All right. Good afternoon, everyone. My name is Brandon Fokes. I am one of the biopharma analysts here at HC Wainwright, and joining me for a fireside chat from Zevra Therapeutics is CEO Neil McFarlane. Neil, thank you very much.
Yeah, thank you for having us.
Maybe just to start, do you want to just spend a few minutes giving people a quick overview of Zevra and the products that you currently have?
Yeah, absolutely. I want to make sure I make the disclosure that we will maybe be making forward-looking statements, take a look at our most recent SEC filings for the most up-to-date information. Again, thanks for having me and the Zevra team here. It's been a great conference so far. Zevra is a commercial stage rare disease company. We've got two commercial programs in the U.S. market today, along with a pipeline and a program that is in phase three, as well as an end of phase two, phase three ready program that we have as well. Well capitalized, and we're in the process today of executing on the launch of our most recently approved product. Let me go through just quickly in regards to the products and the disease areas that we're in.
We have a program that is most recently launched, as I mentioned, for Niemann-Pick disease type C, and that is MIPLYFFA. That is in its launch phase right now. We have another program in certain urea cycle disorders, which is called OLPRUVA. We can get into some more of this as we go through the meeting. In phase 3 development, we have a program which is called Celiprolol, and it's being developed for vascular Ehlers-Danlos syndrome, a rare connective tissue disorder. As I mentioned, we finished a phase 2 and developed a package to the end of phase 2 meeting with the agency.
We have a single pivotal phase 3 with confirmatory data and some safety information that we'll need to bring forth for our KP1077 program and rare sleep disorders that we made the determination to go and look for strategic alternatives at the end of last year.
Great. Thanks very much. Maybe can you just talk a little bit more about MIPLYFFA and especially the patient population that it serves?
Sure. As I mentioned, MIPLYFFA was most recently approved first-in-class product for the treatment of Niemann-Pick disease type C. It's a rare lysosomal storage disorder that gets cholesterol and lipid buildup in the cell and causes cell death and heterogeneous disease presentations. In the U.S., there are about 900 patients from a prevalence perspective. In Europe, about 1,100 patients from a prevalence perspective. Again, bringing it back to the U.S. and our most recent launch here, we are of those 900 patients, about 300-350 of those patients have been diagnosed in the U.S., of which, in our most recent quarterly call, we spoke about 122 patient enrollment forms in total since launch at the end of last year.
In our first full quarter and let's call it five weeks at the end of Q4, we have about a third of the diagnosed patient population with enrollment forms. The launch is going very well in the U.S. and exceeding expectations for sure. In Europe, I want to talk quickly about Europe because in our call that we had about a few weeks ago here in our earnings call, we talked about reaffirming our MAA filing in the second half of this year, which we're moving towards right now in Europe, about 1,100 patients from a prevalence perspective. However, it's a much more mature market in Europe. There's been an approved product in Europe for well over a decade, and then a large number of those 1,100 patients have actually been diagnosed and have been on some type of treatment.
In the U.S., we're a little bit behind in regards to the number of diagnosed patients, but we're hopeful that disease state education, along with a lot of the product awareness that we're putting in, will continue to identify patients and treat them earlier.
You touched on it, but maybe, you know, given the ultra-orphan nature of the disease, can you just talk more about the launch and how you approach a launch in this space?
Yeah, we see three cohorts of patients of the 900 patients in the U.S. The first cohort was the patients who had early access or expanded access, and they were in our trials. We ended, or in our EAP program, we ended that with about 83 patients. So that's 83 of the 300-350 patients diagnosed. Then we talk about that diagnosed cohort of that 300-350 patients. You've been diagnosed, you're on some type of therapy. It could be you're on a treatment for a symptom, but you at that point were not on disease-modifying therapy. With MIPLYFFA in combination with Miglustat, our label indicates that you halt the progression of this devastating disease versus on Miglustat alone. And that's with an acceptable safety profile. So that diagnosed patient population, we are also moving forward with.
The third cohort is how are we unlocking the undiagnosed patients? That is building the 300-350 to the 900. I'm pleased to say that our efforts around disease state awareness and product awareness and going after from earned media to what we do with the physicians to date and conferences and data and so on and so forth, we're actually identifying patients in all three cohorts. The first cohort, we've actually enrolled all of our EAP patients into enrollment forms. That cohort is now finalized. We're moving in the other two, the rest of the diagnosed patients as well as the undiagnosed patients.
