With the continuous maturity of cell engineering 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 treatment prospects from cancer to HIV infection. According to the medical database, the global cell therapy field of 2021 H1 involves about 60 financing (including IPO Financing), with a total financing amount of more than $7.3 billion
Overview of financing rounds: round a financing accounts for the highest proportion (28%), involving technologies such as popular car-t and IPSC cell therapy, as well as emerging myeloid cell therapy and car-nkt; Followed by IPO (22%), the technologies involved are mainly T cell therapy and stem cell therapy.
According to the analysis of cell therapy types, T cell therapy accounts for more than half of the total, and the financing amount exceeds US $5.5 billion; Followed by stem cell therapy (26%, over $1.8 billion), NK cell therapy (11%, over $570 million) and macrophage therapy (5%, over $130 million). These data once again verify the heat of T cell therapy and stem cell therapy. In addition to the above classification, spot immunocell therapy also deserves attention. In 2021h1, the financing amount of spot immunotherapy for cancer treatment exceeded US $400 million.
2021h1 spot immunocell therapy for cancer
Spot immune cell therapy is one of the development trends of cell therapy. Taking car-t as an example, the traditional car-t therapy has high cost, high price, long preparation time, limited quantity and quality of T cells of cancer patients due to “personal customization”, and the spot cell therapy derived from stem cells (such as IPSC) can solve these problems.
In this field, on June 17, American biotechnology company Century therapeutics announced an IPO to raise US $211 million. Century is committed to using the potential of adult stem cells to develop spot cell therapy for cancer. In March this year, the company just completed a round C financing of US $160 million.
The technology platform of century, which attracts gold frequently, relies on induced pluripotent stem cells (IPSC) with unlimited self-renewal ability to create a main cell bank through multiple rounds of cell engineering. These cells can expand and differentiate into immune effector cells, so as to provide a large number of allogeneic and homologous cell therapy products. Century’s spot T cell and NK cell therapy can avoid host rejection, is 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 fat therapeutics. In February 2019, FDA approved the ind application of fat’s IPSC derived spot NK cell therapy ft516 for clinical trial for hematoma. This is the first IPSC derived cell therapy approved by FDA for clinical trial in the world.
On August 19 this year, fate announced its phase I clinical dose climbing results of ft516 for recurrent / refractory B-cell lymphoma: 8 (73%) of 11 patients with different doses of ft516 achieved objective remission, of which 6 were complete remission (55%). The treatment was well tolerated, did not reach the toxic limit dose, and did not occur the common graft-versus-host disease (GVHD) of allogeneic cell therapy. The results were roughly equivalent to that of spot car-t. Thus, the hot progress in the field of spot cell immunotherapy can be seen.
A variety of emerging technologies have attracted attention
In 2021h1, more emerging technologies have attracted attention. The financing of these technologies is mostly concentrated in the early stages, such as:
Car-nkt therapy: inductor bio (seed round), immunonai (round a), Appia bio (round a)
Myeloid cell therapy: myeloid therapeutics (round a)
Car-m therapy: ceptor bio (seed round), Carisma therapeutics (round b)
γδ T cell therapy: acepodia (round b)
Among them, Appia bio, an American early biotechnology company founded in 2020 and completed a round of financing of US $52 million on May 11, deserves attention. Not long after round a financing stepped out of the stealth mode, Appia bio reached a cooperation and licensing agreement with Geely Tech’s kite on August 5 to develop constant natural killer T cell (car iNKT) therapy expressing chimeric antigen receptor for cancer by using the former’s “acua” allogeneic cell therapy technology platform.
NKT is a unique subgroup of T lymphocytes, which expresses both NK cell receptor and T cell related receptor (TCR), and then has both non-specific killing function of NK cells and specific killing function of T cells. INKT expresses constant TCRV α 14 and NK cells partially identify CD161 (NK1.1) molecule and NK cell receptor nkr-p1c. INKT cells are also considered to be classical NKT cells.
It has been 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 is possible to make extensive use of this powerful immune cells to treat tumors.
In the process of anti-tumor immunity, iNKT cells can activate other immune cells to participate in innate and acquired immunity by secreting cytokines. Because of its unique antigen recognition mode, iNKT cells will not cause graft-versus-host disease. However, the amount of such cells in human body is too low (about 0.01% – 2% of peripheral blood monocytes). Like traditional car-t therapy, it is a great challenge to isolate iNKT cells from patients to generate car-inkt cell therapy.
Appia bio’s method is to use hematopoietic stem cells (HSCs) 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 becomes a new outlet
On January 28, MSD and artiva biotherapeutics, an American biotechnology company committed to developing anti-cancer NK cell therapy, announced the signing of a global exclusive cooperation and license agreement with a total amount of more than US $1.8 billion to develop a new car-nk cell therapy for solid tumor related antigens by using artiva’s spot allogeneic NK cell manufacturing platform and proprietary car-nk technology.
In June, shoreline Biosciences, which used intelligent technology to develop allogeneic, standardized, IPSC derived NK and macrophage targeted cell immunotherapy, successively received olive branches from Baiji Shenzhou and Geely Tech’s subsidiary kit, and reached two cooperation projects within 10 days, with a total amount of more than US $2 billion.
In terms of clinical progress, at this year’s AACR annual meeting, affiliated reported that umbilical cord blood derived NK cells combined with innate cell engager (ice ®) The early clinical trial results of afm13 (cd16a / CD30) in the treatment of CD30 positive lymphoma, with a 100% response rate, brightened the industry. In general, NK cell therapy has become a hot field.
Overview investment and financing in the field of 2021h1 cell therapy. In addition to hot T cell therapy and fierce competition, some new wind directions also emerge, such as spot cell therapy and NK cell therapy to overcome the defects of traditional car-t therapy.
Since the discovery of IPSC technology, great progress has been made in stem cell biology. IPSC has pushed forward spot immune cell therapy, solved the problems of high price, long preparation time and limited quantity and quality of T cells in cancer patients, and greatly increased the accessibility of patients. Car-t, car-nk and car-m from IPSC have been published successively, both preclinically and clinically It has achieved positive results and has broad application prospects.
In addition, although car-t has a high response rate in some blood tumors, its persistence and safety are problems that need to be solved. 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 not limited; 2) good safety and will not cause cytokines Release syndrome or graft-versus-host disease; 3) different from car-t cell therapy, car-nk cells do not need strict HLA matching and can become allogeneic therapeutic drugs. Pharmaceutical giants such as BMS, Sanofi and MSD are seizing the market through investment and trading.
At present, the pipelines of many companies cross involve two technologies: spot cell therapy and NK cell therapy, such as century therapeutics, fat therapeutics, artiva biotherapeutics and Appia bio.
In conclusion, the financing in 2021h1 cell therapy shows that T cells and stem cell therapy occupy a high ground, and a variety of emerging technologies bloom, including the rising popularity of NK cell therapy and spot cell therapy, and the new outlet of osteoblast therapy.