Shanghai, China – March 9, 2026 – Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the Investigational New Drug (IND) application for HLX3901, a novel tetra-specific antibody independently developed based on the company's proprietary T-cell engager (TCE) platform that targets DLL3xDLL3xCD3xCD28 , has been approved by the National Medical Products Administration (NMPA), for the treatment of advanced and metastatic solid tumors. It is expected to offer a breakthrough immunotherapy option for patients with neuroendocrine carcinoma(NEC)such as small cell lung cancer (SCLC).
DLL3 (Delta-like ligand 3), an inhibitory Notch ligand1-2, is highly expressed in approximately 80% of SCLC and neuroendocrine carcinoma3-5, while exhibiting minimal expression in normal tissues6-7. This profile establishes DLL3 as an ideal target for the treatment of SCLC and has driven the development of T-cell engagers (TCEs) as a research hotspot in targeted therapies. Currently, bispecific TCEs targeting DLL3 and CD3 have been approved 8 and have demonstrated promising therapeutic potential9. However, insufficient T-cell infiltration and the immunosuppressive state within the tumor microenvironment (TME) remain critical bottlenecks limiting the efficacy of TCEs10-11. Activation via CD3 alone (signal 1) in the absence of co-stimulatory signals (signal 2) can lead to T-cell anergy12, preventing durable and deep anti-tumor responses. CD28 is a key co-stimulatory molecule expressed on T cells. By binding to its ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APCs), CD28 provides the essential second signal for full T-cell activation13-14.
HLX3901 is an innovative tetra-specific antibody with intellectual property, targeting dual epitopes of DLL3, along with CD3 and CD28. As a next-generation T-cell engager, HLX3901 is designed to enhance the cytolytic activity of T cells, overcome the immunosuppressive tumor microenvironment (TME), and optimize the therapeutic window of T-cell engagers in solid tumors. Its mechanism of action is primarily characterized by:
1）Dual activation of T cells through simultaneous engagement of CD3 (signal 1) and CD28 (co-stimulatory signal) on the T-cell surface, thereby enhancing the targeted killing of DLL3-positive tumor cells and improving anti-tumor efficacy.
2）Simultaneous engagement of CD3 and CD28 enhances T-cell activation, proliferation, and survival, promoting a prolonged T-cell response that drives potent anti-tumor activity even in tumors with low T-cell infiltration.
Preclinical studies indicate that HLX3901 exhibits enhanced cytotoxic effects at low effector-to-target ratios. In human pan-T cell reconstitution models, HLX3901 demonstrated stronger and more durable anti-tumor activity compared to reference molecules such as Tarlatamab. Furthermore, preliminary toxicity studies in cynomolgus monkeys showed that HLX3901 was well-tolerated with a broad therapeutic window.
HLX3901 represents a pioneering effort in Henlius' emerging immune cell engager pipeline. Developed through the synergistic integration of AI‑driven molecular design and the company’s T‑cell engager (TCE) platform, HLX3901 exemplifies a next‑generation TCE engineered to overcome key limitations of earlier constructs in solid tumors—achieving sustained and specific T‑cell activation, improved efficacy in the tumor microenvironment (TME) with low TIL density, and a reduced risk of cytokine release syndrome (CRS). The company has built a multidimensional innovation platform matrix, encompassing a PD(L)1-based checkpoint inhibitor platform, an immune cell engager platform (e.g.multi-specific TCEs), the proprietary Hanjugator™ ADC platform, and the AI-powered, all-in-one early-stage R&D platform HAI Club. This robust infrastructure ensures the quality and efficiency of individual projects while providing sustainable, systematic support for building a globally competitive mid-to-long-term innovative pipeline.
Rooted in addressing high-unmet medical needs, the company is efficiently expanding its early-stage pipeline with high-potential molecules, several of which have recently achieved significant milestones. HLX37 (an innovative anti-PD-L1/VEGF bispecific antibody) has received IND approval for advanced solid tumors and finished dosing its first patient. HLX701 (a novel SIRPα-Fc fusion protein) has initiated a Phase 2 clinical trial in China, leveraging its potentially improved safety profile. HLX97 (a novel oral small molecule KAT6A/B inhibitor) has recently received IND approval from the CDE. Furthermore, multiple preclinical candidates are accelerating towards the clinic, including HLX3902 (a STEAP1xCD3xCD28 trispecific antibody TCE), HLX49 (HER2xHER2 Novel Bi-paratopic ADC), HLX48 (an EGFRxcMET bispecific antibody ADC), and HLX105 (a fusion protein), continuously injecting new momentum into the company's innovation pipeline.
Looking ahead, Henlius will continue to adhere to its "patient-centric" R&D philosophy. Leveraging its integrated, platform‑based innovation engine, the company is committed to accelerating the development of a differentiated, globally competitive innovative pipeline, striving to provide more accessible and effective treatment options for patients worldwide.
References
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