Mabwell's 6MW5311 LILRB4×CD3 Bispecific Antibody Cleared by NMPA for AML, CMML and Multiple Myeloma Trials

On June 24, 2026, Mabwell (688062.SH, 02493.HK) announced that China's National Medical Products Administration had cleared the Investigational New Drug application for 6MW5311 — a LILRB4/CD3-targeting T Cell Engager (TCE) bispecific antibody for hematologic malignancies, including acute myeloid leukemia, chronic myelomonocytic leukemia, and multiple myeloma. The IND is a meaningful first for the field: no T Cell Engager has been approved anywhere in the world for AML or CMML, and the indications remain dominated by cytotoxic chemotherapy, hematopoietic stem cell transplantation, and mutation-specific targeted therapies such as FLT3 and IDH inhibitors.

Mabwell is one of a small group of Chinese biotechs — alongside Akeso, CARsgen, Antengene, and Oricell — pushing a new generation of bispecifics and cell therapies into hematologic indications that have been left behind by the global pipeline. The 06-24 announcement is also notable for the molecule's structural choices: a "2+1" asymmetric format that combines two LILRB4-binding arms with one CD3-binding arm, and a steric hindrance modification on the CD3 arm that is designed to keep T cells quiet in the absence of tumor cells.

What 6MW5311 does, and why the format matters

T Cell Engagers are bispecific antibodies that bridge a tumor-surface antigen to CD3 on T cells, forcing the T cell into an immunological synapse with the cancer cell and triggering cytotoxic killing. The class has produced approved drugs in B-cell malignancies and multiple myeloma — glofitamab, mosunetuzumab, elranatamab, talquetamab, teclistamab — but the same template has not worked in myeloid leukemias. The targets that work in B cells (CD19, CD20, BCMA) are not expressed at high density on AML blasts, and the targets that do appear on AML cells (CD33, CD123, CLL-1) overlap with normal hematopoietic stem and progenitor cells, which raises the prospect of prolonged cytopenias and bone-marrow failure if the engager is too broadly active.

LILRB4 — leukocyte immunoglobulin-like receptor subfamily B member 4 — has been a known AML target for several years. It is expressed at high levels on monocytic AML blasts and on leukemic stem cells, but has restricted expression on normal tissue. Several groups have tested LILRB4-directed therapies in early-phase trials, including monoclonal antibodies, antibody-drug conjugates, and CAR-T constructs. What Mabwell has done differently is build a TCE that targets LILRB4 with one arm and CD3 with the other, and then engineer a steric hindrance modification on the CD3 arm that holds the T cell in an inactive conformation until the LILRB4 arm finds its target. The intent is to solve a long-standing problem in TCE biology: systemic T-cell activation, which produces cytokine release syndrome (CRS) and off-target tissue damage even in patients whose tumors do not express the target.

Preclinical data behind the IND

Mabwell's June 24 release reports three sets of preclinical findings that justified the IND:

• In vitro cytotoxicity: 6MW5311 produced potent killing across multiple AML cell lines and against primary patient-derived samples, including LILRB4-high and LILRB4-low expressers.
• In vivo tumor inhibition: In mouse xenograft models of LILRB4-high and LILRB4-low AML, 6MW5311 produced significant tumor inhibition, with complete tumor clearance in the high-expression arm.
• Cynomolgus monkey safety: The molecule demonstrated a favorable safety profile in non-human primate safety evaluation, the standard IND-enabling toxicology package for biologics in China and the United States.

The 2+1 asymmetric structure — two LILRB4-binding arms plus one CD3-binding arm — is a design choice seen in several modern bispecifics (vabbritamab, runimotamab, and others in development). The argument for the format is that two tumor-binding arms increase avidity at the cancer cell surface, which means the engager does not need a particularly high-affinity CD3 arm to trigger T-cell activation. A weaker CD3 arm, in turn, gives the steric hindrance modification room to do its job. The result, in theory, is a TCE that wakes up T cells only when it is bound to a LILRB4-positive cell, and stays inert in the bloodstream and in LILRB4-negative tissue.

The three indications: AML, CMML, and multiple myeloma

Mabwell's IND covers all three indications in a single clinical-trial program — a structure the company has not yet detailed publicly (specific Phase 1 protocols, dose levels, and enrollment targets are expected in the IND filing records once the first sites come online). The three indications sit in different positions in the hematology treatment hierarchy, and each one has a different competitive context.

