Good morning, everyone. I'm Brandon Folkes, one of the equity research analysts here at H.C. Wainwright. Next up, we have a fireside discussion with Zevra Therapeutics. Joining me from Zevra is CEO Neil McFarlane and Justin Renz. Thank you both for joining us. Neil, do you want to say some opening statements and just sort of go over any disclosures you want to make?
Yeah. Thank you for having us. I will be making some forward-looking statements today along with Justin. Please take a look at our most recent SEC filings for most up-to-date information, and we're really looking forward to having a conversation here post-earnings and getting into some of your questions.
Great. I appreciate it. I'll just dive in. Yeah, I'm going to start at a high level. Just as you mentioned, we've just been through earnings, you know, Zevra's changed a lot in the last year. A lot of good stuff has happened, right? The company's in a tremendous place of strength. How do you view Zevra today and longer term, just in light of all the progress that has been made over the last 12 months?
Yeah. Thank you. It has been an absolute journey, and it's been a journey based on a plan that we put together back at the end of 2023 into 2024, our first rendition of our strategic plan that really allowed us to focus on doing a few things well. Centered around the patients, centered around how we can make a tremendous impact, being able to drive what you mentioned in regards to performance. It's three real areas that we've been focused on. One has been our U.S. business.
How can we make sure that the launch of MIPLYFFA in the U.S. continues to drive, not just for the diagnosed patient population, but start to unlock the undiagnosed patient population to see if we can really drive the business towards that TAM. We're a lot more confident today than we were a year ago, but we're continuing to drive that forward. The other one was focusing on the regulatory and geographic expansion for our products globally. You saw that we filed our MAA last year. We've been through the process. It's a standard review process, and we're continuing to make sure that we drive with the robust package that we put together for the FDA, drive that with the European Medicines Agency as well.
Lastly, outside of Europe, outside of the U.S., how can we think about making and broadening access for MIPLYFFA ex-U.S.? We've been starting to do that. In the Q1 call, you heard that, you know, some of our relationships with our distribution networks have started to bring named patient pre-commercial revenue in. More importantly, broadening access, and the pull for the product remains globally. Lastly, it's been about focusing on our pipeline. You know, we've made some progress, some significant progress in the last year, reestablishing celiprolol, getting the enrollment going. We're starting to see some events. In a parallel track, we're also working with the agency to be able to see how can we drive accelerating development.
It's really just been about focusing on doing a few things well while making sure that some of the non-core focus that we have is we've executed in getting those out of our, out of our business. It's been a heck of a ride. A lot's transpired in 12 months. I think one of the keys for us in the future is moving our headquarters to Boston. We still have facilities in Florida and Copenhagen, but tapping into the talent as we grow into our strategic plan over the next five years, and the ecosystem in Boston is really important.
Okay. Maybe just touching on that, moving the headquarters to Boston, does that imply that you're open to bringing in development stage assets? You know, just that talent that you're tapping in there. Is it just sort of commercial expertise? Can you just dig deeper into that strategic move, moving the headquarters to Boston and the talent in Boston you will look to tap into to drive Zevra's growth?
Yeah. you know, it's interesting. A lot of folks think, "Well, you just made a decision to move to Boston."
We didn't, actually. What we did was we put a strategic plan together, and we said, "If we want to become a leading rare disease company, let's go out and see what are the types of positions we need, commercial, regulatory, development, and then let's figure out where that talent is." There are companies that'll do that for you. You need X amount of technical operations people, X amount of whatever. Within a 45-minute radius, where do you go? Well, between San Francisco, Boston, San Diego, New Jersey, what have you, what we needed to be able to create the longer term vision for the organization and to tap into all of those areas, commercial, development, regulatory, was Boston was our best bet. That's, and that's why we chose that.
In regards to your question around, you know, does that mean that we're moving into development stage, we are in development stage today. We have a late-stage development asset. We're having constructive dialogue with the agency around what we're doing for celiprolol. We've gotten a CRL through the U.S., through AdComs and all the challenges that you know, deal with in our industry to allow that. It allows us the optionality to grow while we're focusing on what we're executing on today, both domestically and, quite frankly, in Europe as well.
