Thank you again for everybody for joining us at the Citizens JMP Life Sciences Conference. Excited to be joined next by Zevra Therapeutics, and CEO Neil McFarlane. Zevra is a company that is focused now on rare diseases, so, a lot of exciting things going on. Look forward to the presentation. Thanks, Neil.
Thanks, Jason. Appreciate you having us. I want to start off by stating that I'm going to be making some forward-looking statements, so I'd ask everybody to take a look at our most recent filing, online. It's been quite a journey. We are becoming a leading rare disease company by focusing our efforts right now on going from a number of previous organizations under one umbrella with an experienced team of rare disease experts. A commercial excellence that is allowing us to be able to move ourselves forward, and growing a pipeline of new products.
So earlier this year, we actually made the journey of going from a development phase organization to a commercial stage organization, and launching our first product in January, to having a PDUFA that's coming up in September, to having phase II data that came out a few months ago. And now also embarking on an additional phase III program, all in the rare disease space, with the end goal of becoming a leading rare disease company, and bringing some life-changing therapies to patients with rare diseases. That comes off the back of a team that is got a lot of deep expertise in the rare disease space. You see some of these names here, the Genzymes, the BioMarins of the world.
The team that's been assembled here have launched a number of products in the rare disease space, and this expertise that we're building in the organization, I think it'll take us both from the development expertise as well as the commercial expertise, as I talk about going into the partnerships we have. We're doing this not just with a team, but we're doing this by leveraging the infrastructure of the advocacy organizations in the rare disease space. Some of the names you see here are some of the brands of patient organizations that, quite frankly, have spent their entire lives to be able to try and not only diagnose patients with rare diseases, but also help to then get these products through development, and then start to commercialize and support the commercialization of products.
I'll spend a little bit of time on this slide here. We've got a diversified portfolio, and that's both with a commercial product in Olpruva, that is for urea cycle disorders. We launched that at the end of January, fully in the United States. We have arimoclomol, that is, currently in the agency with a PDUFA of September 21st, for Niemann-Pick disease type C. We announced on our earnings call last week that, part of the acquisition of our Acer Therapeutics acquisition at the end of last year, that brought us Olpruva. There was an additional phase III asset that had enrolled patients under a SPA with celiprolol for vascular Ehlers-Danlos syndrome, that we, we've actually now, restarted enrollment.
The KP1077 program is an in-house program that we developed at Zevra, and is being developed for idiopathic hypersomnia. We had our Phase II trial complete, and data that will be presented at Sleep 2024 in early June. In parallel, we're moving forward with an end of Phase II meeting in Q3 this year, while we bring this data through the advisors, both on the patient side, as well as on the healthcare professionals side, between now and then. And we're also exploring additional potential for KP1077, with narcolepsy and other sleep disorders.
Underneath all of that, we actually developed and have licensed out AZSTARYS, which is a product of serdexmethylphenidate and dexmethylphenidate, that is being currently commercialized by a partner in Corium, that they're doing a great job in doing that for ADHD, and we receive royalties and milestones from them. So what you see here is a company that is quickly gone from a late stage development organization to a commercial organization with one focus, and it's in the rare disease space. I'm gonna talk a little bit about our commercial path here, and our goal to becoming a commercial excellence organization. It really starts in the rare disease space, of having the ability to have depth of our sales specialists, which we did.
We hired sales specialists to launch Olpruva, which I'll talk about in a moment, which also has a direct overlap with our arimoclomol organization that, with an approval, we'll be able to leverage. But we actually hired individuals who have 20- and 30-year experience in the centers of excellence across the United States, along with the patient reimbursement services, the marketing team, the account management team, who've made a lot of progress. We'll talk a little bit more about in a minute. And then layer that with a medical affairs and patient advocacy organization in this ultra-rare space that makes all the difference to becoming a successful organization. So this commercial product that we have on the market today, Olpruva, it's a nitrogen scavenger.
I'll talk a little bit about urea cycle disorders, which it is approved for, which are about six enzymes and a couple of transporters, and a few of those enzymes that break down nitrogen and also break down the byproducts of protein. If you have a problem with one of these enzymes, you actually get to a place where you get excess ammonia levels in the bloodstream, and which can lead to hyperammonemic crises that allow for patients to actually have hospitalizations, emergency room visits, and a coma, and also can die from it.... This is an orphan indication.
There are approximately 1 in 100,000 in U.S. prevalence, which relates to about, well, sorry, it doesn't relate to, but in the U.S. today, we have about 1,100 patients diagnosed, and greater than 800 of these patients that are treated today. About 80% of the patients that are treated today have mutations of kind of three or four common enzymes, CPS, OTC, or AS.
