"Self -knife" 2.5 billion U.S. dollars, Bilemei Shi Guibao Gambling Revelation

Source: amino observation/Fang Taozhi

The troubles between pharmaceutical companies and pharmaceutical companies are not interactive.

For small pharmaceutical companies, the troubles are mainly to develop a blockbuster bomb; but for big pharmaceutical companies, the troubles may be: two heavy bombs can only be left, who choose?

Belle Miki Bao encountered this problem.

Time returns to January 2019. At that time, Beltay Schimingbao announced that it would acquire the new foundation, a "Century M & A" up to $ 74 billion in a $ 74 billion.

However, the curtain was generally stuck as soon as it was pulled, and it was the US Federal Trade Commission.

From the perspective of the US Federal Trade Commission, the merger and acquisition involves the "monopoly" problem:

At that time, Xinji company had an OTEZLA for being approved for listed psoriasis oral drugs, and there was also a psoriasis oral Tyk2 inhibitor Deucravacitinib in the Bellet Schimi Bao Pipeline.

If Deucravacitinib has been successfully developed, Brexit Schimingbao, the entire psoriasis oral medication, will become stronger, which is unwilling to see the Federal Trade Commission.

To dispel the scruples of the Federal Trade Commission, Belief Schimingbao is facing the "two choices" of two drugs. This is a difficult choice.

Otezla is a heavy bomb that has been approved for listing and annual sales exceeding one billion US dollars. Although Deucravacitinib is in the clinical stage and family members have high side effects, the early clinical data surpass the former is still worth looking forward to.

In the end, after weighing the advantages and disadvantages, Beliance Schimibao chose to leave his child Deucravacitinib to sell Otezla. In the future, Bellet Mei Shibao successfully realized:

"Fighting, Mobike becomes motorcycle."

/ 01 /

Baili Mei Si Gui Bao to endure love to cut love behind

For the management of Beltay Schimibao, it is bound to experience a fierce discussion before making a decision. After all, Otezla and Deucravacitinib are like two pieces of meat on the back of the company's palms. No matter which one is selected, it will be "painful."

First of all, Otezla, at that time, Otezla was the only oral medicine on the market that was approved to treat psoriasis.

Psoriasis is a common chronic, systematic immune media, which affects nearly 7.5 million people in the United States. In addition, psoriasis is called "immortal cancer". Patients often need to take medicine for life until the medicine cannot be able to cannot L.

Two major factors have caused the size of psoriasis market. In 2019, the market size has exceeded 20 billion US dollars, including the success of the Medicine King Atada, which is inseparable from psoriasis indications.

However, oral preparations are Otezla's killing tricks. Compared with the frequent injections of mainstream drugs at that time, the advantages of oral preparations are more obvious, and patients have higher compliance. Therefore, it is necessary to say more about Otezla's imagination.

Without talking about the future, the performance of Otezla at the time of acquisition is quite dazzling. In 2018, Otezla's sales reached 1.6 billion US dollars, which is a "heavy bomb" drug with no suspense.

Wall Street analysts have given accounts to Otezla's future, with peak sales of $ 2.5 billion.

The problem is that, although Otezla's prospects are available, Deucravacitinib potential should not be underestimated.

At that time, although Deucravacitinib had just entered the clinical phase of the third phase, whether it was successful, but according to the second phase of clinical data disclosed earlier, the effectiveness of the high dose group can even be comparable to the preferred plan of the second -line treatment of psoriasis. It is worth looking forward to.

Based on this research results, many people believe that Deucravacitinib is expected to change the competitive pattern in the field of psoriasis.

However, Deucravacitinib also has a hidden concern as a Tyk2 inhibitor. Because Tyk2 is a member of the Jak family, many people are worried that the Tyk2 inhibitor may have safety problems as other members of the Jak family.

Many of the JAK inhibitors approved by the FDA before, many of the black frame warnings that warned security. Safety issues will restrict JAK drugs that cannot be pushed to a more front -line treatment, which will affect commercial space.

Based on this background, whether the TYK2 inhibitor can become an exception on security issues, many people still maintain doubt.

In this case, how would you choose one by one, how would you choose? I believe that many people may choose the former, but our story protagonist, who is used to the tip of the knife and licking blood, chose the latter without hesitation.

/ 02 /

JAK drug adverse reaction curse finally breaks

In June 2019, Beltay Schimi Bao decided to sell Otezla.

At that time, many people believed that the decision of Belief Schimibao was not wise. However, now it seems that Belief Schimi Bao does not need to regret the original gambling.

On September 9, 2022, Belky Schimibao announced that the FDA approved its Deucravactinib listing for the treatment of patients with adults to severe plaques psoriasis. The product was named SOTYKTU.

Regardless of safety or curative effect, Deucravacitinib left by Belical Schimi Ribeta is regarded as expected.

First of all, the effect of the FDA for Deucrivacitinib is based on the third phase of clinical results called POETYK PSO-1 and Poeyk PSO-2. These two clinical trials proved that among 1684 patients with a moderate to severe plaques, the DEUCRAVACITINIB effect once a day is better than the comfort and the OTEZLA that takes twice a day.

Of course, as a member of the Jak family, whether it can solve security is the key to determining the future of TYK2.

So how is Deucravacitinib's performance in terms of security?

