On November 9, 2021 Palleon Pharmaceuticals, a company pioneering the field of glyco-immunology to treat cancer and inflammatory diseases, reported data on a novel mechanism of action of the company’s EAGLE sialoglycan degradation therapeutic platform (Press release, Palleon Pharmaceuticals, NOV 9, 2021, View Source [SID1234594943]). Preclinical studies, presented in a poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), show that EAGLE therapeutic candidates’ desialylation of T cells enhances T cell anti-tumor immunity, and that lead candidate E-602 (Bi-Sialidase) is efficacious and safe in animal models.
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"The exciting package of data we are presenting at SITC (Free SITC Whitepaper) demonstrates for the first time that Palleon’s EAGLE platform could offer a novel immunomodulatory approach to enhancing T-cell immunity for cancer treatment," said Li Peng, Ph.D., Chief Scientific Officer of Palleon and the poster’s principal author. "These findings will bolster our upcoming IND filing for E-602 and continue to deepen our understanding of the therapeutic potential of the EAGLE platform."
Upregulation of sialoglycans on tumors has been observed for decades and correlates with poor clinical outcomes across many tumor types. Recent findings made possible by advances in the tools used to study glycobiology have shown that these sialoglycans are immunosuppressive. In addition to tumor cells, most immune cells present substantially more abundant sialoglycans than non-hematological healthy cells, which may also contribute to immunosuppression. Palleon utilized various assays to study the effect of E-602 on naïve, exhausted, and effector T cells. These studies found that desialylation by E-602 enhanced naïve T cell priming/activation, restored exhausted-like T cell functions, and enhanced effector T cell function.
Further studies evaluated the single-agent antitumor activity of E-602 in multiple syngeneic mouse tumor models, and its safety profile in rat and non-human primate models. These studies found that E-602 demonstrated single-agent antitumor activity and a wide safety margin.