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Image source: The Motley Fool. Monday, Aug. 3, 2026 at 4:30 p.m. ET Chief Financial Officer - Thomas Leggett Chief Executive Officer - Ian Smith Chief Medical Officer - Barry Ticho Chief Patient Officer - Jason Hoitt Need a quote from a Motley Fool analyst? Email [email protected] Operator: Hello, and welcome to the Stoke Therapeutics Second Quarter 2026 Business and Financial Update. [Operator Instructions] Be advised that today's conference is being recorded. It is now my pleasure to introduce CFO, Thomas Leggett. Thomas Leggett: Good evening, and welcome to Stoke Therapeutics Second Quarter 2026 Business Update Conference Call. I'm Thomas 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. Ian Smith: 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 1 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. We'll continue 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. And from a 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've entered a period where execution is increasingly important. 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. Barry Ticho: 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 submissions, 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 8 of the study and therefore have received either the 2 loading doses of 70 milligrams of zorevunersen or sham. More than half of patients have only 1 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 percent 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. First, 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. Second, the study design assumed a certain percentage of patient discontinuation. And as previously mentioned, we have had 0 discontinuations to date. Finally, 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 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 studies, as well as various levels of maintenance doses used in the OLE studies. 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 studies. 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 studies, including loading doses that were lower than the 2 70 milligram doses we are evaluating in our Phase III studies. Importantly, all improvements in Vineland scores shown here are measured against patient 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 dataset for zorevunersen. Of the 81 patients enrolled in our Phase I/IIa studies, 93% or 75 patients continued treatment in the OLE studies. 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 5 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 supports 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 5-year period, offer insight into the ongoing benefits with chronic dosing. Analyses from this clinical dataset 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. The data generated to date and successful advancement of zorevunersen in EMPEROR reinforce our belief in the potential of our platform to address the underlying cause of a number of severe genetic diseases. We are particularly focused on diseases caused by haploinsufficiency, where we believe we have a unique opportunity to use our proprietary scientific approach to restore protein expression from the healthy copy of a gene. In the near term, we are advancing STK-002, our investigational medicine for ADOA. ADOA is a progressive genetic disease that leads to degeneration of the optic nerve and loss of vision starting in the first decade of life. It is the most common inherited optic nerve disorder. The majority of cases are caused by mutations in one allele of the OPA1 gene, resulting in haploinsufficiency, or 50% of the OPA1 protein. There are currently no approved treatments for ADOA. STK-002 is designed to increase OPA1 protein expression with the aim to improve vision in people with ADOA. Phase I dose escalation study is ongoing in the U.K. and Europe and recently completed dosing of the first cohort of 3 patients. Dosing for our second cohort is scheduled to begin this week, with the third and fourth dose cohorts to follow, subject to ongoing safety assessments. We anticipate early safety and efficacy results in the first half of next year to guide our next steps for development. We are encouraged by our preclinical data, as well as emerging data from the field, demonstrating that upregulation of OPA1 proteins has disease-modifying potential. We look forward to sharing additional updates as the program advances. With that, I will turn the call over to Jason. Jason Hoitt: Thank you, Barry. Today, I'll focus on 3 areas: the market opportunity in Dravet syndrome, how we think about label and access, and the progress we're making toward a potential U.S. launch. I'll start with the patient population. There are an estimated 38,000 patients with Dravet syndrome across the 7 major markets where we're running the EMPEROR study: the U.S., U.K., EU4, and Japan, including approximately 16,000 in the U.S. alone. Our estimates are based on an epidemiology analysis that scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years that was then adjusted for Dravet specific mortality. In the U.S. the Dravet population highly concentrated around centers of excellence and other key treatment centers. Approximately 50% of identified U.S. patients are cared for by the top 50 sites that are experienced in administering intrathecal medicines. Half of them are already participating in a zorevunersen trial. This provides a strong foundation for early adoption and allows us the ability to maximize this opportunity with a lean commercial infrastructure, including approximately 25 sales representatives who will build upon our longstanding relationships with treating physicians established by our medical affairs teams. We're confident we know where 70% to 80% of the patients 25 and younger are being cared for today. Out of the estimated 16,000 total U.S. patients, we estimate 6,000 are under the age of 25 and likely under the care of a pediatric provider. These are patients who would be immediately addressable at the time of potential U.S. launch. Pediatric neurologists and epileptologists tend to develop strong and lasting relationships with patients and families and therefore continue to care for them well into early adulthood. As such, this group of clinicians follow the field closely and are typically the most well-informed about the disease and current treatment options. In addition, an ICD-10 code was established in 2020 and is used to track confirmed Dravet diagnoses. This data provides support for our assumptions as well as insight into where patients are in their diagnosis and treatment journey, along with the providers who care for them. We believe diagnosis rates will increase over time as zorevunersen and other genetically targeted treatments continue to advance. We will continue to invest in targeted disease awareness and educational efforts to emphasize the importance of genetic testing to confirm a Dravet diagnosis. Looking ahead to our NDA submission, product labeling and patient access, we continue to believe that the totality of evidence generated for zorevunersen supports a differentiated value proposition in Dravet syndrome. At the time of our NDA submission, we expect to have approximately 6 years of safety and efficacy data available from our Phase I/II and OLE studies, providing insight into the durability of treatment effects and the potential for disease modification over time. We intend to incorporate these data into our NDA submission for inclusion in the label. The FDA guidance is clear that in addition to pivotal study data, clinical study data that provide important information about a drug's effectiveness and that would be useful to practitioners in their clinical decision making should be included in the label. We believe that the longitudinal data from our OLEs are relevant within that framework, and we know from market research that payers and healthcare providers already consider these data to be the most compelling evidence that we may have at the time of potential approval. As Ian mentioned, we have a pre-NDA meeting with the FDA later this year. We plan to initiate the NDA in the first quarter of 2027, beginning with our chemistry, manufacturing and controls module. We recently completed commercial scale manufacturing validation for both drug substance and drug product and are currently finalizing product specifications. We continue to expect that if approved, zorevunersen would be granted a broad label for the treatment of Dravet syndrome consistent with our breakthrough therapy designation. This broad label, combined with the existing concentration of Dravet providers and well-established infrastructure for administering intrathecal therapies, positions us for a smooth and efficient adoption with a lean commercial infrastructure at the time of launch. While we remain focused on accelerating access in our commercial territories in North America, our partners at Biogen are focused on expediting access in countries around the rest of the world. In addition, we plan to initiate a study of zorevunersen in the adult population by the end of this year. This study is intended to expand clinician conviction for zorevunersen in adults and support access among adults living with Dravet. Taken together, the strength of the clinical package, the continued positive feedback from payers and providers, and the progress we're making across commercial readiness activities give us confidence in our preparations for a potential U.S. launch in early 2028. With that, I'll turn the call over to Thomas. Thomas Leggett: Thank you, Jason. I will remind you that full financial results can be found in our 10-Q. Today, I'll focus on the strength of our balance sheet position. We ended the quarter with $354.3 million in cash, cash equivalents and marketable securities. Shortly after the close of the quarter, we raised an additional $65.7 million in net proceeds through our ATM program, selling approximately 2.1 million shares of common stock to a high-quality, long-only fundamental investor. This resulted in a pro forma cash position of approximately $420 million. Along with the reimbursement we received from Biogen for zorevunersen-related expenses and a potential development milestone payment, we expect our cash position to fund our operations through a potential U.S. launch in early 2028. In terms of our priorities, we continue to invest in advancing our Phase III study and preparing the organization for potential U.S. commercialization while progressing our pipeline and maintaining a strong financial position. Thank you, and I will now ask for the line to be open for Q&A. Operator: [Operator Instructions] One moment, please. Our first question comes from the line of Andrew Tsai with Jefferies. Lin Tsai: The first one is, you guys have provided a lot of nice numbers this quarter where patients are exactly in the EMPEROR study. So, maybe bigger picture, what should we be taking away on these various data points as we track study progress and await the Phase III timelines? And then secondly, it sounds like you have this pre-NDA meeting with the FDA in the second half, in part to talk about the SAP plan for EMPEROR. So, may I ask what you guys are hoping to get alignment on? Is it kind of confirming the hierarchy of the 5 subdomains of Vineland-3, maybe confirming which ones need to stat sig for you to file? Just a little bit more color would be helpful. Ian Smith: Andrew, this is Ian, and thanks for the question. It's good to chat to you again. We did provide a lot of, as you put it, nice numbers on the call. I'm going to ask Barry to reiterate those. There were a lot of them, but there are metrics internally of how we measure the trial every single week. And they're very important to us in terms of measuring the progress of the trial. So, Barry, why don't you provide those numbers again, and then I'll take the discussion on the NDA. Barry Ticho: Sure, thanks, Ian and thanks, Andrew, for the question. So the study is progressing quite well, and patients are going through trial milestones. Again, as we said, enrollment is complete and we enrolled 162 patients in the study. Of those, 145 patients are through their week 8, which means they've received 2 loading doses of the 70-milligram or sham treatment. About half of the patients have gone through week 24, and so they have only 1 dose left in their 52-week treatment period. Importantly, 60 patients have completed their week 28 visit, and that means that they have hit the time point of the primary endpoint, which is seizure frequency. And we're also very pleased that very soon, patients will start to be reaching their week 52 endpoint, which is the important part of the treatment period study. Again, no patients dropped out of the study, which is important. And this progress gives us a lot of confidence in EMPEROR to date and is consistent with the data that we've had from the OLE studies as well as our Phase I/II data. Ian Smith: Thank you for that, Barry. Yes, I'll just reiterate the data that we're seeing in terms of no discontinuations with -- given the large number of progress of these patients through the study, continues to emphasize that this medicine is generally well tolerated. That's also consistent with the 5-year data we have in Phase I/II and the OLE, where we've dosed between 70 and 80 patients and continue to show that the medicine is generally well tolerated. To your second question, Andrew, about the pre-NDA meeting, I'll kind of answer it in a bigger way and tell you all about the meeting. So firstly, the meeting will occur in early fall, so not too far away. This is an ordinary course when you're at the stage of Phase III development, when you're in registration studies. And -- so we're going down to the FDA with 3 objectives or 3 topics. The first being to discuss the sequence of submission of data for our rolling submission. We anticipate initiating a rolling submission in Q1 of 2027, and that would start with the CMC package followed by the preclinical data, and then closing out that rolling submission in the third quarter of 2027 with the clinical data. So that's the first piece. Second, as you point out it is the SAP, the