect of reducing drug reduction as CytomX's imagination. Among the 5mg/kg dose group with the best effect, the adverse reaction rate greater than the level 3 has reached 100%.

Therefore, after the announcement of clinical data, investors also voted with their feet, and CytomX's stock price fell 40%.

And this is just the beginning.

On July 6 this year, CYTOMXS targeted CD166's frontal antibody ADC drug CX-2009 still ended in failure in the clinical clinical of Sanyin breast cancer.

If ADC is originally complicated, the failure of the front antibody ADC is reasonable. Then the performance of the pre -antibody monoclonal resistance is surprising.

At this year's ESMO conference, Beltay Schimi Bao announced the first clinical data of the CTLA-4 anterior antibody single medicine or combined with PD-1 treatment of advanced physical tumors, and the data was pulled down.

The objective relief rate of the CTLA-4 anterior antibody single drug treatment group was 0%, and the disease control rate was 26%; the objective relief rate of the joint treatment group was 16%, and the disease control rate was 38%.

It is not difficult to see that the treatment effect of CTLA-4 anterior antibody single medicine is very small. If there is no effect, it seems that the drug safety is good.

In successive failure, CytomX's stock price began to go downhill, with a market value of only 98 million US dollars.

This also means that CytomX has basically lost its financing function, and has to continue to survive, abandon the research and development of its antibody drugs CX-2043 and CX-2009, focusing on the development of two other types of anticancer drugs. 40%.

Thinking back a few years ago, CytomX was still the star of Wall Street sought after by everyone, but now it is impressive.

/ 03 /

The research and development story of the former antibody drug has finished?

Of course, this does not mean that the research and development story of anterior antibody drugs has ended.

The development of science and technology has always been spiral, and new technologies and new products will never appear out of thin air, nor will it disappear out of thin air.

The development of new technology is a gradual process, and the development of new drugs is a process of eliminating difficulty and constantly moving forward.

From the previous experience, this process will not be too easy and not too short.

For the development of ADC drugs, although the research and development of ADC drugs is in full swing today, from the theoretical proposal to a complete success of a hundred years.

In contrast, the front antibody technology has only been decades from the appearance to development. It can be said that this technology is still very young.

For such a new technology, just because of CytomX's defeat, it is not rational to judge the "death penalty".

What's more, it is CytomX's folding halberd that the latecomers clearly realize the technical problem of the pre -antibody technology.

For example, the off -target effect of the pre -antibody technology.

The lifting of the pre -antibody drug shielding peptide relies on tumor special proteinase, but if the health tissue also contains trace proteases, the anterior antibody drug may play a role in normal tissue and the decisive effect occurs.

Even if the drug can be released in the tumor, there may be some drugs that may enter the normal tissue through circulation, and it will still produce off target effects. Therefore, in the future, you need to try your best to reduce the decisive effect.

For another example, the choice of hidden peptide shielding ability.

If the shielding ability of the concealment peptide is too strong, then entering the micro -environment can not completely cut the shielding peptide, which will also affect the effect of the drug. However, if you reduce the combination of concealed peptides, and it is easy to increase the problem of decision, so how to find a folding binding force is also an improvement direction.

In addition, there is a choice of connection.

Ideally, the shielding peptide can be cut in the micro -environment of the tumor, but in fact, it is not easy to choose a suitable connection to make it accurately in different environments.Knowing where the problem is, in the direction of the problem, it is more likely to find a solution.After the re -positioning of the current route again and again, the story of the pre -antibody can be reopened.

In fact, the development of innovative drugs is like a long -lasting journey, and all difficulties are only staged.The front antibody is no exception, and its story is far from the time when shouting.

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