Conference Transcript - STOK 2026-06-08

Kevin Strang, Analyst — Goldman Sachs

All right, well, it is my pleasure to introduce Ian Smith, CEO, and Jason Hoyt, Chief Patient Officer of Stoke Therapeutics. My name is Kevin Strang. I'm one of the biotech analysts here at Goldman Sachs. Welcome. And I guess we'll just start, you know, getting right into a question for you, Ian. You know, what were your priorities when you took on the CEO role at Stoke? And can Can you sort of provide a mark-to-market on your progress against those priorities and what you're focusing on from here?

Ian F. Smith, CEO

Yeah, so first of all, thank you for everybody joining us on the webcast and those that are in the room with us today. Just as stepping back, I've been on the board of Therapeutics for three years now and while I was on the board at Stoke Hale, so was an advisor to the company. About 15, 18 months ago now, 8, 15 months ago, the board asked me to transition with the CEO at that time. I was the interim CEO for six or seven months, and I took the permanent CEO position in October of last year. That's the background. How did I think about goals and achievements for the company? Well, first of all, it started with I wanted to help the company become the greatest advocate it could be for what Dravet was as a disease, the devastation of Dravet. And once you understand that and understand what our medicine is doing for Dravet children, you actually start to become a very strong advocate for your medicine as well. That is kind of the meta-goal, so to speak, for the company today. But what that translates into is understanding the audiences that need to understand that. So the physicians, the physicians that treat Dravet or seizures today with medicines that only treat the seizures. Our medicine treats beyond the seizures based on all the data we've received so far. We treat beyond the seizures in Dravet. And so educate the healthcare environment to what our medicine can do to those children. Also to then understand how to progress the medicine to get it to these children that deserve the medicine, the families that deserve the medicine, and build a company. And frankly, I worked with Vertec Pharmaceuticals for 20 years and saw medicines for cystic fibrosis over 20 years come from the bench all the way to changing the children with CF, changing their lives. And you have to build a whole company to augment that, and that means building a development organization to run the studies, having a regulatory group that has the right and appropriate interactions with the FDA, including breakthrough designation and seeing if there's accelerated pathways through to these patients, building a medical affairs group that educates market, building more of a business function in terms of manufacturing and commercial, and frankly, understanding Wall Street as well in terms of educating the investment community to the opportunity that Stoke is creating in terms of an investment. and I think all those areas needed acceleration and investment of time and people and then you asked me Kevin about marketing to market I'm really happy with how the company has progressed over the last 15 months it really has accelerated the awareness in terms of the advocacy of the medicine and that means also the advocacy of the disease and I'm very happy I wish from a stock price I wish our stock price was a little higher, but who doesn't? But the company is building itself out, would make great progress in the phase three, which we're sure we're going to talk about. And there's a greater understanding of the medicine

Kevin Strang, Analyst — Goldman Sachs

and the opportunity to that. I'm very happy with it. Great. That's a great place to start. You mentioned, you know, the disease itself, Treve. You know, at a very high level, what is that unmet need that you see today? You mentioned ASMs versus disease modification. How do you view that unmet need? and then we can get into Zorvinurcin's ability to meet that.

Ian F. Smith, CEO

Yeah, so just consistent with what I said about being an advocate for the disease first, just a little quick, what is Dravet syndrome? And genetically, Dravet syndrome is the depletion of SCN1A, and therefore you don't express AB1.1 in the brain. What our medicine does, so even us, it boosts the allele or the gene SCN1A that is functional and to express NAP 1.1. What we've seen, what that results in, is that it not only reduces seizures in Dravet because you go to the root cause of the disease, but it also provides cognition and behavioral benefits to these kids. In Dravet, they neurotypically develop through to 18 months old, 24 months old, and unfortunately when they get to about that age, they stagnate. So even when they're 20 years old, neurotypically or neurodevelopment-wise, they're still two years old. What our medicine does by giving back that expression of NAV 1.1 is it provides a gain of function while you're on the medicine because you're expressing NAV 1.1. And there's still neuroplasticity there. So whether you come on to the medicine as a 2-year-old, 5-year-old, 10-year-old, 12-year-old, what we're seeing is there is a gain of cognition and behavior as measured in our clinical studies. And so that is not provided anywhere for these Dravet children. There are very good anti-seizure medicines that are anti-seizure medicines and reduce seizures. but seizures is still one of the, unfortunately, uncontrollable symptoms of Dravet. And all of our data, which shows 75% reduction in seizures, improvements in cognition and behavior, is on top of standard of anti-seizure medicines. So we're driving that benefit even on the medicines that are available today. And that's because we go to the root cause of the disease of Express and Nav 1.1.

