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

Yeah, okay, great. Great to be here. Thanks, Josh, and appreciate the opportunity to take the stage with you and to discuss an exciting time at Denali. I think the best way to frame Denali right now is that there are really four major aspects. The first is that we have our first product in AVLAYAH, as you pointed out. It has been a very exciting year to launch our first medicine. That product ends up, for us, validating the platform. So we have product and then platform, and that platform has now led to a broad portfolio. We are going to get into some details, and I think the simplest way to view our portfolio is the enzyme replacement therapies, and then we have Alzheimer's as well, and a number of key readouts coming in in 2027.

The fourth point, so we have product, platform, pipeline, and the fourth point is having the capital now to execute into 2029, so about $1.1 billion in cash. Obviously we are spending a significant amount of our resources on the portfolio. We have, of course, early signs of a strong launch with AVLAYAH. But I think what is probably not appreciated, as you pose that question is the fact that this platform has the ability to deliver now a number of products. We have five additional clinical stage programs with a lot of data coming out in 2027. So it is clearly an exciting time.

Obviously, we launched this product ourselves, as a company to go from discovery to development and now to delivering medicines to patients. I think, Josh, as we were just commenting before the fireside chat, it is really rewarding to be part of the patient community and actually delivering a medicine.

Right. If you look at the label, it's essentially pediatric patients. The key term in the label which really differentiates it, I think, from obviously the standard of care is neurologic manifestations. This doesn't mean neuronopathic and non-neuronopathic, it means that the medicine is really approved for neurologic manifestations, which represents essentially all Hunter patients. For example, even attenuated patients have hearing loss, as I think one of the probably more powerful pieces of data that was published in our New England Journal article earlier this year. We're seeing benefit in hearing, obviously cognition, behavior, and it's using cerebrospinal fluid, heparan sulfate as the biomarker for this accelerated approval, but a lot of data supporting the fact that that was predictive of clinical benefit. If you look at the pediatric population, it's about 375 of the 500 patients.

Importantly, every year there's about 30 new Hunter patients. This is all just U.S. So worldwide, there's 2,000 worldwide, but we're just talking about U.S. numbers here with the U.S. accelerated approval. You can think about what that spectrum looks like. There's the newly diagnosed, there's the patients that are eagerly awaiting, there are those that are just about to become adult. There are many patients that have been on, for example, intrathecal delivery, and who have been also eagerly awaiting. There are older patients. That's how really the frame, the total patient population, about 375 patients today, the prevalent population, that are eligible for AVLAYAH.

That is right. There is a complexity, and I think this is where what we basically in our first quarter, we described obviously the revenue, and then we have given a revenue target for the next quarter and likely for the fourth quarter as well, early on. Part of that is because it is really complex, right? It is weight-based dosing. You have very small, young, pediatric, newly diagnosed, 10 kilogram. Then all the way up to 16-year-olds. That is exactly right. It is weight-based dosing, and there is a pretty broad spectrum.

Yeah. It is definitely a meaningful number of new patients coming on, but it is also the dose escalation, and it is exactly the reason why I think we took the unusual step of just guiding towards a revenue because of that complexity. The question itself sort of highlights the complexity. I think importantly, the vast majority of patients who have started are not crossing over from our clinical trials. That will, by end of year, most of the patients that are in the phase I/II will have crossed over to commercial product, but this first real set of revenue is coming majority from new patient starts. Most of those are switches. Most of those are patients who have been on Elaprase and are switching to AVLAYAH.