2021H1 cell therapy financing exceeds 7.3 billion U.S. dollars: T cell and stem cell therapies occupy high ground, NK cell therapy has become a new trend, spot-type therapy is worthy of attention

With the continuous maturity of cell engineering methods and gene editing technology, cell therapy is also developing rapidly: new technologies are blooming; popular technologies are gradually improved; indications are also expanding, showing good therapeutic prospects from cancer to HIV infection.

.

Global: 60 financing events, 12 company IPOs

Global: 60 financing events, 12 company IPOs

According to the PharmaInvest database, the 2021 H1 global cell therapy field involves about 60 financings (including IPO financing).
The total financing amount exceeds 7.
3 billion U.
S.
dollars, of which domestically exceeds 2 billion U.
S.
dollars and foreign countries exceed 5.
3 billion U.
S.
dollars
.

The overview of the financing rounds is shown in the figure below.
The A round of financing accounted for the highest proportion (28%).
The technologies involved include popular CAR-T and iPSC cell therapies, as well as emerging myeloid cell therapies, CAR-NKT, etc.
; followed by IPO (22%).
The technologies involved are mainly T cell therapy and stem cell therapy
.

Overview of 2021H1 cell therapy financing round

Analyzed by cell therapy type, T cell therapy accounted for more than half, and the financing amount exceeded US$5.
5 billion; followed by stem cell therapy (26%, more than US$1.
8 billion), NK cell therapy (11%, more than US$570 million), giants Cellular therapy (5%, over 130 million US dollars)
.

These data have once again verified the popularity of T cell therapy and stem cell therapy

The proportion of different types of cell therapy financing in 2021H1 (left) and financing amount (right)
.

Note: A single financing event can include multiple types of cell therapies, which are separately counted.

In addition to the above classification, spot-type immune cell therapy is also worthy of attention
.

2021H1.

2021H1 Spot-type immune cell therapy for cancer

Spot-type immune cell therapy is one of the development trends of cell therapy
.

Taking CAR-T as an example, traditional CAR-T therapies are “customized”, costly, expensive, time-consuming to prepare, and limited in quantity and quality of T cells in cancer patients.

In this field, on June 17, American biotechnology company Century Therapeutics announced an IPO of US$211 million
.

Century is committed to using the potential of adult stem cells to develop spot cell therapies for cancer treatment.

Century, which frequently attracts gold, relies on induced pluripotent stem cells (iPSCs) with unlimited self-renewal ability.
Through multiple rounds of cell engineering, a master cell bank is created.
These cells can be expanded and differentiated into immune effector cells, thereby providing a large number of identical cells.
A kind of allogeneic and homologous cell therapy products
.

Century's spot-type T cell and NK cell therapies can avoid host rejection, are suitable for repeated administration, and can enhance durability and durability

In the field of iPSC-derived cell therapy, I have to mention the leading iPSC company Fate Therapeutics
.

In February 2019, the FDA approved Fate's IND application for iPSC-derived spot NK cell therapy FT516 for clinical trials of hematoma

On August 19 this year, Fate announced its Phase I clinical dose-climbing results of FT516 for relapsed/refractory B-cell lymphoma: 8 (73%) of 11 patients who used different doses of FT516 reached the objective Remission, of which 6 cases were complete remission (55%)
.

The therapy is well tolerated, the toxicity limit dose is not reached, and graft-versus-host disease (GvHD), which is common in allogeneic cell therapy, has not occurred.

As a result, the field of spot-type cellular immunotherapy is making rapid progress, which can be seen
.

Domestic: CAR-T Red Sea competition remains the same

Domestic: CAR-T Red Sea competition remains the same

Overview of Domestic Investment and Financing of 2021H1 Cell Therapy

Consistent with the overall trend, 2021H1 domestic investment and financing events are mainly concentrated in the fields of T cell (especially CAR-T) therapy and stem cell therapy
.
Among them, the IPOs of two CAR-T therapy companies are worthy of attention
.

On January 8, Genxi Biologics was listed on the Nasdaq and raised US$209 million, making it the fourth Chinese cell therapy company to land on the capital market after Nanjing Legend, WuXi Biologics, and Yongtai Biologics
.

Genxi Bio has two core platform technologies
.
FasTCAR platform technology can develop autologous CAR-T cell products with younger phenotype, less exhaustion, stronger activity and better lethality
.
This T cell is produced in 22 to 36 hours and can be harvested the next day
.
Traditional CAR-T cell production time is generally 2 to 6 weeks, while FasTCAR platform technology combines activation of T cells, transfection and expansion into one step, greatly shortening the production time
.
This advantage can be described as a race with death for advanced patients
.

In addition, the TruUCAR platform technology can develop spot CAR-T products that are derived from healthy donor T cells and do not require HLA matching
.
Because it can be mass-produced in advance and does not need to bridge bone marrow stem cell transplantation in clinical use, this spot-type allogeneic CAR-T cell therapy has the advantages of low cost and high convenience
.

