Abstract Details

Title Pharmacokinetics, Pharmacodynamics (PK/PD), and Safety Profile of Ulviprubart: Results from a 48-week, Open-label, Phase 1 Study in Patients with Inclusion Body Myositis (IBM)

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (11:45 AM-12:45 PM)

Poster/Presentation
Number 11-012

Objective

To describe the PK/PD and safety profile of ulviprubart 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. There are no disease-modifying therapies currently available for patients with IBM. Ulviprubart is a monoclonal antibody that selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting the cell-surface marker KLRG1 expressed on the vast majority of IBM-muscle–infiltrating T cells. Ulviprubart may have clinical activity in patients with IBM.

Design/Methods In this phase 1, open-label study (NCT04659031), patients received subcutaneous ulviprubart (0.1, 0.5, or 2.0 mg/kg) as a single dose and approximately 6−12 months later were dosed once every 8 weeks (Q8W) or received initial multiple dosing of 2.0 mg/kg Q8W, for up to 48 weeks. PK/PD and safety assessments were performed at multiple timepoints.

Results Nineteen patients (mean age, 66 years; 79% male; mean disease duration, 10 years) 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 a half-life of 14−21 days. Depletion of peripheral CD8+ KLRG1+ and CD4+ KLRG1+ T cells was evident on day 1 postdose, with mean CD8+ KLRG1+ T cell maximum depletions of 69%, 97%, and 98% achieved by weeks 2–3 after a single dose of 0.1, 0.5, and 2.0 mg/kg, respectively. Depletion was sustained through the study. Protective regulatory T cells and B cells were preserved. No serious adverse events (AEs) or discontinuations due to AEs were reported.

Conclusions Ulviprubart led to deep and selective depletion of peripheral blood KLRG1+ T cells in patients with IBM. Together with the favorable safety profile, these data support the continued development of ulviprubart.

Authors/Disclosures
H Jeffrey Wilkins, MD PRESENTER	Dr. Wilkins has received personal compensation for serving as an employee of Abcuro.
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.
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.
Christina L. Liang, MBBS, FRACP (Royal North Shore Hospital)	Dr. Liang has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Australia Pty Ltd. Dr. Liang has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Products Pty Ltd. Dr. Liang has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen Australia Pty Ltd. Dr. Liang has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Roche Products Pty Ltd. The institution of Dr. Liang has received research support from NHMRC Medical Research Future Fund. The institution of Dr. Liang has received research support from Abcuro for reimbursement of studies' costs.
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.
Steven A. Greenberg, MD (Brigham and Women's Hospital Neurology)	Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abcuro, Inc.. Dr. Greenberg has stock in Abcuro. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care.

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