This is exciting because you reported earnings yesterday and everything's going really, really well.
Yeah.
Let's talk about MIPLYFFA. You just gave the update. A really solid quarter. Let me start it there and ask you to give a quick 30-second intro.
Yeah. Thank you, Jason, and thanks for having us. I will be making some forward-looking statements, so please take a look at the most recent SEC filings, which was yesterday, or on Monday rather. We have been through Zevra, as you know, we're a commercial-stage rare disease organization, focused on bringing life-changing products to patients that have no other options. As we think about how the year went last year, we launched MIPLYFFA the year before for Niemann-Pick disease type C. We've been moving that, and launch has gone really well. We'll talk a little bit more about that.
We also, in parallel though, have been looking at our geographic expansion opportunities by bringing the product and expanding access to MIPLYFFA/arimoclomol to outside of the United States and now also outside of Europe, which is an end of the year achievement that we kicked off. Then, on top of that, we've got Celiprolol. Celiprolol continues to enroll patients for vascular Ehlers-Danlos syndrome. I'm looking forward to talking to you a little bit more about the parallel track that we're doing, continuing to drive enrollment in the trial while also pursuing regulatory options to accelerate the clinical development.
You've had, you know, like you said now, more than a year of, like, commercial experience. I think you kind of maybe sometimes because the commercial story is going so well, we forget about the drug itself. Can we talk about, like, just the clinical profile, what, you know, the value that this brings to NPC patients?
Yeah. As we've been discussing, NPC is a lysosomal disorder that has a buildup of cholesterol in the cells, basically the transporter of cholesterol in and out of the cells. Get too much cholesterol in the cells and the cells die. Primarily, the neurological implications are when cells die in the brain. When they do, we have a symptomatology that's quite heterogeneous, from you know movement challenges at gait, fine motor skills, speech, swallow, and it's progressive. These patients most of the times move on to death. It also is unique in the fact that it starts off both as an infantile version because it's genetic, all the way through to adults. It can actually be.
Its symptomatology can be very different from an adult patient. Their first symptom could be a psychiatric break, to a child whose first symptoms could be just clumsiness before they continue to progress. Quite heterogeneous. Our organization has put together a lot of tools, and I'm looking forward to chatting with you about to try and make sure that we can bring this diagnostic odyssey a little bit earlier.
Right.
To be able to identify patients who may have and look like NPC patients earlier. Then also, how do we take care of the overall patient population that's diagnosed? Today, you know, the prevalence of NPC in the U.S. is about 900 patients, and about 300-350 of those patients have been diagnosed. Those diagnosed patients have an ICD-9 or ICD-10 code. We're actively working through education and making sure that as we've brought MIPLYFFA, which is the only disease-modifying therapy out there that's got a rapid onset within 12 weeks of therapy.
You've got now a robust set of data that brings the ability to halt the progression of the disease, not through 12 months, which is within our data package that we did through the FDA, but now all through four, five, six years, which with a very acceptable safety profile, I might add. So for us, we think bringing the only therapy to market that has the ability to modify the disease early and keep patients from progressing is really a benefit to the patients, the families, the caregivers, and the system.
When you're out there talking to healthcare providers, what are the key messages that you're really leaning in on for, you know, you have some experience of having patients on drug for over a year in the commercial setting longer if you think about the development timeline too?
Yeah. The opportunity to lean into the disease modification is really important. That differentiation is what, quite frankly, has allowed us to be so successful in our, you know, first full year of launch. And then in the back of the year, as we announced, you know, we had 24 enrollment forms in Q4, and our total revenue is $106.5 million. We broke that hundred million dollar threshold now. And we had 30% growth in quarter-over-quarter growth in revenue. Total revenue. It's starting to feel like we are executing at a higher level as we're driving up the performance level. This is also a rare disease.
With rare disease, you have variability in the diagnosis of new patients, which I'm looking forward to talking to you about because a lot of our tactics are starting to allow patients to be diagnosed earlier and earlier. Quite frankly, newly diagnosed patients, we saw it a little bit in Q2. We didn't talk much about it. In Q3, we started to see more and that's through our efforts in genetic testing efforts that we're doing. In Q3, we saw more, and in Q4, we saw even more. That's given us a lot of confidence that the addressable market is somewhere between that 300 and 350 diagnosed patients and the 900 prevalence. We're continuing to double- down on those efforts.
Let's talk about that a little bit more. The efforts you've said, like, you know, really now there's a treatment, you can go out and find the patients that didn't have a treatment before. The diagnosis rates, what are you actually doing to drive those diagnosis rates higher?
