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 accomplishments, followed by a review of first quarter financial results. I encourage you to read our financial results news release, which was distributed this afternoon, and is available in the Investors 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 for joining us this afternoon to review our strong progress and the ongoing execution of our 4 strategic pillars. Let me start with commercial excellence. We are delivering on our 2 commercial launches to bring innovative therapies to people living with rare diseases. We have exceeded our internal expectations for the MIPLYFFA launch and have enrolled over one-third of those diagnosed with Niemann-Pick disease type C or NPC in the United States. With OLPRUVA for the treatment of certain urea cycle disorders or UCDs, we refined our marketing efforts to further increase awareness and access for patients and providers. Moving on to pipeline and innovation. We are focused on where our capabilities have the greatest impact for patients as we progress our development programs. Our Phase 3 Discover trial of Celiprolol, our late stage asset for the potential treatment of vascular Ehlers-Danlos syndrome or VEDS, which has received both orphan drug and breakthrough therapy designations, continues to progress with patient enrollments. Additionally, we continue assessing value enhancing strategic alternatives for our Phase 3 ready asset, KP1077, for rare sleep disorders. These clinical stage assets provide optionality and diversification to our portfolio. Turning to talent and culture. We have a passionate, highly motivated, experienced, and mission-driven team focused on our vision to bring life-changing therapies to people living with rare diseases. Our team's strong execution is being acknowledged. For example, we earned a spot on fast company's top 10 most innovative companies list in the medicines, therapeutics, and pharmaceuticals category. Finally, corporate foundation. This underpins all other pillars and allows us to responsibly invest in our long-term transformation through disciplined capital allocation while maintaining our position of financial strength. With the recent monetization of our pediatric rare disease priority review voucher or PRV, we added $148.3 million of non-dilutive capital to our balance sheet, bolstering our financial strength. With this, we have ample resources and financial flexibility to execute on our strategic priorities independent from the capital markets. Driving a little deeper into our commercial programs, we are pleased with early success in MIPLYFFA launch for the treatment of NPC, which is an ultra rare neurodegenerative, progressive, and fatal disease. The launch is characterized by 3 unique patient cohorts, those who are participants of our expanded access program or EAP, those who are diagnosed and may or may not be receiving treatment, and finally those who are undiagnosed and living with NPC for whom we seek to accelerate diagnosis and treatment. We received a total of 122 prescription enrollment forms from launch through March 31, with 13 in the first quarter of 2025. Even in these early days of the launch, we have received prescription enrollment forms from all 3 patient cohorts, affirming the early impact of our commercial strategy. Notably, as we have previously reported, all active U.S. EAP participants have been enrolled to receive MIPLYFFA, and we have now closed the program, including locking the database and deactivating study centers ahead of our previously stated guidance. We are focused on providing MIPLYFFA to people living with NPC and have been educating prescribers and payers on the clinical benefit, which demonstrates in combination with miglustat, a halting of disease progression through 12 months of treatment. Beyond the pivotal trial, MIPLYFFA's safety profile and the long-term treatment effect have been evaluated in open label extension studies and through our multi-center EAP, with patients having as many as 5 to 7 years of experience on treatment, which significantly differentiates MIPLYFFA and positions it as the cornerstone therapy. Josh will provide additional details related to our launch metrics later in today's call. Beyond the successful U.S. launch, our goal is to provide access to as many people living with NPC as possible by expanding the availability of MIPLYFFA outside of the U.S. We are diligently working towards expanding our regulatory submissions with an immediate focus on a marketing authorization application or MAA in Europe in the second half of this year, where we estimate approximately 1100 people are living with NPC. As a reminder, the European market is already well established with access to a marketed treatment for more than a decade. Further, we're expanding our global EAP, which has recently increased to approximately 85 NPC patients compared to the previously reported 70 to 80 patients. Our continued investment in MIPLYFFA's global EAP in combination with a more established market could accelerate commercialization upon approval in Europe. Turning to OLPRUVA. From initial product availability in July of 2023 and including

