Stoke Shares 2-Year Data from FALCON Study in ADOA

Stoke Therapeutics has announced two-year results from its FALCON study, the largest prospective natural history study to date in individuals living with autosomal dominant optic atrophy (ADOA), a rare, inherited eye disease that causes progressive and irreversible vision loss, typically beginning in childhood.

The data were shared as part of the company’s ongoing effort to build a deeper understanding of ADOA and to inform the design of future interventional clinical trials, including the development of STK-002, Stoke’s investigational treatment for ADOA.

Study Overview: Largest Prospective Study in ADOA

FALCON was a 24-month, multicenter, prospective natural history study that enrolled 47 participants aged 8 to 60 across 10 sites in the United States, United Kingdom, Italy, and Denmark. Patients underwent comprehensive assessments at baseline, 6, 12, 18, and 24 months.

The study’s primary goal was to observe how ADOA-related disease parameters evolve over time to provide a clinical framework for future treatment strategies.

Key Findings

The findings confirmed that OPA1-associated ADOA progresses slowly; however, there are notable signs of functional decline:

• 24% of patients experienced a ≥5-letter loss in low-contrast visual acuity (LCVA) over the two-year period

• Increased mitochondrial dysfunction was observed in patients with ADOA compared to healthy individuals

• No significant anatomical changes in the retina were detected, suggesting that retinal dysfunction may be reversible if treated early

“These findings suggest that impaired function in the retina and the optic nerve occurs before permanent cell loss,” said Patrick Yu-Wai-Man, MD, PhD, Professor of Ophthalmology at the University of Cambridge and Principal Investigator of the Phase 1 OSPREY study. “By increasing levels of naturally occurring OPA1 protein to improve mitochondrial function, it may be possible to stabilize and even restore vision in people with ADOA.”

About STK-002

The FALCON results are expected to support the development of STK-002, Stoke’s proprietary antisense oligonucleotide (ASO) therapy currently being evaluated in the Phase 1 OSPREY trial.

STK-002 is designed to upregulate OPA1 protein expression by leveraging the wild-type (non-mutant) copy of the OPA1 gene, with the goal of maintaining or improving visual function in patients with ADOA.

STK-002 has received Orphan Drug Designation from the FDA, underscoring its potential as the first disease-modifying treatment for ADOA.

“The FALCON study is the largest prospective natural history study to evaluate the effects of ADOA,” said Barry Ticho, MD, PhD, Chief Medical Officer of Stoke Therapeutics. “These data will provide important context as we initiate our Phase 1 study of STK-002.”

Understanding ADOA: A Rare Disease with High Vision Loss Burden

ADOA is a rare genetic optic neuropathy caused by mutations in the OPA1 gene, leading to mitochondrial dysfunction and progressive degeneration of the optic nerve. Symptoms typically begin in the first decade of life, and up to 46% of affected individuals are registered as legally blind.