Stoke Therapeutics, Inc. Common Stock 2026 Q2 Earnings Call

Good evening, and welcome to Stoke Therapeutics second quarter 2026 business update conference call. I'm Tommy Leggett, the Chief Financial Officer of Stoke Therapeutics. Joining me on today's call are Ian Smith, our Chief Executive Officer, Dr. Barry Ticho, Chief Medical Officer, and Jason Hoitt, Chief Patient Officer. As a reminder, today's webcast presentation is available in the investors section of our website. This webcast is being recorded and will be available for replay later this evening. Before we begin, please note that today's discussion includes forward-looking statements. These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially. Please refer to our filings with the SEC for additional information. On today's call, we will review recent progress across the breadth of our business. Ian will start with an overview and share an update on the ongoing phase III EMPEROR study.

This study is progressing nicely toward a data readout in the third quarter of 2027. Barry will then provide additional detail on EMPEROR and our longitudinal data set from our ongoing open label extension studies, also known as our OLEs. He will also review the advancement of other pipeline opportunities that we are progressing, including our investigational medicine for autosomal dominant optic atrophy, or ADOA. We'll then hear from Jason on our commercial planning activities to deliver zorevunersen to all patients who may benefit in the U.S. following a potential FDA approval by early 2028. I will review our financials and specifically the strength of our balance sheet, and then we will open for Q&A. I will now hand the call over to Ian.

Thank you, Tommy, and thank you to those joining us on the call tonight. Starting with our phase III EMPEROR study. The recent completion of enrollment of 162 patients in just 10 months speaks to the awareness and enthusiasm of zorevunersen and its potential to change the course of Dravet syndrome by addressing the underlying genetic cause of this disease. Patients in the study are advancing through key study milestones, and importantly, there have been no treatment discontinuations. We are now within a year of our phase III readout to data that would support the completion of our NDA. We continue our discussions with the FDA and have scheduled a pre-NDA meeting later this year as we prepare to initiate our rolling NDA submission in the first quarter of 2027.

The meeting will focus on further educating the agency on the long-term safety and efficacy of zorevunersen using prior and ongoing analyses from our phase I, II and OLE studies. We'll also cover the details of our NDA submission, including the data to be included, the statistical analysis plan, and the timing of each module. Beyond Dravet, we have a unique opportunity with our platform in additional disease areas. We continue to advance STK-002, our investigational medicine for ADOA. Our phase I study recently completed dosing of the first cohort of patients, and we have moved into a higher dose in a second cohort of patients. While continuing our work in SYNGAP1-related disorders, we are also expanding our early research efforts with new targets in haploinsufficient diseases, mainly focused in CNS, given our expertise in the field.

Consistent with our investment in other pipeline opportunities, in July, we strengthened our leadership team with the addition of Tom McCauley, our Chief Scientific Officer, who will help guide the next phase of platform expansion and translational research. From financial perspective, our business investment is well supported by our pro forma cash position of approximately $420 million, providing a runway through to potential U.S. launch of zorevunersen by early 2028. We have entered a period where execution is increasingly important, and we remain focused on delivering the data and completing the regulatory and commercial readiness activities necessary to bring zorevunersen to patients as quickly as possible. With that, I now pass you to Barry, who can provide more detail as to our progress.

Thank you, Ian. Tonight, I will start with an update on the progress with the EMPEROR study. EMPEROR is a global, double-blind, sham-controlled phase III study of zorevunersen in patients with Dravet syndrome. In June, we announced completion of enrollment of 162 patients into EMPEROR. This puts us on track for our phase III readout in the third quarter of 2027. Data from these patients are expected to be the final data necessary to complete our rolling U.S. NDA submission, which we expect to submit in the second half of next year. As Ian mentioned, the study is progressing well. To date, more than 140 patients are through week eight of the study and therefore have received either the two loading doses of 70 milligrams of zorevunersen or sham.

More than half of patients have only one dose left in the 52-week treatment period. Approximately 60 of these patients have also completed their week 28 visit The time point at which the primary endpoint of % change in major motor seizure frequency is measured.

