576 Intasyl PH-762: Intratumoral Immunotherapy Targeting PD-1

PH-762 is an INTASYL compound designed to silence PD-1 mRNA, using a self-delivering RNAi technology that allows efficient delivery to various cell types without specialized systems. Administered via intratumoral injection, PH-762 reduces systemic side effects compared to conventional treatments. In vitro studies show PH-762 effectively silences PD-1 mRNA in human T cells, increasing IFN-γ secretion to inhibit tumor growth. Preclinical studies in mice demonstrate that PH-762 silences PD-1 mRNA in tumor T cells, enhances IFN-γ secretion, and inhibits tumor growth, with extended effects on untreated tumors. Toxicokinetic studies in marmoset monkeys show PH-762 is well-tolerated at high doses without cytokine-release. These findings support further clinical development for treating cutaneous malignancies.