Ligand announces data from preclinical studies on small-molecule oral G-CSF receptor agonist

Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announced that data from preclinical studies on its granulocyte colony stimulating factor (G-CSF) receptor agonist program were featured in a poster presentation today at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans.

In preclinical studies, Ligand evaluated the ability of LGD-7455 to stimulate neutrophil (white blood cell) counts in cynomolgus monkeys and investigated the role that metal ions play in the activity of LGD-7455 on the G-CSF receptor (G-CSFR). Additionally, the effects and mechanisms of LGD-7455 on tumor cell growth were examined.

The key findings include:

  • LGD-7455 is a novel small-molecule, selective human G-CSFR agonist that activates the receptor in a manner distinct from native G-CSF, but similar to the mechanism of small-molecule oral thrombopoietin receptor (TPOR) agonists.
  • LGD-7455 significantly increases peripheral blood neutrophils, demonstrating the first reported proof-of-concept for a small molecule G-CSFR agonist in a primate model.
  • LGD-7455 inhibits tumor cell growth and increases apoptosis, mediated by intracellular metal chelation and an increase in reactive oxygen species formation.

"We are pleased to present this scientifically important work from one of Ligand's internal un-partnered programs," said Matthew W. Foehr, Chief Operating Officer of Ligand. "Ligand's R&D team continues to make scientific advancements like this first reported proof-of-concept for a small molecule G-CSF in a primate model. Further optimization of the LGD-7455 series may lead to a novel oral anticancer therapy that also serves as a supportive care agent to treat neutropenia in patients receiving bone-marrow suppressive treatments. The worldwide market for injectable G-CSF is currently over $6 billion, and we believe there is a substantial unmet medical need and market opportunity for a G-CSF receptor agonist that offers a novel route of administration and differentiated profile with the potential to have anti-tumor efficacy in addition to increasing neutrophils."

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