{
  "abstract": "Background Bepranemab is a recombinant, humanised, full-length IgG4 monoclonal antibody targeting a mid-region tau epitope. Two phase 1 studies assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of bepranemab.Methods UP0047 ( NCT03464227) and UP0065 (NCT03605082) were phase 1, double-blind, placebo-controlled, single-dose, dose-escalation studies of intravenous bepranemab in healthy participants (Caucasian and Japanese descent, respectively). Primary endpoint: safety and tolerability of single ascending doses of bepranemab. PK were assessed in serum and cerebrospinal fluid (CSF); PD (levels of free tau) in CSF. A physiologically based PK/PD (PBPK/PD) model was developed to predict dose response.Results UP0047: Caucasian participants (N=52) were randomised to bepranemab 0.3 mg/kg, n=2; 1 mg/kg, n=6; 3 mg/kg, n=6; 10 mg/kg, n=6; 30 mg/kg, n=6; 60 mg/kg, n=6; 120 mg/kg, n=6; placebo, n=14). UP0065: participants of Japanese descent (N=24) were randomised to bepranemab 30 mg/kg, n=6; 60 mg/kg, n=6; 120 mg/kg, n=6; placebo, n=6). No serious treatment-emergent adverse events (TEAEs) or discontinuations due to TEAEs were observed. One participant (bepranemab 60 mg/kg) experienced treatment-related TEAEs of headache (moderate intensity), nausea and vomiting (mild intensity). There was no effect of ethnicity on PK parameters. A dose-response effect of bepranemab on free tau levels was observed. Data applied to a PBPK/PD model supported a dose of 90 mg/kg of bepranemab every 4 weeks to achieve a reduction in mean change from baseline in free tau levels of up to 90%.Conclusions Safety, PK and PD data support continued investigation of bepranemab for the treatment of tauopathies.",
  "authors": [
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Tim J Buchanan"
    },
    {
      "affiliations": [
        "UCB, Slough, UK"
      ],
      "name": "Colin Ewen"
    },
    {
      "affiliations": [
        "UCB, Madrid, Spain"
      ],
      "name": "Irene Rebollo Mesa"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Massimiliano Germani"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Shikiko Watanabe"
    },
    {
      "affiliations": [
        "UCB, Slough, UK"
      ],
      "name": "Joby Jose"
    },
    {
      "affiliations": [
        "UCB, Oakville, Ontario, Canada"
      ],
      "name": "Omobola Famodimu"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Anny-Odile Colson"
    },
    {
      "affiliations": [
        "UCB, Braine-l’Alleud, Belgium"
      ],
      "name": "Steven De Bruyn"
    }
  ],
  "title": "Two phase 1 randomised studies investigating the safety and pharmacokinetics of bepranemab in healthy participants of different ethnicities",
  "uid": "843b4c8b-8be8-5e0d-9411-dc7c59039130"
}