Update date: September 2026

As of 2026, 19 bispecific antibodies (BsAbs) have received global regulatory approvals from the FDA, EMA, and NMPA for oncology, hematology, ophthalmology, and other disease areas. Unlike conventional monoclonal antibodies (mAbs), bispecific antibodies are genetically engineered immunoglobulins designed to simultaneously bind two distinct antigens—or two epitopes on a single antigen—thereby enabling precise redirection of immune effector functions ).

Key Highlights in this Guide:

• Global Approved List: 19 FDA/EMA/NMPA approved bispecific drugs with targets & indications.
• Clinical Mechanisms: cell engagement, non-cell bridging, and receptor–ligand blockade .
• Emerging Pipeline: Next-generation Bispecific ADCs (BsADCs) - Izalontamab brengitecan (BL-B01D1, Iza-bren) approved

Table 1. Approved bispecific antibodies by 2026

What Are Bispecific Antibodies

Unlike traditional monoclonal antibodies (mAbs) that typically target a single antigen, bispecific antibodies are a type of antibody that features two distinct binding domains, allowing them to simultaneously target two different antigens or two different epitopes on the same antigen. This dual specificity opens up a wide range of applications, including redirecting T cells to tumor cells, blocking two different signaling pathways simultaneously, dual targeting of different disease mediators, and delivering payloads to targeted sites.

Bispecific antibody therapies are rapidly advancing through clinical development, demonstrating breakthrough potential. As more clinical data becomes available, innovations in molecular design and target expansion are expected to drive their precise application across various indications, potentially transforming existing treatment paradigms.​

How Bispecific Antibodies Work?

The mechanisms of action of bispecific antibodies can be broadly classified into three categories: cell engagement, non-cell bridging, and receptor–ligand blockade [3]. 

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Figure 1. Classification of bsAb and multispecific antibodies by mechanism of action. [3]

Cell-engaging therapies

Cell-engaging therapies bring immune cells and tumor cells into close proximity to trigger targeted tumor killing.

• TCEs & TCR-Based Engagers: T-cell engagers (TCEs) physically bridge T cells and tumor cells to drive direct cytotoxicity. Multispecific formats combining CD3 with two tumor-associated antigens (TAAs) may improve tumor selectivity and reduce off-tumor toxicity. 
• NK & Macrophage Engagers: NKCEs, including BiKEs and TriKEs, activate NK cells through receptors such as CD16a and NKG2D, with some formats incorporating IL-15 to enhance NK-cell activity. Macrophage engagers can block CD47–SIRPα “don’t eat me” signaling and promote antibody-dependent cellular phagocytosis (ADCP). To improve tumor selectivity and reduce systemic toxicity, some designs use high TAA affinity with lower CD47 affinity.

Non-Cell-Bridging Therapies

Non-cell-bridging bispecific antibodies enhance antitumor immunity without directly connecting two cells.

• ​Checkpoint & TME Modulation: Dual- or multi-checkpoint blockade (e.g., PD-1 × CTLA-4 or PD-L1 × LAG-3) may enhance immune activation and help overcome resistance. TME-targeting approaches, such as PD-L1 × VEGF or TGF-β × PD-L1, aim to reduce local immunosuppression and enhance antitumor immune responses.
• Co-stimulation & Dual-Signal Synergy: Dual co-stimulatory agonists (e.g., OX40 × 4-1BB) can enhance T-cell activation but may pose a risk of systemic immune activation. More targeted approaches include TAA-restricted co-stimulation (e.g., TAA × CD28/4-1BB) and multispecific constructs such as TAA × CD3 × CD28, which are designed to provide more spatially controlled Signal 1 and Signal 2 activation and potentially support sustained T-cell activity.

Receptor–Ligand Blockade

Receptor–ligand blockade targets receptor signaling, receptor interactions, or receptor–ligand binding to inhibit pathways involved in tumor growth and survival.

• ​Pathway & Dimerization Inhibition: Dual targeting of redundant or compensatory pathways (e.g., EGFR × MET) may help overcome bypass signaling, while blocking receptor heterodimerization (e.g., HER2 × HER3) can suppress downstream oncogenic signaling.
• Biparatopic Binding & Ligand Trapping: Biparatopic antibodies targeting two epitopes on the same receptor (e.g., HER2 × HER2) can enhance receptor crosslinking, internalization, and degradation. Other bispecifics simultaneously bind a receptor or ligand pair to form an inactive complex, as exemplified by VEGF × Ang-2.

Advances in Bispecific ADC Development

Izalontamab brengitecan (BL-B01D1, Iza-bren) | EGFR/HER3 bispecific ADC

In 2026, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved izalontamab brengitecan (iza-bren; formerly BL-B01D1) for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) whose disease has progressed following prior platinum-based chemotherapy and PD-1/PD-L1-directed therapies.

Bispecific ADCs represent further opportunities in this field by leveraging bispecific antibodies that simultaneously bind two distinct targets, potentially improving tumor selectivity, internalization efficiency, and therapeutic efficacy while reducing systemic toxicity. Besides Izalontamab brengitecan, there are many bispecific ADCs under development. 

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References:
[1] https://www.businesswire.com/news/home/20250319587489/en/Bispecific-Antibody-Market-Opportunity-Clinical-Trials-Insight-2030-Bispecific-Antibody-Drug-Sales-Forecast-to-Quadruple-by-2030-Driven-by-Oncology-Innovations---ResearchAndMarkets.com 
[2] Surowka M, Klein C. A pivotal decade for bispecific antibodies? MAbs. 2024 Jan-Dec;16(1):2321635. doi: 10.1080/19420862.2024.2321635. Epub 2024 Mar 11. Erratum in: MAbs. 2024 Jan-Dec;16(1):2335597. doi: 10.1080/19420862.2024.2335597. PMID: 38465614; PMCID: PMC10936642. 
[3] Fontana E, Grochot R, Kotecki N et al. , Evolution of bispecific and multispecific antibodies in cancer therapy, The Lancet Regional Health – Europe, 2026; 64
[4]  SystImmune Announces First Approval of Iza-bren for the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma in China https://www.prnewswire.com/news-releases/systimmune-announces-first-approval-of-iza-bren-for-the-treatment-of-recurrent-or-metastatic-nasopharyngeal-carcinoma-in-china-302806766.html