Stoke Therapeutics Announces First Patient Dosed in Phase 1 Study of STK-002, a Potential Disease-Modifying Medicinefor the Treatment of Autosomal Dominant Optic Atrophy (ADOA)
Stoke Therapeutics, Inc. a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced that the first patient has been dosed in the Phase 1 OSPREY study of STK-002, an investigational medicine for the treatment of Autosomal Dominant Optic Atrophy (ADOA). ADOA is a rare genetic disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Approximately 80 percent of people with ADOA are symptomatic by age 10, and approximately half are expected to become legally blind. There are currently no approved treatments for ADOA.
Data from our natural history study suggest that for some people affected by ADOA, the disease progresses more rapidly than previously thought. Based on a growing understanding of the disease biology, we believe that increasing naturally occurring OPA1 protein may help restore vision in people with ADOA,” said the lead principal investigator of the study Dr. Patrick Yu-Wai-Man, M.D., Ph.D., Professor of Ophthalmology at the University of Cambridge and
honorary consultant neuro-ophthalmologist at Addenbrooke’s Hospital, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, United Kingdom. “There are currently no medicines available for people living with ADOA, and there is a lot of interest in this study from the ADOA community given the potential for STK-002 to restore vision by addressing the root cause of the disease.
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. Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Data from the OSPREY study will help to inform potential future development of STK-002.
“ADOA is a haploinsufficient disease, one of many that we believe are ideally suited for our ASOs that are designed to increase naturally occurring protein levels to improve health,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “We are pleased to be expanding our approach into a new disease area, leveraging our learnings from Dravet syndrome and applying them to the development of a potential disease-modifying medicine for people living with ADOA.”
The OSPREY study is actively recruiting in the United Kingdom and Germany. Additional European sites are expected to activate in the coming months.
About Autosomal Dominant Optic Atrophy (ADOA)
ADOA is the most common inherited optic nerve disorder, affecting approximately one in 30,000 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. More than 400 different disease-causing OPA1 variants have been reported in people diagnosed with ADOA. 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, most of which 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 maintain or 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 U.S. Food and Drug Administration (FDA) as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 in people with ADOA is now underway.
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.
Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Data from the OSPREY study will help to inform potential future development of STK-002. The OSPREY study is actively recruiting in the United Kingdom and Germany. Additional European sites are expected to activate in the coming months.
About Stoke Therapeutics
Stoke Therapeutics 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.
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