Yeah. It's not a single thing that we're doing. I think in the ultra-rare disease space, you've got sales reps that are out there leveraging their expertise in educating physicians and dieticians and geneticists and all of the stakeholders in the centers of excellence and now broadening out to the community centers as well. We've got patient services organization that is really driving also to be able to make sure that once a patient gets a prescription, it is white glove therapy. A white glove service, I should say, for everything that we do to be able to ensure that a patient can get seamlessly, and seamlessly is a tough word because it's not easy, but to get them on therapy.
We've got a medical group that continues to drive and analyze the data and get it published and making sure that we can get there. All of that is underpinned by the global disease state awareness work that we're doing. We've got campaigns that are out there that are driving the awareness of NPC. We've also got genetic testing that we're working with a number of parties, and yesterday announced also an additional effort that we're working with one of the parties we've been working on, GeneDx. We're gonna be able to leverage their footprint as well for patients who have an index of suspicion for NPC. They will also be going out and making available exome testing for those patients at our cost.
It'll allow them to be able to get diagnosed earlier.
I think there's two parts to this question. You mentioned 350 patients diagnosed today, prevalence rate of 900, but those numbers are going up. The data you have today, how confident do you feel that they're A, you can get a bigger portion of those 900 patients diagnosed, but also is there a potential that that 900 number goes up as well?
Yeah. Since launch, we've had 161 patients that have had a prescription enrollment form, and now that is encompassing some newly diagnosed patients, but the large majority of those have been the 300-350 patients that are out there. What's giving me and I think our organization a lot of confidence is the fact that we're starting, through our efforts, through the genetic testing, through the disease state awareness, getting newly diagnosed patients. That's what's gonna get you from 300 to 350 to 900. What I can't tell you is what is it closer to, 350, or is it closer to 900?
What I can tell you is that these newly diagnosed patients today, we would have expected through our efforts maybe a year or two years from now to start to build that. It's happening now, and we also have a comp. In Europe, 1,100 patient prevalence, a much more mature market. Miglustat was on the market for well over a decade identifying NPC patients, and the prevalence number is closer to or sorry, the diagnosed and treated number is closer to the prevalence number. We have a comp in Europe.
We have now the newly diagnosed patients who are coming on board earlier through our efforts and that are getting genetic testing and everything else, and we've got the execution of those diagnosed patients, and that's what a little bit of the trifecta is for us to give us real confidence that we're somewhere between 350 and 900.
Got it. Where are the newly diagnosed patients coming from? Are they, you know, is it through advocacy groups? Is it through centers of excellence? To what extent, you know, is this happening in the community setting too?
Yeah. That's a really good question. We're still trying to understand the journey of every patient that comes through. Much like what you've seen and what I've seen in my career in rare disease for decades now is you know one patient.
Mm-hmm.
Every patient's journey is different. The one thing that I think we have been seeing, though, is that if a physician, I should say, in a center of excellence who have seen, been educated, diagnosed, and gotten a patient on treatment and has experience with NPC, you're more likely to see and understand when a patient comes in that may have some of the early signs of clumsiness or speech impediment or ataxia or what have you. You're more likely to think NPC today than you were before and then get that patient tested. We wanna try and lower the barrier 'cause a lot of times it's really challenging for patients to get that testing that they need to get a really definitive confirmed answer. That's one of the things we're seeing.
The journey on every patient is different. There is no single thing I can tell you. What I can say, though, is that in our patient population, when we did our clinical trials, what we saw was primarily children in the randomized controlled trial. When we then went through our expanded access program, we started to see more adults that were coming in that were diagnosed and then on therapy. Of the 83 patients we had when we got approval, that were in our EAP, it was about 50/50, adults and children. Today, we're also seeing newly diagnosed adults in their 30s and 40s.
We're also seeing newly diagnosed children, but the mix of adults and children has remained 50/50 all the way now through the 161 total enrollment forms that we've gotten, which as a reminder is somewhere between 40%-50% market share in your first full year of launch. That I have not seen before in the launch of a product.
I asked the question on the earnings call, and you said it's too early, but talk to us to the extent you can about persistency and how when you get a drug on therapy how long they stay on therapy, because you have the expanded access experience. You have now patients that have been new to product commercially for over a year. To the extent you can give us some insights into persistency, that'd be great.
Yeah. The biggest bolus of patients we had, these EAP patients, many of them were on product for multiple years. What we saw was, primarily, patients only stopped taking therapy if they died.
Mm-hmm.
They progressed to a point where they no longer needed therapy. We're seeing very similar experience in the real world today. A small number of patients, and it's gonna happen, have passed away unfortunately. Our refill rates, which I can talk about, are very high. They're at the similar level to that of what we saw in our EAP. Persistency, as you know, it's measured on an annualized basis, so we have a bolus of patients, but it's really too early. What I can say, it's really high and mirrors what we saw in our EAP. We can continue to see that moving forward as we then get through 18 months, two years and then get a persistent number that we can say.
If it stays the way that it is right now, which is very high, we'll be able to announce a really good persistence number. Today it's just too early.