Fantastic. I want to come back to the MIPLYFFA launch. You obviously done tremendously well in terms of the enrollment forms. You know, you received roughly half of the diagnosed patient enrollment forms for, you know, roughly half of the diagnosed patient population in the U.S. Going forward, how do investors think about where the next leg of growth comes from? I know you've been, you know, very forthcoming in terms of it's gonna come from multiple layers and multiple legs, the diagnosed and undiagnosed. Can you just help us think about, you know, what are the levers that you pull to drive growth in those two patient segments, the diagnosed and undiagnosed? Any way to contextualize sort of the growth drivers, how we should think about the diagnosed patients from here?
You know, could you get close to 100% of the diagnosed patients on MIPLYFFA? You know, quite frankly, why not? Similarly, you know, how do you drive an undiagnosed. I know there's a lot in there, but I want to just wrap in AI because there was a lot of discussion this morning about how AI, you know, can help identify patients and what it does well. If I look at the enrollment forms over the last six months and your mentions of AI, you do seem to be doing something very well on that side. I know a lot in there, but, you know, can you help us unpack sort of the growth?
Yes, I'm gonna see if I can answer a lot of questions with one answer. It's not a yes or no. It is we are learning a lot as we're in the launch mode. As you mentioned, of a prevalence in the U.S. of Niemann-Pick C that's around 900 patient prevalence. Very similar to that of what we see in Europe at about 1,100 patient prevalence. As we've been discussing, the maturity and the investment over time in disease state awareness has grown the European diagnosis and treatment to a much more mature level than that in the U.S. That 300 to 350 diagnosed patients, that's based on claims data.
That's based on the claims data that we do a cutoff. Over the last two years, if you had an NPC diagnosis and something that has allowed you to be able to get claim, we know those patients are there, and we're working diligently. Our teams of medical, commercial, reimbursement, patient services, you name it, they're working diligently to bring those diagnosed patients through. We've done really well. That undiagnosed patient population from the 300 to the 900, there are a lot of ways that we're looking and working, and some of them are ways that were utilized over 12+ years in Europe to actually get those patients diagnosed and treated. I'll speak very briefly about some of our AI activities.
We have a bespoke model that's been put together utilizing both electronic health records as well as multiple data sources around our claims data that then we end up putting and feeding that machine with the learnings that we have. Every patient that comes in, we try to understand as much about their journey as possible. When you triangulate all those pieces together, you then have an opportunity to go to a specific, I'm gonna just call it zip code in this situation, and say, within this zip code, the suspicion index that was generated in Europe a long time ago about NPC, along with the electronic health records and the claims data, you should be seeing patients that look like and potentially have NPC in this geography with this physician population.
We can go out now and have conversations with those specific physicians targeted around educating about NPC because they should have, based on all of the triangulation I just talked about, a patient that looks like NPC. The more you do that is the more you're gonna be able to then say, "Okay, this patient was." And we're seeing this, we said this in our call. Patients who have been misdiagnosed, a patient living with multiple sclerosis for 20 years, decompensating until they actually said, "Wow, your symptomatology looks like it's in addition to MS." Suspicion index-wise, you would say that patient from an AI perspective could have been picked up earlier, diagnosed earlier, gotten genetic testing, and then getting on a therapy that could potentially halt or, you know, stop the progression of their disease.
That is the work that we're doing that I think is providing us a lot more confidence about the TAM being somewhere between 300 and 900, because since Q2 of last year, we've seen newly diagnosed patients every quarter since then. We feel really good about it, but we're learning. We had another patient who was on the autism spectrum that ended up progressing that got tested that also came through out of Europe into our compassionate use program. These AI models, we have to continue to feed them, so they learn and get smarter, and we are learning and getting smarter with every patient's journey that we understand more and more deeper, you know, deeper, while we're asking the questions.
Just maybe staying on that, you know, you've got the filing in Europe. Should you get approved and come to market in Europe, does that bring a wealth of information to feed that AI model that it even gets better in the U.S.?