Great. You talked about sort of the undiagnosed patients and sort of the 900 prevalence with the 300-350 being diagnosed. Why haven't those patients been diagnosed? What are some of the challenges to diagnosis for these patients?
Yeah, that's a great question. NPC is a heterogeneous disease. It can present in the early forms with more visceral type symptoms, i.e., hepatosplenomegaly and failure to thrive, other types of neurological symptoms as well, all the way to patients that are adult patients that actually will present with a psychotic break or they'll present with epilepsy as their primary symptom. As you think about rare disease in general, not just Niemann-Pick C, you know one patient, you know how they might progress one patient at a time. The heterogeneous nature of the disease makes it somewhat complicated to notice that a patient with epilepsy might have additional symptoms that then you would test them for Niemann-Pick disease type C.
Our efforts and what we're investing in around disease state awareness, where you may see epilepsy, but if you see something else that goes along with it, then we'd like you to make sure that you think about Niemann-Pick disease type C because there's now a treatment available that, based on our label, halts the progression of this progressive disease.
Great, thanks. Maybe just what are the next steps in the launch here? You sort of touched on sort of going into what the three pillars and going into those three pillars. How do you get further penetration? Would you say those 300-350 patients that are diagnosed, are most of them, if not all of them, good candidates for MIPLYFFA?
Yeah, I think there's a couple of questions in there. Let me see if I can try to answer the first one. How do we get to both the undiagnosed patients and the diagnosed patients? We fully expect that our efforts and looking at the playbook, if you will, of Europe, which with 1,100 patients, there was an approved product and a lot of investment in disease state awareness as well as product awareness, and the rate of diagnosis in Europe is much higher than that of the U.S. We're taking that playbook to the U.S. now that we have an approved product, and we're investing in all of those types of activities around raising the awareness, making sure from a physician perspective, a patient perspective, community perspective, we're raising the awareness of NPC and the fact that there's a disease-modifying treatment.
Our hope is that we'll be able to utilize those same activities that have proven successful in Europe, also in the U.S., along with what we announced, some of the efforts that we announced on our earnings call around genetic testing. We've partnered with a leading genetic testing organization that's been testing for Niemann-Pick disease type C for some time through lysosomal storage disorder panels. We're working with them to make sure that as an NPC patient may come up in the panel, we have the ability to educate those physicians and let them know that there's product availability to halt the progression of the disease, but also in addition to that, make treating, sorry, diagnosing patients also available. We're making that testing available with this partner that we have.
Again, the efforts that we're putting into raising awareness are not really that unique to us, but we're targeting those efforts primarily to those physicians, patients, and groups that can most benefit.
Thank you. Where are the majority of the Niemann-Pick patients diagnosed? What is the physician? Similarly, how should we think about those patients that have Niemann-Pick but are undiagnosed? Where might they be being treated for something else currently?
It's a question that we still are in the process of answering. I don't think I can give you a definitive there. We're in the first quarter of launch. What we've heard from physicians to date that are part of these, let's call them centers of excellence that have a large number of patients in our EAP that we're treating, not one patient, but treating a dozen patients. Obviously, those patients were being diagnosed and taken care of at those sites. We're now moving outside of those sites to where neurologists and geneticists and pediatric folks are getting exposed. Actually, even on the psychiatry side, patients are being diagnosed. It's a little early for me to tell you that we know everything about where these patients are and what they're presenting with.
I will tell you that we're making a lot of effort and focusing that effort into where we can hone in the NPC, the diagnosis, and then treat patients faster.
I have to try. All right. You talked about the EAP, right, and the very good enrollment that you've had to date. Can you just help us understand the journey that these patients have from the EAP to enrollment to Zevra transitioning them into paid patients?
Sure. I think it's important to note that prior to our advisory committee last summer, we had approximately 70 patients in the EAP. These patients were some patients who were in our original clinical trial that then enrolled over into the OLE program. From the open label extension, they were enrolled then into the EAP program. That 70 patients was pretty level. After our advisory committee, we had an influx of patients who went to these sites and asked to be part of the EAP. We ended about six weeks later, a month or so later, with about 83 patients. I think one of the things that's been most impactful is the majority of these patients that were in the EAP program have been in the program for a very long period. We're talking about some patients with data up to five years.
That is meaningful because when you launch a program, and for those who have been in the commercial business for a while, you usually launch a program and then you go and present the package insert to a physician, you provide all the data and they say, "This is great, but I need more data. I need another year's worth of data." You go with another year's worth of data. They say, "Well, I need two years' worth of data." The good part about what we have and continuing the EAP program for this amount of time is we have longitudinal data of patients who have been on therapy in an EAP and benefiting from it.
