Ruishun Bio's RC1012: China’s First Allogeneic DNT Cell Therapy for Relapsed/Refractory AML Granted IND Approval

Breakthrough Achievements of Immunotherapy in Curing Advanced Tumors Have Completely Transformed the Current Landscape of Clinical Oncology Treatment.

Previous small-molecule drugs (including targeted therapies) and large-molecule antibody drugs have primarily targeted tumor cells, focusing on strategies to kill them. In contrast, the mechanism of action of immunotherapeutic agents centers on restoring the normal function of patients’ immune cells. By leveraging a “normalized” immune system, these therapies eliminate cancer cells in the blood and tissues, inhibit tumor growth, and enhance the body’s immune competence, demonstrating significant therapeutic potential in cancer treatment.

With the U.S. FDA’s approval of two CAR-T cell therapy drugs in 2017, interest in cell therapy has been steadily rising, making it a hot area of research in current oncology treatment.

Cellular immunotherapy can be classified according to the source of its cells intoAutologous Immune Cell TherapyandAllogeneic Immune Cell Therapytwo major categories. Currently, all cell-based therapies approved internationally are autologous cell products, which involve extracting a patient’s own immune cells, processing them ex vivo, and then reinfusing them into the same patient. These autologous products have several drawbacks, including lengthy manufacturing times (typically 2–3 weeks), difficulties in standardizing production processes, high costs, and the inability to successfully manufacture products for many patients due to poor quality of their own cells. Therefore,The development of allogeneic immune cell products has become a current international hotspot.

DNT cells are a type of adoptive cellular immunotherapy. Unlike autologous immune cell products,DNT cells are prepared from peripheral blood of healthy donors, with a mature and controllable manufacturing process that enables large-scale in vitro expansion. The cells can be manufactured in advance and stored in liquid nitrogen at -196°C.Available for use as needed by patients. Completed non-registrational clinical trial results have demonstrated that allogeneic DNT cells exhibit favorable safety and efficacy in clinical practice.More than 100 days after DNT cell infusion, the patient's DNT cell count remained higher than the pre-infusion level.

Ruishun Biotech focuses on the research and development of a series of non-gene-edited, off-the-shelf universal immune cell products based on its core DNT cell technology platform. The company currently has eight product pipelines in development, targeting the treatment of hematologic and solid tumors.The product under development is a Class I innovative drug that has not yet been marketed either domestically or internationally.

Among these, the allogeneic DNT cell product RC1012 injection developed by the company received implicit approval for clinical trials from the Center for Drug Evaluation of the National Medical Products Administration of China in November 2020. The intended indication is relapsed/refractory acute myeloid leukemia. This product is derived from healthy donors and does not require HLA (human leukocyte antigen) matching, holding promise to becomeThe First Globally Innovative Allogeneic Immune Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia.

DNT cells refer to a subset of CD3+CD4-CD8- T cells that are normally present in human peripheral blood, accounting for 1%–5% of the total T cell population. DNT cells express CD3 molecules and either αβ or γδ T cell receptors (TCRs) on their surface, with over 80% being γδ T cells, but they do not express CD4 or CD8 molecules.

Yang Liming, founder and chairman of Ruishun Biotech, is a postdoctoral fellow at the Faculty of Medicine, University of Toronto, Canada, with 30 years of experience in the field of immunology.is one of the core inventors of DNT cell technology.

After more than 20 years of basic, translational, and clinical research, researchers have discovered that DNT cells possess unique advantages in tumor therapy. According to Dr. Yang, the advantages of the DNT cell technology platform products are mainly reflected in four aspects:

First, DNT cells are extracted from healthy donors, offering low preparation costs, enabling the establishment of standardized production processes, and allowing for advance preparation.It avoids the limitations associated with autologous cell-based therapies, such as cell sourcing, scalable manufacturing processes, and accessibility. Meanwhile, allogeneic DNT cell products are not recognized or rejected by the patient’s immune cells, thereby avoiding host-versus-graft reactions.

Second, the combination of DNT cells with other small-molecule drugs and immune checkpoint inhibitor antibodies, such as anti-PD-1 antibodies, can produce a synergistic effect where “1+1>2”.Monotherapy with PD-1 inhibitors for non-small cell lung cancer (NSCLC) has an objective response rate of only around 20% and requires continuous administration. In contrast, the combination of DNT cells and PD-1 antibodies achieves an objective response rate exceeding 50%, effectively enhancing therapeutic efficacy in NSCLC while reducing treatment costs. Ruishun Biotech is currently developing a DNT + PD-1 combination therapy to improve treatment outcomes for non-small cell lung cancer.

