Neurogene Stifel 2026 Healthcare Conference 2026

Yeah. Thanks, Paul. Thanks for the invitation. Really happy to be here. So again, Rachel McMinn, founder and CEO of Neurogene. We are a late-stage clinical genetic medicines company focused on developing treatments for rare, devastating neurological disorders. Our lead program is NGN-401, for the treatment of Rett syndrome, which is really just a very devastating disease, huge unmet need, somewhere between 15,000-20,000 people in the U.S., as well as major European markets that have this disease. There are no treatments that really address the underlying disease course. So this is a really exciting opportunity for the community, for Neurogene. NGN-401 completed dosing of our pivotal study, and I know we will have lots of questions on that, but we completed dosing. We announced that in early June. It is a 12-month study, so we will have data in the second half of next year.

Then in terms of kind of what is going on in the overall state of the state, it is a really exciting time. We are in the process of literally transitioning into a pre-commercial, kind of commercial-stage company in anticipation of a future BLA approval. So there is a lot of work going on at Neurogene right now, both on the pre-commercial build-out, and we can talk a little bit about that, and medical affairs team out in the field, and continuing to build and grow the commercial function for pre-commercial activities. Then on the science side, just continuing to generate new data to help differentiate NGN-401, and I know we will get to that as well.

So just a really exciting time for the company, and I guess maybe two other things I should mention on the pre-commercial front is very much on track for completing PPQ before the end of the year. So this is a CMC activity, which, for anyone who is in gene therapy, there is a lot of work, and our team is actively completing PPQ as we speak. BLA authoring has already kicked off, so we are really trying to get a jump on this and front-load as much of the work as possible, so that we can very efficiently file after top-line results in the second half of 2027.

Yeah. As a reminder, we dosed 10 participants at a 1E15 vector genome dose. These patients ranged anywhere from four years to 18 years of age, and they had a clinical and genetic disease severity spectrum from mild, moderate, severe. All of these patients are very impaired, but in terms of the scale for Rett syndrome. So really representing the broad range of patients out there. All patients improved as assessed by the CGI-I, as well as gaining one or more developmental milestones. In terms of what that looked like over time, what we saw is patients gaining milestones as early as the first three-month assessment. The number of milestones and the breadth of milestones continued to augment at six months, nine months, 12 months, and beyond. In terms of durability, really important question, right?

If you're giving a gene therapy for a disease like Rett syndrome, which is a chronic, lifelong, absolutely debilitating disorder, you want to make sure that these milestones are durable. I'm happy to report that all of our participants, once a milestone has been gained, they've been able to retain that.

This is really verified through an independent rater of caregiver videos or clinician-based videos in the clinic. It is a combination of those things. It is things that we can document.

We dosed 25 participants in Embolden. This is on top of the 10 participants that we talked about with phase I/II, so a total safety database of 35 participants at the 1E15 dose. While we are not making detailed safety comments on a quarter-by-quarter basis, it is an ongoing, active registrational trial. That would not be appropriate. What we have mentioned is, as of November 8, our earnings release that we just put out mentioned that NGN-401 continues to be well tolerated. To the extent that folks have concerns about an earlier toxicity that had happened with a much higher dose, HLH, we have reaffirmed that we have not seen anything like that. If you were to see that would happen very close in time to dosing, and we are well past that treatment window. I think we are feeling very good about the tolerability profile.

Yeah. So, multiple questions in there, but let's just take a step back. The Embolden trial is a baseline-controlled study, and what that means is that these participants are actually serving as their own control. This was really unique and special, and we were able to design this in consultation with the FDA. The primary endpoint, I alluded to it before, but just to be very clear, it's a composite endpoint of both an improvement in the Clinical Global Impression-Improvement, or CGI-I, as well as a gain of one or more pre-specified, predetermined 28 developmental milestones. To give you a sense, because a lot of people, it's like, "Developmental milestones, what does that mean?" For folks who have kids, this might be more obvious, but being able to hold a cup and drink that unassisted, that is a developmental milestone.

Being able to sit unassisted or go up the stairs by yourself, being able to express yourself, whether somebody has given a gesture or not, but being able to react to a command and do what your mom actually tells you to do, "Put your backpack over here," or, "Go eat your food." These are the kinds of things that we're looking for in the Embolden study. The way this works is participants come in, they have a very rigorous baseline assessment to kind of establish what is that baseline, right? Because all of these girls are different, and one of the really strong rationales to have a baseline control is you wouldn't be able to get a homogenous, like, "Well, everybody does this," because no two Rett girls are really the same. They all have slightly different levels of function.