Stoke Therapeutics Presents STK-002 Preclinical and Clinical Data at AAO 2026, Advancing RNA-Based Approach for Autosomal Dominant Optic Atrophy
Stoke Therapeutics, Inc., a biotechnology company focused on restoring protein expression by harnessing the body’s potential with RNA medicine, has announced two presentations of data for STK-002 at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting, held October 9–12 in New Orleans, Louisiana. The presentations highlight findings from research into autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder, and provide additional support for the ongoing clinical development of STK-002, an investigational RNA-based medicine designed to address the underlying biology of the disease.
The data span ADOA disease biology, findings from the FALCON natural history study, preclinical research evaluating STK-002, and progress in the Phase 1 OSPREY clinical study. Together, these findings support the scientific rationale for increasing functional OPA1 protein expression as a potential way to modify the course of ADOA.
ADOA is primarily associated with variants in the OPA1 gene that lead to haploinsufficiency, a condition in which one functional copy of a gene does not produce enough protein to maintain normal biological activity. In people with ADOA, this can result in approximately 50% of normal OPA1 protein expression. Because OPA1 is important for mitochondrial function, insufficient levels of the protein can contribute to retinal ganglion cell dysfunction, optic nerve degeneration and progressive vision loss.
STK-002 is designed to increase the amount of functional messenger RNA (mRNA) produced from the healthy copy of the OPA1 gene, with the goal of increasing functional OPA1 protein levels. By targeting the underlying protein deficiency rather than only addressing the symptoms of visual impairment, Stoke Therapeutics aims to develop a potential disease-modifying treatment for people living with ADOA.
The company reported that dose escalation is ongoing in the Phase 1 OSPREY study, with dosing in the first two cohorts complete. The third cohort is expected to complete dosing by the end of 2026. Subject to ongoing safety assessments, dosing in the fourth cohort is expected to follow. Initial safety and efficacy data from the later cohorts are anticipated in the first half of 2027.
STK-002 Targets the Underlying Biology of ADOA
ADOA is an inherited optic nerve disorder that can cause progressive visual impairment, often beginning during childhood. The condition is primarily linked to variants in the OPA1 gene, which encodes a protein essential to mitochondrial function.
Mitochondria are responsible for producing much of the energy required by cells. Their proper functioning is particularly important in retinal ganglion cells, which help transmit visual information from the retina to the brain through the optic nerve. These cells have substantial energy requirements and depend on healthy mitochondrial activity to maintain their function.
When OPA1 variants reduce the amount of functional protein available, mitochondrial performance can be disrupted. Over time, this dysfunction can contribute to the degeneration of retinal ganglion cells and the optic nerve, ultimately resulting in impaired vision.
The disease’s genetic basis provides a potential opportunity for a targeted therapeutic approach. Rather than attempting to compensate for vision loss after damage has occurred, STK-002 is being developed to increase functional OPA1 protein expression by acting on the RNA produced from the healthy copy of the gene.
Messenger RNA carries genetic instructions used by cells to produce proteins. By increasing the amount of functional mRNA generated from the healthy OPA1 gene, STK-002 is intended to help cells produce more OPA1 protein. The approach is designed to address the insufficiency that contributes to ADOA’s underlying disease process.
The company’s presentations at AAO 2026 connect this biological rationale with evidence from natural history research and preclinical investigations. The findings are intended to inform the ongoing clinical evaluation of STK-002 and help determine whether increasing OPA1 expression can produce measurable improvements in visual function.
At present, there are no approved treatments for ADOA, according to the company’s announcement. This unmet medical need underscores the importance of investigating approaches that could target the biological mechanisms responsible for disease progression.
FALCON Natural History Findings Support the Therapeutic Rationale
One of the key areas highlighted in the AAO presentations was the natural history of ADOA, including findings from Stoke Therapeutics’ FALCON natural history study.
