In the second half of the industry, what will innovative pharmaceutical companies bet on tomorrow?

In 2022, the innovative drug industry will be particularly deserted.

But in fact, winter is not scary, just carry it over; what is scary is that this kind of expectation that has been shrouded in the industry for a long time makes people lose sight of their heads

In such a period of downturn in the industry, various innovative pharmaceutical companies are using their own methods to fight the earth-shaking changes in the industry

"No business"

Last year, Junshi Bio's total revenue was 4.

The new crown neutralizing antibody has turned into a "money printing machine", and it has been the same for a while, but whether such a miracle can continue in the future is full of uncertainty

In addition to the above two drugs, Junshi also has a commercial product

The sales force was starved of food, and with each passing day, R&D and sales expenses were as greedy as gold-eating beasts

The sales force was starved of food, and with each passing day, R&D and sales expenses were as greedy as gold-eating beasts

But whether to seize the wind is sharp or speculative, and the recognition and doubts of the outside world are also accompanied

- 01 -

- 01 -

inescapable opponents

inescapable opponents

In 2018, Junshi's PD-1 monoclonal antibody (toripalimab injection) won the first "domestic PD-1" title, but missed the first opportunity to be included in medical insurance and increase its volume

When people talk about Junshi, they can't do without comparing Xinda with it

In November 2019, the medical insurance negotiation of toripalimab failed, and Cinda's sintilimab entered smoothly with a price reduction of 63%

In 2020, it will be exclusively included in the medical insurance catalogue, allowing Cinda's sintilimab to rapidly increase the volume and successfully complete the market promotion.

"Not getting medical insurance in the first year" is often regarded as a major strategic mistake of Junshi by the outside world

Not only Junshi, but for the four major PD-1 manufacturers in China, enrolling in medical insurance has become a non-negotiable matter

Now, the 2021 PD-1 transcript has been released, and the results of the four PKs are very obvious

Many people sighed at the bleak sales of Junshi PD-1: it was launched at almost the same time as Cinda's PD-1 (December 2018), but now sales are sky-high
.
Competitors who start at the same time are often compared
.

Some investors are not surprised by Junshi PD-1's relatively backward earnings: "Junshi's inclusion in medical insurance is a small indication, and doctors still have concerns about its off-label use (over-indication)
.
"

In 2021, toripalimab will only be covered by melanoma, and the domestic market for this indication is limited
.
According to Frost & Sullivan's analysis, the annual market size of PD-1 for melanoma is about 400 million yuan, accounting for about 1% of the tumor market
.

Last year, toripalimab was approved for marketing for two indications, namely urothelial carcinoma and nasopharyngeal carcinoma
.
But in fact, the patient groups for these three indications are relatively small, and they are incomparable with the common major indications of PD-1 such as lung cancer and liver cancer
.

Obviously, Junshi has taken the route of entering the PD-1 field with multiple small indications
.
Cinda moved to the direction of large indications earlier.
After Hodgkin's lymphoma, a lesser diseased indication, was listed and included in medical insurance, the following three major cancer indications were approved one after another: non-squamous Non-small cell lung cancer, squamous non-small cell lung cancer, first-line advanced liver cancer
.

At present, Junshi is also conducting clinical trials for indications with larger patient groups at the same time to drive the market expansion of larger indications
.
Xiong Jun, chairman of Junshi, said at a communication meeting not long ago, "We can finally have a better indication layout" and will harvest multiple exclusive indications this year and next
.

Some people in the industry are optimistic about its two major indications of PD-1 adjuvant therapy - liver cancer adjuvant and non-small cell lung cancer adjuvant exclusive approval
.
Junshi's co-CEO Li Cong has predicted that sales of toripalimab could double this year
.

However, in order to double the performance, the number of indications is not enough, and the sales ability is the most direct performance promoter and guarantee
.
"Innovent's sales (>
.
An industry insider familiar with Cinda revealed
.

