2 million sky-high therapies hard to carry the cold winter

CAR-T cell therapy is stress testing

A single injection of 1.

THE COMMERCIAL SIGNIFICANCE OF CAR-T is beyond itself, cold and poignant, there must always be a warrior to touch the ceiling, test the environment for cutting-edge therapy, and even the tolerance

By this month, Fosun Kate Agironse Injection has treated more than 200 patients, and WuXi Junorry Kiolanza Injection has completed the infusion treatment of 260 patients (including clinical research and commercialization stages).

Domestic CAR-T has been commercialized for more than a year, and less than 500 patients have completed the return of infusion, which is not enough

In the case of downstream CAR-T manufacturers losing money and not putting in volume, upstream CGT (cell gene therapy) CDMO is also under pressure

01 300,000 yuan to pay the ceiling

Due to differences in payment environments, there is a conversion ratio of us-China pharmacoeconomics, about 1/7,

Car-T therapy is priced at $475,000 for Novartis Kymriah and $373,000 for Gilead Yescarta in the United States, and therapy is in the range of 475,000 to 373,000 yuan in China in order to achieve an acceptable equilibrium price.

According to the International Journal of Cancer, a single car-T production costs about $

What is the ceiling for Medicare payments?

At present, there are nearly 3,000 drugs in the medical insurance directory, and the maximum payment amount of the medical insurance fund is 300,000 yuan

A big suspense in this year's medical insurance negotiations is whether the ceiling of 300,000 yuan can be broken?

How does Medicare support cutting-edge therapies? CMS (Center for Medicare and Medical Services) pays $400,000 for patients treated with Gilead CAR-T and $500,000 for patients treated with Novartis CAR-T through Medicare Part B

CAR-T has been included in more than 30 cities in China

Shangbao has the rising trend, which greatly alleviates payment anxiety, but the above patients still need to pay more than 1 million yuan out of their own expenses, which is an unbearable burden

The effects of cell therapy are so amazing

02 Panorama of domestic cell therapy enterprises

Cracking the accessibility problem requires the payment environment and technology iteration to work together

The universal CAR-T (UCAR-T) can scale and standardize the production process, which is expected to reduce production costs by 90%.

There are 3 UCI-T pipelines

Beiheng Bio UCR-T pipeline reached 7, the fastest progress TA101 in March this year received cde clinical trial implied license, is the first domestic immune cell therapy product based on CRISPR gene editing technology, but also the second general-purpose CAR-T therapy
to enter the clinical stage.

There are 3 UCR-T pipelines in Koji, KJ-C2111 targeting BCMA for the treatment of multiple myeloma (MM), which is currently in the IIT experimental stage, and KJ-C2114 is still in the preclinical research stage
.

Solid tumor CAR-T therapy has a wider coverage and can also reduce costs
through large-scale production.
In 2019, there were 18.
5 million cancer patients worldwide, of which 17.
3 million were solid tumor patients, accounting for 93%.

Coji Pharmaceutical's core product CT041 targets Clauddin18.
2 for the treatment of gastric cancer/esophageal gastric junction adenocarcinoma and pancreatic cancer, is the world's first and only solid tumor CAR-T that has entered a key Phase 2 clinical trial, plans to submit NDA to China in the first half of 2024, and plans to launch a Phase 2 clinical trial
in North America in the second half of this year.

Keji Pharmaceutical lost 376 million yuan in the first half of the year and had a cash reserve of 2.
74 billion yuan, which can support R&D activities for more than 4 years and has a stronger
ability to control costs than legendary biology.
Judging from the market performance, the status of its domestic first-line CAR-T enterprises has been recognized
.

Compared with mature CAR-T therapy, NK cell therapy is still in the early stages, but the potential advantages are prominent, the industrial mass production potential is greater, the indications are wider, the safety is better, the cost is lower, the killing speed is fast, and it can be used as a general-purpose spot product
.
Domestic enterprises are laid out in BeiGene, Youkairui, Chengnuo Medicine, Chongqing Precision Biology, Ascoli, CoronBotai, Inbry, Boshengji, Zailing Biology, Xingyi Ang, Bess Biological, Qihan Biological, Enkaisai Medicine, Jingda Biology, Heluo Xintu, Xinchuan Biology and Ziyin Biology
.

