The Anxiety and Opportunity Behind Evolving Innovative Enterprises to Biopharma

In the season of centralized disclosure of financial reports for another year, public opinion has once again focused on innovative drug companies
.
It is interesting to note that many innovative companies with halos have unsatisfactory financial reports
.
On March 29, Microchip Bio, a pioneer in the field of original innovative drugs in China and the "first stock of innovative drugs" on the Science and Technology Innovation Board, released its 2021 financial report
.
During the reporting period, the total revenue was 430 million yuan, a year-on-year increase of 59.
74%; the net profit fell by 29.
19% to 21.
984 million yuan, and the non-net profit was -3.
9065 million yuan
.
On March 31, Junshi Biotech, which became popular for holding the first domestically produced PD-1, was even more surprising: although the revenue in 2021 was 4.
02 billion yuan, most of it was technology licensing revenue, and the core product Trip The sales revenue of limumab was 412 million yuan, a year-on-year decrease of nearly 60%
.
In addition, as of April 1, the stock prices of star companies such as Microchip Bio, Junshi Bio, Innovent Bio, Kangfang Bio, and Rongchang Bio, which has just entered the "A+H" era, have all halved from the highest level, with some declines.
More than 2/3, even Rongchang Biotech, which has entered the Science and Technology Innovation Board again, could not escape the situation of breaking service on the first day
.
This is just an appearance.
What needs to be thought deeply is that the primary and secondary markets are gradually cooling down innovative drug companies.
At present, it is a critical period for these companies representing China's cutting-edge innovative forces to evolve from Biotech to Biopharma.
Innovative drugs are Has it become a real red ocean or is capital doing strategic persuasion? Losing the pursuit of hot money, where will innovative companies go? The actual exam questions have been issued, and every enterprise is an answerer
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PD-1: Technology bubbles are more vigilant than capital bubbles At present, PD-1 has almost become synonymous with innovative drug bubbles
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A senior securities analyst said bluntly, "The primary market has already stopped the PD-1 project
.
" She explained that the PD-1 market has been very thorough.
Except for the listed products, no matter what stage the other research projects are in, the capital will Timely exit stop loss
.
"As the saying goes, the tuyere seen by one person can often make him a lot of money; the tuyere seen by a group of people can usually make this group of people "leek to be cut".