From Cinda's 2021 financial report, we can find evidence that it has invested heavily in sales
.
As of December 31, 2021, its annual sales and marketing expenses were about 2.
541 billion yuan, accounting for nearly 60% of total revenue
.
In contrast, Junshi's sales expenses are less than one-third of its sales, only 730 million yuan, accounting for 18% of total annual revenue
.
Sales expenses directly expand the size of the sales team.
It is reported that as of the end of last year, Junshi's sales team had more than 800 people
.

It is reported that as of the end of last year, Junshi has a sales team of more than 800 people
.

It can be said that Cinda has done a lot of "heavy" in sales from the very beginning, and spared no expense to cultivate its own sales team
.
Some institutions once conducted field research on Cinda and believed that Cinda's sales were learned from Hengrui, which was very wolfish, but its accumulation was not as good as Hengrui's
.
"If the follow-up varieties are promoted in the way of PD-1 in the future, it may become bigger and stronger
.
"

In the long run, a strong sales team is the right-hand man for future pipeline promotion
.
However, if there are few or no drugs on the market, the hole for this sales legion to burn money will get bigger and bigger
.
In other words, a certain number of pipelines need to be "feeding" continuously
.

Today, Cinda is facing the challenge that the "sales machine" cannot be idle.
Since the number of its own pipelines for promotion is limited, it is better to be the "pharmaceutical agent" of other pharmaceutical companies than to be idle
.
Recently, Cinda issued an announcement stating that the company will obtain the exclusive commercialization rights of a number of Eli Lilly's drugs in mainland China
.

Junshi's commercialization ideas are somewhat tortuous.
In February last year, it first "held hands" with AstraZeneca, hoping that this multinational pharmaceutical company, which is known as the most understanding of China, could bring toripalimab a big sale
.
At that time, many people were optimistic about the cooperation between the two parties and predicted that the domestic sales of Junshi's PD-1 mAb would increase by more than 50% in 2021, reaching 1.
6 billion to 1.
8 billion yuan
.

Reality is skinny
.
"It is really difficult for foreign companies to promote commercialization when the indications are not covered by medical insurance
.
" Finally, in January this year, Junshi Bio announced the termination of the promotion cooperation with AstraZeneca and took back the toripalimab agreed in the original agreement.
The right to promote injection
.

On the one hand, the beautiful illusion of commercial cooperation has been disillusioned, and on the other hand, the turbulence of Junshi's internal commercialization team has arisen one after another
.
In November last year, its chief commercial officer, CCO Qian Wei, resigned four months after joining Junshi.
Qian Wei had worked for AstraZeneca, Roche and other multinational pharmaceutical companies
.
It is worth noting that Junshi has replaced three chief commercial officers in three years
.

Junshi Biotech admitted in its annual report that frequent team changes have greatly affected the stability of the team, the team's execution ability has declined, market activities cannot be executed stably, the effectiveness of market activities has declined, and customer cooperation confidence has been greatly affected
.

, The frequent team changes have greatly affected the stability of the team, the team's execution ability has declined, the market activities cannot be executed stably, the effectiveness of the market activities has declined, and the customer's confidence in cooperation has been greatly affected
.

"The biggest challenge Junshi faces is the construction of a commercial system
.
" Xiong Jun admitted at the above-mentioned communication meeting that in the next 1-2 years, its PD-1 monoclonal antibody will add about 11 new indications, and the construction of its sales force can Whether it can keep up completely, the pressure is still quite large
.

- 02 -

- 02 -

How high and how long can you fly by taking advantage of the new crown concept?

How high and how long can you fly by taking advantage of the new crown concept?

Looking at the annual reports of the four major domestic PD-1 pharmaceutical companies last year, Junshi has a completely different >
.

The biggest contributor to Junshi’s revenue last year came from the COVID-19 neutralizing antibody, ectelizumab, which was jointly developed by Junshi and the Institute of Microbiology, Chinese Academy of Sciences in 2020, and was approved by the FDA in February 2021.
Eli Lilly is responsible for Its commercialization in the United States
.

Junshi did not directly announce the specific benefits brought by neutralizing antibody therapy, but it is estimated that it is at least 2 billion yuan
.
During the reporting period, Junshi's technology licensing and franchise revenue from Eli Lilly was approximately RMB 2.
365 billion, exceeding 50% of the total annual sales
.