According to the company, results from FALCON showed that people with ADOA experience higher levels of mitochondrial oxidative stress than healthy individuals. The study also found a strong correlation between increased oxidative stress and decreased visual acuity.
Oxidative stress occurs when the production of reactive molecules exceeds the body’s capacity to neutralize them. In cells that depend heavily on mitochondrial activity, elevated oxidative stress can be associated with cellular dysfunction and damage. In ADOA, where insufficient OPA1 protein can disrupt mitochondrial function, these findings offer additional insight into the biological processes associated with impaired vision.
The reported relationship between oxidative stress and visual acuity is important because it links a biological measure associated with mitochondrial dysfunction to a clinically relevant aspect of the disease. Visual acuity measures the clarity or sharpness of vision and is one of the measures used to evaluate visual impairment.
The findings support the hypothesis that OPA1 deficiency and mitochondrial dysfunction play an important role in ADOA. They also provide a rationale for investigating whether increasing functional OPA1 protein levels could influence the disease process.
However, natural history findings and correlations do not establish that increasing OPA1 expression will necessarily improve vision or prevent disease progression. The potential clinical benefit of STK-002 must be assessed through clinical studies that evaluate safety and determine whether treatment produces measurable effects on visual function.
For Stoke Therapeutics, the FALCON findings provide a foundation for linking the biological mechanism targeted by STK-002 with clinical measures that can be evaluated during the OSPREY study.
Preclinical Research Demonstrates Dose-Dependent Activity
The AAO 2026 presentations also included preclinical proof-of-concept findings for STK-002. The research was designed to assess whether the investigational medicine could increase functional OPA1 expression and influence mitochondrial function in models relevant to ADOA.
Across preclinical studies, treatment with STK-002 demonstrated dose-dependent increases in retinal exposure, target engagement and OPA1 protein expression, according to Stoke Therapeutics.
Dose-dependent findings indicate that the measured response changes with the amount of treatment administered. In this context, the results provide evidence that STK-002 can reach the intended tissue, engage its biological target and increase the expression of the protein it is designed to restore under the conditions examined.
Retinal exposure is relevant because the retina contains the retinal ganglion cells involved in transmitting visual signals through the optic nerve. Establishing that a candidate medicine reaches the target tissue is an important part of evaluating its potential for an inherited optic nerve disorder.
Target engagement refers to evidence that a treatment interacts with or influences its intended biological target. For STK-002, the relevant objective is to increase functional mRNA production from the healthy copy of the OPA1 gene and thereby increase OPA1 protein expression.
The preclinical studies also reported improved mitochondrial function in ADOA patient-derived cells carrying different OPA1 variants. This finding suggests that the investigational approach may have activity across more than one disease-associated genetic variant, although the extent to which these laboratory observations will translate into clinical benefits remains to be determined.
Patient-derived cell models can help researchers investigate how a candidate treatment affects biological processes in cells associated with a particular disease. They can also provide information about whether a treatment’s mechanism appears relevant across different genetic backgrounds. Nevertheless, such findings are preliminary and cannot substitute for evidence from human clinical trials.
Taken together, the reported preclinical results support continued evaluation of STK-002. They suggest that the treatment can influence the intended molecular pathway and improve mitochondrial function in the models studied, providing a scientific basis for testing the medicine in people with ADOA.
Phase 1 OSPREY Study Continues Dose Escalation
STK-002 is being evaluated in OSPREY, a Phase 1, first-in-human, dose-escalation study involving people with OPA1-associated ADOA.
The primary purpose of the study is to evaluate the safety and tolerability of STK-002 at different dose levels. It will also assess whether the medicine’s ability to increase OPA1 expression translates into measurable effects on visual function.
Dose-escalation studies generally evaluate successive dose levels under defined safety-monitoring procedures. Investigators review available safety information as participants progress through the study, helping determine whether it is appropriate to proceed to subsequent cohorts.
Stoke Therapeutics reported that dosing in the first two OSPREY cohorts is complete. Dosing in the third cohort is expected to be completed by the end of 2026, followed by the fourth cohort, subject to ongoing safety assessments.
