Zevra Therapeutics, Inc.

Good afternoon and thank you for joining Zevra's second quarter 2025 financial results and corporate update conference call. Today's call is being recorded and will be available via the investor relations section of the company's website later today. The host for today's call is Nicole Oshner, Zevra's vice president of investor relations and corporate communications. Please go ahead.

Thank you and welcome to those who are joining us. Today, we will provide an overview of our recent accomplishments, followed by a review of our second quarter financial results. I encourage you to read our financial news release, which was distributed this afternoon and is available in the investor relations section of our website. Before we begin the call, please note that certain information shared today will include forward-looking statements. Actual results may differ materially from those stated or implied by any forward-looking statements due to risks and uncertainties associated with Devereux's business. Forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties, and other important factors that may lead actual results to differ materially from the projections made. and should be evaluated together with the risk factor section in our most recently filed quarterly report on Form 10-Q, annual report on Form 10-K, and other filings with the SEC. In addition, we will disclose certain non-GAAP information on today's call, specifically adjusted net loss and adjusted net loss per share. Reconciling information to GAAP can be found in our financial results news release. I'm pleased to welcome Zebra's management team members participating in today's call. Neal McFarlane, Zebra's President and Chief Executive Officer, Liz Wayne Clifton, our Chief Financial Officer, and Josh Schaefer, our Chief Commercial Officer. Our Chief Medical Officer, Adrian Cortell, will be available for today's question and answer session. Now, it's my pleasure to hand the call over to Neal.

