Zevra Therapeutics - Q4 2025

Transcript

Operator (participant)

Good afternoon. Thank you for joining Zevra's fourth quarter and full year 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 Nichol Ochsner, Zevra's Vice President of Investor Relations and Corporate Communications.

Nichol Ochsner (VP of Investor Relations and Corporate Communications)

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 fourth quarter and full year 2025 financial results. I encourage you to read the 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 forward-looking statements due to risks and uncertainties associated with Zevra's business.

Forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties and other important factors that may lead to actual results differing materially from the projections made and should be evaluated together with the Risk Factors section in our most recent quarterly report on Form 10-Q, our annual report on Form 10-K and other filings with the SEC. I'm pleased to welcome Zevra's management team members participating in today's call. Neil McFarlane, Zevra's President and Chief Executive Officer and Josh Schafer, our Chief Commercial Officer. Our Chief Medical Officer, Adrian Quartel and our Senior Vice President of Finance and Corporate Controller, Timothy Sangiovanni, will be available for today's question-and-answer session. It's my pleasure to hand the call over to Neil.

Neil McFarlane (President and CEO)

Thank you, Nicole and welcome to everyone joining our quarterly call this afternoon. I wanna start off by welcoming our newly appointed Chief Financial Officer, Justin Renz, whose official start date is today. Justin brings more than 25 years of biopharmaceutical financial leadership experience with a strong track record supporting global commercial operations, along with extensive experience in capital markets and investor relations. He will share a few brief remarks at the end of the call. However, he will not be taking questions on today's call. At Zevra, we're on a mission to redefine what's possible in delivering life-changing therapies to people living with rare diseases. As a commercial stage company with a late-stage pipeline, we have a unique opportunity to make meaningful impacts for patients.

Our vision comes to life through our strategic plan and our core values of patient centricity, integrity, accountability, innovation and courage. Guided by the execution of our plan and demonstrating our values, 2025 was a banner year with net revenue of $106.5 million, driven by the performance of MIPLYFFA, which delivered $87.4 million in revenue. Specifically in the fourth quarter, we generated $34.1 million in total net revenue, which included $26.4 million from MIPLYFFA sales. This momentum set the stage for multiple growth drivers in 2026. Our success was reflected in the strong commercial performance of MIPLYFFA, with 24 prescription enrollment forms received in the fourth quarter, bringing the total in the first full year of commercialization to 52 enrollment forms and a total of 161 enrollments since launch.

MIPLYFFA is our foundational treatment for Niemann-Pick disease type C, or NPC. This increasing penetration means that more patients are gaining access to the therapy they need. Importantly, this growth is being driven by previously diagnosed patients and increasingly by newly diagnosed patients. This trend reinforces our confidence in the estimated U.S. prevalence of approximately 900 affected individuals, of whom 300-350 are currently diagnosed. Later on the call, Josh will review some of the initiatives that are fueling our traction in the identification of newly diagnosed patients. As a reminder, MIPLYFFA has exclusivity in the U.S. through 2031 under the Orphan Drug Designation. We are diligently pursuing a patent term extension, which is currently under review by the U.S. Patent Office. It's important to note that additional exclusivity would represent positive upside to our existing runway.

We're expanding access to MIPLYFFA or arimoclomol beyond the U.S. through our global expanded access program or EAP, which had 113 patients enrolled at the end of 2025. Over the past year, we've built a strong reputation across Europe, in particular through our global EAP, enabling clinicians to gain firsthand experience with arimoclomol. In the fourth quarter, we established a new distribution agreement to extend the global EAP to select territories outside of Europe and initiated shipments of named patient supply prior to year-end. As is common with these types of distribution agreements, we anticipate variability in ordering patterns and the rate of new enrollments in the first few years until the patient base has stabilized. We're pleased with the rapid execution by our partner to ensure swift delivery to patients.

Importantly, in late July of last year, we submitted our Marketing Authorisation Application to the European Medicines Agency, supported by a robust data package, including our pivotal Phase II/III trial Open-label extension study, expanded access programs and our pediatric sub-study. As a part of the standard review process, we received a 120-day list of questions from the EU regulators at the end of 2025. At this time, we're fully prepared to respond to these questions within the regulatory 90-day clock stop period and look forward to our continued engagement with the agency to make arimoclomol available to the EU NPC community. In Europe, NPC prevalence is estimated at approximately 1,100 individuals and our current EAP is supporting nearly 10% of this population.

