Good afternoon, everyone. I'm Sumant Kulkarni, a Senior Biotechnology Analyst with Canaccord Genuity. It's my pleasure to have Zevra Therapeutics here today. Zevra is focused on rare diseases, and they really are changing what the company is all about, going all into rare disease. They have a couple of products on the market already, both of which target high unmet need indications. I think most of the investor focus is on the product called Miplyffa, or arimoclomol for Niemann-Pick type C. That's been out in the market for a few quarters already. With that, I'll turn it over to you. You have Neil, the CEO, LaDuane, CFO, and Josh, the Chief Commercial Officer. You guys can feel free to give a little bit of intro about yourselves, and then we'll head straight into Q&A.
Sure. Quick intros, and then I'll talk a little bit about the company.
Yeah, Josh Schafer, Chief Commercial Officer. I've been with Zevra for 2.5 years.
I'm R. LaDuane Clifton, the CFO. I've been with the company since 2015, so a little more than 10 years, pre-IPO, but we've come a long way since then.
Thanks. Neil McFarlane, CEO. I joined in October of 2023. Just to give you a quick little flavor around the company, we're a commercial stage biotech company. We have two ultra-rare disease products that are in the market today, one that is for certain urea cycle disorders and another that's for Niemann-Pick disease type C, both ultra-orphan indications. We also have a pipeline in a program that is being developed for another rare disease called vascular Ehlers-Danlos syndrome, a rare connective tissue disorder that is in phase III and enrolling patients now. An internally developed program called KP1077 has been developed for idiopathic hypersomnia. That program read out its phase II, and we're in the process of looking for strategic alternatives for that program.
Underlying all of that, we actually have royalties and milestones from another program that was developed that's in the ADHD space that we receive quarterly regulatory payments from. I think that's good for now. I'll have LaDuane talk about the balance sheet as we get through the conversation.
Cool. I thought you were going to read the whole forward-looking statement thing. We also have Nichol Ochsner in the audience. She heads up IR for the firm. I'll start with the topic of the day, I guess, which is Miplyffa. You reported earnings last night. We saw your patient enrollment. You had 129 patient enrollment forms so far. You added seven in the quarter. To be fair to you, you've never set any expectations on exactly what we should expect on the outside for patient enrollment. You said that this was in line with your expectations. How should we think about growth on patient enrollments going forward, which is somewhat like what I asked you last night, but I'd like to peel the layers of the onion a little bit more here.
Yeah, great question. Thank you for that. Just to shape the question a little bit, let me give a little bit of a background for those who may not be aware. In the United States , Niemann-Pick C has a prevalence of around 900 patients. The most recent data we have says that 300- 350 of those patients have been diagnosed. Through our, what I would call not meeting expectations, but exceeding expectations launch, we've actually enrolled in what we call a patient enrollment form, 129 patients. That's about 40% of the diagnosed patient population. At this stage of an ultra-rare disease launch, that's pretty impressive. When we think about seven patients going from 13 patients in Q1 to seven patients in Q2, we're a bit of a product of our own success.
The reality is that's still a 2% market share growth in seven patients in a market that is an ultra-rare disease space. The important components that we see in terms of our launch and how we're gauging success is absolutely bringing patients in the top of the funnel. 40% of the diagnosed patient population is exceptional at two full quarters of post-launch. The other component is how are we able to be able to pull those patients through. Josh can talk a little bit more about the outstanding effort of the team. How do you get those patient enrollment forms through the payer system, through the reimbursement system, and then into commercial revenue? What you saw was a 26% quarter-over-quarter growth in revenue from Q1 to Q2.
With that, maybe I'll ask Josh to talk a little bit about some of the outstanding work that the team's doing to pull patients through and bring them on the top of the funnel.
Yeah. As Neil mentioned, we had seven enrollments in the quarter, which is a reflection of our ability to find these patients who are either previously diagnosed, maybe not getting a treatment for NPC, or new patients who have never previously been diagnosed. This is through our efforts to raise awareness around the disease, as well as making available genetic testing so that more people can receive the benefit of Miplyffa as early as possible. Miplyffa is the only drug that's been able to show that it can halt the progression of disease through 12 months. More recently, we released some data from an open-label extension study that shows that it halts the progression of the disease up to five years. We're eager to find these patients, get them diagnosed as early as possible so that they can get on treatment and halt the progression of their disease.