statistical analysis plan. Again, this is normal practice. Before you get to the end of your Phase III and certainly during your Phase III, you don't want to leave it too late. You need to go down the line on the details of the SAP. The way that our protocol has currently been constructed is that our primary endpoint is not in discussion in terms of the detail, but we will talk about the secondary endpoints. And the way that the study protocol has been described so far is that we will look at the secondary endpoints in either a hierarchical analysis, and that means taking individual Vineland domains in a hierarchical manner, or we will look at it on a composite basis where you combine those individual Vineland domains. The study is designed, and we've communicated that it is designed in terms of collecting both sets of data. What we want to do is we want to go to the FDA and discuss exactly how they would like us to present that data. I will just point out that the first, in terms of the hierarchical secondary endpoints is actually continued seizure reduction, I'll just point that out. And then it goes into the Vineland domains. And then the third topic is the OLE data. As you know, each year we’ve gone down to the FDA and discussed the OLE data. Last year we were discussing with the FDA in the latter part of 2025. This year we have the access to the 4-year OLE data being updated from last year's 3-year. And we're going to discuss that again. Why are we doing that? Because it's the importance of that data to show this is a drug that is a chronically administered drug, and this data has now been administered in patients for up to a period of 5 years. And we've been able to measure both durable seizure reduction and the continued improvement each year of Vineland scores, which is just a measure of skill and task acquisition of these children that unfortunately have a, you could call it, a Dravet age of approximately 24 months, but we're potentially providing them task acquisition and skill acquisition that then is more typical, more neurotypical of the children that have a greater age and are healthy. And so the importance of that data, obviously we just discussed before, is it does help us understand the effectiveness of the medicine as Jason has described in his remarks, and we continue to be part of the NDA submission when we file our clinical data around the middle of next year. Operator: Our next question comes from the line of Alyssa Larios with Leerink Partners. Alyssa Larios: This is Alyssa on for Marc Goodman. I was just wondering if you could walk us through what parts of the NDA you expect to submit starting in Q1 and what will still be left once the EMPEROR data come in. Barry Ticho: Alyssa, sorry, you didn't come through. So you're asking about the sequence of the NDA submission? Ian Smith: You just didn't come through, Alyssa, there's some background noise. So as I just mentioned, we anticipate starting our rolling submission in Q1 of 2027. That will initiate with the filing of our CMC package. Jason had a number of comments in his prepared remarks where we are -- we've made great progress in that area, including quality, and so that would be the initiation of the submission in Q1 of 2027. And the final part of the submission will be clinical data, which will occur in Q3 of 2027, and that data will conclude with the week 52 secondary endpoint measurements to complete that submission in Q3 of 2027. Operator: Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Pete Stavropoulos: First question that I have is, going back to the Vineland-3 subdomains for the Phase III readout, what gives you confidence that 1-year time point is sufficient to sort of see separation between the active arm and sham for the secondaries? And the second question I have is, one point of discussion has been potential pricing of zorevunersen if approved, specifically around data, what data may be needed to translate to a label that suggests or states disease modification that will ultimately impact pricing. And so can you just provide your thoughts and plan and possible scenarios for getting disease-modifying outcomes into the label? And if achieved, how should we be thinking about pricing? Ian Smith: Thanks, Pete. Number of questions there. Maybe start with asking Barry to help you understand the powering of the study. I'll then talk about the data we have that informed us and support our confidence that achieving both primary and secondary endpoints. And I'll ask Jason to comment on the work we've been doing, which is extensive, to understand the value of the medicine, aka pricing. Barry Ticho: Yes, thanks. So, the powering of the study was based on our Phase I/II and OLE data. And the confidence that we have in showing a difference from sham based on the fact that the secondary endpoints, the Vineland endpoints, are powered at 90% or greater, greater than 90% to show a 0.01 or less p-value. And so those results were based on 150 patients enrolling in the study. And as we mentioned, we now have 162. So that increases our confidence that we'll be able to show a significant difference from sham in the study. Ian Smith: Yes. Thanks, Barry. I'll just pick up from where Barry mentioned. And so -- and I would say increasing confidence with 162 versus the initial powering calculations of 150. What I would also add is, in that 150 that was the initial powering assumption, it did also assume a 15% discontinuation rate in that Phase III. As Barry mentioned in his prepared remarks, we have seen 0 discontinuations to date in the study. So if you work the analysis back it was powered, as Barry says, to a 90% confidence level for a p-value of 0.01 to the secondary endpoints from approximately 125 to 130 evaluable patients. At this point in time, we have 162 enrolled still in the study and 0 discontinuations. Then the data that we used to power the study, frankly, was data from the Phase I/II and the OLE data. But notably, you asked about the confidence, Pete, and this time last year, we provided data to help understand the impact of a regimen that had similar dosing to that in our Phase III study. That data was provided at EPNS last year. I believe we showed it on our Q2 conference call. If not, there was a disclosure that was very close to August of 2025. And that data showed that in Vineland scores for the 5 key domains that we've been discussing, showed Vineland scores of between 8 and 11 in terms of Vineland scores of each of those domains. And I would just point out that our Phase III study secondaries are powered for a 2 to 3 point delta in Vineland scores. So we have high confidence of hitting these secondary endpoints, given the data that we have, both from the Phase I/II and the OLEs, and in particular, that dosing regimen that is consistent with the Phase III dosing regimen of 2 70-milligram doses and 2 45-milligram doses, which accumulates to approximately 230-milligrams of dosing. Jason Hoitt: Yes, and then on your last question, Pete, around pricing and the implications around pricing, it's timely that you asked the question because just earlier this year, we conducted some pretty extensive market research across our constituent audiences, including healthcare providers, payers, caregivers, et cetera. Specific to the healthcare providers and payers, we wanted to understand the potential implications of different label scenarios and how those audiences think about the data that are included in the label versus other data that may be available in the public domain, published, presented at scientific conferences, et cetera. And I think the long and short of it is that the data to be included in the label are going to be most important for promotional purposes, right? So how our commercial teams are able to educate healthcare providers on the efficacy and safety of zorevunersen at the time of approval. And when we asked those 2 audiences, both payers and healthcare providers, talking about the different potential scenarios, what could be and would be the most compelling pieces of evidence that they would have at their disposal to drive, in the case of healthcare providers, prescribing for their patients, and in the case of payers, medical policies that support reimbursement for a broad population of patients with Dravet syndrome. Across the board, the 5-year open-label extension data and Phase I/II data that we anticipate having at the time of approval were the most compelling piece of evidence. So when you think about payers, it's less important that it's included in the label and more important that the data are disclosed and peer-reviewed. So payers are going to look at the totality of the evidence. They'll look at published manuscripts, data presented at scientific congresses, the Phase I/II and OLE data that we've generated to date, right? 4 years of OLE data plus the Phase I/II. And I think it's not all anchored to the secondary endpoints. One of the things payers told us loud and clear is that the additional seizure reductions that you're seeing on top of the best standard of care medicine will drive significant value. But with that being said, they will look at the totality of the evidence. They'll look at the data that are published in, for example, the New England Journal, right? That comes with a significant amount of credibility, and so we're feeling really confident in how we think about the value proposition and value story for zorevunersen, and that it really should command rare genetically targeted disease-modifying pricing potential consistent with what we've been talking about over the last few months. So hopefully that answers your question a little bit, Pete. Operator: Our next question comes from the line of Yaron Werber with TD Securities. Yaron Werber: Congrats on really terrific progress. Maybe I have a couple of questions. The first one is, given that you're going to have 6-year data from the OLE, which potentially can be label-enabling, how does that sort of jibe with the Phase III data? Can they be sort of synergistic? Do you need to hit all the same points in the Phase III that you showed in the Phase I/II? I mean, you noted to us obviously that the delta that you're looking for is a lot smaller and you're obviously very overpowered. And then secondly, I know you don't know exactly how you're going to rank order hierarchically yet in the SAP, the secondary endpoint, but maybe from you, based on your data, what is sort of your wishlist? Which endpoints are the most important? Ian Smith: Yaron, thank you for the question. As I mentioned in my earlier comments, we're heading to the FDA to discuss the pre-NDA, and to have a pre-NDA discussion, one of those topics is the -- will be the 6-year data or the 5-year OLE data. You asked whether it's synergistic. Absolutely, yes, it is synergistic. It is also additive. The importance of that data is that it demonstrates how the medicine is benefiting these patients as well as safety, but is benefiting these patients over a chronic period. This is a chronic disease and our medicine is a chronically dosed medicine. And so the OLE data allows us to understand the benefits these patients are gathering with seizure reductions being durable through a 5-year period and also to see these cognition behavioral gains that they're having over a 5-year period. So it is absolutely consistent and additive and synergistic to how we think about the Phase III and will be supplementing the Phase III data in our submission. That's why we continue to discuss it with the FDA. So it's really important, and as Jason says, the OLE data is also important in terms of how we want educate payers, they look at the totality of the data. But I'll also say prescribing physicians, a really important piece upon approval of this medicine, will be having physicians understand how to use the medicine but what benefits it provides to patients beyond the 1-year registration trial and those clinical endpoints. So we're in great shape with that data and as you said, Yaron, we'll have 6 years of data by the time that we start our NDA submission of that clinical data package. You asked about the importance of the secondaries and the hierarchy. We have, at this point in time, we look at the hierarchy of endpoints, number one, in terms of the primary secondary endpoint is actually continued seizure reduction. But once you get beyond there, you get into the Vineland points. But we've included communication, receptive and expressive communication as being the key measures in terms of the hierarchy. That's on the basis of physician and caregiver feedback, and we're fortunate that's where we're seeing benefit through our OLE data as well. And just to give you an idea, because when we talk about Vineland as a measurement tool of cognition and behavioral benefits, what that actually means is these children that unfortunately stagnate at the age of approximately 24 months don't acquire other skills while they chronologically age. But we appear to be providing benefit where we're giving them function and giving them skill. And in the communication area, for example, we appear to be helping these young children who can barely talk and have a minimal number of words they can use; we're providing the ability to many more words, to actually use sentences, and that's a progression they wouldn't otherwise see. We're also seeing them receiving communication, which allows them to respond and respond to their parents as a real-world example. And then when you go on further and look at some of the motor skill acquisition, you're seeing children that improve their motor skills and that includes non-ambulatory, becoming more ambulatory, frankly. And this is data that's been collected from our OLE study. And we've shared that, well, it's been shared with videos that are in the New England Journal of Medicine, so have that validation and credibility. So that's what Vineland means. And it is for us now to turn these Vineland scores into what real-world skill and task acquisition is for a Dravet child that otherwise would stagnate at the unfortunate age of 24 months. And we want to provide them skill and acquisition based on the use of our medicine. Barry Ticho: