Mabwell (688062.SH), an innovation-driven biopharmaceutical company with a fully integrated industry chain, announced that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for its innovative LILRB4/CD3 TCE bispecific antibody (R&D code: 6MW5311). The drug candidate is being developed for hematologic malignancies, specifically Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML), and Multiple Myeloma (MM).

6MW5311 is the world's first innovative LILRB4/CD3 TCE bispecific antibody for which a clinical trial application has been submitted. It possesses broad prospects for clinical development and significant market potential. The U.S. IND application is currently in the pre-IND phase, with plans to formally submit it to the FDA in the second quarter of 2026.

6MW5311 is developed based on the T Cell Engager (TCE) technology platform and features a “2+1” asymmetric molecular structure. It simultaneously targets LILRB4 and CD3, forming an immunological synapse by bridging tumor cells and T cells, thereby activating T cells to efficiently kill tumors.

The molecule incorporates a unique steric hindrance design. This structure significantly reduces the binding activity of the CD3 antibody to T cells in the absence of tumor cells. T cells are specifically activated only when tumor cells are present, which substantially enhances safety while improving anti-tumor efficacy.

In vitro studies have demonstrated that 6MW5311 exhibits potent cytotoxic activity across multiple tumor cell lines and patient-derived samples. In vivo pharmacodynamic studies have shown that 6MW5311 achieves significant tumor inhibition in both LILRB4-high and LILRB4-low expressing AML tumor models. Notably, it achieved complete tumor clearance in high-expression models. Furthermore, 6MW5311 demonstrated a favorable safety profile in cynomolgus monkey safety evaluation models.

As a key technological approach for directly mobilizing T cells to kill tumors, TCE has shown significant clinical value in various lymphoma indications, with multiple products successfully launched. However, current treatments for AML and CMML primarily remain primarily limited to chemotherapy, hematopoietic stem cell transplantation, and targeted therapies for specific mutations; no TCE products have been approved for these indications to date.

About Acute Myeloid Leukemia (AML)

AML is a group of clonal malignant disorders originating from myeloid stem cells, characterized by high heterogeneity and mortality. Globally, approximately 172.4 thousand new cases of AML were diagnosed in 2022, with the number projected to reach 221.4 thousand by 2035, representing a compound annual growth rate (CAGR) of 1.94%. In China, approximately 30.8 thousand new AML cases were diagnosed in 2022, accounting for approximately 17.9% of the global total. The number is expected to reach 36.7 thousand by 2035, representing approximately 16.6% of the global total, with a CAGR of 1.36%.

About Chronic Myelomonocytic Leukemia (CMML)

CMML is a clonal hematopoietic stem cell disorder that shares overlapping features with both myelodysplastic syndrome (MDS) and Myeloproliferative Neoplasm (MPN). It is characterized by significant monocytosis in peripheral blood and carries an inherent risk of transformation to AML (approximately 15-20% within 3-5 years). CMML is a rare disease with an annual incidence of approximately 3-4 per 100,000, and currently lacks effective treatment options.

About Multiple Myeloma (MM)

MM is a clonal plasma cell malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow. This leads to the overproduction of abnormal immunoglobulins and subsequent end-organ damage, manifested as hypercalcemia, renal impairment, anemia, and bone lesions (collectively known as CRAB features). Globally, MM accounts for approximately 1%-2% of all cancers and about 10% of hematologic malignancies. The median age at diagnosis is approximately 69 years, with higher incidence rates observed in males and individuals of African descent. Over the past two decades, patient survival rates have significantly improved thanks to the application of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. However, MM remains largely incurable, and most patients experience multiple relapses during the course of the disease.