Good afternoon, everyone. Welcome back to the Second Annual Guggenheim Healthcare Innovation Conference. My name is Eddie Hickman. I'm one of the Biotech Analysts here at Guggenheim. This morning, I'm welcomed by Zevra Therapeutics CEO, Neil McFarlane. Neil, thank you for joining us today. Glad you made it. Maybe before we get started, just for those who are listening who aren't familiar with Zevra, maybe just give like a two-minute history of the company and where we are today moving forward. Yeah, thanks, Eddie, and thanks for having us. I will be making some forward-looking statements, so please take a look at our most recent SEC filings for the most up-to-date information. So Zevra, Zevra is a commercial-stage rare disease company. We have two commercial products that are in urea cycle disorders as well as in Niemann-Pick disease type C, two ultra-orphan indications we can talk a little bit more about later. And in addition to that, we have a late-stage development program in vascular Ehlers-Danlos Syndrome that's in phase III and enrolling patients today. And to kind of round out the portfolio, we also have royalties and milestones from a program that we developed in ADHD that is currently being commercialized by another party. And on top of all of that, we have a balance sheet that is fairly robust with about $230 million in capital today. If I think about some of the real focus points for us today, it's around our Niemann-Pick disease type C program. In the U.S., there's about 900 patient prevalence of Niemann-Pick disease type C. We got approved just about a year ago. As a matter of fact, we had commercial product in the channel at the end of November last year, so not even quite a year, and to date, we've been able to actually have 137 prescription enrollment forms for Niemann-Pick disease type C. That's about 40% of the diagnosed patient population, that 300-350 patient population, so our launch has gone really well. Last quarter, we put eight new enrollment forms in to make the 137. I know that we'll talk a little bit more about the details, but really proud of where we are. But in addition to that, in Niemann-Pick disease type C, we filed our Marketing Authorization Application at the end of July, which has now been validated, and we're on the 120-day clock of which we'll get the responses by the end of this year. So we're active in looking at expanding the TAM and addressing patients in Europe with NPC. And in Europe, we have that prevalent patient population of about 1,100 patients, but much more mature market with an approved product that's been there for well over a decade. So we see that as a marketplace that, with the strength of the data package we have going into the regulators, but also the clinical and real-world experience we're seeing in the U.S. as a real benefit for patients in Europe. So we're just in the start of our launch. It's going well, but we're really looking forward to the upcoming catalyst of executing today on our launch in the U.S., getting our Miplyffa, or our arimoclomol in Europe approved, and then moving forward with creating this leading rare disease company we aspire to be. Yeah, I was just going to say, last year at this conference, we were talking about just sort of like the initial launch and what we should expect for the first quarter, and now you're a year out. You just reported the third quarter earnings last week, so this is a timely conversation. Do you want to just give a quick overview on what you reported in terms of where those patient enrollment forms, how much of that is revenue, and sort of how should we think about how to sort of capture the rest of those 60% of patients that you know about? Yeah, so maybe I can take a step back and start a little bit at the 300-350 patients. We've had a lot of questions in regards to, do we know where those patients are? Do we understand the diagnosed patients, the journey? If we think of NPC, it is kind of four archetypes of the same disease. The infantile version that usually you're diagnosed because of failure to thrive, you're having these problems really early on, but the progression of the disease is very fast. You have then these children who are primarily normal. They're on the growth trajectory of a normal child, and then they start to get a little clumsy, and then they start to have speech impediment, then they have swallowing challenges and gait challenges, and then they start to progress at a different pace than the infantiles. But then you have the young adults. We know of a case of a young lady who's valedictorian of her class, goes to college, has some problems concentrating, her cognitive abilities start to go bad, she starts to get clumsy, she starts to have some speech and swallowing challenges, and gets diagnosed, then a very different disease progression, but yet still cognitively impaired, has the neurological implications, and then you have some patients who are in their 30s, 40s, or 50s that are diagnosed for the first time with a psychotic break, and that's their first entry, and then you find out that they had some gait issues and what have you. So in like a lot of rare diseases, the journey that you go on to try and diagnose a patient, you know one patient. So backing up to the 300 and the 350 patients, we know these patients have an ICD-10 code that is NPC. We know that of that, they've been seen by a doctor for something, and that code has come up within the last two years multiple times, not just a single time. And our commercial and medical groups are out there educating and working with the physicians, as we mentioned in our prepared remarks, not just with the center of excellence where primarily every patient is diagnosed, but then also in the community docs. So we're expanding the breadth, which is still a close relationship between the community docs and the centers of excellence, but we're expanding that relationship now, and we're getting and having conversations with physicians in these community centers and saying, "Hey, you have an NPC patient. Here's what we have as a disease-modifying agent for a 30-year-old that's been diagnosed for 10 years that you didn't know that was there." So it's been a real eye-opener for us as we are now in the fourth quarter of launch to say we're getting these early-enrolled patients that are, let's call them