Stoke Therapeutics, Inc. Common Stock Canaccord Genuity's 46th Annual Growth Conference

Thanks for the question, and good morning, everybody. I do have to provide my safe harbor statement, so if you'd see our SEC filings for all the forward-looking statements are covered in our SEC filings. Just last week, we had the opportunity to have our second quarter call, and we did provide an update at that point on the phase III study. Just to kind of broadly, it's a phase III study, sham-controlled, 162 patients study with a primary endpoint at week 28 and a secondary endpoint at week 52. As far as the progress of the study, we couldn't be happier. First of all, 162 patients enrolled. We did target 150. We ended at 162. Of those 162, 145 are already through week 8. Why is that an important time point?

Because at week 8, you've taken 2 doses of 70 milligrams, and it also means that all you have to take now is 2 doses of 45 milligrams over that 52-week period. Also, in terms of the progress of the study, we have approximately 80 patients that are through week 24. Week 24 is important because you've now received 3 of the 4 doses you'll receive over the 52-week period. Lastly, as a mark of the progress of the study, we have 60 patients that are already through the primary endpoint at week 28. So 60 of the 162 patients are through the primary endpoint. Progress so far, which I think is also reflective of a well-tolerated drug, is we have zero dropouts. So zero dropouts at this point.

The drug clearly is well-tolerated, which is also supported by the totality of the data that we have gained from an OLE study that is now extended dosing through a four-year period. A five-year period in total if you include the phase I, IIs. All is proceeding very well with our phase III study. We look forward to give you another update probably towards the end of the third quarter.

Well, it is a remarkable statistic in terms of a phase III. Just to, again, to reiterate, it's a phase III, and we have a lumbar puncture sham control. We did plan for discontinuations, as you might expect with a sham control lumbar puncture. We planned for a 15% discontinuation rate. That was in the powering of the study of 150 patients, 15% discontinuation, so approximately 125 to 130 valuable patients to hit our primary and secondary endpoints. Why is it that we have no dropouts? Well, first of all, I think it's a well-run study. Our team, our field team, our medical directors are working well with the sites, and the sites are well-educated to what our drug can potentially do for these patients based on the data we've provided at medical conferences. One is a statement of fact.

The drug must be well-tolerated to date. Otherwise, we would have seen dropouts related to the drug. We have no dropouts, so that must be a mark to the well-tolerated profile of the drug. Secondarily, at this point, no dropouts from the study could also point to we have an OLE or a second treatment period that all these patients can roll into. If you're in the sham control and you're not sure whether you're on drug or on sham, because of the education we've provided around this drug, you're probably hoping that you can move into that post week 52 treatment period where you're guaranteed drug. The second part to what I'm saying is obviously a little bit of speculation, because we're blinded to all the data.

The trial's going very well, and the education around this drug because of the five-year data set that we have in terms of safety and efficacy, I think is also educating the physician who is managing the patient as well.

Yeah. First of all, start with we have breakthrough designation to treat Dravet syndrome, not to treat seizures, to treat Dravet syndrome. That breakthrough designation was provided on the submission of data for both seizure reductions and our Vineland scores after 2 years of patients being on drug. We submitted the OLE data and the phase I data where we showed seizure reductions but also showed cognition and behavioral gains, and we submitted that to the FDA to request breakthrough designation. They gave us the breakthrough designation because they recognized it in the behavioral and cognition gains that the patients were receiving within that phase I/II and the OLE data set. We then designed a phase III trial that one, as a primary endpoint, does measure seizure reductions at week 28, as I mentioned.

But also at week 52, we're measuring the cognition and behavioral gains through an assessment called Vineland-3. It's got multiple domains such as receptive communication, expressive communication, motor skills, interpersonal skills, social skills, things like that. It's a questionnaire within each one of these domains that a neuropsych provides to the caregiver. The caregiver can see whether the child responds to the caregiver's voice, to their name, whether the child was non-verbal and is now using words. That's what's within the Vineland domains, whether it's receptive or expressive communication and motor skills. We've designed the secondary endpoints to measure those behavioral and cognition gains. That's consistent with what we've seen in our 4-year OLE data.