Third, leveraging the inherent property of DNT cells to not induce GvHD, universal CAR-DNT series products can be developed by directly introducing CAR gene fragments without the need for relevant gene knockouts, thereby significantly improving development efficiency and reducing costs.Ruishun Biotech’s first CAR-DNT cell pipeline has demonstrated potent, rapid, and sustained in vitro tumor-killing effects against CD19+ acute lymphoblastic leukemia and non-Hodgkin lymphoma. Preclinical studies are currently being planned to evaluate its safety, efficacy, and pharmacokinetic profile in animal models.

Fourth, DNT cells can undergo gene editing to further enhance their tumor-killing activity.Enhancing DNT Cell Infiltration into Solid Tumors to Eliminate Tumor Cells.

Leveraging the numerous advantages of DNT cells, Ruishun Biotech has established eight R&D pipelines to explore the therapeutic potential of DNT cells in hematologic malignancies (relapsed/refractory acute myeloid leukemia and non-Hodgkin lymphoma) and solid tumors (non-small cell lung cancer, liver cancer, gastric cancer, colorectal cancer, cervical cancer, and ovarian cancer).

RC1012 Injection is the core product of Ruishun Biotech. The product received implicit approval for clinical trials from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in November 2020, with the intended indication being relapsed or refractory acute myeloid leukemia (AML). It is currentlyThe First Allogeneic Immune Cell Product Approved for Registration Clinical Trials in China.

Chemotherapy and hematopoietic stem cell transplantation (HSCT) are currently the primary treatments for relapsed/refractory acute myeloid leukemia (AML). However, both approaches have critical limitations, including high toxicity and a significant risk of relapse. Approximately 70% of patients experience relapse within two years after chemotherapy, necessitating subsequent HSCT. Nevertheless, HSCT imposes stringent requirements on patients’ physical condition and age, and finding a suitable donor is often challenging. Even after successful transplantation, patients require lifelong immunosuppressive therapy, which compromises overall immune function and increases the risk of secondary infections and malignancies.

RC1012 Injection isChina's First Allogeneic Immune Cell Therapy Product Derived from Healthy Donors, Requiring No HLA MatchingThis product demonstrates in vitro and in vivo antitumor activity against blasts in patients with relapsed/refractory acute myeloid leukemia (AML). Repeated infusions enhance its antitumor efficacy without inducing graft-versus-host disease (GVHD) or host-versus-graft reaction.

Exploratory clinical trial results demonstrated that RC1012 injection exhibits favorable safety and efficacy. Among 11 patients with relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation who were treated with RC1012 injection, no severe adverse reactions were observed in any patient. The complete remission rate was 54.5% (6/11), with three patients maintaining complete remission for over 12 months, and the longest duration exceeding 17 months.

Dr. Yang stated that the approval of RC1012 injection for clinical trials marks a significant milestone in the development of DNT cell products. “It signifies that we have reached the end of the dark tunnel and seen a ray of sunlight. We are confident that Ruishun Biotech will forge a broad and promising path in the DNT cell therapy sector.”

Next, Ruishun Biotech will rapidly advance the clinical trials of RC1012 injection to further validate the safety and efficacy of this product in treating relapsed/refractory acute myeloid leukemia (AML) in registration-enabling clinical trials.

Based on the currently known mechanisms of DNT cells in tumor killing,DNT cells demonstrate therapeutic efficacy against approximately 90% of human tumors.As human life expectancy extends and the incidence of tumors rises, the DNT cell technology platform holds immense development potential. Accordingly, Ruishun Biotech will leverage its DNT cell platform to continuously expand indications, thereby benefiting more patients.

Zhao Songguo, General Manager of Ruishun Biotech, stated that the company’s vision isTo establish an innovative R&D and manufacturing enterprise for off-the-shelf universal immune cells, primarily focused on universal immune cell therapies, with a foothold in China and a presence in the global market.“It is expected that by 2023, the RC1012 injection will strive for its global debut launch in the Chinese market, becoming the world’s first allogeneic immune cell therapy product for the treatment of relapsed/refractory acute myeloid leukemia. In addition, it is hoped that two other products will enter Phase II clinical trials and three products will receive clinical trial approval in 2023, further consolidating the company’s core competitiveness in the immune cell therapy market.”