S-4321
/ Seismic Therap
- LARVOL DELTA
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September 15, 2025
S-4321, a novel dual-cell bifunctional PD-1:FcγRIIb selective agonist antibody for autoimmune disease, maintains expression of PD-1 on target cells and enhances inhibitory receptor expression on T cells in vivo
(ACR Convergence 2025)
- "In contrast to first-generation PD-1 agonists, treatment with S-4321 does not result in loss of PD-1 expression on T cells, induction of proinflammatory cytokines, or depletion of PD-1+ Tregs. S-4321 enhances TIGIT expression on PD-1+ T cells. S-4321 has the potential to restore immune homeostasis in cell-mediated autoimmune diseases and its high bioavailability will allow for convenient drug administration."
IO biomarker • Preclinical • Graft versus Host Disease • Immunology • Inflammatory Arthritis • PD-L1 • TIGIT • TNFA
May 16, 2025
S-4321, a Novel Dual-Cell Bidirectional PD-1:FcγRIIb Selective Agonist Antibody for the Treatment of Autoimmune Disease
(FOCIS 2025)
- "S-4321 also selectively engages FcγRIIb, avoiding the induction of proinflammatory cytokines and undesirable depletion of PD-1 expressing T cells, such as Tregs, by antibody-dependent cellular cytotoxicity (ADCC) through engagement of activating FcγR. In summary, S-4321 engages inhibitory receptors on both sides of the T cell-APC synapse, decreases T cell activation, preserves target expression and does not result in the elimination of PD1+ T cells important for the maintenance of a normal immune homeostasis."
IO biomarker • Giant Cell Arteritis • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • IL2 • PD-1 • PD-L1
April 10, 2025
Seismic Therapeutic Doses First Cohort in Phase 1 Clinical Trial of S-4321, a Novel Bifunctional Antibody that Agonizes PD-1 and FcγRIIb Inhibitory Receptors for the Treatment of Autoimmune Disease
(Businesswire)
- "Seismic Therapeutic, Inc....today announced the dosing of the first healthy subject cohort in a Phase 1 clinical trial of S-4321, a novel bifunctional antibody for the treatment of a range of autoimmune diseases....S-4321 has the potential to treat autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and lupus....The Phase 1 study is a randomized, placebo-controlled, double-blind clinical trial to assess the safety, tolerability, and pharmacokinetics of S-4321 in healthy subjects and will include measures of its pharmacodynamic activity."
Trial status • Immunology • Inflammatory Bowel Disease • Lupus • Rheumatoid Arthritis
September 25, 2024
S-4321, a Novel Dual-cell Bidirectional PD-1:FcγRIIb Selective Agonist Antibody for the Treatment of Autoimmune Disease
(ACR Convergence 2024)
- "S-4321 is a novel DcB PD-1:FcγRIIb agonist that engages inhibitory receptors on both sides of the T cell-APC synapse. It agonizes PD-1 without causing target or cell depletion and its high bioavailability allows for convenient administration. In vivo, S-4321 decreases T cell activation that contributes to the pathogenesis of autoimmune diseases and avoids the depletion of Tregs, important for restoring peripheral tolerance."
IO biomarker • Giant Cell Arteritis • Graft versus Host Disease • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • CD4 • IL2 • PD-1 • PD-L1 • TGFB1
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