When we now go to physicians and payers, by the way, as well, and we talk about the impact of our label and the opportunity to halt the progression of a devastating disease versus the control arm, I think it's meaningful that we have this longitudinal data of patients who've been through this process and now converted to a commercial script.
Great. Just two follow-ons. You touched on two very important points there, right? Maybe just firstly, how do you feel about current reimbursement levels?
I'm very proud of the team. I would say I'm proud of the team, but I'm also very happy that physicians and patients are also willing to work through the hurdles that the payer community has around high-value therapeutic and new products to market. We do not talk about specific reimbursement rates, but we give enrollment forms that come into the top, which is a leading indicator. We talk about covered lives. On our most recent call, we talked about 38% of covered lives. As you know, covered lives does not equal reimbursement. Reimbursement is the heavy lifting that is done through the medical exception process that allows for patients to then come and get on to commercial therapy. We have been very successful.
I applaud the families that have to do a lot of heavy lifting, the physicians who have to do a lot of heavy lifting. I also will say that between our field reimbursement specialists that are out there helping the families and physicians to navigate, our medical folks that are in there every day educating payers around the disease, our sales reps that are in the offices making sure they're educating on the label. This collective effort has pulled through a number of patients. When we talk about conversion of a patient enrollment form to a script on the bottom that's being reimbursed, it's a lot of effort. All the pieces of the pie have come together. Really happy with that so far. We have to continue doing that. That's not something that you stop doing.
From a payer perspective, I think the strength of the data as well as the pull from the patients and the families and the physicians willing to do the work is what you see in our performance.
All right. The other part of that that you mentioned, that in your EAP, you had patients on therapy for a very long time. The EAP obviously then suggests that patients do stay on therapy. Can you just talk about once a patient goes on therapy, do they generally stay on therapy? How much support does Zevra need to put behind those patients to keep them on therapy?
We're only a quarter in, one full quarter into the launch. I do think that the stability of patients that have remained in the expanded access program in the U.S., but also in Europe, we have an expanded access program, which we call our global EAP that has historically had 70-80 patients enrolled in that program. After our approval and we announced this last quarter, that's up to 85 patients now in a small number of European countries. They've remained fairly consistent and stable there too. It's too early for me to tell you what the duration of therapy is going to be of the patients who have transitioned to commercial product. I will say, though, that we're here for those patients in terms of supporting them through the payer landscape, in terms of supporting them through our patient services group.
If history repeats itself, those patients will continue on therapy because they really have stayed in a long time. I think it's important to note an Expanded Access Program is not an easy program for families either. That's a commitment to have to travel to a center maybe sometimes outside of your state once a quarter to get evaluated. We collect data along with that in addition to then get your supply from the sites to then go back to your center, go back to your home. It's a commitment. I think that that has paid off. The patients and the support of the physicians obviously helped us with our data collection. Now we have the ability to get this data out to the community and help to support the long-term use of MIPLYFFA.
Fantastic. You have touched on Europe before, but it is quite interesting the sort of prevalence and number of diagnosed patients out there. I guess, what do they do differently to have a higher diagnosis rate in Europe versus the U.S.? Do you feel whatever it is that they do or the reasons for that higher diagnosis rate, is that directly transferable to a U.S. model?
I do think it is transferable. Let me start with that. It's a great comparable for us to think about what has worked. Now, my answer to that is that when you have, and this is not just for Niemann-Pick disease type C, but in all rare diseases that I've been associated with, when you have no available therapy, it is challenging for a physician to think about what they would do for that disease state. As therapies become approved and the momentum starts to pick up, you start to see physicians thinking about that disease. I don't think it's any different for Europe. Europe had an approved product well over a decade ago. They went from fewer diagnosed patients than we had in the U.S. and now have been able to really ramp up the diagnosed patient population.
A lot of times that has to do with obviously interest of the patients and the caregivers to get diagnosed and have access to earlier diagnosis. It is about the physicians who are willing to do the heavy lifting to help those patients to get through the diagnostic odyssey earlier, pulling them in earlier, getting them tested, and then onto some type of a therapy. Obviously, the companies that are out there that have been investing for well over, or the company that has been investing for well over a decade of physician education, patient awareness, and disease state awareness. I think it is absolutely transferable to the U.S. We are starting to see that now by having all three cohorts that I talked about, the EAP, the diagnosed patients, as well as the non-diagnosed patients. In our first full quarter, we have had patients from all three of those cohorts.