Also, what Neil was talking about was trying to get patients into the top of the funnel, which is really sort of a measure of immediate demand. Then getting those patients who come through, getting them paid, helping them through their reimbursement challenges and overcoming any hurdles that they might have there, and then making sure that they continue to stay on drug. Our patient services team has done an exceptional job in getting those patients who come in, despite maybe an initial denial or some pushback from payers, we were able to get almost all of these patients covered and then, importantly, continue to receive drug month after month after month, which is reflected in the 26% quarter-over-quarter growth in net revenue.
Right. We know the prevalence of Niemann-Pick type C. We know the diagnosed patients. We know your patient enrollment forms, which is 129. Share is around 40%. Could you get a comment on any peak sales or share expectation that you might have and the timeline you might take to achieve that?
No, we don't. What we do have, in providing guidance and peak penetration at this point, is a comp. That comp is actually based on Europe. In Europe, there was a product filed and has been approved for well over a decade. Unlike in the U.S., where we have 900 patient prevalence, in Europe, there are 1,100 patient prevalence. Throughout that decade plus of having an approved product with a label, which happens to be miglustat, which is the product that our U.S. label has in combination with miglustat, is where you see the greatest value on treatment effect for Niemann-Pick C patients. The majority of those patients have been identified over a decade-plus time frame.
When we think about our ability to be able to get the U.S. market, which has not ever had a product approved for NPC, where we're the first product approved, the ability to be able to unlock that 300- 350 patients and get closer to the prevalence patients by the work that Josh talked about, all of our disease state awareness, the fact that these initial bolus of patients that were in our EAP, we're able to pull through in less than a year, which is, again, an impressive feat. Now those physicians and those centers of excellence, we've also mapped the local physicians who are taking the diagnosed patients out of the COEs, going back into the centers, to the local centers, and then driving those patients. We've done that as well.
The great opportunity for us, and I can't give you a number because we're two quarters into the launch of the product, is what we see as an opportunity to unlock that diagnosed patient population and get closer to the prevalent patient population in the U.S. over time. Hopefully, it won't be 10 years, but over time, that allows us a good comp.
Okay. You probably know this, but I'm going to ask you this question again in a different way. Of the 300- 350 patients that are approved, we know the off-label standard of care is miglustat in the U.S. What's your understanding of what the share of miglustat is, given miglustat's been approved in the U.S. for Gaucher for some time now?
Yeah, really tough question because you hit it on the money. You said that it's off-label. It's a very unique situation that we're in, where we have a product that we use in combination with Miplyffa that is actually off-label. It's utilized via multiple generics and also utilized in varying disease states. It's very hard for us to triangulate. What we know from the physician community that's taking care of patients, as well as the patient community, is that although miglustat can be challenging with the side effect profile that it has, the majority of patients are being tried, or at least experienced miglustat, after they get a diagnosis of Niemann-Pick C. Our impression through our own experience with our clinical trial was about 80%. We've seen other clinical trials that are between 80% and 90% of patients on miglustat.
We also have the European experience, which I think is the most mature experience we have. That's also fairly high.
Yep. In the U.S., 80%- 90% of diagnosed patients have been on miglustat at some point.
We believe that's right.
Right. Okay, because it's almost like you've got.
I'll just also add that of those diagnosed patients, many of them are on some other treatment for another underlying symptom related to NPC, whether that's epilepsy or seizures or any movement disorder treatment. We're able to find those patients. They've got a diagnosis of NPC, but might not be on an NPC-specifically indicated treatment at this point.
Right. Yeah, I was trying to see. It's like miglustat is almost on-label, given it's on your label now.
Unfortunately, that's not how the FDA sees it. We do promote the product to our label.
Right. You reported $21.5 million in sales of Miplyffa. We know that this is a rare disease product, an ultra-rare disease product. It's sold through specialty pharmacies. Is it fair to assume it's just-in-time kind of inventory management on that? I know you made some comments on shipping versus pull-through yesterday.
Yeah, that's right. We have a target level of inventory that we maintain, and we are careful to keep that pretty narrow. Our specialty pharmacy is doing a great job of getting it to patients when they present. We maintain that every quarter so that it doesn't really impact revenue.
