AB0019 TREATMENT OF AUTOIMMUNE AND INFLAMMATORY SKIN DISEASES USING SKIN-TARGETING BIFUNCTIONAL ANTIBODIES: A LOCALIZED IMMUNOMODULATION APPROACH

Abstract

Background:Current treatment approaches for autoimmune conditions comprise primarily of systemic immunosuppressants or cytokine blockade. The concentration of therapeutic molecules to the tissues that are the sites of autoimmune and inflammatory diseases is a promising approach with the potential to induce therapeutic benefit and avert risks associated with systemic immunotherapies. Pandion Therapeutics is developing a bifunctional antibody platform that can drive localized immune modulation by combining a “tether antibody” that targets a tissue of choice and “an effector end” that activates specific regulatory immune pathways to restore immune-homeostasis.Objectives:Here we report the engineering of a skin-tethered PD-1 agonist and a skin-tethered CD39 that inhibit T cell activation and function and deplete local ATP, respectively, modulating different arms of the immune system in a tissue specific manner.Methods:Biophysical assays were performed to characterize Skin-tethered immune effectors for drug-like properties and in vitro and in vivo assays for target binding, cellular activity and tissue specific-localization. Moreover, these bifunctionals were tested in pathway-relevant preclinical models such as Vitiligo and Contact Hypersensitivity.Results:Biophysical characterization of the bifunctional molecules showed desired drug like properties including specificity, stability, and manufacturability. The skin tethered bifunctionals showed effector activity in in vitro assays and selectively localized to the skin. Skin localization strikingly correlated with a tether-dependent efficacy compared to a non-tether control.Conclusion:We believe that this therapeutic approach has the potential to drive the resolution of cutaneous inflammation, providing an opportunity for developing new targeted therapies for autoimmune and inflammatory skin diseases.Disclosure of Interests:Susmita Borthakur Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion therapeutics Inc., Purvi Mande: None declared, Daniel Rios: None declared, Patrick Halvey: None declared, Angela Boisvert: None declared, MIchael Rowe: None declared, Anisha Agrawal: None declared, Minasri Borah: None declared, Mike Cianci: None declared, Joanne L. Viney Shareholder of: Pandion therapeutics Inc., Consultant of: Harpoon, Finch, Quench, HotSpot, Employee of: Pandion Therapeutics Inc., Katalin Kis-Toth: None declared, Kevin L. Otipoby Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion Therapeutics Inc., Ivan Mascanfroni: None declared, Nathan Higginson-Scott Shareholder of: Pandion Therapeutics Inc., Consultant of: Mediar Tx, Employee of: Pandion Therapeutics Inc.