Stoke Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thanks, Pete. You can breathe now. Pete just arriving. Thank you for the introduction. Happy that you took time out of your day to listen to the Stoke story and go through the Q&A with Pete. Today, Stoke is a company that has a phase III medicine to treat Dravet syndrome. We've fully recruited that phase III study. Anticipated readout should be the middle of next year, probably within the next 12 months. I'm happy to answer all questions regarding the opportunity of that phase III readout and how we think about it, how the trial is going, and also how post-data and also approval, how we think about the market.

That includes patients and what this medicine may be doing for those patients, as well as the value of that medicine, not just to the patients, but also to Stoke as a company, given that this medicine was created by Stoke from the bench- all the way through, hopefully, to the patients.

We've advanced as a company significantly over the last couple of years, rapidly and growing. We also have a growing pipeline. We have another medicine focused on ADOA, which is a genetic form of loss of eyesight, loss of vision. That study is progressing nicely in a dose escalation phase I/II study. We're into our second cohort of patients and expect to be soon into our third cohort of patients and talk about that. Financially, the company is in a very strong position. The balance sheet data that we provided to the investment community as of June 30, we had over $400 million of pro forma cash that took us through to early 2028. We're well capitalized and in a good position to continue to develop our medicines through to launch.

Obviously, the data readout from our phase III, that's within the 12 months, if we transport ourselves forward in that time machine. Looking back the 12 months, yes, clearly the readout from the phase III is a very important value-creating event. It'll establish the medicine. It'll establish the profile of the medicine. The design of the study goes beyond treating seizures for Dravet, but it goes to maybe a disease-modifying medicine to treat both the seizures and also cognition and behavioral morbidities within this disease. That would be the one big achievement, looking back.

I think also, throughout the next 12 months, if I now transport myself back to today, looking into the future, I think as the trial progresses and continuous updates on the trial and how the patients continue to move through the trial and potentially into a second treatment period in open label study post the 52-week trial, I think those are important metrics of how the study progresses. On the ADOA side, I do feel as though with cohort 3 and 4 in a four cohort for phase I, phase II, we start with cohort 3 and 4 getting into what we think is a therapeutic level of dosing. And we have potential to show that impacting OPA1, which is the genetic target, but impacting OPA1 does upregulate mitochondrial function and therefore enhances vision, as in improves vision. Doesn't just stabilize vision, but improves vision.

That's also within the next 12 months, and I think would be a defining event for the company as well because it'll be also emerging pipeline.

Yeah. To be honest, it's a long answer because when I think about the medicine itself, zorevunersen, just to give you a brief understanding of its mechanism of action, its target, this is a genetic therapy targeting the SCN1A depletion. What that means is that when you have a mutant gene, you're not producing enough protein, NAV1.1, which is the root cause of Dravet. Going from the bench targeting SCN1A to upregulate the protein NaV1.1 has always been the principle of this medicine because it addresses the root cause of the disease. Our studies preclinically have shown that we can get to potentially wild-type levels of NaV1.1 in our animal models.

Translating that through to the dose that we're using in the clinic and ultimately through to the Phase III, because you're addressing the root cause of the disease, our anticipation is that you would significantly reduce seizures, which we do see. To one of your questions, Pete. Also, we're seeing these patients that plateau at the age of 18 months to 24 months. We're starting to see them gain function when they go onto medicine. What I mean by gain function is like gaining tasks and ability to do certain tasks, the ability to communicate, ability to receive communication. We've seen all of that. What is really interesting today, and to your point, Pete, is the data that we have in our open label study.

Once these patients were through the Phase I, II study of this medicine, they had the opportunity to go to an OLE study, and certain patients have been in that OLE study now for four years. This is a chronic disease, and we dose the medicine chronically. As we dose the medicine chronically over a longer period of time, the seizure reduction has been sustained at levels of 75% plus minus. Also, we see this continuous gain of function and task as measured through a questionnaire called Vineland-3. You do see improved communication. You do see improved motor skills. That's what's been really fascinating about the longevity and the durability of the OLE data to support a chronic disease, but you're giving back function the longer they're on medicine, as well as sustaining those reductions in seizures.

Now, we have to now proceed and run a phase III trial that has seizure reductions as a primary endpoint and cognition and behavior as the key secondaries. We are well into that, and the trial is progressing very nicely.