Thank you, Nicole. And thank you to everyone who's joining our update call this afternoon. At Zevra, our vision is to build a leading life sciences company whose core mission is to serve patients by bringing life-changing therapeutics to people living with rare diseases. We are demonstrating our ability to execute in a complex regulatory, clinical development, and commercial environment to advance promising therapies with an approach that balances science with patient needs. As a reminder, this vision is driven by the four pillars of our corporate strategy, commercial excellence, pipeline and innovation, talent and culture, and corporate foundation. The execution of our strategy delivered remarkable performance in the second quarter and set the strong foundation for continued momentum in Q3. On today's call, we'll highlight several key achievements. Q2 net revenue reached $25.9 million. reflecting robust demand and effective operational execution. We completed the sale of our PRV for $150 million, a strategic transaction that strengthened our balance sheet. We also submitted our Marketing Authorization Application, or MAA, for our Markle Modeling Europe, marking an important milestone in our geographic expansion efforts. Let's dive in with an update on the U.S. launch of MyKleifa. the first approved treatment for people diagnosed with Niemann-Pick disease type C, or NPC, and the only treatment that has been shown to halt disease progression by addressing its underlying pathology. As a quick reminder, NPC is an ultra-rare, relentlessly progressive neurodegenerative disease caused by inherited lysosomal storage disorder and leads to premature mortality. In the U.S., we estimate that roughly 300 to 350 patients have been diagnosed with MPC out of the estimated 900 people living with the disease. The approval of myClypha marked a fundamental shift in the treatment paradigm, and we believe that its ability to address disease progression is an important differentiator that will lead to long-term success. We are incredibly proud of the work our team is doing to support the healthcare community and eligible patients with an intense sense of urgency. We've received positive feedback from both patients and physicians, which is reflected in the strong performance since launch, with a total of 129 prescription forms through the end of Q2, of which seven were enrolled in the quarter. Through rapid uptake in the early stages of launch, we have been able to reach over one-third of those diagnosed with MPC in the United States. This group primarily included patients in our Expanded Access Program, or EAP, who have been treated with MIPLIFER for up to seven years, with the majority of patients remaining on therapy. Following the success of our early launch penetration, our commercialization efforts are focused on increasing both diagnosis and treatment access. The second segment of patients that we're focused on are those who have received an NPC diagnosis but may or may not be currently receiving treatment. These patients typically were diagnosed at centers of excellence and managing coordination with a local provider for ongoing care. We've mapped these referral patterns beyond the centers of excellence and are engaging the broader group of prescribers. The last segment of our patients are those living with NPC but who have not been diagnosed. Part of our contribution and responsibility to the patient community is to increase awareness and shorten the time to diagnosis for this devastating disease. We are demonstrating leadership through our disease state awareness campaign to help drive early diagnosis. The treatment of NPC is multifaceted and our program offers education and genetic testing options for individuals with suspected lysosomal storage disorders. With growing awareness of MyPlytha, we look forward to extending our reach to serve additional patients. Our work with advocacy organizations is very important, and our support has been well received. We also provide more details on our strong presence at recent conferences where Xevra and our specialty pharmacy engage with caregivers and people living with NPC. These are some of the ways that we're building our reputation as a reliable partner. Another exciting opportunity for MyPlyfor is in Europe, where we estimate approximately 1,100 people are living with NPC. One of our priorities is to secure European approval and determine the optimal go-to-market strategy to ensure access for a greater number of patients. Just a few weeks ago, we announced the submission of the Aramocomal MAA to the European Medicines Agency, delivering on the early side of our second half of 2025 guidance. This is another significant and timely milestone for Zebra. To support the submission, we received guidance from EU regulators and assembled a robust data package, including new mechanistic and long-term clinical data generated since our FDA submission. We have demonstrated a synergistic effect with Miglestat, which is approved in Europe for MPC and is the standard of care in this more mature market. where we have an established EAP program, which increased to 89 patients enrolled at the end of the second quarter. And to further our efforts in the scientific and medical community, our data from the Open Label Extension Study was recently published in the Journal of Molecular Genetics and Metabolism. The paper presents the impressive long-term efficacy and safety outcomes for NPC patients treated with MyPlypha in the 48-month open-label extension phase following the end of the 12-month pivotal trial. Additionally, we published data showing that MyPlypha upregulates expression of genes, belonging to the Coordinated Lysosomal Expression and Regulation Network, or the CLEAR network, targeting the underlying pathophysiology of NPC to improve autophagy, reduce cholesterol accumulation, and prevent cell death. As the NPC marketplace evolves, shaping treatment guidelines will become more important for the NPC community. We believe our success in establishing myPlypus benefit through the largest data set of NPC clinical trial patients and having these data published in peer-reviewed journals will help inform treatment decisions. Turning now to Opruva, which is a treatment for certain urea cycle disorders. We've previously discussed the limited pull-through we experienced in this launch, which continued in the second quarter, with one prescription in woman form. Our refined marketing efforts over the last several months have focused on identifying the patients for whom OPruva is best suited, strengthening our patient support services, and addressing reimbursement challenges. However, adoption continues to be slow, and we remain cautious. Josh will provide more detail on the product performance, and LeBwayne will provide financial details on the non-cash charge related to the prevailing trend later in the fall. Moving on to our pipeline, we're advancing Solipilol as a potential treatment of vascular Ehlers-Danlos Syndrome, or VEDS, in the Phase III DISCOVER trial. VEDS is a severe genetic connective tissue disorder characterized by a risk of dissection and rupture of the arteries, gastrointestinal tract, and uterus. Solipilol is an adenoceptor modulator believed to decrease mechanical stress on the vascular wall of large arteries and hollow organs. In the second quarter, we enrolled seven patients in the DISCOVER trial, bringing the total to 39 patients enrolled out of the 150 patients required for complete enrollment of the trial. The genetic testing initiative to identify patients who have the COL3A1 gene mutation, which causes the disease, is ramping up in collaboration with patient advocates, KOLs, treating physicians, and clinics, providing increased visibility and has the potential to accelerate future enrollment. We are making progress in advancing our vision of becoming a leading rare disease company through focusing on the patients we serve. Our strategy balances near-term operational excellence with the agility and financial flexibility to support initiatives that build sustainable value for patients and shareholders alike. Let me turn the call over to Josh, who will provide more details on our commercial products. Josh?