Diagnosis rates are significantly higher than in the U.S. due in large part to the European approval of miglustat for the treatment of NPC, which provided a clear treatment pathway and has led to stronger physician awareness and higher patient identification. As we continue expanding access and strengthening relationships with key opinion leaders, we are well-positioned to maximize our commercial impact in Europe through strategic partnerships or independently. Beyond MIPLYFFA, we're advancing celiprolol for the treatment of vascular Ehlers-Danlos syndrome, or vEDS, a rare inherited connective tissue disorder caused by COL3A1 gene mutations. These mutations lead to defects in type III procollagen in the walls of blood vessels and hollow organs, resulting in arterial dissections and organ ruptures. In the U.S., approximately 7,500 individuals have been diagnosed with vEDS.

Celiprolol acts as a selective adrenoceptor modulator, reducing mechanical stress on collagen fibers. Data on celiprolol generated outside of the U.S., including results from the BBEST study and two long-term European cohorts, demonstrated a reduction in major vascular events and improved overall survival among patients receiving treatment. Our ongoing phase III DiSCOVER Study designed to confirm the clinical benefit observed in prior studies. We enrolled eight patients in the fourth quarter, bringing the total number of enrolled patients at year-end to 52 of the planned 150 patients to be enrolled in the study and one confirmed event out of the 28 events required to trigger the interim analysis.

We are continuing to implement strategies to boost our enrollment, including building a network of genetic testing centers to help diagnose individuals with vEDS, as well as connecting with specialists that care for these patients, such as the vascular surgeons who intervene when a patient experiences an event. In parallel, we recently engaged the FDA in a Type C meeting to discuss our regulatory options to accelerate the development program. While discussions are in their early stages, we appreciate the agency's responsiveness to our request and look forward to further engagement in the second half of the year. Finally, from a corporate standpoint, we've moved our headquarters to Boston, a strategic step that strengthens our foundation for long-term growth and positions us at the center of one of the world's most dynamic biotech ecosystems.

This move enhances our ability to collaborate with industry leaders and access a deep pool of highly specialized talent, ensuring we remain well-equipped to deliver on our strategic plan. Before turning the call over to Josh, I would like to recognize that February was Rare Disease Awareness Month. To coincide with this, we were invited to ring the opening bell at Nasdaq. It was a powerful tribute to the patients who inspire our mission and drive us forward every day. It's especially important to connect with the community. During the month, we also held an all-hands meeting where we had the privilege of hearing from a mother of two children with NPC.

Her story reinforced the importance of expanding access to diagnosis, treatment and support for the community and it was a moving reminder of why we do what we do for people living with rare diseases. Josh?

Joshua Schafer (CCO)

Thank you, Neil. Good afternoon. We are thrilled by the commercial performance and the momentum we are seeing in the U.S. market. With 52 prescription enrollment forms in 2025 and 24 of them received in the fourth quarter, as well as our strong refill rate, we are building confidence in the continued growth and long-term potential of MIPLYFFA. We believe this reflects the compelling clinical benefit demonstrated by MIPLYFFA as the only disease-modifying therapy for NPC, shown to have both a rapid onset of improvement within 12 weeks of treatment and to halt NPC progression at 12 months with durable efficacy and safety maintained for more than five years. This clinical differentiation is resonating across stakeholders and is catalyzing adoption of MIPLYFFA.

We are seeing strong adherence to therapy once a patient begins treatment, similar to what we observed in the long-term U.S. EAP. A reminder, NPC is a devastating and often fatal genetic disorder caused by mutations that impair intracellular lipid transport. As a result, cholesterol and other lipids progressively accumulate within cells, leading to widespread neurological and organ dysfunction. NPC is clinically heterogeneous, with significant variability in symptom presentation and rate of progression. Although it has traditionally been considered a pediatric disease due to its genetic origins, approximately half of the people treated with MIPLYFFA are adults, underscoring the need to recognize NPC across the lifespan. Neil mentioned, the growth we saw in the fourth quarter was driven not only by the increased adoption among previously diagnosed patients but also meaningfully by people who were previously undiagnosed.

