Discovering the Potential Powers of Cells, Bringing New Hope to Life
Focusing on Cell Therapy, Guarding the Light of Life
1. γδ T-cell platform: γδT cells possess broad-spectrum tumor recognition and cytotoxicity capabilities. Critically, γδT cells are MHC-unrestricted in target antigen recognition, thereby eliminating the risk of graft-versus-host disease (GVHD). We have established large-scale γδ T-cell expansion platform, and developed off-the-shelf CAR-γδ T-cell therapeutic product.
2. Gene-edited allogeneic αβ T-cell platform: We use CRISPR-based gene editing technology to modify healthy donor-derived T cells, by targeting immune rejection-related genes and T-cell inhibitory genes. This dual editing strategy significantly reduces host immune rejection while enhancing tumor-killing potency.
To overcome the limitations of autologous CAR-T manufacture (prolonged timelines, technical complexity, and high costs), we are developing an in vivo modified CAR-T platform that generates functional CAR-T cells directly within patients.
1. mRNA-LNP platform: utilizing lipid nanoparticle-formulated mRNA to reprogram T cells in vivo, by which dramatically simplifies the procedure of CAR-T preparation, and also significantly reduces the cost. Moreover, mRNA-LNP-mediated in vivo modified offers enhanced controllability and safety profiles.
2. Lentiviral in vivo delivery platform: We developed a lentiviral vector system engineered for T-cell-specific tropism, enabling efficient delivery of CAR genetic cargo into endogenous T cells, thereby achieving direct in vivo generation of CAR-T cells.
BG1805 is a CAR-T cell therapeutic product targeting CLL1 (CLEC12A) for the treatment of relapsed or refractory acute myeloid leukemia (AML). CLL1 is highly expressed on AML stem cells (LSCs) and the majority of AML blasts, but demonstrates low or absent expression on normal hematopoietic stem cells (HSCs) and lymphocytes. This selective expression profile indicates that CLL1-targeted CAR-T therapy holds significant potential for treating a broad spectrum of AML patients while significantly reducing the risk of severe off-target toxicity. The antibody utilized in BG1805 has undergone affinity screening and humanization, endowing it with high specificity and low immunogenicity. BG1805 has received Orphan Drug Designation (ODD) from both the US FDA and the European Medicines Agency (EMA). Additionally, BG1805 has received two IND approvals from China's National Medical Products Administration (NMPA) for conducting clinical trials in adult and pediatric patients with relapsed or refractory AML. BG1805 is currently in an IND-based phase I clinical trial, and its efficacy and safety are being evaluated in multiple clinical center in China.
BG2201 is a CAR-T cell therapeutic product targeting CD7 for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL). CD7 is a transmembrane glycoprotein expressed on the surface of T cells, NK cells, and their precursors. During lymphocyte development, CD7 functions as a co-stimulatory receptor mediating interactions between T and B lymphocytes. Clinical research has demonstrated that CD7 is highly expressed on T-ALL cells, as well as on undifferentiated leukemic cells and leukemia stem cells (LSCs). To overcome the critical challenge of CAR-T cell fratricide (self-killing) inherent in targeting CD7, BG2201 utilizes endoplasmic reticulum (ER) retention technology to reduce CD7 expression levels on the manufactured BG2201 CAR-T cells. BG2201 has been evaluated in investigator-initiated clinical trials (IITs) and is currently in the IND-enabling stage.
CAR-T therapies targeting BCMA have markedly improved survival for patients with relapsed or refractory MM (R/R MM), a subset of patients still experience antigen escape or disease progression after BCMA-targeted therapy. GPRC5D (G Protein-Coupled Receptor Class C Group 5 Member D) is an orphan receptor whose ligand and signaling mechanisms remain unclear. GPRC5D is highly expressed on the surface of MM cells, including BCMA-negative subpopulations, while its expression in normal tissues is largely limited to the basal keratinocytes of hair follicles. Thus GPRC5D can be considered as a substitutive target for R/R MM. BG2202 is a CAR-T cell product targeting GPRC5D, which has been evaluated in investigator-initiated clinical trials (IITs). Our clinical study demonstrated that GPRC5D-targeted CAR-T therapy could be a promising treatment option for patients with R/R MM, especially for those who were refractory to BCMA-targeted CAR-T therapy.