faster-progressing, we're getting the diagnosed patients and having meaningful conversations with physicians that are then getting them diagnosed. But the most promising thing of our Q3 results was really that we're starting through our efforts in disease state awareness and genetic testing counseling offering that we're doing, we're starting to see patients who have been never diagnosed before. We saw some in Q2. We didn't talk about it much because it was kind of a small number, and we weren't so certain. But in Q3, we added more newly diagnosed patients. When we think of the 300-350 patients, not all of them are going to qualify, but we do see the market now greater than the 300-350 patients. Probably we know it's somewhere between 300, 350 and 900. Where that is, we don't know, but we're now starting to unlock that opportunity. It is learning as you go, as you know, in these launch phases, but we're really focused on the right things. Where we know the diagnosed patients are, we're working through those patients one by one and the docs and making sure there's an awareness and drive. Then we're also now working on the disease state and the genetic testing to get patients diagnosed earlier. Yeah, I think it's interesting to sort of look at those buckets when you're talking about where you can put your focus. You had an EAP, a pretty extensive EAP that you were able to really rapidly convert into paid drug. How should we consider how that population sort of mimics the overall population, or do you think that was, when you're thinking about those different buckets, like how is the EAP diversified across those buckets? Yeah. It's a really good point. So our EAP originally was populated by patients who came out of either our OLE program or the clinical trial program, and those were primarily patients under the age of 19. As we then moved through our EAP process, we saw more real-world level experience. So our EAP at the time when we closed the EAP at 83 patients was 50-50, 50% adults, 50% kids. What we've now seen in the 137 patients, it's mirroring our EAP, which we have about 50% adults and 50% kids. So our EAP really, and actually we're even seeing that in the dosing of patients where we have its weight-based dosing, we're seeing an equal kind of separation of dosing that's representative of adults and children too. So moving forward, I expect that ratio of 50-50 will continue because the law of small numbers is getting bigger and it's continuing. So to change that ratio is going to take a lot of one or the other. Right. And you mentioned you're using genetically these genetic screens for these younger patients. So can you talk about sort of what the different, from a physician standpoint, but also from like a commercial and payer standpoint, like what the different lifts are for a younger, maybe infant patient that's just been diagnosed with genetic screen and then maybe a 30-year-old who is now just discovering that they have NPC and trying to get on it? Those are obviously two very different populations, but the same commercial team, the same set of KOLs and experts. It is. And I have to say that this is the beauty of being in the rare disease business for decades now. You know one patient, you know one patient. It's really hard to extrapolate what a patient's journey is and how they've presented and how they move forward. But the one thing that I can say almost unequivocally, and you maybe ask a poll of 100 industry representatives and maybe even clinicians, once you get a disease-modifying product on the market that can halt the progression of the disease through 12 months like our label, and you start to see that awareness grow and there's something available, physicians start to find new patients. And they start to have one patient, and a lot of times even in a community setting, you'll have one patient, but that community doc may never have ever seen an NPC patient. They're going to be on the lookout for it now. They're going to think, when you see Parkinsonism and ataxia, they may not have thought of NPC before. Putting those two together, now they're going to think about it. When they see cognitive decline in a younger person, they're going to think NPC versus just thinking, "Oh, you're just clumsy," or whatever the case may be. So the learnings that we're taking from our going out and speaking with the physicians who we know have these NPC patients, one of the COEs may have been the diagnosing center, but you may have four or five different community docs that see that one patient from a gastroenterologist to a psychiatrist to a primary care person. We're seeing maybe sometimes three docs that are the same patient and going at it from education perspective, and this is what NPC is. You have a patient, we know. Your ICD-10 code says you've had a claim here in the last two years. It's that education that then I think we will see more and more physicians have it in their mind because we're telling them they have a patient and educating them on the disease. Yeah, I think you said something on the call about how there are some patients that maybe get diagnosed in the first dose at a center of excellence, but then they can go back. Is that a fair way of thinking about it? So those community docs are now aware of the treatment because they've sort of been referred out. And are those the neurologists that are doing it in the community setting, or who's really prescribing it outside of those COEs? It is fascinating to me, but all the above. And we're learning. Let me give you two anecdotes. We had a, I don't know the exact age, let's call it 30-40-year old female that had been diagnosed 10 years before with Niemann-Pick disease type C at a center of excellence, but there was no disease-modifying therapy. Our rep went into that doctor's office, educated that physician on NPC. They said, "We don't have an NPC patient." That patient came in a few weeks later for something totally outside in a primary care setting, totally outside of an NPC issue, but had a cane and had speech impediment and swallowing impediments. This physician went through the chart, said, "You've been diagnosed with NPC. I just had somebody in my office talking to me and educating me on NPC." They called our rep, they called our medical folks, we went and did the education, and that patient got the prescription