I might just add, Yaron. This is Barry. So despite the wishlist that we have, the powering of the study for the key secondary endpoint is for each of the individual Vineland subdomains. So we power to the one that we think may even be the least likely to achieve, but each one of those have their own high degree of power. Operator: Our next question comes from the line of Laura Chico with Wedbush. Laura Chico: Maybe just one for Jason on commercial. You previously indicated most U.S. Dravet cases are managed at centers of excellence. How should we be thinking about site capacity to treat this intrathecal ASO program? And I guess I'm thinking a little bit more about logistical constraints like procedure slots and imaging. How do you think about site capacity and the impact on a commercial zorevunersen launch? We obviously saw this was important for drugs like SPINRAZA. I'm just kind of trying to understand how things might have changed in the landscape. Jason Hoitt: It's a great question, Laura. I think, we provided some additional details here this afternoon around specifics for the top 50 sites, for example. So, if you think about those top 50 sites, all of them have 20 or more patients that are under their care, but all 50 of those sites also have experience administering intrathecal therapies, most of them SPINRAZA. And so, given the efficiency that they've developed administering other intrathecal products and their familiarity with the procedures and process that goes into it, we feel like they are really set up incredibly well to handle the capacity that comes through at the time of the potential approval, which we expect to be robust, if based on nothing else, based on the speed with which we recruited the EMPEROR study, but it's also consistent with what we hear in market research. So we still have more work to do around site readiness and site qualification over the course of the next year or so, but going in, we're definitely benefiting from the fact that there are other intrathecally administered antisense oligonucleotides available in the commercial context and that institutions have protocols already in place with how they're administering those therapies, which gives us a huge advantage going into a launch like this. Operator: Our next question comes from the line of Sumant Kulkarni with Canaccord Genuity. Sumant Kulkarni: Nice to see the progress. On slide 11 in your presentation accompanying this update, you mentioned that HCPs and payers indicate that OLE data may be the most compelling data at the time of approval. You alluded to this a little bit and we understand reduction in seizure frequency over and top of standard of care and totality of evidence matters, but what specific components of the OLE data resonate most and does the relative importance of the components of the OLE data vary for HCPs and payers or are those factions looking at them largely in the same way? Ian Smith: Sumant, thanks for that question. Obviously, Jason's going to take this question, but I just want to reiterate what Jason's about to tell you about the importance of that data is, yes, it's our belief, but this is feedback from prescribers and payers. It's what they're telling us. It's not what we are telling you. It's actually what the payers and the prescribers are telling us because we've gone out and as you appropriately should be doing at this stage of drugs development is you should be doing diligence with your payers and your prescribers and helping them understand the medicine. But Jason? Jason Hoitt: Yes. It's a great question, Sumant. Thank you for it. You know, when we, and I'll take those 2 audiences in sequential order there. So starting with the healthcare providers, I think it goes back to when you ask healthcare providers and caregivers specifically, what are the greatest unmet needs that exist in Dravet today. First and foremost, the number one that you hear is persistent seizure burden. The fact that very few patients ever reach seizure freedom is number one. And I think that from a caregiver perspective, relates back to, watching your child undergo a seizure, for example, right? But not far behind the persistent seizure burden is the lack of efficacy across the non-seizure manifestations of the syndrome and the lack of any targeted medicines that address the underlying genetic cause. And so when we talk to healthcare providers and they talk about what's most compelling to them, obviously the long-term data are the most compelling because as a clinician, they're sitting across from a patient where they're thinking about prescribing a chronic lifelong treatment, they want to understand what the implications are of administering this medicine to these patients over a long period of time. And so I think they're reassured by the long-term safety profile now going out 4 years of OLE plus the Phase I/II, they're reassured by the persistent reductions in seizures that they're seeing, the durability of that seizure response. And they're certainly reassured by the fact that you see the consistent gains in adaptive behavior and the neurocognitive endpoints as measured by the Vineland Adaptive Behavior Scale. And then in addition to that, it's quality of life matters, right? As you think about what matters to families, the ability for a child to continue to -- or a child to be able to communicate with their family, the ability to, for example, feed themselves, all of those little activities of daily living and acquired skills, as Ian mentioned, really matter a lot. And then when you think from a payer perspective, payers matter less -- payers care less about, for example, the nomenclature associated with disease modification. What they care about more is, is this new treatment offering something that what I currently have at my disposal for my members isn't? And so it's what we're doing in the non-seizure manifestations of Dravet syndrome above and beyond the seizure suppression. So they're seeing the additional seizure suppression on top of the best standard of care as being a real value driver. But above and beyond that, the fact that we're affecting other elements or other manifestations of the syndrome really go a long way with payers in driving that value proposition associated. Operator: Our next question comes from the line of Kevin Strang with Goldman Sachs. Kevin Strang: Just a quick one on, you mentioned a study for infants and toddlers under 24 months of age as well as generating new data in adults. I just wanted to ask about those 2 bookends, anything on trial design, potential timelines for both of those, and then for adults specifically, is there any data that you can leverage from your OLE in terms of patients that have crossed over into adulthood? Ian Smith: Yes, thanks, Kevin, and appreciate the recent initiation and also the data you sent to us this week about some analysis you've done at the market. So, first of all, the infant-toddler study is part of the requirement for a PIP in Europe, so we're running that study there. It really is as straightforward as that, although the data will help us potentially expand the label and treat even younger patients. And obviously with the genetic medicine, the earlier you can treat a patient, the more potential you have to put them back on a more neurotypical pathway as well as prevent those seizures. So it is a very important study to get to these Dravet children as early as possible. For the adults, it's a different rationale. The adults, we anticipate that on successful data and approval that our label would be for 2 years and older, and therefore we will have access to be able to have prescriptions to adults. What the adult study will do, though, it will help us understand the benefit for adults and help provide access and reimbursement for those adult patients. And you are correct. Our studies have been run so far for ages 2 through 18 years of age. And the OLE does have patients that have progressed, that started in their late teens and have progressed into their early 20s now. And we continue to track that data, and that data continues to show seizure reduction, a durable seizure reduction, and cognition and benefit from the first start of dosing when measured to their baseline when they were in their teens. And our own principle on this is, given that the root cause of Dravet is the lack of normal expression of NaV1.1, whereas we upregulate NaV1.1 protein, and therefore there should be no difference in providing benefit to a, let's say a 15-year-old versus a 21-year-old. And so we'll use all that data. But we will also run an adult study that begins later this year. You also asked as far as the design of those studies, they'll initiate later this year. As they initiate, we'll provide you study design at that time. Operator: Our next question comes from the line of Joseph Stringer with Needham & Company. Joseph Stringer: Just a follow-up on the market opportunity in Dravet syndrome. You estimate the prevalence in the U.S. is around 16,000. What do you estimate the current diagnosis rate is in the U.S.? And if there is a disease-modifying therapy available, such as zorevunersen, how significantly do you think the diagnosis rates could improve in the U.S.? And maybe as a follow-up question, I guess, what are the most appropriate drug comps that we should think about that have a similar setup to what there is for Dravet syndrome now, just multiple approved drugs on the market for several years but no disease-modifying therapy available. Jason Hoitt: Yes, so thanks for that, Joey. So maybe taking the first part of your question of the 16,000. When we look at claims data, we have a pretty good idea where about up to 80% of the 25 and younger patients are being cared for today. I would say that the diagnostic -- the genetic testing status in the U.S. has really grown dramatically over the course of the last 5 to 10 years. And so I would say that pediatric epileptologists, pediatric neurologists are doing a really nice job at diagnosing pediatric patients even earlier. But the gap -- there is a gap that still remains for the older patients. And so the disproportionate, I would say majority of the diagnosed patients today are the diagnosed patients that are 25 and younger, of whom we expect there are about 6,000 that will be immediately addressable at the time of a potential approval. That's based on both epi and what we're seeing in claims data, so if you look at total unique claims across all ages, you get pretty close to that 6,000 number in the U.S. But then when you break it down and you apply machine learning where you're looking at that peri-diagnostic period, looking at concomitant meds, concomitant procedures, CPT codes that are commonly used for Dravet patients and apply that to the total claims universe, that's how we get to knowing where approximately 80% of the patients are being cared for. But not surprisingly, one of our focal points right now is enhancing and increasing genetic confirmation of diagnoses in that, young adult into adult cohort of patients. With that being said, we feel like the DMT introduction with the potential approval of zorevunersen will dramatically increase the volume of genetic testing in the U.S. And we've actually asked that question to healthcare providers and healthcare providers themselves anticipate that genetic testing will increase 85% to 90% compared to today with the introduction of the disease-modifying treatment. So, the foundation is there. Our hope is to be able to drive those earlier diagnoses and in the case of the adult patients intervention before approval with additional diagnoses and genetic testing. And then from a comps perspective in terms of -- Joey, from a comps perspective with I think, SPINRAZA is a, the SMA market is a good comp. I think potentially the CF market is a good comp where you had symptomatic treatments available before the introduction of the first disease modifiers. Operator: Our next question comes from the line of Jessica Fye with JPMorgan. Adam Ferrari: This is Adam on for Jess. I really just want to talk about the SYNGAP program and just curious on timelines here. When can we expect a candidate to maybe enter the clinic? Ian Smith: Adam, thank you for joining the call. So I'll start with, SYNGAP remains a very important disease area for us. Just why? Because there's a lot of closeness of SYNGAP to Dravet in terms of being a neurodevelopment disease. Our platform that upregulates the effective gene to create protein in these patients is applicable to Dravet, as we talked about today. But it also goes to SYNGAP, and so SYNGAP becomes a very important area that we are focused on. We currently have 5 potential drug candidates that we're studying pre-clinically. We're working through our animal models. And in 2027, we hope that we will pick a development candidate to move then towards the clinic. But I want to reiterate that it's a really important disease area for us to continue our efforts. Now we have success and using Dravet as a proof of principle that our platform can work in these kind of disease areas. And so we will continue our efforts there to do the best for the patients. Operator: Our next question comes from the line of Delma Caiati, with Guggenheim. Delma Caiati: So on the ADOA program, the Sentinel cohort dosing is now complete. Can you give us any color on how many patients were dosed and at what dose level? And what did the Sentinel safety review show that supported the decision to escalate? And then for the readout in the first half of '27, what magnitude of change would you consider as proof of concept threshold? Ian Smith: So Delma, I'm going to have Barry summarize the program more holistically to help you understand the decision we made to go into the clinic, which was based on pre-clinical data, obviously. But then where we are in advancing a dose-escalating study where we are already into the increased doses. So Barry, please. Barry Ticho: Yes, thanks. And thanks for the question, Delma. So, just as a reminder, ADOA is due to a haploinsufficiency for half the normal amount of OPA1 protein, which is required for mitochondrial function. And we do have preclinical data in an NHP