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Good morning, everyone. I'm Samanth Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and it's my pleasure to have Zevra Therapeutics with us here today. ZevrA, as you might know, has a product that's approved and on the market already for an ultra-rare disease called Niemann-Pick Type C. The product is called MyPlypha, and its been launched for some time now, and we've had some interesting things back and forth with Europe as well, the medicines agency there. So we have a bunch of questions for you guys, and thanks for making it. And for ZevRA, We have CEO Neil McFarlane and CFO Justin Renz. And out there in the audience, we have Nicole Oshner, who knows everything about the company as well. So we'll keep this interactive. We do have a mic going around. So please feel free to raise your hands, and we'll get the mic across to you in case you have any questions. So with that, I'll kick it off. So Neil, can you set the stage a little bit on exactly what's happening with MyPlyFar, the unmet need that that product serves, the Neiman Pick Type-C community, and how it's received that, and what you've done so far with the product? Yeah, thank you, Suman. Thanks for having us. and we'll be making some forward-looking statements, so take a look at our most recent SEC filings for the most up-to-date information. Yes, we had our earnings last week, and we ended up announcing a very good quarter, and again, we are three prongs on a stool here. We have MyPlyfor in the U.S. that remains our core focus on driving value for patients in combination with Miglestat. We are also working through our geographic expansion strategy. We'll talk a little bit more about that in a moment, not only with our MAA process in Europe, which is going through a re-examination right now, but also in our market expansions that we're working on through named PN reimbursement and expanding access there. And then lastly, our Solipolol program, where we are driving with, you know, engaging with the FDA in the second half of this year after earlier this year, engagement on how we can accelerate the development of this program for patients with vascular Eilers-Danlos syndrome. So very proud of the execution in the first half of the year, and looking forward to taking some questions and having a conversation today. Thanks for that. So you mentioned prongs in the stool. I'm going to ask you to pick the highest priority prong right now. Is it my Plypho in the U.S.? Is it the MePlyphopending application or the resubmission that you have into the EMA or something else entirely? Yeah, I'm not sure. Clearly, our focus is on the U of my play for business, but I don't know if there's one that's more important than the other today. All of them, I think, provide the opportunity for us to access meaningful therapeutics and potentially meaningful therapeutcs to patients with rare diseases. So from a standpoint of how we see the evolution of our business and the growth of our businesses in the coming three to five years, these three prongs on the stool that I discussed about start with executing in the U.S. from IPLIFA. The team has done a remarkable job so far. As you know, we had 184 prescription enrollment forms from launch to date in this marketplace where I think we're starting to generate not only patients who were currently diagnosed, but also continuing to unlock those newly diagnosed patients, which gives us that confidence that the market in just a short period of time is greater than the 300 to 350 patients that are currently diagnosed and more between that 350 and the 900 patients of a prevalent marketplace. So we're pleased with what we're doing, but we're not stopping here. We're going to continue to lean into the future. So this is a bit of a question related to that. Now that MyPlaifa has been on the U.S. market for some time, what can you say is working in your efforts on the commercial side versus where you think the company could do better? And has the Niemann-Pick type C market surprised you in any way? Let me start with the last question, because I do think that the NIEMAN-PICK C market has surprised us in one way, and it's in a good way. You know, we for years have thought of Nieman-Picks disease type C as a childhood disease. We've always known that it had kind of four different phases from infantile to an adult version of the disease. I think the biggest surprise has been the number of adult patients that we're seeing in our enrollments as, you know, we've become more, getting more real-world data. Today, when we, actually, when мы launched the product, our EAP was comprised of about 50% adults and 50% kids. Today you know we've surpassed that number by well over 100, and we're continuing to see this adult population and child population continue to remain about 50-50. That's a big surprise. Number one, it's a big surprise because patients have been either misdiagnosed for a long period of time with something else, which we've seen. We talked about this on our earnings call. We've had some patients who had multiple sclerosis for many years who then, you know, continued to progress in symptomatology that was not necessarily defined in multiple sclerosis patients. And they have been genetically tested and then had NPC. We've had some patients who had autism spectrum disorder, but then progressed in