Thank you Neil, and good afternoon. Today, while discussing our commercial products, we will provide the following metrics, prescription enrollment forms for the quarter, the percent of covered lives, and net revenue. Beginning with MIPLYFFA, as Neil stated, the launch is progressing well and exceeding our expectations. With our EAP cohort fully enrolled, we're focused on reaching the diagnosed and undiagnosed cohorts. We've seen steady growth in the first quarter with 13 prescription enrollment forms, all representing individuals new to MIPLYFFA, which indicates a broadening of both the patient and prescriber base. This is a result of our ongoing efforts to raise awareness of NPC and to educate prescribers about MIPLYFFA's clinically differentiated profile. We estimate that there are approximately 900 people living with NPC in the U.S., of which only 300 to 350 have been diagnosed. Since launch through March 31, we have received a total of 122 prescription enrollment forms, meaning that roughly one-third of the estimated individuals diagnosed with NPC in the U.S. have been enrolled to receive MIPLYFFA. As a reminder, a prescription enrollment form is a prescription submitted to our specialty pharmacy, initiating the benefits investigation process to determine reimbursement and can lead to a thirty-day paid dispense of MIPLYFFA. Regarding market access, many payers have not yet formalized their formulary coverage or reimbursement policies, and our team has been actively engaging with payers to secure reimbursement. Through the end of the first quarter, we have achieved 38% of covered lives, which is in line with our expectations at this stage of launch. We have been able to secure reimbursement authorization for many of our patients through direct formulary coverage or via the medical exception process. While initial denials are commonplace among rare disease products, we are very pleased with our team's ability to swiftly address payer challenges by presenting MIPLYFFA’s robust and differentiated clinical data. NPC is a lysosomal storage disorder that is caused by progressive lipid buildup, leading to cell death and ultimately organ dysfunction in the spleen, liver, and brain. The difficulty in diagnosing NPC patients centers around variability in age of disease onset and the heterogeneity of symptoms. As a result, the disease progression is measured by the only clinically validated tool, the 4-domain NPC clinical severity scale, which evaluates 4 key domains deemed by NPC experts to be the most important, including ambulation, fine motor skills, speech, and importantly, swallow abilities. MIPLYFFA is the only product approved by the FDA based on the NPC clinical severity scale, and the data in our label demonstrate that MIPLYFFA, in combination with miglustat halts disease progression through 12 months of treatment, as shown by a greater than 2% improvement in patients receiving MIPLYFFA and miglustat compared to those receiving miglustat alone. It's important to note that only a 1 point improvement is needed to demonstrate a clinically meaningful difference with a well tolerated safety profile. Additionally, MIPLYFFA is the only FDA approved product for NPC with more than 5 years of clinical data in its label and with more than 270 NPC patients, who have participated in our pivotal trial, our open label extension study, or our EAP. In our view, these data, in addition to its well tolerated safety profile, establishes MIPLYFFA as the cornerstone of therapy for NPC. Building on our strong body of evidence, we recently issued a publication discussing mechanistic insights into MIPLYFFA's mediated effects on lysosome function and NPC in the Journal of Molecular Genetics and Metabolism. The elucidation of MIPLYFFA's differentiated mechanism of action marks a critical step in understanding its interactions with NPC at a cellular level. These insights substantiate how MIPLYFFA addresses the underlying pathology of NPC and supports the long-term benefit observed in our clinical trials. During our fourth quarter call, we unveiled numerous initiatives to reach the NPC patient cohorts, namely those who are diagnosed and may or may not be receiving treatment, as well as the undiagnosed population. We continue to analyze claims data to identify existing patients, and we are employing targeting techniques to identify new and undiagnosed patients based on related symptoms and conditions. In addition, our targeted media campaign to build awareness and educate about early signs and symptoms of NPC is proving to be successful. We've expanded to a national scale, reaching households across the U.S. Our team is amplifying the reach of these new segments through branded geo-targeting efforts in the corresponding regions. And these new segments are increasing awareness of NPC and the availability of treatment options and are primarily designed to resonate with individuals who have been diagnosed, but are not yet receiving treatment. We also launched our disease state awareness campaign, learn NPC, Read Between the Signs on Rare Disease Day this past February, and it's driving disease recognition and early diagnosis. Treatment of NPC is multifaceted, and our program provides education and genetic testing options for individuals with suspected lysosomal storage disorders. We have already seen the impact of this initiative with new patients, who were not previously diagnosed with NPC being identified, enabling us to facilitate earlier diagnosis and offer MIPLYFFA as a treatment option. In summary, we are encouraged by the early results of our efforts to engage the diverse patient cohorts, and we're looking forward to sharing our ongoing progress and future success with the program. Now, let's turn to OLPRUVA, our commercial product for the treatment of certain UCDs. UCDs are a group of rare inherited metabolic disorders resulting from a defect in 1 of the 6 enzymes or 2 transporters in the urea cycle, causing an accumulation of ammonia known as hyperammonemia, which can be toxic and lead to neurocognitive damage or even death. As we have discussed in prior quarters, we have moderated our expectations for the pace of the launch, given the unique dynamics of the UCD commercial landscape. From initial product availability in July of 2023 and including