that has a genetic mutation that's similar to what patients have and has a similar phenotype to patients. And there when we administered 002 to those animals, they showed an improvement in their mitochondrial function, as well as an improvement in the function of the optic nerve. So that gave us a high degree of confidence moving forward into the clinic as well as other data that has come in the field. So the study is a typical dose escalation study, a single ascending dose study. And the first cohort had 3 patients in it. The Safety Monitoring Committee reviewed those data and are approving the escalation to the next dosing level. We have right now 4 dosing levels that are planned. And each of those are being reviewed for safety on a variety of levels after the injection. And we'll also be looking for potential improvement in vision because since we are improving the mitochondrial function in the patients, we expect that the retinal ganglion cells that are important for vision will be improving in their function as well, and that will allow for better visual acuity as well as improvement in the measure of mitochondrial function, which is what we call the FPF. Those data we anticipate being able to discuss next year. Ian Smith: Delma, I would just point out that as we progress through these 4 cohorts of increased dosing, we anticipate, based on our preclinical work, that we may start to see efficacy in cohort 3 or 4, and that's why Barry is referring to readouts, data readouts that would be in the first half of 2027. Operator: And our next question and last question comes from the line of Rudy Li with Wolfe Research. Guofang Li: As we finish enrollment of the Phase III trial, can you maybe provide more color on the patient population, baseline characteristics as expected, any notable difference versus the Phase I/II trial? Ian Smith: So the patient population for the EMPEROR Phase III study is consistent with the patients that came into the Phase I/II and progressed into the OLE study. And just to ensure that we had an 8-week screen period that required certain baseline characteristics to be tested through that 8-week screen period before they were allowed into the Phase III EMPEROR study. Characteristics, obviously, age, had to be screened for the SCN1A depletion gene and also a certain number of seizures, and so there is a similarity and a consistency between the Phase I/II OLE patients and those that are in our Phase III. Operator: I'll now hand the call back over to CEO, Ian Smith, for closing remarks. Ian Smith: Yes, thank you. I just want to say thank you for taking the time out to join us this evening. We look forward to talking to many of you throughout this week and probably next week and continue to update on the progress of the company. Thank you for your time this evening. Operator: Ladies and gentlemen, thank you for participating. This does conclude today's program, and you may now disconnect. Before you buy stock in Stoke Therapeutics, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Stoke Therapeutics wasn’t one of them. The 10 stocks that made the cut are built for long-term growth and could produce monster returns in the coming years. 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As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Stoke Therapeutics (STOK) Q2 2026 Earnings Call Transcript was originally published by The Motley Fool

Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Management attributes the rapid 10-month enrollment of 162 patients in the Phase III EMPEROR study to high clinical enthusiasm for a therapy addressing the underlying genetic cause of Dravet syndrome. The study is progressing well and is tracking toward a data readout in the third quarter of 2027. with zero patient discontinuations to date, which management views as a strong indicator of the drug's long-term tolerability. Performance is bolstered by longitudinal data showing that patients on chronic treatment for up to five years continue to see durable seizure reduction and statistically significant gains in cognition and behavior. Strategic positioning focuses on haploinsufficiency, using Dravet syndrome as a proof-of-concept for a platform that upregulates protein expression from healthy gene copies. The company is transitioning from a research-focused entity to a commercially-ready organization, evidenced by the completion of commercial-scale manufacturing validation. Management emphasizes that Dravet syndrome is a neurodevelopmental disorder, not just a seizure disorder, necessitating a treatment that addresses cognitive stagnation occurring around 24 months of age. A rolling NDA submission is scheduled to initiate in Q1 2027, starting with the CMC module and concluding with clinical data in Q3 2027. Management assumes a potential U.S. launch by early 2028, supported by a pro forma cash runway of approximately $420 million that extends through the launch period. The Phase III study is significantly overpowered (90% at p-value 0.01) for secondary endpoints, assuming a 15% dropout rate that has not yet materialized. Future growth initiatives include expanding the addressable market by initiating studies for infants under 24 months and adult populations by the end of 2026. The pipeline is expected to reach a key milestone in the first half of 2027 with early safety and efficacy results from the STK-002 program for ADOA. The company strengthened its pro forma cash position to $420 million via a $65.7 million ATM raise from a long-only fundamental investor post-quarter end. Management highlighted the addition of Tom McCauley as Chief Scientific Officer to lead the next phase of platform expansion into new CNS targets. Commercial infrastructure is planned to be lean, utilizing approximately 25 sales representatives to target the 50 sites that manage 50% of identified U.S. patients. A potential development milestone payment from partner Biogen is factored into the long-term cash runway projections. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here. Management aims to align with the FDA on whether secondary Vineland-3 endpoints will be analyzed via a hierarchical structure or a composite basis. The meeting will also focus on integrating 5-year longitudinal OLE data into the clinical package to demonstrate chronic effectiveness. Management believes the totality of evidence, including peer-reviewed OLE data, supports pricing consistent with rare, genetically targeted disease-modifying therapies. Payers have indicated that long-term data on non-seizure manifestations (cognition/behavior) are the most compelling drivers for reimbursement policy. Management noted that the top 50 treatment sites already have experience with intrathecal ASOs like SPINRAZA, benefiting from the efficiency and familiarity institutions have developed with administering other intrathecal products. Half of these high-volume sites are already participating in zorevunersen clinical trials, providing a built-in foundation for rapid commercial adoption. While 6,000 pediatric patients are immediately addressable, management expects genetic testing rates to increase 85% to 90% following the introduction of a disease-modifying treatment. The planned adult study is strategically designed to secure reimbursement and clinician conviction for patients over age 18, despite an expected broad label.

This article first appeared on GuruFocus. Cash Position: Ended the quarter with $354.3 million in cash, cash equivalents, and marketable securities. Pro Forma Cash: Approximately $420 million after raising $65.7 million in net proceeds from an ATM program. ATM Program: Sold approximately 2.1 million shares of common stock. Financial Runway: Cash position expected to fund operations through a potential US launch in early 2028. Warning! GuruFocus has detected 5 Warning Signs with STOK. Is STOK fairly valued? Test your thesis with our free DCF calculator. Release Date: August 03, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Stoke Therapeutics Inc (NASDAQ:STOK) completed enrollment of 162 patients in the Phase 3 EMPEROR study in just 10 months, with no treatment discontinuations to date, indicating strong patient and physician interest and a well-tolerated profile. The company has a robust financial position with a pro forma cash balance of approximately $420 million, providing a runway through a potential US launch in early 2028. Long-term data from the Phase 1/2 and open-label extension (OLE) studies show durable seizure reduction and statistically significant improvements in cognition and behavior (Vineland-3 scores) over four years, with no new safety findings. Stoke Therapeutics Inc (NASDAQ:STOK) is advancing its pipeline, including STK-002 for ADOA, which has completed dosing of the first cohort and is progressing to higher doses, with early results expected in the first half of 2027. The company has a clear regulatory path, with a pre-NDA meeting scheduled for late 2026 and a rolling NDA submission planned to begin in Q1 2027, supported by a broad label expectation and commercial readiness activities. Commercial planning is well underway, with a lean infrastructure of ~25 sales reps targeting a concentrated US patient population, and market research indicates that payers and healthcare providers view the OLE data as the most compelling evidence for the drug's value. The Phase 3 EMPEROR study is still blinded, and the primary endpoint data (percent change in major motor seizure frequency) will not be available until Q3 2027, leaving significant clinical and regulatory uncertainty. The company faces potential delays or challenges in the NDA submission process, as the pre-NDA meeting with the FDA will need to align on the statistical analysis plan, including the hierarchy of secondary endpoints, which could impact the approval timeline. Stoke Therapeutics Inc (NASDAQ:STOK) has not yet demonstrated efficacy in the Phase 3 trial, and the success of the program relies on replicating the strong OLE data, which may not be achieved in a controlled setting. The company's cash runway is dependent on potential milestone payments from Biogen and successful execution of its ATM program, which may not be sufficient if development costs increase or timelines slip. The ADOA program is at an early stage, with only three patients dosed in the first cohort, and there is no guarantee that higher doses will be safe or that efficacy will be observed, as the company anticipates potential efficacy only in later cohorts. The market opportunity for Dravet syndrome is limited to a relatively small patient population (estimated 16,000 in the US), and the company faces competition from existing symptomatic treatments and potential future therapies, which could impact adoption and pricing. Q: What should we take away from the various data points provided on patient progress in the Phase 3 EMPEROR study, and what are you hoping to get alignment on at the pre-NDA meeting with the FDA?A: Ian Smith (CEO) and Barry Ticho (CMO) highlighted that enrollment is complete with 162 patients, 145 are through week 8, about half are through week 24, and 60 patients have completed the week 28 primary endpoint visit. Crucially, there have been no treatment discontinuations. Regarding the pre-NDA meeting, Ian Smith (CEO) explained it will cover three topics: the sequence of the rolling NDA submission (starting with CMC in Q1 2027), the statistical analysis plan (SAP) for secondary endpointsspecifically whether Vineland domains will be analyzed hierarchically or as a compositeand the long-term OLE data to demonstrate durability of effect and safety. Q: What gives you confidence that the one-year time point is sufficient to see separation on the Vineland-3 secondary endpoints, and what data may be needed to translate to a label that suggests disease modification for pricing purposes?A: Barry Ticho (CMO) stated the study is powered at 90% or greater to show a p-value of 0.01 or less for the secondary Vineland endpoints, based on 150 patients, and the enrollment of 162 increases confidence. Ian Smith (CEO) added that the study assumed a 15% discontinuation rate, but zero discontinuations have been observed, further strengthening the powering. He noted the Phase 3 is powered for a 2-3 point delta in Vineland scores, while data from a similar dosing regimen showed improvements of 8-11 points. Jason Hoitt (Chief Patient Officer) explained that market research shows payers and HCPs consider the long-term OLE data the most compelling evidence, regardless of label inclusion, and that the totality of evidence, including additional seizure reductions on top of standard of care, will drive a rare genetically targeted disease-modifying pricing potential. Q: Given you will have six years of OLE data, how does that synergize with the Phase 3 data, and what is your "wish list" for the hierarchy of secondary endpoints?A: Ian Smith (CEO) confirmed the OLE data is synergistic and additive to the Phase 3 data, demonstrating durable seizure reduction and cognitive/behavioral gains over a chronic period. He explained the hierarchy of secondary endpoints begins with continued seizure reduction, followed by Vineland domains, with communication (receptive and expressive) being the key measure based on physician and caregiver feedback. He emphasized that Vineland scores translate to real-world skill acquisition, such as children gaining the ability to use more words or sentences, which they would not otherwise achieve. Barry Ticho (CMO) added that the study is powered for each individual subdomain, including the one least likely to achieve significance. Q: How should we think about site capacity to treat this intrathecal ASO program commercially, given logistical constraints like procedure slots and imaging?A: Jason Hoitt (Chief Patient Officer) noted that all top 50 sites caring for Dravet patients have experience administering intrathecal therapies, most commonly Spinraza. This existing infrastructure and familiarity with procedures gives the company a significant advantage for launch. He acknowledged there is still work to be done on site readiness and qualification over the next year, but the established protocols for other intrathecal