The unmet need today, although all phenylbutyrates that are on the market today actually work the same way as a nitrogen scavenger and are approved to treat certain UCDs, the palatability of some of these agents, the odor, the route of administration, and how they're packaged leads to about 25% of the 1,100 patients who go on to having these hyperammonemic crises and end up in the emergency room. So those stem from poor adherence. And some of those challenges were exactly why Olpruva was developed. It's a unique formulation of a product that is a single-dose envelope that is a dual-coated formulation that actually allows for the masking of the taste as it... and how it was formulated.
There are other phenylbutyrates on the market today, that have this, you know, vile odor, vile type of odor, or, they're an oily substance to take, or quite frankly, with some of the capsules, people can have to take up to 40 capsules a day in order to be able to get the same benefits. So when we brought Olpruva to market, the better palatability, the less odor, the ease of administration, and the patent protection that we have allows for a clinically differentiated profile to be brought into this area, where you still get this non-compliance. Again, 25% of the patients, of those 1,100, that still have these non-compliance. We believe that Olpruva is well-situated to be able to provide patients and physicians with an option.
The current market today is about $350 million. It is dominated by one player. But we believe that with OLPRUVA in the marketplace today, it allows us to be able to penetrate that 25% of all these patients that are still not being treated or not being compliant. Let me move quickly to our pipeline. We have a program that's currently our lead program, as I mentioned before, that's got a PDUFA date of September 21st in Niemann-Pick disease type C. Niemann-Pick disease type C, or NPC, is a lysosomal storage disease that basically cholesterol builds up in the cell, where cholesterol is heavily based in the brain and in other areas of large organs, like the liver and the spleen.
These NPC1 genetic malformations or NPC2 gene malformations leads to this progressive lipid accumulation in the body that leads to cellular impairment, cell death, ultimately these organ dysfunctions, but in the brain, also relates to cognitive challenges, speech challenges, swallowing challenges, fine motor skills, and ambulation. Heterogeneous in how it is presented. Early patients that are diagnosed early in life can have failure to thrive and other areas you can imagine with liver challenges. As you move forward, they can actually turn out to be cognitive challenges in the teenage and adult years. But the ultra-rare components that you see here have a prevalence of 1,800 patients between the U.S. and Europe, about 900 of those patients in the U.S.
Approximately 300-350 of those patients in the U.S. are being treated with some type of symptomatic control of this heterogeneous disease, but there's a significant unmet need. These patients have decline year over year. It's irreversible, it's fatal. The mean age of death in these patients is 13 years old, and there's no approved treatments in the U.S. Arimoclomol is poised to be a first-in-class oral treatment. It has been studied in a number of other disease areas, where over 600 patients have been treated in those other disease areas.
We have about 200 of those patients that have actually been treated in Niemann-Pick disease type C, with long-term data, ongoing, expanded access program that has about 150 patients treated between the U.S. and Europe, with up to over 4 years of data. Some patients actually, that were in the original, trial, went into open label, went into the expanded access, and over 6 years of treatment today, and continuing. This is an orphan disease, as I mentioned previously, with only about 900 patients in the U.S., and, it's got all of the appropriate regulatory designations, Fast Track, Breakthrough Therapy. It is in the agency today with an approval. Would also come with a priority review voucher, estimated today of about $100 million. Moving to our next program, it is vascular Ehlers-Danlos syndrome.
As I mentioned previously, we brought this program in with our Acer acquisition. This is a connective tissue disorder that leads to vascular ruptures. Maybe I'll just talk about this a little bit in a moment here. VEDS is a disease that is actually a COL3A1 gene dysfunction that allows for stiffness and lack of collagen flexibility in the vessels, that then leads to vascular ruptures and of the large to medium-sized arteries, as well as hollow organs, and the GI and urine as well, that can lead to ruptures. The median survival age of these patients is about 51 years old, and I think it's an important perspective for us. There's no approved treatments for this in the United States.
Events occur in 25% of patients before the age of 20, and about 90% of these events happen by the age of 40. This is a disease that has about 7,500 diagnosed patients in the United States today. No approved options. Celiprolol is a selective adrenergic modulator, and it actually allows for smooth muscle relaxation and vascular dilation in the vessels that are affected, and it may actually reduce mechanical stress inside these vessel walls as you get the pulsations of arterial pressure. It's actually been studied in Europe and in the clinical experience for a number of years. It is actually the standard of care in certain European countries today, but it's never actually come to the U.S.
