S-4321

S-4321 is a novel bifunctional antibody developed for the treatment of autoimmune diseases. It acts as a dual-cell bidirectional agonist by targeting and agonizing two key inhibitory immune receptors: programmed cell death protein 1 (PD-1) on T cells and low affinity immunoglobulin gamma Fc region receptor II-b (FcγRIIb, also known as CD32B) on antigen-presenting cells (APCs). Unlike first-generation PD-1 agonists, S-4321 is designed to avoid depletion of PD-1-expressing cells such as regulatory T cells (Tregs), thereby preserving immune regulation. The Fab domain binds PD-1 with low affinity to mimic natural ligand activity without causing target depletion or excessive IL-2 production. The Fc domain selectively engages FcγRIIb, preventing proinflammatory cytokine induction and avoiding antibody-dependent cellular cytotoxicity (ADCC). Preclinical studies show that S-4321 promotes the induction of Tregs in vitro and reduces pathogenic T cell expansion and cytokine production in models of graft-versus-host disease. Subcutaneous administration in non-human primates demonstrates high bioavailability (~70%). Clinical development is underway for several autoimmune indications.