Scientists compromise companies, investors numb Me-too or FIC drugs end up?

Six years ago, when the "722 tragedy" occurred, few people knew exactly where the pharmaceutical industry was heading toward another village
.

The old medical man who lay flat in the past wailed everywhere, and finally had to accept the verdict of the policy
.

After the foundation stone of Circular 44 was laid, the desperate new medical professionals also gradually saw the light

With the improvement of the approval environment for innovative drugs and the open environment of “tailor-made” by the capital market for biomedicine, the biomedical industry has quickly become the “darling” in the turbulent environment
.

Suddenly influx of funds has always been keen, hoping to make a big picture, but for the biomedical industry where there are high-tech barriers and closed, they seem a little bit helpless, and the original "smart funds" have become less smart

At first, most institutions did not have the ability to select potential projects and wanted to share the dividends of the development of innovative drugs, so they could only choose to follow along
.

Some investors once confessed to the E-pharmaceutical managers of the binding relationship between the institutions, and expressed the strong demands of LPs (limited partners, people who pay the institutions) for popular targets

Due to multiple factors, the creation of Chinese innovative drugs under the carnival has developed abnormally, which is also defined as "involution" by everyone
.

The so-called "involution" is mainly manifested in the gathering of popular targets, repeated declarations of a large number of me-too drugs, and huge investment bubbles

The most embarrassing thing is PD-1.
As a milestone drug in China's pharmaceutical innovation, even the world is a dividing line drug.
China's Biotech (BaiGene, Cinda, Junshi) uses it to move to the center of the stage, and the local Big Pharma (Hengrui) uses it to accelerate innovation and transformation
.

But now PD-1 has become synonymous with homogeneity

Now criticizing homogeneity has become a "trend".
Almost everyone is calling for First-in-class (FIC), but it seems that they can't see the action.
The industry has fallen into a "dead loop" of mutual condemnation
.

Wu Xiaobin, President of BeiGene, once told the E-pharmaceutical managers that now they dare not communicate with their peers without First-in-class drugs

Is the dilemma of China's innovative drug creation just because it can't create First-in-class? What is the real dilemma? How do the government, enterprises, and capital view this kind of ``involution''? Do you want to do FIC? At this stage, Me- Can't too medicine be done? How to do source innovation?

01 Aspects of the industry

The true development of China's innovative drugs has only been three or four years.
In terms of the industry's life cycle theory, it is in a period of vigorous growth, but it is considered to be in a serious involution and there is no source of innovation
.

Universities are "not confident", scientists are "compromise", entrepreneurs are "self-deception", investors are "self-numb", supervision is "hesitating", CXO is "indifferent".
.
.
Each link in the industry chain has its own considerations.
These considerations lead to The chain cannot be opened up, the transformation of innovation achievements is difficult to achieve, the homogeneity is obvious, and the source innovation is "buried in the snow
.

"

Universities and scientific research institutions are at the top of the innovative drug industry chain, and in foreign countries, they often become supply stations for source innovation
.

In China, the poor implementation of innovation and transformation in colleges and universities has become a commonplace problem

"We have discovered the absorption mechanism of the third generation of small nucleic acids in the body, which makes it possible for small nucleic acid drugs to become the third largest class of drugs in the three pillars of small molecule drugs and antibody drugs
.

For more than ten years, we have been crazy to everyone Sales, but with little effect
.
On the contrary, after the mRNA vaccine came out last year, suddenly, both the investment community and the industry became interested in us
.
" Zhang Chenyu, Dean of the School of Life Sciences, Nanjing University, described his personal experience
.

Under the predicament, the transformation of colleges and universities has moved towards a middle ground
.
According to Gu Zhen, Dean of the School of Pharmacy at Zhejiang University, leaving aside the gap with Western countries, there is still a phenomenon of "innovation and transformation" in colleges and universities.
Simply put, it is the articles published on professors' bookshelves and the last things sold on the shelves.
Sometimes it is not consistent, or it is relatively easy to sell things on the shelf
.
Institutions do not invest, and companies rarely cooperate with universities.
This is the norm
.

