Okay, thank you for joining us here today for our fireside chat with Neil McFarlane, the CEO of Zevra Therapeutics. So to start, Neil, maybe for those that don't know the story, tell us a little bit about your company, where you are now, and what your vision is for the next five to ten years.
Thanks, Louise, and thanks for having us. This is a great opportunity for us to talk about Zevra and where we're going. Zevra is a commercial-stage rare disease organization. We launched our first product earlier this year, OLPRUVA, for urea cycle disorders. We're in the process of a regulatory submission for arimoclomol right now, which is imminent, or I should say PDUFA date of September 21st . We have two pipeline programs, one in idiopathic hypersomnia and another one that is in vascular Ehlers-Danlos syndrome, and it's an exciting time for us.
Okay, great. So why don't we start at the top here? I guess we should talk about arimoclomol. So you're getting approved on Friday afternoon or Monday afternoon?
Well-
Falls on a Saturday, right? So-
The PDUFA date is September 21st.
Yeah.
When we'll see the, you know, potential approval from the agency usually is prior to the date, but we've also seen it past the date as well.
Okay. And from a communication perspective, are you gonna host a conference call once you hear a decision? Is it just gonna be a press release? You know, what are you thinking there?
Yeah, so we're planning for all of the above, so the answer is D. We have right now the opportunity, if approval comes early, to be able to host a call. Approval comes on time to be able to communicate via PR, and if it comes over a weekend, for us to be able to communicate. So we're planning for all of the above. It's gonna take the action from the agency for us to figure out which one of the planning cycles that we're in that we'll actually pull the trigger on. But it's our hope to be able to get information out to the public as soon as we possibly can.
Okay.
The sooner, the better.
Okay, great. I don't wanna trip any wires here, but I do wanna ask you, is there anything you can publicly disclose about your interactions with the agency? Obviously, you're, you know, right in front of your PDUFA date, so you've obviously must be speaking to them on a regular basis.
We are, and we mentioned on the end of our Q2 call that we had received our labeling from the agency within a week after our Advisory Committee. I can't talk about the labeling discussions, but those labeling discussions have been ongoing. I think one thing, though, that I feel very comfortable in saying is that the agency has a precedent to provide a label based on what you studied.
For us, you know, we studied arimoclomol versus placebo with underlying routine care that was stratified to miglustat or not miglustat when it came to 80% of the patients in routine care being on miglustat. So we feel very comfortable that our conversations, the advisory committee, what data has been shared, has all been right down the middle of the fairway in regards to receiving a label that really represents what we studied.
Okay. Do you have enough product to launch with? Why don't we start there?
One wonderful question. We do. We have enough product to launch with. We are in the process right now of obviously labeling discussions. How do we then get the appropriate carton and vial labels, or not vial in this bottle in this regard, bottle labels, and we believe that eight to 12 weeks post-launch, we'll be able to get drug in the channel.
Okay. And then in terms of patients that are on your expanded access program, both in the U.S. and outside the U.S., how many do you have? And is it wrong for me to think that within twelve months, those will turn into, you know, full commercial patients at whatever launch price you have, so you sort of have an established base of sales?
So let's separate the two because we are moving forward with a potential U.S. approval. In the U.S., we have about 70 expanded access program patients that are currently enrolled in our program. In Europe, we have about 70-80 of those patients. I think separating those patients from the U.S. patients is important. It is our goal to be able to transition our U.S. EAP patients within 12 months of approval. That comes with all of the work that our team has been doing over the last, you know, 6 months since we launched OLPRUVA. Getting the 14 of the sites in the U.S. that are enrolling our EAP program patients, letting them know that arimoclomol's PDUFA date is coming.
How do we ensure that we go from a ninety-day supply to a sixty-day supply, that allows patients and their family members to be able to get more frequent visits, that allows us to then help them with our patient services, activities that we have ongoing, to help them with that seamless transition from EAP to commercial product? But our goal is to make sure that we transition all of those patients who obviously fit within the labeling and we can support them through our patient services.
Okay, and this 12-month estimation is based on discussions you've had with payers. How are you coming to that 12 months?
No, we feel that's a good window for us to be able to transition EAP patients, know whether if you're a government pay patient or if you're, you know, a commercial payer, that we'd be able to establish even the smallest niche payer that has, you know, five million lives that they cover, that has an NDC block and all the other things that you see with launching of specialty products. We think we'd be able to overcome all of those potential challenges within 12 years and leave no patient left behind.
Okay, and how are you thinking about pricing, or how should we think about pricing? Like, what are the bookends here?
Yeah, great, great question. Funny, we get that a lot in terms of what the pricing is. And it really has to be dependent upon what our final label is. We are almost there. We're having these conversations, and like I said, I can't talk about the label, but the value proposition that we see for arimoclomol was really demonstrated in the clinical program. Again, routine care, which includes, you know, which included miglustat 80% of the time, arimoclomol versus placebo, and we still saw this beautiful, you know, separation of the curves when it came to disease progression when you're on arimoclomol with routine care. We're hopeful to be able to have a price point that allows us to be representative of the value that we bring on top of miglustat.
Okay, great. Can we talk a little bit about the market opportunity, what the standard of care is, and where you, you know, cover some unmet needs? So how many patients are there?
Yeah.
in the U.S.?
