Third Quarter 2026 Business and Financial Update - STOKE THERAPEUTICS INC

Financial Performance:

• Ended Q3 2026 with $358.8 million in cash, cash equivalents, and marketable securities (excluding $3.2 million restricted cash).
• Reported a net loss of $73.6 million for the three months ended September 30, 2026.
• Non-cash stock-based compensation expense was $11 million for the quarter.
• Current cash reserves, combined with anticipated Biogen reimbursement milestones and development payments, are projected to fund operations into early 2028.

Guidance and Future Outlook:

• Reiterated timeline for EMPRA Phase 3 data readout in Q3 2027 and planned NDA submission in the second half of 2027.
• Anticipates potential U.S. approval and commercial launch in early 2028.
• Plans to initiate rolling NDA data submissions to the FDA in the first half of 2027.
• Scheduled to begin dosing the fourth cohort of the STK002 Phase 1 Osprey study in early 2027.
• First half of 2027 expected to yield initial safety and efficacy data from STK002 cohorts three and four.
• Two additional Zoriva-Nursen clinical studies (adults and infants/toddlers) are targeted to begin by the end of 2026 to support safety and reimbursement.

Business Segments and Product Lines:

• Zoriva-Nursen (Dravet Syndrome): Approximately 110 of 162 enrolled patients completed the Week 28 visit (primary endpoint), and 20 completed Week 52; zero treatment discontinuations to date.
• STK002 (Autozomal Dominant Optic Atrophy/ADOA): Phase 1 Osprey study progressing; dosing underway in the third cohort with preclinical and early clinical data showing increased OPA1 protein expression and improved mitochondrial function.
• Commercial Readiness: Established field market access team, hired head of patient services, and deployed payer account teams; engaging with top 50 U.S. treatment centers to ensure infrastructure readiness for intrathecal delivery.

Market and Competitive Landscape:

• Estimated 38,000 Dravet syndrome patients across seven major markets (US, UK, EU4, Japan), with ~16,000 in the U.S. and ~6,000 under age 25 immediately addressable at launch.
• New patient diagnosis rates estimated at 500–600 annually due to increased genetic testing awareness.
• High concentration of patients at top 50 U.S. centers, all experienced in intrathecal administration; 80% of addressable patients currently identified.
• Growing stakeholder support via the American Epilepsy Society's Presidential Task Force on Disease Modifying Therapies, signaling a shift in treatment paradigms.

Risks and Challenges:

• Complex disease heterogeneity in Dravet syndrome requiring multi-component assessment to evaluate cognition and behavior changes effectively.
• Regulatory uncertainty in European markets regarding pricing and differential value assessments compared to the U.S.
• Need to secure broad label approval without upper age limits, supported by ongoing adult and infant studies.
• Competitive pressure to demonstrate disease-modifying benefits (cognition/behavior) which typically take longer to manifest than seizure frequency.

Management Commentary and Tone:

• Management expressed high confidence in the EMPRA study design, patient retention (no dropouts vs. 15% projected), and the multi-component statistical approach.
• Tone emphasized strong alignment with the FDA regarding the NDA plan and the inclusion of five-year long-term exposure data in the potential label.
• Leadership highlighted a proactive approach to commercial readiness, focusing on patient support programs and payer education to minimize launch delays.

Analyst Questions and Answers:

• Data Quality & Vineland Collection: Confirmed use of a trained central rater, consistent caregiver reporters, and daily internal review to ensure data uniformity; European submission will utilize a net treatment benefit approach for individual subdomains, while the U.S. uses the multi-component MC4 score.
• FDA Advisory Committee: No Advisory Committee meeting (AdCom) is anticipated for the U.S. submission.
• Statistical Methodology: The FDA agreed to the multi-component MC4 assessment (averaging four subdomains) to enhance statistical power and avoid hierarchical testing; MMRM models will be used to leverage longitudinal data, eliminating the need for strict hierarchy among subdomains.
• Clinical Significance: A score change of "0 to 1" on Vineland subdomains (e.g., a child never responding to their name to sometimes responding) is considered clinically meaningful; the study has 90% power to detect a 46–53% seizure reduction and 1.8–2.1 raw score point improvement in the MC4 score.
• STK002 Dosing: The program is moving into therapeutic dosing levels (0.3mg–0.5mg) in subsequent cohorts; no mandatory additional dose-ranging study is required before pivotal development, pending the first-half 2027 data readout.
• Financial Spend: Expected Q4 2026 and 2027 spend should be modeled similar to the Q3 run rate.

Other Key Points:

• The FDA confirmed that including five years of Open Label Extension (OLE) data in the label is a "review issue," supporting the totality of evidence argument.
• STK002 addresses haploinsufficiency in ADOA, a condition affecting ~13,000 patients in the U.S., UK, EU4, and Denmark, with no current approved treatments.
• Zoriva-Nursen's mechanism is designed to increase functional protein production to address the underlying genetic cause, distinguishing it from symptomatic anti-seizure medications.