ASOs position them well to handle the expected robust demand. Q: What specific components of the OLE data resonate most with HCPs and payers, and does the relative importance vary between these groups?A: Jason Hoitt (Chief Patient Officer) explained that for healthcare providers, the most compelling aspects are the long-term safety profile, durable seizure reductions, and consistent gains in adaptive behavior and neurocognitive endpoints (Vineland). Providers are also reassured by improvements in quality of life, such as communication and daily living skills. For payers, the focus is less on nomenclature like "disease modification" and more on what the treatment offers beyond current options. Payers value the additional seizure suppression on top of standard of care and the impact on non-seizure manifestations of Dravet syndrome, which drives their value proposition. Q: Can you walk us through what parts of the NDA you expect to submit starting in Q1 and what will be left for when the EMPEROR data comes in?A: Ian Smith (CEO) clarified that the rolling NDA submission will begin in Q1 2027 with the CMC (Chemistry, Manufacturing, and Controls) package. The final part of the submission will be the clinical data, which will occur in Q3 2027, concluding with the week 52 secondary endpoint measurements from the EMPEROR study. Q: What is the current diagnosis rate for Dravet syndrome in the US, and how significantly could diagnosis rates improve with a disease-modifying therapy available?A: Jason Hoitt (Chief Patient Officer) stated that genetic testing has grown dramatically over the last 5-10 years, and pediatric epileptologists are diagnosing patients earlier. However, a gap remains for older patients. He estimated there are about 6,000 patients aged 25 and younger who are immediately addressable at launch, and the company knows where 70-80% of these patients are cared for. He noted that healthcare providers anticipate genetic testing will increase by 85-90% with the introduction of a disease-modifying treatment, which will help drive earlier diagnoses and address the adult patient gap. Q: What are the timelines for the SYNGAP1 program, and when can we expect a candidate to enter the clinic?A: Ian Smith (CEO) confirmed SYNGAP1 remains a very important disease area due to its similarity to Dravet as a neurodevelopmental disease. The company currently has five potential drug candidates in preclinical studies. They hope to select a development candidate in 2027 to move toward the clinic, leveraging the success of Dravet as a proof of principle for their platform. Q: On the ADOA program, can you provide color on the sentinel cohort dosing, the safety review, and what would be considered a proof of concept threshold for the readout in the first half of 2027?A: Barry Ticho (CMO) explained that the first cohort of three patients has completed dosing, and the safety monitoring committee approved escalation to the next dose level. The study is a single ascending dose study with four planned dose levels. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Interested in Stoke Therapeutics, Inc.? Here are five stocks we like better. EMPEROR remains on schedule: Stoke completed enrollment ahead of plan with 162 Dravet syndrome patients, and expects primary data in Q3 2027. The company plans to begin a rolling U.S. NDA in Q1 2027 and potentially launch zorevunersen in early 2028 if approved. Encouraging long-term data and commercial readiness: Open-label studies showed durable seizure reductions and improvements in cognition and behavior through four years, with no new safety findings. Stoke has also completed commercial-scale manufacturing validation and estimates its pro forma cash of approximately $420 million can fund operations through a potential launch. Pipeline expansion continues: STK-002 advanced to a higher-dose cohort in its Phase I study for autosomal dominant optic atrophy, with early results expected in the first half of 2027. Stoke is also evaluating five potential candidates for SYNGAP1-related disorders and expects to select a development candidate in 2027. Stoke Therapeutics (NASDAQ:STOK) said its Phase III EMPEROR study of zorevunersen in patients with Dravet syndrome remains on track for a data readout in the third quarter of 2027, following completion of enrollment ahead of the company’s planned rolling new drug application submission. The global, double-blind, sham-controlled study enrolled 162 patients in 10 months, exceeding the company’s target of at least 150 participants. Chief Executive Officer Ian Smith said the enrollment pace reflected awareness of the investigational treatment and interest in its potential to address the genetic cause of Dravet syndrome. → Lost in Space: Why Aerospace Valuations Are Plummeting Right Now Stoke plans to begin a rolling U.S. new drug application, or NDA, submission in the first quarter of 2027, starting with its chemistry, manufacturing and controls package. The clinical-data portion of the submission is expected in the third quarter of 2027 after the EMPEROR study’s 52-week assessments are completed. The company expects a potential U.S. launch in early 2028 if the product is approved. Chief Medical Officer Dr. Barry Ticho said more than 140 EMPEROR participants had passed the week-eight milestone and received either two 70-milligram loading doses of zorevunersen or sham treatment. More than half of enrolled patients had only one dose remaining in the 52-week treatment period, while about 60 participants had completed their week-28 visit. → MarketBeat Week in Review – 07/27- 07/31 The study’s primary endpoint is the percentage change in major motor seizure frequency at week 28. Key secondary endpoints assessing cognition and behavior will be measured at week 52, and the trial will remain blinded through that point. “Thus far, no patients have discontinued treatment in EMPEROR,” Ticho said. He added that the company’s statistical assumptions had included patient discontinuations and a smaller enrollment population than ultimately enrolled, factors management said reinforced its confidence in the study’s statistical powering. → GE HealthCare Stock Climbs on Vital Diagnostics Demand Stoke plans to meet with the FDA in the fourth quarter in a pre-NDA meeting. Smith said discussions are expected to include the sequencing of the rolling application, the study’s statistical analysis plan and the company’s long-term open-label extension data. The company expects to discuss whether secondary endpoints should be analyzed hierarchically or through a composite analysis of Vineland-3 adaptive behavior domains. Beyond the pivotal population, Stoke expects an additional European cohort of about 30 patients to complete enrollment in August. It also plans to begin a study in infants and toddlers younger than 24 months later this year, intended to support earlier intervention. A separate adult study is also expected to begin by year-end. Stoke highlighted data from its ongoing open-label extension studies, in which patients have received zorevunersen on top of standard anti-seizure medicines. Ticho said the data showed durable seizure reductions through four years, along with statistically significant improvements in cognition and behavior, as measured by Vineland-3, in each year through four years compared with open-label extension baseline. The company said more than 930 doses have been administered across its clinical programs, with certain patients treated for more than five years. Of the 81 patients enrolled in the Phase I/IIa study, 75 entered the open-label extension and 57 remain in the studies. Ticho said no new safety findings had emerged and zorevunersen continued to be generally well tolerated. Chief Patient Officer Jason Hoitt said the company estimates there are approximately 38,000 people with Dravet syndrome across the seven major markets included in the EMPEROR program, including an estimated 16,000 patients in the U.S. Stoke estimates roughly 6,000 U.S. patients are younger than 25 and likely under pediatric care, making them immediately addressable at a potential launch. Hoitt said about half of identified U.S. patients are treated at the top 50 sites, all of which have experience administering intrathecal medicines. Half of those sites are participating in a zorevunersen study. Stoke expects to use a commercial organization of approximately 25 sales representatives if zorevunersen is approved. The company recently completed commercial-scale manufacturing validation for both drug substance and drug product and is finalizing product specifications. Hoitt said Stoke continues to expect a broad Dravet syndrome label if approved, consistent with the therapy’s breakthrough designation. Stoke is also advancing STK-002, an investigational treatment for autosomal dominant optic atrophy, or ADOA, a genetic disorder involving optic nerve degeneration and progressive vision loss. The company said there are currently no approved treatments for ADOA. The Phase I dose-escalation study in the U.K. and Europe completed dosing in its first cohort of three patients. A safety monitoring committee cleared the program to proceed to a second, higher-dose cohort, with third and fourth cohorts planned subject to continuing safety reviews. Stoke expects early safety and efficacy results in the first half of 2027. In addition, Smith said Stoke is continuing preclinical work in SYNGAP1-related disorders, where it has five potential drug candidates under evaluation. The company expects to select a development candidate in 2027. Stoke also appointed Tom McCauley as chief scientific officer in July to support platform expansion and translational research. Chief Financial Officer Tommy Leggett said Stoke ended the second quarter with $354.3 million in cash, cash equivalents and marketable securities. After the quarter ended, the company raised $65.7 million in net proceeds through its at-the-market program by selling about 2.1 million common shares. That financing brought Stoke’s pro forma cash position to approximately $420 million. Leggett said that, together with reimbursement from Biogen for zorevunersen-related expenses and a potential development milestone payment, the company expects its cash to fund operations through a potential U.S. launch of zorevunersen in early 2028. Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biopharmaceutical company focused on developing genetic medicines to upregulate protein production for the treatment of rare neuromuscular and neurological disorders. Founded in 2014, the company applies its proprietary Targeted Augmentation of Nuclear Gene Output (TANGO™) platform to design antisense oligonucleotides that selectively modulate RNA splicing and enhance expression of functional proteins. The company's lead program, STK-001, is an antisense oligonucleotide therapy designed to increase production of the sodium channel protein SCN1A and is currently in clinical development for Dravet syndrome, a severe childhood-onset epilepsy. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Stoke Therapeutics Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for August 2026.

– Phase 3 EMPEROR study of zorevunersen in Dravet syndrome: Enrollment of 162 patients complete with data readout anticipated in Q3 2027 – – Pre-NDA meeting with FDA scheduled for H2 2026; rolling U.S. NDA submission planned to initiate in Q1 2027 – – Phase 1 OSPREY study of STK-002 in patients with ADOA: Dosing complete in sentinel cohort; dose escalation continuing and initial data anticipated in H1 2027 – – $420M in cash, cash equivalents and marketable securities based on $354.3M as of June 30, 2026 and $65.7M from a subsequent ATM sale; expected to fund operations through to potential U.S. commercialization of zorevunersen in early 2028 – – Webcast and conference call for analysts and investors at 4:30PM Eastern Time today – BEDFORD, Mass., August 03, 2026--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK) is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine and has a lead investigational medicine, zorevunersen, in development as a first-in-class potential disease-modifying treatment for Dravet syndrome. The Company today reported financial results for the second quarter ended June 30, 2026, and provided business updates including progress of the global Phase 3 EMPEROR study, preparation for a rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) and the advancement of STK-002 as a potential treatment for Autosomal Dominant Optic Atrophy (ADOA). Stoke will participate in a pre-NDA meeting with the FDA during the second half of 2026 as the Company prepares to initiate the planned rolling NDA submission for zorevunersen in the first quarter of 2027. With the June 2026 completion of enrollment of 162 patients into EMPEROR, a Phase 3 readout is anticipated in the third quarter of 2027. These data are expected to complete the rolling U.S. NDA submission in the second half of 2027. Beyond zorevunersen, dose escalation is underway in the Phase 1 OSPREY study of STK-002 in patients with ADOA, the most common inherited optic nerve disorder. Safety and efficacy data are anticipated in the first half of 2027. "We have made significant progress across our business this year, including the rapid enrollment of 162 patients into the Phase 3 EMPEROR study and progression of these patients through key study milestones with the first patients now approaching the end of the 52-week treatment period," said Ian F. Smith, Chief Executive Officer and Director of Stoke Therapeutics. "With no treatment discontinuations to date in EMPEROR, and supportive four-year safety and efficacy data from the ongoing open-label extension studies, we have confidence in the potential of zorevunersen to change the course of Dravet syndrome. We look forward to our upcoming pre-NDA meeting with the FDA to align on the overall data package content and timing, as well as the statistical analysis plan, as we prepare to initiate our rolling U.S. NDA submission in the first quarter of 2027." Mr. Smith continued, "Beyond Dravet syndrome, we are advancing our pipeline. Dose escalation continues in our Phase 1 study of STK-002 in patients with ADOA and