Currently, 12 TCE drugs have been approved for marketing globally, 9 of which are used to treat hematological malignancies, targeting tumor antigens such as CD20, BCMA, CD19, and GPRC5D. Meanwhile, a number of emerging targets are beginning to appear in the pipeline.

Recently, Maiwei Bio announced that the NMPA has accepted its clinical trial application for its independently developed 6MW5311, which is intended to be developed for hematological malignancies (acute myeloid leukemia, chronic myelomonocytic leukemia and multiple myeloma).

It is worth noting that 6MW5311 is the world's first innovative bispecific antibody targeting LILRB4/CD3 TCE to be submitted for clinical trials. Its application for clinical trials in the United States is already in the pre-IND stage, and the company plans to formally submit the application to the FDA in the second quarter of 2026.

01
Differentiation targeting the "drug shortage" market

LILRB4 (a member of the leukocyte immunoglobulin-like receptor subfamily B) is a novel immune checkpoint molecule that has gradually come into the industry's view in recent years.

This is a type I membrane protein primarily expressed on the membranes of myeloid-derived immune cells, mainly involved in the negative regulation of the immune response. Studies have found that LILRB4 is significantly highly expressed in monocytic acute myeloid leukemia (AML) and is closely associated with poor prognosis. In chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM), this target is also significantly expressed, and its expression profile in normal tissues is narrow, providing an ideal therapeutic window for targeted therapy.

Currently, monoclonal antibodies, CAR-T therapy, and ADC therapies targeting LILRB4 have entered clinical trials globally, but no TCE bispecific antibodies targeting LILRB4/CD3 have yet reached the clinical stage . Maiwei Biotech's 6MW5311 has been the first to submit a clinical application and is expected to become the first breakthrough in this field.

In terms of indications, Maiwei Bio has adopted a consistent differentiation strategy.

Currently approved TCE drugs mainly cover hematological malignancies such as B-cell lymphoma, lymphocytic leukemia, and multiple myeloma. However, no TCE products have been approved for hematological malignancies such as AML and CMML.

AML is the most common acute leukemia in adults. In 2022, there were approximately 172,400 new cases of AML globally, and this number is projected to grow to 221,400 by 2035, representing a compound annual growth rate of 1.94%. Of these, approximately 30,800 new cases of AML were reported in China, accounting for about 17.9% of the global total. Although demethylating agents combined with regimens such as Veneclare have improved treatment outcomes in recent years, refractory/relapsed patients still face significant challenges.

CMML is a rare hematologic malignancy with an annual incidence of approximately (3-4) per 100,000. Currently, apart from allogeneic hematopoietic stem cell transplantation, there is a severe lack of effective treatments for CMML patients.

MM patients are plagued by relapses and still need to find new targets and new mechanisms for treatment.

LILRB4, as a novel immunotherapy target, could offer new hope for these patients if TCE bispecific antibodies prove effective. 6MW5311 precisely targets these underserved areas, aiming at unmet clinical needs.

6MW5311 employs a "2+1" asymmetric molecular structure, simultaneously targeting LILRB4 and CD3. It bridges tumor cells with T cells to form an immune synapse, activating T cells and efficiently killing tumor cells. Its key design lies in the introduction of a unique steric hindrance structure— significantly reducing the binding activity of CD3 antibodies to T cells in the absence of tumor cells, specifically activating T cells only in the presence of tumor cells.

This "conditional activation" approach has garnered significant attention within the industry. A major challenge in TCE drug development lies in safety, as the therapeutic window is closely related to whether T cell activation can be strictly confined within the tumor microenvironment.

In vitro studies showed that 6MW5311 exhibited potent killing activity against multiple tumor cell lines and patient-derived samples; it also demonstrated good safety profile in a cynomolgus monkey model .

In vivo pharmacodynamic studies have shown that 6MW5311 exhibits a clear tumor-suppressive effect in both LILRB4-high and low expression AML tumor models, and can achieve complete tumor clearance, especially in the high expression model.

