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<p>Myostatin and growth differentiation factor 11 (GDF11) are closely related members of the transforming growth factor-β superfamily (TGF-β) that negatively regulate skeletal muscle growth. Pharmacologic inhibition of myostatin has been shown to preserve lean mass during glucagon-like peptide-1 receptor agonist (GLP-1RA) -mediated weight loss in persons with obesity. We developed IBIO-600, a long-acting monoclonal antibody which was engineered for dual neutralization of myostatin and GDF11. We evaluated IBIO-600 activity across cellular and preclinical models. Our evaluation of IBIO-600 demonstrated it reverses ligand-mediated suppression of myoblast differentiation in primary human skeletal myoblasts. In mechanistic in vitro studies, we further observed that GDF11 more potently modulates human myocyte and adipocyte biology than myostatin. In diet-induced obese mice treated with GLP-1RA, IBIO-600 preserves lean mass relative to GLP-1RA monotherapy. In aged, obese cynomolgus monkeys, a single administration of IBIO-600 demonstrates an elimination half-life of approximately 52 days and produces sustained improvements in body composition. These findings support further development of IBIO-600 as a differentiated approach to enhance muscle preservation and improve the quality of weight loss achieved with GLP-1RA–based therapies.</p>

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Preclinical development of an extended half-life anti-myostatin monoclonal antibody

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月30日

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  • Tom Hsu,
  • Cody Moore,
  • Alexander Taguchi,
  • Tam Phuong,
  • Hongyu Zhang,
  • Matthew Dent,
  • Arjan Hada,
  • Courtney Zour,
  • Justin DiMartino,
  • Patrick Crutcher,
  • Martin Brenner,
  • Cory Schwartz

摘要

Myostatin and growth differentiation factor 11 (GDF11) are closely related members of the transforming growth factor-β superfamily (TGF-β) that negatively regulate skeletal muscle growth. Pharmacologic inhibition of myostatin has been shown to preserve lean mass during glucagon-like peptide-1 receptor agonist (GLP-1RA) -mediated weight loss in persons with obesity. We developed IBIO-600, a long-acting monoclonal antibody which was engineered for dual neutralization of myostatin and GDF11. We evaluated IBIO-600 activity across cellular and preclinical models. Our evaluation of IBIO-600 demonstrated it reverses ligand-mediated suppression of myoblast differentiation in primary human skeletal myoblasts. In mechanistic in vitro studies, we further observed that GDF11 more potently modulates human myocyte and adipocyte biology than myostatin. In diet-induced obese mice treated with GLP-1RA, IBIO-600 preserves lean mass relative to GLP-1RA monotherapy. In aged, obese cynomolgus monkeys, a single administration of IBIO-600 demonstrates an elimination half-life of approximately 52 days and produces sustained improvements in body composition. These findings support further development of IBIO-600 as a differentiated approach to enhance muscle preservation and improve the quality of weight loss achieved with GLP-1RA–based therapies.