Thank you, Neil, and good afternoon. Let's begin with Mike Leifa for NPC. NyQuifa, in combination with Niglistat, is the only treatment shown to halt disease progression, 12 months in a pivotal placebo-controlled study using the NPC clinical severity scale, which is the only validated measurement of NPC progression, assessing clinically meaningful markers such as impairment of mobility, cognition, speech, and swallowing. In the second quarter, we received seven prescription enrollment forms, and we have increased our product net revenue by 26% quarter over quarter, a reflection of new patient demand, as well as access and retention. A new enrollment is defined as a prescription submitted to our specialty pharmacy, which begins the benefits investigation process to determine reimbursement eligibility. In the second quarter, our coverage reached 52% of all covered lives. It's consistent with our expectations at this stage of the launch. Those other patients who were not immediately covered, we've been able to achieve reimbursement through medical exception pathways. We remain actively engaged in discussions with payers to facilitate reimbursement. And our current focus is on demonstrating the clinical value of MyPlaifa to payers. especially leveraging our long-term open-label extension data, which show durable clinical benefit for up to five years. Our field team, including case managers, continues to play a critical role on the front lines, working with patients and healthcare providers to navigate the reimbursement landscape. Their efforts have been instrumental in helping to overcome access barriers and allowing patients to receive timely support to secure coverage. Additionally, our Amplify Assist program, which is a centralized resource that assists clinicians' offices and patients in navigating the reimbursement challenges and supporting coverage for all of our commercialized products, has been well received. To bolster our penetration into the second segment of patients, those NTC patients who have been diagnosed and are either on other treatments or not being treated, we have a number of initiatives underway. We are emphasizing the robustness of our data with its strong presence at scientific, medical, and advocacy-related conferences where physicians and patients can learn more about mycoifas' therapeutic impact. Last month, at the National Niemann-Tick Disease Foundation Conference, Dr. Barbara Burton, a key opinion leader and professor at Northwestern University's Feinberg School of Medicine, presented an overview of myClypha and our unprecedented long-term data. We had a similarly strong presence at the Southeastern Regional Genetics Group Conference with four poster presentations. As Neil mentioned, the recent publication of our open-label extension study is our long-term 48-month data to the forefront for physicians, highlighting the duration of clinical benefit Specifically, an improvement in disease progression was seen at the first evaluated time point at 12 weeks and then continued for more than five years in a heterogeneous population of NPC patients with no new safety concerns. These results align with our pivotal trial data, which showed that Miplyza in combination with Miglistat halted disease progression compared to placebo over a one-year study duration. Presentation of Key data and insights like those provided in these recent publications are an important part of our strategy to raise awareness of the clinically meaningful impact that myPlexi can have for patients. And we will continue to execute our publication strategy to support prescribing decisions. The third segment of patients, those that are undiagnosed, are an important population for us. It is critical to shorten the time to diagnosis, to halt the progression of disease sooner. Our disease state awareness campaign, Learn MPC, Read Between the Signs, is designed to provide educational and genetic testing resources to support the diagnosis of new MPC patients. This program is helping to drive awareness of the disease, as well as identifying patients who were previously undiagnosed and may be candidates for MyPlypho. Turning to Alprova, UCDs are rare inherited metabolic disorders characterized by an excess accumulation of ammonia, which can be neurotoxic and lead to neurocognitive damage or even death. Although current treatments are effective, over 25% of hyperammonemia crises are caused by poor adherence to treatment. Alprova was launched based on established efficacy and safety profile but with an innovative formulation that offers a palatable option in convenient, pre-measured, single-dose envelopes for ease of use and ammonia control on the go. We believe in the benefits that Alprova offers people with UCDs. However, we have seen slower-than-expected uptake. The mature UCD market and patient satisfaction with existing treatments resulted in one prescription enrollment form in the second quarter. An authorized generic to the market leader is anticipated, eventually creating a shift in the competitive dynamics. We believe Alprova's profile, as well as our patient support activities, will position us to compete in this changing landscape. We have been actively engaged in strategic negotiations with payers to facilitate reimbursement. In the second quarter, we saw our overall coverage increase to 79%. In summary, our commercial organization has reached critical mass, and the strength of our capabilities are being leveraged across our portfolio, with the primary focus on MyPlypho. We are prioritizing and executing on key strategies to deliver value to patients living with rare diseases. I will now pass the call to LeDwayne, who will present the financial results for the second quarter of 2025.