form because the patient didn't even know there was a disease-modifying agent because they had been diagnosed with NPC, 10 years before and just continued to progress. Then that's just N of 1. We had a psychiatrist that had a patient, an older patient that had no idea. We went and talked to them, the psychiatrist then ended up, and a psychiatrist is not usually in a position to initiate treatment of a drug that is disease-modifying in rare disease. Put them in contact with the center that diagnosed the patient, worked through that process, and got the psychiatrist with our patient support services and AmplifyAssist to actually support that patient's prescription. These are two separate anecdotes so far off that that's the kind of work that our teams are doing on a daily basis while they're doing the disease state awareness and offering genetic testing to patients who may have NPC. So what feedback do you hear now that it's been almost a year? How does the sort of tolerability and safety and compliance comparing to what you saw in the clinical trials and in the EAP? So we had a field and market research recently over the last few months, and we actually talked about this a little bit on the call. This market research, obviously anonymous, we want to understand a year in what are the learnings and how is the market perceiving Miplyffa. And we saw a couple of things that we talked about on our call. Anecdotally, patients are saying that they're having improvements in gait and they're having improvements in swallow. We're having physicians that said that it's their preferred agent based on the long-term data. And recall, since our approval, we've actually now published our OLE 5-year data that reinforces the strength of the data. We're in the process of, we've gotten abstracts up in the process of delivering on our 5-7 -year EAP data. We did a pediatric study, sub two years old, that hasn't read out data yet, but we actually submitted that as part of our MAA package and dossier. All this data now is coming in. Physicians have come back to us in our survey and said, "We believe this is the preferred agent to be able to move forward as a disease-modifying agent." Payers have also, in that market research, said to us that patients and physicians want multi-modality treatments for such a heterogeneous disease. So if there's data and there's availability, they're trying to get patients on product, as many products as they can. Physicians are doing that. Some physicians are doing that in a disciplined approach, add one, add one, add one. Others are saying, "Let's get them all together." What we're seeing is payers are paying for them as well based on the strength of our data. Yeah. And I appreciate that color. And when we're talking about the patient funnel, right, because you're reporting patient enrollment forms and patients that are coming in and then your revenue down. So what are the sort of key challenges or delays in getting a patient from that initial patient enrollment form down to a paid drug that they are hopefully getting continual refills monthly from? Let me start at the end. Our adherence and persistency rates are the highest I've ever seen in my career and very much mirror what we saw in our EAP. In our EAP, patients just did not stop taking therapy unless they progressed to a place where they were now in hospice or needed palliative care only, or they passed away. Otherwise, patients were continuously taking therapy. It's the highest persistency rate and adherence I've seen. We have a very similar type of persistency rate that we're seeing in the market today, but it's too early for me to say I got a metric for you. But I can tell you that it's mirroring our EAP persistency. Moving up to the rest of the question, it's hard for me to say what those challenges are and if they're any different to what any other high-value therapeutic has. Payers, for the most part, want to see the data to ensure that they're paying for something that adds value for patients. Physicians are getting through the medical exception process with the quality of data we have. I've said this a few times. Usually, you launch a product, you have a package insert, and that package insert's all you have. Fortunately or unfortunately, we have not just a package insert that's very strong that talks about the halting of disease progression through 12 months on the NPC CSS in combination with miglustat. We also have five years' worth of data, OLE data that you're going to a payer and say, "Hey, here's our label, but also, by the way, you asked for one more year data. Here's five years' worth of data, so we have that strength of data in the package that's really been helpful in both our teams pulling through, our patient services group helping pull through, but also it's really helpful for payers to have that strength of data too to get it through their system. Yeah, absolutely. Now, I want to talk a little bit about the European opportunity, but before I get to that, how will you continue to sort of guide the street moving forward into the second year of the launch in terms of patient enrollment forms or revenue? Have you sort of thought about how you might communicate your expectations moving forward? Yeah, giving guidance is really based on a lot of the market opportunities that we've seen. To date, what I would tell you is that I would not have thought a year into a launch, not even a year into commercialization, right? We put product in the market at the end of this month that we would have converted all of our EAP patients, all of our EAP patients. I thought would have happened like this quarter. It happened really early. If I think about where we are now in getting new patients that are newly diagnosed patients in the top of the funnel with our efforts that we've started in the last six to eight months of disease state awareness and offering genetic testing, I probably would have said to you that we wouldn't be seeing the fruit of that labor and getting new patients yet. So all of the market dynamics make it very challenging and a lot of small numbers make it very challenging for me to say about guiding you moving forward. What I can say, and I think is probably one of the important parts, is this 300 and 350 patients that we know where they are and we're uncovering those and those are coming