The company indicated that the third and fourth cohorts have the potential to reach therapeutic levels of dosing. These cohorts are designed to help assess whether STK-002 can produce measurable effects on visual function in addition to providing further information about safety and tolerability.
Initial safety and efficacy results from these later cohorts are anticipated in the first half of 2027.
The distinction between early safety findings and potential efficacy signals is important at this stage of development. Completion of dosing in the first two cohorts represents progress in the clinical program, but it does not establish that the treatment is effective. Additional clinical data will be needed to determine how STK-002 is tolerated, whether it meaningfully increases OPA1 expression in people, and whether any biological effects correspond with changes in visual function.
The planned results from the later cohorts are expected to provide an important opportunity to evaluate these questions as dose escalation advances.
Clinical Investigators Highlight the Need for New Treatment Options
Patrick Yu-Wai-Man, M.D., Ph.D., Professor of Ophthalmology at the University of Cambridge and the UCL Institute of Ophthalmology, Honorary Consultant Neuro-ophthalmologist at Addenbrooke’s Hospital and Moorfields Eye Hospital in the United Kingdom, is the lead investigator for the Phase 1 OSPREY study.
Yu-Wai-Man emphasized the impact of ADOA and the importance of investigating treatments that address its underlying biological cause.
“ADOA can cause severe progressive visual impairment often beginning in childhood, and there are currently no approved treatments,” Yu-Wai-Man said. “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.”
His comments reflect the clinical challenge associated with a disorder that can affect vision from an early age and progressively impair patients’ ability to see clearly. The absence of approved treatments also highlights the need for research into therapeutic strategies that may address the mechanisms driving the disease.
STK-002 represents one such approach, using RNA medicine to increase functional protein expression. The OSPREY study is intended to establish the early clinical evidence needed to assess whether the strategy can be advanced further.
Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics, also highlighted progress in the clinical program.
“We’re encouraged by the progress in the Phase 1 OSPREY study of STK-002 in people with ADOA, with the first two dose cohorts now complete,” Ticho said. “Dose cohorts three and four are designed to show measurable effects on visual function, and we look forward to safety and efficacy results from these latter cohorts in the first half of next year.”
Ticho’s comments underline the company’s focus on progressing through dose escalation and obtaining additional data from the cohorts expected to reach potentially therapeutic dose levels. The anticipated findings will help inform the next stages of STK-002’s clinical development.
AAO Presentations Connect Disease Biology With Clinical Development
The two presentations at the AAO 2026 Annual Meeting brought together several components of the STK-002 development program: an understanding of the genetic and biological mechanisms underlying ADOA, natural history observations from the FALCON study, preclinical evidence of target engagement and increased OPA1 expression, and progress in the first-in-human OSPREY trial.
This combined evidence supports the rationale for evaluating STK-002 as a potential disease-modifying treatment. The approach is designed to address OPA1 haploinsufficiency, which can result in approximately half the normal level of OPA1 protein expression and contribute to mitochondrial dysfunction in retinal ganglion cells.
The FALCON findings add to the understanding of disease-associated oxidative stress and its relationship with visual acuity. Preclinical results provide evidence of dose-dependent activity and improved mitochondrial function in ADOA patient-derived cells. The ongoing clinical study will determine whether the treatment can be administered safely and whether its biological mechanism translates into measurable changes in visual function in people.
Each stage of the development program answers a different question. Natural history research helps characterize the disease and identify relevant biological patterns. Preclinical studies assess the candidate medicine’s activity in laboratory models. Early clinical research evaluates safety and tolerability while beginning to investigate potential effects in patients.
Although the findings reported at AAO 2026 support continued research, STK-002 remains investigational. The available information does not establish clinical efficacy, and further results will be required to determine its potential benefits and risks.