LeDwayne Wilson Thank you, Josh, and good afternoon, everyone. In addition to the financial details included in today's call, we encourage you to refer to ZEVRA's quarterly report on Form 10-Q for more detailed information, which we intend to file later today. In the second quarter of 2025, we reported net revenue of $25.9 million, which includes $21.5 million from MyPlaifa, $300,000 from AllProva, $2.6 million in net reimbursements from the French EAP for Ermacomal, $1.2 million from royalties and other reimbursements under the Astaris license, and an upfront payment of $300,000 from the outlicense of Dextropin during the period. For our commercial products, MyPlaza and Dolprova, we recognize revenue when shipments are received by the specialty pharmacies. Cost of product revenue for Q2 2025 was $14 million, which includes 1.6 of non-cash intangible asset amortization. We conduct quarterly assessments of the recoverability of certain intangible assets in inventory in accordance with U.S. GAAP. Based on the prevailing trends for Old Peruvia, including enrollments, paid authorizations, as well as market and competitive landscape dynamics, we have recognized a non-cash charge of $58.7 million for impairment of intangible assets and an inventory write-down of $11.7 million as of June 30th, 2025. Operating expense for the second quarter was $24.2 million, which was an increase of 1.1 compared to the same quarter a year ago. R&D expenses were $3.4 million for Q2 2025, which was a decrease of 7.1 compared to Q2 2024 due to a decrease in third-party and personnel-related costs following the completion of the 1077 Phase 2 trial. SG&A expenses were $20.8 million for Q2 2025, which was an increase of 8.2 due to professional fees incurred related to the proxy contest earlier this year, as well as other expenses associated with our commercial activities. During Q2 2025, we also recognized $147.9 million in other income, which includes $148.3 million in net proceeds from the sale of the PRV asset, which was completed on April 1, 2025. This one-time transaction has provided significant non-diluted capital for the company and has further strengthened our financial position. Net income for the quarter was $74.7 million, or $1.24 per basic share and $1.21 per diluted share. Excluding the one-time PRV sale, the one-time non-cash impairment charge, and the inventory obsolescence charge recognized during the quarter, adjusted net loss was $3.2 million or $0.06 adjusted net loss per basic and diluted share for Q2 2025. For the same quarter in 2024, we reported a GAAP net loss of $19.9 million or $0.48 for basic and diluted share. We are pleased with the early stages of the MyPlypho launch and our continued progress in building our corporate foundation through solid execution. Our focus remains on executing the launch of our commercial products and on the development of our pipeline, which includes supporting both the Aramacumum MAA in Europe and the ongoing phase three trial for Soliphalol. As of June 30th, 2025, total cash, cash equivalents and investments were $217.7 million compared to 68.7 at the end of the prior quarter. Total debt was approximately $60.7 million. We believe that our existing capital resources continue to be sufficient to allow us to execute on our strategic priorities independent of the capital markets. Now I will turn the call back to Neil for his closing remarks.

Thank you, LeDwayne. We're fortunate to be in a unique position with commercial therapies, a late stage development program, and a solid balance sheet to execute on our priorities. We attribute our success and momentum to staying true to our mission and the dedication of our team committed to making an impact on the lives of people living with rare diseases. Our focus moving forward remains firmly on executing across our four strategic pillars to accelerate our trajectory for transformative growth and long-term value creation. Thank you. We'll now open the call for questions. Operator?

Thank you. At this time, if you would like to ask a question, please press star 1 on your telephone keypad. You may remove yourself from the queue by pressing star 2. We'll take our first question from Brandon Foulkes with HC Wainwright.

Hi. Thanks for taking my questions, and congratulations on all the progress. Maybe just starting in the U.S. in the most new patient starts in 2Q or sort of just any, well, I guess an enrollment. And any trends you're starting to see in the U.S. in terms of enrollment, in terms of where they may be coming from?

Brandon, you cut out a little bit in the first part of your comment. It sounded like you were asking about U.S. MyPlypha and any trends. But can I ask you to repeat the question?

Yes. Absolutely. Just any specialties contributing most to new patient enrollments in 2Q and since launch as well? Just any trends you see in the U.S. in terms of patient enrollments who weren't in the EAP program?

I'll ask Josh to comment on the specifics around specialties, but maybe I'll take the opportunity to be able to talk a little bit about the strong performance in Q1 to Q2 overall. You know, in Q1, we had my Pfeiffer revenue of about $17.1 million and a 26% growth from from Q1 to Q2 with 21.5 million. And that's really a lot to do with the pull-through of patients from the patient enrollment forms on our patient services group and field reimbursement, walking through to help to drive patients through that funnel, through the reimbursement hurdles to get them onto commercial products. a tremendous job by the team in pulling that through. And if you look at our total enrollments from Q1 to Q2, we're at 122 total enrollments, and then ending Q2 at 129. That's coming from a fairly small number, but it's still a third of the patient population today that's been diagnosed, the 300 to 350. I'll pass it off to Josh a little bit to talk a little bit about the specialties and trends. But recall, these are small numbers in terms of the total number of patients in the US.