Acute myeloid leukemia (AML)

AML is the largest of the three indications by patient count and the one with the highest unmet need. According to the figures cited in the Mabwell release and consistent with the 2022 GLOBOCAN estimates, approximately 172,400 new AML cases were diagnosed globally in 2022 — a number projected to reach 221,400 by 2035 (1.94% CAGR). China accounts for roughly 17.9% of that total, with 30,800 new cases in 2022 and a projected 36,700 cases by 2035 (1.36% CAGR).

Standard first-line therapy remains "7+3" induction chemotherapy (seven days of cytarabine plus three days of an anthracycline), followed by consolidation with either additional chemotherapy or allogeneic hematopoietic stem cell transplantation for eligible patients. Targeted therapies have entered the field for specific mutations — midostaurin and gilteritinib for FLT3, ivosidenib and olutasidenib for IDH1, enasidenib for IDH2, and the recently approved menin inhibitors revumenib and ziftomenib for KMT2A-rearranged and NPM1-mutant disease — but none of these are curative on their own, and the median overall survival for adults with AML over 60 is still measured in months rather than years. There is no approved TCE for AML, and the TCE programs that have reached the clinic (most notably the CD33/CD3 and CD123/CD3 candidates from Amphivena, GT Biopharma, and Macrogenics) have not advanced to registrational trials.

Chronic myelomonocytic leukemia (CMML)

CMML is a rare clonal hematopoietic stem cell disorder that sits at the overlap of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN). It is defined by persistent peripheral-blood monocytosis (a sustained monocyte count above 1 × 10⁹/L) and carries an inherent risk of transformation to AML — approximately 15-20% of patients progress to overt AML within three to five years of diagnosis. Annual incidence is roughly 3-4 cases per 100,000 population, putting global new diagnoses in the low tens of thousands per year. Treatment options remain limited: hypomethylating agents (azacitidine, decitabine) are the standard of care, but most patients eventually progress, and the only curative option is allogeneic stem cell transplantation, which is restricted to a small minority of fit patients. There is no approved TCE for CMML, and the small patient population has historically made it a difficult indication for biotechs to pursue. Mabwell's decision to include CMML in the 6MW5311 IND — rather than splitting it into a separate filing — reflects the shared biology between CMML and AML (both are myeloid clonal disorders with monocytic differentiation), and the practical benefit of running a single Phase 1 protocol that can enroll both populations.

Multiple myeloma (MM)

Multiple myeloma is the most commercially contested of the three indications. The TCE field already has three approved drugs — elranatamab, teclistamab, and talquetamab — all targeting GPRC5D or BCMA. Mabwell is pursuing LILRB4 as a third antigenic target in MM, on the rationale that LILRB4 is expressed on a subset of myeloma cells (particularly those with a more plasmacytoid-monocytic phenotype) and that LILRB4-positive clones may be enriched in patients who have relapsed after BCMA-directed therapy. The LILRB4 angle in MM is a different hypothesis from the AML/CMML angle, and Mabwell has not yet disclosed whether the MM arm of the IND will run in parallel with the myeloid arm or be sequenced after the AML/CMML cohorts produce initial safety data.

Mabwell's broader pipeline context

6MW5311 is one of nine disclosed candidates in Mabwell's pipeline, and the third to reach the clinic in 2026. The company's strategic focus is on oncology and aging-related disease, with a fully integrated manufacturing footprint that includes cell-line development, process development, pilot manufacturing, and commercial-scale production at the company's Shanghai Jinshan site. Mabwell's 2024 revenue was approximately ¥1.02 billion (RMB), with the company's first commercial product ( Mailiejing / denosumab biosimilar) approved by NMPA in 2023.

The bispecific pipeline is the area where Mabwell is most clearly differentiated from the larger Chinese biotechs. Akeso's bispecifics (ivonescimab, cadonilimab, ligufalimab) are based on a different structural scaffold, and CARsgen is firmly a cell-therapy company. Antengene's ATG-201 (CD19 × CD3 TCE for autoimmune disease) and Oricell's Ori-C101 (GPC3 CAR-T for hepatocellular carcinoma) sit in adjacent but distinct technical spaces. Mabwell is one of the few Chinese biotechs with a published LILRB4 program, and the 2+1 asymmetric format with steric hindrance is a technical choice that maps onto a broader industry trend toward "masked" or "tumor-restricted" T Cell Engagers — a category that includes Harpoon Therapeutics' HPN328 (now under Merck), Janux Therapeutics' PSMA-TRACTr, and Cullinan Oncology's CLN-978.

