Good afternoon. We're back, and this time we have Neil McFarlane, the CEO of Zevra Therapeutics. Neil, thank you for joining us. Thank you for having us. Yes. So tell us a bit about yourself because you're a recent CEO of Zevra, for sure. I should start off by saying that I'm probably gonna make some forward-looking statements here. Yeah. Take a look at our SEC filings, and we announced this morning that we're gonna be having our Q4 earnings call on the 28th of March, so we should have updated numbers for everybody to dive into. Great. It's been an exciting few months. I started in October, and you know the beauty of Zevra is that it spoke to me in regards to the impact potential that the products that we're developing can make for patients. In addition to that, it was a bit of an unknown story. It was a story that a company that transitioned was wanting to make the development to commercialization pivot, and an opportunity for me to be able to leverage some of the skills that I had developed in my previous stints as CEO and developing products. Then, to be able to figure out how do we then put this company together, building on the company as we have with some acquisitions to unlock the value moving forward. So it really spoke to me, and the beauty of it is that, now that having been here since October, I've made the right decision. Okay, so having teed up the enthusiasm, what are you looking forward to telling investors over the rest of this year, and is there any one in particular you're more excited about than the others? I don't know that there is any product that we have or initiative that we're working through that's more important than another. I think what I'd like to be able to communicate is that we're building a team of company builders, of entrepreneurs, that have a mission that they want to deliver products to rare disease patients that have no other therapies. And for me, building that team, working along with our patient advocacy organizations and delivering on what our key areas are around the commercialization of our first product in urea cycle disorders. We have a PDUFA now coming up on the 21st of September for another rare disease program, and we have a phase II readout here in the first half that we've spoken about in idiopathic hypersomnia. So it's a busy time. We have to focus, and quite frankly, execute on those, and then we'll earn the right to continue to do it, and do it, and do it, and become a leading rare disease company. Neil, tell us about OLPRUVA. You bought Acer Therapeutics, that gives you OLPRUVA. I'm sure a lot of people don't really know a lot about your urea cycle disorders. Tell us how it works and, you know, why it should be commercially successful. Great. So OLPRUVA is a product that was approved in 2023 for certain urea cycle disorders. Urea cycle disorders are... They're, they're, the urea cycle has about six enzymes that process ammonia and nitrogen that allows you to then filter it out through the cycle. When you have a breakdown in one of those enzymes, you build up ammonia, and then you build up nitrogen and ammonia, and that can really become toxic to folks who have neurological challenges. It can lead to coma, and it can lead to death. What we have is a program which is the base of it is sodium phenylbutyrate, and sodium phenylbutyrate is a nitrogen scavenger. It actually takes the nitrogen out of the system before it gets into the urea cycle and helps the body to metabolize it. So for patients who have urea cycle disorders, OLPRUVA allows you to be able to get the nitrogen, the ammonia, and then actually metabolize it, along with diet, controlling protein in the diet and other areas. So, we have developed this program with our acquisition of Acer Therapeutics to handle the unmet needs that we heard from patients and physicians. The other products, the other sodium phenylbutyrate products that are on the market today, have some challenges in a liquid that's quite challenging to take from a taste and perspective. The tablets that are out there today, you have to take a huge pill burden in order to be able to capture that. And then there's a powder as well that you can sprinkle on food or take that has a very short-acting process that they utilize to be able to not have the offensive taste. We have, it's dosed by weight. We have a package that is dosed specifically three times a day, like all of the other products, in a small sachet that allows you to mix it in water. It allows for the double-coating polymer that we have allows for it to be able to be the taste and the challenges of sodium phenylbutyrate to be held back for about five minutes, that allows you to take this in just a little bit of water. So between the palatability, the portability, and our ability to be able to have this polymer coating that allows for a delay in the taste, it really allows for patients to hopefully have better compliance. And again, this is gonna take some time. We don't have that in our label today, but we're working through that to be able to collect some data in the future. Right. So you clearly like it. So what do docs think about OLPRUVA? What kind of feedback do you have already? Great question. So we closed our Acer transaction at the end of November, and we ended up fielding a commercial medical affairs and patient services organization to be the field-facing elements of that by the second week of, or third week of January, and then we launched the product with folks on the ground. So it's very early. Our initial feedback today has been that the awareness is very low, but once physicians understand that you're here answering some of the questions and concerns I just talked to you about with the product, they haven't heard about Zevra before, and they hadn't heard about OLPRUVA. Now they're able to actually understand where that benefit and the potential for patients is. So we actually right now are quite excited, and I think that the synergies that we plan to have with our next product and the commercial infrastructure that we're building or have built, and we'll