Three domestic cell therapy companies have IPOs, CAR-T in China from the full commercialization of how far?

Read: 2020 is the year of the rise of CAR-T cell therapy in China.
So far in 2020, Fosun Kate and Pharmaceuticals have applied for NDA and been accepted; Legendary Bio, Yongtai Bio and Pharmaceutical Ming Juno have applied for listing, including Yongtai Bio and Legendary Bio have successfully landed in Hong Kong and NASDAQ, respectively; and the FDA has once again approved the listing of a third CAR-T cell therapy product via fast track.
since Novart's Kymriah and KITE's Yescarta two CAR-T products went on sale in 2017, while the domestic cell therapy industry has continued to climb in the tier one market, there has been little improvement in product approvals.
three years of industry, in 2020, finally came the time for an outbreak.
now we take the application of Pharmaceutical Ming Juno for listing on the Hong Kong Stock Exchange as a guide, and look again at the three declared listed Chinese cell therapy companies to see where the industry is heading? Look at the obstacles to commercialization? JUNO and KITE, opening a second battleground in China In April 2016, Drug Mingkang and Juno Therapeutics announced a partnership to establish Amoebo, a joint effort to build China's leading cell therapy company in combination with Juno's inlay antigen-binding and T-cell-insorbic (TCR) technologies, as well as Pharmaceutical Mingkangde's research and development production platform and extensive experience in the local Market in China.
when it comes to the drug, I have to mention another very similar company, Fosun Kate.
January 2017, following the collaboration between JUNO and Pharmaceuticals, KITE also entered into a partnership with Fosun Pharma, which also established a joint venture to revive Kate and bring KITE's Yescarta (not yet approved, codenta KTE-C19) to the Chinese market.
competition between JUNO and KITE runs through the development of CAR-T products.
the two companies have a very similar trajectory, from their formation, to their financing processes, to their product development, to their eventual acquisitions by New Base Pharmaceuticals and Gilead, respectively.
2016, JUNO was also one of the strong contenders for the first CAR-T product.
in July 2016, one of JUNO's head products, JCAR015's Phase II clinical trial, resulted in the death of two leukemia patients due to neurotoxicity and was immediately called off by the FDA.
JCAR015 has not had any more news, JUNO still has other product pipelines, not weaker than similar competition.
JCAR017II clinical trial data released at the ASH Annual Meeting at the end of 2017, THE ORR (overall response rate) was 80% (12/15) and CR (full remission) was 73% (11/15) for 15 patients treated at dose level 2.
2018-2019, JUNO is also continuously updating JCAR017 data, but has not yet declared a listing.
the other side, Yescarta, the first product of old rival KITE, has entered markets in Europe, Japan and other regions, and the second has been approved by the FDA.
reactions to early products may have more or less affected the JUNO's approval path.
in Europe and the United States, JUNO has clearly fallen into the downwind.
europe and the United States market is large, but the Chinese market can not be underestimated.
JUNO and KITE overlap again on the trajectory of the Chinese market.
two joint ventures, Fosun Kate and Pharmaceutical Ming Juno, have always maintained a strong in the domestic cell therapy industry's first echelon, research and development progress is also very tight.
June 2018, relma-cel, JWCAR029) IND applications for re-entry were approved, and in September of that year, FKC876 for Revival Kate's Iquillilon Injection (FKC876) was approved.
by 2020, the NDA application for the revival of the Ketjili Lunsai injection was first accepted by the CDE in February and subsequently entered the priority review channel, while the drug Ming-Juno showed no signs of weakness, and the NDA application for the Ricky Lindsay injection was accepted by the CDE in June.
who will be China's first approved CAR-T product remains to be determined.
but we can see that junO, which has fallen into the downwind in the European and American markets, has once again opened up competition with KITE, relying on the continuous promotion of the drug Mingjuno.
JUNO's first product or through the drug Mingjuno in China's first market drug Mingjuno in the research pipeline said the return drug Mingjuno, the company's current pipeline is all from Licein, which includes the introduction of CD19 and BCMA target products from JUNO, but also from Yuriko introduced several AFP and GPC3 target related products.
products for hematoma adaptation are mainly from JUNO, the core product is Relma-cel (JWCAR029), or JUNO's JCAR017.
junO has completed a relatively complete development process abroad, but has never been approved for listing abroad.
drug Ming-Juno has been localized and promoted the progress of many domestic clinical trials.
now this product has been declared in the domestic NDA and accepted, perhaps the first product of the drug Ming Juno can borrow the hand of the drug Ming Juno, the first in the domestic market.
Relma-cel is currently listed as a third-line treatment for DLBCL (diffuse large B-cell lymphoma).
completed Phase I. and II. clinical trials, Relma-cel successfully reached its intended primary endpoint, with a three-month ORR of 58.6 percent.
best overall efficacy, ORR and CR reached 75.9% and 48.3%, respectively.
's other clinical trials related to figular lymphoma and heterocytic lymphoma have also entered a critical clinical trial phase, and although the drug meth has not disclosed the results of the early clinical trials of these two indications in its prospectus, the clinical value of junO's previously disclosed results is no less than that of several products already on the market.
the solid tumor pipeline of the drug Ming-Juno, which was introduced from an innovative company, Yuriko.
, a Chinese-founded cell therapy technology company, is also closely linked to JUNO.
January and June 2016, Yuriko authorized the development and commercialization of two of its products to JUNO, targeting BCMA and MCC16, respectively.
of the three main products introduced from JUNO by the drug Mingjuno is a BCMA target and is likely to have originally come from Yuriko.
