All right, good afternoon, everyone. Welcome back to Guggenheim's 2025 SMID Cap Biotech Conference. My name is Eddie Hickman, and I'm one of the analysts here. This afternoon, I'm joined by Zevra Chief Commercial Officer Josh Schafer. Josh, thanks for joining us. Before we get started and jump into the Zevra story, can you maybe just, for those who aren't following us closely, maybe just give us a quick overview of Zevra and sort of some of the milestones in 2024 and what you're looking forward to in 2025?
Sure. Well, first of all, thanks for the invitation to come and talk about Zevra. Zevra is a commercial stage company that is really focused in rare diseases, specifically currently in rare pediatric diseases, UCD, urea cycle disorders, and Niemann-Pick type C. So we have recently just transitioned into becoming a commercial company. We have two products on the market, and we've built out a rare disease commercial team focusing in on 30 or 40 of the centers of excellence that are treating patients with urea cycle disorders and Niemann-Pick type C. In addition to that, we have a late-stage clinical pipeline. We have two programs in clinical development now. One is for idiopathic hypersomnia. That's called KP1077.
Idiopathic hypersomnia is a disease that is characterized not only by excessive daytime sleepiness, but also the inability to wake up in the morning, regardless of how many alarms a patient might set. That's called sleep inertia. KP1077 had some Phase 2 data that were presented last year that showed that there was a really positive trend towards the treatment of IH. We've also had an FDA meeting that has given us an end of Phase 2 meeting with the FDA that's given us clarity on our path forward with the Phase 3. We have another program called celiprolol, which is a Phase 3 program that is actively recruiting patients for another rare genetic disease called vascular Ehlers-Danlos syndrome, of which there are about 7,500 patients in the U.S.
This is a disease that's characterized by a genetic deficiency that results in a lack of elasticity in the vasculature and in hollow organs. These patients can have just abrupt ruptures of the arterial or hollow organs, and it can oftentimes be fatal if it goes untreated. That program, again, is actively recruiting and will be giving more updates along the way. Just a couple of other points. With the approval of Miplyffa, our program for NPC, we got that approved in September of last year, September 20th, as the first FDA-approved treatment for Niemann-Pick. We're really excited about being able to bring Miplyffa to patients in the U.S. With that as well came a priority review voucher, which we've announced that we're looking to monetize as well. Yeah.
Yeah, no, lots going on. And I know there's a big focus on the early Miplyffa launch. I want to spend some time on that first. And so you have an ongoing Expanded Access Program. Can you sort of remind us of how that came to be, how big it is, sort of how broad it is, and then sort of how far along you are in sort of converting those patients?
Sure. So the Expanded Access Program is in two geographies. We had one in the U.S. that had 83 patients at the time that we got approval. And then we have another 70 or 80 patients being treated outside of the U.S. in six European countries. And from that, we're actually generating revenue, about $2-$2.5 million per quarter. The U.S. program, we are no longer enrolling patients into that now that Miplyffa is approved. And as we noted in our last call, as of October 30th, so about a month after approval, we had enrolled 69 of those 83 patients into a commercial drug. The remaining 21 of those 90 enrollments were patients who had not yet been exposed to Miplyffa. So we're not in our EAP and so new to Miplyffa.
And so I think your core goal is getting those patients sort of transitioned over. What are the key payer discussions like? And what does a patient need to do and sort of what would be an inhibitor of that?
Yeah. So Miplyffa was approved and is indicated in combination with miglustat. And that's actually turned out to be a real benefit for patients because most of these patients are most of the diagnosed patients, of which there are about 300 diagnosed and treated patients in the U.S., the total prevalence of NPC is about 900 in the U.S. About 600 patients are living with the disease, but don't yet know it. They haven't been diagnosed or their symptoms have not yet gotten severe enough for that to be known. The other 300 patients are receiving some sort of treatment. And the standard of care has been miglustat, which is an off-label drug that was approved for Gaucher, but most of its use now is in Niemann-Pick. So about 80% of those patients are on miglustat.