But such a surge in revenue faced the brakes in January this year.
On January 24, the FDA announced that it would limit the use of Regeneron and Eli Lilly/Junshi's new crown neutralizing antibodies
.
It can only be used unless it is a mutant strain such as Delta that is sensitive to these new crown neutralizing antibodies
.
"Because the new crown virus mutates too fast, the life cycle of (neutralizing) antibodies is only one or two years, and the imagination is limited
.
" An investor familiar with the research and development of new crown oral drugs explained
.

"Because the new coronavirus mutates too fast, the life cycle of (neutralizing) antibodies is only one or two years, and the imagination is limited
.
"

Recently, what has affected the secondary market nerves is its new crown small molecule oral drugs, including VV116 (targeting RdRp) and VV993 (targeting 3CL protease), the former and Merck's Molnupiravir and Gilead's Remdesivir principle.
Similarly, the latter is the same target as Pfizer’s new crown oral drug Paxlovid (hereinafter referred to as: P drug)
.
These two targets are also the mainstream targets for the current research and development of new crown oral drugs
.

At present, VV116 has received the most attention and made the fastest progress.
In December last year, the Ministry of Health of Uzbekistan approved the emergency use authorization of the drug, and VV116 has subsequently become the fourth oral drug approved for the treatment of new coronary pneumonia in the world
.
The latest development is that in the Shanghai Public Health Clinical Center, the first patient has completed the enrollment and administration of the drug
.

In fact, Junshi's new crown drug research and development pipeline has reached 4 models
.
It can be said that it is not one of the four largest domestic PD-1 manufacturers that bet on new crown drugs
.
A company's growth path is often branded with the genes of its decision makers
.
As the actual controllers of Junshi, Xiong Fengxiang and Xiong Jun and their sons have been controversial because of their background in the fund industry and no medical background.
They have been criticized by the media for affecting their product development
.

It is undeniable that this bet on the new crown oral drug has the investment color of the financial industry, showing sensitivity to popular trends
.
The biomedical practitioner "Lucky Little Yellow Duck" revealed: "Junshi's new crown oral drug project was selected and followed up by Xiong Jun.
He is not just a fund manager that the outside world thinks, but is actually very skilled in business
.
"

"Junshi's new crown oral drug project was selected by Xiong Jun and has been following up.
He is not just a fund manager that the outside world thinks, but is actually very skilled in business
.
"

A large company needs to mobilize a lot of resources to promote a new business.
Junshi, a tumor-targeted drug company, has deployed new crown products at the first time, which is faster than many companies in the field of infection, which is also confirmed from the side.
this
.

Now that the new crown drug is increasingly becoming the fulcrum of its valuation imagination, the proportion of Junshi's anti-virus business is gradually increasing
.
At the node where PD-1 performance is lagging behind and the revenue of new crown neutralizing antibodies is unsustainable, can the new crown oral drug that is about to be released next "provoke the lead"?

There are indeed many optimistic aspects.
First of all, from the perspective of external factors, Pfizer's P drugs cannot dominate the market
.
The first price is more expensive, whether it is the price in the United States (about 3367 yuan/box) or the domestic price (2300 yuan/box); secondly, the production capacity is limited and cannot swallow all the market, and its annual production plan in 2022 is about 1.
2 90 million boxes will be produced in the third and fourth quarters of this year
.

In terms of price and production capacity, P drugs have left a certain window period for latecomers
.
The above-mentioned industry insiders made an assumption: if the sales volume of VV116 is 10 million copies, and the prices are 200 yuan, 500 yuan, and 1,000 yuan per copy (1/10 to 1/2 of the price of P medicine), the corresponding markets are 2 billion yuan, 5 billion yuan, 10 billion yuan
.