Second, there are fewer and fewer pioneers in the industry.
Scientists are either compromised or marginalized in the late stage of entrepreneurship, unable to determine the direction of the R&D pipeline
.
An industry scientist who focuses on source innovation said in an interview with E-pharmaceutical managers: The root cause of homogeneity is that only 1% of domestic investment institutions are truly capable and willing to invest in true source innovation, so start-ups It is almost a must for companies to compromise to obtain financing and do Me-too medicine concurrently
.

A dean of the MNC China Research Institute believes that another important internal cause is the change in the identity of scientists
.
"Most of the scientists nowadays are "migrant workers" like me.
In order to survive, they think about how to post articles, how to apply for funds, and how to become academicians
.
" Whether it is China, the United States, or Europe, they should invest in them.
More funds go to basic research and encourage everyone to do pioneering research before they can find new targets
.

However, true science never stops, and more and more scientists are beginning to participate in the transformation of basic research
.
Recently, the first product of Viterilon, RIP1 inhibitor, founded by Academician Wang Xiaodong, was accepted by the NMPA for clinical trial applications
.
Established in 2018, Viterilon focuses on neurodegenerative diseases and inflammatory diseases, mainly based on the basic research of Wang Xiaodong’s laboratory in the mechanism of apoptosis, and the development of small molecules for the mechanism of apoptosis in Wang Xiaodong and Zhang Zhiyuan’s laboratories The ability of drugs
.

Third, the "self-deception" imagination of entrepreneurs permeated the entire industry
.
"In the entire development of China's biomedicine, everyone thinks that they are Me-better, not Me-too
.
" Tian Zhigang, an academician of the Chinese Academy of Engineering, said bluntly
.

As we all know, the gold standard for measuring Me-better is a head-to-head test
.
When each Me-too drug is released, the creator of the new drug will attach a unique label to each "new drug" to distinguish it from the new drug already on the market, instead of choosing to be head-to-head
.
Therefore, Me-better is "speaking" in China, and it is difficult to go abroad
.

Sometimes E-medicine managers ask those interviewees who homogenize drugs whether they are going to be head-to-head? Almost all they get are negative answers, mostly because of cost considerations
.
For products with serious homogeneity, such as PD-1, when the E-pharmaceutical manager once asked a new pharmaceutical company whether it was going to stop, the other party's answer was "I can't stop it!" This subtext means that although it will face fierceness in the future However, the discounted benefit after listing is still greater than the investment cost of suspending R&D
.

Fourth, capital is considered to be the main driver behind the homogeneity, and always keen investors, regardless of objective or subjective reasons, seem to be "self-numbing"
.
For popular targets, it is inevitable for investment institutions to scramble for projects
.
"Some institutions have rushed to join in order to grab the project and did not make enough adjustments.
This is something that has never been done before," one investor said bluntly
.
And this time, regardless of whether it is really to meet unmet clinical needs, anyway, as long as you wear the cloak of "innovation", you can attract attention
.

At the same time, the valuation methods of innovative pharmaceutical companies, especially the leading innovative companies, by funds with strong capital and long cycles are quietly changing
.
The basis of this change is that investors firmly believe that 10 years from now, the top 20 companies in the pharmaceutical industry must have one or more seats among innovative pharmaceutical companies
.
Therefore, even if the valuation method of the secondary market is used to complete the investment in the primary market, investors will choose to "make heavy bets
.
"

Fifth, the attitude of the regulators is very difficult for the homogeneity of the flood
.
A drug reviewer once told the E-drug manager that the country would be happy to see the results of companies clustering together drugs for the same target, because the more they do, the earlier they can push that class of drugs to the stage similar to generic drugs.
, On the one hand, it can reduce the cost of government expenditures, on the other hand, it can improve patients’ access to medicines
.
Especially under limited medical insurance conditions, as more and more new drugs are approved, the more room for bargaining during medical insurance negotiations
.

