Abstract Details

Title Imaging CD8+ T Cells in Patients With Inclusion Body Myositis (IBM) Treated With Ulviprubart

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S7 - Updates on Muscle Disorders (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Objective Evaluate the effect of ulviprubart on CD8+ T cells in patients with IBM.

Background IBM is a rare, progressive disease characterized by invasion of healthy muscle by highly differentiated cytotoxic CD8+ T cells and associated with loss of grip strength, difficulty walking, and/or dysphagia. Ulviprubart is a monoclonal antibody that selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting the cell-surface marker KLRG1, which is found on the majority of IBM-muscle T cells and may have activity in patients with IBM. Here, an investigational positron emission tomography (PET) tracer was used for noninvasive imaging of skeletal muscle CD8+ T cells in patients with IBM following ulviprubart administration.

Design/Methods

This was a substudy of an open-label phase 1 trial (NCT04659031). Patients with IBM received 1.0 mCi of the CD8+ T-cell−specific PET tracer [⁸⁹Zr]Zr-Df-crefmirlimab and underwent whole-body PET/CT imaging 24 hours later. Ulviprubart (2 mg/kg) was administered subcutaneously after the initial scan and at week 8. Pharmacodynamic activity in muscle (ie, tracer uptake) and blood was assessed at baseline and week 12.

Results Eight patients enrolled (75% male; mean age: 66.5 years); 2 patients with severe disease and minimal baseline tracer uptake were excluded. Five of 6 patients demonstrated reductions in tracer uptake (ie, CD8+ T-cell depletion) in ≥1 muscle group with ulviprubart. Mean percentage reductions were observed in the anterior calf (right, −23%; left, −19%), posterior calf (−14%; −15%), thigh (−14%; −15%), buttock (−13%; −16%), shoulder (−3%; −9%), and forearm (−6%; −4%). Five of 6 patients showed sustained depletion of CD8+ KLRG1+ cells in blood (maximum depletion, range: 90–100%). No serious adverse events or discontinuations due to adverse events were reported.

Conclusions In this study, 2 doses of ulviprubart treatment reduced CD8+ T cells in muscle, and ulviprubart was safe and well tolerated. These results suggest that ulviprubart has pharmacodynamic effects in skeletal muscle.

Authors/Disclosures
Michael Farwell, MD PRESENTER	Dr. Farwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abcuro. The institution of Dr. Farwell has received research support from ImaginAb.
Robert Henderson, MBBS (Royal Brisbane Hospital)	Dr. Henderson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Henderson has received publishing royalties from a publication relating to health care.
Merrilee Needham, MD	Dr. Needham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for teva. Dr. Needham has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for abcuro. Dr. Needham has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for sanofi aventis.
Dulce Soler-Ferran, PhD	Dr. Soler-Ferran has received personal compensation for serving as an employee of Abcuro. Dr. Soler-Ferran has stock in Pfizer.
H Jeffrey Wilkins, MD	Dr. Wilkins has received personal compensation for serving as an employee of Abcuro.

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