Stoke Therapeutics Advances Its RNA Medicine Approach
Stoke Therapeutics is developing medicines intended to restore protein expression by harnessing the body’s potential through RNA-based approaches. The company’s STK-002 program applies this strategy to ADOA by seeking to increase functional OPA1 protein production from the healthy copy of the OPA1 gene.
The program’s progress reflects an effort to connect a defined genetic cause with a targeted therapeutic strategy. By focusing on protein insufficiency and its consequences for mitochondrial function, Stoke Therapeutics is investigating whether correcting an underlying biological deficit can help preserve or improve visual function.
The next important milestone for STK-002 is the continued progression of the OSPREY study. With the first two dose cohorts complete and the third cohort expected to finish by year-end 2026, the company is working toward the anticipated initial safety and efficacy results from the later cohorts in the first half of 2027.
Those findings are expected to provide additional information about the safety and tolerability of STK-002 and whether treatment can produce measurable effects on visual function.
For people living with ADOA, the absence of approved treatment options leaves a significant unmet medical need. The combination of disease biology research, natural history findings and preclinical evidence provides a rationale for continued clinical investigation, while the OSPREY study will be essential in determining whether STK-002 can translate that rationale into a meaningful therapeutic benefit.
Through its presentations at the AAO 2026 Annual Meeting, Stoke Therapeutics has highlighted progress across the STK-002 program and the scientific basis for its RNA-based approach. As dose escalation continues, future clinical data will help clarify the investigational medicine’s potential role in addressing OPA1 deficiency and the progressive visual impairment associated with autosomal dominant optic atrophy.
About Autosomal Dominant Optic Atrophy (ADOA)
ADOA is the most common inherited optic nerve disorder, affecting approximately one in 25,000 people globally with a higher incidence of one in 10,000 in Denmark due to a founder effect. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Approximately half of people with ADOA fail driving standards and up to 46% are registered as legally blind. Currently there are no approved treatments for people living with ADOA.
About STK-002
STK-002 is a proprietary antisense oligonucleotide (ASO) in clinical development for the treatment of ADOA. Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. An estimated 65% to 90% of ADOA cases are caused by variants in the OPA1 gene, of which more than 600 have been reported in people diagnosed with ADOA. Most of these variants in the OPA1 gene lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation.
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 improve vision in people with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. STK-002 has been granted orphan drug designation by the FDA as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 in people with ADOA is ongoing.
About the Phase 1 OSPREY Study
The OSPREY study is a Phase 1, dose-escalating open-label study of children and adults ages 6 to 55 who have an established diagnosis of ADOA and have a confirmed disease-causing variant in the OPA1 gene. The primary objectives for the study are to assess the safety and tolerability of single ascending doses of STK-002, as well as to determine the exposure in blood. Secondary objectives are to assess changes in visual function, ocular structure and quality of life after single doses of STK-002.
The OSPREY study follows a standard dose escalation design with participants enrolled into sequential cohorts receiving increasing dose levels of STK-002. Dosing of the first two cohorts of patients is complete, with dosing of the third cohort expected to complete by the end of 2026. Subject to ongoing safety assessments, dosing of the fourth cohort is expected to follow. Initial safety and efficacy results are anticipated in the first half of 2027. Data from the OSPREY study will help to inform potential future development of STK-002.
All eight planned OSPREY clinical trial sites are now active in the UK, Germany, Denmark, Italy and Austria. For more information on the OSPREY study, please visit:
About the FALCON Study
FALCON was a multicenter, 24-month, prospective natural history study of people ages 8 to 60 who are living with ADOA. FALCON aimed to provide a better understanding of how ADOA disease parameters change over time to inform potential future interventional clinical trials and was designed to evaluate the rate of change in structural and functional ophthalmic assessments. No investigational medications or other treatments were provided.
The study enrolled 47 patients across 10 sites in the United States, United Kingdom, Italy and Denmark. All participants had a confirmed diagnosis of ADOA caused by an OPA1 variant. Patients underwent assessments at baseline, 6 months, 12 months, 18 months and 24 months. 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.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study.
Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts.