SPC4061

SPC4061 is a 13-mer locked nucleic acid (LNA) antisense oligonucleotide designed to target the messenger RNA (mRNA) of proprotein convertase subtilisin/kexin type 9 (PCSK9). Developed by Santaris Pharma A/S, it utilizes a gapmer design with LNA-modified ends flanking a DNA core to enhance serum stability and binding affinity. By binding to PCSK9 mRNA, SPC4061 triggers its degradation, thereby reducing the production of PCSK9 protein. Since PCSK9 normally promotes the degradation of low-density lipoprotein receptors (LDLR) in the liver, its inhibition leads to increased LDLR levels on the hepatocyte surface and a subsequent reduction in circulating low-density lipoprotein cholesterol (LDL-C). In preclinical studies involving nonhuman primates, SPC4061 demonstrated the ability to lower serum PCSK9 and LDL-C levels, although it was found to be less potent than its related compound, SPC5001.