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@ARTICLE{Hglinger:285476,
      author       = {Höglinger, Günter and Vandenberghe, Wim and Woitalla,
                      Dirk and Corvol, Jean-Christophe and Van Tricht, Hans and
                      Ewen, Colin and Van Den Steen, Bart and Rebollo Mesa, Irene
                      and Germani, Massimiliano and Garric, Elodie and Arnould,
                      Tasmin and Jose, Joby and Strong, Nancy and De Bruyn, Steven
                      and Buchanan, Tim J},
      title        = {{S}afety, tolerability and biomarker results of bepranemab
                      in participants with progressive supranuclear palsy: a
                      randomised, multicentre, double-blind, placebo-controlled,
                      phase 1b trial.},
      journal      = {BMJ neurology open},
      volume       = {8},
      number       = {1},
      issn         = {2632-6140},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DZNE-2026-00253},
      pages        = {e001396},
      year         = {2026},
      abstract     = {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:
                      $44\%;$ bepranemab n=18, placebo n=7). Seventeen $(94.4\%)$
                      in the bepranemab group reported ≥1 TEAE (five
                      participants; ten investigational medicinal product
                      (IMP)-related TEAEs), versus placebo (n=7; $100\%).$ In the
                      bepranemab and placebo groups, respectively, three
                      participants $(16.7\%)$ and one participant $(14.3\%)$
                      discontinued due to TEAEs. Incidence of IMP-related TEAEs
                      and severe TEAEs was similar between groups; no deaths were
                      reported. Reduction $(80.41\%)$ in mean free tau
                      cerebrospinal fluid levels was observed in the bepranemab
                      group.Multiple doses of bepranemab 90 mg/kg were well
                      tolerated with an acceptable safety profile in participants
                      with PSP. High target occupancy was observed.},
      keywords     = {ALZHEIMER'S DISEASE (Other) / CLINICAL NEUROLOGY (Other) /
                      RANDOMISED TRIALS (Other) / SUPRANUCLEAR PALSY (Other)},
      cin          = {Clinical Research (Munich)},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41789119},
      pmc          = {pmc:PMC12958890},
      doi          = {10.1136/bmjno-2025-001396},
      url          = {https://pub.dzne.de/record/285476},
}