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. 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?
Yeah. First of all, thank you for having us. We've had a great day today. We really appreciate the support of the Morgan Stanley. 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. Rare disease is not as unique as it once was 20 years 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 United States, and we have a phase III program also going in vascular Ehlers-Danlos syndrome. 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 have 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 MIPLYFFA in the Niemann-Pick disease type C space. About a 900 patient prevalent population in the U.S., about 300 to 350 of those patients. This is a commercial opportunity for us. We have been now at it for about six quarters in terms of the launch. We will get into some more of this detail later on. But in addition to that is one leg on the stool. The other leg on the stool for us is our global expansion. We are trying to be able to get MIPLYFFA into, or arimoclomol, I should say, into the Europe through an MAA process that we will talk about a little bit more as well.
Yeah.
We are globally expanding into regions and territories where we can leverage our U.S. label into other markets. Then we have our third leg on the stool, which is our pipeline, our phase III development program for vascular Ehlers-Danlos syndrome, which has enrolled about 66 patients out of 150 today, and we will 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 three legs on a stool. It is a U.S. opportunity that has a lot of untapped potential. It is a global expansion opportunity in our second leg on the stool, and thirdly, it is around celiprolol in the pipeline.
Great. So maybe we will start with Niemann-Pick type C. You are the first and only FDA-approved treatment. You have been, 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 are having. As I mentioned, 900- patient prevalent in the U.S. About 300 - 350 of those patients were diagnosed. 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. That is primarily those patients. We also are even more excited today than we were a year ago because we have been learning. We have been learning, number one, that it is 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 disease patient that has been recently published, actually about a quarter or two ago, that was misdiagnosed.
With this, we're learning. 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, it's 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 Niemann-Pick disease type C as childhood Alzheimer's. Today we're understanding more, we're learning more. 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.
That's been probably the biggest surprise for us, that there is real opportunity for growth beyond the 350 patients. 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. The reason for that is miglustat was originally approved well over a decade ago. 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. 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—
Yep.
—to get closer to 900 than 350 patients.
Yeah. As you said, as you are uncovering new adult patients, the way people think about the overall number of patients that are out there, it is probably only going to grow and you will hopefully find more patients that really need your therapy. Maybe shifting a little bit in terms of your launch. You are now generating about $30 million a quarter, only just less than two years into launch. What is driving that momentum, and how is your patient-finding approach reaching newly diagnosed patients, including roughly half who turn out to be adults, as you said? I will just add for the audience, even recently a colleague of mine reached out to me to be referred to you all, as their son is suffering from NPC.
I think it really speaks volumes in terms of your ability to continue to execute and find new patients. Just walk me through the momentum that you have 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 is also important to have something that we can offer them. That has 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 disease type C Clinical Severity Scale, with our data in combination with miglustat.
Now we have 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 is also out four years with some pediatric data, part of our pediatric investigational plan that is out there too in the literature. We package all of that together with now that we have got newly approved therapies, the clinicians have now published consensus guidelines. They have updated that based on the fact that there is now a product that is approved and multiple products that have come to market here recently.
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. 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, 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 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.
Yeah.
With a great safety profile, I should add.
Yeah. I think you're really changing your position as a potential foundational therapy. Maybe just on that note, as you said, NPC 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 starting to be updated to support combination use, how do you fit into that evolving landscape? What kind of work that you're doing? What is your 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 in 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. Then, a treatment, if there is one available, is unique. And for us, 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 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.
Yeah.
That's what we're trying to do.
Got it. Thank you. 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, we call it white- glove service. The reality is that it is almost a 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 is not like you are just on one product. They are all specialty products.
We have a patient 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 are 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.
Yeah.
We are learning there too, by the way. There are certain things that we did really well that we are doubling down on, certain things we were not doing so well. 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. 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. What I can say is that we saw very high levels of persistency in our expanded access program. We saw very low levels of discontinuation rates. 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.
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 anytime soon, we'll be able to potentially provide more persistence and/or adherence rates.
Got it. On Europe, we talked about kind of the significant identified patient population base there, and 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? I will say, I believe what you have is one of the largest NPC datasets that's ever been assembled. 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 had mentioned earlier throughout our process with open-label extension data out four years, expanded access program data out four years. The pediatric investigational plan was complete and submitted as well. 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 AHEG meeting, similar to a scientific advisory group meeting, that will address the remaining issues under the current regulatory framework that exists in Europe.
