RuiShun Biotech's Investigational CD19-CAR-DNT Cell Therapy for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma Receives IND Acceptance from China CDE

Expected to be the world's first

ZhongshanOctober 27, 2023PR Newswire -- Recently, the new drug registration clinical research application for RJMty19 Injection, an immune cell product under development by Zhejiang Ruishun Biotech Co., Ltd. (hereinafter referred to as "Ruishun Biotech") for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (r/r NHL), has been officially accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Acceptance No.: CXSL2300725).

The main active ingredient of RJMty19 Injection is CD19-CAR-DNT cells. It is an innovative off-the-shelf universal double-negative T cell (DNT) therapy product developed by Zhejiang Ruishun Biotech Co., Ltd. based on a globally patented humanized CD19-CAR domain.

CAR-T (Chimeric Antigen Receptor T-cell) cells targeting CD19 are currently one of the most popular immunocyte therapies for treating B-cell lymphoma. Over the past six years, nine CAR-T cell products have been approved globally for the treatment of hematologic tumors, six of which target CD19.

But currently, CAR-T cell products on the market must be manufactured on a one-to-one basis, meaning one CAR-T cell product for each patient, and cannot be universally applied. This results in the current CAR-T cell therapy being extremely expensive, costing over a million RMB, making it unaffordable for many patients. In contrast, CAR-DNT cells have a natural advantage in this aspect.

DNT cells are a naturally occurring subset of T cells in human peripheral blood, accounting for 1-10% of the total T cell population. Numerous studies have shown that allogeneic DNT cells do not cause graft-versus-host disease or host-versus-graft reactions. Therefore, DNT cells extracted from healthy donor peripheral blood and expanded in large quantities in vitro can be used for all patients, demonstrating universality.

As early as 2020, the research team led by Professor Zhu Xiaoyu from the Department of Hematology, First Affiliated Hospital of University of Science and Technology of China, was the first in the world to complete an investigator-initiated clinical study. The study explored the safety and efficacy of using DNT cells extracted from healthy donor peripheral blood and expanded in vitro to treat patients with post-transplant relapsed acute myeloid leukemia (AML). The findings showed that multiple infusions of DNT cells were well-tolerated, with no severe adverse reactions such as graft-versus-host disease observed clinically.

In August this year, a breakthrough was achieved in the world's first investigator-initiated clinical study of RJMty19 injection (CD19-CAR-DNT cells) for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), led by Professor Qian Wenbin from the Department of Hematology at the Second Affiliated Hospital of Zhejiang University School of Medicine. Among the 12 patients who completed dose-limiting toxicity evaluations, no instances of Grade ≥3 cytokine release syndrome, graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome, or serious adverse events were observed, demonstrating good clinical safety.

According to Dr. Liming Yang, Chairman and Chief Scientist of Zhejiang Ruishun Biotech Co., Ltd., the company has successfully developed an off-the-shelf universal DNT cell product. The DNT cells, prepared from healthy donor sources, can be manufactured in advance and stored in liquid nitrogen at -196°C. After thawing, they maintain biological activity similar to that before freezing, meeting the requirement for immediate use as a drug. This makes expensive cell therapy potentially more affordable as a "cell drug."

Zhejiang Ruishun Biotech Co., Ltd. is the pioneer of global DNT cell immunotherapy and currently the only biopharmaceutical company in the world with a DNT/CAR-DNT cell product entering registered clinical trials.

Dr. Yang Liming pointed out that the natural advantages of DNT cells, along with Zhejiang Ruishun Biotech Co., Ltd.'s leading position in manufacturing off-the-shelf universal DNT cells, will not only allow China to stand at the forefront and lead the world in this field but also enable Chinese patients to benefit significantly from safer, more accessible, and more convenient cell-based therapies.

The anti-tumor efficacy of DNT/CAR-DNT cell therapy has also "begun to show its potential" in multiple clinical studies.

Clinical research conducted by Zhejiang Ruishun Biotech Co., Ltd. in collaboration with Professor Zhu Xiaoyu's team found that among 10 patients with acute myeloid leukemia who completed three infusions of DNT cells, 5 showed treatment efficacy, with 4 achieving durable complete tumor remission. The longest-surviving patient has lived over 4 years.

Clinical research results of CD19-CAR-DNT in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma, conducted by Zhejiang Ruishun Biotech Co., Ltd. in collaboration with Professor Qian Wenbin's team, showed that clinical efficacy significantly improved with increased cell dosage; all three subjects in the fourth dosage group achieved varying degrees of clinical remission after a single administration, with one patient achieving complete remission.

"We look forward to the CD19-CAR-DNT cell registration clinical study, which has been accepted by the CDE, being approved as soon as possible to accelerate subsequent clinical trials, bringing hope for this world's first cell product to become the first off-the-shelf universal immune cell drug," said Dr. Yang Liming with great anticipation.