Veledimex racemate

Veledimex, combined with Ad-RTS-hIL-12, is in phase I/II clinical trials for the treatment of melanoma and breast cancer. Intratumoral administration of Ad-RTS-mIL-12 along with oral administration of veledimex elicits dose-dependent antitumor effects in murine melanoma, breast cancer, and glioma models, which correlates with increased plasma exposure of veledimex. The increase in tumor veledimex levels in combination with Ad-RTS-mIL-12 results in a dose-related increase in the IL-12 mRNA (switch on) leading to dose-related increases in IL-12p70 in the tumor with minimal increase in serum IL-12. The increase in tumor IL-12 correlates with an increase in tumor CD8+ cytotoxic T cells and a concomitant decrease in regulatory T cells in the tumor microenvironment, which leads to Ad-RTS-mIL-12 + veledimex–elicited dose-related decreases in tumor growth rate with no significant change in body weight in both breast and melanoma syngeneic mouse models. Veledimex 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^[1].