Scribe Therapeutics presented late-breaking preclinical data at the 94th European Atherosclerosis Society Congress showing that a single dose of an STX-1150 prototype produced ldl-c reductions up to 68% and pcsk9 reductions up to about 90% in non-human primates, with the lowest dose yielding greater than 50% ldl-c reduction for more than 22 months and ongoing.
The company also reported that CMC-scaled STX-1150 demonstrated at least five-fold greater potency in primary human hepatocytes versus primary cynomolgus hepatocytes, supporting human dose translation. In vitro assessments reportedly showed no off-target gene expression changes at three times EC90, in vivo liver enzyme profiles at 0.75 mg/kg were comparable to saline, and a GLP toxicology study found no test-article-related adverse findings.
STX-1150 is an investigational, liver-targeted CRISPR-based epigenetic silencing therapy composed of mRNA encoding the ELXR epigenetic silencer and a guide RNA encapsulated in a liver-tropic lipid nanoparticle.
The therapy is being evaluated in a first-in-human, open-label, single ascending dose Phase 1 study in adults with elevated LDL-C, and Scribe has regulatory clearance from the Australian Therapeutic Goods Administration, with enrollment underway in Australia and additional sites planned in New Zealand.
The data support continued development of STX-1150 as a potential ultra-long-acting LDL-C-lowering approach that does not permanently alter DNA, according to the company.
