Just as the recombinant DNA technology of the 1970s enabled the birth of biotechnology, research tools developed and refined in the early 21st century have opened a drug discovery frontier centered around glycans, the sugar molecules that coat cell surfaces.
Palleon is transforming these discoveries into therapeutics designed to manipulate glycans and their receptors to treat a wide variety of serious conditions. Leveraging our unrivaled scientific expertise and our proprietary platform technologies, Palleon is uniquely positioned to realize the potential of the glycobiology revolution for patients.
Sialoglycans’ Role in Immune Regulation
Sialoglycans are biomolecules that contain one or more carbohydrate chains and
terminate with sialic acids.
Sialoglycans are the central node in a highly redundant immunosuppressive network that identifies human cells as “self.” A broad array of immune cells — including dendritic cells, macrophages, natural killer cells, and T cells — have sialoglycan-sensing receptors that block immune activation when they encounter a sufficient density of sialoglycans.
Changes in sialylation are a major driver of immune dysfunction in many diseases. For example, upregulation of sialoglycans on both cancer cells and immune cells results in immune suppression. Downregulation of sialoglycans removes this suppression of the immune system, making “self” tissue vulnerable to autoimmunity.
Our approach
Cancer
Hypersialylation of tumors and T cells results in pan-immune suppression and immune escape. Decades of research have demonstrated that the upregulation of sialoglycans on tumor cells is correlated to poor clinical outcomes. Palleon’s research shows that sialoglycans are upregulated on exhausted T cells, which suppresses T-cell function.
Sialoglycan-mediated immune suppression in cancer cannot be targeted with conventional approaches due to the redundancy of the receptors and the vast number of sialoglycan ligands. Palleon’s EAGLE platform enables the development of therapeutics that strip sialic acids — the critical and common dependency of this axis — from both immune cells and cancer cells. Desialylation of both tumors and immune cells enables innate and adaptive immune cells to target the tumor, resulting in a pan-immune response with adaptive memory.
Palleon’s lead candidate, E-602 (Bi-Sialidase) removes sialic acids on both T cells and tumor cells, potentiating an anti-tumor immune response. Palleon is also developing bifunctional sialidase molecules that enable more efficient desialylation of tumor cells.
EAGLE Platform
Palleon has pioneered a novel strategy to reverse the immunosuppressive effects of sialoglycans by enzymatically removing the terminal sialic acids from tumor and immune cell surfaces. This approach solves for two of the main challenges in developing glyco-immunology therapeutics: the high degree of receptor redundancy and the vast number of distinct sialoglycan structures.
Our EAGLE platform is based on engineered human sialidase enzymes that degrade sialoglycans on tumors and across immune cell types. Engineering human sialidases for manufacturability and stability was a key element in the development of the EAGLE platform, as these enzymes have an inherently poor expression profile. Multiple EAGLE therapeutic candidates are under development in oncology, including Bi-Sialidase and several bifunctional sialidases. View our pipeline >
HYDRA Platform
Palleon has developed the powerful HYDRA platform to support our portfolio of cancer therapeutic candidates. HYDRA is an immunohistochemistry-based translational research technology which allows the identification of a patient’s specific tumor surface sialoglycan signature. Previously undetectable cell surface glycan patterns can now be interpreted by HYDRA.
We are leveraging HYDRA for indication prioritization, as well as for future clinical patient enrichment strategies and to guide optimal dosing of our therapeutic candidates.
Inflammatory diseases
Changes in sialylation can also contribute to immune dysfunction in inflammatory and autoimmune diseases. Research has shown a correlation between low levels of sialylation and autoimmunity. Targeting sialoglycans and/or their receptors could have therapeutic potential in suppressing the immune system in these diseases. Palleon is developing multiple strategies, including glycan-editing and Siglec-targeting programs, to address this therapeutic area.