The BBEST clinical study had about a 76% reduction in arterial events observed in this COL3A1 population. Through the development of trying to get a paper filing through the agency, the agency has actually helped us to move forward through a SPA that allows us to be able to move forward with this study. There are about 17 patients that have been enrolled previous to our taking it over, and now we've done our preliminary assessment and and decided that this is worthwhile preserving the value by continuing the enrollment in this study and moving it along. Solid intellectual property and a phase 3 study ongoing today. Idiopathic hypersomnia is our phase 2 program that is a sleep disorder. It is a that causes excessive daytime sleepiness, sleep inertia, and brain fog.
A lot of what you see in the other sleep disorders, but idiopathic hypersomnia really has a large unmet need in this sleep inertia component. Sleep inertia is when you just can't get up, and these patients have some real challenges, and it's debilitating, unknown pathophysiology. Sleep inertia becomes an unmet part of this sleep disorder that really challenges patients. I was on an advisory board just a week ago, with patients and these patients have a hard time keeping their jobs. They have a hard time going to school. It is an incredibly challenging disease. The unmet need here is large as well. The incidence is about 10.3 per 10,000 patients in the U.S., with a prevalence that's about 37,000 patients. The total population may be larger.
There's a lot of diagnostic challenges between certain narcolepsies, as well as idiopathic hypersomnia. There's some diagnostic challenges for physicians. The current treatments don't continue to not address the needs. If we did some patient work, and they rate their current medications' effectiveness as a 5.4 out of ten. And I think that if you talk to these patients, they would tell you that the challenges that they have in sleep inertia become more and more challenging because the products that they're on today seem to work for a while, and then they just stop working.
There are inadequate treatments today, comorbidities that are out there with cardiovascular and in certain patient demographics, drug-drug interactions in the younger, patients with contraceptives, antidepressants, antihistamines are the current therapies that are out there today. KP1077 is a unique prodrug PK profile of a product, that I actually talked to you about briefly earlier on. It is a main ingredient in AZSTARYS, which is serdexmethylphenidate. It is, this proprietary prodrug, as I mentioned, that has potential to address primary IH symptoms. Two dosing regimens were being explored in our phase II study. One was to be able to provide a very high level of serdexmethylphenidate once at bedtime, and then actually split that dose into once at bedtime, and then actually also providing, the second dose, in the morning.
The full data package will be provided at the Sleep 2024 meeting next month. But this ability for you to be able to get a very high level of a stimulant at night, that then has this beautiful PK profile, where you are able to get high levels in the morning when you need to wake, that then releases slowly during the day to provide you the ability to stay awake, really addresses both the sleep inertia components of the challenges of getting awake with a high level of a stimulant, on board in the morning when you need to get up. And then also providing you with the ability to continue to overcome your excessive daytime sleepiness, which is also a very large part of idiopathic hypersomnia. The profile of this product, we believe, can overcome these key symptoms.
However, it also comes with some of the work that we've done so far in the tolerability, lower cardiovascular effects that we've seen with some of the data that's been presented, and then a lower threshold of drug-drug interactions on some of the key drugs that are taken in this patient population with hormonal contraceptives, antidepressants, and the like. We do have orphan drug designation, solid IP, as well as, I think one of the key areas that we continue to hear from physicians is schedule, you know, the ability to get a Schedule II product versus a Schedule IV product in the U.S. has that less abuse potential, and today, SDX is designated as a Schedule IV.
We've got our top-line data out, as I mentioned, that came out a few weeks ago or a few months ago, I should say now, where we saw clinically meaningful benefits across the ESS, the IHSS, and certain brain fog scales that allow us to be able to then move forward with a Phase III. And we're planning an end of Phase II meeting in Q3. So let me stop here so I can open up for a few questions, Jason. We're focused in four key pillars of growth. We've got a rare disease team with strong experience that's delivering today for our current product.
We've got Olpruva, that is now on the market. We're utilizing that exact same infrastructure to be able to prepare for arimoclomol's launch. We're growing our pipeline with this PDUFA, September 21st, celiprolol and their ongoing phase III program. KP1077 with the phase II trial, that is complete now, with the full data package coming next month, and planning for an end of phase II meeting in Q3 2024. Underpinning all of this, we just refinanced and have a debt facility that was closed last month for $100 million, of which we've taken down $60 million, to extend our maturity and provide us with cash and cash equivalents going out to into 2026.
With that, I wanna thank you for your attention, and look forward to answer some questions.
Great. Thank you, Neil. I'll kick it off. Maybe starting with arimoclomol, can you just walk us through the regulatory history here, and, you know, whether you expect or what your view is in terms of a potential advisory committee before the PDUFA?