"Not only can it be circulated internally, but VV116 can also expand the market of countries along the 'Belt and Road'
.
However, although a country like Uzbekistan has a population of tens of millions, it is limited by the level of consumption, and sales are temporarily unpredictable
.
"

"Not only can it be circulated internally, but VV116 can also expand the market of countries along the 'Belt and Road'
.
However, although a country like Uzbekistan has a population of tens of millions, it is limited by the level of consumption, and sales are temporarily unpredictable
.
"

Many people are optimistic about the performance of Junshi VV116 after its launch.
For example, it can at least bring valuable cash flow, and it can also help it establish a good relationship with the domestic medical system and feed back innovative drugs
.
However, the basis of all this is that the effect of Junshi's new crown oral drug cannot be too different from that of the pharmaceutical giants.
It would be better if the effect is comparable
.
Blacksmithing needs to be hard on its own
.

In fact, it is difficult for VV116 to carve up the European and American markets, which is a large market with considerable size
.
As for the reason, the above-mentioned industry insiders believe: "P drug is very competitive and will become the main force in the European and American markets
.
In addition, in terms of clinical progress, Gilead's second-generation remdesivir may be approved in the United States first, and the FDA has no motivation to do so.
approve a similar drug
.
"

At the same time, Shenlanguan interviewed and learned that the second-generation remdesivir has applied for two compound patents in Europe and the United States, but only one has been applied for in China.
VV116 has been developed on this basis, so it may avoid patents in China.
Disputes, but in Europe and the United States, it cannot be ruled out that it will receive a patent lawsuit from Gilead
.

The RdRp field where VV116 is located is relatively good.
The 3CL protease inhibitors represented by Pfizer’s P drug are more competitive, and Junshi’s VV993 may not prevail
.

"Junshi's VV993 comes from the lead compound found in traditional Chinese medicine, and it is a new skeleton that is re-modified through AI
.
" Junshi's progress is fast, but the progress of other pharmaceutical companies is not slow, such as Zhongsheng, Guangshengtang, Xianshengyao industry,
etc.

"Progress and efficacy are the keys to determining competitiveness.
Everyone is
chasing me.
Pfizer's me-too drug will be relatively stable, and the new skeleton of VV993 needs to wait for the results of clinical trials
.
"

Oral drugs for new crowns with other research and development mechanisms are also coming, such as azvudine (anti-arabinoside dual-target drug) from Real Bio and Prokluamide (androgen receptor antagonist) from Kintor Pharmaceuticals
.
It is reported that the Phase III clinical trial of the former may be unblinded in the near future, and a marketing application may be submitted in late April
.
The latter has just released phase III clinical data not long ago
.
"The data on prokalutamide still needs to be reviewed by the FDA, and it remains to be seen whether it can pass and whether further data needs to be supplemented
.
"

So far, Kintor, Real Bio and Junshi Bio have entered the "final circle" together, and everyone has the hope of becoming the first approved domestic oral drug for COVID-19
.
The first approval also means occupying the first-mover advantage in the market, and sometimes a step behind the market size may open a big gap
.

- 03 -

- 03 -

Live before you live well

Live before you live well

Starting from 2021, the atmosphere of the innovative drug industry, which has not been hot for a long time, has become more and more deserted
.
PD-1, which was the beginning of the entire hope for innovative drugs, is now almost equated with the "inner volume" of innovative drugs
.

According to incomplete statistics from Southwest Securities, 85 of the 154 PD-1 drugs in the world were developed or jointly developed by Chinese companies, accounting for more than half
.

The sales performance of K medicine and O medicine at every turn of billions or even tens of billions of dollars attracted a number of domestic pharmaceutical companies to enter the market, and the domestic PD-1 market expectations have been pushed up
.
However, with the launch of five domestic PD-1 inhibitors one after another, four of which have entered the medical insurance industry.
Observing the latest financial reports of various companies will find that the domestic PD-1 market size is not what it used to be: including the inhibition of PD-1 by foreign pharmaceutical companies The sales of the agent in China, the whole market together has not sold 15 billion yuan
.

It is worth noting that Junshi's PD-1 performance lags behind, in fact, it has little to do with the price, because its price is the lowest domestic price of 29,800 yuan / year
.
This shows that a simple price reduction can no longer attract a large number of doctors and patients
.
"(Toripalimab) is very difficult to turn around because the competition is getting fiercer
.
If it can't be better than the (PD-1 inhibitor) that has entered the hospital, it is difficult to replace
.
"

Instead of just staring at the shrinking pools of the native land, swim to the wider lake
.