Genxi Biological Product Pipeline (Source: Genxi Biological Official Website)

On June 18, Keji Pharmaceuticals successfully landed on the Hong Kong Stock Exchange.
The total IPO funds raised was approximately US$400 million.
The funds raised will mainly be used to further develop its core product candidate BCMACAR-T (CT053), as well as for other pipeline candidate products.
R&D activities provide funds to cultivate comprehensive manufacturing and commercialization capabilities
.

As a local innovative pharmaceutical company focusing on CAR-T therapy, its CAR-T candidate products are evidence-based new tumor-associated antigens, and are carefully designed and optimized to reduce the common side effects of existing CAR-T therapies
.
In addition, Keji Pharmaceutical is exploring the proprietary allogeneic CAR-T technology THANK-uCAR, which aims to overcome the problems of low efficiency of allogeneic CAR-T cell expansion and persistence
.

The company already has 11 product candidates, of which the fastest research and development progress is the upgraded version of the fully human anti-targeted BCMA CAR-T product CT053.
The indication is multiple myeloma, which has entered a key phase II clinical trial in China.
In the first half of 2022, an NDA application will be submitted to the China Food and Drug Administration
.

Keji Pharmaceutical is committed to using technological innovation to overcome the challenge of CAR-T cell therapy for solid tumors.
In the existing independent research and development pipeline, except for CT053, CT032, KJ-C2111, the remaining 7 CAR-T candidate products are used for treatment Solid tumors
.

Keji Pharmaceutical Product Pipeline (Source: Keji Pharmaceutical Official Website)

Abroad: A variety of emerging technologies attract attention

Abroad: A variety of emerging technologies attract attention

Overview of foreign investment and financing for 2021H1 cell therapy

2021H1.
Compared with domestic, there are more emerging technologies gaining attention from abroad
.
The financing of these technologies is mostly concentrated in the early stages, such as:

CAR-NKT therapy : Inceptor Bio (Seed round), Immunai (A round), Appia Bio (A round)

CAR-NKT therapy

Myeloid cell therapy : Myeloid Therapeutics (round A)

Myeloid cell therapy

CAR-M therapy : Inceptor Bio (seed round), CARISMA Therapeutics (B round)

CAR-M therapy

γδ T cell therapy : Acepodia (round B)

γδ T cell therapy

Among them, Appia Bio, an early-stage biotechnology company in the United States, which was established in 2020 and completed $52 million in Series A financing on May 11, is worthy of attention
.
Not long after the Series A financing stepped out of the stealth mode, Appia Bio reached a cooperation and licensing agreement with Kite, a company of Gilead Sciences, on August 5 to use the former "ACUA" allogeneic cell therapy technology platform to develop Constant natural killer T cell (CAR-iNKT) therapy expressing chimeric antigen receptors is used for cancer
.

NKT is a unique subgroup of T lymphocytes, which expresses both NK cell receptors and T cell related receptors (TCR), and thus has both the non-specific killing function of NK cells and the specific killing function of T cells
.
iNKT expresses constant TCRVα14 and partly identifies the CD161 (NK1.
1) molecule of NK cells and the NK cell receptor NKR-P1C
.
iNKT cells are also considered classic NKT cells
.

Studies have found that iNKT cells play an important role in the regulation of a variety of immune responses, including autoimmune diseases, metabolic diseases and cancer
.
With CAR technology, it becomes possible to use this powerful immune cell to treat tumors extensively
.

In the process of anti-tumor immunity, iNKT cells can secrete cytokines and activate other immune cells to participate in innate immunity and adaptive immunity after being activated
.
Due to the unique antigen recognition method, iNKT cells will not cause graft-versus-host disease
.
However, the number of these cells is too low in the human body (about 0.
01%-2% of peripheral blood mononuclear cells).
The separation of iNKT cells from patients to generate CAR-iNKT cells like traditional CAR-T therapy faces a great deal.
Challenge
.

Appia Bio's method is to use hematopoietic stem cells (HSC) to produce CAR-iNKT cells.
In addition, its ACUA platform also has the potential to improve the efficacy and safety of HSC-derived CAR-iNKT cell therapy and streamline the production process
.

Giant deal: NK cell therapy has become a new trend

Giant deal: NK cell therapy has become a new trend

2021H1 Cell Therapy Field Pharmaceutical Giants Cooperative Transactions

2021H1.
A number of giants announced their latest moves in the field of cell therapy, and NK cell therapy continues to grow hot
.

On January 28, Merck and Artiva Biotherapeutics, an American biotechnology company dedicated to the development of anti-cancer NK cell therapies, announced the signing of a global exclusive cooperation and licensing agreement totaling over 1.
8 billion U.
S.
dollars to utilize Artiva’s spot-type allogeneic NK cell manufacturing platform and Proprietary CAR-NK technology to develop new CAR-NK cell therapy for solid tumor-related antigens
.

In June, Shoreline Biosciences, which used intelligent technology to develop allogeneic spot type, standardized, iPSC-derived NK and macrophage-targeted cellular immunotherapy, received another olive branch from BeiGene and Gilead Sciences subsidiary Kite within 10 days.
Two cooperations were reached, totaling more than 2 billion U.
S.
dollars
.

