Stoke Therapeutics Presents Preclinical Data on the Biodistribution, Target Engagement and Safety of STK-001 in Non-Human Primates That Support the Planned Clinical Development of STK-001 for the Treatment of Dravet Syndrome
STK-001 showed distribution throughout the brain after a single intrathecal injection;
Safety findings showed STK-001 to be well-tolerated at both dose levels studied
IND submission on track for early 2020; Phase 1/2 study anticipated to start in 1H 2020
“The effects of Dravet syndrome go beyond seizures and often include cognitive regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. The disease is believed to affect multiple areas of the brain, with the cerebral cortex playing a particularly important role,” said
Dravet syndrome is a severe and progressive form of genetic epilepsy that affects approximately 35,000 people in
Stoke selected two dose levels of STK-001 for this non-GLP study in order to evaluate safety, brain biodistribution, target engagement and Nav1.1 protein expression. On day 1, treatment-naïve cynomolgus monkeys were administered a single, bolus intrathecal lumbar (IT-L) injection at one of two dose levels of STK-001. After dosing, the animals underwent standard clinical and neurological observation, and blood samples were collected. STK-001 concentration level, gene expression, and protein expression were assessed in the brain on day 3 and on day 29.
The following are highlights from today’s poster presentation.
- Brain tissue exposure to STK-001 was observed on day 3 and day 29. In the high dose group, exposure of STK-001 was observed in all brain regions examined, except pons and thalamus. STK-001 levels in cortical brain regions were generally higher than in deeper structures and were also increased from day 3 to day 29.
- Nav1.1 protein levels were observed to increase up to 3-fold in some regions of the cortex on day 29 in the high dose group. No or marginal changes in Nav1.1 protein levels were observed on day 29 in the low dose group, or on day 3 in either dose group.
- Significant target engagement (SCN1A expression) was observed on day 29 throughout the cortex and the limbic lobe in the high dose group. No or marginal change in SCN1A levels in brain tissues were observed at the low dose of STK-001, or on day 3 in either dose group.
- A favorable safety profile was demonstrated for STK-001 at both dose levels with no change in neurological or physical measures, even in animals that overexpressed Nav1.1 protein above wild type levels.
Stoke plans to submit an investigational new drug (IND) application to the
Details of today’s presentation are as follows:
Presentation Title: TANGO Oligonucleotides for the Treatment of Dravet Syndrome: Safety, Biodistribution and Pharmacology in the Non-Human Primate
Session Date & Time:
Session Title: Poster Session 2
Poster Number: 2.195
Data from preclinical studies of STK-001 in a Dravet syndrome mouse model were presented at
The posters presented at
STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the
About Dravet Syndrome
Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include cognitive regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome affects approximately 35,000 people in
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 ability of STK-001 to improve survival and reduce seizure frequency in mice, as well as its biodistribution, target engagement and ability to increase protein expression in non-human primates; our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production. Statements including words such as “plan,” “continue,” “expect,” 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 do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause our actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company’s ability to develop, obtain regulatory approval for and commercialize STK-001 and its future product candidates, the timing and results of preclinical studies and clinical trials, the company’s ability to protect intellectual property; and other risks set forth in our filings with the
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