continue to execute on, work out the bugs. We'll be able to kinda make sure we can continue to deliver product to patients, and then the next product will come right on top of that. So it's a real win-win for us at this point. So what can you say about pricing, especially vis-à-vis the, what I think is an egregiously priced competitor, Ravicti, and Amgen doesn't seem to have much care about dropping that price to compete? Well, actually, let me go back to the previous question for a moment before I talk about pricing. You know, one of the things that we also have understood when it comes to building this awareness, which is what we're here to do today, and our field organization is doing, is that we also understand because of this low awareness, that we needed to be able to increase the brand awareness. But so we instituted a program that will allow for trial and utilization through a quick start program. So patients and physicians will be able to write for it and experience it for a free sampling program. I think that's part of this maturity that we have in our infrastructure and in the team that we've built. We see things aren't. We get data, and then we actually drive towards executing on it and pivoting quickly. So we have that program now, and that trial and utilization for physicians and patients is there. In regards to pricing, we are priced at approximately 50% of the competitor today, as you discussed. It's a good time for us. Payers, I think, have also been pushing back on exclusion of products that are highly priced in that regard. So we feel like we've priced for value. We wanna make access available for all of the patients that are out there today. Our market access and coverage at the end of last year, we landed around 50% of covered lives. We're still making progress now in Q1 on building that. We'll talk a little bit more about that on our earnings call, but, in terms of where we are in terms of covered lives, excuse me, but we feel good about, the initial progress of our sales force. And so for what% of the market is it relevant where payers are pushing back on Ravicti and saying, "You first, then them," because of the massive price differential? We're seeing that Ravicti has been put on the exclusion list at some of the payers out there. In terms of the percentage, it's a little hard for me to answer that today because it's a dynamic process. But we are seeing that bringing another product to market really allows for the payers to make decisions, and we're seeing that exclusion list make an impact as patients who are being excluded have the opportunity then to experience other products like OLPRUVA. Okay, so to move from OLPRUVA to arimoclomol, the drug has been a little bit around the block. It's yours now. And, you know, you filed, you refiled the Yep. NDA. Why'd the FDA move that PDUFA date from June to September? So we did file at the end of December. If you recall, we had a few areas of that the CRL pointed to. We answered those areas with our refiling. They gave us a PDUFA date of June 21, and as part of that, we were fielding information requests, of which we've been able to field and answer those questions in a timely manner. However, the agency did say that one of those information requests ended up being a major amendment, and we've been extended to three months. Quite frankly, we see it as a positive sign in regards to the agency really diving deep and needing some more time to review our package. 'Cause remember, as we talked about at the end of Q4 when we filed the submission, this is a fairly robust package. We've now talked about the scale. We've had the four-point revised scale versus the five-point scale. We've worked about the FDA preferred analyses that now we have provided, along with the original analyses, and then, the confirmatory evidence components of the non-clinical, clinical, alignment and, and really driving towards connecting the dots to the clinical trial outcomes we've also done. So it was a robust filing that we provided back to the agency. Not surprising they needed more time. Did you think that what they wanted from you after they gave you a PDUFA date was something that could have gone a worse way, where they would have said, "No, refile after providing this information," and you kinda dodged a bullet by having them give you a PDUFA date, then want more information, and then only really be able to give you a three-month delay? Actually, I think it's fairly common practice when you refile from a CRL, that if you get a PDUFA date, you've answered the questions, or else you would not get a PDUFA date. The additional information requests are not a request for additional data, per se. It's clarification- Okay. - of the data that you have provided to them. So I, I don't think in the in today's world, and we see this more common practice across the regulatory agencies, that they need more time, but also when you need more time, we believe that there's an opportunity for them to, to dive in, do the deep dive, and, and hopefully with success on the back end. Okay, so Niemann-Pick is another, you know, rare one. And so tell us about, tell us about Niemann-Pick and, and how you guys believe arimoclomol works to benefit those patients? Niemann-Pick is a devastating disease. It's a lysosomal storage disease that impacts the metabolism of cholesterol in the lysosome, that then builds up and really challenges these patients. You know, the average survival of these patients is about 13 years old. Devastating, impactful disorder. What we have with arimoclomol, and I think this confirmatory evidence package we've put together and the additional work we've put together, really lends itself to being able to improve the metabolism of the lysosomes' ability to metabolize cholesterol. A lot of that data is not out yet. We'll be working through telling that story, not only with our, the agency indicated that they'd like to have an AdC om, so we're hopeful that we'll have that AdC om and the ability to be able to tell that story broadly. But I think that then allows for people