I think it bodes well for the future, but Europe is a very good baseline for us to build on.
Great. You talked about the MAA or potential MAA filing. How are you thinking about entering Europe and helping those patients with MIPLYFFA, especially in terms of commercial footprint versus partnering? What are you considering at this stage?
Yeah. So our focus is squarely on the MAA in the second half of this year. As we've mentioned before, a lot of the issues that the CHMP brought up were very similar to that of the CRL. We've made a lot of effort in regards to ensuring that we can answer those questions and then resulting in an FDA approval. We'll build on that information and provide it to the European authorities to allow them to know that the ultimate impact that MIPLYFFA in combination with Miglustat makes on the Niemann-Pick disease type C patient population is significant. We strongly believe that this is a product that is worthwhile approving in Europe. We are going to provide that additional data. As I mentioned also, we are now continuing to invest in our EAP program and expanding that EAP program within Europe.
We've gotten inbounds that we're able to now satisfy by this program. We've gone from 70-80 patients up to 85 now. We'll continue to invest in that. We'll also explore our go-to-market strategy in Europe. There's nothing off the table today. We will look at all of the avenues that we can take. Most importantly, we're investing today in understanding what that market looks like from a macro lens perspective, from a policy lens perspective, which in today's market, it is a changing policy and pricing and how pharmaceuticals are dealt with both the U.S. and abroad. It's a dynamic space for us right now. We're putting all that into the equation. We have enough time to be able to make a very good decision for both our patients to make sure that the patients are taken care of and our shareholders.
Great. Zevra is a lot more than just Miplyffa. I do want to just shift gears with, I think, the three minutes we have left here. Can you just talk about your other products and programs that you have and what success looks like for those?
Yeah. The other commercial product, I'll start there, is OLPRUVA, as I mentioned. It's approved for certain urea cycle disorders. Excuse me, where it's an ammonia scavenger, a nitrogen scavenger. That product came out of the chute a little slow. We moderated our expectations. We've actually pivoted our strategy at the end of Q3 last year to be able to go after really where the benefits of the product really resonate with the patients. Active patients that are looking for both the palatability, the portability, and the personalized dosing, which is the differentiation that OLPRUVA brings to the table. We announced a few weeks ago in our first quarter results that we had five enrollments exactly in the strategy in which we've been moving forward.
I think there's some optimism there for us that we're going to be able to continue to see that over the next few quarters around the strategy that we've put forward. We need some time, but making progress. The other product that we have that we also announced is that we reestablished enrollment at the end of Q3 last year around our Celiprolol program. As a reminder, Celiprolol is being developed for vascular Ehlers-Danlos syndrome, a devastating disease that is a collagen deficiency and genetic footprint is called 3A1 positive patients. You can have aortic aneurysms and dissections as well as hollow organ ruptures. We are now investing in driving the enrollment of that. It's a 150-patient two-to-one randomized trial that we now have 32 patients enrolled in the trial.
We're focusing our efforts into those centers who are taking care of already genetically diagnosed call 3A1 patients and allowing them to go to this decentralized trial. Decentralized trial sounds easy. You don't have physical sites and you're not managing a lot of different sites. You're managing one site. However, getting patients to actually drive to those sites and getting patients who are appropriate patients to drive to those sites does take a lot of effort. It's not as easy as it sounds. I think we've got the right prescription as we're now seeing some uptake in the enrollment.
Fantastic. I'm going to sneak one more in. What I'm not going to ask you is your cash runway. What I am going to ask you is, given how you've shored up your balance sheet of late, how do you think about capital deployment across the board? You've touched on the number of programs you have going on right now. Given your strong balance sheet, how do we think about Zevra deploying that capital over the next couple of years?
Yeah. Just so for clarity purposes, we announced on our earnings call that with our pro forma $217 million in cash in the bank, we have the ability to operate independent of the capital markets at this point, which we believe strongly in. That capital will allow us to be able to do the things that we're really focused on. One is the commercial launch of our two products, making sure that we do everything to get patients taken care of and commercializing those products. The last one is to make sure that we're investing into our Celiprolol program and maximizing the efforts there. Lastly, I think this is an area that we haven't talked a lot about previously because we needed to be focused on what we're doing. Our European filing is an important and significant future milestone for the company. We're executing on that.
Today, it's about executing what's in front of us today before we think about what we do next.
Great. It is a good position to be in. I am going to leave it there. I think we are out of time. Neil, thanks so much for joining us.
Appreciate having me.