Zevra Therapeutics, Inc. (ZVRA) September 2026 Conference Transcript

All right. Great. Thank you all for coming to the Morgan Stanley Healthcare Conference. My name is Rok Byun. I'm the head of West Coast Healthcare Investment Banking at Morgan Stanley. I have the pleasure of hosting the management team from Zebra. I know it's been a long day for you. Hopefully, we'll get through this efficiently, but also be able to have an opportunity to explain your story to the folks here today and those listening in. So maybe before we get started, Neil, your mission is to redefine what's possible for people with rare diseases. What does that mean to you and your team?

First of all, thank you for having us. We've had a great day today. We really appreciate the support of Moving Family. I will be making forward-looking statements, so I'd ask for everybody to take a look at our most recent SEC filings to ensure that you get the most up-to-date information. On behalf of Justin and the rest of the team, I really appreciate answering this question because what we do in the rare disease world is clearly a challenging part of pharmaceutical development and bringing medicines to people who otherwise have no other opportunity to get medicines. Now, rare disease is not as unique as it once was 20 or 30 years ago, but what we do hasn't changed much. We're trying to develop medicines and redefine how we get them to patients to then impact their lives. For us, we're doing that in a commercial sense today, primarily with commercial programs and Neiman-Pick disease type C, ultra-orphan along with UCD. But in addition to that, we're also expanding globally to patients outside of the United States, and we have a phase three program also going in vascular Isler's Danlos Syndrome. So for us, it's ultra-orphan diseases. We're talking about prevalence rates of less than 1,000 for some of them and less than 7,500 for others. But I'm looking forward to getting into that more with you as we move forward. But it's a real privilege for us to be able to be working in the rare disease space and thinking differently about how we impact the lives of patients living with rare diseases.

Great. Thank you for that. Now, how would you describe Zebra to an investor hearing the story for the first time?

Yeah, we've taken a little bit of a different tact. We are a commercial stage organization that has been a commercial stage organization for just a few years. Today we have a U.S. opportunity in my play fund in the Neiman-Pick disease type C space, about 900 patient prevalent population in the U.S., about 300 to 350 of those patients. This is a commercial opportunity for us. We've been now at it for about six quarters in terms of the launch. We'll get into some more of this detail later on. But in addition to that, that's one leg on the stool. The other leg on the stool for us is our global expansion. We're trying to be able to get my Plypha into, and our Moklomol, I should say, into the Europe through an MAA process that we're talking about a little bit more as well. And we're globally expanding into regions and territories where we can leverage the European, I'm sorry, our U.S. label into other markets. And then we have our third leg on the stool, which is our pipeline, our phase three development program for vascular islers-Danlos syndrome, which is enrolled about 66 patients out of 150 today. And we'll talk a little bit more about that later on. But that is in a place for us today that we can really go to the agency and start to have some conversations around how do we accelerate the development. So Zevra today is three legs on a stool. It's a U.S. opportunity that has a lot of untapped potential. It's a global expansion opportunity, and our second leg on the stool, and thirdly, it's around salipolol in the pipeline.

Great. So maybe we'll start with Neiman-Pick type C. Now, you are the first and only FDA-approved treatment, and you've been, you know, you said, in the market for about six quarters. Where are you in that journey today, and frankly, what are you most excited about to go from here?

