Stoke Therapeutics Presents New In-Vivo Data That Demonstrated Dose-Related Target Engagement and OPA1 Protein Upregulation in Retinal Tissue Following Administration of STK-002
– Data presented at the
– ADOA is the most common inherited optic nerve disorder –
ADOA affects approximately one in 30,000 people globally with a higher incidence (one in 10,000) in
“The progressive vision loss experienced by people living with ADOA is typically the result of a mutation in their OPA1 gene, which leads to insufficient protein production and a loss of retinal ganglion cells,” said
In this study, NHPs were given bilateral IVT injections of either placebo or STK-002 at low, mid or high doses. Assessments were made at four weeks for all dose groups and at eight weeks for the mid- and high-dose groups.
Highlights from the presentation include:
- IVT administration of STK-002 was well-tolerated in NHPs;
- Target engagement was demonstrated by the dose-related reductions in nonsense-mediated decay (NMD) transcripts in retinal tissue observed at four weeks and eight weeks;
- Significant increases in OPA1 protein in retinal tissue at four weeks that persisted at eight weeks in the mid- and high-dose groups;
- Dose-related increase in OPA1 protein in RGCs treated with STK-002 was detected using immunofluorescence;
- Concentrations of STK-002 in retinal tissue persisted at substantial levels at four weeks and at eight weeks in the mid- and high-dose groups; and
- Dose-related increases in STK-002 in RGCs were observed.
Details of Stoke’s presentations at the ARVO Annual Meeting:
Presentation Title: STK-002, an Antisense Oligonucleotide (ASO) for the Treatment of Autosomal Dominant Optic Atrophy (ADOA), is Taken Up by
Session: Gene therapy and other novel therapeutics in ophthalmic diseases 1
Presentation Number: 1111
In addition, a presentation of data from an in vitro ADOA model of OPA1 haploinsufficient RGCs was presented in a poster session today. In this study, haploinsufficient induced pluripotent stem cells (iPSCs) carrying OPA1 mutations were treated with STK-002 and showed a dose-responsive reduction of non-productive OPA1 mRNA and an increase in total OPA1 mRNA in total neurospheres. The results support the hypothesis that TANGO ASOs can potentially be used to treat ADOA caused by OPA1 haploinsufficiency and provide a useful in vitro model to evaluate TANGO ASOs.
Poster Title: Models of Autosomal Dominant Optic Atrophy (ADOA) using iPSCs and response to Targeted Augmentation of Nuclear Gene Output (TANGO) Antisense Oligonucleotides (ASOs) Treatment
Session: Animal models of human ocular disease
Poster Number: 1895 – A0041
The presentations at ARVO are now available online on the Investors & News section of Stoke’s website at https://investor.stoketherapeutics.com/events-and-presentations.
About Autosomal Dominant Optic Atrophy (ADOA)
Autosomal dominant optic atrophy (ADOA) is the most common inherited optic nerve disorder. 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. Roughly half of people with ADOA fail driving standards and up to 46% are registered as legally blind. ADOA is considered a haploinsufficiency disease, as most people living with ADOA have genetic mutations in the OPA1 gene that result in only half the necessary OPA1 protein being produced. More than 400 OPA1 mutations have been reported in people diagnosed with ADOA. Currently there is no approved treatment for people living with ADOA. ADOA affects approximately one in 30,000 people globally with a higher incidence in
STK-002 is a proprietary antisense oligonucleotide (ASO) in preclinical development for the treatment of Autosomal Dominant Optic Atrophy (ADOA). Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. 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 stop or slow vision loss in patients with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the Company’s preclinical data and study results regarding STK-002; the ability of STK-002 to treat the underlying causes of ADOA; the timing and expected progress of clinical trials, data readouts and presentations for STK-002 and the Company’s other product candidates; the timing or receipt of regulatory approvals; and the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. Statements including words such as “could,” “plan,” “will,” “continue,” “expect,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to: the ability of STK-002 to safely and effectively treat the underlying causes of ADOA; the Company’s ability to timely and successfully advance its preclinical studies, regulatory filings, clinical trials, data readouts and presentations related to STK-002 and its other product candidates; the Company’s ability to obtain regulatory approval for and to commercialize STK-002; the results of preclinical studies and early clinical trials not being necessarily predictive of future results; the Company’s ability to protect its intellectual property; the ability of TANGO to successfully design medicines to increase protein production and the expected benefits thereof; the direct and indirect impacts of the ongoing COVID-19 pandemic and its variants on the Company’s business; and other risks and uncertainties described under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended
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