Our indication in combination with miglustat showed that patients have really benefited from this combination. Miplyffa was approved based on something called a Niemann-Pick Severity Score, and that measures a bunch of neurological symptoms. It's a composite of four or five different domains, and we demonstrated that we had a 2.1-point improvement on that scale. And to put that in context, a one-point improvement is the difference between a patient needing a wheelchair and being able to walk on her own or being able to feed herself versus needing a caretaker to feed her. And we had a 2.1-point improvement. In addition to that, we showed that we delayed the progression of disease through 12 months of treatment, and we had some patients who were continuing to receive drug for two years and some up to five years.
So with all that in mind, the only restrictions that we've seen so far are those that are on the label. There is an age cutoff. They have to be two years or older, and they have to have a diagnosis of NPC.
Do you expect patients that are currently not on miglustat to, are there reasons why they're not on miglustat because it's not approved? And do you think the use of miglustat could go beyond the sort of 80% that you sort of have predicted in your studies? Is there a reason why those 20% can't be on miglustat for some reason?
No, I think the biggest reason is that there are some tolerability issues with miglustat, but I think that can be managed by a physician. So we really don't see any restrictions to patients being able to get miglustat. And perhaps now that there's a combination of miglustat plus Miplyffa, you'd see an increased use of miglustat, but that's just speculation.
Got it. But you don't, oh, go ahead.
No, I was just going to say, but what our data showed and what we're seeing in the marketplace now is that the combination of miglustat plus Miplyffa is really becoming the cornerstone of treatment for these patients, and then as they progress, as symptoms present themselves, then other options might be added to that combination.
Got it. So this is a weight-based drug. So how should we think about the sort of net price evolution as you transition those patients and then start to sort of target de novo patients in terms of where we are now to where we could be at the end of next year into 2026?
Yeah, so it is a weight-based dosing, and the price is $9.50 per milligram, and if you look at the composition of our Expanded Access Program, which I think is really reflective of the general population, these patients skewed towards the higher doses and the higher weights, which gave us an average monthly price of about $85,000 as a wholesale acquisition cost.
You expect that to be sort of the steady state going forward given the representation that that was?
We do. In the early weeks of launch, we haven't seen anything to suggest otherwise.
Gotcha. So when we're thinking about the transition, I guess we'll get an update in the next month or so from you guys officially on the revenue. But you started, I think you were available at the end of November. The drug was available in the channel. So can you talk about what the fourth quarter might look like in terms of who are those sort of early adopters and sort of how are you booking that revenue and what should we expect to see in those early days of the drug being available?
Yeah, so again, we gave numbers as of cutoff of October 31st, which was four or five weeks after approval. The drug had not yet been in the channel. What we announced at approval was that it would be eight-12 weeks until we had drug into the channel. And we were able to do that on the lower end of that. We did that within eight weeks, so as of November 20th, I believe, we had drug in the channel and we began shipping at that point. As a reminder, we book revenue when our specialty pharmacy receives drug. And because of that, we didn't book revenue until November 20th they began to receive drug. We then immediately started shipping. Given it wasn't a full quarter, but we did have probably some patients who got refills in that fourth quarter.
We'll be reporting all of those numbers in terms of enrollments and that revenue in our fourth quarter call.
So how will we sort of dissect how much of that is sort of stocking and preparation for Q1 and how much of sort of the use of patients on drug?
This is really almost an on-demand type of ordering. It doesn't take very long to go from our warehouse or from our wholesaler to our specialty pharmacy. There is very little stocking.
Okay, so we should expect that the revenue in Q4 is patients that were taking the drug in Q4, not in preparation for.
For the most part.
Gotcha.
For the most part, yeah.
I know we talked about this a little bit, but there is another drug that was also recently approved for NPC, and I want to sort of see how that is interrupting the payer discussions, and does there appear to be a preference in terms of how some of these payers or even physicians are thinking about using this now sort of three combination of drugs?
Yeah. So you're absolutely right. There was another product that was approved just a few short days after Miplyffa. It's important to note that the two had very different clinical profiles. Our product was approved based on 12 months of clinical data, and it was approved based on what is considered the standard clinical endpoint of the Niemann-Pick Severity Score, as opposed to Aqneursa, which was approved based on a functional SARA score, which really measures a symptom of ataxia. We see the two drugs not necessarily as competitive, but as complementary in the treatment for these patients. Again, miglustat and Miplyffa are going to be the foundation or the cornerstone of therapy to prevent the progression of disease. As patients present with other symptoms, then we believe that other treatments would be added to treat those symptoms.