I do think so. We're learning, by the way, through that, as much as we can, and I think it's an important perspective here. It's not that we have the access to collect all the data on all the patients, but we do have a very broad physician base and a global expert network that speaks to each other. Because they know that we're trying to feed the system, our teams are out there working with them to try and get as much as the patient journey work so we can go earlier and be able to treat earlier. Much like the guidelines that were published very recently in the Journal of Inherited Metabolic Disease.
Those guidelines now being published are actually taking from those expert panels and pushing towards the things that we've been saying. One, treat early, get diagnosis. The holy grail is the NPCCSS as well as the, you know, full genetic testing to get patients tested as early as possible, and utilize the varying modifying, disease-modifying agents to be able to halt the progression of disease as early as possible. A really important tool for us as an organization, but also very important for us to continue to learn from.
Fantastic. It's so interesting. I do want to bring what we've been talking back to sort of granularity and sort of numbers, patient enrollments, right? We ask you this all the time, you know, what's the patient enrollment number for next quarter? How's it going to look? Taking a step back, you had a tremendous fourth quarter followed by a very strong first quarter in patient enrollments, right? You've long said don't sort of look at it on a quarter-by-quarter basis. If I now look at it on a six-month basis, you had a very strong six months versus the trailing six months. How much of what you're talking about, you sort of, is coming through in that? How do we think about patient enrollments going forward? Should we still think about it, you know, having ebbs and flows from here?
Or is it the snowball that's building and, yes, we'll have ebbs and flows, but you're seeing a lot of success on the ground with a lot of things you've talked about in terms of patient identification, better diagnosis, things like that.
No, I would continue to caution against some type of straight line in terms of growth in the ultra-rare disease market in general. We will see variability on a quarter-over-quarter basis. I think the best thing you can do is look at year-over-year information when it comes to what we're doing. We have a pipeline of patients that we have been working on now that are the diagnosed patient population, right? That continues to move forward. As you mentioned, in Q4, we had 24 enrollment forms that came through. A lot of those enrollment forms are patients and physician calls that were being made in February of the year before, you know, in the summertime.
The pipeline of all of these 300 to 350 patients that we're working through, while also building the undiagnosed patients every quarter. It is very variable. It's gonna continue to be variable. Quite frankly, some of it is the law of small numbers. It is also in a heterogeneous disease that has presentation from an infantile presentation that's very different than that of a late adult onset presentation. It's just like what we say, "You know one patient, you know one patient."
Mm-hmm. Okay. You know, the importance of one patient, right, is very important in this patient population. I do want to touch on potential seasonality, right? I know on your earnings call you talked about and we'll look at the insurance side of things too, right? You talked about your insurance coverage, the good progress you've made there, but also the very good progress on medical exceptions.
Yes.
What about seasonality in patients in terms of bringing patients onto paid therapy? Any learnings now that you've had the product on market for a bit, gone through a first quarter? You know, there's many other companies talked about a tough first quarter. You produced a very good first quarter. Can you just help us think about learnings about seasonality and insurance on the product?
Yeah. I, you know, we are not immune to what every other specialty and high-value therapeutic product goes through. A lot of times in the first quarter, you go through reauthorizations. People change insurance plans. It's a natural part of what every specialty pharma company goes through. You know, a lot of what we are able to do and have been able to do from that front was we launched it, the product, in a large bolus of patients in the November timeframe, right? That's when the drug came on the market. Some of those authorizations were for three months, some were for six months, some were for 12 months. We kind of have a more spread out authorization cadence, if you will.
We're hit like every other company with patients who are changing insurers and we're navigating through the reauthorization of the first quarter of the year. It'll take a few years for us to get the hit in the Q1 timeframe like every other company that has to go through that reauthorization because of the fact that we had a big bolus in Q4. It is part of what we do now. I will say that our team did a tremendous job back in the October timeframe in preparing for reauthorization season and working with our specialty pharmacy and the payers, sorry, and the patients in providing them with the information ahead of time, so that way we could try to mitigate any challenges to getting patients reauthorized.
