STP888

STP888 is an investigational oligonucleotide-drug conjugate (ODC) developed by Sirnaomics. It consists of a double-stranded small interfering RNA (siRNA) targeting the checkpoint kinase 1 (CHK1) mRNA, with gemcitabine—a cytotoxic small molecule—incorporated into the sense strand in place of cytidines. The construct is chemically stabilized to improve tumor cell targeting and reduce toxicity to normal cells. Upon binding to CHK1 mRNA, the siRNA induces degradation of the target transcript, reducing CHK1 protein levels; concurrently, degradation of the sense strand releases gemcitabine intracellularly for a synergistic anticancer effect. This dual mechanism aims to enhance antitumor efficacy by combining gene silencing with chemotherapy within a single molecular entity. Preclinical studies have demonstrated potent activity against various cancer cell lines including pancreatic, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and ovarian models[1][7].