BG2301 is a CAR-T product targeting both BCMA and GPRC5D, for the treatment of relapsed/refractory multiple myeloma (MM). Although the emerging target GPRC5D is effective for BCMA-negative patients, it is difficult to achieve comprehensive clearance of BCMA-positive tumor cells. BCMA/GPRC5D dual-targeted CAR-T cells can broadly kill BCMA-positive/GPRC5D-negative, BCMA-negative/GPRC5D-positive, and dual-positive tumor cells, minimizing the risk of antigen escape.
B7H3 is a type I transmembrane protein belonging to the B7 family of immune co-stimulatory and co-inhibitory molecules. It has immune-suppressive functions, which can reduce the release of type I interferons (IFN) by T cells and decrease the cytotoxicity of NK cells. B7H3 has limited expression in normal tissues but is abnormally expressed in most malignant tumors. The overexpression of B7H3 in tumor cells is usually closely associated with reduced tumor-infiltrating lymphocytes, accelerated cancer progression, and the prognosis of malignant tumors. Due to its wide expression in various solid tumors, B7H3 has become a potential target for cancer immunotherapy. BG2002 is a B7H3-targeted CAR-T product, for the treatment of various B7H3-positive solid tumors.
Claudin family proteins are key molecules in tight junctions, which form the paracellular barrier and regulate the flow of intercellular molecules. Their abnormal expression plays an important role in the pathogenesis of various diseases. Claudin18 (CLDN18) is a member of this family, among which Claudin18.2 maintains the barrier function of the gastric mucosa in normal gastric tissues. Studies have found that Claudin18.2 is highly expressed in primary gastric cancer cells, and its high expression is closely related to tumor invasiveness and metastasis. These characteristics indicate that Claudin18.2 is an ideal therapeutic target for tumor immunotherapy. BG2103 is a CAR-T product targeting Claudin18.2, for the treatment of malignant gastric cancer.
BG2204 is a CAR-T cell product targeting CDH17, for the treatment of malignant colorectal cancer. CDH17 (cadherin 17), is a transmembrane glycoprotein mainly expressed in gastrointestinal epithelial cells. It plays a crucial role in maintaining intestinal barrier function and intercellular communication. In recent years, studies have found that CDH17 is abnormally highly expressed on the surface of various tumor cells, including gastric cancer, pancreatic cancer, and colorectal cancer. The high expression of CDH17 on tumor tissues makes it an ideal target for the development of tumor-specific immunotherapy.
BG2205 is a dual-target CAR-T cell product developed for autoimmune diseases, simultaneously targeting CD19 and BCMA. CD19 is ubiquitously expressed on B-cell surfaces and represents a well-established therapeutic target for B-cell malignancies. BCMA is highly expressed on plasma cells and serves as a validated target in multiple myeloma therapy. As a bispecific CAR-T product, BG2205 effectively eliminates na?ve B cells, mature B cells, and plasma cells, which results in profound depletion of B-lymphocyte population in patients, thereby inducing immune reconstitution and restoration of normal immune function.
BG2401 is a CD19-targeted CAR therapeutic product, developed through the in vivo CAR platform for the treatment of autoimmune disorders. As a signature molecule of B lymphocytes, CD19 is ubiquitously expressed on B-cell surfaces, making it as a key therapeutic target for both B-cell malignancies and autoimmune diseases. Administration of BG2401 enables specific and robust expression of CD19-targeted CAR molecules on patient T cells, thereby effectively eliminating pathogenic B cells and ultimately inducing immune reconstitution.
