{
  "abstract": "Objective Bile salt-stimulated lipase (BSSL) is a digestive lipolytic enzyme and a potential novel drug target for treatment of rheumatoid arthritis (RA). Here, we report the results of the first-in-human study of SOL-116, a first-in-class humanised IgG4 monoclonal antibody targeting BSSL, conducted in healthy participants and patients with RA.Methods This was a randomised, double-blind, placebo-controlled study of ascending single doses (0.075–6.075 mg/kg) and multiple doses (4 doses of 3.0 mg/kg every 4 weeks) of subcutaneously administered SOL-116 in healthy participants, as well as a single dose (2.025 mg/kg) in patients with RA. Safety and tolerability were assessed as the primary objective and pharmacokinetics (PK) and immunogenicity as secondary objectives. Exploratory objectives included evaluating BSSL concentrations and inflammatory markers.Results SOL-116 was safe and well tolerated at the tested dose levels in 48 healthy participants and 8 patients with RA. There was a dose-proportional increase in area under the curve and maximum concentration across the single dose cohorts in healthy participants, with comparable PK characteristics between healthy participants and patients with RA and a low frequency of anti-drug antibodies. Notably, SOL-116 effectively reduced free BSSL levels in circulation, confirming target engagement although no clear changes in other exploratory inflammation markers were observed.Conclusions This study demonstrated that SOL-116 has a favourable safety and PK profile. Combined with effective reduction of free BSSL in the circulation, findings in this study support ongoing clinical development of SOL-116, with a focus on elucidating the efficacy and mechanism of action of BSSL in the treatment of chronic inflammation, primarily RA.Trial registration number NCT05576012.",
  "authors": [
    {
      "affiliations": [
        "Centre for Human Drug Research, Leiden, The Netherlands",
        "Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Anouk C Meijs"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden",
        "Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Johan Kolmert"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden",
        "Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden"
      ],
      "name": "Susanne Lindquist"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden"
      ],
      "name": "Peter Hovstadius"
    },
    {
      "affiliations": [
        "Centre for Human Drug Research, Leiden, The Netherlands"
      ],
      "name": "Hendrika W Grievink"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden"
      ],
      "name": "Anneli Hällgren"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden"
      ],
      "name": "Agneta Wennerholm"
    },
    {
      "affiliations": [
        "Centre for Human Drug Research, Leiden, The Netherlands"
      ],
      "name": "Naomi B Klarenbeek"
    },
    {
      "affiliations": [
        "Lipum AB, Umeå, Sweden",
        "Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden"
      ],
      "name": "Olle Hernell"
    }
  ],
  "title": "First-in-human (phase I) trial of SOL-116, a humanised IgG4 monoclonal antibody targeting bile salt-stimulated lipase, in healthy participants and rheumatoid arthritis patients",
  "uid": "64966022-07f8-5710-adf8-87140c97b88b"
}