Cancer uses multiple pathways to evade the immune system, and Glyco-Immune Checkpoints are a significant and under-appreciated axis of immunosuppression in cancer. Glyco-Immune Checkpoint receptors function as “off switches” on immune cells, inhibiting immune activity after sensing specific glycan patterns. Tumors exploit Glyco-Immune Checkpoints through the alteration of glycans on the surface of their cells, impairing both innate and adaptive immune cells and resulting in a broad, comprehensive suppression of the anti-tumor immune response. Glyco-Immune Checkpoints had been overlooked relative to other anti-cancer strategies due to the complexity of glycoscience, and, until recently, the lack of scientific tools to demonstrate their relevance to immuno-oncology. Palleon has assembled the technologies needed to overcome these barriers and make drug development in this field possible.
Glyco-Immune Checkpoints can be targeted by either impairing the tumor cell surface glycan function, or blocking the receptors on immune cells that sense the tumor glycans. Palleon has developed two platforms, CONVERGENCE and EAGLE to pursue each approach.
Palleon’s CONVERGENCE platform enables the efficient development of drugs that target Glyco-Immune Checkpoint receptors on immune cells. One of the key challenges for drug development in this area is the significant differences that exist between human and mouse biology. The Siglecs are the largest and most important family of Glyco-Immune Checkpoint receptors. Human beings have ten Siglecs unique to humans, while mice have five Siglecs unique to mice. Consequently, traditional mouse models cannot be used effectively to target this pathway. Palleon’s CONVERGENCE platform addresses these human-mouse differences by integrating human biology into every step of the drug development process, including target validation, in vitro models, in vivo models and translational research. In this manner, the CONVERGENCE platform enables Palleon to overcome human-mouse differences and target the Siglecs as a new class of receptors for antibody therapeutics.
Palleon’s EAGLE platform enables the development of drugs that inhibit Glyco-Immune Checkpoints by disabling the immunosuppressive function of tumor cell surface glycans. The critical challenge in this area arises from the complexity, heterogeneity and rapidly evolving nature of the tumor glycans. Palleon’s EAGLE platform employs an enzyme/antibody bi-specific construct, which removes terminal sialic acids, the molecules that are responsible for suppressing the immune system, from cancer cell surface glycans in the tumor micro-environment. This enzymatic approach uniquely overcomes tumor glycan heterogeneity. EAGLE makes tumors vulnerable to both innate and adaptive immune responses, which is critical for targeting patients who are resistant to current therapies.
Palleon’s HYDRA platform is a proprietary patient stratification technology that enables the selection of patients based on the unique glycan signature, or glyco-code of each tumor.
Palleon’s three platforms, CONVERGENCE, EAGLE and HYDRA will facilitate the development of therapeutics that address a wide range of cancer patient populations.
Palleon has several cancer drug discovery programs underway. Beyond oncology, other important areas where Glyco-Immune Checkpoints may play a role include infectious diseases, neurodegeneration, inflammation and fibrosis.