On reimbursement trends, how satisfied are you with the trend as you see it now?
I'll ask Josh to comment, but maybe I'll give him a big kudos here. What we have seen is from the initial part of our launch in terms of reimbursement to where we are today, a faster time to reimbursement, which has to do with a lot of what Josh and the team have been doing. Probably more importantly than that, the ability for our data and the strength of our data and working with payers for them to be able to actually say, okay, you're halting the progression of the disease. That's what we've been asking for, and that's what we're willing to be able to pay for. Yeah, you want to go for it?
I would just.
Take the victory lap.
I won't do that yet. I would say that we're at 52% of covered lives, meaning of all the commercial and federally covered patients, we are on a formulary of 52% of those right now. That's exactly where we would expect to be at this point in launch. That number is going to increase as more commercial plans review the data and put Miplyffa in front of its P&T. We feel good about where we are in terms of covered lives. More importantly, as Neil was alluding to, we are able to get coverage for those patients through other medical exception pathways. We have had an extraordinarily high success rate in terms of getting patients paid or getting coverage for those patients and getting them paid and staying on drug.
Correct. What's your denominator for the covered lives calculation?
I'm sorry?
What's your denominator for the covered lives, 52% of?
52% of all covered lives, and I think that's roughly about 180 million U.S. lives. That's all the commercial plans, Medicaid, Medicare, and all the supplementals.
Right. How would that translate to the, like, how do patient enrollment forms translate to the number of paid patients that you have on the product as of now?
We don't report on that. I think the best, you know, again, if you look at 129 enrollments that are coming in, the best way to measure the paid rates is to look at the net sales and to be able to see that quarter-over-quarter, we went from 17 last quarter to $21.5 this quarter. That's sort of the calculus that needs to be done to be able to determine paid lives.
Right. If you look at patient enrollment forms for the next quarter or two, you can give numbers if you like. Qualitatively, what should we be thinking about the direction of those enrollment forms relative to the seven you had this quarter and the numbers you had in the prior quarters?
We're only two quarters into the launch, so I think it's really challenging for us to give any sense of trend or guidance at this point. What I can tell you is, having been out now for a little more than two quarters, we're seeing awareness of Miplyffa raise, particularly outside of those centers of excellence. We're seeing that more of the patients, they get maybe initially diagnosed in a center of excellence, then they go to a community neurologist or physician. The awareness within that community doctor or within the community is really raising. Again, too early to tell, but we are seeing some positive trends and more patients coming in who were previously undiagnosed, which I think is also a good harbinger that our tactics and initiatives are really starting to take traction.
Right. This is because we've got a lot of investor focus on enrollment forms. That's the reason why I'm asking you so many questions on this. The seven patients, right? Is that somewhat of a steady state growth-wise? Any kind of info you might give there would be really helpful growth rate-wise or steady state-wise.
I'm going to try this too.
Assuming we hit the 350?
I appreciate that. I think that it's an important question because our goal here is to be able to impact as many patients' lives as we can. There's also an expectation that we have that we're going to be able to maximize Miplyffa for every patient with NPC. The efforts that we're putting forth and the tactics and the resources that we're putting into this marketplace, from patient advocacy to we've been at every one of the meetings. We've brought our specialty pharmacy to the patient and caregiver meetings in North Carolina at the annual meeting to make sure that patients that are impacted have their pharmacy there to help them in the event that they need to. All of the tactics and efforts that we're doing are about impacting and maximizing the value of NPC.
What I can tell you, though, is at this time last year, we didn't have this number of patients and a 40% share of the market in our numbers for the next couple of years. You're rightfully asking the question around, is it going to be seven next quarter? What I can tell you is that we're making no lack of investment and effort. I talked about the sense of urgency that this team has in terms of its ability to go out and try to impact patients. Everything is being done to do that. We have a great model in the ability to not just, as Josh mentioned, go out and actually get patients who've never been diagnosed. We're offering genetic testing today. That genetic testing is identifying patients who've never been diagnosed before. Every time we impact the patient's lives, it's a big deal.
If it's seven, if it's more than that, if it's less than that, we're going to continue to drive to make sure that we can get closer to the 900 people living with NPC.