Yeah, most excited about the learnings we're having. As I mentioned, 900 patient prevalence in the U.S. About 300 to 350 of those patients were diagnosed. And now the opportunity for us six quarters in, at the end of Q2, we had 184 prescription enrollment forms so far. That is an amazing impact that our team has been able to drive so far. With only 350 patients, getting 184 of those in six quarters is pretty good. Now, that's primarily those patients. We also are even more excited today than we were a year ago because we've been learning. We've been learning, number one, that it's not only a pediatric disease anymore. About 50% of our patients are adult patients. That learning is now informing how we try to get newly diagnosed patients into the mix. So I'll give you an example. We have had patients that have been misdiagnosed with multiple sclerosis, adult patients that then, you know, have progressed with other symptoms that are more attuned to Neiman-Pick disease type C, get them genetic tested, and then they've eventually gotten on the product based on the fact that they had NPC, not MS. We've had a Wilson's disease patient that has been, you know, recently published, actually about a quarter or two ago, that was misdiagnosed. So with this, we're learning. And in any rare disease, the more you learn about the journey of patients that are getting them to the ultimate diagnosis and then on treatment, is it better off that we can then tailor our patient-finding programs to being able to then get more newly diagnosed patients? If I look back at the last six quarters, a year ago today, I would not have told you that 50% of our patients would be adult patients. They used to coin Neiman-Pick disease type C as childhood Alzheimer's. And today we're understanding more, we're learning more, and now those newly diagnosed patients are giving us a lot more confidence that the market is somewhere between that 350 currently diagnosed patients and the newly diagnosed patients, that quarter over quarter, we're seeing more of those now that we're learning. So that's been probably the biggest surprise for us, that there is real growth, very similar, real opportunity for growth beyond the 350. And that's very similar to Europe. In Europe today, there are about 1,100 patient prevalence, and the majority of those patients have been diagnosed. and on some type of therapy. And the reason for that is Miglastat was originally approved well over a decade ago. A previous company went out and invested in disease state awareness and diagnostic modalities in publishing the Suspicion Index. And that market has been more mature over the last decade of identifying and diagnosing patients closer to the 1,100 patient population in Europe. So we have a lot of confidence that if we can continue to invest in disease state awareness, continue to get diagnosis earlier, that we, too, will be able to continue to build newly diagnosed patients to get closer to 900 and 350.

Yeah, and I think, as you said, you know, as you're kind of uncovering new adult patients, at the way, you know, people think about the overall, you know, patient, number of patients that are out there. It's probably only going to grow and, you know, you will hopefully find more patients that really need your therapy. So maybe shifting a little bit in terms of your launch. You're now generating about $30 million a quarter, only just, you know, less than two years in the launch. What is driving that momentum, and how's your patient-finding approach reaching newly diagnosed patients, including roughly half who turn out to be adults, as you said? And maybe I'll just add for the audience, recently a colleague of mine reached out to me to be referred to you all as their son is suffering from NPCs. So I think really speaks volumes in terms of your ability to continue to execute and find new patients. But yeah, just walk me through the momentum that you've had with your launch process.

Yeah. Thank you for talking about that personal journey. This is what makes it really special what we do, the opportunity to impact the lives of people suffering from NPC. But it's also important to have something that we can offer them, and that's been one of the drivers of success. We have recently been able to get published our open label extension study in addition to our clinical trial data that showed about the halting of the progression of the disease through 12 months based on the Niemann-Pick C severity scale with our data in combination with Miglestat. Now we've been able to also get the published data from our open label extension study going out four years that supports that trajectory, along with our expanded access program now that's also out four years with some pediatric data, part of our pediatric investigational plan that's out there, too, in the literature. We package all of that together with now that we've got newly approved therapies, the clinicians have now published consensus guidelines. And they've updated that based on the fact that there's now a product that's approved and multiple products that have come to market here recently. So these clinical guidelines have been able to reinforce the need to treat early, to diagnose with genetic testing, so you hopefully don't have misdiagnosis, and then to treat with combination therapies, which is what we have in our label, and disease-modifying therapy. So all of this longitudinal data helps to be able to get patients onto therapy and then have that therapy paid for by payers because you're able to provide convincing evidence of efficacy. On top of that, you know, we're able to now work with physicians who may have never seen NPC before or understand what it looks like. we can get them engaged with other experts that are in there, but we can also provide, you know, reference to clinical guidelines that show disease-modifying therapy, use-combination therapy, and my Plyphine combination with Miglostat has a benefit for you, has a potential benefit for those patients. And a great safety profile, I should add.

Yeah, and I think you're really changing the kind of your position as a potential foundational therapy. But maybe just on that note, as you said, MPC historically had no approved options. Now, as you mentioned, starting to see some new entrants. Now, as the first FDA-approved therapy and with treatment guidelines being starting to be updated to support combination use, how do you fit into that evolving landscape? What kind of work that you're doing? How are you, you know, what is your kind of approach to physician education?

