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Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

Cai Lei is in urgent need of help at the moment

Believe in the power of believing!

文/叶檀☞ 手中无剑 | 心中有爱

The hard-hit pharmaceutical companies will eventually become phoenixes, which is the firm conclusion we have reached after visiting a series of pharmaceutical companies. This is good news for those who are suffering from illness.

Doctors are benevolent, and pharmaceutical companies are the source of benevolence. George Merck, the late Merck president, said:

We should remember that medicine is for the patient. We should never forget that pharmaceuticals are for people, not for profit, and profits come with it. If we remember this, it (profit) will never be broken, and the more we remember, the more it will come.

Since my illness, since I communicated with many friends who have been tormented by illness, since Cai Lei has worked hard to seek life as a patient with ALS, since I heard Chen Xingjia tell the story of saving children with leukemia, our attitude towards the pharmaceutical industry has undergone subversive changes, not so much that this is an industry or an industry, but that this is a civilization and the most profound philosophy of mankind.

We must also respect other lives equally.

From the perspective of commercial interests alone, the persistence and dedication of most new drugs are worthless, but the reason why people are human beings is because, in addition to interests, there are more precious things, because innovation will eventually pay off.

I'm not the god of medicine, we all need the god of medicine.

Ten billion dollars at the cost of life

At the end of December 2023, Cai Lei said in an interview that he was "very close to death".

In the past 4 years of illness, more than one billion dollars have been spent, and the story of defeating the Buddha has brought everyone to tears. As one of the most difficult rare diseases to overcome, ALS has no cure, and a series of previous attempts have been very sad and helpless.

There are countless human tragicomedies in the cancer treatment area of every hospital, and every patient and family knows that the key to deciding treatment is the drug.

In "The Story of New Drugs", the author, Dr. Liang Guibai, wrote:

According to the latest statistics, the cost of developing a new drug is more than $1 billion. Therefore, when setting drug prices, big pharma must consider the number of years of patent protection and market demand, in order to recover costs and have a surplus. The final drug price is basically independent of the production cost of the pills, and only in this way can pharmaceutical companies have the ability to invest a lot of manpower and material resources in the research and development of new drugs, and we can hope to conquer those cancers and other diseases that still threaten human health.

$1 billion, that's just the cost of capital, time is more expensive than money.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

In the field of new drug research and development, there is a "double ten law", in addition to investing 1 billion US dollars in a new drug, it also has an average R&D cycle of about 10 years.

Why Does It Take So Long?

A paper published in the scientific journal "Nature" pointed out that in chemical space, the number of drug molecules that can be discovered by humans is as high as 10 to the 60th power, while all the atoms in the solar system are added together, only about 10 to the 54th power.

Finding a needle in a haystack, in the vastness of orders of magnitude larger than the solar system, to capture the ethereal hope may be the most difficult task humanity is currently encountering.

According to a report released by BIO, InformaPharma Intelligence and QIS, a global biotechnology industry organization, in the decade from 2011 to 2020, the average success rate of 9,704 drug development projects approved by the FDA was about 7.9%.

In Suzhou Industrial Park, we have had in-depth exchanges with the founders of innovative pharmaceutical companies, some of them have spent 20 years without results and are still persevering, some are in turmoil every year because of the ups and downs of funds, and some have invested in many small pharmaceutical innovation companies.

China's innovative pharmaceutical companies have their own distinctive characteristics.

Acknowledging the gap We are not the country with the highest level of innovative drugs

Frankly admit the gap, we are not the first echelon of innovative drugs.

According to Bio, in 2022, the number of new drugs approved worldwide is as follows:

The US FDA's Center for Drug Evaluation and Research (CDER) approved a total of 37 new drugs, of which 25 were approved for the first time in the world, and the European EMA approved a total of 51 new drugs, of which 8 were approved for the first time in the world.

A total of 48 new drugs have been approved by the Japanese PMDA, of which 12 are approved for the first time in the world;

The National Medical Products Administration (NMPA) approved a total of 40 new drugs throughout the year, of which 11 were approved for the first time in the world.

Since the return of Dr. Ding Lieming, the founder of Betta Pharmaceuticals, to China and the birth of icotinib, the first small molecule targeted anti-cancer drug with completely independent intellectual property rights, in 2011, China's innovative drugs have ushered in a highlight moment, but there are very few first-in-class first-in-class innovative drugs.

