The frontier track of investment and financing blowout may give birth to a number of top and cutting-edge companies

The quality of the industry's prospects can be seen from the financing situation
.

Take the field of cell therapy as an example
.

Since the beginning of this year, the investment and financing enthusiasm in the field of cell therapy has remained at a high level
.

Since the beginning of this year, the investment and financing enthusiasm in the field of cell therapy has remained at a high level
.

In the field of cell therapy, the number of investment and financing events and the amount of investment and financing ranked first

The momentum of investment and financing blowout has fully reflected the capital's optimism
about the future prospects of the cell therapy field.

The investment and financing enthusiasm of NK cell therapy track has increased significantly

The investment and financing enthusiasm of NK cell therapy track has increased significantly

Among the cell therapy segments, there is nothing more prestigious than CAR-T therapy
.

But in fact, the NK cell therapy track is also favored
by capital.

▲Source: Medicine Cube

However, after entering 2022, the investment and financing enthusiasm of domestic NK cell therapy has increased significantly, and the proportion of investment and financing events in domestic companies has reached 67% (10/15)
in the world.

After entering 2022, the investment and financing fever of domestic NK cell therapy has increased significantly, and the proportion of investment and financing events in domestic companies has reached 67% (10/15)
in the world.

Existing shareholders Lilly Asia Fund, Sherpa Capital and IDG Capital continue to make additional investments
.

The strength of the company's founding team is also an important factor
.

In particular, Wang Liqun served as CEO of Fosun Kate (a joint venture between Fosun Pharma and Kite under Gilead Science) and took less than four years to launch China's first CAR-T cell therapy drug, Achillense Injection (trade name: Yi Kaida
).

And in less than four years, China's first CAR-T cell therapy drug Achillense injection (trade name: Yi Kaida) was pushed to the market
.

▲Source: Xing Yi Ang

In addition, some members of the management team of Xingyi Ang worked for Fosun Kate Company, and as the core members, they led Fosun Kate to complete the technology transfer, facility construction, clinical trial and drug supervision review of "Yi Kaida" in China, and finally achieved commercialization approval in China, with rich professional technology and R&D management experience
.

Some of the management team members of Xingyi Ang have worked for Fosun Kate

Under the leadership of the core team, an innovative biopharmaceutical company focused on the development and industrialization of iPSC-CAR-NK's general availability of mass-produced immune cell products was born
.

A company focusing on the development and industrialization of iPSC-CAR-NK general-purpose ready-to-produce immune cell products

As Wang Liqun said in an interview, the reason for leaving Fosun Kate is "little interest in business work.

Develop next-generation cell products to solve the challenges of cell therapy to overcome solid tumors and commercialization
.

Based on this, Xingyi Ang has had a clear innovation pipeline goal and global strategic positioning from the beginning of its establishment: it is committed to developing innovative immune cell drugs that are generally spot-based, mass-produced, treatable to solid tumors, and have clinical value-oriented, thereby greatly reducing the production cost of cell products and providing effective therapeutic drugs for cancer patients around the
world.

It is committed to the development of innovative immune cell drugs that are commonly available, mass-produced, treatable solid tumors, and have clinical value-oriented, thereby greatly reducing the production cost of cell products

At present, the core team of the company has designed a new concept of allogeneic immune cell therapy product technology platform and its related process routes
by virtue of the successful listing experience of autologous CAR-T products, aiming at the weaknesses of autologous cell products and using the latest research results in related fields.

A new concept of allogeneic immune cell therapy product technology platform has been designed, and its related process routes
.

In addition, the company completed a preliminary iPSC-CAR-NK differentiation process study
on the existing platform.
Through 3D culture of iPSC, the team has obtained a relatively uniform embryoid body, successfully differentiated into CD34+ HSC (hematopoietic progenitor cells), and further realized the differentiation of CD34+ HSC to NK cells (up to 95%)
.

Completed the preliminary research on the differentiation process of iPSC-CAR-NK
.

CAR-T therapy has limitations, and CAR-NK therapy has unique therapeutic advantages

CAR-T therapy has limitations, and CAR-NK therapy has unique therapeutic advantages

As mentioned above, the track where Wang Liqun founded Xingyiang is not the CAR-T cell therapy launched by Fosun Kate, but the new generation of iPSC-CAR-NK therapy
.