Yeah, we want to continue to learn. And every day that we have the opportunity to identify the journey of a new patient, because one thing is for real, and I have been in this industry for a while in the ultra-rare space and multiple different companies, you know one patient, you know one patient. Every patient's journey to getting to the ultimate diagnosis of a rare disease and then a treatment, if there is one available, is unique. And for us, you know, having the mentality that we can continue to learn from what we're seeing in the marketplace for every patient and try to understand from the physicians, even the payers, by the way, and the rest of the community how best to be able to take that learning, move their diagnosis journey earlier to then allow them to be genetic tested earlier and then get them on therapy earlier, that allows for us today, based on our therapy, to be able to halt the progression of the disease and have a better outcome for patients. So, you know, if I think about, you know, the other products that are being developed and the rising tide that is kind of lifting all boats around disease state awareness expert connect programs that we have to get people who are not understanding of what NPC is and get them connected with somebody who's an expert. And that expert, by the way, might only have two patients. It's not like a lot of physicians have ever heard or seen of NPC. So that rising tide, getting these case reports out, having the ability to tell the story about each and every patient's journey, then get somebody else to think NPC. And that's what we're trying to do.

Got it. Thank you. And so on that note, you mentioned it is a progressive disease where staying on therapy matters enormously. Now, once patients start MIPLIFA, what are your strategies for keeping them on therapy long-term?

Yeah, we have a fairly robust patient services group that helps through our specialty pharmacy and through our own efforts. It really helps to be able to decrease the burden of getting their shipments, decrease, you know, we call it white glove, you know, service. But the reality is that it's almost a cost of doing business for ultra-rare disease patients. They have a challenging time getting multiple therapies for their disease, you know, for Neiman-Pick disease, type C specifically, but for all rare diseases. It's not like it's just you're just on one product. They're all specialty products. So we have a patient services group that really tries to handhold and support through reimbursement support, through monthly shipments, through, you know, contact directly with the families to be able to get the shipment to their homes at the time that they're going to be there that they can receive the shipment and actually sign for the shipment and get it there. Because this happens every month. And we're learning there, too, by the way. There's certain things that we did really well that we're doubling down on, certain things we weren't doing so well. So the surveys that we get back from patients and families, we can then actually improve the quality of the service that we provide to those patients and caregivers.

Got it. Thank you.

There's one additional thing that I think is important. We don't publicly talk about the persistence rates or the compliance rates, but I think we're asked that question on a regular basis in these meetings. And when you're talking about one number difference of a patient that's persistent month over month versus one that might discontinue, it can skew your numbers because it's hard to be able to provide that. But what I can say is that we saw very high levels of persistency in our expanded access program, and we saw very low levels of discontinuation rates. And primarily, these are patients who their disease progressed and unfortunately passed away from their disease. We're seeing very similar types of high persistency, high refill rates, and low discontinuation rates that we saw then. And, you know, as we continue our launch and, you know, this trajectory that we're on, this high level of trajectory that we're on in identifying new patients, once we get to some steady state, which I don't foresee any time soon, then we'll be able to potentially provide more persistence and or adherence rates.

Got it. Now, on Europe, we talked about, you know, kind of the significant identified patient population base there and, you know, the work that you're doing through obtaining approval with EMA. How are you thinking about the path forward and the opportunity to bring the product to European patients? Now, I will say I believe what you have is one of the largest MPC data sets that's ever been assembled. So just maybe you can fill us in on kind of your EU application process.