to understand what that looks like in terms of the impact for the Niemann-Pick community. This is a disease where there's about 1,800 patients across the U.S. and Europe. Europe having about 1,000 of those, the U.S., 800-900. But of those 800-900, there's only 350 patients that are currently being diagnosed and treated today. Of those patients, we have an early access program and have had an early access program in order to be able to collect data on the long-term impact of arimoclomol. So we have about 70 patients in the United States, of that 350 patients, and we're hopeful that we'll be able to actually drive and assist those patients to being able to convert early in the appro-- after the approval process, if we're approved. Help people understand, you know, how the NDA originally received a CRL, and maybe just very briefly, the points that you addressed. Sure. in your refiling. Sure. So, I think it's very important that I lay out the fact that the agency has never asked us to redo the clinical study. There have been, questions that were asked around three major areas. One was the NPC-CSS, which is a Niemann-Pick C severity scale. It's a scale that has a number of different areas, where there are five major areas: swallowing, fine motor, cognition, and one that I'm skipping on right now. And as part of that, the agency asked questions about the scale, and specifically the cognition and the swallowing. Oh, swallowing. Cognition and the swallowing. The cognition component that quite frankly, we understood and the agency understood, that cognition doesn't change much over a 12-month period, so we removed that. And then we also rescored the swallowing based on some criteria that was there, submitted that information back to the agency. In addition to that, they—there's missing data that happens sometimes, and how to be able to work with that missing data from a statistical perspective, the process that the original NDA had, FDA had some questions on, and we were able to actually address those questions with the FDA preferred analyses and then resubmit that as well. And then lastly, was about the confirmatory evidence. Does the story have the biologic plausibility to have the non-clinical, clinical, and then the results of the output of your trial, add up? And we were able to do some additional work on the non-clinical side, actually provide the agency with additional, natural history data and the open label extension study, some patients out to four years, that then tied that story, the confirmatory evidence story, directly to our clinical trial outcome. And those were really... You know, I don't think that one of those was more important than another. Quite frankly, all of those together, I think will provide additional evidence of the totality of the data for the FDA to be able to make their ultimate decision. Right. And so at the highly likely AdC om, you know, are you expecting some sort of outsized performance with the patient advocates? So, you know, this is an area which we take a lot of pride in, working very closely with our patient advocacy community across all of our areas of development. The patient advocacy community, about a half a dozen of them came together and actually put forth an informal petition that was recently made public about a week or two ago. Like how many? There were upwards of 1,000 participants in there, of which were made up of patients, caregivers, family members, as well as clinicians in support of the approval for arimoclomol. We think that goes a long way. We're also familiar with two other advocacy organizations that put letters in that were not public, but also put letters of support in. The AdC om, we're hopeful to not only have the support, which we believe we do have the support of the patient advocacy community, but in addition to that, it'll allow us to be able to tell the story of this confirmatory evidence that we had we previously had not been able to do because we're still working through generating the data and driving that. So, it's our goal that, if we are asked for this, highly likely, I like the way you put it, highly likely, AdC om, that we would be in a very strong position to tell the story and give as much evidence as we have for the FDA and the advisors to be able to opine on. You know, to take this and, you know, distill it toward money, where do you think you can price this drug? You know, that extra kicker that you might get, a priority review voucher, what do you think you could sell that for? Well, we're not clear on pricing at this point. And I think that our goal is to be able to make sure that we have access to arimoclomol and all of our products for patients that are out there. We need to get through the labeling discussions and understand where we are to make sure that we're putting forth a value story across all stakeholders: patients, payers, providers. And I think that once we do that, then we'll have the opportunity to put forth the appropriate price for the product and add value to the system. Okay, well, I think that addresses arimoclomol fairly well. One that's a little more organic for you guys, KP1077. It's in the clinic for idiopathic hypersomnia. Tell us about... I mean, the mechanism is pretty straightforward, but you can mention it and maybe how it's differentiated from something else out there for that, and just talk about the market a little bit, size for IH? Great. So I hope you're seeing a common theme here, that we try to listen to patients and understand what the unmet needs are, and then we try to make sure that we're building products in that rare disease space that do that. This is another great example. The idiopathic hypersomnia community still has unmet need. There is a product that's approved in that area, but the ability for these patients to actually get to overcome this excessive daytime sleepiness and specifically the sleep inertia, that ability to get up is just so hard for them, that we believe that the hypothesis given for our serdexmethylphenidate program, as you mentioned, it is a prodrug of a stimulant