other ways that you would normally not see in autism, that they then got genetic testing and came on board. And just recently, actually, there was an article published last month, or actually, no, we're in August, June. And it talked about a case study around a patient who had Wilson's disease for many years, who then had copper chelation and so on and so forth, but yet still progressed. They did genetic testing and came up with Niemann-Pick disease type C, an adult. So this learning is a big surprise for us in regards to what we're seeing in the marketplace. Additionally, last week, we got our expanded access data published, and that expanded access data had a very large cohort of adult patients for the first time, with some of them out to four years. So that's a big surprise, but that also then reinforces the market and the potential for expansion of the TAM between that 350 to 900. The other tactics that we're doing, I can't say there's one tactic that is the one thing that has been driving all the new enrollments, or one thing that has been really key to us educating physicians of patients that they have, it's really a multitude of factors. We're doing the disease state awareness, we're offering genetic testing, we are driving our publication efforts to make sure that that's out there. The clinical guidelines have recently been published, which really gives a lot of strength to diagnosing early, utilizing combination therapy, and those things. So all of the pieces of the puzzle is really an integrated strategy that I think has been rising the tide and lifting the diagnosis and treatment of patients. So patient enrollment forms, this is a metric that investors are keenly focused on every quarter and maybe overly keenly. So what can you do there that might make those more predictable for you and for us in the sense that you might start giving us what to expect on that? It is really challenging with the law of small numbers. I mean, we're talking about 900 patients in the United States from a prevalence perspective. I wish I had an answer that I could tell you that we're going to find X amount per quarter or per month. But in rare disease and in ultra rare disease, once you know one patient, you know, one patient. And I think the diagnostic odyssey that patients have, the journey that they have in their disease, everyone is different. So it's not something where I could say, if I do X, I'm going to see Y. We're doing a multitude of activities across the, I'd like to say, the rare disease playbook. We'll scale some up that are working and scale some down that may not be. But I think that the playbook of supporting patients and physicians for a new disease, we're starting to see those efforts pay off in the newly diagnosed patients and the expansion of the market correct so you mentioned roughly 180 or so cumulative enrollment forms how representative is that of true patient share within 300 to 350 diagnosed and treated patients so 184 patients from to date that represents the majority the majority of that represents patients who were already diagnosed in that 300 to 300 however as i I mentioned last year, this time, we were starting to see newly diagnosed patients, kind of early in the launch, but newly diagnosed patience. We've seen newly diagnosed patients every quarter since then. So that's what's given us the confidence that the market and the TAM is expanding beyond the 300 to 350. And actually, that's something that we've had communicated back to us with those folks who've got access to claims data, they are also seeing it. Even with the lagging claims data they're seeing the marketplace rise based on the activity. So it's good and now with guidelines and the efforts of our team and our medical team and everything else it's really picking up. So just to clarify the 180 or so it corresponds to one patient, new patient every time? 184 prescription enrollment forms comprises the majority of those comprise patients who were previously diagnosed, and a smaller part of that is the newly diagnosed patients. So, the 300 to 350, the majority of our 184 prescription enrollment forms are in that 300 to 250 with the newly-diagnosed patients coming. Sure. So it's 184 distinct patients, though? It is 184. There's no refill component or anything like that? That is one prescription for one patient. Okay, got it. At what point would you be willing to share what fraction would be newly diagnosed patients in the patient enrollment form number that you have? I think it's really too early for us to provide any guidance in that regard. And I think it is important also to note that we have a very small population of a very high impact product, but also a high value therapeutic that me guiding you with one patient difference is a significant and meaningful change in our numbers. So it is really hard for me to give view that right now until we get to a steady state. And I don't know when that steady state is because our growth rate both in the U.S. on a quarter over quarter basis, as we were having this conversation last year, this time it was certain quarters were single digit enrollments, certain quarters for double digit enrollents and very hard to navigate. But on a full year, we did about 52 enrollments last year. To date this year, although we had a single digit enrollment a double-digit enrollment you what we have now is 23 patients