2. Academic Validation
  3. Preclinical evaluation of ELP-004 in mice

Preclinical evaluation of ELP-004 in mice

  • Pharmacol Res Perspect. 2024 Aug;12(4):e1230. doi: 10.1002/prp2.1230.
Jamie L McCall 1 2,  Werner J Geldenhuys 3,  Lisa J Robinson 4,  Michelle R Witt 1 4,  Peter M Gannett 5,  Björn C G Söderberg 6,  Harry C Blair 7,  Jonathan Soboloff 8,  John B Barnett 1 2
Affiliations

Affiliations

  • 1 Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
  • 2 ExesaLibero Pharma, Inc., Morgantown, West Virginia, USA.
  • 3 Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, West Virginia, USA.
  • 4 Department of Pathology, West Virginia School of Medicine, Morgantown, West Virginia, USA.
  • 5 College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, Florida, USA.
  • 6 C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia, USA.
  • 7 Departments of Pathology and Cell Biology, The Pittsburgh VA Medical Center and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • 8 Fels Cancer Institute for Personalized Medicine and Department of Cancer and Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
PMID: 38940379 DOI: 10.1002/prp2.1230
Abstract

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP-004 was non-mutagenic, did not induce chromosome aberrations, non-cardiotoxic, and had minimal off-target effects. Using in vitro hepatic systems, we found that ELP-004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP-004 inhibits osteoclast differentiation without suppressing overall T-cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.

Keywords

CYP450; metabolism; mice; osteoclast; pharmacokinetics; preclinical.

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