This progress within the newly diagnosed segment strengthens our confidence in the overall market potential. We attribute this success to our three-pronged approach to education and diagnosis through our disease awareness campaign called Learn NPC: Read Between the Signs, our custom AI-driven targeting model and our collaboration with providers of genetic tests to confirm diagnosis. Our disease awareness campaign has become a trusted go-to resource to effectively educate the community on the need for early detection and treatment of NPC, whether through engagement at medical congresses or providing resources for individuals seeking reliable information online. We have developed a bespoke AI predictive model to identify potential patients who may be misdiagnosed or undiagnosed. Using claims data and electronic health records, we analyze the symptoms and diagnosis and treatment journeys of patients who are confirmed to have NPC.

We apply these insights to a broader claims database to find undiagnosed patients with similar profiles. We recently expanded our partnership with GeneDx, which adds to our existing collaborations with companies that provide genetic testing to confirm a diagnosis of those suspected to have NPC, serving to accelerate time to diagnosis and new patient identification. Eligible patients will be able to receive GeneDx's ExomeDx test at no charge and results will be provided to clinicians and their patients in as little as three weeks to facilitate clinical decision-making. This strategy revealed a number of unique patients who match these patterns and were previously unknown, allowing us to engage physicians with targeted education, turning data into action and giving newly identified patients a chance for earlier intervention in their disease.

We continue to educate the community on our robust clinical data and differentiated mechanism of action. At the WORLDSymposium last month, we presented four posters highlighting new data on MIPLYFFA. The growing body of evidence continues to support the impressive results we saw in our clinical trials, reinforced by the long-term real-world data we are generating. There were multiple presentations resulting from the data generated through our U.S. EAP program. In a multiyear subgroup analysis of participants with up to four years of follow-up, MIPLYFFA demonstrated durable treatment effects, sustained clinical benefit and safety, with significant patient adherence over that time.

At World, we also presented new analyses evaluating the adult NPC population and found those treated with arimoclomol in the U.S. EAP showed disease stabilization over the four years while maintaining a favorable safety profile consistent with the broader results. Importantly, our market access strategies remain strong and we continue to drive access for our patients. We are at 68% of total covered lives, which is in line with where we expect it to be after the first full year on the market. For the remaining patients, we have been able to secure high reimbursement rates through the efforts of our market access and patient services team. Our success reflects the benefits demonstrated by data generated in the clinical studies, as well as long-term real-world experience, which show MIPLYFFA's ability to halt disease progression with a favorable safety profile.

In just four full quarters in the field, the team has built meaningful momentum and delivered measurable impact. We couldn't be more proud. We are expanding access to diagnosis and enabling disease-modifying treatment while demonstrating clear leadership through our comprehensive support services and commercial execution. As a result, we are steadily establishing ourselves as a trusted partner of choice in the rare disease space. Now, I will turn the call back over to Neil.

Neil McFarlane (President and CEO)

Thanks, Josh. I'll briefly review a summary of our financial performance and encourage you to refer to our press release and SEC filings for more detailed information. As I mentioned, in the fourth quarter, we generated $34.1 million in total net revenue. This included $26.4 million from MIPLYFFA sales, $400,000 from OLPRUVA, $5.6 million in net reimbursements from our global EAP, $1.8 million from royalties and other reimbursements under the AZSTARYS license. Operating expenses for the fourth quarter was $23 million, which was a decrease of $1.5 million compared to the same quarter a year ago. R&D expense was $2.6 million for Q4 2025, which was a decrease of $5.8 million compared to the same quarter in 2024, primarily due to a decrease in personnel-related third-party costs.

SG&A expense was $20.4 million for Q4 2025, which was an increase of approximately $4.3 million compared to the same quarter in 2024, largely due to investments to support our launch activities. Net income for Q4 2025 was $12.2 million or $0.20 per basic and $0.19 per diluted share. For the same quarter in 2024, we reported a net loss of $35.7 million or $0.67 per share. Turning to the full year, our 2025 net revenue of $106.5 million included $87.4 million from MIPLYFFA sales, $800,000 from OLPRUVA, $13 million in net reimbursements from the global EAP and $5 million from royalties and other reimbursements under the AZSTARYS license. Operating expense for the full year 2025 was $90.4 million which was a decrease of $6.6 million compared to 2024.

R&D expense was $12.7 million, which was a decrease of $29.4 million compared to the prior year, primarily due to a decrease in personnel related costs, combined with a decrease in third-party costs. SG&A expense was $77.6 million, which was an increase of $22.7 million compared to the prior year, mainly due to an increase in third party costs related to MIPLYFFA, combined with an increase in personnel related costs, professional fees and other expenses associated with our commercial, medical and launch activities. Net income for the full year 2025 was $83.2 million or $1.40 per basic and $1.35 per diluted share, compared to a net loss of $105.5 million or $2.20 per basic and diluted share for 2024. As of 31 December 2025, total cash equivalents and investments were $238.9 million and total debt was approximately $61.9 million.