initial data are anticipated in the first half of 2027 to guide future clinical development. We are also expanding our early research efforts to identify new haploinsufficient disease targets, and we recently strengthened our leadership team with the addition of Tom McCauley as Chief Scientific Officer to help guide this next phase of platform expansion and translational research. In parallel we continue to enhance our commercial capabilities, enabled by our strong financial position of approximately $420 million that will take us through to a potential U.S. launch of zorevunersen by early 2028 and support the Company’s next phase of growth." Program Highlights Dravet syndrome (zorevunersen) Pivotal Phase 3 EMPEROR study progress: Continuing awareness of Dravet syndrome and appreciation for zorevunersen with 5 years of clinical data: Pipeline beyond zorevunersen The Phase 1 OSPREY study of STK-002 for the treatment of ADOA is continuing through dose escalation cohorts. All eight planned clinical trial sites are now active in the UK, Germany, Denmark, Italy and Austria, and dosing of the first cohort of patients (n=3) is complete with no serious or severe safety events observed to date. Dosing of the second cohort is expected to begin in August 2026. Subject to ongoing safety assessments, dosing in the third and fourth dose cohorts are expected to follow with a readout of safety and efficacy results anticipated in the first half of 2027. Lead optimization is underway to identify a clinical candidate for the treatment of SYNGAP1-related disorders. SYNGAP1-related disorders are severe and rare neurodevelopmental diseases. Stoke is expanding its early research efforts with new targets in haploinsufficient diseases, primarily focused on central nervous system (CNS) diseases. Thomas McCauley, Ph.D., joined Stoke as Chief Scientific Officer in July to support this pipeline growth, leveraging the Company’s proprietary RNA medicines platform to advance its pipeline of potential treatments for severe genetic diseases. Second quarter 2026 financial results The Company has $420.0 million in cash, cash equivalents and marketable securities based on $354.3 million as of June 30, 2026 and $65.7 million in net proceeds generated from an ATM sale to a single investor after June 30, 2026. These funds are expected to support operations through to potential U.S. commercialization of zorevunersen in early 2028. Revenue recognized for the three months ended June 30, 2026, was $9.3 million, a decrease from $13.8 million for the same period in 2025. Revenue is generated from satisfying contractual obligations of the collaboration and licensing agreements with Acadia and Biogen. Net loss for the three months ended June 30, 2026, was $61.6 million (including non-cash stock-based compensation expense of $10.8 million), or $0.93 per share, compared to a net loss of $23.5 million (including non-cash stock-based compensation expense of $7.6 million), or $0.40 per share, for the same period in 2025. Research and development expenses for the three months ended June 30, 2026, were $49.5 million, compared to $25.9 million for the same period in 2025. The increase was driven by increased activities and personnel expenses to support the advancement of zorevunersen. Sales, general and administrative expenses for the three months ended June 30, 2026, increased to $25.3 million from $15.3 million for the same period in 2025. The increase was driven by growth in personnel and launch readiness expenses. Year-to-Date 2026 Financial Results Revenue recognized for the six months ended June 30, 2026, was $15.6 million, a decrease from $172.4 million for the same period in 2025. The decrease in revenue is primarily driven by the recognition of $150.8 million related to the Biogen IP license performance obligation during the six months ended June 30, 2025. Net loss for the six months ended June 30, 2026, was $111.6 million (including non-cash stock-based compensation expense of $19.6 million), or $1.73 per share, compared to a net income of $89.4 million (including non-cash stock-based compensation expense of $14.4 million), or $1.50 per diluted share, for the same period in 2025. Research and development expenses for the six months ended June 30, 2026, were $89.2 million, compared to $58.5 million for the same period in 2025. The increase was driven by increased activities and personnel expenses to support the advancement of zorevunersen. Sales, general and administrative expenses for the six months ended June 30, 2026, increased to $45.2 million from $29.9 million for the same period in 2025. The increase was driven by growth in personnel and launch readiness expenses. Stoke Webcast and Conference Call for Analysts and InvestorsStoke management will host a webcast and conference call for analysts and investors on Monday, August 3, 2026, at 4:30PM Eastern Time. The webcast will be available on the Investors & News section of Stoke’s website at https://investor.stoketherapeutics.com/. Research analysts who plan to join the call and participate in the Q&A session may register here to receive the dial-in details and a unique PIN. All other participants are invited to access the listen-only webcast by clicking here. A replay of the webcast will be archived and available for at least 90 days following the event. About Dravet SyndromeDravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. Even when treated with the best available anti-seizure medicines (ASMs), up to 57 percent of patients with Dravet syndrome do not achieve ≥50 percent reduction in seizure frequency. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP; up to 20 percent of children and adolescents with Dravet syndrome die before adulthood due to SUDEP, prolonged seizures, seizure-related accidents or infections 1. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan 2. There are no approved disease-modifying therapies for people living with Dravet syndrome. About ZorevunersenZorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the unaffected (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function in the SCN1A gene, and China’s Center for Drug Evaluation has granted zorevunersen Breakthrough Therapy Designation. Stoke has a strategic collaboration with Biogen (Nasdaq: BIIB) to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights. Zorevunersen is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory authority. About the Phase 1/2a and Open-Label Extension StudiesTwo Phase 1/2a open-label, multicenter studies evaluated the effects of zorevunersen in patients with highly refractory Dravet syndrome ages 2 to 18 years (N=81). Primary endpoints were the safety profile, plasma pharmacokinetics (PK) and exposure in cerebrospinal fluid (CSF) of single and multiple doses of zorevunersen. Secondary endpoints included percentage change from baseline in major motor seizure frequency, overall clinical status (a measure of patients’ overall functioning) and quality of life. The ADMIRAL Phase 1/2a study included an exploratory endpoint to evaluate changes in neurodevelopmental status (cognition & behavior) as measured by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). The Phase 1/2a studies were completed in November 2023. Following treatment in the Phase 1/2a studies, eligible patients continued treatment with zorevunersen every four months in one of two OLEs. There was at least a 6-month gap between the last dose administered in the Phase 1/2a studies and the first dose administered in the OLEs. The primary endpoints are the safety profile of multiple doses of zorevunersen. Secondary endpoints include PK parameters, percentage change from baseline in major motor seizure frequency, change in overall clinical status, and change from baseline in quality of life. Exploratory endpoints include changes in neurodevelopment status as measured by Vineland-3. The OLE studies are ongoing. About the Phase 3 EMPEROR StudyThe Phase 3 EMPEROR Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety and tolerability of zorevunersen in children ages 2 to SCN1A gene not associated with gain-of-function. Stoke completed enrollment of 162 patients in the United States, United Kingdom and Japan in June 2026, and a data readout is anticipated in the third quarter of 2027 to support the submission of a rolling New Drug Application (NDA) to the FDA. Approximately 30 additional patients are expected to enroll in Germany, Spain, France and Italy, with completion of enrollment anticipated in August 2026. Participants are randomized 1:1 to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an 8-week baseline period. Following the completion of the study treatment period, eligible participants will be offered ongoing treatment with zorevunersen as part of an open-label period of the study. The primary endpoint of the study is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen as compared to sham. The key secondary endpoints are the durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains, including expressive communication, receptive communication, interpersonal relationships, coping skills and personal skills. Additional endpoints include safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C) and the Bayley Scales of Infant Development (BSID-IV). For more information, visit https://clinicaltrials.gov/study/NCT06872125. About Autosomal Dominant Optic Atrophy (ADOA)ADOA is the most common inherited optic nerve disorder, affecting approximately one in 30,000 people globally with a higher incidence of one in 10,000 in Denmark due to a founder effect. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Approximately half of people with ADOA fail driving standards and up to 46% are registered as legally blind. More than 400 different disease-causing OPA1 variants have been reported in people diagnosed with ADOA. Currently there are no approved treatments for people living with ADOA. About STK-002STK-002 is a proprietary antisense oligonucleotide (ASO) in clinical development for the treatment of ADOA. Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. An estimated 65% to 90% of ADOA cases are caused by variants in the OPA1 gene, most of which lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. STK-002 is designed to upregulate OPA1 protein expression by leveraging the non-mutant (wild-type) copy of the OPA1 gene to restore OPA1 protein expression with the aim to maintain or improve vision in people with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. STK-002 has been granted orphan drug designation by the FDA as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 in people with ADOA is now underway. About the Phase 1 OSPREY StudyThe OSPREY study is a Phase 1, dose-escalating open-label study of children and adults ages 6 to 55 who have an established diagnosis of ADOA and have a confirmed disease-causing variant in the OPA1 gene. The primary objectives for the study are to assess the safety and tolerability of single ascending doses of STK-002, as well as to determine the exposure in blood. Secondary objectives are to assess changes in visual function, ocular structure and quality of life after single doses of STK-002. The OSPREY study follows a standard dose escalation design with participants enrolled into sequential cohorts receiving increasing dose levels of STK-002. Dosing of the first cohort of patients (n=3) is complete, and dosing of the second cohort is expected to begin in August 2026. Subject to ongoing safety assessments, dosing in the third and fourth cohorts are expected to follow with a readout of safety and efficacy results anticipated in the first half of 2027. Data from the OSPREY study will help to inform potential future development of STK-002. All eight planned OSPREY clinical trial sites are now active in the UK, Germany, Denmark, Italy and Austria. For more information on the OSPREY study, please visit: https://www.ospreyclinicaltrial.com/ https://www.isrctn.com/ISRCTN41725621 About Stoke TherapeuticsStoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow us on LinkedIn. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the Company’s quarterly results and cash runway; its future operating results and current or future financial position and liquidity; the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; the potential benefits, safety and efficacy of zorevunersen; the design, timing and results of clinical studies, enrollment timelines, data readouts, regulatory submissions or decisions and other presentations for zorevunersen and STK-002; the timing and potential outcomes of meetings with regulators regarding the zorevunersen program; the Company’s ability to achieve an NDA submission or approval on the expedited timeframe disclosed or at all; the ability of STK-002 to treat the underlying causes of Autosomal Dominant Optic Atrophy (ADOA) and maintain or improve vision; our expectations, plans, aspirations and goals, including those related to the potential of zorevunersen and our collaborations with Biogen and Acadia. Statements including words such as "anticipate," "expect," "plan," "will," or "may" and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause the Company’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: the Company’s ability to advance, obtain regulatory approval for, and ultimately commercialize its product candidates; that if the Company’s partners were to breach or terminate their collaboration with the Company, the Company would not obtain the anticipated financial or other benefits; the possibility that the Company and Biogen may not be successful in their development of zorevunersen and that, even if successful, they may be unable to successfully commercialize zorevunersen; the potential that positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; the Company’s ability to protect its intellectual property; the Company’s ability to fund development activities and achieve development goals into 2028; and the other risks and uncertainties described under the heading "Risk Factors" in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, its quarterly reports on Form 10-Q, and the other documents it files with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Financial Tables Follow References: Symonds, J. et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain. 2021;144(9):2879-2891. Based on Stoke Therapeutics’ preliminary estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by Wu et al., Pediatrics, 2015. View source version on businesswire.com: https://www.businesswire.com/news/home/20260803082079/en/ Contacts Stoke Media & Investor Contacts: Susan WillsonVice President, Corporate [email protected] 415-509-8202 Investor [email protected]