Yeah, thanks for the question. We're seeing initially, as we expected, that the early patients were coming from Those clinicians who were part of our EAP and those are largely neurologists and pediatricians. Now keep in mind that while many of these clinicians might have done training as a pediatrician, they are seeing both both children and adult patients with NPC. We're also seeing medical geneticists treating these patients, and we're starting to see an emerging small group of psychiatrists who are seeing these patients as well. So this is very consistent with what we expected, and we're very pleased with what we're seeing so far.

Great. Thanks very much. And then if I may just shift gears to Europe You've obviously done a tremendous job in the U.S. in terms of EAP conversion. Can you help us just think through the pushes and pulls of converting the EAP patients in Europe should you be approved there versus sort of what we saw in that sort of really quick and very good execution in the U.S.? ?

Thanks, Brandon. So you're absolutely right. You know, if you're taking note, we've gone from this time last year, maybe 70 to 80 patients in our, what we call it is our global EAP, which is in Europe primarily, in a small number of markets. And each quarter, we continue to give you a number that's a little higher. We ended with 89 patients at the end of Q2. And that's from a small number of European markets that we have this expanded access program. These patients, if we think about the durability and how long they've been on therapy, and then the ability for us at a market-by-market level after approval, you know, reimbursement in Europe is going to be by country. So it's variable in regards to making that happen. But I do think our continued growth in the EAP program in Europe, along with the durability of patients that have been in the program for a long period of time bodes well for us to be able to pull those patients through once we get reimbursement in those countries.

Great. Thank you very much, and congratulations on all the progress.

Thanks. We'll go next to Kristin Kluska at Kantor.

Hi, everyone. Congrats on another good quarter. So first I wanted to ask, you talked about the different patient segments out there, one of them being patients that are diagnosed but not on any therapies yet. Can you walk us through what that means? Are these newly diagnosed and they're taking the steps? Are they interested in therapies, hoping to learn more? And then I have a follow-up.

All right, Kristen, I'm going to try and quarterback this here. But that one, I think, goes directly to Josh to be able to talk a little bit about our diagnosed patient population and how we plan to get the rest of those patients exposed to MyPlypha. And then while we're continuing to unlock the newly diagnosed patients as well, which we're starting to see as well.

Josh? Yeah. So specifically your question around those patients who are diagnosed but not receiving treatment. Those are typically patients who maybe were diagnosed a year ago prior to any therapies being on the market, and at that time maybe their symptoms weren't severe enough for them to receive any treatment. We're finding that those patients are now coming back into the offices, either their local clinicians who are now being made aware of treatment options, or going back to those COEs. And so we're finding those patients now that we've been on the market for nine months or so, and we're building that awareness and being able to bring those patients who had not previously received treatment to be eligible for MyPlyful.

Yeah, and Kristen, one of the things I might just follow up on Josh, you know, and maybe from the prior question as well, when we think about these centers of excellences and we think about the local physicians who are working in concert with the diagnosing center of excellence, as we've talked about in the prepared mark, we've mapped those physicians that are not in the actual centers of excellence, and our field organizations optimized to be able to go out and make sure that we can educate and offer MyPlypa to those physicians in the event that they had more than one, right? A lot of these physicians have only ever seen one patient. and only have one patient to rely on that center of excellence. Now that they've got experience with MyPlypha, we have the opportunity to be able to make sure that we're providing them with the disease state awareness campaign and everything else to know that if they see it once, maybe they can see it twice.

Okay, thanks. And then can you provide us a sense of what percent of patients are on paid mid-slypha? And then our checks support that those patients that are on combination, that reimbursement has gone well, but curious what you're seeing from your end. Thanks so much again.

I might start that one off. Kristen, we give metrics that are around the prescription enrollment forms coming in the top that allows for us to show kind of the top of the funnel, if you will. And then we provide that covered lives, and we provide also the reimbursement, sorry, the revenue number When we talk about those patients that are on paid drug, you'll see that you go from 17.1 million Q1 to 21.5 million in Q2. That's a 26% increase quarter over quarter in paid drug. But going from 122 enrollment forms to 129, it's obviously not 26%. So we're hopeful that the guidance we're giving you around revenue, which is what comes out of the bottom, we'll be able to provide that that takeaway on paid performance.

Yeah, and I would just add to that part of the question, Kristen, that our patient services team has done a phenomenal job of being able to convert enrollments to paid patients and make sure that these patients are able to receive myoclipo. Also importantly, making sure that they continue to get their refills. And so the retention rate of these patients is also really quite high. I think you had a second question, which was really around combination, and what are we seeing in terms of patients receiving a combination of therapy?

