Xinchuan Biologics Advances iPSC-Derived CAR-NK Therapy Toward Clinical Trials Within 1–2 Years

The technical and industrial thresholds for iPSC-derived CAR-NK are extremely high. Currently, only a few companies have the courage to tackle iPSC-derived CAR-NK, and Xinchuan Biotech is one of them.

Dr. Wenjun Zhang, the co-founder of the company, serves as the Chief Medical Officer. With over 20 years of clinical work experience, Dr. Zhang has served as the Deputy Director of the Hematology Clinical Research Center at a well-known tertiary hospital in China and has long been engaged in basic and clinical research on immunotherapy for hematological tumors and targeted intervention of leukemia stem cells.

In clinical practice, Dr. Zhang Wenjun has encountered many cancer patients who developed drug resistance after conventional radiotherapy and chemotherapy, leading to a dilemma of having no available treatment options. The emergence of CAR-T cell therapy has significantly improved the clinical outcomes for patients with relapsed/refractory tumors, but due to its high cost, a large number of patients still cannot benefit from it.

How to solve the dilemma of patients having "no drugs available" or "astronomically priced drugs"? It cannot rely solely on clinicians; efforts must also be made at the source of drug development. This prompted Dr. Zhang Wenjun to move from clinical practice to the pharmaceutical industry, co-founding XinChuan Biotech with like-minded individuals in October 2021.Focus on iPSC-derived CAR-NK Therapy, develop inclusive cell therapy products, and improve the accessibility of cell therapy drugs.

It is reported that the chief scientist of Xinchuan Biotechnology holds dual doctorates from the Institute of Zoology, Chinese Academy of Sciences, and the University of Versailles in France, with nearly 20 years of experience in stem cell biology and epigenetics. The chief technology officer has 15 years of experience in cancer research and specializes in the development and clinical application of targeted tumor cell therapy products.

The founding team consists of both clinical doctors and cell therapy technology experts, forming a highly complementary set of capabilities.Ensure the clinical value of the cell therapy products developed by Xinchuan Biotech.

Focusing on hematological tumors (B-cell lymphoma) and solid tumors (lung cancer, colorectal cancer, liver cancer, etc.), Xinchuan Biotech has developed multiple product pipelines. At the same time, the company is also building a cell bio-sample bank, a CAR+Binder library and gene-editing platform, and a high-throughput drug screening platform. In March 2022, less than half a year after its establishment, Xinchuan Biotech completed a nearly 100-million-yuan seed round of financing.

Currently, the global cell therapy market is dominated by CAR-T therapy, with various novel cell therapy products such as CAR-NK, TCR-T, and TIL playing a supplementary role. Data shows that there are 520 ongoing clinical trials of immune cell therapies worldwide, utilizing 64 different CARs, 96.4% of which involve CAR-T cells, while the CAR-NK cell field is still in its infancy.

However, all CAR-T therapies approved for marketing globally are autologous products, and there are still many limitations.First, autologous CAR-T therapy extracts the patient's own immune cells, which are then processed ex vivo and reinfused into the patient. This approach faces challenges such as long preparation time, difficulty in standardizing the manufacturing process, inability to achieve mass production leading to extremely high costs, and insufficient efficacy against solid tumors. Additionally, many patients have poor-quality immune cells, which limits treatment outcomes. Second, autologous CAR-T therapy is associated with severe toxic side effects, and cell therapy must be performed in experienced medical institutions, significantly restricting the product's accessibility.

Dr. Zhang Wenjun believes that, "Compared with autologous cell products,Universal cell therapy products have the advantages of controllable and mature preparation processes, lower costs, the ability to be prepared in advance, immediate availability for patients, and the capability for large-scale mass production.It is the direction that is more promising now and will be an inevitable trend in future development.”

Currently, the development of universal cell therapy products is proceeding rapidly, particularly in universal CAR-T therapies and universal cell therapies based on NK cells.

Among them, the current stage of using gene editing methods to develop universal CAR-T therapy has high technical difficulty, significant safety risks, and limited cost reduction potential. However, NK cells do not need to rely on extracting NK cells from patients, have low immunogenicity, can be allogeneic transfused, and possess higher safety, making CAR-NK an ideal choice for universal cell therapy. In recent years, with the maturation of NK cell culture technology, the popularity of CAR-NK therapy has rapidly increased, leading companies such as Sanofi and Bristol-Myers Squibb to successively invest in this field.

