WALTHAM, Mass. — Palleon Pharmaceuticals has unveiled new preclinical data and announced the launch of a first-in-human clinical trial for a novel cancer therapy designed to boost the body’s immune response against tumors.
The experimental treatment, known as E-688/HLX316, was highlighted during an oral presentation at the American Association for Cancer Research Annual Meeting as part of the “New Drugs on the Horizon” session. The therapy represents what the company describes as the first tumor-targeted enzymatic desialylation agent to enter clinical testing.
E-688/HLX316 is engineered to target B7-H3, a protein commonly expressed on tumor cells, and works by removing sialic acid molecules from the surface of cancer cells. This process aims to counteract tumor “hypersialylation,” a mechanism that allows cancers to evade the immune system by suppressing both innate and adaptive immune responses.
“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.”
According to the company, traditional treatments such as antibodies and small molecules have struggled to overcome this form of immune suppression. Palleon’s approach instead uses an engineered human sialidase enzyme to remove sialic acid from tumor surfaces, potentially restoring immune system activity against cancer cells.
The new therapy builds on earlier work with Palleon’s first-generation sialidase, E-602, which demonstrated proof of mechanism and a favorable safety profile in prior clinical studies and is currently in Phase 2 development for autoimmune diseases. Insights from that program guided the development of E-688/HLX316, which was designed to sustain tumor-targeted activity and directly kill cancer cells.
Preclinical results presented at the conference showed that the therapy maintained tumor surface desialylation for more than seven days in animal models and outperformed anti-PD-1 therapy as a single agent in humanized tumor models. The treatment also enhanced both innate and adaptive immune responses against tumors, the company said.
The newly launched clinical trial is evaluating E-688/HLX316 as a monotherapy in patients with platinum-resistant ovarian cancer in China. The study is being conducted in collaboration with Henlius, which received regulatory clearance from China’s National Medical Products Administration to begin the trial.
Palleon said it plans to expand development of the therapy into other cancers characterized by high levels of B7-H3 expression and hypersialylation, including lung and prostate cancers.
The announcement marks a step forward in efforts to develop next-generation immunotherapies that target alternative pathways of immune evasion beyond the widely studied PD-1/PD-L1 axis.