In closing, we have meaningful value inflection points squarely ahead of us. In the U.S., we're driving commercial execution to further unlock the NPC opportunity, as well as pursuing a patent term extension. In the EU, we have our MAA filing before the regulators with one of the most comprehensive NPC datasets, along with expanded access through our global EAP in markets beyond Europe. For our pipeline opportunity with celiprolol, we look forward to further engagement with the FDA regarding potential options to accelerate our development plan. The key takeaway is that strong execution, grounded in meaningful therapeutic benefit for patients, is translating into tangible bottom-line results.

We remain committed to prioritizing our investments towards high impact initiatives which gives us the flexibility to explore additional ways to create meaningful value for our shareholders and the rare disease community that we serve. As I mentioned earlier, today's Justin's first official day with the company. We're very pleased to have him joining us. Before we open the call for questions, I've asked him to share a few brief remarks. Justin.

Justin Renz (CFO)

Thanks, Neil. It's great to be officially starting at Zevra today. In a short time, I've already seen the depth of experience and the genuine dedication to bringing meaningful therapies to patients living with rare diseases. Over the coming weeks, I look forward to listening, learning and engaging with many of you while partnering with the team to support Zevra's continued execution and long-term value creation. With that, I'll turn it back to Neil.

Neil McFarlane (President and CEO)

Thank you. Justin. We're glad to have you on board. Operator, please open the line for questions.

Operator (participant)

At this time, if you wish to ask a question, please press star one on your telephone keypad. You may remove yourself from the queue by pressing star two. We'll take our first question from Kristen Kluska with Cantor. Your line is open.

Kristen Kluska (Equity Research Analyst)

Hi, good afternoon. Congrats on a great quarter. Justin, I'm looking forward to working with you. Welcome on board.

Justin Renz (CFO)

Thank you. Good afternoon.

Kristen Kluska (Equity Research Analyst)

2024, start form is certainly impressive. You tripled it from 3Q. Can you give us any more color or details around the split of how many of those or % were new diagnoses versus those getting identified patients on drug? Then how should we be thinking about the cadence moving forward? How does the pipeline look now? Are you still seeing people undergo the genetic testing diagnosis or looking more into the AI predictive targeting model?

Neil McFarlane (President and CEO)

That's great, Kristen. Thank you so much. Let me start off by saying that, you know, we've talked about this on a quarter-over-quarter basis. You're gonna see some variability. 52 enrollment forms in the full year is I think the number that we're really lined into. When we think about the total of 161 total enrollments since launch, it reinforces our confidence in the U.S. prevalence especially and I'll ask Joshua to talk a little bit about this, especially with the identification of newly diagnosed patients, which from Q2 to Q3 to Q4, we continue to see some growth there. Joshua?

Joshua Schafer (CCO)

Thanks, Kristen, for the question. As Neil mentioned, we've seen pretty meaningful growth in the newly diagnosed patients from Q1 all the way through Q4. That is really attributable to the strength of the clinical data of MIPLYFFA. Moreover, the real-world experience that HCPs are now having with their patients. It's also attributable to the efforts that we've put behind our disease awareness campaign, all driving greater diagnoses, as well as some of the collaborations that we have with genetic testing companies. As we mentioned in the remarks, we have recently expanded that collaboration and so we do expect that we'll see continued diagnosis in 2026.

Neil McFarlane (President and CEO)

Yeah. Kristen, just to add on that, you know, when we talk about the opportunity to have these efforts that Josh and the team are working through in identifying newly diagnosed patients or misdiagnosed patients, quite frankly. This is a reinforcement to us that the market opportunity is somewhere between these 300 and 350 patients that are currently diagnosed and the 900 patient prevalence. Getting these newly diagnosed patients early in the launch cycle versus a year or two years from now is really providing that confidence.

Kristen Kluska (Equity Research Analyst)

Got it. Thanks. Just, you know, now that you're collecting more quarter-over-quarter data, do you have like an average sense or a range of the time it's taking for an initial suspicion to be confirmed or not confirmed to a actual diagnosis?