Kevin Strang, Analyst — Goldman Sachs

Got it. And that's from your phase one, too, as well as your recently shared four-year open-label extension data. Do you just want to highlight, especially with the four-year data, what that means? And that's very recent data that you shared. So maybe just, you know.

Ian F. Smith, CEO

So we're in a unique position where the company has been in development since they're even nursing now for six years. Yet it is a truly breakthrough genetic medicine. And typically with medicines like that, you know, my history, CF, you move quicker in the clinic. But we've been in the clinic now for six years, and by the time that we file an NDA, we will have been in the clinic for seven years. What that has allowed us to do, though, is for that first patient that came in the Phase I-II study six years ago or five years ago, they went through the Phase I-II dose escalating study but then rolled over into an OLE. that OLE we now have captured four years worth of longitudinal data so we're in this rare position where we have a genetic medicine that gives back function and we're able to measure how much function it's giving back over a four year period now while also seeing the durability of seizure reduction over a four year period and all that data what it shows is we're seeing seizure reductions of approximately 75% on top of the standard of care medicines that is durable out to four years now. And in terms of the cognition behavior, we've even run a statistical analysis that shows for each of the key domains of Vineland, which is how you measure cognition, behavior, and improvements, all the five key domains year one, two, three, and four were statistically significant in terms of improvements each year in cognition and behavior of five key Vineland domains.

Kevin Strang, Analyst — Goldman Sachs

Great. So moving on from that data to your currently running Phase III Emperor study, I believe you're guiding to completing the randomization of that study this month. That would enable a readout middle of next year. Can you talk about how that study was designed to capture both the seizure benefit and then the neurodevelopmental outcomes, the Vineland III secondary endpoints?

Ian F. Smith, CEO

So it is a 52-week study, anticipated to be 150 to 160 patients. We're anticipating completing enrollment this month, the month of June. Primary endpoint is week 28, measuring seizure reduction. Secondary endpoints are Vineland 3, which is a measurement tool of cognition and behavior, and that's run at week 52. so that's the design of the study patients go through the study and ultimately can roll over to an OLE study if they're in sham and they continue on the study they have the option as far as the study and the progression of the study I can't give an update today on webcast but a month ago we had recruited or enrolled 130 patients of 150 or 60. Of those 130, approximately 90 were through the first two doses of 70 milligrams, and we had zero drop use, which is quite remarkable. And that might be driven by the intent to get to an OLE, which also shows that the drug is very well tolerated.

Kevin Strang, Analyst — Goldman Sachs

Great. So you mentioned the SAM control arm. you know, I guess how do you sort of approach, you know, how did you approach powering for that sham control arm? And, you know, you've done some natural history work as well, and you've also looked at natural history work. You know, talk to us in terms of that data and what you expect, or what you expected when you designed the trial on that 52-week endpoint. And I believe you represented last year some 18-month data as well. And so I guess if you could go over that.

Ian F. Smith, CEO

Yes, good question. You know, there's maybe something that is a little different of our Phase III program is we've powered the study based on the secondary endpoints, not the primary. The primary endpoint of seizure reduction, the seizure reduction is so demonstrative as what we've seen in all our data that we actually moved to the secondary endpoints and powered the study of the secondary endpoints. The powering in the study of the secondary endpoints is powered to a p-value of 0.01 with a confidence level of 90%. So it's conservatively powered, and that brought us to 150 patients. We anticipated that there could be a 15% dropout, and we anticipated 150 patients to come into the study. So far, we don't have a dropout, and I anticipate that the study could be as high as 160 patients. So we're very well powered. Now, the data that led to that powering calculation was data we provided to the investment community and at a medical conference in August of last year, and that showed that when you take a dosing schema or regimen, complete dosing regimen, that's similar to the phase 3 dosing of 230 milligrams over a 12-month period. We actually showed violent improvements of around 8 to 12 points, I believe, I think, or 8 to 11 points. The study has powered to show 2 points improvement. So we're very well-powered. We're in good shape. We've also provided a statistical analysis of that regimen rather than just showing the absolute violence court. and we compared that to a natural history study and we showed that we hit statistical significance with certain time points and that was with an N of 8.