According to the "2022 Drug Evaluation Report" released by the State Food and Drug Administration, 21 innovative drugs were approved through the review in 2022, of which 3 were first-in-class;

In 2023, there were a lot of innovative drugs in China, and according to WuXi Online, a total of 34 Category 1 new drugs were approved in China that year, and 32 were domestic innovative drugs, a record high in recent years.

Among these 32 drugs, 5 first-in-class drugs have been recognized by regulatory agencies, namely the c-Met inhibitor glumetinib from Haihe Pharmaceutical, the 3CL protease inhibitor leretrelvir from Zhongsheng Ruichuang, the proton pump inhibitor aneprazole from Xuanzhu Pharmaceutical, the EPO drug pemosatide from Haosen Pharmaceutical, and the zebetuzumab from BioPro Biologics.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

The situation is expected to be much the same in 2024.

In the past decade or so, only about 5% of the number of first-in-class drugs approved in China has been developed, compared to 30-40% of the new drugs approved by the U.S. Food and Drug Administration each year.

Follow-the-trend innovation has become the mainstream, and companies that can withstand loneliness and are willing to take risks have become a niche.

The real advantage of China's pharmaceutical industry is that there are many entrepreneurs, fast followers, and many pipelines

Innovative drugs seem to be prosperous, but in fact, they are not innovative enough.

But we have our own unique advantages.

Almost all the scientists we have seen in pharmaceutical companies from Suzhou to Hangzhou have given up their high salaries and comfortable lives to start their own businesses again. We are deeply touched that they want to be worthy of themselves and worthy of the times.

The more dilapidated their offices and the more expensive their research equipment, the more we will gain our respect from the bottom of our hearts.

In order to survive, a better follow-up strategy is to build a dense pipeline in the relevant field of possible R&D areas to maximize the likelihood of success. In the event of poor financing and a downturn in the industry, it will be able to survive through the sales pipeline.

According to statistics from AVIC Securities, since 2015, the overall growth rate of China's drug R&D pipeline has remained high, exceeding 30%, and as high as 56% in 2019, much higher than the overall global level and much higher than the level of the United States.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

In 2022, the size of Chinese companies' drug development pipelines was roughly the same as in the United States in 2002. According to the Pharmprojects database, as of August 8, 2022, there were 3,716 drugs in active R&D processes headquartered in Chinese mainland, including drugs from License in.

The R&D of Chinese pharmaceutical companies is concentrated, with anti-tumor drugs accounting for 47.6%, and the targets are more concentrated, with the most popular 30 targets covering 24.7% of all target drugs, which is higher than the global level.

Look, it is very similar to the new energy industry, manufacturing, and venture capital, and is unwilling to invest in the early stage, willing to follow, with a comprehensive layout and fast speed.

Laying out pipelines is the way for latecomers to survive.

In August 2023, the biggest news in the pharmaceutical industry was GSK's acquisition of Aiolos Bio for a US$1 billion upfront payment + US$400 million regulatory milestone.

The only core pipeline of Aiolos Bio is the TSLP monoclonal antibody authorized by Hengrui Pharmaceutical, and investors jokingly call it "the first brother of Chinese medicine is made by the middleman to make the difference".

Either way, this deal is yet another example of how worthwhile some pipelines are.

The reason for the increase in pipeline density is that there are more and more expensive R&D personnel in China, which is exactly the same reason Munger bought BYD.

From 1998 to 2020, a total of 6.35 million master's and doctoral students in science and engineering are expected to accumulate by 2035, which is equivalent to the same period in the United States.

The average salary of China's major listed CXO companies in 2021 was 200,000 yuan/year, while the average salary of the U.S. pharmaceutical industry in 2021 was 46,752 US dollars/year, equivalent to about 300,000 yuan, an overall difference of 50%.

Scientists from more than one pharmaceutical company told me that the speed at which our new drugs are launched on the market is not slow, and it will not be two years slower than that of the United States.

Judging from some subtle links, real large-scale innovation will also come in the near future.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

It is difficult for innovative drug companies to survive in the downward cycle

Pharmaceutical companies have a clear cycle and are currently in a downward cycle.

