E-688/HLX316 activates both innate and adaptive anti-tumor immunity through tumor-targeted enzymatic desialylation

Initiation of a first-in-human clinical trial of E-688/HLX316 is underway in China, following IND approval granted to strategic collaborator Henlius by the National Medical Products Administration (NMPA)

Palleon Pharmaceuticals today presented preclinical data and announced the initiation of a human clinical trial for E-688/HLX316, a first-in-class B7-H3 targeted sialidase, in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting “New Drugs on the Horizon” session. The presentation, titled “E-688/HLX316: A First-in-Class B7-H3 Targeted Sialidase for Boosting Innate and Adaptive Anti-Tumor Immunity” introduces the first ever tumor-targeted enzymatic desialylation agent to enter the clinic.

Tumor hypersialylation — the upregulation of sialic acid-containing glycans on the surface of cancer cells — activates several sialic acid-dependent immune regulatory pathways that suppress anti-tumor immunity. This axis of immune evasion is present across the majority of solid tumors and correlates with poor clinical outcomes in dozens of published studies. Conventional antibodies and small molecules cannot effectively disrupt this redundant glycan-mediated immunosuppression. Palleon’s engineered human sialidase overcomes this challenge by enzymatically removing sialic acid from the tumor surface, broadly neutralizing sialic acid-mediated immune suppression.

Palleon’s first-generation sialidase, E-602, established human proof-of-mechanism and a favorable tolerability profile in a previous clinical trial and is now in Phase 2 development in autoimmunity. This early clinical experience helped define the additional design requirements needed for the oncology clinical setting: durable tumor-localized desialylation and direct tumor cell killing. E-688/HLX316 was engineered to satisfy both conditions, and preclinical data confirm that it extends tumor surface desialylation to more than seven days in vivo and outperforms anti-PD-1 as a single agent in humanized tumor models, enhancing both innate and adaptive anti-tumor immunity.

“Tumor hypersialylation is now an addressable axis of immune evasion that is independent of PD-1/L1 biology,” said Jim Broderick, M.D., CEO and Founder of Palleon Pharmaceuticals. “Our first-generation clinical experience identified the attributes of an effective oncology sialidase and informed the design of E-688/HLX316. The preclinical package confirms the approach works as intended.”

E-688/HLX316 is being evaluated in a first-in-human monotherapy trial in platinum-resistant ovarian cancer in China led by Palleon’s strategic collaborator Henlius. Palleon’s clinical roadmap includes a systematic expansion into other large cancer populations characterized by high B7-H3 expression and hypersialylation, including lung and prostate cancer.

About Palleon Pharmaceuticals
Palleon Pharmaceuticals is a clinical-stage biotherapeutics company developing first-in-class engineered sialidase therapies for the treatment of cancer and autoimmune disease. Co-founded on the glycobiology research of Carolyn Bertozzi (2022 Nobel laureate in Chemistry), Palleon is the first company to translate this science into human therapeutics targeting cell surface sialoglycans. Palleon’s platform has generated two clinical programs: E-602 (Phase 2, membranous nephropathy) and E-688/HLX316 (first-in-human, platinum-resistant ovarian cancer). www.palleonpharma.com

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