Palleon Pharmaceuticals Announces First Patient Dosed in Phase 1 Clinical Trial of E-688/HLX316, a First-in-Class B7-H3-Targeted Sialidase for Advanced Solid Tumors

– E-688/HLX316 is the first tumor-targeted human sialidase to enter clinical trials, designed to restore both innate and adaptive anti-tumor immunity by removing immunosuppressive sialoglycans –

– Trial is being conducted in China by strategic partner Shanghai Henlius Biotech –

WALTHAM, Mass.--(BUSINESS WIRE)--Palleon Pharmaceuticals, the first company to translate glycan editing science into clinical-stage therapeutics for immune modulation, today announced the first patient has been dosed in a Phase 1 clinical trial of E-688/HLX316, a first-in-class B7-H3-targeted sialidase. The study is being conducted in China by strategic collaborator Shanghai Henlius Biotech in patients with tumors prone to B7-H3 overexpression and hypersialylation, with an initial focus on platinum-resistant ovarian cancer.

This milestone marks the clinical translation of a fundamentally new mechanism — glycan editing for immune modulation — grounded in the pioneering glycobiology research of Nobel laureate Carolyn Bertozzi. Tumor hypersialylation, the upregulation of sialic acid-containing glycans on the surface of cancer cells, can suppress anti-tumor immunity by activating sialic acid-dependent immune regulatory pathways. This axis of immune evasion is present across many solid tumors and correlates with poor clinical outcomes in dozens of published studies.

"E-688/HLX316 is designed to enzymatically remove sialic acid from tumor cell surfaces at the site of B7-H3 overexpression, unmasking tumors to the immune system in a durable, mechanistically distinct way. This first-in-human trial is a critical step toward validating glycan editing for immune modulation as a new therapeutic paradigm across hypersialylated solid tumors,” said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "The protocol includes a planned expansion into platinum-resistant ovarian cancer, where high B7-H3 expression and hypersialylation provide a compelling biological rationale for this approach."

About E-688/HLX316

E-688/HLX316 is generated from Palleon's EAGLE (Enzyme-Antibody Glycan-Editing) platform and combines a human sialidase enzyme with a targeting arm directed at B7-H3, a tumor antigen broadly overexpressed across solid tumors and associated with aggressive disease biology and poor prognosis. By enzymatically removing sialic acid from tumor cell surfaces, E-688/HLX316 restores immune recognition through glycan-binding receptor pathways, disrupts the immunosuppressive tumor microenvironment, and is designed to generate durable anti-tumor immune responses — activating both innate and adaptive immunity through a mechanism distinct from existing checkpoint therapies.

In preclinical studies, E-688/HLX316 demonstrated tumor surface desialylation lasting more than seven days in vivo and showed improved anti-tumor activity relative to anti-PD-1 monotherapy in humanized tumor models.

Phase 1 Trial Design

The Phase 1 first-in-human trial will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics, and preliminary anti-tumor activity of E-688/HLX316 monotherapy, comprising a Phase 1a dose escalation in B7-H3+ advanced solid tumors and Phase 1b dose expansion in platinum-resistant ovarian cancer. Palleon and Henlius intend to expand the program into additional solid tumor indications characterized by high B7-H3 expression and hypersialylation.

About Palleon Pharmaceuticals

Palleon Pharmaceuticals is pioneering glycan editing for immune modulation, a new approach to the treatment of autoimmune disease and cancer. Co-founded on the glycobiology research of Carolyn Bertozzi (2022 Nobel Laureate in Chemistry), Palleon's pipeline includes E-602 (Phase 2, membranous nephropathy) and E-688/HLX316 (Phase 1, advanced solid tumors). www.palleonpharma.com