Shanghai Henlius Biotech (HKEX: 2696) dosed the first patient in the HLX316 clinical trial, a Phase I first-in-human study evaluating the B7-H3-targeting sialidase Fc fusion protein in patients with advanced or metastatic solid tumours in mainland China. The milestone follows approval of the investigational new drug application by China's National Medical Products Administration in March 2026.
First-in-class mechanism
HLX316 is a heterodimeric biologic constructed from two distinct components joined via a human IgG1 Fc region. The first is an engineered human sialidase Neu2, modified for improved stability and manufacturability relative to the wild-type enzyme. The second is a heavy-chain-only antibody variable domain, or VHH, that binds selectively to B7-H3, a cell-surface protein encoded by the CD276 gene and broadly overexpressed across a wide range of solid tumour types.
The molecule was created by fusing Henlius's proprietary VHH targeting B7-H3 with a sialidase bifunctional fusion protein licensed from Palleon Pharmaceuticals in May 2024, where the compound is also designated E-688. The design is intended to concentrate sialidase enzymatic activity at the surface of B7-H3-expressing tumour cells, driving localised cleavage of sialylated glycans that coat those cells.
That glycan-stripping mechanism sits at the centre of the scientific rationale. Tumours accumulate dense layers of sialic acid-rich carbohydrates on their surface, a process known as hypersialylation, which suppresses both innate immune effectors such as natural killer cells and macrophages, and adaptive T-cell responses. By directing sialidase activity to B7-H3-positive cells, HLX316 is designed to remove this glycocalyx shield locally, restoring immune recognition without triggering systemic immune activation. Preclinical studies cited by Henlius showed potent antigen-directed desialylation on tumour cells in vitro, tumour growth inhibition in humanised mouse models, and no indication of off-target systemic immune effects.
Trial design and objectives
The HLX316 Phase I study registered as NCT07541534 is an open-label, dose-escalation and dose-expansion trial conducted in mainland China. It is structured in two stages. Phase Ia covers dose escalation across five cohorts, ranging from 1.0 mg/kg to 30.0 mg/kg administered once weekly. The lowest cohort uses an accelerated titration design, while the four higher cohorts follow a standard 3+3 escalation scheme. Dose backfill at selected levels is permitted following safety review.
Phase Ib will expand enrolment at dose levels selected on the basis of safety and preliminary efficacy data from Phase Ia, with dosing regimens matched to the corresponding Phase Ia cohorts. The primary objectives are to characterise the safety and tolerability profile of HLX316, establish the maximum tolerated dose and the recommended Phase II dose, and generate an initial read on anti-tumour activity. Primary endpoints include the incidence of dose-limiting toxicities, the maximum tolerated dose and recommended Phase II dose determinations, and objective response rate assessed by the investigator.