It's early days yet in terms of our payer conversations, but we've not really seen any major reasons to think otherwise.
Gotcha. Now, assuming you can, I mean, you've guided that you can close the EAP maybe in the first half of this year. So where do you go after that? I mean, you have these patients, you have some new patients that even entered the EAP after the trial is over, but I know you stopped that. And then you have patients that were never on the EAP that now have been on drug. And then you have these other 600 patients that don't even know they have the disease. So how do you think about stepping through those patients and how do you prioritize your sales force to make sure you're able to do that?
Sure. So again, just to kind of paint the full prevalence picture, 900 prevalent patients, 600 of whom are undiagnosed but living with the disease, roughly 300 who have been diagnosed and receiving some treatment, a subset of about 83 who are on our Expanded Access Program. So our initial efforts were to convert as many of those patients on the Expanded Access Program as possible who are already receiving Miplyffa so that they can continue the continuity of their care. And that effort has continued. And since the October 31st cutoff, we've continued to enroll more and more of those EAP patients. Then within the remainder of those 300, and we've also seen many patients who were undiagnosed as of October, that cutoff, we had 21 who were diagnosed but not previously received Miplyffa. And those patients are continuing to be enrolled as well.
We have a number of various promotional and medical activities going on now to help identify new patients who have not been previously diagnosed.
What about, how should we think about when we model this discontinuation rates? I know these are severe patients sometimes, and there's other comorbidities that have other, but how should we think about these EAP patients that have been on drug for a while? Should we expect them to continue to be on drug, or is there some discontinuation rate that we should model in thinking about a steady state level of dropping?
Yeah. I mean, a couple of things to point out. One is that unfortunately, this is a chronic and fatal disease. And so patients typically will stay on drug until expiration. And we saw that in our EAP program. Very few patients discontinued for any other reason than passing away. We would expect that to continue. I'm sure once we get into the larger patient population, there may be some discontinuation rates, but it's too early for us to be able to see that.
To that end , can you remind us about the tolerability profile a little bit? And were there major concerns in the clinical studies that docs sort of need to pay attention to when patients are going on drug?
No. In fact, Miplyffa is very well tolerated, and I think that speaks to the number of patients from our open label and Expanded Access Program that were able to remain on drug for two years and some as long as five years.
So I want to move quick in the last few minutes here to a couple of other programs, including Europe. So I know sort of when Orphazyme controlled this drug, I think they had a filing that they pulled. So I'm sort of curious what the status is of your conversations in Europe and are there other studies you need to run? Are there other sort of considerations, or is this just sort of a waiting game for approval in Europe?
Yeah. So, as soon as we got approval in the U.S., we announced that we were going to move as quickly as we could towards a filing of an MAA in Europe. And those discussions and activities are underway. We're working to really understand what that filing will look like and what might be required to submit that filing. And we'll have more data on that in terms of timing specifically for that in coming earnings calls. But getting Miplyffa as widely available to patients is a priority for Zevra.
And I think miglustat is approved for NPC in Europe, if I'm not mistaken. So how does that change the commercial dynamic there and being a sort of more mature market?
Yeah. Again, I think the fact that it is approved in Europe really helps the combination of miglustat and Miplyffa and being able to ease some of the barriers that might exist in terms of getting miglustat paid for with Miplyffa in most of those countries. The pricing is variable by region or by country. But Europe is actually a really good analog for the U.S. in that there is an approved treatment with miglustat. There's roughly about the same number of patients in terms of prevalence in Europe, but the diagnosis rate is significantly higher. And we believe that's because there is greater disease awareness and there is an available and approved treatment for NPC. So we're using that as an analog to kind of demonstrate how we can grow the market here and increase the diagnosis rate for patients in the US.
Do you expect to have to run any other studies, or do you expect to have any concerns about pricing or safety? I'm just sort of wondering if there are hurdles that you have to sort of.