BEDFORD, Mass., July 27, 2026--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK) is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine and has a lead investigational medicine, zorevunersen, in development as a first-in-class potential disease-modifying treatment for Dravet syndrome. Today, the Company announced that management will host a webcast and conference call for analysts and investors on Monday, August 3, 2026, at 4:30 p.m. ET, to discuss second quarter 2026 business and financial updates. The webcast will be available on the Investors & News section of Stoke’s website at https://investor.stoketherapeutics.com/. Research analysts who plan to join the call and participate in the Q&A session may register here to receive the dial-in details and a unique PIN. All other participants are invited to access the listen-only webcast by clicking here. An archived replay of the webcast will be available for at least 90 days following the event. About Stoke Therapeutics Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ and follow us on LinkedIn. About Zorevunersen Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the unaffected (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function in the SCN1A gene, and China’s Center for Drug Evaluation has granted zorevunersen Breakthrough Therapy Designation. Stoke has a strategic collaboration with Biogen (Nasdaq: BIIB) to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights. Zorevunersen is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory authority. View source version on businesswire.com: https://www.businesswire.com/news/home/20260727018377/en/ Contacts Stoke Media & Investor Contacts:Susan WillsonVice President, Corporate [email protected] 415-509-8202Investor [email protected]

Stoke Therapeutics, Inc. (NASDAQ:STOK) just released its latest quarterly results and things are looking bullish. Revenues of US$6.2m beat estimates by a substantial 21% margin. Unfortunately, Stoke Therapeutics also reported a statutory loss of US$0.79 per share, which at least was smaller than the analysts expected. The analysts typically update their forecasts at each earnings report, and we can judge from their estimates whether their view of the company has changed or if there are any new concerns to be aware of. With this in mind, we've gathered the latest statutory forecasts to see what the analysts are expecting for next year. This technology could replace computers: discover the 20 stocks are working to make quantum computing a reality. Following the recent earnings report, the consensus from eleven analysts covering Stoke Therapeutics is for revenues of US$26.2m in 2026. This implies a definite 18% decline in revenue compared to the last 12 months. Per-share losses are expected to explode, reaching US$3.29 per share. Before this earnings announcement, the analysts had been modelling revenues of US$26.9m and losses of US$3.46 per share in 2026. It looks like there's been a modest increase in sentiment in the recent updates, with the analysts becoming a bit more optimistic in their predictions for losses per share, even though the revenue numbers fell somewhat. Check out our latest analysis for Stoke Therapeutics The consensus price target rose 8.2% to US$45.10, with the analysts increasingly optimistic about shrinking losses, despite the expected decline in revenue. It could also be instructive to look at the range of analyst estimates, to evaluate how different the outlier opinions are from the mean. Currently, the most bullish analyst values Stoke Therapeutics at US$60.00 per share, while the most bearish prices it at US$35.00. These price targets show that analysts do have some differing views on the business, but the estimates do not vary enough to suggest to us that some are betting on wild success or utter failure. Looking at the bigger picture now, one of the ways we can make sense of these forecasts is to see how they measure up against both past performance and industry growth estimates. We would highlight that revenue is expected to reverse, with a forecast 24% annualised decline to the end of 2026. That is a notable change from historical growth of 72% over the last five years. Compare this with our data, which suggests that other companies in the same industry are, in aggregate, expected to see their revenue grow 22% per year. It's pretty clear that Stoke Therapeutics' revenues are expected to perform substantially worse than the wider industry. The most important thing to take away is that the analysts reconfirmed their loss per share estimates for next year. On the negative side, they also downgraded their revenue estimates, and forecasts imply they will perform worse than the wider industry. Even so, earnings per share are more important to the intrinsic value of the business. We note an upgrade to the price target, suggesting that the analysts believes the intrinsic value of the business is likely to improve over time. Keeping that in mind, we still think that the longer term trajectory of the business is much more important for investors to consider. At Simply Wall St, we have a full range of analyst estimates for Stoke Therapeutics going out to 2028, and you can see them free on our platform here.. Don't forget that there may still be risks. For instance, we've identified 2 warning signs for Stoke Therapeutics that you should be aware of. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team (at) simplywallst.com. This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Interested in Stoke Therapeutics, Inc.? Here are five stocks we like better. Stoke Therapeutics said its lead drug zorevunersen showed durable seizure reductions and improved cognition/behavior in four-year extension data, supporting a potential disease-modifying effect in Dravet syndrome. The company expects to finish enrollment in the Phase 3 EMPEROR trial in June and remains on track for a mid-2027 data readout, with a potential U.S. launch targeted for late 2027 or early 2028 if the program succeeds. Stoke ended the quarter with $411 million in cash, which it says should fund operations through the Phase 3 readout and a potential launch, while it also raised $80.7 million via its at-the-market equity program. Stoke Therapeutics (NASDAQ:STOK) said its lead investigational therapy zorevunersen continued to show durable seizure reductions and improvements in measures of cognition and behavior in four-year open-label extension data, while the company remains on track to complete enrollment in its pivotal Phase 3 EMPEROR study in June. On the company’s first-quarter 2026 business and financial update call, Chief Executive Officer Ian Smith said Stoke has seen increased awareness over the past 12 to 18 months around both Dravet syndrome and the potential role of zorevunersen, an investigational antisense oligonucleotide designed to address the underlying cause of the disease. → Insider Sales: Top AST SpaceMobile Insider Cuts Postion Over 30% Smith said the company is preparing for a potential U.S. launch in late 2027 or early 2028, contingent on successful Phase 3 data and regulatory approval. He added that Stoke expects to begin a rolling New Drug Application submission in the first quarter of 2027, with Phase 3 data expected to complete the submission in mid-2027. Chief Medical Officer Dr. Barry Ticho reviewed new top-line four-year data from Stoke’s ongoing Phase 1/2 open-label extension studies. Of the 81 patients who received at least one dose of zorevunersen in the Phase 1/2 studies, 75, or 93%, continued into the extension studies, receiving zorevunersen on top of standard anti-seizure medicines. → Light Speed Returns: Corning Cashes In on NVIDIA Growth Ticho said approximately 77% of patients remained in the studies at the time of the four-year data cut. In patients initially treated with one, two or three 70 mg doses before entering the extension studies, median reductions in major motor seizure frequency ranged from 59% to 91% through month 28 compared with Phase 1/2 baseline. The company said the latest four-year data also showed statistically significant improvements in five Vineland-3 subdomains compared with open-label extension baseline at years one, two, three and four. Vineland-3 is used to assess behavioral outcomes across domains such as communication, motor skills, socialization and daily living. → Years in the Making, AMD’s Upside Movement Has Just Begun Ticho said the findings provide support for the potential disease-modifying effect of zorevunersen, noting that Dravet syndrome is associated with severe neurodevelopmental consequences in addition to seizures. “These data suggest that zorevunersen may durably reduce seizure frequency and lead to improvements in cognition and behavior in patients whose neurodevelopment generally stagnates around the age of two,” Ticho said. Ticho said Stoke now has more than five years of clinical data across the Phase 1/2 and extension studies, with more than 850 doses administered. He said no new safety findings have emerged and zorevunersen continues to be generally well-tolerated. Elevated cerebrospinal fluid protein lab values occurred in approximately 94% of patients, with 59% classified as treatment-emergent adverse events. Ticho said no serious or severe clinical manifestations have been associated with the CSF protein elevations, and there have been no reports of hydrocephalus. Stoke’s Phase 3 EMPEROR study is a global, double-blind, sham-controlled trial of zorevunersen in Dravet syndrome. The company plans to enroll approximately 150 patients in the U.S., U.K. and Japan, where sham is administered via lumbar puncture. Ticho said data from those patients are expected to be used for the U.S. NDA submission. As of May 5, approximately 130 patients had been randomized to zorevunersen or sham, and approximately 18 had completed the week 28 visit, which is tied to the study’s primary endpoint of change in seizure frequency. Ticho said no patients had discontinued treatment in EMPEROR to date, and approximately 91 had received two loading doses of 70 mg of zorevunersen or sham. The study will remain blinded for the full 52-week treatment period because secondary endpoints measuring cognition and behavior will be assessed at week 52. Stoke expects the final patient in the U.S., U.K. and Japan cohort to be randomized in June, keeping the company on track for a Phase 3 readout in mid-2027. The company is also enrolling a European cohort where sham will be administered by needle prick. Ticho said at least 20 patients are planned for enrollment in Europe, but the cohort is not planned for the NDA submission. Screening in Europe is underway, with 15 of 16 sites active, and enrollment is expected to be completed in the third quarter. Chief Patient Officer Jason Hoitt said Stoke estimates there are about 38,000 patients with Dravet syndrome across the seven major markets where the EMPEROR study is running, including approximately 16,000 in the U.S. He said the company estimates approximately 6,000 U.S. patients will be addressable at the time of a potential launch, based in part on patients under age 25 who are likely under pediatric care and claims analyses of diagnosed patients. Hoitt said the U.S. Dravet population is concentrated, with about 70% of patients seen by roughly 1,200 healthcare providers and approximately 124 sites of care. He added that Stoke expects to pursue a lean commercial infrastructure given the rare disease market’s concentration. During the question-and-answer session, Hoitt said payers have indicated they would evaluate the totality of the zorevunersen data, including longitudinal data, rather than relying solely on label language. He said Stoke plans to deploy national account directors in the second half of 2026 to begin payer education through pre-approval information exchange presentations. Smith and Hoitt also discussed the company’s goal of including long-term open-label extension data in the zorevunersen label if approved. Smith said the data would be shared with the FDA and could help inform physicians about the medicine’s safety and efficacy in chronic use. Chief Financial Officer Thomas Leggett said Stoke ended the first quarter with $411 million in cash, cash equivalents and marketable securities. The company expects that balance to fund operations through a potential U.S. launch in late 2027 or early 2028. During the quarter, Stoke raised $80.7 million in net proceeds through its at-the-market program by selling approximately 2.6 million shares of common stock to what Leggett described as high-quality fundamental investors. Leggett said the company continues to invest in advancing its clinical work, preparing for potential commercialization, advancing its pipeline and maintaining a strong financial position. Smith said the company is funded well beyond the Phase 3 readout and through a potential U.S. launch of zorevunersen. Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biopharmaceutical company focused on developing genetic medicines to upregulate protein production for the treatment of rare neuromuscular and neurological disorders. Founded in 2014, the company applies its proprietary Targeted Augmentation of Nuclear Gene Output (TANGO™) platform to design antisense oligonucleotides that selectively modulate RNA splicing and enhance expression of functional proteins. The company's lead program, STK-001, is an antisense oligonucleotide therapy designed to increase production of the sodium channel protein SCN1A and is currently in clinical development for Dravet syndrome, a severe childhood-onset epilepsy. The article "Stoke Therapeutics Q1 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for May 2026.

