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Introduction & Market Context
Stoke Therapeutics (NASDAQ:STOK) presented its second quarter 2025 business update on August 12, highlighting progress across its pipeline of RNA-based therapies for severe genetic diseases. The company’s stock closed at $13.16, up 2.81% for the day, with after-hours trading showing an additional 1.98% gain, reflecting positive investor sentiment following the presentation.
Stoke is developing precision medicines that address the underlying causes of severe genetic diseases by upregulating protein expression. Its lead program, zorevunersen for Dravet syndrome, has advanced to Phase 3 clinical trials, while its second program for Autosomal Dominant Optic Atrophy (ADOA) has entered Phase 1 testing.
Executive Summary
Interim CEO Ian F. Smith outlined four key pillars positioning Stoke for success: execution of the global Phase 3 EMPEROR study for zorevunersen, supportive long-term clinical data, platform expansion with a second program now in the clinic, and financial strength to deliver on its objectives.
As shown in the following strategic overview, the company is building on clinical progress while expanding its pipeline:
"We’ve reached a significant milestone with the first patient dosed in our EMPEROR Phase 3 study," Smith noted during the presentation. "Our three-year open label extension data continues to support the potential disease-modifying effects of zorevunersen, addressing not just seizures but also the cognitive and behavioral aspects of Dravet syndrome."
Strategic Initiatives: Zorevunersen for Dravet Syndrome
Dravet syndrome is a rare, genetic epilepsy characterized by frequent, prolonged seizures and significant developmental delays. While multiple medicines are available for seizure management, Stoke emphasized that no current treatments address the broader aspects of the disease, including cognitive and behavioral challenges.
The company’s Phase 1/2a studies of zorevunersen demonstrated substantial reductions in convulsive seizure frequency, with benefits sustained through three years of treatment in open label extension studies. The data showed not only seizure reduction but also improvements in cognition and behavior compared to natural history data.
The following graph illustrates the comparison between zorevunersen-treated patients and those from a natural history study, showing marked improvements across multiple domains of functioning:
The EMPEROR Phase 3 study is designed to assess the potential disease-modifying effects of zorevunersen. The trial will enroll approximately 170 patients aged 2-18 years at about 70 sites globally, with a primary endpoint measuring the percent change in major motor seizure frequency at 28 weeks. Key secondary endpoints include durability of effect at 52 weeks and improvements in behavior and cognition.
The study design includes an 8-week baseline period followed by a 52-week treatment period with a dosing regimen of two 70mg loading doses followed by two 45mg maintenance doses:
Barry Ticho, Chief Medical (TASE:BLWV) Officer, reported that pre-screening has already identified approximately 130 patients, with more than 10 clinical trial sites now initiated across the U.S., UK, and Japan. The first patient was dosed in August 2025, with data anticipated in the second half of 2027.
Long-Term Data Supports Disease-Modifying Potential
Kimberly Parkerson, SVP and Head of Neurology Clinical Development, presented 36-month data from ongoing open label extension studies, showing durable reductions in seizures on top of standard of care therapies:
Beyond seizure reduction, the company highlighted continued improvements in cognition and behavior through three years of treatment. The Vineland-3 assessment tool, which evaluates adaptive behavior across multiple domains, showed progressive improvements over time:
"These data are particularly encouraging because they suggest potential disease modification, not just symptomatic improvement," Parkerson explained. "The progressive nature of these improvements over 36 months supports our hypothesis that addressing the underlying cause of Dravet syndrome can lead to meaningful functional benefits."
Safety data from over 700 administered doses showed zorevunersen to be generally well-tolerated with long-term dosing. The most common treatment-related adverse events were CSF protein elevations, which occurred in 86% of patients in the OLE studies but were not associated with clinical manifestations in most cases.
Pipeline Expansion: STK-002 for ADOA
Stoke’s second program, STK-002 for Autosomal Dominant Optic Atrophy (ADOA), represents an expansion of the company’s RNA-based therapeutic approach to another genetic disease with high unmet need.
ADOA is a progressive vision disorder affecting approximately 13,000 people in the U.S., UK, EU-4, and Denmark. The disease is caused by mutations in the OPA1 gene that lead to haploinsufficiency, resulting in 50% OPA1 protein expression:
Preclinical data presented during the call showed promising results for STK-002, including dose-dependent increases in OPA1 protein expression in multiple animal models and improvements in mitochondrial and retinal function in a non-human primate model of ADOA:
Based on these encouraging preclinical results, Stoke has initiated a Phase 1 study of STK-002 in the UK. The open-label study will investigate safety, tolerability, and exposure of single ascending doses (0.1, 0.3, 0.5, and 0.7 mg/eye) administered via intravitreal injection in adult ADOA patients. The 48-week study will also assess changes in visual function, ocular structures, quality of life, and electroretinographic measures.
Forward-Looking Statements
Thomas Leggett, Chief Financial Officer, indicated that Stoke is well-funded with runway through its Phase 3 readout to mid-2028. The company’s financial strength is supported by its collaboration with Biogen (NASDAQ:BIIB), though specific financial details were not disclosed in the presentation.
The company highlighted recent key leadership hires and increased focus on Medical Affairs, Regulatory, and Commercial capabilities as it prepares for potential commercialization of zorevunersen, pending positive Phase 3 results.
In his closing remarks, Smith reiterated the company’s four strategic pillars and expressed confidence in Stoke’s ability to deliver on its mission of developing the first potential disease-modifying treatments for both Dravet syndrome and ADOA.
"With our first Phase 3 trial underway, long-term data supporting our approach, expansion of our platform to a second indication now in the clinic, and the financial strength to execute our plans, Stoke is well-positioned to create significant value for patients and shareholders," Smith concluded.
Full presentation:
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