Bioheng Therapeutics Receives NMPA Approval for China's First Off-the-Shelf UCAR-T Therapy CTA101 in Relapsed/Refractory B-ALL

On March 17, the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) showed that the CTA101 UCAR-T Cell Injection, independently developed by Nanjing Bioheng Biotech Co., Ltd. (hereinafter referred to as Bioheng Biotech, product acceptance number: CXSL2101509), has officially received the clinical trial implied permission from the NMPA. CTA101 is the first "off-the-shelf" UCAR-T cell therapy product approved by the CDE in China, intended for the treatment of adult relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Acute lymphoblastic leukemia is a malignant proliferative tumor originating from precursor B or T lymphoid progenitor cells in the bone marrow, blood, and extramedullary sites. It predominantly occurs in children and accounts for 15%-20% of adult acute leukemia cases. With continuous improvements in chemotherapy regimens, the complete remission (CR) rate in children exceeds 95%, and the 5-year survival rate surpasses 80%. However, the prognosis for adults with relapsed or refractory acute lymphoblastic leukemia remains poor, with an overall 5-year survival rate of less than 10%.

CTA101 is a cell injection independently developed by Bioheng Biotech with independent intellectual property rights. It is the first immunotherapy product in China based on CRISPR gene-editing technology, and the first UCAR-T innovative drug in China. It is a dual-target UCAR-T cell injection for CD19 and/or CD22 positive adult patients with relapsed/refractory acute lymphoblastic leukemia.

It is reported that CTA101, developed using Bioheng Biotech's universal CAR-T technology platform, is an "off-the-shelf" CAR-T cell therapy. It utilizes CRISPR gene editing technology to knock out the TRAC gene to prevent graft-versus-host disease (GvHD), while also knocking out the CD52 gene and combining with anti-CD52 monoclonal antibodies to avoid patients' rejection of CAR-T cells (HvGR), thereby extending the in vivo persistence of UCAR-T cells. UCAR-T is prepared using T cells from healthy donors. Compared with autologous CAR-T, UCAR-T has the advantages of high anti-tumor activity, low cost, and high accessibility.

According to reports, the results of the CTA101 exploratory clinical study (IIT) were published in April 2021 as an original article in Clinical Cancer Research. Six patients who had previously undergone heavy treatment received CTA101 infusion; three of them had high white blood cell counts before enrollment, three had high-risk genetic damage, and one had relapsed within three months after previous anti-CD22 autologous CAR-T treatment. The six subjects received doses of 1E+06 CAR+ T cells/kg (3 patients) and 3E+06 CAR+ T cells/kg (3 patients). The safety profile was favorable, with no dose-limiting toxicity (DLTs), graft-versus-host disease (GvHD), neurotoxicity, or genome editing-related adverse events observed. All subjects experienced cytokine release syndrome (CRS), mainly mild to moderate, with only one subject developing grade 3 CRS. Five subjects achieved complete remission (CR) with minimal residual disease (MRD) negativity, resulting in a CR rate of 83.3%, and two subjects achieved long-term remission.