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Dr Jo Viney,Ph.D. is co-founder, President and CEO of Seismic Therapeutic, a clinical stage autoimmune diseasefocused company. Aseasoned biotech executive, she has co­ founded.J companies in MA-the firstof which,Pandion Tx, was acquired by Merck in 2021 for $1.85B. Prior to Pandionshe heldresearch leadership positions at Biogen, Amgen, and lmmunex. Sheis anexperienced director on both private and public company boards. Jois an advocateforworkplace inclusiveness and regutarlyvolunteers her timewith organizations focused on increasing diversity.

Inhibitory receptors play a critically important role in maintaining tolerance and restoring normal immune homeostasis following inflammatory challenge. Here we describe creation of a bifunctional antibody designed to optimally agonize the inhibitory receptors PD-1 and FcgRIIb. PD-1 is an inhibitory receptor that is upregulated on effector T cells by activation and functions to “apply the brakes” to return cells to a resting state. PD-1 is also expressed on Treg and functions to maintain stability. FcgRIIb is an inhibitory receptor expressed on B cells and antigen presenting cells where it functions to prevent B cell receptor signaling as well as inhibiting production of proinflammatory mediators from myeloid cells. The PD-1:FcgRIIb bifunctional agonist antibody, S-4321, attenuates inflammatory responses in vitro and in vivo in preclinical studies and is on track to enter Phase Ib clinical trials in patients with dysregulated cell-mediated immunity.