Overall, Maiwei Bio has chosen a challenging but logically sound target, cleverly designed its molecular structure, and adopted a "conditional activation" strategy to enhance efficacy while reducing toxic side effects. However, the final efficacy still requires human data to confirm.

02
A market worth hundreds of billions

Behind 6MW5311 is Maiwei Bio's independently developed innovative TCE technology platform.

of this platform is a group of modified CD3-targeting antibodies with different binding characteristics and activation properties . These antibody molecules, with proprietary intellectual property rights, possess varying binding activities and activation capabilities: maintaining high affinity for human CD3 while exhibiting cross-reactivity with cynomolgus monkey CD3. This characteristic provides a crucial tool for accurately assessing the safety of TCE molecules in non-human primate models.

In recent years, T-cell adaptors (TCEs) have become a hot topic in next-generation immunotherapy. One end of their molecules targets the CD3 molecule on T cells, while the other end precisely binds to cancer cell-specific antigens, directly "bringing" the distance between T cells and tumor cells, triggering the targeted killing effect of T cells, thus combining targeting and high efficiency.

According to Frost & Sullivan's forecast, the global TCE drug market is expected to grow from approximately US$1 billion in 2022 to over US$121.1 billion in 2035, with a compound annual growth rate (CAGR) of over 40%. Frost & Sullivan's latest "2026 Global Antibody Drug Industry Development Blue Book" further points out that T-cell adaptor bispecific antibodies (TCEs) are projected to surge from 1.2% of the global antibody market in 2024 to 17.9% in 2035, becoming one of the fastest-growing segments.

Accompanying the high market growth is fierce competition. According to data from PharmNet, the number of TCE pipelines in development has increased significantly in recent years, with most of them in the preclinical and early clinical stages, indicating that a large number of pharmaceutical companies are entering this field.
At this point, platform-based innovation capabilities become the core of competition.

Most TCE products currently use a single CD3 antibody, with a fixed activation intensity. However, the threshold requirements for T cell activation vary greatly depending on the target and the tumor type.

Maiwei Biotech's CD3 antibody library approach essentially places the 'choice' at the molecular design stage, which may enable a more refined development strategy in the future.

This antibody library covers a complete spectrum of activity, from potent to mild activation. Researchers can select the most suitable CD3 antibody for assembly based on the target expression level and the characteristics of the tumor microenvironment, thereby achieving "on-demand regulation of T cell activation intensity".

In addition, Maiwei Bio has proactively planned for next-generation TCEs, introducing co-stimulatory signals and exploring molecular forms such as triple antibodies and multiple antibodies. Through multi-target synergistic activation, it enhances the sustained killing ability of T cells in solid tumors and immunosuppressive microenvironments.

Currently, in addition to 6MW5311, Maiwei Bio expects several other TCE projects targeting solid tumors to enter the preclinical stage.

03
The synergistic effect of TCE+ADC dual engines is expected.

In the era of tumor immunotherapy 2.0, TCE is becoming another promising technological direction after ADC.

With its world-first LILRB4/CD3 TCE bispecific antibody 6MW5311, Maiwei Bio has taken the lead in entering the niche market of hematological malignancies such as AML and CMML, which lack effective treatments. At the same time, relying on its differentiated TCE technology platform, it has formed a complete moat from target selection to molecular design.

Meanwhile, Maiwei Bio has established an advantage in the ADC field, possessing multiple potential ADC drugs in clinical stages, such as 9MW2821 (Nectin-4 ADC), 7MW3711 (B7-H3 ADC), and 7MW4911 (CDH17 ADC).

Industry experts generally believe that the combined use of ADCs and TCEs has the potential to become a new standard of care for cancer treatment. The former can precisely and efficiently kill tumor cells, and has the potential to replace traditional chemotherapy; the latter can effectively activate the body's own immune system to attack cancer cells; the two are expected to create a synergistic effect.

Maiwei Bio possesses both ADC and TCE technology platforms, leaving room for future exploration in combination therapies, and is worthy of continued attention.

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