Before 2022, the financing of China's pharmaceutical industry grew explosively, and from 2015 to 2021, the financing scale increased from 40.9 billion yuan to 279.2 billion yuan, an increase of nearly 7 times.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

Source, Qingke Science and Technology Innovation Think Tank

All related companies enjoy capital dividends because of high valuations.

Starting from 2022, the biomedical field has entered a financing winter. According to data from the official account Gazelle, in 2023, due to the rapid decline in the scale of investment and financing, the number of bankruptcies of global biotechnology companies will hit a record high.

According to market data firm PitchBook, the total financing of the biopharmaceutical industry in 2023 will be about US$24 billion, a significant decrease from US$38.1 billion, US$53.9 billion, and US$36.9 billion in 2020-2022.

According to incomplete statistics from China Times in 2023Q3, at least 15 of the 120 Hong Kong-listed pharmaceutical companies have cash flow of less than 1 billion yuan.

Since 2020, more than 30 biotech companies have filed for bankruptcy, and more than half of the listed start-ups it tracks have cash that cannot be sustained for two years, according to an article by Medical Mike News.

On January 23, 2024, Info reported that Boji Biomedical Technology, the first biopharmaceutical company to file for bankruptcy at the beginning of this year.

There are too many monks and little porridge, and they can't be evenly wetted with rain and dew, and innovative drugs are facing the most severe supply-side reform in more than ten years.

At this time, the risk of homogeneous competition of innovative drug companies is fully exposed.

Represented by PD-1/PD L1, dozens of pharmaceutical companies are developing at the same time, and after the popularity of weight loss drugs in the United States, a similar situation has occurred, and at least 13 applications for IND have been received by the China Center for Drug Evaluation.

Because of homogeneous competition, there is no absolute technical strength to crush, so you have to fight for sales. What's worse is that the proportion of China's innovative drug sales is not high, according to the official account Archimedes, the 10 major products of Chinese hospital drugs, 7 corresponding to the original drug have been on the market for the first time in the world for more than 15 years, and are out of touch with innovation.

According to BCG data, in 2021, the sales of innovative drugs in the United States accounted for 79% of all drug sales, and the sales of domestic innovative drugs accounted for only 11% of the national drug sales.

On the one hand, the competition is fierce, and on the other hand, in order to curb the price of innovative drugs, after being included in the medical insurance, the profits of innovative pharmaceutical companies have dropped significantly.

In a dilemma.

In the process of treatment, I have seen that some patients from poor families with advanced and severe diseases have given up treatment, and some people usually say that the strength of treatment is true, economic ability is an important factor, of course, not the only factor.

The domestic medical insurance department has made every effort to centralize the procurement and inclusion of innovative drugs. According to Cyberblue and other media reports, in 2022, the average price reduction rate of domestic innovative drug medical insurance negotiations will be 60%, and the highest price reduction will reach 94%, and in 2023, the average price reduction will be 61.7%.

There are some innovative drugs with large reductions, such as nusinersen sodium injection, Biogen's drug for the treatment of spinal muscular atrophy, which will be reduced from 700,000 to 33,000 after entering the medical insurance list.

The surging news said that after six rounds of adjustments, through negotiation of price reductions and medical insurance reimbursement, a total of more than 600 billion yuan has been reduced for patients.

AVIC Securities compared the annual cost of treatment of anti-tumor drugs in China and the United States, and most of the treatment costs in China are about half of those in the United States.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

The huge disparity in national income makes it still unbearable to reduce the cost of "half".

Deeply integrate into the international industrial chain and go to sea to survive

You can only break the game by jumping out of the circle.

In order to break the situation, more and more domestic pharmaceutical companies choose to go overseas, and the most respected way is to license out, which is to authorize the project to other pharmaceutical companies for late-stage clinical research and development and marketing, and obtain clinical results at each stage and a certain percentage of sales share after commercialization according to the milestone model.

This method is flexible and convenient, with a low threshold, and can quickly return funds, but it requires pharmaceutical companies to have deep insight into the future drug prospects, as well as superb negotiation skills.

According to the data of Pharmacube, in 2023, the transaction amount and number of innovative drug license out transactions in China will reach a new high. This year, there have been nearly 70 innovative drug license out transactions in China, with a total disclosed transaction value of more than US$35 billion.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

China's innovative enterprises have been deeply integrated into the international industrial chain, and the leading enterprises are no longer facing the test of life and death because of the domestic business cycle.