It is worth mentioning that,The potential of iPSC-derived CAR-NK has received significant attention from the industry.Dr. Zhang Wenjun said, "Compared with peripheral blood-derived, umbilical cord blood-derived, and NK-92 cell line-derived sources, iPSC-derived CAR-NK can be prepared on a platform, has unlimited proliferation potential, minimal immune rejection, high cell consistency, cost reduction, and better assurance of CAR-NK therapy quality, offering numerous application advantages."

In the selection of NK cell sourcing technology routes, Xinchuan Biotech has made careful considerations. Dr. Zhang Wenjun stated: "In terms of safety, the NK-92 cell line carries a risk of carcinogenesis. For product stability, it is necessary to choose cells capable of infinite passage, while there are variations between different batches of peripheral blood and cord blood. Considering all factors, iPSC-derived CAR-NK is a superior choice."

Comparison of NK Cells from Different Sources

Currently, CAR-NK derived from peripheral blood is progressing slightly faster, while CAR-NK derived from iPSC is still in the early stages of development globally. Overall, CAR-NK, unlike CAR-T therapy, has not yet been able to strongly demonstrate its efficacy and remains in the experimental stage, but it also presents numerous opportunities waiting to be explored.

For the development of CAR-NK therapy, the Xinchuan Biotechnology team has established multiple technical platforms. Among them,iPSC Seed Cell Bank from Multiple Cell Sources, when preparing NK cells, it is possible to select cell sources with higher differentiation efficiency, stronger killing ability, and greater persistence;iPSC Gene Editing PlatformGene editing of cells at the iPSC stage can induce CAR-NK with stronger killing ability and persistence.Differentiation PlatformCan differentiate NK cells more efficiently.

In hematological tumors, cell therapy has more successful experiences (currently approved CAR-T therapies and the majority of clinical studies focus on hematological tumor targets). However, the solid tumor market is larger, but the application of CAR-NK in solid tumors is more limited due to the influence of the tumor microenvironment.

Specifically, in the research of hematological tumors, Xinchuan Biotech has already validated the feasibility of CAR-NK therapy in B-cell lymphoma through animal experiments. "Whether in vivo or in vitro, CAR-NK demonstrated excellent cytotoxic effects on B-cell lymphoma without noticeable toxic side effects. Further optimizations will be made to the process later.Advance this pipeline into the clinical trial stage within 1-2 years."Dr. Zhang Wenjun said."

Xinchuan Biotech's Chief Technology Officer has deep expertise in solid tumor cell therapy and tumor microenvironment research.Xinchuan Biotech aims to conquer hematological tumors and solid tumors. While developing targeted B-cell lymphoma cell products, it is also advancing the development of CARs targeting solid tumors, including lung cancer, colorectal cancer, and liver cancer.The company has collaborated with partners to screen out high-affinity fragments on the target, for the development of CAR-NK therapy with high targeting and high killing power.

Xinchuan Biotech Product Pipeline Layout

As numerous pharmaceutical giants and emerging innovative drug companies continue to enter the cell therapy market, enterprises must build core competitiveness in technical strength. Next, Xinchuan Biotech will leverage its team's core technical capabilities to construct an iPSC biobank, gene editing, and induced differentiation technology platforms, rapidly advancing the research, development, and translation of CAR-NK therapies for hematologic malignancies and solid tumors.

Xinchuan Biotech was founded in October 2021, with its headquarters located in Beijing Economic and Technological Development Zone. The company's founding team members have been deeply engaged in the field of stem cell research for over a decade and have already achieved abundant research results in the field of cell therapy; the core members are all authoritative experts from the fields of life sciences and clinical medicine. Based on its comprehensively innovative iPSC-CAR-NK immune cell therapy and organoid high-throughput screening technology, Xinchuan Biotech has developed multiple CAR-NK product pipelines targeting high-incidence cancers such as lung cancer, colorectal cancer, liver cancer, and B-cell lymphoma. It is committed to becoming a world-leading platform for the research, development, and production of cell-based drugs, promoting the development of original immune cell drugs aimed at curing solid tumors.