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The PD-1 field is vividly interpreted with real cases
.
At present, there are more than 150 PD-1/L1 under research in the world, and Chinese companies participate in cooperative R&D, which accounts for half
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In the first half of the domestic PD-1 field, the battle for indications and medical insurance has come to an end, and the market pattern has quietly changed: Junshi Bio’s PD-1 has not changed the trend even if it handed over the promotion rights to AZ in non-core cities in China; In contrast, Kangfang Bio's piamprilumab sold a total of 212 million yuan in more than 3 months
.
The latter granted the exclusive sales rights of PD-1 in China to Chia Tai Tianqing
.
Hengrui Medicine's camrelizumab surpassed K drugs in the domestic market, reflecting that the domestic market has entered the second half-competition of marketing and promotion
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Including Henlius’ slulimumab, 9 PD-1 products have been launched in China, and the market has been shrinking.
All PD-1 products have begun to target overseas markets
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It's just that in February this year, Innovent Bio's PD-1 failed in the United States
.
On March 24, the application of Daboshu combined with pemetrexed and platinum-based chemotherapy for the first-line treatment of patients with non-squamous non-small cell lung cancer was not approved by the FDA, and PD-1 going overseas is also full of many uncertainties
.
Due to the continuous optimization of the policy environment, capital and public opinion have conspired to fuel the fire and make the PD-1 track prosperous and crowded
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From gene sequencing to medical AI, the bubbles disappear one by one, and capital is also betting that it can exit before the bubble bursts
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However, PD-1 is a new anti-cancer drug that has not been encountered in the past ten years.
The total annual sales in China exceeds 20 billion.
In the second half, we need to see the level of marketing
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Returning to rationality, it is worth considering that, on the one hand, PD-1 projects are swarming, and the use of off-indications is moderately relaxed in clinical practice, but the research on adverse reactions has not been paid enough attention
.
Professor Wu Yilong of Guangdong Provincial People's Hospital has called for many times: "Research on the toxic and side effects of immunotherapy in the real world should be strengthened
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Compared with chemotherapy, although the toxic and side effects of immunotherapy are lighter and most of them are easier to deal with in the early stage, doctors should be good at finding Corresponding measures to study new problems
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Is it necessary to add new observations to address cardiotoxicity? Using big data to find out the average time from medication to the occurrence of cardiotoxicity, it can help doctors to judge the possible time of side effects in advance, so as to make predictions and take corresponding measures
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With the rapid advancement of off-indication use and combination drugs, the research on toxic and side effects should be highly valued, and this is where breakthroughs should be made at the technical level
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On the other hand, compared with the capital bubble, we should be more alert to the technology bubble
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By the end of 2021, more than 350 PD-1 clinical trials in China have been publicized, involving more than 450 research centers and 2,427 researchers
.
Only this The repetition of a high-end technology not only causes a waste of innovation resources, but also hedges against the iterative upgrade of advanced technologies just like the original low-level repetition.
There was a "Tini explosion" before, the existing PD-1 track was crowded, and ADC drugs got together later.
, it is urgent for innovative companies to get rid of technology bubbles
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Uncertainty: Anxiety and Opportunities for Source Innovation and jumping out of the shackles of current innovation inertia is the biggest anxiety of many companies
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As mentioned in the book "Innovative Survival": Anxiety comes from uncertainty, and the career that everyone believes in and devotes to can be subverted instantly
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"The same is true of pharmaceutical innovation, which tests every innovative company
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When talking about drug innovation in China, we have to mention the star product "chidamide"
.
This original small molecule anticancer drug approved for the market in 2014 is the first in Chinese history.
It is an original chemical new drug
.
In 2001, Chipchip Bio, which completed the first round of financing of 50 million yuan, was established and started the road of original drug research and development
.
At that time, it was the golden age of generic drugs in China.
However, the new drug research and development was not favored by the capital at that time, and it fell into financial difficulties several times.
In the end, under the pressure of investors, Microchip chose to "exchange patents for funds"
.
In 2006, the price of chidamide was 28 million US dollars.
of foreign patents licensed to a U.
S.
company
.
Although such a strategy has brought a chance for Microchip Bio to survive, Chidamide has lost all international markets except China, which has also laid hidden dangers for today's situation
.
According to its 2021 financial report, Chipchip Bio has successfully launched two original drugs: Chidamide and Siglitazone sodium, a new drug aimed at improving adult type 2 diabetes
.
The latter went public in October last year, with revenue of only 3.
258 million yuan
.
Chidamide sales revenue of 387 million yuan, plus related patent licensing revenue, accounted for more than 99% of the total revenue
.
In 2021, its R&D investment is only 130 million yuan, an increase of 40% over the previous year, but it is far from other innovative companies.
As of 2021, Microchip Bio has applied for a total of 407 invention patents worldwide, and follow-up products.
The online conversion ability and the establishment of a nationwide marketing ability improvement will be the biggest test of breaking the game
.
Another case with a very different path is BeiGene.
Innovative drug companies listed in the three places have fallen in U.
S.
and Hong Kong stocks since 2022
.
As of April 1, the STAR Market had fallen about 40% from the issue price
.
In 2021, its revenue is US$1.
176 billion, a year-on-year increase of 280%; the net loss is US$1.
413 billion, which is behind the high R&D investment - US$1.
459 billion in research and development expenses during the reporting period
.
In terms of composition, more than 50% comes from drug sales, and the rest comes from technology licensing income.
Its accumulated losses in the past ten years have exceeded 33 billion yuan
.
The support behind it is continuous financing, and more than 100 clinical trials have been deployed around the world
.
Although zanubrutinib’s full-year U.
S.
sales were about $120 million, a year-over-year increase of 535%
.
However, under the background of increasingly rational capital, how to balance source innovation and financial situation is still a big test
.
The U.
S.
Securities and Exchange Commission recently included 5 Chinese concept companies in the tentative list of the "Foreign Company Accountability Law", and BeiGene is among them
.
In fact, the innovative drug bubble that has lasted for several years has begun to burst.
Since 2021, the stock prices of companies such as Innovent Bio and Affinity Bio have fallen by nearly 80%.
Without hot money, what should corporate innovation do? ADC drugs have become another hot direction after PD-1
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As of the end of 2021, a total of 408 ADC drugs are in various stages of development globally
.
Soul torture: Where are the real innovation opportunities? Many companies have put forward soul torture, and there are both big and comprehensive paths and small and beautiful strategies to move towards Biopharma
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Some experts say that in addition to the above two types of models, there are also companies that are benchmarking against Regeneron in the United States
.
Established in 1988, the first three clinical studies of Regeneron’s products all ended in failure.
Compared with contemporary innovative companies, it took nearly 20 years for it to win the first new drug approved by the FDA, but in this process, it took many years Dormant established the Trap technology platform and the VelocImmune technology before it began to emerge
.
Regeneron started the operation mode of "walking on two legs": on the one hand, through cooperation with external pharmaceutical companies, it brought huge cash flow to support the development of its self-developed products
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Nearly 1/4 of the fully human mAbs under development, FDA-approved and authorized worldwide come from Regeneron's technology platform; on the other hand, Regeneron has developed a number of mAbs and dual (multi-)specific antibody drug candidates.
etc.

_ By the end of 2020, the per capita yield was US$930,000
.
Where the opportunities lie mainly depends on the comprehensive strength and strategic decision-making power of individual enterprises.
Platform innovation and super marketing power will become two sharp swords
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