Positive topline data from a phase 1 clinical study (NCT04814498) of cudetaxestat (BLD-0409) have been presented by Blade Therapeutics, a South San Francisco biopharmaceutical company.
The study evaluated the effect of cudetaxestat on the pharmacokinetics of a combination of probe substrates for CYP450 enzymes. No alteration of plasma levels of substrates for cytochromes 3A4, 2B6, 1A2, and 2C9 was seen in healthy subjects.
The few interactions that occurred included weak inhibition of 2D6 and induction of 2C19. A favorable safety and tolerability profile was shown for this drug, with no severe adverse events or drop-outs due to adverse events, according to a news release from the company.
Cudetaxestat is a noncompetitive reversible inhibitor of autotaxin. Excessive autotaxin levels and autotaxin enzymatic activity play a central role in liver, lung, kidney, and skin fibrotic diseases, and occur in response to epithelial cell/tissue damage.
Autotaxin is responsible for generating the potent signaling lipid lysophosphatidic acid (LPA). Binding of LPA to its receptor on myofibroblasts triggers a signaling cascade that leads to myofibroblast activation/differentiation. This results in the production of extracellular matrix proteins that comprise the scarring associated with the fibrotic lesion.
Direct antifibrotic activity of cudetaxestat has been demonstrated in preclinical studies, supporting its potential role in treating lung and liver fibrosis. Inhibition of the autotaxin pathway has been clinically validated in idiopathic pulmonary fibrosis (IPF).
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A completed phase 1 study demonstrated that cudetaxestat, an investigational medicine, “was well tolerated with a demonstrated pharmacokinetic/pharmacodynamic correlation and biomarker activity, and a supportive clinical safety profile,” according to the news release. Cudetaxestat has been granted orphan drug designations for the treatment of IPF and systemic sclerosis (SSc).
According to Wendye Robbins, MD, president and CEO of Blade, the company plans to initiate a phase 2 study of cudetaxestat in patients with IPF in the first half of 2022.
Blade Therapeutics announces positive topline data from phase 1 clinical study of cudetaxestat, a noncompetitive autotaxin inhibitor in clinical development for idiopathic pulmonary fibrosis. News release. Blade Therapeutics, Inc.; November 30, 2021.