Specifically, the most common adverse reactions of patients using Deucravacitinib are upper respiratory tract infections, high hemoglobin phosphate, simple herpes, oral ulcers, etc., and do not have severe thrombosis, infection, etc. reaction.

In the 16th week's POETYK PSO trial, Deucravacitinib, placebo, and Otezla were seriously adverse incidents of 1.8%, 2.9%, and 1.2%, respectively.

Although Deucravacitinib is not as good as Otezla on this indicator, Deucravacitinib has more advantage at another indicator.

Among patients using Deucravacitinib, the group rate of retirement due to adverse reactions was 2.4%, which was lower than 3.8%and 5.2%of the use of placezla and 3.8%and 5.2%.

As mentioned above, psoriasis requires almost lifelong medicine, so even if patients can tolerate side effects, insisting on taking medicine is undoubtedly extremely critical.

Based on the above clinical trials, the FDA approved Deucravacitinib for the treatment of psoriasis on September 9. More importantly, the FDA is not like other JAK drugs, adding a black frame warning to Deucractinib.

In view of the performance of Deucravacitinib, Belief Schimi Bao boldly predicts that its sales peak can reach US $ 4 billion, far exceeding Otezla's expectations.

Bellet Mito's gambling gambling is a beautiful result.

/ 03 /

Victory based on differentiated structure design

The development of innovative medicines is a dual contest of luck and strength. It is more lucky, and the strength must be more. This is the case for Beltay Schimibao to stand out in Tyk2 inhibitors.

As a member of the JAK family, Deucravacitinib can crack the security restraint, thanks to the exquisite structural optimization of Belief Schimibao.

As of now, a total of four members have discovered the JAK family:

JAK1: It is mainly related to acute lymphocyte leukemia, acute osteomy leukemia, and physical organ malignant tumors;

JAK2: It is mainly related to diseases such as hypernexia, bone marrow fibrosis, primary platelets, and other diseases;

JAK3: It is mainly related to diseases such as leukemia, T -cell leukemia, and lymphoma;

Tyk2: It is mainly related to skin lymph proliferation diseases and T cell leukemia.

Most of the JAK inhibitors currently have not selected.

This is because these JAK inhibitors are combined with ATP sites in the catalytic domain (JH1 domain) responsible for activating enzyme activity in JAK protein.

However, the JH1 domain of different JAK family members is very similar, so when the drug dosage is low, these JAK inhibitors can also selectively combine with the corresponding Jak kinase.

However, with the increase of the concentration of intracellular drugs, a JAK inhibitor may also affect the combination of ATP and other JAK kinases and lose its selectivity.

As shown in the figure above, JAK1 can be completely blocked at a low concentration, but as the drug concentration rises, JAK2 has also begun to be blocked.

Each member of the Jak family plays a variety of role, so when Jak drugs are suppressed in other JAK family members, there will be a variety of side effects.

Deucravacitinib uses a differentiated structural design, which is combined with Tyk2's pseudo -kinase domain JH2 to make TYK2 a non -active structure.

Unlike the JH1 domain, the JAK family members' JH2 structures are not the same. Therefore, by suppressing this domain, it can only block the signal conduction of IL-23, IL-12 and I interferon dominated by TYK2. , And not inhibit other JAK channels.

In fact, people have discovered that this change point exists, but the idea of ​​only inhibiting TYK2 by combining with JH2, instead of the idea of ​​inhibiting the members of the Jak family only stays in the concept.

Until the transformation procedure developed by Tyk2, Beltay Schimibao increased the selectivity of TYK2 several orders of magnitude, exceeding all other previous methods. In the end, Deucravacitinib's clinical trial was successful, and this concept was confirmed.

In addition, during the research process, Byshimme Schimibao also found that a key methyl group of TYK2 inhibitor selectivity is very easy to be metabolized. The results of the laboratory test also proved that no adverse reaction signals were found in patients with Deucravacitinib for treatment.

It can be said that after layer of transformation and optimization, Bellet Mei Si Guibao finally got a successful Tyk2 inhibitor.

At present, Deucravacitinib is being evaluated for various immune media such as psoriasis, arthritis, and lupus erythematosus. In the field of self -exemption, a new forces who cannot be ignored are slowly appearing.

/ 04 /

Summarize

After Deucravacitinib was approved to go public, it also completely made Tyk2 inhibitors a "air outlet". The second -generation Tyk2 inhibitors such as Nimbus, Ventyx, Alumis, etc. attracted much attention.

On September 12, Ventyx's stock price rose sharply by 64.98%, with a market value of more than 2 billion US dollars.

A chase battle about Tyk2 inhibitors has begun, and domestic pharmaceutical companies have not fallen.

At present, pharmaceutical companies such as highlight pharmaceuticals, Jiayue Pharmaceuticals, Qiyuan Biology, Nuochengjian, Hylk, and Baiji Shenzhou are carrying out the research and development of TYK2 target drugs.

Although the problem of security has always been like Darmoris's sword hanging on Jak drugs.

But Bellers Shi Guibao told us with personal experience that everything can be solved through technology.

This further explains that the core research and development capabilities are importance to the innovative pharmaceutical industry.

From the perspective of domestic innovation medicines today, Fast Follow is difficult to break the internal rolls. In the future, through innovative structural optimization and differentiated structural design, it is the right way to FIRST In Class / Best in CALSS.

Who can succeed? let us wait and see.

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