He is specifically from reimbursement. Sorry.

Reimbursement, yeah. Well, you know, I would remind you that by label, patients who are receiving myplifer are also receiving miglistat. And so that, by definition, is a combination of those two therapies. We're not seeing any pushback or very limited pushback from a reimbursement standpoint. As we noted in the prepared remarks, we currently have 52% coverage, and for those who are not immediately covered, we're able to get reimbursement through medical exception pathways.

Thanks again.

Thanks, Preston. Once again, ladies and gentlemen, it's star one. If you had a question, we will go next to Jason Butler with Citizens.

Thanks for taking the questions and congrats on the quarter. Two questions that I understand that you're still early in the launch and you may need to run time to get complete clarity on, but do you have a sense now that you're a couple quarters in of what the average time is taking from enrollment form to getting a patient on reimbursed drug? And then in terms of retention, do you have enough data yet to speak to whether the retention rate for patients that were not in the EAP is consistent with the retention rate that you saw in the EAP? Thanks.

Jason, I appreciate the call. I'll ask Josh to be able to talk a little bit about the time from enrollment form to getting those patients through the system and then into commercial drug. It's improving for sure. uh josh talked about that in regards to our retention rate of patients that are newly on product we're only in the second full quarter of launch it's really hard for us to be able to tell you about persistency rates and or adherence rates to prescriptions at this point only the second quarter You know, some patients have only received one commercial fill. Others have received, you know, seven. So I think it's a little early for us to go there. And usually we need about six quarters to be able to actually get a true persistency and adherence rate. So it'll take a little bit more time for us to get to that. But one thing I can say is that of our EAP patients who converted, to commercial product, they have been, the majority of those patients have been consistent on product. And we've had limited, if any, of folks come off product.

And I would just add to that point that we're really not seeing any differentiation from a payer perspective as to whether a patient was on the EAP or not. And so we're looking at retention rates more holistically and haven't seen any differences really materially between a patient who was enrolled in the EAP and those new patients who have come to my PLEFA since then who were not on the EAP. So our retention remains quite high across all of those patients. In terms of the time from enrollment to paid, again, that varies widely based on the type of plan that a patient might be on, whether that's commercial or Medicaid. And then within commercial, there's a high degree of variability. But what I can tell you is that that timeframe across all payers is being reduced dramatically, so much that in some instances we're seeing patients getting covered within 72 hours. Now, not all of them, of course, but we are seeing some patients with very rapid conversion from enrollment to pay. And we continue to see that improve quarter over quarter.

Great. And then, just one more from me on AllProve. Obviously, you're thinking carefully about the strategy here. Can you speak to what the magnitude of investment in commercializing the product that doesn't overlap directly with MyPlypha? Just trying to get a sense of, essentially, how much you're investing in the product and how you're thinking about continuing that investment.

Thanks, Jason. So I think hopefully we made it really clear in our prepared remarks, and I'll reiterate it here. You know, we are today got a commercial infrastructure that is actually running really well. When we talk about, you know, handling our enrollment forms as well as pulling those patients through, our field reimbursement support, all the things that are working for us to be able to deliver this strong performance in Q2 for myPlypha. It's synergistic with Old Prove all the way. This question you're asking around if we took out, I think is what you're asking, if we took out, you know, my plight out of this, what would it be costing you to be able to run Old Prove up? And the reality is that it would be fairly similar to what you see in our SG&A today because of the high level of overlap and our ability to be able to truly execute on what our business plan is. having these centers of excellence, 40 of them or so across the country, that we can provide value across the chain from commercial to medical to disease state awareness and really help this rare disease community. It's hard for me to break it out. It's very limited in regards to one or the other, but the synergies are huge for us. That provides us with a great opportunity to be able to do this really well, earn the right to go do it again someday.

Great. Thank you. Thanks for taking the questions.

We'll go next to Sumant Kulkarni with Concord.

Thanks for taking that question. You said the seven additional patient-indulgent farms in Mariposa takes you up to 129 in total. Is it in line with your expectations at this stage of the launch? How should we think about growth in patient-indulgent farms going forward, and how do you think the availability of Acneursa, which is also a food funding and big type C, is impacting patient-indulgence?