Yep, yep. You have the pivotal data on the label. You also started to generate real world experience as well. Just where do you think you are from an awareness perspective among prescribers, and what still needs to be done from a med affairs perspective?
I wanna answer that question in two ways. The first one is, you know, in the ultra-rare disease space, a lot of times you don't get a final diagnosis unless you hit one of these centers of excellence. There are about 40 of them in the United States. That community physician then, you know, will bring a patient to X, Y, and Z, a center of excellence, and then they'll coordinate that effort. You know, when we first launched, we had a high concentration of physicians who were writing for MIPLYFFA that were coming out of those centers of excellence, and then you kind of saw them go towards their community physicians.
Today, the breadth of physicians who are writing for the product, and most of them are writing for one patient because it is so ultra-rare, has really broadened. I think that they still have that connection back to the center of excellence. We're actually helpful in that making sure those connections continue to remain intact. It's the best way for patients to get coordinated care and I think have the best outcomes to keep that going. Our medical affairs group has really been working now for and not just medical affairs. I mean, the clinical group has been trying to make sure that we're continuing to dive into the data we have that and if you recall, we closed the database for our EAP in March of last year, so it's just one year since we've closed it.
We're still kinda getting that data out. We presented data at WORLDSymposium that showed the durability of a response over four years. A lot of times, as you know, when you launch a product, you launch a product with your package insert.
Yeah.
Whatever you did in your clinical trial, that's what you're out there working with payers and physicians and what have you. We have the luxury now of not just having a package insert, but having manuscripts and abstracts and a plethora of data for a long term that is really driving a lot of the success on the reimbursement side as well.
U.S. going really well. You mentioned it before actually, the European numbers are bigger, right? Can you just talk about the maturity of the market and plans to execute in Europe as well?
Yeah. I think the biggest success factor that we see in the future is the fact that we're actually continuing to grow our global EAP patients.
Right.
We're up to 113 patients that we announced on our call this week. That's primarily Europe, but we did add an EAP program outside of Europe as well. That's given us a lot of confidence because we don't have boots on the ground there. We're doing compassionate use and some pre-commercial revenue in France out of that program. I'll say that on a quarter-over-quarter basis, since our approval, we've been getting the pull from a small number of European countries and KOLs that are trying to get their patients on product. We are incredibly proud of the fact that we can service some of these patients. What we really wanna do now, though, is continue to broaden that access across Europe because it is more mature.
I mean, if you think about, you know, in Q3, we announced that we added approximately 92 patients in the European, primarily European group. That's like 10% of the diagnosed population in those markets, right?
Right.
We're penetrating the market without being there. It shows us that there's a real pull for the product.
I know I'm not getting a complete answer from the next question, but let me do it real simple. What is the go-to market strategy for Europe?
Well, let me try to answer it as completely as I can. The go-to market strategy for us has been making sure we understand the market needs, making sure we understand the market dynamics within each of the countries, where the patients are, where the providers are, what the level of education necessary is, what are the resources that we're gonna have to put in to understand how to unlock it, and then maximizing the access for patients. We've done a lot of that work over the number of years. As a matter of fact, we inherited a lot of that work when we acquired the product too, and have been able to refine that. We then took the opportunity, understanding what the market is, how do we think about the pricing opportunities. We've done a lot of the pricing research now.
Most of last year, we did a lot of effort in regards to understanding what the potential is. When we put those two together, the last bit of information we need is a label, and once we get and understand that label, then it'll allow us to be able to make a determination, is a go-to-market strategy best in our hands as we continue to add patients quarter- over- quarter- over- quarter in Europe, or is it best. Or can somebody come to the table and say, "We can do it better. Here's why, and here's why it's better for launching in Europe, and here's why it's better for your shareholders." That is what we're open to.
We don't have a prescribed approach today, but we're looking at the scenarios across the spectrum to be able to make the best decision once we get the label.
Let me expand that. How does that extend to other countries ex-U.S. as well?
Yeah. That is a very balancing act that we've been doing for some time. We'd like to be able to expand access to the product everywhere all at once, but with the uncertainties around the most-favored-nation pricing, with some of the uncertainties around the fact that we have a U.S. WAC price that we have to be able to continue to sustain to grow our business moving forward, we've been very careful to provide compassionate use where we can for those patients, you know, pre-commercial revenue in those expanded access countries, but then also looking at markets that have a patient population like the Uniphar agreement that we signed at the end of the year.
That was a lot of months or quarters of work to make sure there were patients that are there, that on a named patient could be then put into the system, and that we could put a distribution network in place that could get them the product fast. That's what we've done, and that was part of Q4's EAP numbers that you saw in terms of the U.S. WAC pricing, that we're able to get into to some of those markets, and that variability over time will you know smooth out in the next couple of years, and we'll see how many patients we can impact there. That is part of our strategy.
