STK-009 (Stoke Therapeutics)

STK-009 is an antisense oligonucleotide (ASO) being developed by Stoke Therapeutics for the treatment of autosomal dominant optic atrophy (ADOA). It utilizes Stoke's proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) platform technology to address OPA1 haploinsufficiency, which is the primary cause of ADOA. Most cases of the disease result from mutations in one copy of the OPA1 gene, leading to a 50% reduction in OPA1 protein expression. STK-009 is designed to bind to the pre-mRNA of the functional OPA1 allele and modulate its splicing, specifically by reducing the occurrence of non-productive splicing events. This mechanism increases the production of functional OPA1 protein, aiming to restore protein levels to a therapeutic range, maintain mitochondrial function in retinal ganglion cells, and prevent or slow vision loss.