Zevra Therapeutics, Inc. (ZVRA) Earnings Call Transcript & Summary

It's been a long day for you. 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?

Yes, that, 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 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 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 in Niemann-Pick disease type C, ultra-orphan, along with UCD. But in addition to that, we're also expanding globally to patients outside of the U.S. And we have a Phase 3 program also going in vascular Ehlers-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. How would you describe Zevra 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 with Miplyffa for Niemann-Pick disease type C, 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 1 leg on the stool. The other leg on the stool for us is our global expansion. We're trying to be able to get Miplyffa (arimoclomol, I should say) into Europe through an MAA process that we'll talk about a little bit more as well. And we're globally expanding into regions and territories where we can leverage the European, sorry, our U.S. label into other markets. And then we have our third leg on the stool, which is our pipeline, our Phase 3 development program for vascular Ehlers-Danlos syndrome, which has 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. Zevra today is 3 legs on a stool. It's a U.S. opportunity that has a lot of uncertainty. Untapped potential. It's a global expansion opportunity in our second leg on the stool, and thirdly, it's around celiprolol in the pipeline.

Great. So maybe, um, we'll start with Niemann-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 from?

to go from here? Yes, 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 1 year ago because we've been learning. We've been learning, number one, that it's not only a pediatric disease anymore. We've, about 50% of our patients are adult patients. That learning is now informing how we try to get newly diagnosed patients into the mix. I'll give you an example. We have had patients that have been misdiagnosed with multiple sclerosis, adult patients that then have progressed with other symptoms that are more attuned to Niemann-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 and then on treatment, is it better off that we can then tailor our development program, sorry, our patient finding programs to being able to then get more newly diagnosed patients. If I look back at the last six quarters, 1 year ago today I would not have told you that 50% of our patients would be adult patients. You know, they used to coin Niemann-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 on some type of therapy. And the reason for that is, Miglustat was originally approved well over a decade ago. The previous company went out and invested in disease state awareness and diagnostic modalities in publishing the suspicion index, and that 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, as you're kind of uncovering new adult patients, the way people think about the overall number of patients that are out there, it's probably only going to grow and you'll 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 2 years into launch. What is driving that momentum and how's your patient finding approach reaching newly diagnosed patients, including the roughly half who turn out to be adults, as you said. And maybe I'll just add for the audience, you know, even recently a colleague of mine reached out to me to be referred to you all as their son is having, suffering from NPC. So I think it really speaks volumes in terms of kind of your ability to continue to.

execute and find new patients. But yeah, just walk me through kind of the momentum that you've had with your launch process. Yeah, it 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 1 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 Miglustat. Now we've been able to also get the published data from our open-label extension study going out 4 years that supports that, that, uh, that, that, uh, trajectory, along with our expanded access program now that's also out 4 years with some pediatric data, that, uh, 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 modification. So all of this longitudinal data helps to be able to get patients on the 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, if you've 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 reference to clinical guidelines that show disease-modifying therapy, use combination therapy, and Miplyffa in combination with Miglustat has a potential benefit for those patients. It's a great safety profile, I should add.

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, NPC historically had no approved options. Now, as you mentioned, starting to see some new entrants. Um, now, and as the first FDA approved therapy and with treatment guidelines 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?

Now, we want to continue to learn. And every day that we have the opportunity to identify the journey of a new patient, because 1 thing is for real, and I have been in this industry for a while in the ultra rare space in multiple different companies, you know 1 patient, you know 1 patient. Every patient's journey to getting to the ultimate diagnosis of a rare disease and then a treatment, if there is 1 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, if I think about 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, you know, aware of what NPC is and get them connected with somebody who's an expert. And that expert, by the way, might only have 2 patients. You know, 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 journey, 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 Miplyffa, 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 the cost of doing business for ultra rare disease patients. They have a challenging time getting multiple therapies for their disease, for Niemann-Pick disease type C specifically, but for all rare diseases. It's not like it's just you're just on 1 product. They're all specialty products. So we have a patient's services group that really tries to handhold and support through reimbursement support, through monthly shipments, through 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 1 additional thing that I think is important. We have, uh, we don't publicly talk about the persistence rates or the compliance rates, but I think, uh, you know, we're asked that question on a regular basis in in these meetings. And, uh, and whilst when you're talking about 1 number, you know, difference of a patient that's, uh, persistent, uh, you know, month over month versus 1 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 as we continue our launch and 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 pathway? board and the opportunity to bring the product to European patients. Now, I will say I believe what you have is 1 of the largest NPC data sets that's ever been assembled. So just maybe you can fill me in on kind of your EU application process.

Yes, 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 additional that I mentioned earlier throughout our process with open-label extension data out 4 years, expanded access program data out 4 years, the pediatric investigational plan was complete and submitted as well. So we feel highly confident about that. Today we're in the re-examination process, which we've filed for re-examination as well as an ad hoc meeting similar to a scientific advisory group meeting that will address the remaining issues under the current, um, regulatory framework that exists in Europe. So we are, we are, um, bringing that data to life through our reassessment process, or re-examination process, and they'll have experts there to be able to help to, yes, 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 just not a few, but maybe 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 pull is giving us a lot of confidence that there remains, you know, unmet need. Um, going forward, how we go to market in Europe or how we, you know, assess what our strategy is, 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.