Seismic Therapeutic has dosed the first healthy participant cohort in the randomised Phase I trial of bifunctional antibody S-4321 to treat various autoimmune conditions.
The trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the antibody.
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Designed with the company’s IMPACT platform, the antibody ‘agonises’ the programmed cell death protein-1 (PD-1) and Fc-gamma receptor IIb (FcγRIIb).
FcγRIIb and PD‑1 are said to be key inhibitory receptors that are ‘expressed’ on various immune cell types.
Seismic noted that the therapy functions as a non-depleting antibody, featuring ‘low-affinity’ binding to PD‑1 to optimally agonise T-cells, alongside highly selective FcγRIIb binding, agonising, antigen-presenting cells.
The placebo-controlled, double-blind trial will be carried out in two segments: a single ascending dose stage and a multiple ascending dose stage.
It aims to build upon preclinical evidence highlighting the antibody’s dual-functional properties.
In the trial, the mechanistic activity of PD-1 agonism, as well as selective FcγRIIb binding, will be assessed in healthy participants.
Seismic Therapeutic research and development (R&D) head and chief medical officer John Sundy said: “We are excited to begin clinical investigation of S-4321, to explore its safety and pharmacodynamic biomarkers in human subjects.
“By engaging inhibitory receptors on both sides of the T-cell/antigen presenting cell synapse, S-4321’s unique dual-cell activity has the potential for clinical benefit in diseases driven by dysregulated cell-mediated immunity.”
The company plans to develop the therapy for treating autoimmune conditions, such as inflammatory bowel disease, lupus, and rheumatoid arthritis.
According to the company, S-4321 differentiates from first-generation PD-1 agonists by targeting PD-1 without depleting the cell, thereby ‘preserving’ regulatory T-cells (Tregs).
Last month, the company dosed the initial cohort of healthy participants in a randomised Phase I trial of S-1117, a treatment for autoimmune diseases.