Yeah, a couple of things that I'll try to mention, and obviously we're in the process right now, so I can't get into a lot of detail. What I will say is that we remain highly confident in the robust nature of the data in our dossier. This has been supplemented with the data that I mentioned earlier throughout our process with open level extension data out four years, expanded access program data out four years. The pediatric investigational plan was complete and submitted as well. So we feel highly confident about that. Today we're in the reexamination process, which we've filed for reexamination, as well as an AHEG meeting, similar to a scientific advisory group meeting, that will address the remaining issues under the current regulatory framework that exists in Europe. So we are bringing that data to life through our reexamination process, and they'll have experts there to be able to help to, yeah, get to the bottom, if you will, of the questions. In regards to getting the product to European patients, you know, we have a global EAP program ongoing today. At the end of Q2, we had about 132 patients that were enrolled. Primarily, those are in Europe in a very small number of markets. This has grown tremendously over the last couple of years from where we started with, you know, just not a few but maybe even half that number of patients, and that continues to show us that there's a real pull for the product post-FDA approval in the U.S. for Europe as well as other markets in the globe, too, that we've been addressing through name-patient basis reimbursement utilizing the U.S. label. So that poll is giving us a lot of confidence that there remains, you know, unmet need for the program. Going forward, how we go to market in Europe or how we, you know, assess what our strategies, it really has got to be taken care of after the FDA, sorry, the EMA process is done. We'll understand what a label could look like in the event of a positive outcome, and then we can address what that market approach will be in terms of go-to-market.

Great. Now, shifting gears beyond MPC, maybe we can talk a little bit around vascular Ehlers-Danlos Syndrome, which is really a serious condition with no approved therapy in the U.S. Now, can you elaborate a little bit around where the program currently stands and what excites you about this program?

Yeah, so this is another one of those ultra-rare diseases, about 7,500 patients from a prevalence perspective in the U.S. Soliprolol is currently under investigation in our Phase III program for that disease. It is a 150 two-to-one randomized trial that we have been enrolling in. We have about 66 patients in that trial as of the end of Q2. And I think importantly, and we've said this publicly many times, this is a therapy that exists for patients outside of the United States today. It's never been approved anywhere for vascular Islers-Danlos syndrome. It's been approved for other indications. But it's utilized primarily as a standard of care in a lot of ex-U.S. markets. We're running this trial under a spa with a decentralized process of enrolling this trial. But we also recognize that the event rate has been slower than we would want to see it. That has led us to being able to engage with the FDA earlier this year to let them know that we are running the trial, the enrollments are coming, the events are not coming as fast as we'd like, and we'd like to be able to work with you to understand what are some options for us to accelerate getting this product to U.S. patients. They left us with some homework, very informative meeting that we had earlier this year, and we've said publicly that we have a second half of this year time to reengage with the FDA after some of the homework that we've done, and we're on track to be able to do that. But our goal here is to be able to try and find ways to accelerate getting the product to patients in the United States.

Maybe talking a little bit around your corporate strategy and maybe one area to start is your unique financial position. You're very well capitalized. You, I believe, ended the quarter with $230 million of cash. You haven't been burning that much capital, if at all, I think, which is very, frankly, unusual for a company in your stage. So how does that position you, and how are you thinking about your capital allocation going forward?

Justin? Yeah, thank you. Thank you for having us again. We are in very good shape, and Neil and the Zebra team have really positioned us well over the last couple of years with the success that we've had. particularly around the MyPleifel launch. We finished second quarter $260 million in cash, and we are very focused on our spend. We're very disciplined in all we do. But as we started our conversation today, our three priorities are very crystal clear. Growth of MyPleifel in the U.S., rest-of-world expansion, and moving Celepro all forward. So that is our eyes on the prize, and we really take that to heart. However, we're always looking to see what else we can do. And so as an example, earlier this year, the team monetized a future royalty stream and some non-core assets to generate some money that we use to repay double-digit interest rate debt. And so now we're debt-free, which is fantastic, and that balance sheet flexibility that it's now afforded to us gives us a chance to do what we need to do to stick to those three core messages I mentioned, as well as take a look to see what else we can do to grow our company.

Got it. I think, you know, what you have been able to do is, you know, run your company in a very, with capital light milestones to come. But, you know, I think maybe thinking about, you know, how investors, you know, many of the equity investors sitting here today, how should they think about, you know, what are the right value-inflecting milestones? what will be important for them as they are kind of trying to build their own investment thesis.