Great. So yes, let me answer the last question first. When we got our PDUFA date back in January of this year, the original PDUFA date, the FDA stated that they intended to put the program into an advisory committee. Part of the communications with the agency, we actually had information requests that came through, that then extended the PDUFA from June 21st to September 21st, and that three-month extension, they did also reiterate that they intend to actually bring us to an advisory committee. We have been preparing for that advisory committee since prior to actually submitting, resubmitting, our NDA, and feel good about our thorough preparation. Let me take a step back. The product had a CRL about two years ago, that were focused in three areas.
One was in the scale, the NPC-CCSS, the Niemann-Pick C Severity Scale. It's a five-domain scale. There were one of the domains in cognition was taken out as part of the conversations with the agency, and the swallowing score was rescored. We've done that work, and the same results, we got the same results. The other one was in regards to what to do with some missing data. We were able to actually work with the agency to get an FDA preferred analysis. That analysis has been completed, as well, reinforced the data that was originally presented. The last part in any rare disease program that you develop with a single efficacy trial, you know, of the ability to provide additional confirmatory evidence, is an important component of this.
And that's an area where we had to actually go back and do some additional pre-clinical work, to be able to tell the story of the non-clinical to the clinical data, that were actually matured quite a bit from the initial filing prior to the CRL in the expanded access program, the natural history data, and then actually aligning that directly into the phase III trial results. We were able to pull that together, and also respond back to the agency. We've clearly answered those questions, they've given us a PDUFA date, and the robustness of the package, you know, provided the agency to have an extension, and we look forward to being able to, if an AdCom comes, presenting that package.
One of the important things also in these rare disease areas is that the patient community, as I mentioned in the second slide, is really important. The Niemann-Pick C community came together under the NNPDF's umbrella and actually put together an informal petition to the FDA that had almost 1,000 signatures in support of arimoclomol's review with the agency. And we feel actually honored to be able to have that kind of support for the program.
Great. And then just a commercial question, how should we think about gauging success in the launch of Olpruva in the second half of the year? And then second to that, when you think about the potential of adding arimoclomol into the commercial fold, later this year, what leverage do you have from the current commercial organization, and/or what do you think you need to add?
Great. So yeah, since November, when we closed the transaction, we actually set up our entire field-facing infrastructure, as I mentioned in one of the earlier slides. Our sales reps we hired had deep rare disease expertise in the 40 centers of excellence, and those metabolic and genetic centers of excellence, that kind of make up the vast majority of where our call point is for Olpruva. The call point for arimoclomol is 100% overlap.
Yeah.
our ability to be able to pull forward the investment for arimoclomol, and actually work through the bugs, if you will, of commercializing Olpruva, puts us in a really good place. As a matter of fact, at the SIMD meeting that came up last month, our medical affairs team had the opportunity to engage with both Niemann-Pick C, as well as UCD physicians. That allowed for a lot of cross-pollination in terms of what we could do to elevate the awareness to physicians for Olpruva as well as now in UCD, and what the potential of arimoclomol may be.
Great.
Then I think I didn't answer your first question, which was... Now I'm forgetting my first-
Okay, so.
Well, so-
First, oh! It was gauge success.
Yes
... of the Olpruva launch. It just came to me. You know, I have to tell you that we announced our numbers last week. We had four new patients that came on board in Q1, and two patient request forms that came in. And I think the biggest gauge for us right now, and what gives us a lot of confidence in moving forward, is that the infrastructure that we put forth was able to actually engage with over 90% of our target audience at those 40 centers of excellence in that first few months of launch.
That just further validates to us that we've got the right people on the ground to be able to execute, not only for Olpruva, but also with the potential of arimoclomol coming in to the organization as well.
Got it. I know I'm gonna squeeze one more in quickly. KP1077, obviously data come in in a couple weeks here at Sleep. What are the key things that we should be looking for in that data set as we think about, you know, informing the next development steps?
Yeah, so you know, we actually announced the qualitative data-
Right
... a few weeks back, and we talked about the clinical meaningfulness of the data, both in excessive daytime sleepiness, and IHSS, and some of the brain fog scales that are in there as well. So I think that informing our phase 3, we checked the box. We had safety and tolerability, checked the box. You got the very high levels of stimulant utilization, and didn't see the effects that you might see. So for us, it's about how to inform a phase 3, and the numerical data will come out at Sleep. But we don't think that data changes anything for us in terms of moving forward with our end of phase 2 meeting in Q3.
Got it. Great. Thank you, Neil. Really appreciate you being here with us this afternoon.
Thanks, Jason.