It's too early to know, and certainly we'll be talking about that in a few earnings calls.
Got it. I want to actually jump back to the U.S. again. What other types of sort of guidance do you plan to provide at the earnings call and then throughout the year? I know you gave some guidance on the conversion rates, but I'm sort of wondering what other metrics you're going to provide throughout the launch.
Yeah. What we've stated is that for both of our products, we will give enrollments. We'll give an update on market access or how many covered lives we have. It's probably a little too early to talk about that for Miplyffa, but we'll give some indication of that, and then net sales, so those are the three metrics that we'll use for our commercial products.
Moving to Olpruva, you have a joint sales force there. So can you maybe just talk about that drug's been approved for a bit and we're not seeing much revenue come in yet? So what have been the struggles to sort of getting that launch ramped up?
Yeah. And by joint sales force, just to clarify that, we have one sales force that's able to promote both products because the call point is very similar. Although the diseases are very distinct, those that diagnose and treat urea cycle disorders and Niemann-Pick, there's a high degree of overlap. So our sales force is able to target and reach those prescribers with one small team. The UCD market is very different than the NPC market in that it's relatively well established. All of the products that are available are some sort of analog of sodium phenylbutyrate. And what we've realized is that many of these patients will receive an authorization for their prescription for 12 months. And they need to have a reason to come in and switch. And there's been some inertia to switch within the marketplace.
That catalyst for switching is now in place where we've really repositioned Olpruva to resonate with a certain segment of the UCD patient population, particularly those that are more active, that are transitioning into adulthood and independence, and looking for something that is more palatable, easier to carry, so more portable and personalized dose so they don't have to deal with titration. The other catalyst is that we're seeing that a number of payers are now putting a lot of pressure on the branded product and are forcing patients to look for less expensive alternatives. And we weren't seeing that in the middle of the year because you have these 12-month authorizations. But as patients are now coming up on their benefits renewal and beginning the start of the calendar year, we're starting to see more and more patients looking for alternatives.
I expect we'll get an update on that as well.
Absolutely.
On Ehlers-Danlos, you have a Phase 3 ongoing. Is there anything you can tell us about the timelines of how long that study is expected to take and when we might see some results from that?
Again, we will be giving some more updates during the earnings call, but we're continuing to recruit. This is an event-driven trial, so the timelines are somewhat out of our control. We are optimistic that we're starting to see recruitment increase, and we're putting a lot of energy and resources behind trying to increase those recruitment rates.
Then on the financing side, you mentioned the PRV. What is the timeline for when you might decide to monetize that? And is there sort of a catalyst for something that you would want to spend it on, basically?
Yeah. So in terms of timing, we're in a fortunate position that we don't need to monetize that. We ended Q3 with $95 million on the balance sheet, and that gives us a cash runway into 2027. And that did not include any proceeds from the PRV. So we're in a fortunate position that we don't have any sense of urgency to sell it. Having said that, we have announced that we are looking to monetize it. The most recent PRVs that have sold have all been in the $150 million range, which is a significant increase from just a few short months ago where it was around $100 million. And we would look to use those proceeds to continue to execute against our strategic plan, which is commercial execution, advancing our pipeline, and that's it.
For advancing your pipeline, is there any way you want to prioritize some of those? You mentioned several pipeline products that you're excited about. How should we think about your priorities in terms of spend for UCD, Ehlers-Danlos, idiopathic hypersomnia, and which one?
Yeah. Well, part of our strategic plan, we evaluated our pipeline, and we came to the conclusion that while KP1077 for idiopathic hypersomnia is, we think, potential to confer a lot of benefit for patients with IH, it doesn't really fit our strategic vision in terms of the resources required to commercialize it. It requires a significantly larger sales force, and we announced that we're looking for some strategic alternatives there. So our priorities are really around the commercial execution, being able to make sure that we have the best launch for Miplyffa both here in the U.S. and outside of the U.S., making sure that we continue to commercialize Olpruva and to advance celiprolol.
Great. Anything else I missed?
No.
Awesome. Thank you for being here. We'll look forward to some more launch updates coming up next month, maybe.
Yeah. Thank you. Thanks again for the opportunity.
Thanks for being here.