Stoke Therapeutics Presents Preclinical Data on Potential Treatment For Inherited Optic Nerve Disorder

Stoke Therapeutics announced new preclinical data demonstrating in-vitro and in-vivo target engagement and protein upregulation in OPA1 protein-deficient cells. OPA1 protein deficiency is the primary cause of autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder. This is the first proof-of-concept data for TANGO antisense oligonucleotides (ASOs) in an ocular disease. The results further validate the company’s mutation-independent approach to amplifying protein expression to treat severe genetic diseases. These data will be presented today in a virtual poster session at the American Society of Gene and Cell Therapy (ASGCT) 2020 Annual Meeting.

“These data provide early evidence of the potential to address the underlying cause of autosomal dominant optic atrophy, an optic nerve disorder that causes progressive and irreversible vision loss starting in the first decade of a child’s life. There are currently no approved treatments for ADOA,” Edward M. Kaye, MD, Chief Executive Officer of Stoke Therapeutics, said in a company news release. “Our TANGO technology represents a unique, mutation-independent approach to treating the underlying cause of a variety of genetic diseases, particularly in the central nervous system and the eye. The ADOA program is one of several under consideration for future prioritization, and we look forward to nominating a second product candidate later this year.”

ADOA affects approximately one in 30,000 people globally with a higher incidence in Denmark of one in 10,000 due to a founder effect. An estimated 65% to 90% of cases are caused by mutations in the OPA1 gene.

The data presented demonstrate in-vitro and in-vivo proof-of-concept for TANGO ASOs in an ocular disease. Highlights from today’s presentation include:

• Dose-dependent decreases in non-productive OPA1 mRNA and increases in OPA1 protein expression were observed in-vitro and in-vivo.
• An increase in OPA1 protein expression to approximately 75% of wild-type levels was observed in an OPA1 haploinsufficient (OPA1 +/-) cell line.
• In-vivo increases in OPA1 protein levels in the retina of wild-type rabbits were observed and the test ASO was well tolerated for up to 15 days after intravitreal injection.

Details of today’s presentation are as follows:

Presentation Title: Antisense oligonucleotide mediated increase of OPA1 expression using TANGO technology for treatment of autosomal dominant optic atrophy

Session Date & Time: Tuesday, May 12, 2020; 5:30 p.m. – 6:30 p.m. E.T.

Session Title: Oligonucleotide Therapeutics

Presenter: Aditya Venkatesh, PhD, Senior Scientist, Stoke Therapeutics

Poster Number: 1593

The poster presented at ASGCT is now available online on the Events and Presentations section of Stoke’s website at https://investor.stoketherapeutics.com/.