BEDFORD, Massachusetts — October 12, 2026
Stoke Therapeutics announced new data supporting the potential disease-modifying activity of STK-002, an investigational RNA-based medicine being developed for autosomal dominant optic atrophy (ADOA), at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting in New Orleans. The presentations included findings from ADOA disease biology research, the FALCON natural history study and preclinical investigations of STK-002, supporting the ongoing Phase 1 OSPREY clinical trial. ADOA is an inherited optic nerve disorder primarily associated with variants in the OPA1 gene, which can reduce functional OPA1 protein levels and cause progressive, irreversible vision loss. STK-002 is designed to increase expression from the healthy copy of the OPA1 gene, potentially addressing the underlying biological deficiency rather than only managing symptoms. Stoke reported that dosing in the first two OSPREY study cohorts is complete, while the third cohort is expected to finish dosing by the end of 2026. Initial safety and efficacy data are anticipated in the first half of 2027.
FALCON Findings Strengthen the Rationale for STK-002
Data from the FALCON natural history study highlighted the relationship between mitochondrial oxidative stress and visual impairment in people living with ADOA. The multicenter, prospective, 24-month study enrolled 47 participants aged 8 to 60 years across 10 sites in the United States, United Kingdom, Italy and Denmark. Participants underwent assessments at baseline and at six-month intervals through 24 months, with researchers evaluating changes in structural and functional ophthalmic measures. According to Stoke, the findings showed higher levels of mitochondrial oxidative stress in people with ADOA compared with healthy individuals, with higher oxidative stress strongly correlating with reduced visual acuity. These observations support the biological rationale for increasing OPA1 protein expression as a potential strategy to modify disease progression. OPA1 plays an important role in mitochondrial function, which is particularly important for retinal ganglion cells that form the optic nerve and require substantial energy to function. Reduced OPA1 expression can contribute to mitochondrial dysfunction and optic nerve degeneration. The natural history findings provide context for evaluating whether STK-002 can influence this disease process, although they do not establish that the investigational treatment improves vision in patients.
Preclinical Results Demonstrate OPA1 Target Engagement
STK-002 is a proprietary antisense oligonucleotide (ASO) designed to increase functional messenger RNA produced by the non-mutant copy of the OPA1 gene. The intended outcome is increased production of functional OPA1 protein, potentially helping restore mitochondrial function in affected cells. Across preclinical studies, Stoke reported dose-dependent increases in retinal exposure, target engagement and OPA1 protein expression following treatment with STK-002. The company also reported improved mitochondrial function in ADOA patient-derived cells carrying different OPA1 variants. ADOA is commonly associated with haploinsufficiency, in which a person has insufficient functional gene output; the resulting reduction in OPA1 protein can disrupt the energy-producing functions of mitochondria and contribute to progressive visual impairment. Stoke estimates that approximately 65% to 90% of ADOA cases are associated with OPA1 variants. The company believes that increasing expression from the healthy gene copy could potentially benefit patients across multiple mutation types. STK-002 has received orphan drug designation from the U.S. Food and Drug Administration for ADOA. However, the reported findings are preclinical, and further clinical evaluation is required to determine whether these effects translate into meaningful and durable improvements in visual function.
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Phase 1 OSPREY Study Advances Dose Escalation
The ongoing OSPREY Phase 1 study is an open-label, first-in-human dose-escalation trial evaluating the safety and tolerability of STK-002 in children and adults aged 6 to 55 with confirmed OPA1-associated ADOA. The study’s primary objectives include assessing safety and tolerability following single ascending doses and determining exposure in blood. Secondary objectives include evaluating changes in visual function, ocular structure and quality of life. Stoke confirmed that the first two dose cohorts have completed dosing, with the third cohort expected to complete dosing by the end of 2026. Subject to ongoing safety assessments, dosing in the fourth cohort is expected to follow. The company indicated that the third and fourth cohorts could reach dose levels intended to produce measurable effects on visual function. Initial safety and efficacy findings from these later cohorts are expected in the first half of 2027. All eight planned clinical trial sites are active across the United Kingdom, Germany, Denmark, Italy and Austria. ADOA affects approximately one in 25,000 people worldwide, according to the company, and there are currently no approved treatments for the condition. Stoke is developing STK-002 as a potential first disease-modifying therapy for ADOA, but its safety and effectiveness remain under investigation.
Source::Stoke Therapeutics,, press release
