Stoke Therapeutics Presents Two-Year Data from FALCON Study on Autosomal Dominant Optic Atrophy (ADOA)

Strategic Insights -

Stoke Therapeutics, a biotechnology company dedicated to restoring protein expression through RNA medicines, presented two-year data from the FALCON study at the 2025 American Academy of Ophthalmology (AAO) Annual Meeting. The FALCON study, a prospective natural history study in people with Autosomal Dominant Optic Atrophy (ADOA) (n=47), aimed to provide a better understanding of how ADOA disease parameters change over time. The data have informed Stoke's clinical development program for the proprietary antisense oligonucleotide (ASO) STK-002, currently being evaluated in the Phase 1 OSPREY study.

ADOSA is a rare genetic disease primarily caused by variants in the OPA1 gene that result in progressive and irreversible vision loss. The study found that while OPA1-associated ADOA progresses slowly, 24% of patients experienced at least a five-letter loss in low-contrast visual acuity (LCVA). LCVA detects more subtle changes in optic nerve function, often before standard vision tests show a difference. The study also showed higher levels of mitochondrial dysfunction in people with ADOA compared to healthy individuals. Mitochondrial function is crucial for vision because mitochondria produce most of the energy required by the cells that make up the optic nerve. No significant anatomic changes in the retina were observed, suggesting that retinal dysfunction may be reversible with treatment intervention.

Key Takeaways:

  • ADOA is a rare genetic disease primarily caused by variants in the OPA1 gene that result in progressive and irreversible vision loss.
  • The FALCON study found that 24% of patients experienced at least a five-letter loss in low-contrast visual acuity (LCVA) over two years, indicating progressive disease.
  • Higher levels of mitochondrial dysfunction were shown in people with ADOA compared to healthy individuals.
  • No significant anatomic changes in the retina were observed, suggesting that retinal dysfunction may be reversible with treatment intervention.
  • The data from the FALCON study support the clinical development of STK-002, Stoke's proprietary antisense oligonucleotide (ASO) 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 with the aim to maintain or improve vision in patients with ADOA.
  • An estimated 65% to 90% of cases of ADOA are caused by variants in the OPA1 gene, most of which lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation.
  • Stoke Therapeutics has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002.

Statistics:

  • 47 patients with Autosomal Dominant Optic Atrophy (ADOA) were enrolled in the FALCON study.
  • 24% of patients experienced at least a five-letter loss in low-contrast visual acuity (LCVA) over two years.
  • The study found higher levels of mitochondrial dysfunction in people with ADOA compared to healthy individuals.
  • No significant anatomic changes in the retina were observed in patients with ADOA.

Sources:

  • Stoke Therapeutics press release, October 20, 2025.
  • American Academy of Ophthalmology Annual Meeting, October 18, 2025.
  • US FDA, Orphan Drug Designation for STK-002.
  • National Library of Medicine, Autosomal Dominant Optic Atrophy (ADOA).
  • Stoke Therapeutics website, About Autosomal Dominant Optic Atrophy (ADOA).