– New 4-year longitudinal data from the Phase 1/2a open-label extension (OLE) studies provide additional support for the disease-modifying potential of zorevunersen, an investigational medicine for the treatment of Dravet syndrome – – Statistically significant improvements in cognition and behavior demonstrated at 1, 2, 3 and 4 years of treatment compared to OLE baseline, in addition to continued durability in seizure reductions – – Zorevunersen generally well tolerated, with some patients treated for more than 5 years – – Enrollment of approximately 150 patients into the Phase 3 EMPEROR study expected to complete in June 2026 to support a data readout in mid-2027; these data are anticipated to complete the rolling U.S. NDA submission planned to initiate in first quarter 2027 – – As of March 31, 2026, the Company had $411.0 million in cash, cash equivalents and marketable securities expected to fund operations into 2028, including $80.7 million raised through selective ATM sales in first quarter 2026 – – Webcast and conference call for analysts and investors at 4:30PM Eastern Time today – BEDFORD, Mass., May 07, 2026--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK) is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine and has a lead investigational medicine, zorevunersen, in development with Biogen (Nasdaq: BIIB) as a first-in-class potential disease-modifying treatment for Dravet syndrome. The Company today reported financial results for the first quarter ended March 31, 2026, and announced new 4-year longitudinal data from the ongoing Phase 1/2a open-label extension (OLE) studies that provide additional support for zorevunersen as a potential disease-modifying treatment for Dravet syndrome. Statistically significant improvements were demonstrated in cognition and behavior at 1, 2, 3 and 4 years of treatment compared to OLE baseline. Reductions in major motor seizure frequency were observed through 4 years of treatment in patients taking standard anti-seizure medicines (ASMs). Zorevunersen continues to be generally well tolerated, with some patients treated for more than 5 years in the Phase 1/2a and ongoing OLE studies. The Company also announced an update on progress of the global Phase 3 EMPEROR study. Enrollment of approximately 150 patients in the U.S., UK and Japan is expected to complete in June 2026 to support a data readout in mid-2027. These data are anticipated to complete the rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) planned to initiate in the first quarter of 2027. "These new 4-year OLE data suggest that zorevunersen may change the course of Dravet syndrome by providing children with durable reductions in seizures and the possibility of a more neurotypical development path. Together with the Phase 1/2a results, the ongoing extension studies offer 5 years of clinical data, providing a unique opportunity to understand the long-term benefits and safety of zorevunersen," said Ian F. Smith, Chief Executive Officer and Director of Stoke Therapeutics. Mr. Smith continued, "We look forward to results from our pivotal Phase 3 study, which is on track to complete enrollment of approximately 150 patients in June to support a data readout in mid-2027. As we continue to see this study through to completion, our focus turns increasingly to commercial preparedness and bringing zorevunersen to patients while also building our pipeline for the future. All of this is supported by our strong financial position taking us through to a potential U.S. launch in early 2028." Program Highlights Dravet syndrome (zorevunersen) New 4-year safety and efficacy data from OLE studies: Following treatment in the Phase 1/2a studies 93% (75/81) patients continued treatment in one of two OLE studies. As of the 4-year data cutoff, 77% (58/75) patients remained in these studies. The new 4-year data announced today showed that patients treated with zorevunersen on top of standard anti-seizure medicines continued to experience durable reductions in seizures and ongoing improvements in cognition and behavior. Zorevunersen continues to be generally well tolerated, with some patients treated for more than 5 years in the Phase 1/2a and ongoing OLE studies in which more than 850 doses have been administered. Elevated CSF protein lab values occurred in approximately 94% of patients of which 59% have been classified as a treatment-emergent adverse event. Importantly, no serious or severe clinical manifestations have been associated with CSF protein elevations. There have been no reports of hydrocephalus. Pivotal Phase 3 EMPEROR study progress: U.S., UK and Japan: New patient entry into screening is now closed. As of May 5, 2026, approximately 130 patients had been randomized to zorevunersen or sham. The remaining patients required to achieve the planned enrollment of approximately 150 patients into this cohort are progressing through the 8-week screening period. Following successful completion of screening, these patients will be randomized to treatment with zorevunersen or a sham control administered via lumbar puncture (LP). The final patient is expected to be randomized in June 2026. These data are anticipated to be the final data required for completion of the planned rolling U.S. NDA submission. Europe (Germany, France, Spain and Italy): 15 out of 16 sites are activated and screening is underway for at least 20 additional patients. Enrollment is expected to complete in the third quarter of 2026. Medical and scientific publications and communications continued to drive awareness of Dravet syndrome and the need for disease modification. In April, Stoke presented data at the American Academy of Neurology (AAN) Annual Meeting, the world’s largest gathering of neurologists. In March, The New England Journal of Medicine (NEJM) published zorevunersen data from the Phase 1/2a and OLE studies. An independent editorial that discussed the underlying genetic cause of Dravet syndrome and the disease-modifying potential of zorevunersen accompanied the manuscript. Pipeline beyond zorevunersen In February, the first patient was dosed in the Phase 1 OSPREY study of STK-002 for the treatment of Autosomal Dominant Optic Atrophy (ADOA), the most common inherited optic nerve disorder. To date, two patients have been dosed and recruitment is ongoing at 7 sites across the UK, Germany, Denmark and Austria. Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Lead optimization is underway to identify a clinical candidate for the treatment of SYNGAP1 in 2026. SYNGAP1 is a severe and rare genetic neurodevelopmental disease. First Quarter 2026 Financial Results As of March 31, 2026, the Company had $411.0 million in cash, cash equivalents and marketable securities expected to fund operations into 2028. This includes approximately $80.7 million of proceeds from the sale of 2.6 million shares of common stock from selective use of the ATM facility (Controlled Equity Offering Sales Agreement) during the first quarter of 2026. Revenue recognized for the three months ended March 31, 2026, was $6.2 million, a decrease from $158.6 million for the same period in 2025. The decrease in revenue is primarily driven by the 2025 recognition of $150.8 million related to the IP license performance obligation related to the Biogen Agreement outside of the U.S., Canada and Mexico. Net loss for the three months ended March 31, 2026, was $50.0 million, or $0.79 per share, compared to a net income of $112.9 million, or $1.90 per diluted share, for the same period in 2025. Research and development expenses for the three months ended March 31, 2026, were $39.7 million, compared to $32.7 million for the same period in 2025. The increase of $7.0 million was driven by an increase in activities and personnel expenses to support the advancement of zorevunersen. Sales, general and administrative expenses for the three months ended March 31, 2026, increased to $20.0 million from $14.7 million for the same period in 2025. The increase of $5.3 million was driven by an increase in personnel and launch readiness expenses. Stoke Webcast and Conference Call for Analysts and Investors Stoke management will host a webcast and conference call for analysts and investors on Thursday, May 7, 2026, at 4:30PM Eastern Time. The webcast will be available on the Investors & News section of Stoke’s website at https://investor.stoketherapeutics.com/. Research analysts who plan to join the call and participate in the Q&A session may register here to receive the dial-in details and a unique PIN. All other participants are invited to access the listen-only webcast by clicking here. A replay of the webcast will be archived and available for at least 90 days following the event. About Dravet Syndrome Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. Even when treated with the best available anti-seizure medicines (ASMs), up to 57 percent of patients with Dravet syndrome do not achieve ≥50 percent reduction in seizure frequency. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP; up to 20 percent of children and adolescents with Dravet syndrome die before adulthood due to SUDEP, prolonged seizures, seizure-related accidents or infections 1. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan 2. There are no approved disease-modifying therapies for people living with Dravet syndrome. About Zorevunersen Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the unaffected (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights. Zorevunersen is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory authority. About the Phase 1/2a and Open-Label Extension Studies Two Phase 1/2a open-label, multicenter studies evaluated the effects of zorevunersen in patients with highly refractory Dravet syndrome ages 2 to 18 years (N=81). Primary endpoints were the safety profile, plasma pharmacokinetics (PK) and exposure in cerebrospinal fluid (CSF) of single and multiple doses of zorevunersen. Secondary endpoints included percentage change from baseline in major motor seizure frequency, overall clinical status (a measure of patients’ overall functioning) and quality of life. The ADMIRAL Phase 1/2a study included an exploratory endpoint to evaluate changes in neurodevelopmental status (cognition & behavior) as measured by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). The Phase 1/2a studies were completed in November 2023. Following treatment in the Phase 1/2a studies, eligible patients continued treatment with zorevunersen every four months in one of two OLEs. There was at least a 6-month gap between the last dose administered in the Phase 1/2a studies and the first dose administered in the OLEs. The primary endpoints are the safety profile of multiple doses of zorevunersen. Secondary endpoints include PK parameters, percentage change from baseline in major motor seizure frequency, change in overall clinical status, and change from baseline in quality of life. Exploratory endpoints include changes in neurodevelopment status as measured by Vineland-3. The OLE studies are ongoing. About the Phase 3 EMPEROR Study The Phase 3 EMPEROR Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety and tolerability of zorevunersen in children ages 2 to <18 with Dravet syndrome with a confirmed variant in the SCN1A gene not associated with gain-of-function. Stoke expects to complete enrollment of approximately 150 patients in the United States, United Kingdom and Japan in June 2026, with a data readout on track for mid-2027 to support the submission of a New Drug Application (NDA) to the FDA. At least 20 additional patients are expected to enroll in Germany, Spain, France and Italy, with completion of enrollment anticipated in Q3 2026. Participants are randomized 1:1 to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an 8-week baseline period. Following the completion of the study treatment period, eligible participants will be offered ongoing treatment with zorevunersen as part of an OLE study. The primary endpoint of the study is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen as compared to sham. The key secondary endpoints are the durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains, including expressive communication, receptive communication, interpersonal relationships, coping skills and personal skills. Additional endpoints include safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C) and the Bayley Scales of Infant Development (BSID-IV). For more information, visit https://clinicaltrials.gov/study/NCT06872125. About Autosomal Dominant Optic Atrophy (ADOA) ADOA is the most common inherited optic nerve disorder, affecting approximately one in 30,000 people globally with a higher incidence of one in 10,000 in Denmark due to a founder effect. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Approximately half of people with ADOA fail driving standards and up to 46% are registered as legally blind. More than 400 different disease-causing OPA1 variants have been reported in people diagnosed with ADOA. Currently there are no approved treatments for people living with ADOA. About STK-002 STK-002 is a proprietary antisense oligonucleotide (ASO) in clinical development for the treatment of ADOA. Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. An estimated 65% to 90% of ADOA cases are caused by variants in the OPA1 gene, most of which lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. STK-002 is designed to upregulate OPA1 protein expression by leveraging the non-mutant (wild-type) copy of the OPA1 gene to restore OPA1 protein expression with the aim to maintain or improve vision in people with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. STK-002 has been granted orphan drug designation by FDA as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 in people with ADOA is now underway. About the Phase 1 OSPREY Study The OSPREY study is a Phase 1, dose-escalating open-label study of children and adults ages 6 to 55 who have an established diagnosis of ADOA and have a confirmed disease-causing variant in the OPA1 gene. The primary objectives for the study are to assess the safety and tolerability of single ascending doses of STK-002, as well as to determine the exposure in blood. Secondary objectives are to assess changes in visual function, ocular structure and quality of life after single doses of STK-002. The OSPREY study follows a standard dose escalation design with participants enrolled into sequential cohorts receiving increasing dose levels of STK-002. Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Data from the OSPREY study will help to inform potential future development of STK-002. The OSPREY study is actively recruiting in the United Kingdom, Germany, Denmark and Austria. Additional European sites are expected to activate in the coming months. For more information on the OSPREY study, please visit: https://www.ospreyclinicaltrial.com/ https://www.isrctn.com/ISRCTN41725621 About Stoke Therapeutics Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the Company’s quarterly results and cash runway; its future operating results and current or future financial position and liquidity; the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; the design, timing and results of clinical studies, enrollment timelines, data readouts, regulatory submissions or decisions and other presentations for zorevunersen and STK-002; the timing and potential outcomes of meetings with regulators regarding the zorevunersen program; the ability of STK-002 to treat the underlying causes of Autosomal Dominant Optic Atrophy (ADOA) and maintain or improve vision; our expectations, plans, aspirations and goals, including those related to the potential of zorevunersen and our collaborations with Biogen and Acadia. Statements including words such as "anticipate," "expect," "plan," "will," or "may" and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause the Company’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: the Company’s ability to advance, obtain regulatory approval for, and ultimately commercialize its product candidates; that if the Company’s partners were to breach or terminate their collaboration with the Company, the Company would not obtain the anticipated financial or other benefits; the possibility that the Company and Biogen may not be successful in their development of zorevunersen and that, even if successful, they may be unable to successfully commercialize zorevunersen; the risk that positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; the development goals into 2028 and through potential U.S. launch in early 2028; and the other risks and uncertainties described under the heading "Risk Factors" in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, its quarterly reports on Form 10-Q, and the other documents it files with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Financial Tables Follow References: View source version on businesswire.com: https://www.businesswire.com/news/home/20260507458327/en/ Contacts Stoke Media & Investor Contacts: Susan Willson Vice President, Corporate Communications [email protected] 415-509-8202 Doug Snow Director, Communications & Investor Relations [email protected] 508-642-6485