Neurogene, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

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Yeah, happy to be here. Thank you so much. Great.

Yeah. Thanks for the opportunity. Neurogene is a full-stage biotechnology genetic medicines company, focused on developing treatments for devastating neurological diseases. Our lead program is NGN-401 for the treatment of Rett syndrome. Rett syndrome is a neurodevelopmental disorder that starts in early childhood and is really lifelong. It's a chronic debilitating disorder, where multiple core functions that we think about and take for granted, like communication, our ability to use our hands, our ability to ambulate and walk around normally, all of these are drastically impaired in Rett syndrome. There's a massive unmet need. So 15,000-20,000 patients in the U.S. and major European markets with Rett syndrome. There are no treatments available that really treat the underlying cause of disease, and that's where NGN-401 comes in. It is a genetic medicine.

It's an AAV gene therapy, and we can get more into the design and differentiation shortly. It is delivered as a one-time treatment to really get to the important areas of the brain that matter in Rett syndrome. I think important for this discussion and before we can just kind of give you a high level view, but we presented phase I/II data in June, so very recent cut of the data with 12-30 months of follow-up and saw just really substantial improvement and gain in function, which is again, something that we're privileged to be able to observe in these patients with Rett syndrome. We can talk more about that data, but 100% of patients responded based on both an improvement as judged by the clinician as well as gaining developmental milestones.

We also announced earlier this year in the second quarter that we completed dosing of our registrational trial, Embolden. That is a 12-month primary endpoint with data available in the second half of 2027. So a lot going on for Neurogene. We are rapidly advancing towards commercialization in a market that desperately needs new therapies, and we're very excited about the profile that we've established in phase I/II, to be able to support that.

Yeah. Happy to talk about some of the key design choices. Neurogene, we really take a very intensive biology first approach. We designed this construct from scratch. This was not a business development deal where we in-licensed it. We really had to think about first principles, what are the most important aspects of this drug product that we're going to build in. First and foremost, we wanted to include the full length, MECP2 gene. MECP2 deficiency is what drives Rett syndrome. This is a gene that is highly conserved throughout nature, so very important, and thankfully, it is a gene that readily fits into an AAV. We didn't have to do any tinkering to make the gene smaller in any way to have it fit. That was sort of point 1.

Point 2 was, and this is a little bit what you were alluding to, we know based on both preclinical as well as human data, that too much of this protein, MECP2, can be toxic. As a result of that, we need a little bit of a Goldilocks type situation where we need to be able to control the levels of transgene that is being produced by the vector. In order to be able to do that, we developed a new technology which you referenced. It's called EXACT, and it's a microRNA-based feedback loop that's literally built into the vector.

We have a microRNA, along with the transgene, and complementary suite of microRNA binding sites that are on the transcript such that every time the transgene is produced, you also get the microRNA, which then is able to bind the transcript and then basically cause a shut off valve, if you will, to maintain a therapeutic level of MECP2 without overshooting and getting into that toxic range. That was a key feature. Then finally, the other critical feature in gene therapy is really about delivery, right? We had a very intentional, purposeful choice of ICV delivery. That stands for intracerebroventricular. It's a way to access the cerebral spinal fluid locally in the brain to really maximize the number of brain neurons that we're delivering NGN-401 to.

That's critical because Rett syndrome is a brain disease primarily, and so being able to maximize that exposure was really critical. That's quite different. We could do the compare and contrast, but relative to the other program out there, but we're very pleased with the features. These were very intentional, and it seems to be coming through in a very competitive data profile that we presented in June.

Yeah. Milestones, just to level set. In Rett syndrome, a typical child is gaining developmental milestones all of the time, right? Whether that is learning how to sit up unassisted for the first time, learning how to talk, for their first words, being able to go up the stairs, being able to use a fork. These are basic developmental milestones that anybody who has kids or grandkids, they are sort of front and center. Unfortunately, in the course of Rett syndrome, while girls do start to develop milestones, they do so in a delayed fashion, but more heartbreakingly, they actually go through a regression phase of the disease where they actually lose many of those previously acquired developmental milestones. Universally, these girls become non-verbal. Some of them might have had a 100-word vocabulary, or at least were saying a few words. They stop speaking. They typically had some level of hand function.