ZVRA - NASDAQ

Good afternoon, and thank you for joining

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

Thank you, Nichol, and thank you to everyone joining our update call this afternoon. At

Thank you, Neil, and good afternoon. Let's begin with MIPLYFFA for NPC. MIPLYFFA in combination with miglustat 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 7 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, is consistent with our expectations at this stage of the launch. For those other patients who are 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 MIPLYFFA to payers, especially leveraging our long-term open-label extension data, which showed durable clinical benefit for up to 5 years. Our field team, including case managers, continues to play a critical role on the front lines, working with patients and health care 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 AmplifyAssist 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. Further bolster our penetration into the second segment of patients, those NPC 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 MIPLYFFA's therapeutic impact. Last month, at the National Niemann-Pick Disease Foundation Conference, Dr. Barbara Burton, a key opinion leader and Professor at Northwestern University's Feinberg School of Medicine, presented an overview of MIPLYFFA and our unprecedented long-term data. We had a similarly strong presence at the Southeastern Regional Genetics Group Conference with 4 poster presentations. As Neil mentioned, the recent from study 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 5 years in a heterogeneous population of NPC patients with no new safety concerns. These results align with our pivotal trial data, which showed that MIPLYFFA in combination with miglustat halted disease progression compared to placebo over a 1-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 MIPLYFFA 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 NPC patients. This program is helping to drive awareness of the disease as well as identifying patients who are previously undiagnosed and may be candidates for MIPLYFFA. Turning to OLPRUVA. 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 crisis are caused by poor adherence to treatment. OLPRUVA was launched based on an established efficacy and safety profile, but with an innovative formulation that offers a palatable option in convenient premeasured single-dose envelopes for ease of use and ammonia control on the go. We believe in the benefits that OLPRUVA offers people with UCD. 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 OLPRUVA'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 a primary focus on MIPLYFFA. We are prioritizing and executing on key strategies to deliver value to patients living with rare diseases. I will now pass the call to LaDuane, who will present the financial results for the second quarter of 2025.

Thank you, Josh, and good afternoon, everyone. In addition to the financial details included in today's call, we encourage you to refer to

Thank you, LaDuane. We are fortunate to be in a unique position with commercial therapies, 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 4 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?

We'll take our first question from Brandon Folkes with H.C. Wainwright.

Congratulations on all the progress. Maybe just starting in the U.S. and my [Technical Difficulty] in the most to new patient starts in 2Q or sort of just any -- well, I guess, and enrollment and any trends in terms of enrollments in terms of where they may be coming from?

Brandan, you cut out a little bit in the first part of your comment. It sounded like you were asking about U.S. MIPLYFFA 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?

Well, 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. In Q1, we had MIPLYFFA revenue of about $17.1 million and a 26% growth 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 on to commercial product. 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 1/3 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 U.S.

Yes. 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 a -- 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. 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.

Yes, thanks, Brandon. So you're absolutely right. If you're taking note, we've gone from this time last year, maybe 70 to 80 patients in our -- what we coin as 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, 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 in the -- 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.

Congratulations on all the progress.

We'll go next to Kristen Kluska at Cantor.

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 MIPLYFFA and then while we're continuing to unlock the newly diagnosed patients as well, which we're starting to see as well. Josh?

Yes. 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 9 months or so, and we're building that awareness and being able to bring those patients who have not previously received treatment to be eligible for MIPLYFFA.

Yes. And Kristen, one of the things I might just follow up on Josh and maybe from the prior question as well. When we think about these centers of excellence is 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 remarks, we've mapped those physicians that are not in the actual centers of excellence. And our field organization is optimized to be able to go out and make sure that we can educate and offer MIPLYFFA 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 they've got experience with MIPLYFFA, 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. And then can you provide us a sense of what percent of patients are on paid MIPLYFFA? 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.

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 -- or 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 in 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 takeaway on paid performance.

Yes. And I would just add to that part of your 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 MIPLYFFA. 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 combination of therapy.

Yes, specifically for reimbursement, sorry.

Reimbursement, yes. Well, I would remind you that by label, patients who are receiving MIPLYFFA are also receiving miglustat. And so that, by definition, is a combination of those 2 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 of -- and for those who are not immediately covered, we're able to get reimbursement through medical exception pathways.

We will go next to Jason Butler with Citizens.

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 can you -- do you have a sense now that you're a couple of 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?

