WALTHAM, Mass. — Palleon Pharmaceuticals said the first patient has been dosed in a Phase 1 clinical trial of E-688/HLX316, a first-in-class B7-H3-targeted sialidase being developed for advanced solid tumors.
The Waltham-based biotechnology company said the study is being conducted in China by its strategic collaborator Shanghai Henlius Biotech. The trial is enrolling patients with tumors prone to B7-H3 overexpression and hypersialylation, with an initial focus on platinum-resistant ovarian cancer.
Palleon said E-688/HLX316 is the first tumor-targeted human sialidase to enter clinical trials. The drug candidate is designed to restore both innate and adaptive anti-tumor immunity by removing immunosuppressive sialoglycans from tumor cell surfaces.
The company said the milestone represents the clinical translation of glycan editing for immune modulation, a therapeutic approach rooted in glycobiology research. Tumor hypersialylation, or the increased presence of sialic acid-containing glycans on cancer cell surfaces, can suppress anti-tumor immunity by activating immune regulatory pathways, Palleon said.
“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.”
E-688/HLX316 was generated from Palleon’s EAGLE, or Enzyme-Antibody Glycan-Editing, platform. The drug candidate 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.
Palleon said the therapy is designed to restore immune recognition through glycan-binding receptor pathways, disrupt the immunosuppressive tumor microenvironment and generate durable anti-tumor immune responses 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 compared with anti-PD-1 monotherapy in humanized tumor models, according to the company.
The Phase 1 first-in-human trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of E-688/HLX316 as a monotherapy. The study includes a Phase 1a dose-escalation portion in B7-H3-positive advanced solid tumors and a Phase 1b dose-expansion portion in platinum-resistant ovarian cancer.
Palleon and Henlius said they plan to expand the program into additional solid tumor indications characterized by high B7-H3 expression and hypersialylation.