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

2025 is off to a terrific start for

[Operator Instructions] We will go first to Sumant Kulkarni at Canaccord.

Good afternoon. It's nice to see the progress and thanks for taking our questions. I have a couple. So first, relative to the 122 patient enrollment forms, could you give us any details on the number of patients that are actually on MIPLYFFA right now and what the spread of reimbursed patients might be?

Thanks Sumant. And just before I answer that question, I want to let everybody know that we're taking the call from multiple locations, so that may necessitate a slight delay in responding as we get the folks who are going to be answering the question. I'll hand that question directly off to Josh in regards to the strong performance we've seen with MIPLYFFA so far.

Thanks, Sumant. So as noted, we have seen 122 or received 122 enrollments since the launch through the end of the first quarter. We do not report on how many of those are actively on drug, but I can say that the majority of them are on drug, and those who are not yet are going through a process of benefits investigation and are in some stage of pending. Some might be receiving what we call Quick Start, which is free drug while we investigate the benefits and then intend to convert those patients to paid, and then there may be others that are just in some various stage of benefits investigation.

And one more before I hop into the queue, you mentioned denials of reimbursement at early stages in rare disease launches are to be expected. That's understandable. Could you give us any sense of what the top reason might be for the denial of MIPLYFFA?

Yeah absolutely, and those are 2 different data points. The 38% of covered lives is looking at the total number of patients out there -- the total number of people out there with insurance, 38% of those total covered lives who are receiving commercial insurance, federal insurance, VA are covered currently. And then -- any challenges that we're finding right now. We haven't seen some initial denials, and that's totally to be expected with rare disease product, and that is typical of products that have to go through some sort of prior authorization before they can get approved. We've been able to get coverage for almost all of our patients either through direct formulary -- either direct formulary status or through some sort of medical exception process, which might require a physician writing a letter of medical necessity, but we've had great success in getting that covered, and that's largely due to the demonstrated differentiation that MIPLYFFA has with it being the only drug that demonstrated the halting of disease progression through 12 months. It's got 5 to 7 years of patient experience with more than 270 patients treated, and we have the only clinically validated end point for NPC, which is the Niemann-Pick clinical severity scale.

Thank you.

Yeah Sumant, maybe I'll bring to the forefront. Josh laid it out beautifully. Our differentiation in the clinical profile is what's really driving the strong performance, the feedback from physicians and so far how we've been able to address the market access challenges that come up with every product that's in the specialty space is really demonstrating the strength of the data. That's really what's driving a lot of our performance today.

Thanks.

[Operator Instructions] We'll go next to Jason Butler with Citizens.

Hi, thanks for taking the questions and congrats on the quarter. A couple from me on MIPLYFFA. First of all, how much visibility do you have into whether patients are coming from that undiagnosed bucket versus diagnosed, but on therapy right now and just how should we think about bringing those patients on-board, the cadence you can bring those patients on-board throughout the year and then second question just qualitatively, can you speak to how inventory levels ended the quarter versus the end of 2024?

So Jason, thanks for the question. I'll try to quarterback this a little bit. I'll ask Josh to talk a little bit specifically in regards to the 3 cohorts that we talked about and the visibility, and then I'll ask him to hand it off to LaDuane, which again may take a quick second to talk about inventory levels and our targets and where we are today.

