Background: 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.

Objectives: Here, we describe PK/PD and safety of ulviprubart in patients with IBM.

Methods: 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.

Results: 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 serious adverse events (AEs) or discontinuations due to AEs were reported.

Conclusion: In patients with IBM, ulviprubart led to sustained selective depletion of peripheral blood CD8+ KLRG1+ T cells and had a favorable safety profile.

REFERENCES: NIL.

Acknowledgements: This study is sponsored by Abcuro, Inc.

Disclosure of Interests: Merrilee Needham Abcuro, Inc. − Consultant, Robert D. Henderson Abcuro, Inc. − Consultant, Christina Liang Abcuro, Inc. − Consultant, Dulce Soler-Ferran Abcuro, Inc. – Employment, H. Jeffrey Wilkins Abcuro, Inc. – Employment, Steven A. Greenberg Abcuro, Inc. – Founder, Abcuro, Inc. – Consultant.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.