Maher T, et al. A Phase 1 Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of the Oral Integrin Antagonist IDL-2965 in Healthy Volunteers. Pulmonary Fibrosis Foundation Summit. 2019 Nov 7-9.
Background and Study Objectives
- IDL-2965 is an orally bioavailable small molecule antagonist of the integrins avb1, avb3, and avb6 currently under development for the treatment of serious fibrotic diseases including interstitial lung diseases and nonalcoholic steatohepatitis.
- Integrins are heterodimeric transmembrane proteins that mediate cell-cell and cell-matrix interactions. The integrins avb1 and avb6 are expressed on fibroblasts and epithelial cells, respectively, and modulate TGF-b activation; avb3 is expressed on fibroblasts and mediates fibroblast migration across extracellular matrix and promotes integrin-mediated myofibroblast survival.
- In animal models, low-dose IDL-2965 administered once daily exhibits potent antifibrotic effects across a range of vital organs, including the lung, liver, and kidney.
- The aim of the present study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of IDL-2965 in healthy adult volunteers and patients with idiopathic pulmonary fibrosis (IPF).