Stoke Therapeutics' Earnings Call: Pre-NDA Timing and Phase III Data Claims Don't Match

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Date of Call: Aug 3, 2026

Guidance:

• Phase III Emperor study readout expected in Q3 2027.
• Rolling U.S. NDA submission expected to initiate in Q1 2027, with clinical data submission in Q3 2027.
• Pre-NDA meeting with FDA scheduled for early fall 2026.
• Pro forma cash position of approximately $420 million, expected to fund operations through potential U.S. launch in early 2028.
• Study in infants/toddlers under 24 months of age expected to initiate later in 2026.
• Adult study to expand label and access expected to initiate by end of 2026.

Business Commentary:

Progress in Phase III Clinical Trial:

• Stoke Therapeutics' Phase III Emperor study for Dravet syndrome has completed enrollment of 162 patients in just 10 months, with no treatment discontinuations to date.
• The study is on track for a data readout in the third quarter of 2027, with plans for a pre-NDA meeting with the FDA later this year.
• The rapid enrollment and lack of discontinuations are indicative of strong patient and physician enthusiasm for the potential disease-modifying therapy, Zoriva Nursu.

Long-term Safety and Efficacy Data:

• Longitudinal data from open-label extension studies show improvements in cognition and behavior, with statistically significant results maintained over four years of treatment.
• The data includes all patients from the initial Phase 1-2 studies, demonstrating consistent benefits across various dosing regimens.
• The positive long-term safety profile, with no new safety signals identified, supports the chronic administration of the therapy and reinforces confidence in the platform's potential.

Commercial Readiness and Market Potential:

• Stoke Therapeutics estimates there are approximately 38,000 patients with Dravet syndrome across major markets, with 16,000 in the U.S. alone.
• The company is preparing for a potential U.S. launch in early 2028, leveraging existing relationships with top treatment centers and experienced intrathecal administration capabilities.
• The focus on commercial readiness includes targeted disease awareness and educational efforts to increase diagnosis rates and support patient access.

Financial Position and Runway:

• Stoke Therapeutics ended the quarter with $354.3 million in cash, cash equivalents, and marketable securities, supplemented by an additional $65.7 million from an ATM program.
• The pro forma cash position is approximately $420 million, providing a financial runway through to a potential U.S. launch in early 2028.
• This strong financial position supports ongoing investment in clinical development and commercial preparations.

Expanding Pipeline and Research Efforts:

• Beyond Dravet syndrome, Stoke Therapeutics is advancing its pipeline with STK002 for Autosomal Dominant Optic Atrophy (ADOA) and exploring new targets in haploinsufficient diseases.
• The company recently strengthened its leadership team with the addition of a Chief Scientific Officer to guide platform expansion.
• These efforts reflect a strategic focus on leveraging the company's proprietary platform to address a range of severe genetic diseases.

Sentiment Analysis:

Overall Tone: Positive

• Management expressed confidence in the Phase III study progress and powering, citing 'no treatment discontinuations' and enrollment of 162 patients. They noted 'strength of our balance sheet' and 'continued positive feedback from payers and providers.' The tone emphasized 'executing quickly' and being 'well-supported' with 'pro forma cash' for a potential 2028 launch.

Q&A:

• Question from Andrew (Firm not specified): What should we be taking away from the various data points on study progress, and what are you hoping to get alignment on with the FDA regarding the Statistical Analysis Plan (SAP)?
  Response: Study is progressing well with 145 patients through week 8, 60 patients having completed week 28 (primary endpoint), and no discontinuations. The pre-NDA meeting will focus on the sequence of the rolling NDA submission, details of the SAP (including hierarchy of Vineland 3 subdomains), and the inclusion of long-term OLE data.

• Question from Alyssa Larios (Lyric Partners): What parts of the NDA do you expect to submit first and what will still be left?
  Response: Rolling NDA submission will start with the CMC package in Q1 2027 and conclude with clinical data in Q3 2027.

• Question from Pete Stavropoulos (Cantor): What gives you confidence that the one-year time point in Phase III is sufficient to see separation for secondary endpoints, and what are your plans for disease-modifying label claims and pricing?
  Response: Confidence is based on powering calculations (90%+ for p-value <0.01) and zero discontinuations. Market research indicates that payers and providers find the long-term OLE and Phase I-II data (demonstrating durable seizure reduction and cognitive/behavioral gains) to be the most compelling evidence for the label and value proposition.

• Question from Yaron (Firm not specified): How does the six-year OLE data synergize with Phase III, and what is your hierarchy of secondary endpoints?
  Response: The OLE data is synergistic, additive, and demonstrates durable benefit over five years. The primary secondary endpoint is continued seizure reduction, followed by Vineland domains (communication, receptive/expressive communication, and motor skills).

• Question from Laura Chico (Wedbush): How should we think about site capacity and logistics for a commercial launch, given most patients are at Centers of Excellence?
  Response: The top 50 sites have experience administering intrathecal therapies (like Spinraza) and have 20+ patients each, providing a strong, established infrastructure for efficient launch and site readiness.

• Question from Timon (Firm not specified): What specific components of the OLE data resonate most with HCPs and payers?
  Response: For HCPs, the most compelling data are long-term safety, durable seizure reduction, and gains in adaptive behavior/cognition (Vineland scores). For payers, the value driver is the additional seizure suppression on top of standard care and the broader impact on non-seizure manifestations of Dravet.