Yes. Jason, I appreciate the call. I'll ask Josh to be able to talk a little bit about the time to -- from enrollment form to getting those patients through the system and then into commercial drug. It's improving for sure. I'll have Josh talk 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 in the second quarter. Some patients have only received 1 commercial fill. Others have received 7. So, I think it's a little early for us to go there. And usually, we need about 6 quarters to be able to actually get a true persistency and adherence rate. So, it will take a little bit more time for us to get to that. The 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 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 MIPLYFFA since then who were not on the EAP. So our retention remains quite high across all of those patients. In terms of the time to -- 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 time frame 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 paid and we continue to see that improve quarter-over-quarter.

Great. And then just one more for me on OLPRUVA. 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 MIPLYFFA? 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. We are today, got a commercial infrastructure that is actually running really well. When we talk about 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 MIPLYFFA, it's synergistic with OLPRUVA all the way. This question you're asking around if we took out -- I think is what you're asking, if we took out MIPLYFFA out of this, what would it be costing you to be able to run OLPRUVA. 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 excellences, 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. So 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.

We'll go next to Sumant Kulkarni with Canaccord.

You said the 7 additional patient enrollment forms in MIPLYFFA takes you up to 129 in total is in line with your expectations at this stage of the launch. How should we think about growth in patient enrollment forms going forward? And how do you think the availability of [ ACNEORSA ], which is also approved for Niemann-Pick Type C is impacting patient enrollment?

Yes. Thanks, Sumant, 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 U.S., having 129 of those patients enrolled into our program is a -- quite frankly, just 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. A decade ago, when the miglustat 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 -- 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.

Yes. We're really focusing on these 2 patient segments, those that are diagnosed and perhaps not yet receiving treatment. And that's really around building awareness and really emphasizing the clinical differentiation of MIPLYFFA 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 MIPLYFFA 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 5 years. And 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 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 NPC 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.

Yes. Sumant, maybe I'll just add one more thing. Sorry, go ahead. I'll add to that.

Yes, I did on the pipeline. So you enrolled 7 patients in the DiSCOVER trial for Celiprolol for vascular Ehlers-Danlos 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 that.

Yes, Adrian is here with us, I'll kind of kick it off and hand it off to him. 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 have 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 COL3A1 genetically identified already patient that could then go into the trial 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 give an update here?

Yes, Sumant, we started a genetic testing initiative a couple of months ago where we've also connected with most of the centers where those patients are actually seen and treated, and I mean the COL3A positive patients. And we've got a serious amount of physicians that are interested in referring the patients into the trial and 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.

Sumant, what I was going to say earlier on to your question, when we think about Niemann-Pick C in the U.S. It sometimes goes in the face of what we've been looking at that we're launching this product in MIPLYFFA 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 5 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 are in a very fortunate position. Usually, you're not launching a product for the first time with 5 years of data. So when 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 very robust data sets, it puts us in a wonderful position to be able to bring MIPLYFFA 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.

We'll move next to Sami Corwin with William Blair.

Congrats on the progress this quarter. I was curious how many unique MIPLYFFA 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 MIPLYFFA 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?

Thanks, Sami. 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.

Yes. So, we have seen a pretty significant growth in the number of prescribers. When we first launched, we were dealing with the EAP patients, those were patients who are under the care of just a handful of EAP investigators, and you might have seen clinicians with anywhere from 12 to 8 patients. Now as we move past that into this next cohort of patients, we're seeing clinicians who are treating 3, 4, maybe 1 or 2 patients. And so naturally, the number of prescribers, the 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 1 or 2 patients over the course of the 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 the 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. And that's really more a reflection of plans who just haven't yet put MIPLYFFA in front of their [ PNT ] committee and some plans wait anywhere from 9 to 12 months after a product has been launched before they make those decisions. And so we expect that number to increase over the course of our launch. And a good analog is looking at OLPRUVA, which has been out on the market for a little bit longer in a more mature market. And as we noted, that's at 79%. So, you can see us absolutely growing from the 52% of covered lives to where we are today.

We'll go next to Eddie Hickman with Guggenheim Securities.

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 2/3 of diagnosed patients that you know have MPC and that you've yet to penetrate, should we expect sort of a similar cadence of new patient enrollment forms throughout the next couple of quarters? Or do you reach a point where it starts to get sort of difficult to find those patients? This is sort of beyond finding new patients, but just within those sort of known diagnosed patients? And then just sort of just a logistical question. Can patients start miglustat and MIPLYFFA 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 miglustat before trying to get coverage for MIPLYFFA? Appreciate it.

Yes. Thanks, Eddie. I think those questions, I'll hand over to Josh to handle.

Yes. So, in answer to your second question, patients can absolutely start miglustat and MIPLYFFA at the same time, and we've seen some new patients new to therapy starting both at the same time. So that is absolutely possible. Your other question was really around the cadence of enrollment as and 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 net 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.

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 remark.

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