The study will remain blinded through 52 weeks, given the key secondary endpoints measuring cognition and behavior will be assessed at that point in time. In a couple of weeks, the first patients in the study will reach that milestone and have the opportunity to progress into treatment extension beyond week 52. Thus far, no patients have discontinued treatment in EMPEROR. When we designed EMPEROR, we made several assumptions that are relevant when evaluating the study's statistical powering. EMPEROR was powered to detect statistically significant effects on the secondary endpoint, measuring improvements in cognition and behavior. This resulted in substantial powering for the primary endpoint. The study design assumed a certain % of patient discontinuation, and as previously mentioned, we have had no discontinuations to date.

Our enrollment target was at least 150 patients, and we ultimately enrolled 162 in our primary analysis population. All of this reinforces our confidence in the study powering and the overall likelihood of demonstrating statistically significant effects on the primary and key secondary endpoints. Beyond the 162 patients intended to support our NDA, an additional cohort of approximately 30 patients in Europe is expected to complete enrollment this month. Planning is also underway for a new study of zorevunersen in infants and toddlers under 24 months of age. We expect that study to initiate later this year to support our goal of enabling early intervention with this potentially disease-modifying therapy. Earlier this year, we presented data out to 4 years from our OLE study, which I'll briefly review this evening. I'll begin with our data on seizure frequency reduction.

Here we see 4 years of data in which all patients received treatment with zorevunersen. These effects are demonstrated on top of the standard of care anti-seizure medicine patients were already taking. These data include all patients across dose levels, including various levels of loading doses evaluated in the first year of treatment in the phase I/II study, as well as various levels of maintenance doses used in the OLE study. The orange line most closely reflects our phase III dose regimen. The blue line is patients who received a variety of doses during the phase I/II and OLE. By month 29, all of them had transitioned to receiving 45 milligrams every 4 months, which is consistent with the anticipated commercial regimen pending the results of EMPEROR. While durable seizure control is the most immediate and obvious clinical need, we know that Dravet syndrome is not only a seizure disorder.

It is a severe neurodevelopmental disease in which children develop normally till approximately 24 months of age, when they begin to stagnate in development with minimal improvements in skills and activities such as communication, interpersonal skills, and mobility. This means that regardless of chronological age, gains in cognition, behavior, and daily function are meaningful. To evaluate potential gains in cognition and behavior, we use Vineland-3, a standardized assessment of adaptive functioning. Here are the 4-year Vineland data from our ongoing OLE study. These data demonstrate statistically significant improvements in cognition and behavior each year through 4 years of treatment compared to the OLE baseline. Similar to the seizure data I just showed, these OLE data include patients across all dosing regimens evaluated in our phase I/II study, including loading doses that were lower than the two 70-milligram doses we are evaluating in our phase III study.

Importantly, all improvements in Vineland scores shown here are measured against patients' baseline scores when they entered the OLE study, and therefore do not capture any benefit that may have been observed during the earlier Phase I/II treatment period. Alongside these efficacy findings, we continue to build a long-term safety data set for zorevunersen. Of the 81 patients enrolled in our Phase I/IIa study, 93%, or 75 patients, continued treatment in the OLE study. Of those, 57 patients remain in these studies. More than 930 doses of zorevunersen have been administered to date, with some patients receiving treatment for more than five years. Overall, no new safety findings have emerged, and zorevunersen continues to be generally well-tolerated.

The Phase I/II and OLE safety and efficacy data provide a substantial data set that support the design of our Phase III EMPEROR study and also a detailed understanding of the benefits to patients and how this potential medicine could change the course of Dravet syndrome for patients and their families. These long-term longitudinal data, which include patients who have received up to 16 doses over a five-year period, offer insight into the ongoing benefits with chronic dosing. Analyses from this clinical data set have been well-received at major medical conferences and were published earlier this year in "The New England Journal of Medicine." Our educational efforts will continue throughout the rest of 2026 and into 2027 with new analyses, including effects on seizure severity, improvements in seizure freedom, and quality of life. We'll also continue to share these insights with the FDA.