so it's very challenging i think uh to go quarter by quarter and the variability will will continue as we continue to move forward but but the key here is the total market addressable market we're gaining confidence that it's bigger in our second year of launch got it so on that gaining confidence note i'm going to press but this is going to be a qualitative question you can answer quantitatively if you'd like, but I think you won't, so I'll keep it qualitative. So now that you know that you have a certain number of newly diagnosed patients within those patient enrollment forms, do you feel better about the number of years it might take you to expand that market from 350 to 900 prevalent patients, or are you the same or worse compared to where you were last quarter? We are expanding that market now. Every newly enrolled patient above what was previously the running average of new enrollments, which we are exceeding today on an annual basis, year over year, means we're expanding that market. So we're expanding it now. In terms of quantitatively, I can't answer that question. I tried. Oh, and next time we should get chairs with cup holders. Yeah, yeah. No, it's okay. It's okay, it is. So I guess you have these kind of green shoots that you see on newly diagnosed patients getting into the fold, what needs to happen from a larger or a wider viewpoint, I guess, to get more of those patients in? I know you have genetic testing going on. You have these AI models that you're using. Can you give us a flavor for what those might entail and what exactly needs to happened to get to that number? Well, like I said, it's an integrated strategy here, right? There's no home run. The opportunity to enroll patients earlier and get them diagnosed earlier and on treatment that allows for the halting and progression of this progressive and devastating disease, that's where we're focused on. So some of our efforts are to establishing the diagnostic earlier by educating the physicians and patient groups and everybody else. The other part of it is, as you mentioned, our bespoke AI model that we're utilizing EMR data along with claims data through the suspicion index of NPC to be able to hone in on our representatives who have got some of this data that now allows them to be more efficient when they're in a call of a patient or of a doctor that they know has an NPC patient, can they start to expand in those areas? So that will then drive, you know, our goal is to drive additional patients who are not yet diagnosed and then have it in the back end, lower the barrier for genetic testing for physicians to be able to then have a test available to them at no cost if they need to outside of their own health system. So I think it's through the journey, both the diagnostic journey and the journey of the patient with the disease, to us to be able to look at this more integrated approach upon all these things to help to rise the tide. So I don't think that, yeah, like I said, I don'T think there's one thing. But there is an element of this that is a playbook that we're following. And this is an important component. Miglistat was approved in Europe for NPC for well over a decade. And in Europe, you have a prevalent number that's about 1,100 patients in Europe. And, you know, they have more population than the U.S., so you'd expect a little more. 900 in the U!S., 1, 100 in Europe! But the disease state, the education, and the other things that have happened in Europe have led to a much more mature patient base that is closer to the prevalent number than where we are today in the US. So we're utilizing that playbook to get our numbers closer to the prevalent number. And we're seeing that in the market today. We're seeing that in numbers. On that note, do you think your current spending is appropriate, current spending on the level of education and NBC in the US is appropriate given what your plans might be for the longer term? This may be a great opportunity for me to engage our CFO who's next to me here. We have a regular push and pull with our Chief Commercial Officer Josh to find the best use of our treasure we take shareholder money very seriously so we have regular dialogue on sizing of the team efforts to invest we are in the growth stage so you know when we have 260 million dollars on our balance sheet as of June 30 with no debt and so we the ability to invest but to your point we want to be very disciplined in that we try to demonstrate that in our quarterly results so it's a regular source of discussion we want to make sure that these investments that we're making in building out, because again, we're still in the second year of launch. So there's a lot of room to grow. And I think we're on the right track that we'RE always open-minded. So you've given us the number of diagnosed and treated patients. You've given US what the prevalent population is in the US. At what point will you be in a position to maybe provide us peak sales potential for the product? Yeah, I think that goes back to year guidance question around, can we kind of smooth the lumpiness of our quarterly enrollment? If we are able to get to a place where we could do that, I think it would be then, you know, behoove us to be able to provide that level of guidance. Today, I just can't. But I would go back to the peak opportunity for us in the U.S. goes back to the patient numbers. And