Kevin Strang, Analyst — Goldman Sachs

Great, and for how these secondary endpoints are being looked at in the U.S. versus Europe, can you just remind investors what those differences are and whether they should think of any hierarchy for these subdomains? And even in the patient community or the physician community, are there certain subdomains that are more important than others?

Ian F. Smith, CEO

Yes, so the subdomains that we're looking at for the NDA versus European filing are the same subdomains. It's the same study in terms of the endpoints. To your question in terms of are there higher priority endpoints, if you talk to families and caregivers and physicians, you will find that there is a kind of a priority and they tend to focus on receptive and expressive communication. And then the one difference between the two filing strategies is in the U.S. it is a hierarchical assessment of the secondary endpoints whereas in Europe it's a composite. But the trial design is very similar. There is a slight difference in four European countries is where we're doing a lumbar puncture cohort, sorry, a needle-proof cohort in terms of sham, whereas the US, UK, and Japan is lumbar puncture.

Kevin Strang, Analyst — Goldman Sachs

Got it, and you know, as you move past the data and towards regulatory outlook for azurbanuricin, what does it need to be, you know, what does it need to achieve to be viewed as a disease-modifying therapy? And, you know, by regulators, physicians, payers, et cetera.

Ian F. Smith, CEO

Yeah. I want to jump all the way to, I think it's already being recognized as a disease-modifying therapy because of the totality of the data. When you look at the four-year OLE data and this durable reduction of seizures on top of standard care medicines, 75% reduction of seizures, And then you're seeing these cognition and behavioral benefits in year one, year two, year three, year four, and that each year they're statistically significant. That totality of data is already being recognized in the medical community and the payer community as a disease-modifying medicine. I think you're asking more about what's the regulatory environment and how they look at it. Again, I think it's very similar, whereas you've got to hit a primary endpoint to get the medicine approved. So we're very confident with that. With the secondaries, we're very confident there as well. But I don't think that you have to go and have five out of five secondary endpoints and hit each one. Because you've also got the OLE data, which would be in the label. The label has a part of the label where you've got to show your data from other clinical studies is if it helps a physician understand the benefits and risks of a medicine. It's actually in the FDA guidance, and it's called Section 14, but your clinical studies are required to be in there. This is a chronic medicine. So when you have five-year data, then you should put that in the medicine to help people understand how the medicine is affecting these children.

Kevin Strang, Analyst — Goldman Sachs

You mentioned Section 14. What are good analogs for investors to look to?

Ian F. Smith, CEO

Yeah, I mean, the best analog I could give you is probably Spinraza. Spinraza is, you know, why is it the best? Because it's also an ASO. The Spinraza looked at their primary endpoint at six months. They actually missed their secondaries, but the OLE data was on the label because they followed these children. And if you're familiar with SMA, unfortunately, these children, they don't sit up, roll over. but they die at very young ages. But Biogen, like ourselves, actually continued these patients into an OLE study and measured them, and it helped to understand what the medicine did chronically. And these children lived longer and also had greater movement and function, and all that data went on the label because it helped people understand how the medicine affected these babies in SMA. We see it exactly the same in terms of being an analog that you're asking for. Well, there are others as well. Jason's been involved with some of them.

Jason Hoitt, Other

Coincidentally, Skyclaris and CalSody, also from Biogen, are good examples of observed data being added to the Section 14 of their labels.

Kevin Strang, Analyst — Goldman Sachs

And I guess, you know, on the topic of analogs, and I have a feeling it could be similar for this question as well, but how are you thinking about pricing?

