Stoke Therapeutics, Inc.

Good afternoon and welcome to Stoke Therapeutics' second quarter 2025 conference call. I'm Tommy Leggett, chief financial officer at Stoke. Joining me for prepared remarks are Ian Smith, our interim chief executive officer, Dr. Barry Tico, chief medical officer, and Dr. Kimberly Parkerson, head of neurology clinical development. In addition, Jason Hoyt, our chief patient officer, will participate in Q&A. As a reminder, today's webcast slides are available in the investor section of our website. This webcast is being recorded and will be available for replay later today. Before we begin, please note that today's discussion includes forward-looking statements. These are subject to risks and uncertainties, and actual results may differ materially. Please refer to the filings of the SEC for additional information. With that, I'll turn the call over to Ian. Welcome, everyone,

and thank you for joining us today. I've been working with Stoke Therapeutics for two years as a director and advisor, more recently as the CEO. It has been a great opportunity to get to know the team, the medicines, and the disease areas, and to support the company through this growth period. The key priority is obviously Dravet syndrome and Zoriba-Nursen, as we work to deliver a disease-modifying medicine to patients. What we're seeing with Zoriba-Nursen may be new to the field of epilepsy, but I'm struck with the familiarity of the feeling of being part of something very special, again, which is creating a new -in-class disease-modifying medicine for patients who desperately need it, potentially changing the lives of these children suffering from Dravet syndrome. Let me start by saying that Stoke is in a strong growth position, defined by a late-stage registrational medicine, well-capitalized balance sheet, expanding pipeline of potential medicines, and a very strong partner in Biogen with expansive capabilities to support Zoriba-Nursen outside of North America. Our Phase III Emperor study in patients with Dravet syndrome is off to a strong start, with sites initiated in the US, UK, and Japan, and Europe expected to initiate in early 2026. The first patient is now dosed, and we anticipate rapid enrollment based on the high level of awareness of the study, competitive participation among the study sites, and importantly, the urgent patient need. We continue to generate data that support our understanding of Zoriba-Nursen from our Phase I, II, and OLE studies. We have prioritized sharing this information broadly as the field begins to transition from a symptomatic treatment to a potentially disease-modifying medicine for Dravet syndrome. We continue to educate around the seizure reductions with our medicine, and those reductions are on top of standard care anti-seizure medicines. More recently, we shared data that was used to inform the assessments of behavior and cognition and the powering of our Phase III study, specifically the substantial improvements in cognition and behavior, indicated with a dosing level that is similar to and consistent with the one we are using in our Phase III study. And today, we are sharing with you top-line results from the third year of our open-label extension studies. These data support the long-term potential of Zoriba-Nursen to modify the course of Dravet syndrome, as indicated by durable seizure reductions on top of what can be achieved with standard anti-seizure regimens, as well as continuing improvements in cognition and behavior. Importantly, these long-term follow-up data continue to demonstrate a favorable safety profile. Beyond Dravet, we see significant potential to develop disease-modifying medicines for additional genetic diseases. We've advanced STK-002 into Phase I clinical development for autosomal dominant optic atrophy. Like Dravet, ADOA is a haploin-sufficient disease, and we are uniquely positioned to treat by restoring naturally occurring OPA1 protein expression using our antisense oligonucleotide approach toward the goal of preventing further loss of eyesight and possibly improving vision. Now to our collaboration with Biogen. Found in February, this brings global expertise commercializing high-value disease-modifying medicines for rare genetic diseases and strengthens our balance sheet. The terms of the collaboration retain significant value to Stoke while enhancing our ability to deliver Zoriba-Nursen to patients globally. We have a strong balance sheet and are well-funded through Phase III readout, which is anticipated in the second half of 2027. Our balance sheet and projected investment supports a cash runway through to mid-2028. We continue to build Stoke's internal capabilities by enhancing our leadership team and strengthening key functions, including regulatory, medical affairs, and commercial, all fundamentally important functions at our stage of growth. In short, we are establishing a clear trajectory for value creation for patients, for employees, and for our investors. With that, I'll turn the call over to Barry, who will discuss our Phase III study design and progress. Thank