that's that 350 to 900. A year ago, I didn't have as much confidence in where we were because we were one year into launch and we were doing well and exceeding expectations. Today, I can firmly say and confirm that in the numbers, and you can fact check this, that the growth of the market in the newly diagnosed patients is growing. That is what's giving us confidence that the peak opportunity is now between that 350 and 900. Give us some more time, and we'll let you know, you know. We'll continue to execute on that. I just don't know how to answer that question in such a lumpy and myriad of approaches and such law of small numbers and rare disease. Right. The good news is the patients that come on MyPlypha stay on MyПlypha. So, you have a product here that targets clearly a really high unmet need in NPC. You mentioned to my first question that, or second question, I guess, you were pleasantly surprised about some of the older patients are coming into the fold now diagnosed. Your product is, you know, it's a weight-based dosing. So for us financial types, what does that mean in terms of pricing on a weighted average, no pun intended basis? Yeah, well, we provided some guidance on our initial call post-launch that of our expanded access program patients, which were about 83 patients at the time, the mix of those patients were 50% adults and 50% kids. And that guided us, even though we have multiple strengths and it's weight-based dosing, to be able to provide the $85,000 WAC per month per patient. That has remained, you know, plus or minus a few hundred dollars here or there. That has remained consistent when it comes to our current patient base, which is, again, we've brought on board as many children and adults. So that is consistent. And I think until we see a significant switch between adults and children, which we have not seen, and I have to say we anticipated more children than adults at this point, then we will provide different guidance at that time. Got it. So in the U.S., the label for Miplypha includes a combo therapy with Miglistat, which is the off-label standard of care. Are there any initiatives underway at the company to potentially use Mipleypha as a monotherapy? So the answer to your question is you are correct. we are, the label is in combination with Miglistat. We are very happy with our label. And, you know, it's becoming more apparent that our label is part of the strength of the disease modifying therapies that physicians had at their fingertips now. It became even more apparent with the clinical guidelines that came out last quarter, which basically state, you know, diagnose as early as possible, treat as early as possible and use combination therapy and disease modifying combination therapy. Well, in those guidelines, we are the only product that has combination therapy in the label with randomized clinical trial data that shows, you know, plus or minus my boyfriend with miglestat. And that data along with, you know, what we're seeing in the real world where physicians have been embracing combination therapy, we think that the future of the Neiman-Pick disease treatment paradigm is going to follow the guidelines, which is treat with as many disease-modifying products as you can for the specific patients and utilize the different mechanisms of action to be able to clear cholesterol as best you can that gives people the best chance for lacking of, you know, the progression of the disease. So that has played out pre-launch. It's played out now in the real-world evidence we see, and now it's played out in the clinical guidelines. So we see the strength in our label, actually, that is in combination because that's where the future is, and we're the only product that has randomized control data to show that. Right. So in the competitive landscape, it's you, there's combination use with Miglustat, and there's a product from private intrabio Acneursa, and then And there's a couple of players who are either near approval or have phase three data that's coming. That's Barron and Raphael slash Cyclo. How do you expect this to play out? Do you expect to compete for payer dollars? Are all these complementary? How is the Niemann Pick type C market going to play up from a competitive standpoint? Well, one, as a company, I think as a, as, uh, uh. Company that's focused on, on patients and driving, uh best impact for patients, the more therapies in the NPC space, the better. And as the guidelines state, utilizing multiple mechanisms, I think is great. We've also seen that the investment that's come from these other players have also helped to rise the tide, right? More investment in disease state awareness, more investment in genetic testing, more investment and physician awareness. It's been great and we hope that more products can come in. The other part of this is that our understanding with some of these that you mentioned are they are actually going after a part of our label we don't have. It's the less than two years old, you know, and they would be wonderful if we could have patients who can have access to therapy earlier and hopefully halt or slow the progression of this disease and give those patients an opportunity to have multiple modalities like a MyPlypha and Miglistat in their later lives to help them move forward. So we see this as beneficial for patients. I think the guidelines have clearly stated