Jason Hoitt, Other

Yeah, so, you know, I think, I mean, I'm glad you asked the question, Kevin, because I think historically there had been a misconception that because we're launching in Dravet and the only approved medicine so far in Dravet have treated just some of the symptoms, namely the seizures of Dravet, that we would kind of be pigeonholed or ballpark to that price range. But the reality is, is that what we're doing is addressing the underlying genetic cause of the disease. What we're doing is affecting the syndrome itself by doing so. And therefore, I think more appropriate analogs are genetically targeted disease-modifying medicines for rare disease. And so, you know, the analogs we've been talking about most recently are obviously Spinraza, as you mentioned, the Exxon Skipper from Sarepta, I think, are also appropriate analogs, DEBU, medicines like that that are changing the paradigm in addition to, you know, addressing the underlying genetic cause.

Kevin Strang, Analyst — Goldman Sachs

Got it. And then for, you know, for filing, you've mentioned rolling submission is the plan, And, you know, as soon as first quarter of next year, potentially allowing for a launch, maybe early 28, you know, around that time frame. Any gating factors to getting that initial submission started? And then, you know, what are the advantages that you have with breakthrough and using that rolling submission as the phase three data comes in?

Ian F. Smith, CEO

We'll start with the advantage of breakthrough designation allows us, affords us the rolling submission. We anticipate starting the rolling submission in Q1, 2027. The first section of that rolling submission will be CMC. Jason can update you where we are there, but we're right on schedule, no problems, including inspection and quality. Then the rolling submission would take us through to the last clinical submission. That would be after the Week 52 clinical data that would be in the middle of next year. At that point, when you complete your rolling submission, you get a PDUFA date that would be eight months after the last submission. That would put you in Q1 of 2027 for launch, or PDUFA date of Q1 of 2027. However, if you look at the history of rolling submissions, breakthrough designation, approval generally comes anywhere between four and six months after the last clinical submission, which could potentially put us into Q4 of 2027. We're right on track in terms of what we're preparing for in terms of CMC, preclinical. Obviously, we're ongoing with the clinical data in the phase three study.

Kevin Strang, Analyst — Goldman Sachs

Got it. So potential approval launch later next year, early 28. Moving to the commercial opportunity, I feel like you've recently talked about your estimation of the patients available at launch around 6,000. Can you talk about what goes into that number, be it claims data,

Jason Hoitt, Other

literature, prevalence, et cetera? Yeah. So, you know, I think that the number 6,000 comes from two different ways of looking at it, right? And so you can look at it from an epi perspective where going back a couple of years ago, before we initiated the Emperor study, we wanted to understand overall prevalence in the geographies where we were running the study. And so we initially looked at the core seven geographies around the world, U.S., EU4, U.K., and Japan. And we took 85 years of live birth rates and scaled incidence to prevalence, applying Dravet-specific mortality, which largely is due to sudden unexpected death and epilepsy. And that ultimately got us to a total population for the U.S. of 16,000 patients, approximately. When you break that down by specific ages, about 4,000 of those 16,000 are purely pediatric patients under 18. But in Dravet syndrome, there's this dynamic of patients predominantly being cared for by pediatric neurologists, pediatric epileptologists that are initially the ones that diagnose the patient and care for them throughout their life up until they need to transition to adult care. And as you can imagine, patients, families, they develop a strong bond with the clinician that's been caring for them over time, and there's a reluctance to transition to adult care. So oftentimes the pediatric providers are caring for these patients into their mid-20s. And so the patients that are cared for by that group of specialists that are the most familiar and the most up-to-date with what's going on in Dravet are particularly relevant. And so 6,000 is the number of patients from an epi perspective that are 25 and younger in the U.S. Now, pivoting to patients that are already identified today with an ICD-10 code for Dravet from claims data, there are also coincidentally 6,000 identified patients in the most robust claims database in the U.S. today. That's across all ages, but coincidentally, it also happens to be 6,000. We've, you know, brought several pieces of claims data in-house so that we can mine and analyze the data. And we've applied some machine learning principles to the already diagnosed patients looking at, you know, other CPT codes, treatment codes that are consistent with a Dravet diagnosis and then applied that algorithm to the total claims universe. And in doing so, we feel really confident that we know where about 70 to 80 percent of the 25 and younger patients are being cared for today. And as we launched the disease awareness campaign last year, for example, we have the ability now, because there are linked NPI numbers for clinicians in there, to hyper-target specific messaging to specific segments of clinicians based on the behavior that we're seeing from them from a diagnostic and a treatment perspective in an effort to change the behaviors that we would like to change and educate on the areas where they specifically need education.

