A Study of STX-1150 in Participants With Elevated Low-Density Lipoprotein Cholesterol (LDL-C)

STX-1150 is an investigational therapy designed to lower LDL-C by silencing a gene called PCSK9 in the liver. STX-1150 does not edit or permanently change the gene. STX-1150 comprises an mRNA and guide RNA (gRNA) delivered via lipid nanoparticles (LNP) for intravenous infusion. The mRNA produces a protein that switches off the PCSK9 gene expression without altering the DNA sequence. This process leverages natural mechanisms that regulate gene activity. The study will enroll up to 64 participants with elevated LDL-C across sites in Australia and New Zealand. The follow-up period will be up to 1- year post-treatment.

STX-1150 is an investigational product designed to epigenetically silence the PCSK9 gene. It comprises an mRNA and a guide RNA (gRNA) delivered in a lipid nanoparticle (LNP) for intravenous (IV) infusion. STX-1150 epigenetically silences the expression of the PCSK9 gene in the liver, thereby reducing circulating PCSK9 and LDL-C levels. The active components, an mRNA and a gRNA are encapsulated in lipid nanoparticles (LNPs) for targeted hepatic delivery. The gRNA precisely guides the complex to a specific locus within the PCSK9 gene promoter. By reducing PCSK9 expression, STX-1150 prevents the degradation of LDL receptors (LDL-R), leading to increased LDL-R levels on hepatocytes and enhanced clearance of LDL-C from the bloodstream. This targeted and durable epigenetic silencing represents a promising therapeutic strategy for long-term LDL-C reduction, particularly benefiting patients with elevated LDL-C or a high risk for Atherosclerotic Cardiovascular Disease (ASCVD).

Inclusion Criteria: * Elevated serum LDL-C with or without LDL-C lowering medication * Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures Exclusion Criteria: * Patients with history of an ASCVD event \</= 6 months. * Any uncontrolled or serious disease, or any medical or surgical condition that may interfere with participation * Diagnosis of familial hypercholesterolemia * Active or history of liver disease * Previous treatment with PCSK9-inhibitor or other prior treatment within a specified timeframe * Clinically significant abnormal laboratory values