Neil McFarlane (President and CEO)

That's a really difficult question for us to answer because, as you know, in the rare disease space, as you work with one patient and the myriad of symptoms that a patient may have may be very different from one to the other. We're continuing to lean in and double down on obviously educating physicians. Our, our new AI model that we're working on and the team is really starting to help us to get the education to the right places to ID new patients. Then, as we're thinking about the just, the disease state awareness and all the work that we're doing, it's a, it's a you know, trifecta of things that we're working on that are allowing us to be able to see this moving forward.

The one thing that I will say and that Josh has mentioned previously is that once we're identifying patients, we're able to utilize this depth of data that we have to really work with the physicians and the payers, to get patients on and then to get patients reimbursed.

Kristen Kluska (Equity Research Analyst)

Okay.

Joshua Schafer (CCO)

Kristen, I would. As we mentioned in our prepared remarks, with this new collaboration with GeneDx, the expectation is that from the time there's a test to results available, it's estimated that physicians would know those results within about three weeks.

Kristen Kluska (Equity Research Analyst)

Okay, thanks. Just a quick one, last one. For EMA, if I'm doing my math correctly, you should be submitting responses in the next couple weeks here. After that, you'd expect two months later to get the Day 180 questions. Is that what's next?

Neil McFarlane (President and CEO)

You're spot on in your math around the, our submission within the 90-day clock stop period. We're prepared. We will make that happen. The next one is the 150-day, not 180.

Kristen Kluska (Equity Research Analyst)

Okay. All right. Thanks, everyone.

Neil McFarlane (President and CEO)

Thank you.

Operator (participant)

Thank you. We'll move next to Jason Butler with Citizens. Your line is open.

Jason Butler (Managing Director)

Thanks for taking the questions. Let me add my congrats to Justin joining the team. Can you talk about persistency and are you at a point now where you have enough data to give some estimate of the proportion of patients that stay on therapy for a long period of time?

Joshua Schafer (CCO)

Hey, Jason. Thanks for that question. As you know, persistency is really defined by the number of patients who are on drug for an entire 12 months period of time and it's too early in our launch to be able to give meaningful data on persistency. I can tell you that we're very encouraged by the refill rates that we're seeing and the number of patients that are staying on therapy. Again, this really speaks to the durability of response that we're seeing both in our clinical data and the availability of new data that we're publishing to support that, as well as the real-world experience that clinicians are having with their patients.

Jason Butler (Managing Director)

Great. Can you talk about the initial experience ex-U.S. with the Uniphar collaboration and how should we think about that as a potential growth driver in 2026?

Neil McFarlane (President and CEO)

Yes. We're really pleased with the adding of Uniphar. As you know, we have multiple distributors that are helping us with our global. The opportunity for us to execute that agreement and at the end of the year and in Q4, actually ship and get product to patients in a very short period is exactly what we wanna do as an organization. That will continue. We've actually had additional orders in Q1 already and that will continue.

As I mentioned, in the prepared remarks, you're gonna see some variability in the ordering patterns and the new rate of enrollments as we continue to build on that, much like what we saw in our French EAP program, which continues to be approximately 30 patients, you know, up or down one or two on a quarter-over-quarter basis, it took a number of years to get to that steady state. We're really pleased with that and we expect that we're gonna continue to engage in broadening access for MIPLYFFA outside of Europe as well.

Jason Butler (Managing Director)

Okay, great. Just last question. You've talked a couple quarters now about the number of the encouraging number of new diagnosed patients that you're seeing. Do you have an updated sense of what the total addressable number of patients could be in the U.S. relative to the, you know, the 900 you've historically talked about? Thanks.

Neil McFarlane (President and CEO)

Yeah. You know, I have to say that in the early phases of launch, it's hard for you to say what your end state is but what I can tell you is that we're seeing and we saw it in Q2, a few new patients we saw in Q3 and then we saw even more in Q4. That's giving us a lot of confidence that the market opportunity of those patients who are diagnosed already, the 300-350, we can grow that somewhere between the 300 and 350 and the 900. It's because of this effort that Josh has been talking about on getting the reps to the place where they can be most successful, as well as all of the genetic testing and disease state awareness.

It seems like you see this sometimes in rare diseases, you don't really know what you have until you get a product in the market, then a rising tide starts to lift all boats. We're having more and more confidence on a quarter-over-quarter basis that the addressable market is somewhere between that $300 million and $350 million and $900 million.

Jason Butler (Managing Director)

Great. Thanks for taking the questions.