• Question from Kevin (Firm not specified): What is the trial design and timeline for the infant-toddler study and the adult study?
  Response: The infant-toddler study is required for a PIP in Europe and data will help expand the label. The adult study will begin later in 2026 to support access and reimbursement; design details will be provided at initiation.

• Question from Follow-up on market opportunity: What is the current diagnosis rate in the U.S., and what are appropriate drug comps?
  Response: Diagnosis is concentrated in pediatric patients, with about 6,000 under 25 being immediately addressable at launch. A DMT introduction is expected to increase genetic testing. Comparables include the SMA (Spinraza) and CF markets.

• Question from Adam (Firm not specified): When can we expect a candidate for the Syngap program to enter the clinic?
  Response: A development candidate is hoped to be selected in 2027, with clinical entry thereafter, as Syngap is a clinically important disease area.

• Question from Dalma (Firm not specified): On the ADOA program, how many patients were dosed in the first cohort, and what magnitude of change would be proof of concept?
  Response: The first cohort had three patients. Safety review approved escalation. Proof of concept could include improvements in visual acuity and mitochondrial function (SPF), with efficacy potentially seen in cohorts 3 or 4, leading to data readouts in H1 2027.

Contradiction Point 1

Timeline and Purpose of Pre-NDA Meeting with FDA

Contradiction on when the pre-NDA meeting will occur, impacting the timeline for regulatory alignment and NDA submission.

Andrew (Lyric Partners) - Andrew (Lyric Partners)

2026Q2: The upcoming pre-NDA meeting with the FDA in the second half of 2026 will focus on... - Ian Smith(CEO) and Dr. Barry Tico(CMO)

What are the key takeaways from the Phase III Emperor study data points and what alignment are you seeking with the FDA regarding the Statistical Analysis Plan (SAP)? - Andrew Tsai (Jefferies)

2026Q2: The pre-NDA meeting in early 4Q2026 will focus on... - Ian Smith(CEO) and Barry Ticho(CMO)

Contradiction Point 2

Readiness and Experience of Treatment Sites for Commercial Launch

Contradiction on the level of preparedness and capacity of the top treatment centers, affecting launch logistics and scalability.

Laura Chico (Wedbush) - Laura Chico (Wedbush)

2026Q2: The top 50 treatment sites... are experienced in administering intrathecal therapies... providing a significant logistical advantage. Most have protocols... setting the stage for an efficient launch. - Jason Hoyt(CPO)

What is the strategy for managing site capacity and logistics (e.g., procedure slots, imaging) for Zoriva Nurson's U.S. commercial launch, given patient concentration at centers of excellence? - Laura Chico (Wedbush)

2026Q2: The top 50 U.S. treatment centers... provide a robust foundation for capacity. There is also more work ahead on site readiness and qualification over the next year. - Jason Hoitt(CPO)

Contradiction Point 3

Timeline for Phase III Primary Endpoint Completion

Inconsistent statements about when the primary endpoint (week 28) was completed, affecting the timeline for data availability and regulatory discussions.

Andrew (Lyric Partners) - Andrew (Lyric Partners)

2026Q2: The study is progressing well with 145 patients through week 8, 60 patients have completed the week 28 visit (primary endpoint for seizure frequency), and no treatment discontinuations to date. - Ian Smith and Dr. Barry Tico

What are the key takeaways from the Phase III Emperor study data points and what alignment are you seeking with the FDA regarding the Statistical Analysis Plan (SAP)? - Sumant Kulkarni (Canaccord Genuity)

2026Q1: Key EMPEROR study numbers: 130 patients randomized (zorevunersen/sham); 91 have received two loading doses; 18 have completed the week-28 primary endpoint visit; no discontinuations to date. - Dr. Barry Ticho

Contradiction Point 4

Rolling NDA Submission Timeline and Content

Contradiction on the planned start date for the rolling NDA submission, impacting the regulatory submission schedule.

Alyssa Larios (Lyric Partners) - Alyssa Larios (Lyric Partners)

2026Q2: The rolling NDA submission will initiate in Q1 2027 with the CMC package... - Ian Smith

Which parts of the NDA are expected to be submitted first, and what remains outstanding? - Yaron Werber (TD Cowen)

2026Q1: The rolling submission is anticipated to start in Q1 2027, allowing the final submission (with week-52 data) around mid-2027... - Jason Hoitt

Contradiction Point 5

Strategy for FDA Regulatory Interaction and Data Submission

Contradiction on the company's regulatory strategy regarding the primary endpoint and label design, affecting the approach to FDA discussions and approval.

Andrew (Lyric Partners) - Andrew (Lyric Partners)

2026Q2: The hierarchical analysis of Vineland domains (with continued seizure reduction as the first secondary endpoint)... - Ian Smith and Dr. Barry Tico

What are the key takeaways from the Phase III Emperor study data and the goals for FDA alignment on the Statistical Analysis Plan (SAP)? - Laura Chico (Wedbush)

2025Q3: Stoke believes zorevunersen is a disease-modifying therapy... and aims for a label based on comprehensive disease-modifying data, including secondary endpoints like VABS-III. - Ian Smith(CEO)

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