Sixth, CXO, as the "water seller" of the innovative drug industry chain, will not have the effect of preventing homogenization, and even one molecule changes to different companies, as long as there is a demand from the company
.

02 How to look at "involution"

Almost all leading companies in the subdivision field have expressed an open attitude towards involution
.

Wu Xiaobin, President of BeiGene, believes that China is at the beginning of innovative drugs and is a process that must be experienced.
Whether it is Me-too or Fast-follow, it has greatly solved the problem of patient medication
.
Second, competition is a good thing
.
In the early 1980s, China’s household electrical appliance industry had repeated construction and internal volume was much more serious than it is now.
However, a number of very outstanding enterprises have been trained in the competition.
Now the global household appliance refrigerators, TVs, and washing machines have a market share of more than 50%.
It is a Chinese company
.

"For the leading companies, it is precisely because of competition, whether it is benign or vicious competition, that we are always on our backs and restless every day, thinking about promoting faster and higher-quality products to the clinic.

Going public .
" said InBev, founder of Aibo Biological
.

InBev also stated that mRNA or nucleic acid medicine is slightly different from other fields.
The platform is solid and the products follow.
In the end, a "winner take all" situation may be formed
.
However, in InBev’s view, its mRNA field is far from forming an involute.
Even if an involute is formed, the reorganization and integration after the involute will give top companies more opportunities to integrate the remaining in the market.
Resources
.

For investors, inward roll means higher risk
.

"
Whether it is a bubble or an involution, this is a necessary stage for the development of things .
No matter how you remind them, some money will still go down, and some entrepreneurial impulses can't be killed.
I don't think every entrepreneur will feel that he will be.
The one that failed
.
" Xu Xiaolin, founder of Huagai Capital, said bluntly
.

Xiao Zhi, co-head of the SDIC Innovative Medicine and Health Team, believes that when ten homogenized products appear, investors will calm down and re-evaluate and find new directions
.
However, the License-in model uses a small team of ten people and a small team of twenty people to introduce a few products and rush to the capital market to attract a large amount of capital.
However, it remains to be seen whether the team can do things down-to-earth.
The industry has a great influence
.

The key is how the regulatory authorities view the involution
.
An expert who once served as a new drug review committee said that if all fields want to move forward quickly, there must be a bubble, but the bubble must have a limit
.
Once the bubble bursts, it will be a tragedy for China's entire biomedical field when capital leaves
.

The aforementioned experts believe that the bubble is still accumulating
.
But if we continue to move forward in this state, there will be a disaster in three years.
Now more than half of the 18A companies in Hong Kong have fallen below the issuance
.
Will the "Guiding Principles for Clinical Research and Development of Anti-tumor Drugs Oriented by Clinical Value (Draft for Comment)" burst the bubble? "It depends on who will operate
.
"

03 Me-too or First-in-class?

The industry has a very fierce debate on Me-too and First-in-class, but in summary, the views are roughly the same: between the two, it is not a simple question of FLC replacing me too
.
We need to start doing First-in-class at this stage, but Me-too is equally important
.
What the industry opposes is not Me-too drugs, but We-too drugs
.

Liang Zicai, a well-known domestic small nucleic acid expert, said that at this stage, FIC has become a realistic possibility
.
When it was 50 or 70 years behind in the past, to talk about innovation at the source was actually'finding the moon in the water'
.
Now some people can consider doing source innovation
.
He also believes that source innovation is a basic viability that China must form at this stage, but it cannot become a trend.
It is related to the baton, such as the state's indicators for major special projects, the evaluation indicators of funds for enterprises, and universities' performance for professors.
Assessment indicators
.