In addition, the leading pharmaceutical companies have established many industrial funds, invested in related enterprises, and formed a group, and many small and medium-sized innovative drug companies have joined the group owners to keep warm.

Ye Tan: In order to survive, I dug out the truth about Chinese pharmaceuticals Cai Lei urgently needs help at the moment

The cold winter will always pass, and in the midst of slaughter, a warm breeze will be ushered in.

According to the official account of Tianrui Fengnian, in the first two weeks of 2024, there were 39 investment and financing events in the biomedical track, and the total amount of financing disclosed reached 4.833 billion yuan, a record high since the statistics.

The valuations of some leading companies have recovered, and even if they fall, they will not fall deeply.

If the market lasts for two or three years, it is estimated that many innovative drug SMEs will go bankrupt, especially those without mature pipelines and excellent technical technologies.

In the dry season when there are no water and weeds, the competition is the tolerance of enterprises.

At the dawn of time, for the good companies that survived, when the low price of gold is everywhere, the future has come.

At high tide, low-density floats tend to be the first to float up, and are likely to end up on the tidal flats, losing the chance to stay at the tables.

Chinese pharmaceutical innovation companies are working hard, frankly speaking, we are not the most innovative, strength determines that we cannot afford the cost of large-scale innovation failure at this stage, but we are the most able to learn, which is a boon for China's critically ill patients.

Mama Teresa once said to love yourself, love others, love everything in life that needs love, without any reason. Even if life is so small that it is just a tiny wick, when it burns, it can illuminate itself and others. You can even try to light up a world.

In a race against time, every inch of sunshine is less painful.

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.wx-root[data-weui-mode=care][data-weui-theme=dark],body:not(.pages_skin_pc) body[data-weui-mode=care][data-weui-theme=dark]{--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .85);--weui-FG-HALF: rgba(255, 255, 255, .65);--weui-FG-1: rgba(255, 255, 255, .55);--weui-FG-2: rgba(255, 255, 255, .. 35);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: #ff6146;--weui-ORANGE: #c87d2f;--weui-YELLOW: #cc9c00;--weui-GREEN: #74a800;--weui-LIGHTGREEN: #3eb575;--weui-BRAND: #07c160;--weui-BLUE: #10aeff;--weui-INDIGO: #1196ff;--weui-PURPLE: #8183ff;--weui-WHITE: rgba(255, 255, 255, .8);--weui-LINK: #7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root,body:not(.pages_skin_pc) body{--appmsgExtra-BG: #F7F7F7}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root[data-weui-theme=dark],body:not(.pages_skin_pc) body[data-weui-theme=dark]{--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .8);--weui-FG-HALF: rgba(255, 255, 255, .6);--weui-FG-1: rgba(255, 255, 255, .5);--weui-FG-2: rgba(255, 255, 255, .3);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: #ff6146;--weui-ORANGE: #c87d2f;--weui-YELLOW: #cc9c00;--weui-GREEN: #74a800;--weui-LIGHTGREEN: #3eb575;;--weui-FIRE: #07c160;--weui-BLUE: #10aeff;--weui-INDIGO: #1196ff;--weui-PURPLE: #8183ff;--weui-WHITE: rgba(255, 255, 255, .8);--weui-LINK: #7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .. 6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root[data-weui-theme=dark],body:not(.pages_skin_pc) body[data-weui-theme=dark]{--appmsgExtra-BG: #121212}}@media screen and (min-width:1024px){body:not(.pages_skin_pc)body:not(.pages_skin_pc){background:#191919; background:var(--weui-BG-2)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root[data-weui-mode=care]:not([data-weui-theme=light]),body:not(.pages_skin_pc) body[data-weui-mode=care]:not([data-weui-theme=light]){--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .85);--weui-FG-HALF: rgba(255, 255, 255, .65);--weui-FG-1: rgba(255, 255, 255, .55);--weui-FG-2: rgba(255, 255, 255, .35);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: #ff6146;--weui-ORANGE: #c87d2f;--weui-YELLOW: #cc9c00;--weui-GREEN: #74a800;--weui-LIGHTGREEN: #3eb575;--weui-BRAND: #07c160;--weui-BLUE: 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div.autoTypeSetting24psection > p,div.autoTypeSetting24psection > section{margin-bottom: 24px;}

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