Why LILRB4 in 2026, and who else is in the field

LILRB4 was first characterized as a myeloid-specific immune checkpoint receptor in the early 2010s, and the field has had a difficult time turning it into a drug. The first clinical programs — including monoclonal antibodies from Novartis (MBG453, though that one targets LILRB3, a related receptor) and early-stage CAR-T programs from academic groups — produced mixed results. The biology is real: LILRB4 is expressed on monocytic AML blasts and on a subset of leukemic stem cells, and blockade of LILRB4 has been shown to restore T-cell and NK-cell function in preclinical models. But the receptor's structural similarity to other LILRB family members (LILRB1, LILRB2, LILRB3, LILRB5) makes it hard to generate a fully specific antibody, and the field's move toward bispecifics and cell therapies has, in some ways, re-opened the door by allowing LILRB4 to be paired with a triggering receptor (CD3, in Mabwell's case) that does the heavy lifting on T-cell activation.

The published competitor set for LILRB4-directed therapy is still small. J&J and Johnson Innovation have published on LILRB4 ADCs in preclinical models. The University of Texas MD Anderson group has run a Phase 1 trial of an anti-LILRB4 CAR-T in AML, with early data presented at ASH 2023. A LILRB4 × CD3 BiTE from a smaller biotech (the program was licensed to Astellas in 2024 for further development) reached IND in 2025. Mabwell's 6MW5311 is the first Chinese LILRB4 bispecific to clear an IND, and the first LILRB4 TCE to use the steric hindrance design.

What to watch in the next 12-18 months

The first clinical readout from 6MW5311 will likely come in late 2026 or early 2027, depending on the speed of site activation and dose escalation. The standard Phase 1 TCE readout includes:

• Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
• Rate and severity of cytokine release syndrome (CRS) at each dose level — the key safety signal for any TCE
• Initial anti-leukemic activity (CR, CRh, CRi, MLFS rates in the AML cohorts)
• Pharmacokinetic profile and target engagement

The competitive context for the AML/CMML readout is thin: the next-closest programs (CD33/CD3 and CD123/CD3 TCEs) have been in the clinic for two to three years without producing registrational data, and the global TCE field is now focused on autoimmune indications (CD19/CD3 for lupus, CD20/CD3 for multiple sclerosis) and on solid tumors (claudin18.2, GPC3, HER2). If 6MW5311 produces a clean safety profile and a clinically meaningful response rate in the dose-escalation cohorts, it would be the first TCE to demonstrate convincing single-agent activity in AML, and the implications for the broader LILRB4 target would be substantial.

What this means for medical-tourism readers

Mabwell's IND clearance does not, on its own, make 6MW5311 a treatment option for international patients. The drug is in Phase 1. The trial will enroll in China, at one or more of the major Shanghai or Beijing hematology centers (the specific site list will be posted on chictr.org.cn once activated). International patient access — for patients who might consider traveling to China for a TCE that is not available in their home country — is likely two to three years away, and only if the data support a registrational filing.

That said, the Mabwell announcement is the third LILRB4- or CD47-AML-related regulatory event from a Chinese biotech in the past 60 days, alongside Akeso's ligufalimab CD47 AML data at EHA 2026 (06-18) and the CARsgen satri-cel solid-tumor CAR-T NMPA approval (06-23) for adjacent hematologic and solid-tumor indications. The cluster suggests that the second half of 2026 will produce a steady stream of AML, MM, and lymphoma trial readouts from Chinese biotechs, several of which will be first-in-class globally. Patients with AML, CMML, or relapsed/refractory multiple myeloma who are evaluating cross-border clinical-trial options should track Mabwell's clinicaltrials.gov and chictr.org.cn postings over the next 6-12 months.

For broader medical-tourism context, the Raffles Medical Group 37,000-patient 2025 figure and the Bloomberg/Business Times medical-tourism macro piece both frame the institutional backdrop for these drug-development milestones. New TCEs and bispecifics are a substantial part of why international patients are coming to China — the pipeline depth is one of the country's structural advantages.

Sources

• Mabwell press release (2026-06-24) — PR Newswire syndication via Manila Times, full text including mechanism, preclinical data, AML/CMML/MM epidemiology, and pipeline context
• Mabwell corporate website: mabwell.com/en — pipeline detail, manufacturing footprint, 2024 revenue disclosure
• GLOBOCAN 2022 estimates for AML incidence — figures cited in the Mabwell press release and consistent with IARC/WHO database