In November 2021, the State Food and Drug Administration approved the clinical trial application of Guojian Chengnuo spot allogeneic CAR-NK cell product, which is the first NK cell therapy
in China to enter the clinical stage.
Inberi developed cellular immunotherapy with ADC ideas, and in the first half of this year, the financing amount in the field of NK cell therapy ranked first with 230 million yuan, and 2 products are about to enter IND
.

03 CGT CDMO awaits an opportunity to explode

Downstream CAR-T commercialization is slow, upstream CGT CDMO is still in the cultivation stage, and it is necessary to wait until the general-purpose CAR-T is listed to achieve industrial release
.

Heyuan Bio, which may be the only profitable CGT CDMO in China, was once questioned and was worried about the change of financial
data after the listing.
This year's Q2 revenue of 61.
78 million yuan, an increase of 17.
9% year-on-year, down 15.
6% month-on-month, net profit of 7.
96 million yuan, down 34% month-on-month, although affected by the epidemic, but the performance and the secondary market speculation heat seriously mismatch
.

Heyuan Bio's semi-annual report is also diluting the concept of cell therapy, highlighting its own positioning of focusing on gene therapy, the main customers Shenzhen Yinuo Micro, Shanghai FunuoJian, Kanghua Biology, Beiheng Biology, only one is a CAR-T enterprise
.
In the first half of the year, the CDMO business accumulated more than 130 million yuan of new orders, and the unexecuted orders in hand exceeded 350 million yuan, opening up new types of
stem cells, NK cells and mRNA businesses.

In the first half of the year, the CGT CDMO revenue of Boteng co.
, Ltd.
was 11.
27 million yuan, an increase of 80% year-on-year, which was the only one with faster growth, but the scale was still small
.
Served 32 customers, an increase of 167% year-on-year; 31 new projects, an increase of 244% year-on-year; The newly signed orders were about 92.
08 million yuan, an increase of 68%
year-on-year.
Boteng Bio B round financing of 520 million yuan, the existing 4,000 square meters of R & D and production base in the steady operation, this year's Q4 is expected to add 16,000 square meters of large-scale industrialization base, will have 10 GMP virus vector production lines, 10 GMP cell therapy production lines and hundreds of clean workshops
.
Launched overseas market expansion and deployed process development and analytical testing laboratory capabilities
in North America.

WuXi AppTec's CGT CDMO revenue in the first half of the year was 615 million yuan, an increase of 35.
7% year-on-year, and the adjusted Non-IFRS gross profit was -0.
43 billion yuan, and the gross profit margin was -6.
9%, which was in a state of
loss.
The decline in gross profit was mainly due to the lower utilization rate of the newly opened Shanghai Lingang operation base
.
It has 51 preclinical and Phase I clinical trial projects, 9 Phase II clinical trial projects, and 7 Phase III clinical trial projects (4 of which are in the preparation stage of marketing application).

Kanglong Chemical CGT CDMO is in the integration and investment stage, and the overseas operating costs are too high and temporarily lose money
.

Jinsrui Biotechnology CGT CDMO platform (Boom Bio) is close to breakeven, adding 6,400 square meters of plasmid GMP plants in 2021, 6,400 square meters in China in 2022 and 2023, and 31,000 square meters of plasmid and virus GMP plants
in the US production base in 2024 。 In terms of plasmids, Vigorous Bio is the largest plasmid CDMO supplier in China, with 9 successful experiences in IND declarations in China, the United States and South Korea, and more than 70 IND declaration plasmid CMC projects in progress; In terms of viral vectors, we have successfully provided lentiviral and AAV vectors for multiple cell therapies and Genetherapy, with a total of 3 successful EXPERIENCEs in China and the United States, and more than 20 IND declaration CMC projects with viral vectors in progress; In terms of mRNA plasmids, almost all mRNA vaccine companies in China have established cooperation, and mRNA vaccine projects with Korean and American companies have also been clinically approved in South Korea and Japan; In terms of DNA vaccines, CMC studies that provide plasmids
.

WuXi Biotech and Vigorous Bio are the international CGT CDMO leaders
with a large leading edge.