Jason, as we've mentioned, there are 3 distinct cohorts that we think about. The total prevalence for NPC is roughly 900 patients, 600 of which are so that are undiagnosed, living with the disease and don't even know it, and there are about 300 to 350 that are diagnosed and either receiving some sort of treatment or just sort of waiting and watching; of that subset, we had 83 patients who were in our expanded access program, and those patients have all been enrolled to receive MIPLYFFA. We reported at the end of the fourth quarter 109 patients, and that included those EAP patients plus a combination of diagnosed and undiagnosed. We continue to see a number of -- 2 cohorts, the diagnosed and undiagnosed patients coming in as a direct response to the initiatives that we've rolled out to bring more awareness to the disease and also to MIPLYFFA as a treatment option.

LaDuane, if you can?

Sure, thank you. And so, Jason, with regard to inventory, these are the early days of the launch, and we seek to support patients and remain very nimble. So, we're managing that closely using a target days on hand. When we reported out in Q4, we explained that we had reached it and stocked at that target level, and we are maintaining that as we come into the end of Q1 as well.

Great. Thanks for taking my questions.

We'll go next to Eddie Hickman with Guggenheim.

Hey, good afternoon. Thanks for taking my questions and congrats on the progress so far. Any qualitative metrics on refill rates or patient retention or average net price that you can give us that might be helpful for modeling the durability and treatment effects or trajectory going into the second half of the year? Should we expect this cadence of [indiscernible] patients of maybe around 3 to 4 per month to continue throughout 2025, and what are the challenges in continuing to penetrate those non-EAP patients?

Yeah, so I can give you a little bit of color to say that of those patients that have come in and for whom we've received enrollments and who are receiving active drug, the vast majority of them have received refills and are continuing to stay - stay on drug, certainly as we as we continue through the launch, we would expect to see that maybe diminish a little bit. But really, if you reflect back to our EAP, we had patients who stayed on drug for as long as 5 to 7 years, and so that really speaks to the clinical benefit of MIPLYFFA as well as the durability of response and we would expect to see that commercially as well. Your other questions were around net price, and again, what we're seeing in commercial is something very similar to the distribution of doses that we saw in the EAP with the vast majority of patients receiving 1 or 2 of the higher doses. So that can give you kind of a sense of what the -- the whack price is, and give you a sense of how that's trending as well.

Yeah, Eddie, maybe you have a follow up question here, but before we move forward, when we actually launched the program back in September, we talked about the fact that we were utilizing the average dosing of our EAP patients, which the clinical trial leaned more to younger, lighter weight patients and then our expanded access program really brought more adult patients in too. So, what our real world experience has been so far and the average pricing that we had reported out based on the weight distribution of our 83 patients has really kind of continued the same. So that guidance that we provided is guidance that I would continue to have you move forward with.

Thanks. And then I was curious sort of about the cadence of those new patients starts throughout the year, should we continue to sort of think about 12 to 13 per quarter or will that diminish or growth throughout the year?

Thanks again for the question. I think it's difficult for us, we're not going to provide guidance. We're going to continue to be disciplined in what we do around the metrics that Josh talked about and new patient enrollment forms as well as market access and then revenue to be able to pull through. What I would say to you though is that as we went through the 3 cohorts and accelerating the expanded access programs and continuing to get them really rapidly and take us 12 months, we got it done in just a quarter and a little bit. We're now in the process of getting to these 2 other cohorts, the diagnosed patients who have not been on therapy, as well as those patients who are not yet been diagnosed in Q1, and we expect that we'll continue to see all 3 of those cohorts, -- well now that's the EAP, those are done; but the other 2 cohorts of those patients who are diagnosed and undiagnosed, continue as the strength of the product and the benefits lead to getting patients on therapy. So, I can't give you guidance in terms of where the cadence is going to be, but I can tell you that the strong performance today is based on our data.

Thank you so much.

[Operator Instructions] We will go next to Lachlan Hanbury-Brown with William Blair.

Hey guys, thanks for taking the questions and congrats on the progress. I wanted to ask on the coverage, you said 38% of lives are covered. Can you just elaborate on what that coverage looks like, what the requirements are? Did you contract for that? And maybe, how much of an impact does having that coverage make in terms of the time to get a patient from sort of prescription enrollment form to actually on drug, because I assume it still requires a prior authorization. And then if I could just clarify as well, on the EAP patients, you said that they'd all been enrolled just to clarify, is that, are they all now or are some of them still sort of in the benefits investigation stage?