Operator (participant)

Thank you. We'll move next to Lachlan Hanbury-Brown with William Blair. Your line is open. Please go ahead. Lachlan Hanbury-Brown, you may wanna check your mute switch. Your line is open. We'll move next to Eddie Hickman with Guggenheim. Your line is open. Please go ahead.

Eddie Hickman (VP of Equity Research)

Hey, guys. Thanks for taking the question and congrats on the great quarter. I wanted to follow up on the EAP revenue, which was quite impressive this quarter. Can you clarify if this represents a new recurring quarterly runway that we should take into account or does it include any sort of one-time payments? How should we think about the growth of this revenue stream, going forward and beyond?

Neil McFarlane (President and CEO)

Yeah. Thanks, Eddie. This is part of why we really wanted to make sure that we put into the prepared remarks that these are initial shipments and again, this is named patient basis reimbursed sales. The shipments that are going out are for individual patients. We've identified a number of patients prior to signing the agreement and we continue to on a named patient, so one by one basis, actually get product into to market and to patients. This is the start and as I mentioned that was Q4. We have more that we've continued to ship into Q1. It's gonna take some time and there'll be variability on a quarter-over-quarter basis.

Our goal right now is to make sure that we're leaning in to those patients who have been identified to get them through the system on a one-by-one basis and actually, get product to those patients. Really impressed with what we've been able to do in getting the speed of product to patients so far.

Eddie Hickman (VP of Equity Research)

Understood. Yeah, appreciate that clarification. Have you said any more detail about like, are these in France only or are there other patients in other countries that you're starting to include in this EAP?

Neil McFarlane (President and CEO)

I don't provide guidance very often but this is one where we've had very consistent, you know, guidance. Our French EAP program has approximately 30 patients. It's ±1 on a quarter-over-quarter basis, that has generated approximately $10 million net revenue per year. Anything on top of that right now is coming from additional markets that we're able to service. What you're seeing on top of the quarter-over-quarter basis that we've said with the $10 million net a year, you know, $2.5 million or so a quarter is coming from the new territories.

Eddie Hickman (VP of Equity Research)

Got it. One thing and I apologize if I missed this earlier but how is the gross to net evolving in the U.S. and is there any variability in that price we should be taking into account now as the launch evolves further?

Neil McFarlane (President and CEO)

Yeah. Either our gross to net, as you know, has evolved through the year. We had a one-off in Q3, based on the Inflation Reduction Act. Moving forward, I think we can't really guide you to gross to net but we've taken that into account and nothing has changed in our contracting or our patient base so far moving forward, so in terms of the commercial and government payer mix. We feel like we're in, gonna have a quarter-over-quarter change and can't really tell you what that is today. It's too dynamic.

Eddie Hickman (VP of Equity Research)

Fair enough. Appreciate taking the questions and congrats again.

Neil McFarlane (President and CEO)

Thanks, Eddie.

Operator (participant)

Thank you. We'll move next now to Sumant Kulkarni with Canaccord. Your line is open.

Sumant Kulkarni (Senior Equity Research Analyst)

Good afternoon, nice to see all the progress and thanks for taking our questions. I have a few here. First on U.S. sales of MIPLYFFA, do you expect to see continued sequential growth on that, or could that be lumpy as well?

Joshua Schafer (CCO)

Yeah, I'll answer that one. We see variability in these, you know, with high-value therapeutics and low number of patients in the ultra-rare space. You know, 1 patient makes a difference on a quarter-over-quarter basis. We expect variability moving forward for the duration of the launch and the duration of supporting the patient base out there as we grow the market. Again, the addressable market, we're feeling a lot more confident between that 300, 350 and 900. That means there's variability in our future.

Sumant Kulkarni (Senior Equity Research Analyst)

Understood. What's the average age of patients on MIPLYFFA and what's the average age of newly diagnosed NPC patients? I'm asking because there could be the potential availability of Mandos' Adrabetadex for infantile onset NPC as soon as maybe this year. How prepared is the company for competition from that front?

Neil McFarlane (President and CEO)

I'll ask Josh to talk about some of the specifics but it's important to note that our patient mix remains very similar to what we saw in our expanded access program in the U.S. The 83 patients that we had when we closed the program was approximately 50% adults and 50% children. That mix has continued throughout our launch. In our 161 patients since launch, it's approximately 50-50 still. I'll reiterate what we've also said. We actually believe that our physician base, our patient base really wants to have as many options available to them that's out there.

I'll ask Josh to talk a little bit more about what we've seen in the market, what our market research says and we believe that it actually is helpful for all patients out there.

