Stoke Therapeutics has announced pivotal two-year data from the FALCON study, a comprehensive natural history investigation of autosomal dominant optic atrophy (ADOA) that provides crucial insights for developing the first potential disease-modifying treatment for this rare genetic eye disorder. The findings were presented at the 2025 American Academy of Ophthalmology Annual Meeting and directly inform the company's ongoing Phase 1 clinical trial of STK-002.
Largest Natural History Study Reveals Disease Progression Patterns
The FALCON study represents the most extensive prospective natural history investigation of ADOA to date, enrolling 47 patients aged 8 to 60 across 10 sites in the United States, United Kingdom, Italy, and Denmark. This multicenter, 24-month study aimed to provide a comprehensive understanding of how ADOA disease parameters change over time to inform future interventional clinical trials.
ADOA is described by Stoke Therapeutics as "a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life." The condition affects approximately one in 30,000 people globally, with a higher incidence of one in 10,000 in Denmark due to a founder effect. Notably, 46% of those with ADOA are registered as legally blind, and roughly half fail driving standards.
Key Clinical Findings Support Treatment Potential
The study revealed several important findings about ADOA progression and pathophysiology. While OPA1-associated ADOA progresses slowly overall, 24% of patients experienced at least a five-letter loss in low-contrast visual acuity (LCVA) over the two-year period. LCVA serves as a particularly sensitive measure because it detects subtle changes in optic nerve function often before standard vision tests show differences.
Patients with ADOA demonstrated higher levels of mitochondrial dysfunction compared with healthy individuals. This finding is clinically significant because mitochondrial function is crucial for vision, as mitochondria produce most of the energy required by cells that make up the optic nerve.
Perhaps most encouraging for therapeutic development, the study found no significant anatomic changes in the retina were observed. According to the company, this suggests that retinal dysfunction may be reversible with treatment intervention.
Expert Commentary Highlights Therapeutic Implications
Dr. Patrick Yu-Wai-Man, Professor of Ophthalmology and Honorary Consultant Neuro-ophthalmologist at the University of Cambridge, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, who serves as the primary investigator on the Phase 1 OSPREY study, provided key insights into the findings.
"These findings suggest that impaired function in the retina and the optic nerve occurs before permanent cell loss. By increasing the level of naturally occurring OPA1 protein to improve mitochondrial function, it may be possible to stabilize and even restore vision in people with ADOA," Yu-Wai-Man stated. "Importantly, the FALCON study has identified promising measures of disease progression in ADOA, which can be applied to both natural history and interventional studies of potential new treatments."
STK-002 Development Program Advances
The FALCON data directly support the clinical development of STK-002, Stoke's proprietary antisense oligonucleotide currently being evaluated in the Phase 1 OSPREY study. STK-002 is designed to upregulate OPA1 protein expression by leveraging the non-mutant (wild-type) copy of the OPA1 gene to restore OPA1 protein expression.
An estimated 65% to 90% of ADOA cases are caused by variants in the OPA1 gene, most of which lead to haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. More than 400 different OPA1 variants have been reported in people diagnosed with ADOA.
Barry Ticho, Chief Medical Officer of Stoke Therapeutics, emphasized the significance of the research: "The FALCON study is the largest prospective natural history study to evaluate the effects of ADOA, a rare genetic disease that leads to progressive vision loss and, for many patients, results in blindness. These data will provide important context as we initiate our Phase 1 study of STK-002 as the first potential disease-modifying medicine for ADOA."
Regulatory Recognition and Future Outlook
STK-002 has received orphan drug designation from the FDA as a potential new treatment for ADOA. Currently, there is no approved treatment for people living with ADOA, making STK-002 a potentially groundbreaking therapeutic option.
The company has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA, with the aim to maintain or improve vision in patients with this progressive condition.
