Stoke Therapeutics Q3 Earnings Call Highlights

Key Points

• Stoke’s Phase III EMPEROR trial for zorevunersen in Dravet syndrome remains on track for a third-quarter 2027 data readout, with a potential U.S. regulatory submission later in 2027 and launch in early 2028. All 162 enrolled patients have passed week eight, and no discontinuations have been reported.
• The FDA agreed that Stoke can use a multicomponent Vineland-3 endpoint covering cognition and behavior in its planned NDA. The company does not currently expect an FDA advisory committee meeting and plans to begin submitting materials in the first half of 2027.
• Stoke ended the quarter with $358.8 million in cash, equivalents and marketable securities, which it expects—along with anticipated Biogen reimbursements and a potential milestone payment—to fund operations into early 2028. Its STK-002 Phase I trial for autosomal dominant optic atrophy is advancing, with initial higher-dose data expected in the first half of 2027.

Stoke Therapeutics NASDAQ: STOK said its Phase III EMPEROR trial of zorevunersen in Dravet syndrome is advancing toward a planned third-quarter 2027 data readout, while the company prepares for a potential U.S. regulatory submission later that year and a possible launch in early 2028.

The company also reported progress in its Phase I program for STK-002, an investigational treatment for autosomal dominant optic atrophy, or ADOA, and said its cash position is expected to fund operations into early 2028.

EMPEROR Trial Enrollment Advances

Chief Executive Officer Ian Smith said all 162 patients enrolled in the global EMPEROR study have passed the week-eight point and received either two loading doses of zorevunersen or sham treatment. The double-blind, sham-controlled study is being conducted in the United States, United Kingdom and Japan.

Approximately 110 patients have completed the week-28 visit, when the primary endpoint of change in major motor seizure frequency is measured, while about 20 patients have completed the 52-week treatment period. All patients completing the treatment period have entered the open-label extension, and the company reported no treatment discontinuations to date.

Chief Medical Officer Barry Ticho said the study originally targeted enrollment of 150 patients, based on an assumption that 128 patients would be evaluable after a projected 15% discontinuation rate. The company ultimately enrolled 162 patients and has not recorded any discontinuations.

To preserve study integrity, Stoke said it will not review or analyze trial data until all participants reach week 52. The primary endpoint is assessed at week 28, while secondary endpoints, including measures of cognition and behavior, are evaluated at week 52.

FDA Discussion Supports Multicomponent Endpoint

Stoke said a recent meeting with the Food and Drug Administration addressed the company’s planned new drug application, or NDA, for zorevunersen. A key outcome was the agency’s willingness to accept a multicomponent assessment of Vineland-3 data for evaluating a key secondary endpoint related to cognition and behavior.

The multicomponent assessment will combine four prespecified Vineland-3 subdomains: expressive communication, receptive communication, interpersonal relationships and personal skills. Ticho said the company will calculate treatment effects for each subdomain using a multivariate mixed model for repeated measures, then average the four scores into a single result.

Smith said the approach is intended to reflect the variability of Dravet syndrome, which can affect cognition and behavior differently across patients. He also said the assessment will not require a hierarchy among the four subdomains.

Based on an assumed 150 evaluable patients, Stoke said EMPEROR has 90% power to detect a 46% to 53% relative reduction in seizure frequency between treatment groups at two-sided significance levels of 0.05 to 0.01. For the Vineland-3 multicomponent endpoint, the company said the trial has 90% power to detect a difference of about 1.8 to 2.1 raw-score points.

Smith said Stoke expects to begin submitting NDA materials during the first half of 2027, with completion of the submission planned for the second half of the year. He said the company does not anticipate an FDA advisory committee meeting based on its recent agency interaction, although the agency did not make guarantees regarding a rolling review.

The company also asked the FDA whether long-term open-label extension data could be included in a potential product label. Smith said the agency characterized that question as a review issue. Stoke expects to have five years of clinical data by the time of its NDA filing.

Commercial and Patient-Access Preparation

Chief Patient Officer Jason Hoitt said Stoke estimates there are about 38,000 people with Dravet syndrome across the seven major markets included in the EMPEROR trial, including roughly 16,000 in the United States. The company estimates that approximately 6,000 U.S. patients are under age 25 and likely treated by pediatric providers, making them immediately addressable following a potential launch.

Hoitt said Stoke believes it knows where 80% of those 6,000 patients receive care, with about half of identified U.S. patients treated at the top 50 sites. All 50 sites have experience administering intrathecal medicines, and more than half have participated in a zorevunersen study, according to the company.

Stoke has added a field market-access team and deployed payer account personnel to begin educating insurers’ medical directors. The company is also developing a patient-support program and working with treatment centers on infrastructure, protocols and staffing for potential zorevunersen administration.

By year-end, Stoke plans to initiate two additional zorevunersen studies: one in adults intended to support access and reimbursement, and another in infants and toddlers. The primary objective of both studies will be to evaluate safety, and the company said they are not registrational studies.

STK-002 Program and Financial Position

Stoke’s STK-002 program targets ADOA, a rare inherited optic nerve disorder associated with progressive vision loss. The company said ADOA affects approximately 13,000 people in the United States, United Kingdom, EU4 and Denmark, and that about half of patients may progress to legal blindness. There are no approved treatments for the condition.

The Phase I OSPREY study is evaluating single ascending intravitreal doses of STK-002 in patients with ADOA in the U.K. and Europe. Stoke has completed dosing in the first two cohorts and is dosing the third cohort, with completion expected by year-end. Subject to safety assessments, the company expects to begin a fourth cohort in early 2027 and report initial safety and efficacy data from the higher-dose cohorts in the first half of 2027.

Chief Financial Officer Thomas Leggett said Stoke ended the third quarter with $358.8 million in cash, cash equivalents and marketable securities, excluding $3.2 million in restricted cash. Net loss for the three months ended Sept. 30 was $73.6 million, including $11 million of non-cash stock-based compensation expense.

Leggett said the company expects its cash, along with reimbursement from Biogen for zorevunersen-related expenses and a potential development milestone payment, to fund operations into early 2028.

About Stoke Therapeutics (NASDAQ:STOK)

Stoke Therapeutics, Inc is a clinical-stage biotechnology company focused on developing genetic medicines for severe diseases caused by insufficient protein production. The company uses its proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) platform to design antisense oligonucleotides that can increase the expression of specific genes and potentially address the underlying causes of genetic disorders.

Stoke's leading product candidate is STK-001, an investigational antisense oligonucleotide being developed for the treatment of Dravet syndrome, a severe genetic epilepsy most commonly associated with mutations in the SCN1A gene.

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