Locanabio has reported positive preclinical data from its LBIO-115 programme for treatment of Duchenne muscular dystrophy (DMD). The company is developing small nuclear RNAs (snRNAs) for an exon skipping approach in DMD treatment.
In data that will be presented at the Cure Duchenne Futures 2023 National Conference in California, LBIO-115 demonstrated greater exon 51 skipping in DMD transgenic mice. Exon skipping is an already established therapy model for DMD and Locanabio aims to enhance this with its snRNA platform.
In mice models, the company observed more than 80% exon 51 skipping in skeletal muscle following LBIO-115 intramuscular injection. More than 50% of the muscle fibres were positive for dystrophin protein after four weeks.
According to the company, exon-skipping therapies can clinically benefit around 80% of DMD patients with mutations amenable to exon 51 skipping. Exon-skipping therapies are limited in that they are often co-administered with steroids, and that only patients are suitable for the treatment.
Sarepta’s SRP-9001, which has an approval decision expected in May 2023, is spearheading a changing landscape for DMD treatment that is seeing companies take a multi-pronged approach to treatment which caters for personalised medicine trends.
“We have designed snRNA-based exon-skipping constructs that can target multiple splicing regulatory sites in the dystrophin mRNA for enhanced exon-skipping and production of a near full-length protein with a one-time administration,” said Locanabio’s CEO Jim Burns.
“Based on the strength of these data, we have advanced LBIO-115 into investigational new drug-enabling studies. The vectorised snRNA platform enables rapid expansion to other patient populations and we currently have programs in lead optimization for mutations amenable to exon 53, 45 and 44 skipping,” added John Leonard, Locanabio’s chief scientific officer.