Kevin Strang, Analyst — Goldman Sachs

Got it. So it seems pretty concentrated. Is there anything, you know, in terms of launch execution that you're planning for, field force design? and specific barriers you're looking for based on your work?

Jason Hoitt, Other

Yeah, so obviously this is contributing to how we think about field force design. And to your point, Kevin, this is a highly concentrated market, right? In this market, 50% of patients based on claims data are in eight states. There are 1,200 clinicians that are caring for about 70% of the total Dravet opportunity. And then if you also look at the claims based on centers, sites, or practices that are caring for patients, And it's also, you know, 124 sites represent 70% of the opportunity. That could be group practices, hospitals, et cetera. So with a concentrated opportunity like that, we're looking at a very lean commercial infrastructure that will allow us to completely maximize this opportunity. You're talking 20 to 25 salespeople total, matrix field organization, but a commercial team that's, you know, well less than 100 people to maximize the U.S. opportunity.

Kevin Strang, Analyst — Goldman Sachs

And what does the timeline look for that?

Jason Hoitt, Other

So our medical affairs team is nearly fully built at this point. Obviously, the medical affairs team needs to be out and engaging with clinicians, and they have been for the last couple of years. We have an amazing team of regional medical directors that are engaging with KOLs today. From a commercial perspective, the leadership team is in place, the entire commercial leadership team. All folks that have done this before, gone from a clinical stage company to a commercial stage company, launched the first medicine in rare disease, and the majority of us have done this together before so it's a strong foundation to start from the vast majority of our hiring for you know in particular field-based personnel will start after phase three data uh we'll be gating some of our spend and some of our hiring to that but leadership will be in place before then and obviously all of the work um to prepare for the onboarding of those

Kevin Strang, Analyst — Goldman Sachs

teams will be done before then as well got it and how are you thinking about you know we talked about different age segments uh there's 18 to like the 18 to 25 segment that's often treated by pediatric specialists still there's the above 25 segment how are you sort of approaching that and and do you need additional studies for you know the adult population when it comes to pair

Jason Hoitt, Other

access and things like that yeah so let me take maybe i'll take the first part of that first and um yeah so you know as you can imagine just based on how genetic testing has evolved over the last couple of decades, the claims universe that exists today is disproportionately representative of the younger cohorts of patients, the 25 and younger. So there's more work to be done from a diagnostic perspective to identify those additional 10,000 patients that are largely adult patients. And so the focus of our screening efforts will be on that adult segment, on the adult providers, while we also want to move diagnosis as early as possible for patients. But to your point, payers may limit reimbursement to trial inclusion criteria. And so we anticipate having data for patients that have aged into adulthood from our phase one, two, and OLE studies that we will specifically look at. But in addition to that, later this year, we're going to be starting a small adult study looking primarily at safety, but we're also going to look at seizures. we're going to look at neurocognition, and we're going to look at some endpoints that are specific

Kevin Strang, Analyst — Goldman Sachs

to adults. Great. And I wanted to talk about durability of therapy and sort of how you think about that. I know you obviously have long-term data at this point. In addition to that, what other assumptions are going into how you view the persistence of therapy in the real world?

Jason Hoitt, Other

Yeah, I mean, you know, we've now got four years of OLE data, and the retention in the OLE study has been remarkable. The fact that we're also now, you know, well into the phase three and we've seen zero dropouts to date. I think, you know, the family seeing the benefit is the greatest motivator to stay on treatment. But to your point, we're already starting to build our patient services offering. And so, you know, obviously with a rare genetic disease, we'll have a team of in-house folks that are interacting with families, interacting with offices, helping with everything that we can compliantly help with to get a patient on treatment and ultimately help them stay on treatment.

Ian F. Smith, CEO

Could I just give you a statistic? The OLE, the patients that will 90% have done.

