Key Takeaways

  • STK-002 is an investigational RNA-based therapy designed to increase OPA1 protein expression in patients with autosomal dominant optic atrophy

  • Natural history and preclinical findings support its therapeutic rationale, including improvements in mitochondrial function observed in patient-derived cells

  • The phase 1 OSPREY trial has completed its first 2 dose cohorts, with initial safety and efficacy results from higher-dose cohorts expected in the first half of 2027

Stoke Therapeutics presented new preclinical and natural history data supporting the development of STK-002, an investigational RNA-based therapy for autosomal dominant optic atrophy (ADOA), at the American Academy of Ophthalmology (AAO) 2026 annual meeting in New Orleans.

The presentations highlighted findings from the FALCON natural history study and preclinical research supporting the ongoing phase 1 OSPREY trial, which is evaluating STK-002 in patients with OPA1-associated ADOA.

ADOA is the most common inherited optic nerve disorder and is primarily associated with variants in the OPA1 gene. These variants can reduce functional OPA1 protein expression by approximately 50%, contributing to mitochondrial dysfunction, retinal ganglion cell degeneration, and progressive vision loss.

Results from FALCON demonstrated increased mitochondrial oxidative stress in patients with ADOA compared with healthy individuals. Higher oxidative stress levels were strongly correlated with reduced visual acuity, supporting the rationale for therapies targeting OPA1 protein deficiency.

STK-002 is designed to increase functional messenger RNA production from the unaffected copy of the OPA1 gene, potentially restoring OPA1 protein expression.

In preclinical studies, STK-002 demonstrated dose-dependent increases in retinal exposure, target engagement, and OPA1 protein expression. Treatment also improved mitochondrial function in patient-derived cells carrying different OPA1 variants. The first 2 dose cohorts in the Phase 1 OSPREY study have completed dosing. The third cohort is expected to complete dosing by the end of 2026, with a fourth cohort planned pending safety assessments.

According to Stoke, the third and fourth cohorts may reach therapeutically relevant dose levels, with initial safety and efficacy data anticipated in the first half of 2027.

"These early data are an important step in evaluating whether an RNA-based medicine can address the underlying OPA1 deficiency and ultimately improve visual outcomes for people with ADOA," said Patrick Yu-Wai-Man, MD, PhD, lead investigator of OSPREY.

No treatments are currently approved for ADOA.