that, you know, utilize multiple modalities and for the best outcomes. Correct. So, moving on to the application in Europe, you got the negative opinion from the European Medicines Agency. You've submitted a request for re-examination. We've had a recent case where a product for a rare disease, KDS, strophenatide for Rett syndrome, there was a reversal of a vote. You know, clearly circumstances are different, But what gives you confidence that the EMA will reverse course on your pending application now? Yeah, our confidence has remained consistent. It has to do with the unmet need and recognized unmet need, as well as the totality of the clinical evidence that we have. You know, I stressed on our earnings call, and thank you for the questions on the earnings call. I stressed it on the earning call, and I'll do it again here today. What we have in our global EAP patients and the continuous request for my Plypha and the majority of those EAP patients are in Europe, continues to show the pull for an unmet need for a product that's not even registered. We're utilizing that in Europe mostly compassionate use outside of France which has a specific program and that gives us a lot of confidence that we are trying to fulfill a need. The clinical guidelines have also kind of reinforced that in Europe as well. The other part of this is that we have a clinically significant and statistically significant clinical trial. That's now been bolstered with both real-world evidence on the open-label extension data going out four years last week, the publication of our EAP data going out, four years, the pediatric investigational plan data that's also now been published. So we feel like that robust totality all points in the same direction, which is halting the progression of this disease. So between those two, we're hopeful now as we go and have requested our re-examination, we will now have a higher emphasis on those specific areas of concern that the agency has come up with now that allows for the voices of experts in those areas to come to the table and to bring our story to life. And that's what we're doing here with the re-examination process. And as you also saw in that opinion, we've checked a lot of the boxes that were not checked in the previous application. So we've moved the needle. Now we have to continue to lean in on the totality of our evidence and demonstrate the unmet need. Well, we have a couple of minutes here, so I'll be remiss if I don't ask you any questions on seliprolol. I've pointed that out as flying under the radar. I don'T want to contribute to that myself. So seliprorolol for vascular illicit and low syndrome is the only product in phase three that we know of. There's no product approved specifically for VEDS in the U.S. How are you thinking about what you can do to get that product to patients sooner, given the nature of that trial? Well, we are doing everything. We have invested significantly in the acceleration of the enrollment. And just last month, we were at a regional meeting in Texas and driving through that as well. So we're investing in all of the clinical operations and trial enhancement activities you can think of. We also, though, took the opportunity in the first half of this year to go to the agency and to talk to them about the fact that we have lower event rates and the enrollment, it's not like the screening is not there. We're screening, but the enrollments and the conversion of that lower than we would like. But more importantly, how can we also work with them to find ways to accelerate the clinical development of the program through new regulatory mechanisms? So we had an informative discussion. We have now gone back out based on that and they gave us some homework. We've been doing the homework and we're on track to be able to re-engage with the agency in the second half of this year to be able to have further dialogue around those two areas, accelerating enrollment and or accelerating the development of the program. And the last one, I'm going to squeeze this in for Justin. One of those rare biopharma companies that don't really need to raise capital, but you may want to. So given that luxury, how are you thinking about business development? What kinds of ultra-rare disease assets are there? What might fit? What may not? Those kinds of things. Yeah, great question. We have really built the infrastructure around my point in the U.S. and, of course, modest investments in Europe, very targeted and specifically milestone-driven. So we very much, with our business development team, look for complementary assets. So we'd look for ultra-rare disease, either late-stage or commercial, that could complement the MyPlypho team because we have the infrastructure where we could truly add a product to our offerings at these centers of excellence, calling on the same doctors. And so we are very specific in our look. it has to be the right price, you know, the right drug, the right fit, and so that is absolutely part of our, you know inorganic growth strategy that we look to. Again, we have the flexibility with our capital structure to look, but again, our focus is on my point from the US, Europe, and CelebreLol, one, two, three, with the inorganics growth strategy on top of that. Thank you, and with all our time, thank you everyone for coming and for tuning into the webcast as well. Thank you. Thank you