Yeah, thanks, Suman. And I appreciate the question, and we're looking forward to spending time with you at your conference tomorrow. You kind of set up the question nicely. When we think about 300 to 350 patients diagnosed in the US, having 129 of those patients enrolled into our program is a, quite frankly, I'm incredibly proud of this organization in delivering that. When we think about moving forward and the variability of enrollment on a quarter to quarter basis or a month to month basis, Unlocking this opportunity between the 300 and 350 to the 900 prevalent in the United States, we want to be more like Europe in this regard. You know, a decade ago when the miglestat was approved in Europe, there were a small number of patients who had actually been diagnosed. And with a prevalence of 1,100 in Europe, a majority of those patients are now being diagnosed, have been diagnosed on some type of treatment. So I'll ask Josh to talk a little bit about some of the areas and things that he's doing to be able to ensure that we can continue to drive the performance in the U.S. But we've got a great comp in Europe that shows us that as we continue to invest, we can be much more like this mature market having a product approved for a while in Europe.

Yeah, we're really focusing on these two patient segments, those that are diagnosed and perhaps not yet receiving treatment, and that's really around building awareness and re-emphasizing the clinical differentiation of MyPlypha and all the benefits that it brings in terms of it is the only drug that has demonstrated that it halts the progression of the disease at 12 months. We've been able to demonstrate at the first clinical time point, which was 12 weeks, that we have an impact on disease. We've recently published new data around the mechanism of action, which really draws a strong connection between MyPlypha and its ability to affect the underlying pathology of the disease. And then importantly, the recent open label extension data that shows that the durability of that effect lasts up to five years. We're really emphasizing that data and using every opportunity that we can to reinforce that. For the undiagnosed patients, we have a number of different tactics to try and bring as many of those patients to diagnosis so that they can receive treatment as quickly as possible and ultimately halt the progression of disease. We have a disease awareness campaign, Read Between the Signs. Connected to that is a genetic testing capability to allow physicians to test those patients that they might have suspicion around whether or not they have NPC. And then we're using other really sort of sophisticated machine learning to be able to identify signs and symptoms of patients who have not yet been diagnosed based on a profile of an MPC patient, which will allow us to help continue to educate clinicians around how to identify these patients. So we're really excited about those things. And as Neil mentioned, we see Europe as a model that can help us sort of determine or look forward to how we can see that diagnosis rate increase over time.

Yeah, Sumal, maybe I'll just add one more thing. Sorry, go ahead. I can add to that if you have a question.

Oh, yeah, I did. On the pipeline, so you enrolled seven patients in the DISCOVER trial for celiprolol for vascular Alzheimer's syndrome. How happy are you with the pace of enrollment and at what point will you be able to let us know when we might expect top line data on this?

Adrian's here with us, but I'll kind of kick it off and hand it off to him. You know, when we think about the fact that it was at the end of Q3, early start of Q4, that we reestablished the enrollment of this trial and started to invest in the tactics to screen the outstanding patients that had been in the queue, but also some of the tactics we've been executing on that I'll ask Adrian to talk more about to actually get a higher quality call 381 you know genetically identified already patient that could then go into the trial and be and have the opportunity to be screened and then enrolled i think we're starting to see some traction here but adrian why don't you uh give it up here yes we started the genetic testing initiative a couple of months ago we've also connected with most of the centers where those patients actually seen and treated

And I mean the core 31 positive VET patients. And we've got a serious amount of physicians that are interested in referring the patients into the trial and a significant patient interest. It takes a bit of time to see that come to fruition because it takes quite a bit of time to get those patients to the screening process. So we're very hopeful to report positive outcomes of that in the next quarter. Thanks.

Suman, what I was going to say earlier on to your question, when we think about Neiman-Pixie in the U.S., it sometimes goes in the face of what we've been looking at, that we're launching this product in MyPlytha with the largest clinical data set of NPC patients that have ever been put together. In addition to that, we're not just launching a product with 12 months' worth of data. We're now launching a product that now has got five years' worth of clinical data reinforcing the durability of treatment effect in the open label extension study that was published in this last quarter. We're now also being able to elucidate the mechanism of action work that we've talked about as well. And I think this is just the beginning. We're in a very fortunate position. Usually you're not launching a product for the first time with five years of data. So when, you know, Josh is talking about the pull-through, the work his team is doing on driving the awareness with payers with the strength of our data is what's delivering the strong performance, or part of what's delivering the strong performance in what we're doing. The ability for us to be able to have the MAA file as a new MAA with this new, you know, very robust data sets, It puts us in a wonderful position to be able to bring MyPlaifa to Europe and to the rest of the globe and take care of NPC patients outside of the United States. So we're very fortunate that we're able to be able to really jump on the back of a lot of folks that are out there and have been working in this disease area for a long time and now execute for patients with NPC.