Academician Tian Zhigang also believes that now is the time.
China needs to emphasize research (basic research).
Research has two signs: one is a team.
It does not become a real research when one or two people do it, especially for the future immunization.
Treatment; the second is that the team needs to stick to it and needs long-term accumulation.
In this sense, it may be a huge challenge to research at present
.

But not everyone has to do FIC drugs
.
He Ruyi, the former chief scientist of CDE, believes that China's new drug R&D has only experienced rapid growth in recent years, but it is still in an early stage that is not so mature
.
The reform of the drug inspection system has led to the development of new drugs, but market access has not kept up, so the true source innovation has not received the return it should have
.
Because the risk of source innovation is too high, venture capitalists are reluctant to invest, and the United States is the same
.
Therefore, at this stage, it is unrealistic to require all companies to do source innovation.
Fast-follow is also very meaningful.
China also lacks such drugs.
For example, the annual treatment cost of PD-1 can meet clinical needs of 10,000 to 20,000 yuan
.

Liu Changxiao, an academician of the Chinese Academy of Engineering, also pointed out that more than 90% of the varieties approved for listing in the United States each year are also Me-too, and the key is the question of "how to guide and how to do it"
.

04 Conditions for Source Innovation

The formation of each FIC has its prerequisites
.

For example, the discovery of PD-1 actually started from a huge breakthrough in the concept of immunology, which changed people's understanding of tumors from directly targeting tumors to targeting the interaction between immune cells and tumors
.
Under the breakthrough of concept, the discovery of several targets that recognize each other between immune cells and tumors, it will take a long process from target discovery to promising treatment
.

"No one has the ability to achieve the ultimate in a specific link.
You may have to achieve the ultimate in each link of the chain, and finally work together to achieve one thing
.
" Academician Tian Zhigang said when talking about how to do source innovation
.

The conceptual breakthrough requires basic research
.
Academician Zhang Lihe said: If basic science is not supported, China will always be Me-too in medicine
.

The root cause must be policy first
.
Song Ruilin, executive chairman of the China Association for the Promotion of Pharmaceutical Innovation, said that if scientists are not guided by policies, their lives will be very difficult.
We must implement some truly road-oriented and forward-looking policies to allow scientists to develop their potential and talents
.

With the basic research, when considering the new drug business model, Zhu Xun, honorary chairman of the Freehand New Drug Elite Club, believes that there are three more points that need to be protected:

One is a scientific, standardized, and transparent regulatory system.
Without such a regulatory system, it is impossible to initiate innovation
.
I personally think that this part of the regulations has been basically integrated, but law enforcement, justice, and the popularization of the law are not in place, just like the traffic lights are there, and the zebra crossing is there.
Everyone does not abide by it, and those who do not abide by it will not be punished
.
"The PD-1 should be used for the operation.
You can cut the ground to loosen it first, and withdraw all those who are below 50.
The trend of not showing the spirit of '722' can't be reversed
.
"

Second, there must be a strict intellectual property protection system, not only for patent issues, but also for data protection, including subsequent patent verification
.
Without this system, knowledge achievements can be easily stolen, and no one would be willing to invest
.
"At this stage, China's protection of intellectual property rights is seriously insufficient.
How many consecutive years has China's patents been the world's number one? But in summary data, the conversion rate of China's patents in the medical field is not as good as that of Stanford
.
"

The third is to have a proper payment system for new drugs
.
Take the United States as an example.
60% to 70% of the top 10 pharmaceutical companies in the United States are not domestic companies.
It is precisely because they have an appropriate payment system that global innovative drugs are gathered in the United States
.
Without this payment system, China's First-in-class and Best-in-class will not emerge for a long time to come
.
The per capita medical expenses in the United States are already US$10,000, but we are only US$480, so the country’s next step is to liberalize commercial medical insurance
.

(Note: The content of this article refers to the content of the 3rd Global Biomedical Frontier Technology Conference held in Suzhou with Freehand)