Joshua Schafer (CCO)

Just to reiterate what Neil said and was in our prepared remarks, about half of MIPLYFFA patient enrollments today are patients over the age of 18 or 18 and over. Again, very reflective of what we saw in our expanded access program in the U.S. In terms of new products coming into the market, we are very much aware of Adrabetadex, we welcome all new treatments for patients. We have been hearing from clinicians and seeing in practice that they are looking for multimodal treatments and being able to use as many treatments as they possibly can for these patients. We also hear from them that they view MIPLYFFA as really the foundational treatment and the preferred disease-modifying treatment for patients with NPC.

You know, we're continuing to execute on, as we can and continuing to bring new patients to MIPLYFFA.

Neil McFarlane (President and CEO)

My bottom line, it's a win-win for patients. It increases awareness. Physicians want as many as they can and we're supportive of continuing to rise the awareness of the NPC market.

Sumant Kulkarni (Senior Equity Research Analyst)

Got it. On arimoclomol pending EMA applications, you're on track to submit your 90-day response. Is it fair to assume that the agency has not asked for any new clinical data? On celiprolol, what could you do to accelerate that program given that if the product works really well, the time to event should actually go up?

Neil McFarlane (President and CEO)

Yeah. Let me start with the MAA question. As I mentioned in the prepared remarks, we submitted a robust data package. It's a standard review process where we got a 120-day list of questions and we have not seen any new questions that we were not fully prepared to respond to in that clock stop. We're gonna continue to engage and continue to move forward. Recall, what package we've put forth is the largest dataset of NPC patients ever treated. We're continuing to engage. I won't get into the specifics of what questions are coming or not. There's no surprises that we have seen in the questions that we've seen so far. You asked another question in regards to accelerating celiprolol. You know, we talked about this before.

I'm really pleased that we've been able to reinitiate the study. We have got 52 patients enrolled as of the year-end but I'd like to see more. Part of that we've always said our goal is to accelerate the development program. That 52 patients is great but we also wanted to engage the FDA in a Type C meeting to discuss our regulatory options. They were very responsive. We're going to engage further in the second half of this year as we continue to invest in boosted enrollment. In addition to that, look to ways to get the product to patients as soon as we possibly can.

Sumant Kulkarni (Senior Equity Research Analyst)

Thank you.

Operator (participant)

Thank you. We'll move next to Brandon Folkes with H.C. Wainwright. Your line is open.

Brandon Folkes (Managing Director)

Hi. Thanks for taking my questions. Congratulations on a very good quarter. Neil, maybe just first, you know, obviously there's a tremendous number of enrollments this quarter. If we look at the annual enrollments of 52 in 2025, how do we think about annual enrollment numbers going forward relative to 2025 as we balance, you know, an accelerating enrollment figure that we've actually seen quarterly recently, you know, some of these initiatives you've put in but also the natural launch trajectory here. You know, understanding this variability quarter to quarter, how do we think about the annual enrollments going forward?

Neil McFarlane (President and CEO)

Yeah. Let me Thank you for that question, by the way, because, you know, there have been a lot of questions in regards to what we see on a quarter-by-quarter basis. 52 patients in our first full year post-launch, we think is a really great number moving forward for us. Now, I'm not gonna guide you as to what we see in 2026 because as I mentioned, we've got a lot of diagnosed patients to continue to go after and make sure that we give MIPLYFFA as a potential opportunity for them.

The real, I think, confidence boost is that the efforts that we're making in the newly diagnosed patients or misdiagnosed patients that are becoming newly diagnosed NPC patients is giving us a lot of confidence on the long runway to be able to get that 303-350 patients and the 900 prevalent, getting it closer, you know, somewhere in there, in there. I'm not gonna tell you what that number is 'cause we don't know. It is removing the barriers that we've seen out there, specifically when it comes to diagnosing patients with our efforts around genetic testing as well.

Brandon Folkes (Managing Director)

Great. Maybe just one follow-up for me. Any way to contextualize what portion of diagnosed NPC patients in the U.S. you have engaged through your programs and maybe sort of how we should think about how quickly those patients could convert? Thank you.

Neil McFarlane (President and CEO)

Yeah. I'm gonna ask Josh to tackle that one. That's a tough one.