Thanks. I have a lot more questions for you tomorrow.

Look forward to it. We'll move next to Sammy Corwin with William Blair.

Hey, team. Congrats on the progress this quarter, and thanks for taking our questions. I was curious how many unique MyPipa prescribers there are now and how that's grown over the last quarter and if you are approaching prescriber saturation. And then you expanded the MyPipa covered lives significantly compared to last quarter. How much further do you think you can expand the extent of covered lives, and are you aware of any policies that are still being finalized? Thank you.

Thanks, Sammy. I will actually pass both of those over to Josh, the unique prescribers as well as if there's any prescriber fatigue, which definitely there is not.

Yeah. So we have seen a pretty significant growth in the number of prescribers. You know, when we first launched and we were dealing with the EAP patients, those were patients who were under the care of just a handful of EAP investigators. And you might have seen clinicians with anywhere from 12 to eight patients. Now, as we move past that into this next cohort of patients, we're seeing clinicians who are treating three, four, maybe one or two patients. And so naturally, the number of unique prescribers has grown pretty significantly And we expect that to continue as this really is an ultra rare disease where now we're getting into those clinicians who are seeing one or two patients over the course of a year. And so that prescriber base will continue to grow. And we expect that the number of lives and patients will grow as well. I think you asked a question around reimbursement and covered lives. And as noted, we're at 52% today, which is very consistent with what we'd expect for this stage of a launch. that's really more reflection of plans who just haven't yet put my place in front of their pnt committee and some plans wait anywhere from 9 to 12 months after product has been launched before they make those decisions and so we expect that number to increase over the course of of our launch And a good analog is looking at El Provo, which has been out on the market for a little bit longer and a more mature market. And as we noted, that's at 79%. So, you know, you can see us absolutely growing from the 52% of covered lives to where we are today.

That's very helpful. Thank you. Welcome next to Eddie Hickman with Guggenheim Securities.

Hi. Good afternoon, everyone. Thank you for taking my questions. Congrats on all the progress. I wanted to follow up on a previous question just to sort of double-click on this penetration. If we think specifically about the sort of two-thirds of diagnosed patients that you know have MPC and they have yet to penetrate, should we expect sort of a similar cadence of new patient enrollment forms throughout the next couple quarters, or do you reach a point where it starts to get sort of difficult to find those patients? This is sort of beyond, you know, finding new patients, but just within those sort of known diagnosed patients. And then just sort of just the logistical question, Can patients start Miglistat and MyPlypha at the same time, or do payers ever ask for, or doctors ever ask for a delay in getting a patient sort of stably on Miglistat before trying to get coverage for MyPlypha? Appreciate it.

Yeah, thanks, Eddie. I think those questions I'll hand over to Josh to handle.

Yeah. So in answer to your second question, patients can absolutely start migvastatin and mycolyte at the same time. And we've seen some new patients, patients new to therapy starting both at the same time. So that is absolutely possible. Your other question was really around the cadence of enrollments. as what do we expect in future quarters. I would just have to say it's really early in the launch to be able to give you any sense of that and be able to give you a sense of trends I think as you look at where we are with our enrollments, that is a good reflection of the demand that we're seeing. I think more importantly, looking at the performance from a dent sales perspective of 26% increase really speaks to our ability to convert those patients who have come in and be able to convert them to paid and then retain those patients. And then as we really begin to pull through the initiatives that we've been talking about with new patient identification, building awareness around clinical differentiation, we expect the enrollments to come in over the next couple of quarters, but again, probably too early to give you any sense of trends at this point.

Thank you.

And just a final reminder, it was star one if you had a question. And it does not appear we have any other questions holding. This concludes the Q&A portion of today's call. I will now turn the program back to our presenters for any additional or closing remarks.

Yeah, thank you, operator, and thanks, everybody, for joining the call today. We'll look forward to keeping you appraised on future progress. Have a great week.

Thank you. This does conclude today's program. Thank you for your participation. You may disconnect at any time.