and turning into prescription enrollment forms feels really good. The additional patients between the 350- 900 that we're now seeing enrolling gives me a lot of confidence that we're somewhere between the 350 and the 900 in terms of the market opportunity in the U.S. As I mentioned, as we're going to flip to Europe, 1,100 patient prevalent population in Europe because of the work that was done with miglustat over well over a decade, right, of investing in disease state awareness, investing in reference centers, getting patients on therapy, and at least having an option with miglustat, their patient population that's been diagnosed is much higher than that of the U.S. We think that's a great comp to be able to help us to get closer to the prevalent number than the people who are diagnosed right now. Yeah, no, that's a great segue into the European. So you mentioned that you have your sort of the 120-day clock, but you also sort of the application you submitted did include some of this extra data. So you want to just talk briefly about what was included in this application beyond what the U.S. FDA saw? Yeah, I'll summarize. I know we're running short on time. I'll summarize a little bit. You know, the FDA CRL that we had and the additional work that we did on the mechanism of action, now that is published, the CLEAR network upregulation and how we see the mechanism working. And that biological plausibility now towards gets you all the way to the end on what your clinical outcomes look like. We now have that. We didn't have that when we originally filed. We now have the OLE data out four years, actually five years if you include the original study. That data didn't exist. We now have real-world evidence data that shows not just in the 19 years and under, but also in the adult population that you're halting the progression through the NPC CSS. And then we have this pediatric data, albeit very small numbers. It's an additional data set that was actually based on our PIP that we had to do the Pediatric Investigational Plan. Well, if you have enough time and you didn't get approved, our study, we ran the study and it's done and we actually added that data as well. So we feel really good that the questions that were in the CRL and how we answered them, the stats, the biological plausibility have been answered. And now we're seeing the pull from the community for the product and the stability of the patients that are there that it's robust. On top of that, we have 92 patients, which we discussed in our prepared remarks, that are in an EAP in Europe. About 30 of those patients are in France and the other are in just a small number or a few markets that are actually continuing to grow every quarter. We went from 89- 92. I mean, this time last year, I can't give you, I can't remember the exact number, maybe we're in the 70s, so we are really pleased with the fact that there's a pull from the European market and the patients there, and we have this opportunity to support them through our expanded access program, and as we think about our go-to-market strategy in Europe, whether we do it ourselves having 92 patients already in a small number of markets or we look to partner, that is still TBD, and we're having capabilities presentations on a weekly basis, and we're humble enough to know that if we can get it to patients faster, then we can do it ourselves, which we're doing pretty good right now, then we'll put it in the hands of somebody else or we'll do some kind of a hybrid. But what our goal is to be able to impact as many patients' lives as we can in as fast a time as possible as we can. Right. And so what is your sort of base case for what that European launch looks like in terms of how you're going to prioritize the different countries and sort of talk about pricing as well? So we've done a lot of work over the last nine months on our pricing quarter work. We had external consultants come and help us. That pricing quarter work now, we have the scenarios, what that needs to look like, but we also need to understand what our labeling looks like. So as we go through the marketing authorization process with Europe and the EMA, we'll know closer what that looks like and then it'll kind of put us into the right place in the quarter. In terms of market and penetration, we will have to go market by market for reimbursement in Europe. The markets that we're in today, that we're in, that we are in an expanded access program, we believe will allow us to be able to accelerate our launch or in the hands of somebody else reimbursement and actually start to get that foothold like we did in the U.S. with our EAP program. So we're continuing to invest in our EAP in Europe. We want to be able to support as many patients as we can. And at the same token, we've also seen what good looks like out of the US launch. We want to try and also do that. Yeah. Yeah. And given that those 92 patients and growing are sort of divided across different geographies and different countries, do you think that we should think about upon potential launch a similar rate of conversion of those patients as we saw in the U.S.? I think it was less than two quarters you were able to convert all the U.S. EAP patients. Is that similar or is the different country and pricing dynamic make that a little bit more complicated? Of the 92 patients we have today, and I know we're running short on time, we think that those are fast adoption reimbursement markets, but every market is different, so Germany is going to be different than France. And as you know, in France, we have about 30 patients in our EAP and we today have, through a program that's the EAP program, we have pre-commercial revenue of about $10 million a year, average a year through that program. So we think that we will, France is one of those markets where we will do rapid reimbursement process because we've already been there and we have that process. And now the other markets we think we can also accelerate, but we want to make the product as broadly available as we can for all of the European markets. Yeah. No, I think we're good on time. So I appreciate you joining us today, Neil, and congrats on all the progress. And we'll look forward to some European news later this year or next year maybe. Appreciate it. Thanks for having us. Thank you for being here. Take care.