[Transfer] The current ADC is like the PD-1 of the year

[Transfer] The current ADC is like the PD-1 of the year

Source: amino observation/Fang Taozhi

Of course, a person's fate must rely on self -struggle, and at the same time, you must also consider the process of history.

This is the birth of the domestic biopharma. The advent of PD-1 not only changed the life trajectory of many patients, but also changed the fate of pharmaceutical companies. Biotech, such as Baiji, Cinda, Junshi, successfully advanced to Biopharma with PD-1.

We have already gone through the first wave of innovative medicines, and Qianfan's second wave is coming rapidly. At present, the most capable of becoming the next PD-1 is a high probability that ADC (antibody coupling drug).

Today's ADC track is similar to the former PD-1. The strongest ADC drug DS-8201 detonates the ADC track, and the expectation of the ADC track is full. The global global scale of market global ADC drugs is expected to exceed 100 billion.

The huge imagination space has made overseas join the Geely and Asleycom's heavy money; domestic companies have not been absent, including Hengrui Pharmaceuticals, Rongchang Biological, Coronbutai, Biotai and other companies.

This time, who will have the luck of "Cinda, Baiji"?

/ 01 /

The next star of hope

After PD-1, ADC became the next star of hope.

ADC is not actually a new concept. The earliest ADC drugs can be traced back to 2000, which is mylotarg developed by Pfizer.

Due to security issues, the first -generation ADC was delisted in 2010 without setting off the wave of the ADC track. Later, Roche's second-generation ADC drug T-DM1, the effect can only be said to be good, but it is far from the level of creating the new era of ADC.

Until 2019, the birth of DS-8201 showed the disruptive effect on existing therapies. Since then, it has refreshed people's expectations for ADC drugs again and again. The ceiling of ADC drugs is also continuously improved due to the emergence of DS-8201.

An article published by 2021 "Nature Reviews Drug Discovery" predicts that the market size of ADC drugs in the world will be more than 16.4 billion US dollars by 2026, equivalent to nearly 110 billion yuan.

The popularity of a new medicine was ignited by the entire ADC track, and ADC became the fragrant citron of everyone. According to statistics from Insight databases, as of the end of 2021, a total of 408 ADC drugs around the world are in different R & D stages. Among them, a total of 74 ADCs in China are in different R & D stages, and a total of 17 models have entered the later clinical period.

Just like that year, if there were few PD-1 products in the pipeline, they would be embarrassed to say that they were doing innovative medicines. Today, whether in the first -level market or secondary market, I am embarrassed to say that I have invested in innovative drugs.

It is for this reason that in recent years, heavy transactions around ADC have occurred almost every year. For example, Geely, 2020, acquired the ADC company Immunomedics at a high price of $ 21 billion, setting the highest trading record that year.

In 2021, Rongchang Biological successfully went to the sea with ADC drugs, obtaining the US $ 200 million down payment and $ 2.4 billion milestone in Seattle genes, refreshing the License Out record of domestic innovative drugs that year.

And this year's heavy transactions are likely to come from the ADC field. Not long ago, the Wall Street Journal reported that Meridon was evaluating the possibility of acquiring the acquisition of ADC Giants Seattle genes. At present, the market value of Seattle genes is US $ 32.5 billion. If the two parties can reach an agreement on the acquisition matters, there is no doubt that the ADC field will be born again a heavy transaction.

It can be said that today an excellent ADC can become a hard currency no matter everywhere. Back in China, ADC drugs have almost become the hottest position of new drugs, and even described by the market. Inner rolls are like PD-1.

Rongchang creatures with a relatively advanced progress have been approved for listing. In addition, whether it is Biopharma, such as Baiji Shenzhou, Junshi Biology, Cinda Bio, or Biotech, or Biotech, or East China Pharmaceuticals such as Hengrui Pharmaceutical and East China Pharmaceutical The figure.

A ADC competition is being staged.

/ 02 /

The cruel track that tests strength

Different from PD-1, the ADC track is more cruel and tested.

On the one hand, the difference between the effects between PD-1 drugs will not be too different. On the ADC track, iterated ADC drugs will cause dimension reduction blows to the previous generation ADC.

For example, the second-generation ADC king T-DM1 is currently undergoing the crushing of the third-generation ADC king DS-8201.

Before DS-8201 came out, T-DM1 can be said to be the boss of ADC rivers and lakes. The global sales of T-DM1 in 2021 reached US $ 2.178 billion, well-deserved heavy bombs.

But DS-8201 ruthlessly squeezed T-DM1 down the boss's throne. In the head-to-head clinical trial, DS-8201 defeated T-DMD1. In the US NCCN breast cancer guide, DS-8201 has replaced T-DM1 as the preferred plan for HER2-positive breast cancer. In order to seize more market share before landing in DS-8201, there is no better choice except the price reduction T-DM1. In just half a year, the T-DM1 price was reduced twice, and the overall price decreased by 56.7%. The former ADC boss has ended this situation, let alone the latecomers.