Got it. On that note, targeting the eventual 900, is there an initiative to get the FDA or to convince the FDA that your product could be used as a monotherapy?
No, there isn't. Actually, that's a really great question. We actually just published mechanism of action data talking about some of the early work we've done to be able to put that biologic plausibility from early-stage mechanism of action all the way to our clinical data that we've seen. Now we've been able to uncover long-term data, not uncover, we've been developing it for some time. What you see is a synergistic effect when you give Miplyffa and miglustat together, where you don't see it as monotherapy. I can't say that you don't see it, but we didn't have enough patients who were not on it in our trial to be able to see it. What you do see is a halting of progression of a devastating neurodegenerative disease. That is the hallmark of what patients and families and physicians have been asking for.
How do you stop or halt the progression of this disease? With that in mind, the label that we have allows us the greater, and now this is five-year data in our open-label extension. We will be publishing even longer data in our EAP data. The database was locked at the end of Q1. This now gives us this ability to go out and really drive. The biggest value we can make for patients is when you give it the way that the label is.
Right. In the U.S., how are you thinking about exclusivity, patent life, and life cycle management around the intellectual property associated with Miplyffa?
Yeah, today we have orphan drug exclusivity. The intellectual property in terms of patent term extension, we have filed. We're working through that with the office. I can't tell you what that is until we get that completed. In addition to that, last year, prior to our advisory committee, we did file additional intellectual property around combination therapy and other things that were important for us to protect. I think the team's done a wonderful job. That'll take time through the patent office a nd the speed at which they operate for us to understand. Once we know more, we'll be able to get back to you on that.
Okay. Got it. You mentioned the synergistic effect of using Miplyffa with miglustat. What does that mean for the philosophy that the EMA has around this product and its place as a treatment for Niemann-Pick?
Thank you for that question. I go back to the core. The core of the questions that we had from the first time with the CHMP conversations and the EMA conversations we had when the product was previously filed in Europe, those questions were very similar to the U.S.'s CRL. Not only have we been able to refile that two weeks ago, we filed our MAA application early, I might add. The guidance was in the second half of 2025. We filed it in the last week of July, about six months ahead of what most people were expecting. That came with this additional data that I just discussed. It came with our ability to have the OLE published in a peer-reviewed journal. It came with the mechanism of action data that I discussed a moment ago.
It also came with the pediatric data that we had been enrolling since our original application and trying to put the PIP together. That study is completed. We have not shared that data publicly, but that data was put in. The robustness of the package that we have in Europe now, we believe, will allow us to be able to overcome any previous hurdles, but actually also allow us to be able to have this combination and show to the European authorities, hey, if you're on miglustat alone, we know what that looks like. It's a two-point progression. One point's clinically meaningful. It's a difference between somebody being in a wheelchair and being able to walk. Two points is significant. We see this delta. We'll go into the health technology assessments and evaluations with Europe to be able to show the magnitude of impact that we'll have on patients.
OK. You do have data in hand that shows that patients on miglustat alone would progress at a faster rate or.
Yes.
Adding Miplyffa would help.
That's in our label in the U.S. today. It's about a two-point progression. That's exactly right.
Yes, that's going to augment the application relative to what you'd filed or what was filed in the past.
Previously, that's also with this duration. We have now five years of published OLE data. We submitted to the agency our EAP data in the U.S., where we captured data. That's upwards of seven years of data that we're looking forward to being able to publish soon. That was submitted to the EMA.
Got it. Europe is typically more price-sensitive than the U.S. Now that we have a list price in the U.S., how are you thinking about pricing of this product when it gets approved?
Really too early for us to talk about pricing. We need to talk about label and getting through the data before we do that. What I will say, though, is that we have been actively, and Josh and some of the other folks in the team have been actively refreshing our pricing quarter work based on the value proposition that we've been talking about in this spread of clinical meaningfulness at a country-by-country level to understand how would we do sequencing and how is the best way for us to optimize our go-to-market strategy. Today, with the filing and now knowing the strength of the data that we're bringing, it's an opportunity for us to really look if we're going to do it ourselves. We have been having a lot of capabilities presentations from regional partners, multinationals, local distributors.