We are bringing that data to life through our re-examination process, and they'll have experts there to be able to help to get to the bottom, if you will—
Yeah.
—of the questions. In regards to getting the product to European patients, we have a global EAP program ongoing today.
Right.
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 even half that number of patients. 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.
That pull is giving us a lot of confidence that there remains unmet need—
Yeah.
—for the program. Going forward, how we go to market in Europe or how we assess what our strategy is, it really has got to be taken care of after the EMA process is done. We will 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 NPC, 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. This is another one of those ultra-rare diseases, about 7,500 patients from a prevalence perspective in the U.S. Celiprolol is currently under investigation in our phase III program for that disease. It is a 150, 2: 1 randomized trial that we have been enrolling in. We have about 66 patients in that trial as of the end of Q2. I think importantly, we have said this publicly many times, this is a therapy that exists for patients outside of the United States today. It has never been approved anywhere for vascular Ehlers-Danlos syndrome. It has been approved for other indications, but it is utilized primarily as a standard of care in a lot of ex-U.S. markets. We are running this trial under a SPA with a decentralized process of enrolling this trial.
We also recognize that the event rate has been slower than we had wanted 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 re-engage with the FDA after some of the homework that we've done, and we're on track to be able to do that.
Our goal here is to be able to try and find ways to accelerate getting the product to patients in the United States.
Thank you. 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 or so 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. 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 Zevra team have really positioned us well over the last couple of years with the success that we've had, particularly around the MIPLYFFA launch. We finished the second quarter $260 million in cash.
Okay.
We are very focused on our spend. We're very disciplined in all we do. As we started our conversation today, our three priorities are very crystal clear: g rowth of MIPLYFFA in the U.S., rest of world expansion, and moving celiprolol forward. 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. As an example, earlier this year, the team monetized a future royalty stream and some non-core assets to generate some money that we used to repay double-digit interest rate debt.
Now we are debt-free, which is fantastic, and that balance sheet flexibility that it is 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 what you have been able to do is run your company in a very, with capital light milestones to come. I think maybe thinking about how investors, many of the equity investors sitting here today, how should they think about what are the right value-inflecting milestones? What will be important for them as they are trying to build their own investment thesis?
Yeah. We have three legs on a stool, and 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 addressable market is. Today, I can tell you it is somewhere between that 350 patients and the 900 patients. A year ago, I could not have said that to you outside of the fact that I knew where those diagnosed patients are. A lot of that is because we are now identifying these newly diagnosed patients. I would have expected this three or four years from now, I would not have expected it today. That is telling me that the U.S. opportunity is one worth looking at. If you do the math, I think it is also one worth investing in.
Yep.
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 through our and also the number of patients we are impacting through our global expanded access program today, shows us that there is a real pull for the product ex-U.S. To date, we have been able to expand markets outside of Europe at U.S. WAC pricing. Through this named reimbursement program, we are going to continue to expand those markets, and open access to patients through that mechanism. But then also from the celiprolol perspective, that is 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. We have 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? How do you think about continuing to grow the portfolio from here?
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. That really comes off of the back of executing on our mission today.
Anything that we could do in the future will 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. 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 will have to leverage that infrastructure that we've built.
Great. 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 Zevra and 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.
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-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.
I think on an annual-over-annual basis, which is the lens at which we look through in terms of building newly diagnosed patients, addressing the patients that are diagnosed and getting them, and physicians educated with the awareness around MIPLYFFA, 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 re-examination process when it comes through to Europe. Along those same lines, we call that our geographic expansion strategy. 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. Lastly, we have a second half of this year, celiprolol 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 continue to take a disciplined approach and look to how we can supplement our products. It's not core, but 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. Again, look for those catalysts in the fourth quarter that we just described, and we'll try to move from there.
Great. Last question. If 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. Actually, we have more failures than successes in what we do in this business. Our ability to try and redefine how we take care of patients living with rare diseases, that's what motivates us every day. 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.
Great. Well, thank you very much for your time today, and congratulations on all of your progress and success. We're very excited about what's to come for Zevra. Thank you.
Thank you.