On the other hand, the technical threshold in the ADC field may make some insufficient pharmaceutical companies unsuccessful.

After all, compared with ADC, PD-1 is just a monoclonal control, which is much simpler. The ADC is a complex structure composed of monoclonal anti -resistance and toxins, which determines that its preparation process will be more complicated.

ADC only reports a clinical research application (IND). The workload of chemical composition production and control (CMC) is three times that of monoclonal antibody drugs.

After all, in the production of ADC drugs, anti -toxins need to be connected to the three. Among them, the synthesis reactions of connectors and toxins are relatively easy, but the connection between the connection and the antibody is connected to the chemical small molecules and the macromolecules, and the difficulty will be much more difficult.

In addition, there are too many elements that need to be considered during the preparation of ADC. It is necessary to consider multiple factors such as the drug antibody ratio (DAR) and the distribution of drugs and the removal of free drugs. All in all, multiple factors are intertwined and moved to the whole body.

Although the current ADC track is prosperous, hundreds of ADCs in the R & D stage are not all of the future. In the face of high research and development thresholds, it is still unknown whether it can be truly paddle.

For example, Bioteti, even if I copy the drawing according to the drawing of T-DM1, I failed to make a ME ToO product in the end. What's more, the goal of copying homework has become a more difficult DS-8201.

Pessimism said that Biotet is the first domestic ADC that will not be the last failed research and development.

This also tells us that the premise of discussing the internal volume is that at least the product can be successfully approved to be eligible. If the product has fallen on the halfway, then it is likely that the qualifications of the inner volume are likely.

However, there are always two sides. From another perspective, a higher entry threshold means that perhaps the competition pattern in the ADC field may be better than PD-1.

For pharmaceutical companies, as long as they can successfully get ADC tickets, I hope there are.

/ 03 /

Who is the next Baiji and Cinda?

With the strength of the good wind, I sent me to Qingyun.

Looking back at Baiji, Junshi, and Cinda can be promoted from Biotech to Biopharma, they can't do without the gust of PD-1.

In June 2018, O drugs were first approved to be listed in China, and July K medicine was also approved in China in July. In December of the same year, the PD-1 drug of Junshi Biological was approved to be listed, becoming the first domestic PD-1, with a short scene. The world's martial arts are not broken. This is the key to Junshi's PD-1 that stands out.

As a latecomer, Cinda Bio rely on the battlefield of the price war to hit the PD-1 battlefield. In 2019, the cost of PD-1 of Cinda Bio has dropped from hundreds of thousands to 100,000 yuan. With a low price, it became the only domestic PD-1 that entered the medical insurance directory at that time, thereby achieving the curve overtaking.

Although the way the two are successful are different, they will eventually catch the wind.

So, can the ADC field be reconciled to build a Cinda, Junshi, and Baiji Shenzhou? The answer may be yes.

Although the DS-8201 is extremely powerful, it almost blocks the way of other HER ADCs with its own power. But even as strong as DS-8201, it is not perfect.

The most criticized DS-8201 is safety. In multiple clinical trials, DS-8201 has a chance to trigger interstitial pneumonia, and this is a side effect of possible death, and it is because the DS-8201 is warned by the FDA black frame.

This has also become one of the breakthroughs of the ADC track. If you can develop more ideal ADCs, you can ensure the effectiveness of the drug and the safety of the drug. Then, the inner roll will be not afraid.

In addition, the biggest difference between the ADC track and the PD-1 track is that PD-1 is a drug, and ADC is a type of drug with a wider imagination space.

This also means that the road blocked by DS-8201 is not the only way for ADC to move forward, and many differentiated roads can still be taken out in the field of ADC.

You can choose a differentiated target, and you can also get an ADC entry ticket through differentiated indications, just as the adaptation of Rongchang creature selection of gastric cancer breaks out.

In addition, the ADC drugs have innovative space from targets, to antibodies, connectors, and toxins. Pharmaceutical companies can achieve ADC iteration through differentiated ADC design. Just as DS-8201 did, the second-generation ADC was defeated by upgrading the coupling method and toxins.

Of course, as mentioned above, this is a track that tests the strength of pharmaceutical companies. The ideal is very full of reality, and it is easy to do.

From the second -generation ADC to the upgrade of the third -generation ADC, it took nearly ten years.And the third -generation ADC here may be more difficult to iterate.After all, the third -generation ADC has broken the ceiling. It is easy to increase a test paper from 70 to 90, but it is difficult to achieve full score.However, in the field of new drug research and development, high risks and high income are accompanied.The answer of the ADC's internal roll has long been written, just looking at how pharmaceutical companies choose.

Editor in charge: octagonal

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