We have an eye with 89 patients in our European EAP now. This time last year, we were about 70. 89 patients in our European EAP, we believe that we could do this similar type of rapid penetration in those markets where we can get early access and pricing that we'd be able to launch those markets as well. It is a little early, but we feel pretty confident that the strength of the data, the fact that we're continuing our EAP in Europe and it is growing in a small number of countries, gives us a foot ahead when we think about how to commercialize in Europe.
On that note, commercialization in Europe, do you plan to do it yourselves or are you looking for partners?
It's open right now, Sumant. We are exploring all alternatives. The goal here is for us to be able to make the best choice while we're under review.
Got it. I'll move then to Olpruva for urea cycle disorders. You've had that product now for some time. You've launched it because this is a true new launch effort on Olpruva. There are some dynamics there that are affecting the product. Could you go into that? How are you thinking about the product in the longer term, especially relative to the accounting concept of taking an impairment charge?
I'll ask. You can start, and then you can talk about the impairment charge.
Yeah. Olpruva is a treatment for certain urea cycle disorders. That is a very mature market. There are several other products in the marketplace now. To be quite honest, the enrollments in this quarter, we had one enrollment not living up to the expectations that we had. Nonetheless, we believe that Olpruva has a place in therapy. The market is quite satisfied with the market leader right now, which is Ravicti. There is an authorized generic to that product coming into the market any day now. We believe that is really an opportunity, as there will be a little bit of chaos and disruption in the marketplace.
It's an opportunity for us to continue to emphasize the clinical benefits that Olpruva has, but also to really continue to differentiate ourselves based off of the patient services and the capabilities that we have there, which are used for Miplyffa, but also for Olpruva. We believe that the combination of our product profile and our patient services are really going to help. As patients are being forced off of the market leader, we will be a viable alternative for them. We believe we would offer significant benefits to those patients.
Related to this quarter, we did recognize an impairment charge. Olpruva was one of the assets that came with our acquisition of ACER in 2023, and it gave rise to these assets on the balance sheet that have been amortizing. The accounting guidance is a bit more strict and probably does not take into account all the opportunities that we see, as Josh just mentioned. There were indications of impairment based on the prevailing enrollment trends and the entrance of an authorized generic that could impact that. The auditors look at that with a bit more skepticism. Through that analysis, it was determined we needed to take this impairment charge this quarter. We did that. We also recognized some inventory write-off.
At the same time, I think the original premise not only was that we were going to get an asset with Olpruva, but also that the infrastructure that came with that really allowed us to build out what we needed to support Miplyffa at the same time. Again, elements of value from that that are not really reflected in this accounting determination. We continue to believe in the product and believe that Josh's team and this plan of execution will take advantage of those opportunities that might be presented in this next chapter.
Got it. In the last minute or so, a couple of quick questions. Celiprolol for vascular Ehlers-Danlos syndrome, a lot of unmet need in that. At what point will you be able to give us a timeline on when we can expect top-line data on that phase III? LaDuane, a question for you. What's your latest cash runway?
Okay, I'll take the first one. That trial is a 150-patient trial. It's an event-driven trial. We have to get all enrollments, and then I can give you a time frame as to when we expect those events because that's going to be more statistically driven. I can pass that along to you. Two good things about this trial, I know that we're past time. One is that there's an interim analysis at 28 events. That allows us to be able to, and it's being run under a SPA. I might just say that. It allows us to be able to take an interim look. With that data, fillable if it hits what we need it to hit. If not, we go to 46 events. That'll be the ultimate outcome of the trial. As soon as we get all enrolled patients, timeline coming your way.
Our goal right now, as we mentioned on the call, all the activities, we're starting to see that ramp in the enrollment of call 3A1 positive patients. Our goal is to be able to see that continue in the next few quarters.
Got it.
During Q2, we sold our priority review voucher asset that we had also received with the approval of Miplyffa. Bringing that onto the balance sheet, that was $148 million in net proceeds. This brought our cash balance to $217 million. We just reported yesterday the June 30 balance was still at $217 million, meaning that our cash burn was neutral during the quarter. We can't really predict or project how that's going to go into the future. We've made good progress, and we have a solid balance sheet to execute against our priorities, supporting Miplyffa, supporting the MAA application, and then the celiprolol trial.
Got it. Thanks for that. Eager to see your patient enrollment next quarter.
Appreciate it. Thanks, Neil.