Veledimex (INXN-1001), a synthetic analog of the insect molting hormone ecdysone, is an orally active activator ligand for a proprietary gene therapy promoter system. Veledimex can be used to activate certain genes using the ecdysone receptor (EcR)-based inducible gene regulation system, the RheoSwitch Therapeutic System (RTS). Veledimex can cross blood-brain barrier (BBB) in both orthotopic GL-261 mice and cynomolgus monkeys.

Veledimex (INXN-1001) generally has moderate to low oral bioavailability after a single oral administration in mice and monkeys (-56% in mice and up to 17.4% in cynomolgus monkeys) with mostly low plasma clearance (1399 and 1170 mL/h per kilogram in mice and monkeys, respectively), high volume of distribution (20271 and 9180 mL/h per kilogram in mice and monkeys, respectively), and long terminal half-lives (-10 hours in mice and -30 hours in monkeys) after intravenous administration. Ad-RTS-mIL-12 + Veledimex have demonstrated a dose-related increase in tumor IL-12 mRNA and IL-12 protein expression. Discontinuation of Veledimex resulted in a return to baseline IL-12 mRNA and protein expression in numerous syngeneic mouse tumor models. Veledimex crosses the blood-brain-barrier in both naive and orthotopic GL-261 mice with increased brain tissue level of -6 fold observed in tumor bearing vs. normal mice. Ad-RTS-mIL-12 + veledimex demonstrate a dose-related increase in survival without significant adverse events.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Veledimex (INXN-1001) generally has moderate to low oral bioavailability after a single oral administration in mice and monkeys (-56% in mice and up to 17.4% in cynomolgus monkeys) with mostly low plasma clearance (1399 and 1170 mL/h per kilogram in mice and monkeys, respectively), high volume of distribution (20271 and 9180 mL/h per kilogram in mice and monkeys, respectively), and long terminal half-lives (-10 hours in mice and -30 hours in monkeys) after intravenous administration. Ad-RTS-mIL-12 + Veledimex have demonstrated a dose-related increase in tumor IL-12 mRNA and IL-12 protein expression. Discontinuation of Veledimex resulted in a return to baseline IL-12 mRNA and protein expression in numerous syngeneic mouse tumor models. Veledimex crosses the blood-brain-barrier in both naive and orthotopic GL-261 mice with increased brain tissue level of -6 fold observed in tumor bearing vs. normal mice. Ad-RTS-mIL-12 + veledimex demonstrate a dose-related increase in survival without significant adverse events.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Barrett JA, et al. Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma. Cancer Gene Ther. 2018;25(5-6):106-116.  [Content Brief]

  . Chiocca EA, et al. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019;11(505):eaaw5680.  [Content Brief]