Although both therapies fall under the category of immune cell therapy, the therapeutic advantages are different
.

Although both therapies fall under the category of immune cell therapy, the therapeutic advantages are different
.

In fact, cell therapy is divided into two types
: immune cell therapy and stem cell therapy.
Among them, immune cell therapy refers to the isolation of certain types of immune cells such as T cells, NK cells, B cells, DC cells, etc.
in vitro, gene modification, activation and expansion and other targeted treatment and then infused back into the patient's body, so that it shows the function of killing tumor cells, clearing viruses and so on, and can treat a variety of diseases including tumors, autoimmune diseases and infectious diseases
.

Immune cell therapy is divided into two types
: specific and non-specific.
Among them, the specificity includes CAR-T therapy, TCR-T therapy, TIL therapy and CAR-NK therapy, all of which have different mechanisms of
action.

Specificities include CAR-T therapy, TCR-T therapy, TIL therapy and CAR-NK therapy, all of which have different mechanisms of
action.

In contrast, due to the low technical barriers of CAR-T therapy and the key breakthroughs that have been made before, 8 CAR-T therapies have been approved for listing in the world (including 6 products targeting CD19 and 2 targeting BCMA), but they are all therapeutic hematological tumors, involving domestic companies including Legend Biologics, Fosun Kate, and WuXi Juno (jointly established by WuXi AppTec and Juno in the United States).

At present, 8 CAR-T therapies have been approved for marketing around the world, but all of them are for the treatment of hematological tumors

Although the druggability of CAR-T therapy has been proven, there are still many shortcomings
.
For example, safety issues that are difficult to manage toxicity such as off-target and cell storms; Limited treatment of solid tumors; High manufacturing cost, difficult to prepare on a large scale; High pricing, low penetration, etc
.

Although the druggability of CAR-T therapy has been proven, there are still many shortcomings
.

In contrast, CAR-NK therapy has unique therapeutic advantages
.

In contrast, CAR-NK therapy has unique therapeutic advantages
.

First of all, unlike T and B cells, NK cells are one of the main effector cells for the body to recognize cell malignancy or lesions, and can identify and kill non-self-defined broad-spectrum cells, including tumor cells and virus-infected cells
, without prior immune activation or sensitization.

Second, CAR-NK can be used for allogeneic transplantation, which can enhance the anti-tumor effect of grafts without causing graft-versus-host disease
.
This is because NK cell-mediated cytotoxic effects do not rely on the presentation of their own HLA (human leukocyte antigen) molecules and can therefore be used in allogeneic cell products for immunotherapy
of tumors.

CAR-NK can be used for allogeneic transplantation

In addition, CAR-NK therapy has a broad antitumor profile
.
Can kill homologous, allogeneic or xenoid tumor cells; It can be used for the treatment of solid tumors and blood diseases, and can also be combined with other monoclonal antibodies to treat various types of cancer, and the indications are more extensive
.

CAR-NK therapy has a broad antitumor profile

Finally, since NK cells are the cells with the strongest ability to mediate ADCC (immune cells to destroy pathogenic target cells that have bound specific antibodies), and the recognition mechanism does not depend on the diversity of antigens and activating molecules, it can overcome the heterogeneity of tumor tissue to a certain extent, and has great potential
for comprehensive treatment with targeted drugs.

There is great potential
for comprehensive treatment in combination with targeted drugs.

It is precisely based on the limitations of autologous CAR-T cells that the positioning of Xingyiang is established to develop chimeric antigen receptor allogeneic NK cell therapy (allogeneic CAR-NK)
with universal "spot" potential for solid tumor treatment.

After all, because solid tumors are more sensitive to antigen-dependent NK cells, CAR-NK has an advantage in the treatment of solid tumors, and because NK cells do not require strict HLA matching, immune rejection does not occur for days to weeks, and its safety is better than that of CAR-T therapy and does not cause cytokine release syndrome
.

In addition, in terms of commercialization, allogeneic CAR-NK cell therapy is also more advantageous
.

In addition, in terms of commercialization, allogeneic CAR-NK cell therapy is also more advantageous
.

As mentioned above, the limitation of autologous CAR-T cell therapy lies in the difficulty of large-scale preparation and the inability to obtain the advantage
of large-scale production.