Kevin Strang, Analyst — Goldman Sachs

From a, I want to move on to a competitive standpoint. You know, is there anything that you're looking at in the disease-modifying landscape? I know, obviously, that's sort of how you think about your therapy in the disease-modifying category versus, you know, an ASM. So when you look at that disease-modifying landscape, Is there anything, and then in terms of, you know, gene therapies, could those, you know, potentially be, are those what you look at as complementary, competitive? How do you see that when you look at other, you know, rare diseases?

Ian F. Smith, CEO

We don't see anything that's the same as what we've got.

Kevin Strang, Analyst — Goldman Sachs

You know, we don't see somebody that's maybe trying to make it better as a nurse.

Ian F. Smith, CEO

And, you know, frankly, we don't say it. We've got a very strong IP portfolio. and we also have five years' worth of data. In terms of gene therapy, we do see some interesting approaches. There's a company out there that's doing gene therapy, and we look at that as somewhat validating, putting the SCM1A gene back in. And so that's an interesting approach. It's very early. They've been trying to figure out their dosing, and they put out some data recently. It's interesting, I think. But I kind of look at Zolgensmer and Spinraza, and if you look at the history of an ASO and gene therapy, gene therapy was interesting, but most patients roll on to Spinraza because of the durability, you know, at the point you were just making, I should get, the durability and the consistent response because you're continuously dosing. I think there's a lot of questions that remain about gene therapy in terms of its true one-time dosing and durability of benefit, as well as there's got to be questions on safety, because the administration is going to bore a hole in the skull and inject into the brain, and it's AAV therapy still, and so it must come with some safety concerns as well. So we'll see how the landscape evolves, but there's nothing right now that we look at and say we're concerned about.

Kevin Strang, Analyst — Goldman Sachs

Makes sense. And I wanted to ask briefly on your partnership with Biogen, since we haven't really spoken about that yet. How has that partnership evolved over time? Obviously, there's a lot of overlap with the ASO space and the rare disease space. What's been most valuable to date in terms of that partnership?

Ian F. Smith, CEO

I'll go all the way back to before the partnership existed and say I was on the board as an advisor at the time but I did help the company with its business development opportunities the number one question was do we have the global capabilities to get this medicine approved and launched into patient populations in its single payer markets and the answer two years ago was no so we started a process, competitive process even when we started the competitive process Stoke would like to have had Biogen as a partner because of Spinraza, because of its manufacturing capability, because of its global reach and its capability, and Spinraza and SMA. we closed with Biogen and we closed with Biogen I believe it was February 2025 so just over a year ago and the relationship with Biogen has been excellent, it's been everything we hoped it might be in terms of how they're helping us outside of the North American territories and they bring a lot of capability to the table, we're running the studies we're responsible for the design the progression of the studies, and we keep Biogen updated, but we have a whole governance structure in terms of joint steering committees, joint development committees, joint commercial committees, joint manufacturing committees, and there is daily conversation and exchange information between the two companies, but it's working really nicely.

Kevin Strang, Analyst — Goldman Sachs

Great, and I see we're essentially at time. I wanted to briefly ask about your program in ODOA, STK, OO2. What should we be looking for in that program on the horizon? And then finally, just in terms of your cash position, where are you at today, and what sort of milestones does that get you to?

Ian F. Smith, CEO

Yeah, so quickly, ADOA is a genetic progressive loss of eyesight. We are in a phase one, two dose, single-dose escalating study. We're in our first cohort of dosing. We anticipate four cohorts with cohort three and four, or potentially giving you an efficacy readout towards the end of this year or early 2027. And so we're pretty excited about that. We think OPA1 is the right target to increase mitochondrial function. And then to your second question on cash, we're very well capitalized. We've got over $400 million of cash as of the end of Q1, and that cash supports us all the way through to 2028. We're also supported by Biogen, paying 30% of the development costs for Zareva nursing. So we're in very good shape.

Kevin Strang, Analyst — Goldman Sachs

Great. Well, thank you, Ian, Jason, and the team at Stoke. Appreciate it.

Ian F. Smith, CEO

Yeah, thank you.