that's widely used. We believe that getting those high levels of this prodrug to be given at night- Yeah ... a stimulant at night, that has a beautiful release profile and PK profile that, you know, approximately 10 hours later, you have a high level of stimulant on board to help a patient get up and then have that stimulant on board during the day to allow them to overcome this just amazing need to sleep, and that excessive daytime sleepiness. We believe that that allows for us to be able to do this trial, which we're doing today, which is a fairly traditional sleep study, where you have a run-in period of doses that get quite high, which you can't get to with other stimulants today because they are immediate release or- Right ... slightly delayed release. We're getting to quite level, levels that are quite high based on also safety data that we did with the cardiovascular impact work last year that we reported on. And then, really allow for patients to be able to experience that, that amount of stimulant during the day with the PK curve. So that trial is in phase two. We're studying two different dose regimens, one once at night, and the other once at night and once in the morning. The interim data was released at Q4 last year, and then, we announced a few weeks ago that we had last patient, last visit in our phase two trial. And we will be able to then, announce in the first half of this year, the output of that data- Hmm ... which, quite frankly, will inform our phase 3 program and how we move forward. It should. So, you know, the one thing is, you're looking for this to kick in 10 hours after you take it, if you're taking this, you know, slow-release stimulant at bedtime. In AZSTARYS, where this delayed methylphenidate is, you know, 70% of AZSTARYS, are you expecting unformulated methylphenidate, which is 30% of it, to cover those kids essentially for the first 10 hours of the day before serdex kicks in? Or isn't it supposed to kick in sooner? No ... with AZSTARYS? Yeah. So AZSTARYS has an immediate release- Right ... as well as a longer term, but it's at much lower levels, much lower doses of serdexmethylphenidate. So that's why the profile of AZSTARYS allows you to have an immediate release and then, continued release during the day. We are going to levels that are significantly higher and 100% serdexmethylphenidate in the program that we're moving forward with, that allows you to not have any immediate release. Obviously, you're going to sleep at night. You don't want a stimulant to immediately release when you're trying to go to bed. Right. So we believe that the ability to get to high levels and then have them release at the time of waking and then also during the day will hopefully solve some of the unmet need for these patients. So why first IH instead of narcolepsy? And will this one IH trial inform two different phase three programs? Yes, absolutely. That is a potential. We do believe that the value proposition for the unmet need in sleep inertia, which is much more prevalent in IH patients, that hypothesis and testing it in IH will hopefully allow us to see that separation, both in brain fog, sleep inertia, as well as excessive daytime sleepiness, and allow us to figure out where we would go with the program next. So IH will be one round one, but there is potential for us to explore this in other areas. Okay. So, you know, AZSTARYS, that I alluded to before, it's starting to kick in some milestones, which are not tiny and, you know, come at no dilution, which is really nice. Can you start, maybe give us a, a sense of how frequently we can expect AZSTARYS milestones? So just to make it clear, we outlicensed that program, and it's being commercialized and manufactured by a third party. We did announce at the end of Q3 that we anticipated a milestone in Q4 of $10 million, along with our royalties, which they did hit, and we received those in Q1 of this year. We expect that, and we're very pleased with the way that AZSTARYS program is moving forward, and the group over at Corium is executing. Clearly, in their first full year of launch, they've really started to move forward. So with that, we will continue to gain our royalties and milestones, and we haven't actually disclosed those in terms of where they are, but we fully expect to continue to. I was trying to trick you. Yeah, well, I appreciate the question. We wanna make sure that we respect the integrity of the agreement, but along those lines, very pleased with what they're doing and are wishful that they continue to serve patients with a great drug. Yeah, and so capital that we helped you raise, like, three years ago is still... Yeah, it's a pretty decent cash position. Does that take you to profitability, or, or does it not, or what are you assuming in cash projections? Right. So we, we haven't guided any cash projections since Q3, where we had about $80, approximately $83 million in cash. At that time, we said that that would take us out to, into 2026. That was without any. We were in the middle of our transaction and so on and so forth, and closing in early Q4, the, the Acer transaction. But, but what we said was, is that that was without any arimoclomol revenues, a PRV for arimoclomol, or, or any OLPRUVA revenues. Right. So we feel like our ability now, when we get to our call later this month on the 28th, to refine that is important, but we still feel very comfortable that we can achieve our current catalysts with the cash that we have. We pulled forward our commercial infrastructure, but that was already anticipated in our cash position when we announced in Q3. So we pulled it forward. We've got a full house when it comes to our commercial infrastructure. Remember that that commercial infrastructure we're building today as part of our development and commercialization pivot is the same commercial infrastructure that we will actually utilize to commercialize arimoclomol, if approved. So that allows us to kind of work out the kinks, you know, oil the machine, and make sure that we can take in service patients with their prescri-