Yeah, you know, we have three legs on a stool today. The focus point for us is around this TAM and the expansion of the TAM for the U.S. business. A year ago today, I could not have sat here with the conviction that I have today around what this, you know, addressable market is. Today, I can tell you, it's somewhere between that 350 and the 900. A year ago, I could not have said that to you outside of the fact that I knew where those diagnosed patients are. And a lot of that is because we're now identifying these newly diagnosed patients. I would have expected this three or four years from now. I wouldn't have expected it today. That is telling me that the U.S. opportunity is one worth looking at. And if you do the math, I think it's also one worth investing in. The opportunity for the second and the third leg on the stool around our potential to impact the lives of patients in Europe with an approval and also the number of patients we're impacting through our global expanded access program today shows us that there's a real pull for the product XUS. To date, we've been able to expand markets outside of Europe at U.S. WAC pricing through this named reimbursement program. We're going to continue to expand those markets and open access to patients through that mechanism. But then also from the Soliprolol perspective, that's another upside for us. But the investment thesis for this company today is the three legs on the stool with really the focal area around the U.S. business today and expanding that TAM. That is, we've got a lot of conviction around that.

Great. You've said in the past that you want to be a preferred partner for rare disease assets that fit your commercial infrastructure and your vision. What are you looking for, if you can comment on it? And also, how do you think about continuing to grow the portfolio from here?

Yeah, the vision for us is to become a leading rare disease company. It starts by exactly what we started this conversation with, around how can we make a difference in the lives of the patients with the three legs on the stool or the three areas that we're focused in today. If we do that really well, we'll have earned the right to be able to go out and be a partner of choice for other parties. But that really comes off of the back of executing on our mission today. Anything that we could do in the future, we'll have to be able to leverage what we've built and what we're good at. Today we're earning that right by executing 184 prescription enrollment forms in six quarters post-launch. I mean, it's more than 50% of the diagnosed patient population. That's a big deal in the second full year of launch to be able to do that. So we're kind of earning our stripes around becoming a commercial, rare disease, high-value therapeutic that can pull patients through, keep them on product, and really help them through this process. I think anything we look at in the future, we'll have to leverage that infrastructure that we've built.

Two last questions that I have. One is we've touched on some of this, but back to the point about how investors should think, care about, and maybe starting to do some work on Zebra in the story. What are the key milestones or events that they should be watching out for? I think we've touched on all of those, but just to recapitulate.

Yeah. You know, Justin mentioned the fact that we have resources to be able to invest in the three legs on the stool. I think the important events for investors to look at is, number one, our continued growth in the U.S. business. Quarter, you know, quarter over quarter, it's going to be lumpy. It's rare disease. We're not going to be able to have linear growth in anything we do. But I think on an annual over annual basis, which is the lens of which we look through in terms of building newly diagnosed patients, addressing the patients that are diagnosed and getting them, you know, and physicians educated with the awareness around my playfa, I think that's going to be key. That's number one. Number two is we have in Q4 this year, We'll get clarity around the reexamination process when it comes through to Europe. Along those same lines, we call that our geographic expansion strategy. You know, we're hopeful to be able to also bring on board new markets that we'll be able to support through our named patient program. And then lastly, you know, we have a second half of this year, soliprolol engagement with the U.S. FDA. We're looking forward to that, to understand how we can then accelerate the clinical development of the program to patients in the U.S.

Got it.

Did I miss anything? We're going to take a disciplined approach to how we can supplement our products. It's not core, but, you know, we, as Neil said, we want to earn that right to be a partner of choice. We've built a great infrastructure. We have a strong balance sheet. And so, you know, again, look for those catalysts in the fourth quarter that we just described. and we'll try to move from there.

Great. And last question. If, you know, investors remember just one thing about Zevra from today or anything that we haven't talked about, what would that be?

It's our ability to redefine what's possible in taking care of patients living with rare diseases. What we do in this industry, not just us, but others that are in the rare disease world, is not easy. I mean, actually, we have more failures and successes in what we do in this business. And our ability to try and redefine how we take care of patients living with rare diseases, that's what motivates us every day. And I think that our entire team runs through walls for patients on a daily basis. So that's who we are, and that's what we want to be able to continue to drive.

Well, thank you very much for your time today, and congratulations on all of your progress and success and we're very excited about what's to come for Zebra. Thank you.