Yeah.
Taking a very disciplined approach to ensuring we can maximize access without impacting our ability to commercialize Europe, which is the next market for us.
This is a qualitative question. We have a good sense of the EAP in France specifically, but how impactful to 2026 revenue can the EAP be in the rest of, you know, out beyond France?
In terms of revenue?
Yes.
Um, uh-
Including Uniphar.
Yes. You know, our Uniphar agreement is in its early phases, and it's difficult to answer that question because it's for an individual patient goes through the system and then comes in. Is that individual patient getting an order because that specific payer is paying for a 12-month prescription, so you're doing a 12-month fill, or is it a quarter or a month? That is a type of variability that we're gonna see in every ex-European, ex-U.S., ex-U.K. market that we go into because the demand and the ability to get through it on a patient-by-patient level and how that works, it's just very challenging. If I had an answer for you, it would be wrong.
At this point, I think the best answer I can give you is that we're putting our foot on the gas, and the ability and speed for our distribution partners to get patients when they're identified through the system and then product to that patient, medicine to that patient, is what we've been focused on, and I've been really proud of what the Uniphar agreement has pulled for us.
Before we jump to Celiprolol, let me just ask the big picture question. You've done a great job with MIPLYFFA. You've built a company to focus on rare diseases. How do you think about the longer term vision, with what you have today with MIPLYFFA, what you have tomorrow with Celiprolol, but also, you know, from a both development stage, commercial stage asset, how do you think about building the organization?
Well, I think about and reflect on how we got to the success we've had when I think about what we're gonna do in the future, and that's been focus. We have focused on doing a few things really, really well, and that's been getting the approval of MIPLYFFA in the United States, executing on the commercialization. We're early. Four, five quarters in, we're early in the launch of MIPLYFFA, and a lot of room to grow, as you saw in our performance in Q4. We need to continue to focus on that in order to be able to have an opportunity to do something else. That being said, we're also now really leaning into our geographic expansion. That's next for us. How do we maximize MIPLYFFA?
There's a lot of opportunity there that's yet to be untapped that we're leaning into right now with focus. Lastly, we gotta work on our pipeline. Celiprolol has started to, you know, the investments we've made, it's started to really get the enrollment going, but at the same time, I know that this cannot go on for a long period of time without you know having an ethical issue. How long can you have somebody on a study that is placebo-controlled with a devastating disease? In parallel track now we're working on how do we accelerate that with the agency.
I think that's a lot for a company this size and what we're doing, but the focus on those three areas is really important for us to earn the right to go do something else. Today, I have to say, I'm super proud of what the team has been able to do. We're gonna find ways to be able to then leverage the infrastructure we have, but today, the infrastructure we have has gotta continue executing.
The last piece here is the cash piece, right? You're and I get it. We're not talking about guidance here, but you're not spending a lot of money, right, this year. How do you think about, you know, the cash that you have and what this allows you to go do to build those three pillars?
Yeah. Disciplined capital allocation and making sure we're reallocating things that are working and killing things that are not have been part of the secret sauce here, making sure we're investing in things that are driving the business. For us today, you know, we're in a growth mode. We have the cash to operate independent of the capital markets, right? To do everything I just talked about, from launching Europe, if we do it on our own or in partnership, to continuing to invest in our U.S. launch, to also then driving our Celiprolol program all the way through launch. We have the capital to be able to do that. As we think about growth mode and what we're doing, there's gonna be some ups and downs.
Mm-hmm.
We're investing heavily in our MAA right now. We're investing heavily in Celiprolol. We're also investing heavily in our launch. I would say that the fact that we can operate independent of the capital markets puts us in a good spot, but the opportunity to actually put that capital to work to then grow our organization over time, that's part of our strategic plan. Five years from now, I'm hopeful that we're not just talking about Celiprolol and MIPLYFFA.
Right. The Celiprolol, you spent a long time really looking at the asset, looking at the enrollment rate, and decided to really focus in. Where are you on that enrollment journey, and what gives you the confidence that you can get there with this trial?
Yeah. You know, with the prevalence of 7,500 patients in the U.S. and an awareness level that's pretty high amongst those patients, the lean in that we've been able to really drive on is how do we access patients who are willing to get into a placebo-controlled study that have some apathy? You know, they do, and we understand that because they're living with a disease that is explosive to say the least. I think that when we now lean into the potential to get a product approved that's got, you know, is a standard of care in a lot of European countries that we can bring to the United States and give patients an opportunity, it's when we put our foot on the gas.
All of the work we did around the market analysis, around where the patients are and the fact that patients really need a therapy 'cause nothing is available, we're leaning in. That is, quite frankly, all I can ask the team to do, continue to give it their best.
Great. Neil, really appreciate you being with us this morning. Congrats, and look forward to the rest of this 2026.
Thanks for having us.