Since last year, domestic PD-1 manufacturers have set off a wave of license out, first get the down payment, at least make up a little "blood" in research and development
.

Source: Monita Research

In order to prove their innovation and get a higher value, local companies also try to pass the review gate of the US FDA
.
Domestic PD-1s that have submitted marketing applications in the United States include: BeiGene's tislelizumab, Innovent's sintilimab, Junshi Bio's toripalimab, and Acefang Bio's piezumab Amplizumab
.

Previously (March 23), Innovent failed to pass the FDA
.
It issued an announcement that the FDA has officially rejected the listing of sintilimab for the first-line treatment of non-squamous non-small cell lung cancer (NSCLC) in the United States
.
The latter recommends a "head-to-head" trial with overall survival as the endpoint
.

Junshi will also usher in the FDA's final "trial" on whether its nasopharyngeal cancer indication can be listed in the United States in the near future
.

Some people predict that because nasopharyngeal cancer is a small indication in the United States, it is more likely to be approved
.
"The FDA originally only wanted to put one or two silver carp into the U.
S.
market to stir up the muddy waters.
In the European and American markets, the major indications for K drugs and O drugs have to be 'dead', but it is still possible to meet the needs of orphan drugs and fill the market gap.
Yes
.
" An industry insider once analyzed this
.
From this point of view, Junshi PD-1 inhibitors cut into small indications and found a more convenient way
.

"The FDA originally only wanted to put one or two silver carp into the U.
S.
market to stir up the muddy waters.
In the European and American markets, the major indications for K drugs and O drugs have to be 'dead', but it is still possible to meet the needs of orphan drugs and fill the market gap.
of
.
"

When most of the R&D pipelines are not yet on the market, how to survive the continuous burning of money? Junshi chooses to come first for a round of fixed increase
.
On the evening of March 7, Junshi Biotech disclosed that it plans to raise no more than 3.
98 billion yuan
.
This is also the first fixed increase plan after it was listed on the Science and Technology Innovation Board
.
Fixed increase is a way, but it is difficult to "continue life" by relying on capital market financing all the time
.

According to statistics, Junshi Biology holds 3.
505 billion yuan in cash.
If it successfully raises 3.
980 billion yuan in A-share issuance, it will total about 7.
4 billion yuan; Xinda Bio has 8 billion yuan in cash; Kangfang Bio has only 2.
6 billion yuan in cash
.
The cash flow of Junshi and Cinda can at least support R&D spending for a few years
.

The research and development of innovative drugs is a commercial science, so you need to prove your commercialization ability, and the direct point is to prove yourself by making money
.
Junshi sees the potential of new crown drugs, among which the technology licensing and royalty income of its new crown neutralizing drugs will allow it to achieve a substantial increase in revenue in 2021
.
Now, it is betting on the new crown oral drug
.
So will this be a ticket to support Junshi's survival?

In fact, oral drugs for the new crown are already the second line of defense besides vaccines
.
As of March 21, 2022, less than 50% of the Chinese population had completed booster vaccinations
.
At present, only one domestic antibody drug and one imported small molecule oral drug have been approved in China.
The first domestic oral drug for COVID-19 is chasing after you, so hurry up
.

There are voices that are optimistic about the long-term benefits of the new crown oral drug, and there are also people who question its speculation, worrying that it may follow the footsteps of the new crown neutralizing antibody - the excitement comes and goes quickly
.

——The excitement comes and goes quickly
.

There are voices in the industry who criticize: Is betting on the new crown concept so much that too much energy is scattered on new crown drugs, while ignoring the long-term development of other pipelines? However, when an industry is going down, the company has chased a hot spot and succeeded, which is understandable in itself
.

The essence of innovative drugs has not changed.
They all use the future sales of a drug to support the development of new treatment methods.
In essence, it is a process of betting on the future with tomorrow
.

The difference is that in the past two years, under the hype of the society, innovative drugs have become a game that everyone participates in.
Now that the heat has dissipated, those who persist are still persisting, and those who can cross the cycle will be favored by the times.
selected qualifications
.