13PUlviprubart pharmacokinetics, pharmacodynamics (PK/PD), and safety: phase 1 study results in patients with inclusion body myositis (IBM)

IBM is a rare, progressive disease characterized by invasion of muscle by highly differentiated cytotoxic CD8+ T cells. Ulviprubart, a monoclonal antibody, selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting KLRG1 expressed on most IBM-muscle–infiltrating T cells. Here, we describe PK/PD and safety of ulviprubart in patients with IBM. In this phase 1, open-label study (NCT04659031), initial patients received subcutaneous ulviprubart (0.1, 0.5, or 2.0 mg/kg) as a single dose prior to dosing every 8 weeks (Q8W) ∼6−12 months later, while later patients received 2.0 mg/kg Q8W; patients received ulviprubart for up to 18 months. PK/PD and safety with ulviprubart were assessed. Nineteen patients (mean age, 66 years; 79% male) were enrolled (0.1 mg/kg: n=3; 0.5 mg/kg: n=3; 2.0 mg/kg: n=13). Ulviprubart displayed a long absorption phase, slow clearance, and 21-day half-life. Peripheral CD8+ KLRG1+ and CD4+ KLRG1+ T cell depletion was achieved, with mean CD8+ KLRG1+ T cell maximum depletions of 69%, 97%, and 98% after single doses of 0.1, 0.5, and 2.0 mg/kg, respectively. Effector CD8+ T cell populations (T-cell effector memory [TEM] and TEMs expressing CD45RA [TEMRA]) were depleted to the extent of their KLRG1 expression. Regulatory T cells and B cells were preserved. No treatment-related serious adverse events (AEs) or discontinuations due to AEs were reported. In patients with IBM, ulviprubart led to sustained selective depletion of peripheral blood CD8+ KLRG1+ T cells and had a favourable safety profile.