Joshua Schafer (CCO)

Yeah. That is a bit of a tough one. We've talked about that we believe that there are somewhere between 300-350 diagnosed patients and we have, at the end of the fourth quarter, 161 patients enrolled to receive MIPLYFFA. The majority of those patients are previously diagnosed patients with the, certainly the number of newly diagnosed patients increasing. You know, I think that puts us in a good position where we can comfortably say that we have somewhere between 40%-50% of the diagnosed patients currently enrolled to receive MIPLYFFA.

Operator (participant)

Thank you. We'll move next to Lachlan Hanbury-Brown with William Blair. Your line is open.

Lachlan Hanbury-Brown (Equity Research Analyst)

There you go. Thanks for the question and congrats on a strong quarter and apology if this was asked earlier. My line cut out for a while during the Q&A but on the 24 new patient starts in Q4, was there anything sort of new that you'd started late in Q3 in terms of the identification efforts that maybe contributed to that increase? Or is this just kind of a great example of the lumpiness of quarter-to-quarter new adds, where it sort of leads to you initiated in prior quarters coming to fruition in the same.

Neil McFarlane (President and CEO)

Yeah. Lachlan, thank you for the question and I'm glad that you were able to get on the call. You know, there's no single bullet here in regards to what we did in one quarter. I've mentioned this previously and this is a consistent effort that we've got to be able to continue to put forth to be able to identify earlier patients to get them diagnoses earlier and then support them through the process. I'll ask Josh to talk a little bit about some of the things that we've done but it is really a totality of effort here that is driving this type of performance.

Joshua Schafer (CCO)

Yeah. As Neil mentioned, I think it's certainly is a combination of multiple things. No single magic bullet here. Some of it is by virtue of a full year on the market and giving clinicians enough opportunity to gain some clinical experience. Also enough opportunity for us to build the disease awareness, both through our campaigns as well as our publication strategies. Some of it was our enhanced targeting and commercial execution, where we created a very bespoke AI-driven targeting model, where we looked at known NPC patients and identified their symptoms, understood their journey of clinicians with whom they, you know, got diagnosed and received some treatment.

We were able to find patients that looked like those patients in claims data and EMR data that had not yet been diagnosed to send our reps in a much more targeted way to clinicians' offices to help them identify these patients.

Neil McFarlane (President and CEO)

Josh talked about this a little bit in a previous question but, you know, the centers of excellence that we really focus on and then the community physicians, there is a back and forth that happens between those. That is, that is what we are working with in terms of the next generation of patients and continuing to drive. That breadth, though, of physicians who are prescribing and ultimately supporting patients is widening. As we think about the future, the breadth will continue as we get new patients. You know, this is an ultra-rare disease. A lot of times a physician may only see one NPC patient in their entire lives or entire careers. We wanna make sure that we continue to expand that breadth with all the tools that we're working with today.

Lachlan Hanbury-Brown (Equity Research Analyst)

Great. Thanks. Neil, maybe another question for you, just on a different topic but you've obviously got a very strong balance sheet and you are, you know, more or less sort of cash flow pretty close to cash flow break even, at least by the looks of things. How are you thinking about capital allocation, you know, in terms of you may be approaching that point where, as you said in the past, you've proven your ability to launch MIPLYFFA. Maybe you can start looking at, you know, if there are opportunities to add other things to the pipeline or the portfolio.

Neil McFarlane (President and CEO)

Yeah. We look at capital allocation on a quarterly basis. I think it's important for us to reiterate that we have the cash to operate independently of the capital markets with $238.9 million in cash at the end of the year. It's important for us because we need to execute on what's in front of us right now. We have a number of opportunities we're executing against. The U.S. market and the launch and continued investment into ensuring that we broaden access to as many patients as we can in the U.S. We're talking about geographic expansion right now when we think about Europe and the continued patients that are coming in to the EAP but also the MAA and beyond Europe as we're looking at that.

Then again, we're also investing in our pipeline in celiprolol. As we, you know, continue to invest and allocate our capital to the highest payoff activities that we can, we're well on our way to building a leading rare disease company. We do evaluate it on a quarterly basis.

Lachlan Hanbury-Brown (Equity Research Analyst)

Thanks.

Operator (participant)

Thank you. At this time, we've reached our allotted time for questions. I'll now turn the call back over to Neil MacFarlane for closing comments.

Neil McFarlane (President and CEO)

Thank you, Leo. I wanna appreciate the team here today for a yeoman's effort in the year, last year and the team that we have that's supporting MIPLYFFA and all of our development programs. We look forward to updating you on future calls. Thank you very much.

Operator (participant)

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.