Veledimex racemate, the racemic form of veledimex, is an orally available, small-molecule ligand that activates the RheoSwitch Therapeutic System.

Interleukin 12 (IL-12) is a pro-inflammatory cytokine critical for stimulating anti-cancer immune responses. Ad-RTS-IL-12 is an adenovirus vector engineered to express hIL-12. Veledimex is an orally active small molecule diacylhydrazine, which can control the expression of target genes. The amount of gene product produced by the system and the duration of action depend on the dose level of veledimex and the time of administration.

In murine melanoma, breast cancer, and glioma models, Intratumoral administration of Ad-RTS-mIL-12 along with oral administration of veledimex elicits dose-dependent antitumor effects , 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.