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- W4312688051 abstract "<b>Introduction:</b> Cudetaxestat is a differentiated, non-competitive small molecule inhibitor of autotaxin being developed as daily oral treatment for IPF, SSc-ILD and other fibrotic diseases. <b>Methods:</b> A battery of preclinical in vitro and ex vivo biochemical assays along with pharmacokinetic (PK) and pharmacology studies (mouse bleomycin model) were used to assess the potency and activity of cudetaxestat. Four Phase 1 healthy volunteer (N=216) studies were completed to evaluate safety/tolerability along with PK and pharmacodynamic (PD) activity. These include a double-blind, placebo-controlled SAD/MAD study [NCT04146805]; a relative bioavailability study [NCT04814472]; a CYP substrate interaction study [NCT04814498]; and a DDI with standard of care (SOC) therapies for IPF [NCT04939467]. <b>Results:</b> Cudetaxestat maintained potency against its target in vitro regardless of substrate concentration. It demonstrated significant anti-fibrotic activity in multiple in vivo preclinical models. Plasma LPA (C18:2) levels were measured in the SAD/MAD study and increasing doses resulted in more sustained LPA reduction across the 24-hour dosing intervals. When dosed concomitantly with either nintedanib or pirfenidone, the total exposure for each of these SOC therapeutics was not significantly altered. There were no serious drug-related AE’s in any of the four Phase 1 human trials. <b>Conclusion:</b> Cudetaxestat is a first-in-class non-competitive (allosteric) autotaxin inhibitor with robust preclinical antifibrotic activity and good PK/PD correlations in Phase 1 clinical trials. This body of data provide a dose rationale for Phase 2 clinical development of cudetaxestat in IPF with or without SOC" @default.
- W4312688051 created "2023-01-05" @default.
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- W4312688051 date "2022-09-04" @default.
- W4312688051 modified "2023-09-27" @default.
- W4312688051 title "Cudetaxestat, a differentiated phase 2-ready investigational treatment for idiopathic pulmonary fibrosis" @default.
- W4312688051 doi "https://doi.org/10.1183/13993003.congress-2022.1144" @default.
- W4312688051 hasPublicationYear "2022" @default.
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