We have it just like everybody else. We were able to execute well, and here we are.
I do wanna sort of shift gears to IP quickly.
Sure.
You know, I think it's important, the patent term extension. Can you just give us the update there? Then with that also, you know, if you're willing to discuss, what are some of the barriers to entry for a generic, should one come to market, you know, much later in the future? Just with the infrastructure and everything you've built and the knowledge we've talked about in terms of sort of locating these patients. Firstly maybe just on the patent term extension, and then if you're willing to talk about any sort of additional barriers to entry.
Sure. We have an Orange Book list of a patent today that expires in 2029. We've applied for a patent extension. The open commentary periods have gone through. The last one I believe was the end of March. We are in a process now where we can get up to five years of patent extension, but we don't know what we will receive. And recall, although we have our patent on Orange Book listed through 2029, our orphan drug exclusivity is through 2031. We're just waiting for the patent office now to be able to just do their final determination and send to the FDA and get us some additional time, if we can.
Fantastic. you know, shifting gears maybe staying on pipe over to Europe. Can you just give us the update there in terms of regulatory interactions? How you feel—
Yeah.
—about the questions you've received to date?
So far we have not seen anything that is new to us. We had, as you recall, previously, the package in Europe had very similar questions to that of the U.S. We went through and provided more robust data to the U.S. through the AdCom process and then got the product approved. We're working through those same questions within the European Group. It's a standard review process, and we are in that process. We had our 120-day response that we'd mentioned on our call. Within the clock stop, we've had our 150-day comments back from the rapporteur, and we're moving towards a standard review.
Okay. When we think about the early commercial potential in Europe, you know, should we think about the EAP program as being sort of the low-hanging fruit? How do we think about sort of an initial uptake in Europe?
Yeah.
Given it's not one country.
Really good question. I'll try to answer it quickly. I know we're getting close on time here. We have an expanded access program that is multidimensional. Some are pre-commercial revenue and some are compassionate use. In Europe, we have over the last 18-24 months actually continued to get the pull for patients in both programs. We believe strongly that the small number of markets that we've been in and providing access without, quite frankly, any significant amount of infrastructure on the ground, but yet the pull for the product means and bodes well because the market is more mature and the fact that physicians are global today in regards to how they treat patients and what they're looking for. The pull has been, I think, the best indicator.
The growth in our EAP quarter-over-quarter, in Europe, we think provides a good background for us to be able to help patients in Europe with an approval.
Great. I know we are almost out of time, but I do want to touch on celiprolol, right? Because I think it's a very important potential driver, right, should it come to market. You know, you talked about it on the earnings call, right? You gave us updated enrollment and events. What can you say in terms of, you know, and not getting ahead of the FDA, but potential ways to explore accelerating development there, bringing that product to market and, you know, potentially, you know, the wealth of data you already have on the product to date?
Yeah. To make a long story short, we have seen a great uptick now in enrollment, as I mentioned on the call. We still have two events, and out of the 28 for an interim call, interim analysis. That lack of events has actually brought us to make sure that we had a conversation with the FDA around ways to potentially accelerate the development of the program since we started, and if you recall, it was a CRL previously based on the paper filing with the agency. We went into that conversation with the agency to be able to share everything that's transpired since we had our initial conversations and developed the phase III program under the SPA and breakthrough and everything else.
It was really important for us to make sure that we pull all the strings, whether it's enrolling, you know, changing any criteria and enrolling, or if there are other ways to accelerate development. We're moving on multiple paths now to be able to see if we can accelerate the clinical development. We've guided that we will be having another meeting with the agency in the second half of this year based on some guidance that we got out of that meeting. We're crunching a lot of the data, pulling a lot of the information together to see if we can get to some common ground about accelerating the development path. Again, devastating disease. Last week was actually, Wear Red for vEDS .
We don't say that fast too many times, but absolutely devastating disease, and we wanna make sure that we can probably bring something to market for patients here.
Great. Very exciting, yeah. Neil, Justin, thanks very much for joining me.
Yeah.
I look forward to your update.
Thank you.