Science & Approach

Science & Approach

Our Founding Science

Hear from Dr. Carolyn Bertozzi on glycoscience, glyco-immune checkpoints, and how Palleon is positioned to advance this unexplored area of immuno-oncology to benefit patients.

T cell checkpoint inhibitors have led to positive clinical outcomes in a range of cancers, yet most patients do not respond. New approaches are urgently needed. The Siglec-Sialoglycan axis is a previously underappreciated mechanism of immunosuppression that has recently emerged as a major tumor immune escape pathway. It modulates NK cell, macrophage, dendritic cell, and T cell functions concurrently. Inhibiting the Siglec-Sialoglycan axis offers the potential to activate both innate and adaptive anti-tumor immune responses and treat patients who do not respond to T cell checkpoint therapies.

Targeting the Siglec-Sialoglycan axis is challenging with conventional approaches to drug development. Palleon has developed a suite of technologies to address this significant but highly complex opportunity.

The Science of Glyco-Immunology

Learn more about Siglecs and their role in immunosuppression

The Siglecs are a family of receptors found on innate immune cells such as macrophages, dendritic cells, and NK Cells, as well as adaptive immune cells including effector memory T cells.  The Siglecs inhibit immune cell activation after sensing certain sialic acid-containing glycan patterns, or sialoglycans. Tumors take advantage of these sialoglycan-sensing checkpoints by evolving to express hypersialylated cell surface glycan patterns, which engage Siglecs on innate and adaptive immune cells, resulting in a broad, comprehensive suppression of the anti-tumor immune response.

Targeting the Siglec-Sialoglycan axis of immunosuppression offers two distinct advantages over other immuno-oncology efforts. First, since glycan-mediated immunosuppression affects the full range of innate and adaptive immune cells required for a robust anti-tumor immune response, drugs that target this axis have the potential to overcome resistance to T-cell checkpoint therapies. Second, tumor glycan patterns can be identified, providing insights on which patient populations are most likely to respond to treatments targeting the Siglec-Sialoglycan axis.

Our Platforms and Technology

Palleon has developed three distinct technology platforms to overcome the longstanding technical barriers that have delayed drug development in targeting the Siglec-Sialoglycan axis: EAGLECONVERGENCE and HYDRA.

EAGLE

Pan-Siglec ligand degradation by therapeutic sialidase enzymes.

Each Siglec receptor can bind to many structurally different sialoglycan ligands, and each ligand can bind to more than one Siglec receptor, which makes conventional approaches to targeting the Siglec-Sialoglycan axis for cancer unfeasible. Palleon’s EAGLE (Enzyme-Antibody Glyco-Ligand Editing) platform is a first-in-class modality that overcomes this challenge by enzymatically removing the critical common immunosuppressive moiety – terminal sialic acids – from glycans regardless of their individual structures or Siglec receptor preferences.  EAGLE product candidates have demonstrated striking single agent activity in a range of pre-clinical animal models and human in vitro systems. The company is developing several programs that it intends to advance to clinical testing.

CONVERGENCE

Targeting Siglecs, the immunosuppressive sialoglycan-sensing receptors on immune cells.

Palleon’s CONVERGENCE platform enables the targeting of Siglec receptors as an immune modulation strategy. The Siglecs are challenging targets for drug development because the Siglec family is characterized by significant differences between species. Humans have 10 distinct Siglecs that are not present in mice, and mice have 5 Siglecs that are not found in humans, which makes animal modeling complicated. The CONVERGENCE platform allows researchers to overcome this technical challenge and target Siglecs with antibody therapeutics. The CONVERGENCE platform creates first-in-class opportunities in oncology, as well as in inflammatory and fibrotic diseases, neurodegenerative disease, and chronic viral infections. Palleon has multiple programs targeting Siglec receptors.

HYDRA

Identifying patient populations who are likely to respond to Palleon’s therapies.

Palleon’s HYDRA platform is an immunohistochemistry-based translational research technology which allows the identification of a patient’s specific tumor surface glycan pattern, or tumor glyco-code. The HYDRA technology overcomes the challenge posed by the significant structural heterogeneity of tumor surface glycans by characterizing them by their immunosuppressive function rather than by their structure.

Our Founding Science

Hear from Dr. Carolyn Bertozzi on glycoscience, glyco-immune checkpoints, and how Palleon is positioned to advance this unexplored area of immuno-oncology to benefit patients.