LEUKOTRIENE A4 HYDROLASE AS A NOVEL DRUG TARGET IN PULMONARY INFLAMMATION
Brett A. Premack
Chief Technology Officer, Celtaxsys Inc., Atlanta, GA 30332, United States
There is renewed interest in inhibition of cell migration as a therapeutic modality in many forms of pulmonary inflammatory disease. Innate immune cells and fibroblast precursors are responsive to the potent eicosanoid chemoattractant Leukotriene B4 (LTB4) in the early stages of lung inflammation and fibrotic damage. The new clinical-stage drug CTX-4430, is a first-in-class oral LTA4 Hydrolase (LTA4H) inhibitor for the treatment of lung inflammation. The consequence of inhibiting LTA4H enzyme is to limit production of LTB4 in damaged or fibrotic tissue. This talk will discuss significant reasons why inhibition of chemoattractant ligand production is expected to be more beneficial than surface receptor inhibition in many clinical applications. In addition, in clinical studies, LTB4 itself provides a robust validated biomarker for lung inflammation that can be used as a surrogate efficacy measurement to augment clinical trial endpoints. Also of particular interest, CTX-4430 has a dual effect mechanism of action combining both anti-inflammatory and pro-resolution properties, yielding a product with high potential for market differentiation.