you, Ian. This is a very exciting time here at Stoke. As we take Zoriba-Nursen into this next phase of clinical development and potential registration and approval, Trevay syndrome is a severe, lifelong developmental and epileptic encephalopathy that becomes symptomatic around one year of age. For the vast majority of patients, it caused insufficient levels of the NAD1.1 protein in the brain. There are many medicines available to treat the seizures associated with Trevay syndrome. These medicines have undoubtedly made a difference for patients, but they just aren't enough. Most patients continue to suffer from seizures, and few achieve seizure freedom. Furthermore, side effects of the anti-seizure regimen also present their own challenges for patients and their caregivers. While Trevay syndrome may be best known for its seizure burden, the effects go far beyond seizures. Nearly all patients suffer from one or more behavioral and cognitive effects. The anti-seizure medicines were not intended to address these effects. We intend to change that. The Reven-Hurston is an antisense autogynclytide designed to restore naturally occurring NAD1.1 protein levels. As such, it has the potential to be the first disease-modifying therapy for Trevay syndrome. As we designed our phase three study, we were fortunate to have a large data set available to inform key decisions related to dose level, dose frequency, study endpoint assessment, and powering. Here on slide eight, you see the dramatic reductions in seizures demonstrated in our phase one, two studies among patients treated with initial doses of 70 milligrams as they were given at the time, on top of standard anti-seizure medicine. The most substantial reductions were observed among patients who received either two or three doses of 70 milligrams. Based on these data and additional modeling analysis, we selected a two-dose loading regimen, phase three. The seizures is our primary endpoint for the trial. After receiving their last phase one, two dose, patients were followed for at least six months before restarting treatment in the open-label extension study. When designing our phase three program, we used the initial eight months of data from the OLE that showed substantial and durable reductions in seizures and a favorable safety profile to inform our maintenance dose. We now have an additional year of data on these patients, which are shown here, and support the long-term durable reductions in seizures. Kim will discuss these data later in the call. These new long-term data give us confidence in our loading and maintenance dosing, as well as the durability of effects. On slide 10, we see one of the key analyses that informed our thinking on the phase three design, which Ian referenced earlier, and was presented at EPMS Munich last month. The analysis shown on the left was performed to assess potential effects on foundational behavior using data from patients treated with dose levels that were similar to and consistent with our phase three dose regimen. The effects are striking. Particularly in the context of the results from a matched cohort of patients followed in our natural history study. Little to no change was detected in the natural history that patients treated with cerebral nursing showed cognition and behavioral benefits in the five key subdomains that comprise our key secondary endpoints in EPMS Munich. On this slide, you can see the phase three design. Patients who enroll in EMPEROR will be randomized one to one to Zareva-Nursen or to SHAM. In both study arms, patients will continue to receive standard of care anti-seizure medicine. Consistent with the data I just reviewed, patients in the Zareva-Nursen arm will receive two loading doses of 70 milligrams, followed by two maintenance doses of 45 milligrams. An open label extension treatment period will allow all patients the opportunity to receive treatment with Zareva-Nursen following 52 weeks of treatment in the study. I will now review the EMPEROR study design and conduct in more detail on slide 12. Primary endpoint is changed from baseline in major motor seizure frequency at week 28. The ability of effect on seizures will be measured as a secondary endpoint at week 52. Zareva-Nursen is a potential first in class to these modifying methods. So EMPEROR will also measure effect on behavior and cognition. Powering for these secondary endpoints is robust and designed with the intent to show statistical significance on both individual subdomain and composite specimens. We were pleased with the level of interaction and input from global regulatory agencies and our advisors as we worked together to design the EMPEROR trial. Through these discussions, we aligned around a double-blind, SAM-controlled study with lumbar puncture for all patients. As individual European countries got involved later in the process, they required a modification to the SAM-on to proceed. In order to ensure our commitment to patients in Europe, we now plan to add a cohort of at least 20 patients in Europe where SAM will be administered via needle prick. This cohort of patients will be in addition to and complement the originally planned group of approximately 150 patients who will be randomized to receive Zareva-Nursen or SAM with lumbar puncture in the US, UK, and Japan. We expect to activate at least half of the 70 study sites by year end and European sites to initiate by early 2026. We see significant and growing global interest in EMPEROR, which supports our expectation to complete enrollment in the second half of 2026 with a phase three data readout in the second half of 2020 study. EMPEROR is off to a great start. We have had a high degree of confidence in the study design based on a large data set and the ongoing patient need. Our natural history study has proven invaluable in understanding the effect that crevice syndrome has on patients over time, as well as the limitation of the current standard of care medicine. Our experience with Zareva-Nursen in phase one, two, and the ongoing OLEs has helped us understand the initial and ongoing effect of Zareva-Nursen and has demonstrated an encouraging long-term state. Our assessments of behavior and cognition have been validated and our endpoints empowering are informed by our years of experience and data. As announced yesterday, the first patient was dosed in EMPEROR. Study investigators have identified approximately 130 potential participants and that number continues to increase. More than 10 clinical sites have initiated across the US, UK, and Japan with more coming online weekly. This is exactly the kind of start we were hoping for and it positions us well for continued enrollment success. With that, I would like to turn the call over to Kim for a review of the new three-year open label expansion data.