Great. Well, I'll take your first question around what the 38% of covered lives means. So again, most commercial plans and federal plans will evaluate a drug based on its clinical merits and some plans will not by policy evaluate a product until it's been on the market for 6 months, and some it might be as long as 12 months. And so the 38% of covered lives means that those plans, roughly 75 to 100 plans out there covering several hundreds of millions of lives have reviewed MIPLYFFA and have made it available to their patients, and that represents about 38% of the total lives out there that have insurance. That does not mean that only 38% of our patients will receive drug or be able to get drug reimbursed. That just means that there's a direct route through a formulary status or position. All plans have a medical exception pathway, and we've been very successful in getting our patients reimbursed through a medical exception pathway. We expect that 38% to increase as more plans evaluate MIPLYFFA going forward, and we will continue to see that number increase, and we will continue to have patients reimbursed either through direct formulary status or through the medical exception pathway.

Just to follow up on your question, you asked if all of the patient enrollment forms have been put onto a commercial product, and that's the process that we work through - through this medical exception pathway as well as others to get patients through and convert them from an enrollment form to a paid prescription, if you will, or commercial product. That timeline is not immediate. Some of them are within 24 hours, they can get through the process, and others take time to work through this, peer-to-peer medical exception, so on and so forth process of getting specialty pharmacy products through. What I'm very proud of is the team has actually worked diligently to be able to ensure that when a prescription form comes in, we do everything that we can to make sure that patient and their family receive the product as soon as possible while we're going through the benefits investigation process, and they're actually rapidly working through this really large number, again 122 enrollment forms, a dramatic number of forms and really strong performance and getting through that process. Some are going to take 30 days. Some are going to take 24 hours. Some are going to take 30 days, some are going to take much longer than that. So, I would say that right now our team is doing a great job and you see that based on the revenue numbers that we've got in just our first full quarter post launch of converting those patients.

Thanks.

We'll return now to Sumant Kulkarni at Canaccord.

Thanks for the follow-up. This is on Celiprolol, which seems to be flying under the radar a little bit. You said you have 32 patients enrolled. It's an event driven trial where you're increasing efforts to drive enrollment. If I remember right, this is a 150-patient trial. It looks like the last update on clinicaltrials.gov came about a year ago. Given that the Phase 3 trial for a competitor, [indiscernible] has been suspended for some time now, what does that mean in terms of your ability to give us a timeline on when enrollment might be complete?

So your numbers are absolutely accurate Sumant. You talked about [N] [ph] of 150 patients in a 2 to 1 randomization. I think it's important to just take a quick step back. We inherited this trial after it had actually paused enrollment for some time, with a large number, as we've said publicly previously, of screenings that were ready to go into the trial. We kicked that off in Q3 with our first patients being dosed -- re-enrolled or re-dosed in the trial. And then we've been actually investing in getting through the screening of the previous patients, but also now targeting how we're going to be able to drive future enrollment. We talked about our ability to go to COL3A1 patient centers and physicians to be able to find more readily diagnosed patients who are more keen to be able to go into the trial, and we also talked about some genetic testing that we're also doing as part of our screening, so we get more patients who are already diagnosed have the genetic defect, and we can then offer them the opportunity to be in the trial. Those activities we feel very confident will continue to drive and now accelerate enrollment of the trial, but it's really only been 2 quarters since we got the trial up and going. The learnings as we've walked through and now we've got these 5 additional patients, 32 patients enrolled to date, and there's a high unmet need and no approved therapy, as you know, but we're working through with these clinics and testing centers now to really ramp it. So, in a nutshell, I can't tell you exactly when we will finalize it, but the strategies are starting to pay off in terms of our commitment to moving forward.

Got it, thanks.

And that will conclude the Q&A session. I will now turn the program back over to Neil McFarlane for any additional or closing remarks.

Thanks operator, and thanks everybody for joining our call today. We look forward to keeping you apprised of future progress and look to see you in Q2.