Mabwell's global first-in-class LILRB4/CD3 bispecific reaches IND stage in China for AML

China-based biotech Mabwell (688062.SH) announced on April 15, 2026 that China's National Medical Products Administration has accepted an investigational new drug application for 6MW5311, a LILRB4/CD3 T-cell engager bispecific antibody intended for acute myeloid leukemia, chronic myelomonocytic leukemia, and multiple myeloma. The company described the molecule as the first LILRB4/CD3 TCE bispecific antibody globally to reach this regulatory threshold. A US FDA submission is planned for the second quarter of 2026, currently in pre-IND preparation.

6MW5311 is built on a T-cell engager platform and carries a "2+1" asymmetric molecular structure, simultaneously binding LILRB4 on tumor cells and CD3 on T cells to form an immunological synapse. The design incorporates a steric hindrance mechanism intended to reduce CD3 binding activity in the absence of tumor cells, so that T-cell activation occurs selectively in the tumor microenvironment. According to the company, preclinical in vitro studies showed cytotoxic activity across multiple tumor cell lines and patient-derived samples, while in vivo pharmacodynamic studies demonstrated tumor inhibition in both LILRB4-high and LILRB4-low AML models, with complete tumor clearance observed in high-expression models. Cynomolgus monkey safety evaluations produced what the company characterized as a favorable profile. All supporting data disclosed to date are preclinical; no human safety or efficacy data have been reported.

LILRB4, also known as ILT3 or CD85k, is an inhibitory receptor expressed on myeloid leukemia cells and tumor-associated macrophages. Its expression on AML blasts has been associated with immune evasion, making it a target of interest in myeloid malignancies. The choice to pair LILRB4 with CD3 in a TCE format follows the broader logic that has driven the clinical success of bispecific T-cell engagers in B-cell malignancies, where CD19/CD3 and BCMA/CD3 constructs have reached approval. The challenge in myeloid disease has been that LILRB4 expression varies across patients and disease subtypes, a factor Mabwell's preclinical data attempted to address by testing efficacy across both high- and low-expression tumor models.

AML is a clonal malignancy of myeloid stem cells with high heterogeneity and mortality. Approximately 172,400 new cases were diagnosed globally in 2022, a figure the company projects will reach 221,400 by 2035. In China, roughly 30,800 new AML cases were recorded in 2022, representing approximately 17.9% of the global total. Standard treatment remains chemotherapy, hematopoietic stem cell transplantation, and mutation-targeted agents such as FLT3 and IDH inhibitors, but durable remissions are uncommon outside transplant-eligible patients. No TCE product has been approved for AML to date, leaving a gap that several companies are attempting to fill through different target combinations.

CMML is a rarer disorder, with an annual incidence of approximately 3 to 4 per 100,000, and carries an intrinsic risk of transformation to AML of approximately 15% to 20% within three to five years. It shares features with both myelodysplastic syndrome and myeloproliferative neoplasms, and effective treatment options remain limited. Multiple myeloma, the third indication in Mabwell's program, is a plasma cell malignancy accounting for roughly 1% to 2% of all cancers and approximately 10% of hematologic malignancies. While survival in myeloma has improved substantially over the past two decades through proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies, most patients relapse and the disease is not considered curable with current therapies.

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