May 22, 2026 —
Scribe Therapeutics announced that it has received clearance from the Australian Therapeutic Goods Administration to initiate a first-in-human clinical study of STX-1150, an investigational in vivo therapy for hypercholesterolemia and atherosclerotic cardiovascular disease risk reduction. The program marks Scribe’s first clinical study and reflects the company’s broader strategy to develop durable CRISPR-based medicines for chronic cardiometabolic disease.
STX-1150 is designed to durably lower LDL cholesterol by epigenetically silencing PCSK9 in the liver. PCSK9 is a clinically validated regulator of LDL-C, and inhibiting this pathway has become one of the most effective approaches to cholesterol reduction. Unlike permanent gene-editing approaches, STX-1150 is intended to silence gene expression without permanently altering the underlying DNA sequence.
The therapy uses Scribe’s proprietary ELXR, or Epigenetic Long-Term X-Repressor, technology. STX-1150 consists of messenger RNA encoding a highly engineered ELXR and a single guide RNA targeting the PCSK9 gene, both encapsulated in a liver-tropic lipid nanoparticle. ELXR is built on a nuclease-inactivated, engineered CasX-derived CRISPR protein fused to epigenetic effector domains, enabling targeted histone and DNA methylation marks for long-term but potentially reversible gene silencing.
The planned Phase 1 study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of STX-1150 in adults with elevated LDL-C and increased cardiovascular risk. The study is designed as an open-label, single ascending dose trial followed by a dose expansion phase, with planned enrollment of up to 64 participants across sites in Australia and New Zealand. Participants will be monitored for one year after treatment.
The first clinical site will be Monash Health’s Victorian Heart Hospital in Clayton, Victoria, Australia, led by Principal Investigator Stephen Nicholls, MBBS, PhD, Director of the Victorian Heart Institute at Monash University and Program Director of the Victorian Heart Hospital at Monash Health.
Scribe positions STX-1150 as a potential next-generation approach to LDL-C reduction, aiming to overcome treatment burden and adherence challenges associated with chronic lipid-lowering therapies. If successful, the therapy could provide sustained LDL-C lowering after a single administration while preserving genomic integrity, offering a differentiated path between chronic RNA-lowering therapies and permanent genome editing.