In terms of clinical progress, at this year’s AACR annual meeting, Affimed reported on the early clinical trial results of cord blood-derived NK cells combined with innate cell engager (ICE®) AFM13 (CD16A/CD30) in the treatment of CD30-positive lymphoma.
The 100% response rate is what the industry sees.
Yiliang
.

In China, NK cells have also ushered in a new chapter
.
In February 2021, CDE accepted the clinical trial application of Guojian Chengnuo Biotechnology (Beijing) Co.
, Ltd.
for the treatment of advanced epithelial ovarian cancer targeting mesothelin CAR-NK injection
.
This is the first CAR-NK cell product for the treatment of solid tumors that has received a clinical application from CDE in China, and it is also an important milestone in the treatment of solid tumors with immune cells
.

Taken together, NK cell therapy has become a hot field
.

Overview of investment and financing in the field of 2021H1 cell therapy, in addition to the fierce competition for popular T cell therapies, some new trends have also emerged, such as spot cell therapy and NK cell therapy that overcome the shortcomings of traditional CAR-T therapy
.

Since the discovery of iPSC technology, stem cell biology has made significant progress
.
iPSC promotes spot-type immune cell therapy to move forward, solving the problems of traditional autologous CAR-T therapy, such as expensive price, long preparation time, and limited quantity and quality of cancer patients' own T cells, which greatly increases patient accessibility
.
CAR-T, CAR-NK, and CAR-M derived from iPSC have come out one after another, and have achieved positive results in preclinical and clinical applications, with broad application prospects
.

In addition, although CAR-T has a higher response rate in certain hematological tumors, durability and safety are issues that need to be resolved
.
Like T cells, NK cells can also be modified to better identify specific tumors, and NK cell therapy has unique advantages: 1) Pan-specific killing effect makes the anti-tumor spectrum of NK cells unrestricted; 2) Good safety , Will not cause cytokine release syndrome or graft-versus-host disease; 3) Unlike CAR-T cell therapy, CAR-NK cells do not require strict HLA matching and can become allogeneic therapeutic drugs
.
Pharmaceutical giants such as BMS, Sanofi, Merck & Co.
, etc.
are all competing in this market through investment transactions
.

At present, the pipelines of many companies intersect the two technologies of spot cell therapy and NK cell therapy, such as Century Therapeutics, Fate Therapeutics, Artiva Biotherapeutics, and Appia Bio
.

In summary, 2021H1 cell therapy financing shows that T cells and stem cell therapies occupy a high ground, and a variety of emerging technologies are blooming.
Among them, NK cell therapy and spot cell therapy are gaining popularity and new trends in cell therapy are emerging
.

Note: The data in this article are incomplete statistics, for reference only, and do not constitute investment advice
.

Note: The data in this article are incomplete statistics, for reference only, and do not constitute investment advice
.

Reference materials:

References: References:

1#  Century Therapeutics Announces Pricing of Initial Public Offering (Source: Century official website)

1# 1#  Century Therapeutics Announces Pricing of Initial Public Offering (Source: Century official website)

2#   Genxi Biological Prospectus

2# 2#   Genxi Biological Prospectus

https:// 3#  Keji Biotech submitted the IPO prospectus to the Hong Kong Stock Exchange (Source: Medical Rubik's Cube)

3# 3#  Keji Biotech submitted the IPO prospectus to the Hong Kong Stock Exchange (Source: Medical Rubik's Cube)

4#  KITE AND APPIA BIO ANNOUNCE COLLABORATION TO RESEARCH AND DEVELOP ALLOGENEIC CELL THERAPIES FOR CANCER (Source: Kite official website)

4# 4#  KITE AND APPIA BIO ANNOUNCE COLLABORATION TO RESEARCH AND DEVELOP ALLOGENEIC CELL THERAPIES FOR CANCER (Source: Kite official website)

5#  Original | Fate announces new data on CAR-NK therapy (Source: U.
S.
Chinese Medicine Source)

5# 5#  Original | Fate announces new data on CAR-NK therapy (Source: U.
S.
Chinese Medicine Source)

6#  Affimed Announces Presentation at AACR Highlighting Initial Data from Phase 1 Study of Cord Blood-derived Natural Killer Cells Pre-complexed with Innate Cell Engager AFM13 (Source: Affimed official website)

6# 6#  Affimed Announces Presentation at AACR Highlighting Initial Data from Phase 1 Study of Cord Blood-derived Natural Killer Cells Pre-complexed with Innate Cell Engager AFM13 (Source: Affimed official website)

7# The  first case of Guojian Chengnuo CAR-NK cell treatment of solid tumors was accepted by the State Food and Drug Administration (Source: Financial Report Network)

7# 7# The  country’s first case of Guojian Chengnuo CAR-NK cell treatment of solid tumors was accepted by the State Food and Drug Administration (Source: Financial Report Network)