, which may be further introduced in the future, has the right to purchase T-cell products developed and commercialized in China.
the future, as the product pipeline advances, Thermomino may continue to introduce multiple drug pipelines from JUNO.
, CD22, HER2, MUC16 and other popular target products, are in the scope of consideration.
the main financing purposes disclosed in the current prospectose for the drug, which focuses on product registration and clinical development, with a portion of the funds for further future Licencein.
it is estimated that in the next few years, it is expected that the drug Ming-Juno will continue to move at the current pace of development at a constant pace.
start-ups want to "step fast", cooperation is the key from the development of the three declared listed enterprises in 2020, we can see some of the development trends in the cell therapy industry.
research and development spending on research and development by the three domestic cell therapy companies that have applied for listing, Legendary Bio will spend more than 1 billion yuan on research and development in 2019.
, Yongtai Bio and Pharmaceuticals spend much less on research and development.
the situation of Yongtai organisms is more special, CAR-T pipeline is still in the preclinical stage.
only the core product EAL is advancing in clinical trials.
the product is mainly to the patient's CD8-T cell separation culture back to transmission, its own cost is not high, the corresponding clinical trial costs are easy to control, so it does not have a wide range of reference.
huge research and development expenses of legendary organisms, in addition to the product itself, more from the development of a large number of clinical trials.
core product LCAR-B38M has a Phase III clinical trial, three Phase II clinical trials and one Phase I clinical trial in the study, and other pipelines have entered Phase I clinical.
more than 10 clinical trials at the same time is bound to result in huge research and development costs.
Legendary Creatures dared to invest heavily in research and development, with Kingsley and Janssen Pharmaceuticals behind it.
, the holding company of Legendary Creatures, has continued to provide financial assistance to Legendary Creatures over the past few years.
Janssen Pharmaceuticals has reached an agreement with Legendary To develop, produce and sell LCAR-B38M, a partnership worth up to $350 million in the first advance alone, enough to cover Legendary's research and development spending for 2018-2019.
Then look at the drug Mingjuno, the first number of clinical trials is small, only the core product JWCAR029 several clinical trials in the study;
many factors, the research and development expenditure of the drug Ming-Juno has always been edgy.
of the two companies suggests a business model for cell therapy companies.
research and development of innovative drugs requires a lot of capital investment.
such a huge investment, VC/PE support alone is not enough, start-ups need to seek more industry support.
whether it's working with pharmaceutical giants to develop early business transformation or with CRO/CDMO to further control costs, it's a great choice for innovative companies to control risk.
is actually a good example, several product pipelines have been Liceout to JUNO and pharmaceutical Mingjuno, down payment and future milestone payment will be the driving force for Yuriko's further development.
cd19, BCMA, who will be the next hot target? The pipeline situation of the three declared listed enterprises is currently listed in the three enterprises, the pipeline distribution is obviously more dispersed, the target overlapping products, only CD19, BCMA and CD22 three.
this is also the current CAR-T cell therapy is facing the situation.
novart, KITE and JUNO are competing in the first round around CD19 targets, and so far three products have been launched, attracting a large number of companies to start research and development of CAR-T cell therapy products.
but in terms of target selection, there is very little clinical data on which to use it, except for clinically proven CD19, most of which are stoned across the river.
in the process of "crossing the river", BCMA targets in the multi-party verification began to emerge, JUNO, Bluebird, legendary organisms have published their own products of clinical trial results.
LCAR-B38M, especially the legendary creature, has demonstrated excellent commercial potential in clinical trials of multiple myeloma in China and the United States, with CR (complete remission) reaching more than 70%.
we can also see that all three companies that have submitted IPOs have already made in-depth layouts on BCMA target products.
but after the BCMA, which target will be the next big hit, but no decision has been made.
some people think there is still a lot of room for development in hematoma treatment, some people think that new solid tumor targets should be sought, and some people think that the cost of products should be controlled to do off-the-shelf UCAR-T products.
in such an environment, even giants like KITE seem a little confused.
KITE has just been approved for the market of new products, although in the set of cell lymphoma and acute myeloid leukemia have achieved good clinical results, but the target is still the old target, has always limited room for development.
for start-ups, such an industry environment represents an opportunity.
companies are confused, it's the opportunity for start-ups to take a place in the industry.
legendary creatures in the early days of the BCMA target for focused development, in order to have today's world-leading position.
, the antidote to future payment problems Although CAR-T cell therapy products have entered the domestic market stage, but for domestic patients, want to use this product as soon as possible, there is a big problem of payment.
Kymriah and Yescarta's high prices of $475,000 and $373,000 in the U.S. are a huge burden for patients.
the U.S. commercial insurance system is financially strong enough to provide medical coverage for patients.
, as well as CMS (Centers for Medicare and Medicaid Services), has also fully covered CAR-T cell therapy.
but for the domestic, the payment process is much more difficult.
domestic products, although lower than foreign prices, but for the domestic per capita income level, is still a huge sum.
we can estimate the price of CAR-T cell therapy products that will be available in China than other innovative pharmaceutical products.
PD-1 single-anti-Keytruda unit sells for half the price in the U.S., plus a three-plus-three gift policy, Keytruda actually pays about a quarter of the price in the U.S.
in this proportion, the future domestic market CAR-T cell therapy product price, but also more than 500,000 yuan.
's going to pay for this huge sum? If the patient is to pay for itself, this price is undoubtedly worse for the patient's family.
if it is included in the health care payments, it will be for the country.