TY - JOUR AU - Höglinger, Günter AU - Vandenberghe, Wim AU - Woitalla, Dirk AU - Corvol, Jean-Christophe AU - Van Tricht, Hans AU - Ewen, Colin AU - Van Den Steen, Bart AU - Rebollo Mesa, Irene AU - Germani, Massimiliano AU - Garric, Elodie AU - Arnould, Tasmin AU - Jose, Joby AU - Strong, Nancy AU - De Bruyn, Steven AU - Buchanan, Tim J TI - Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial. JO - BMJ neurology open VL - 8 IS - 1 SN - 2632-6140 CY - London PB - BMJ Publishing Group M1 - DZNE-2026-00253 SP - e001396 PY - 2026 AB - Preclinical evidence suggests targeting the mid-region of tau as a viable therapeutic strategy in diseases such as progressive supranuclear palsy (PSP): a rare, fatal, neurodegenerative tauopathy with no currently approved treatments. Bepranemab is a recombinant, humanised, full-length immunoglobulin G4 monoclonal antibody binding to a mid-region tau epitope. We assessed safety, tolerability and pharmacokinetics of bepranemab in participants with PSP.PSP003 (NCT04185415), a multicentre, double-blind, placebo-controlled, phase 1b study, recruited participants in hospital settings across 13 centres. Participants (aged ≥40 years) met Movement Disorder Society-PSP criteria for possible/probable PSP, could walk ≥5 steps with minimal/no assistance and were stable on treatment for ≥2 weeks prior to baseline. Participants were randomised 3:1 to receive intravenous bepranemab (90 mg/kg) or placebo every 4 weeks for 52 weeks. Primary endpoint: incidence of treatment-emergent adverse events (TEAEs) from baseline to last visit.Twenty-five participants were enrolled (male: 44 KW - ALZHEIMER'S DISEASE (Other) KW - CLINICAL NEUROLOGY (Other) KW - RANDOMISED TRIALS (Other) KW - SUPRANUCLEAR PALSY (Other) LB - PUB:(DE-HGF)16 C6 - pmid:41789119 C2 - pmc:PMC12958890 DO - DOI:10.1136/bmjno-2025-001396 UR - https://pub.dzne.de/record/285476 ER -