On the contrary, because allogeneic CAR-NK cells come from a wide range of sources, they can be obtained from peripheral blood, NK cell line (NK-92), induced pluripotent stem cells (iPSC), mesenchymal stem cells (such as umbilical cord blood), so that multi-dose products with universal spot type, mass production, and the remarkable characteristics of treating solid tumors can be produced in advance, so as to achieve the purpose of
convenient treatment, reduce production costs, and improve drug accessibility.

More than 19 CAR-NK therapies are in research, and hematological tumors account for a relatively high proportion

More than 19 CAR-NK therapies are in research, and hematological tumors account for a relatively high proportion

The unique treatment advantage has attracted many pharmaceutical companies at home and abroad to enter the CAR-NK therapy track
.

At present, the global research and development of CAR-NK therapy is in full swing, and the indications cover the treatment of hematopoietic system malignancies (such as leukemia, lymphoma and multiple myeloma, etc.
) and solid tumors (such as melanoma, ovarian cancer and lung cancer).

In terms of overseas research and development, most of the current CAR-NK therapy research projects are in the early clinical stage, of which the fastest progress is K-NK002 of Kiadis Pharma and GTA002 of Glycostem Therapeutics, which are in clinical phase II.
The indications of the former are to prevent the recurrence of HSCT after transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome, and the indications of the latter are acute myeloid leukemia, multiple myeloma, and solid tumors
。

Among them, the fastest progress is Kiadis Pharma's K-NK002 and Glycostem Therapeutics' GTA002, both of which are in clinical phase II

In China, there are at least 19 CAR-NK therapy research projects at present, but they are basically in the early clinical stage, mainly concentrated in the I.
/II.
stage, mainly based on hematological tumors, only a few solid tumors (hepatocellular carcinoma, gastric cancer, pancreatic cancer, etc.
), involving enterprises including Anke Bio investment in Boshengji Pharmaceutical (5 in research), Asco Bio (4 in research), Kelun Botai (a holding subsidiary of Kelun Pharmaceutical), Qixi Biologics, etc
.

At present, there are at least 19 CAR-NK therapy projects in research, but they are basically in the early stage of clinical practice, mainly hematological tumors

However, although CAR-NK therapy has unique therapeutic advantages, it also faces many challenges
.

However, although CAR-NK therapy has unique therapeutic advantages, it also faces many challenges
.

For example, since the number of NK cells in a single donor is not sufficient for treatment, NK cells need to be expanded and activated, and the mixed T cells inside must be completely cleared to prevent GVHD (graft-versus-host disease), the number of donor cells available is small
.

In addition, CAR-NK therapy also faces the challenge
of building a suitable CAR and choosing the right method to convert CAR to NK cells.
This is mainly due to the fact that the commonly used transfection vectors, whether retroviral vectors or lentiviral vectors, are not the most ideal, safe and practical transfection methods
.

epilogue

epilogue

In summary, both CAR-T therapy and CAR-NK therapy have unique advantages and shortcomings
.
However, compared with the highly competitive PD-1 monoclonal antibody market, the emerging popular track is bound to be favored
by capital.

Looking to the future, if these two cell therapies can solve their respective technical shackles, they will inevitably become the frontier products leading the new round of development of China's innovative drugs, and related companies will also become the "fragrant food"
of the capital market.

【References】

【References】【References】

1.
Financial reports, announcements, and official websites of each company

1.
Financial reports, announcements, and official websites of each company

2.
White Paper on the Development of China's Cell Therapy Industry, Frost & Sullivan

2.
White Paper on the Development of China's Cell Therapy Industry, Frost & Sullivan

3.
"Precision Medicine in the Pharmaceutical Industry: Wash Away the Lead, Precision Medicine is Waiting for You in the Spring", CITIC Securities

3.
"Precision Medicine in the Pharmaceutical Industry: Wash Away the Lead, Precision Medicine is Waiting for You in the Spring", CITIC Securities

4.
"CAR-T Cell Therapy Industry In-depth Report: Due to Disease Conditions, the Sharp Weapon of the Anti-Cancer Battlefield", Everbright Securities

4.
"CAR-T Cell Therapy Industry In-depth Report: Due to Disease Conditions, the Sharp Weapon of the Anti-Cancer Battlefield", Everbright Securities