May 21, 2026 – Henlius (2696.HK) announced that its second innovative T cell engager (TCE), HLX3902—a tri-specific antibody targeting STEAP1×CD3×CD28 developed on the company’s proprietary immune cell engager platform—has received approval from the Human Research Ethics Committee (HREC) in Australia and has been filed with the Therapeutic Goods Administration (TGA). HLX3902 is intended for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and other advanced solid tumours. The company is set to initiate the First-in-Human (FIH) Phase 1clinical trial locally, accelerating the global development of its innovative pipeline. 

As a potential first-in-class STEAP1-targeting tri-specific TCE, HLX3902 represents a significant milestone in translating Henlius’multi-specific immune cell engager platform from technological development to clinical validation.

Dual T Cell Signal Activation to Overcome Cold Tumour Resistance

Prostate cancer (PCa) is one of the most common malignancies in men and the fifth leading cause of male cancer death.^1-2 Early-stage disease can be effectively managed with surgery or radiotherapy; however, once it progresses to metastatic castration-resistant prostate cancer (mCRPC), treatment options are limited and prognosis is poor, highlighting a critical unmet need for novel targeted therapies.³ STEAP1 (six transmembrane epithelial antigen of the prostate 1) is highly expressed in over 85% of prostate tumours while minimally expressed in normal tissues, making it a highly specific therapeutic target.³ Due to its characteristic “immune cold” tumour microenvironment—low T cell infiltration, insufficient antigen presentation, and abundant immunosuppressive factors—traditional immunotherapies such as PD-1 inhibitors show limited efficacy.^4-6 STEAP1-targeted TCEs are designed to redirect T cells toward tumour cells by simultaneously engaging CD3 on T cells and STEAP1 on tumour cells. This approach has demonstrated potent antitumour activity in multiple preclinical models and shows selectivity for tumours with high STEAP1 expression.^7-8 Existing TCEs primarily rely on CD3-mediated primary T-cell activation; however, in solid tumour microenvironments, limited immune cell infiltration and absence of co-stimulatory signals often lead to T-cell exhaustion, restricting sustained antitumour responses. By incorporating a CD28 co-stimulatory signal, the TCE can mimic the physiological dual-signal mechanism of T-cell activation, enhancing the durability and functional persistence of T-cell responses within the tumour microenvironment.

HLX3902 is an innovative trispecific antibody with proprietary intellectual property, capable of simultaneously engaging CD3 and CD28 to enhance T-cell-mediated killing of STEAP1-expressing tumour cells. By optimizing both the primary (CD3) and co-stimulatory (CD28) signals, HLX3902 promotes T-cell activation, proliferation, and survival, prolonging antitumour immune responses even in tumours with low T-cell infiltration.

Preclinical studies demonstrated that HLX3902 induces target-dependent T-cell activation and cytotoxicity, outperforming traditional CD3-based bispecific TCEs at low effector-to-target ratios. Repeated antigen stimulation models further confirmed that CD28 co-stimulation enhances T-cell activation, proliferation, and memory T-cell expansion, sustaining long-term cytotoxic effects. In vivo, HLX3902 showed significant antitumour activity in both C4-2/hPBMC and abiraterone-resistant PDX/hPBMC models, accompanied by increased T-cell infiltration and functional activity. In cynomolgus monkeys, HLX3902 demonstrated favorable tolerability and a controllable safety profile.

Platform-Driven Systematic Innovation

Mechanistically, Henlius’ multispecific TCE platform is systematically optimized. CD3 activation is target-dependent, minimizing off-target T-cell activation in the absence of tumour antigen. CD28 co-stimulation is conditionally triggered only after CD3 engagement, providing synergistic T-cell activation. The CD3 and CD28 binding domains are positioned on the same side of the TCE molecule to promote cis-binding to the same T cell, reducing non-specific activation and fratricide, thus improving safety and widening the therapeutic window. The company’s first innovative molecule developed on this platform, HLX3901 (DLL3×DLL3×CD3×CD28 tetra-specific TCE), demonstrated best-in-class preclinical efficacy and has advanced into first-in-human dosing, representing a critical step in translating the platform from preclinical development to clinical evaluation.

Henlius has established a diversified innovation platform matrix, encompassing PD(L)1-centered immune checkpoint inhibitors, immune cell engagers (including multispecific TCEs), Hanjugator^™ ADCs, and the AI-driven one-stop early R&D platform HAI Club. This platform-driven approach ensures high-quality and efficient project development while supporting the creation of a globally competitive mid- to long-term innovation pipeline. Henlius remains committed to a patient-centric R&D philosophy and a systematic, platform-based innovation strategy to advance differentiated, globally competitive therapies, providing broader access to effective treatments for patients worldwide.