So from a prevalence perspective, we see about nine hundred patients in the U.S. In Europe, there are about a thousand patients. Recall, there is a product approved in Europe, so it's a little bit more mature. In the U.S., of those nine hundred patients, we see three hundred to three hundred and fifty of those patients with an ICD-9 code that's being treated with something. Of those three hundred to three hundred and fifty patients, we've got about seventy of those patients in our EAP program. So when we think about the opportunity to transition the EAP program patients, also recall there are about 40 centers of excellence in the U.S., about 14 of those are in our EAP program. So our goal is to be able to expand to the 350 very, very quickly.
But as part of this, when you have an approved product in a disease area, it's been my experience, and I think the experience of many people who are in the rare disease community, that you can educate and you can start to expand that base of treaters because you now have a product that people can utilize that allows them to get more experience and then broaden it out. So our goal would be to make the product available to everybody that you know within label that allows for arimoclomol to impact.
Okay, great. And what about those other six hundred patients that don't have codes? Are they not being treated, or how are they...?
Yeah, that's part of what we're gonna need to do as we move out, right?
Okay.
We know that from a prevalence perspective, that 600 patients are out there. We got to now figure out how to be able to educate physicians, get quicker diagnoses, make sure that in the differential of diagnoses that physicians have, whether or not they're looking at visceral symptomatology, psychiatric symptomatology, neurological symptomatology, that we're actually educating people to think about testing for Niemann-Pick C, identifying diagnosis, and treating it.
Okay, great. So let's talk about the 70 or 80 patients outside the U.S. What's the opportunity for you there?
Yeah. So I think it's important to rewind a little bit. The product for arimoclomol was originally submitted first in Europe. It was... The submission was retracted by the previous sponsor for a lot of the same reasons why we got a CRL in the United States: longer-term data, more confirmatory data, the ability to expand the randomized control trial into an OLE, so on and so forth. I think we've answered a lot of those questions with our favorable Advisory Committee. We've put forth a very robust package that we feel confident that we can now package this with a US approval and go back to Europe and allow them to check a lot of the boxes that we were not checking at the time.
Yeah.
Focus is important in what we do here. We've got to focus on getting a U.S. approval. Once we do that, you know, that's step one. Step two is, how do we then take this eCTD dossier that's so robust that, you know, knock on wood, allows us to get a U.S. approval to Europe and to European patients?
Okay. And then how-
Those 70-80 patients that you just talked about that are in the global EAP program.
Okay, got it. And then, how do you think about pricing in Europe versus the U.S.? Is it gonna be the same, different, lower?
First we need to get a label in order to be able to talk about pricing. But for the most part, European secondary launches usually don't demand the same pricing potential that we would have in the U.S., but I think we're a little far away from talking about pricing in Europe until we get the regulatory approach locked down.
Okay, great. And what is your patent protection and marketing exclusivity that you'll get upon approval of this product?
Yeah, so the IP will run out prior to the orphan exclusivity. So with orphan exclusivity, we think we have up to seven years for the program in the U.S., and then in Europe, likewise, we'll be able to tap into the orphan exclusivity as well.
Okay, got it. All right. Before we switch gears to... Oh, I do wanna ask you one more thing, the PRV. I did see actually a recent comp for that. How does that work?
Yeah, this is a challenging topic because when we think about PRVs, it's a government-run program that costs the government nothing.
Yeah.
But yet it becomes a hot topic every time the reauthorization bill comes up. Right now, it looks like I know there's ongoing legislation and conversations happening in a House bill that's trying to get in tomorrow.
Yeah.
But yet this reauthorization does right now expire on September thirtieth of this month. And for us, we believe, and I signed my name to a letter to Congress last week with 16 or 17 other pharma companies. We believe that this is an important tool for rare disease, pediatric patients, and small companies to be able to actually allow them to get this non-dilutive capital that investors look to, to having as part of their investment in the companies. But also, I think, it allows for other organizations, larger companies, to be able to take advantage of that accelerated pathway. For us, we will be eligible for a PRV with an approval.
As you may have seen, the supply and demand, and law of economics has showed up, and the last PRV sold a few weeks ago for $158 million, where they had been in the $100 million-$110 million range previously. So, our goal now that we've done a small financing a few weeks or last month, is that we have the opportunity and capital flexibility now to not make an immediate decision to execute on the PRV, and we can kind of watch and see what the market does. And if it demands a higher price, then we can capitalize on it. But we're in no rush at this point, I guess is what I the takeaway message.
We hope that it really does get reauthorized for the patient community.
Okay, and I just wonder if this is going to sunset, and it goes away, I hope it doesn't, then I guess the value of your PRV, do you think about that being worth a lot more? I mean, the-
We do. Yes-
From now, from here on, and-
Historically, that has been the case.
Yeah.
We've seen PRV sell in the $250 million dollar range, $300 million dollar range earlier in the, you know, 2015 timeframe. I think that flexibility that we would have in when to execute on it is really important.
Yeah.
So we'll stay tuned and see what transpires.
Got it. Okay. Before we move on to the rest of your assets and pipeline, wanted to see if anybody in the audience has questions on arimoclomol. Okay. All right, so we'll move on to OLPRUVA right now. So the commercial launch was started in January. How has it progressed relative to your expectations?
Yeah. So OLPRUVA, just to remind everybody, it was formally approved. I like to measure success of launches three ways. One, our commercial and medical folks able to get access, and in this environment in which we operate in today, access for our sales reps in centers is not always easy. We've been doing a really good job there.
We've been able to actually hit 90% of our call points in the first couple of quarters post-launch. That's a big deal, and I think it gives me a lot of confidence that that same sales force, which we've optimized for both OLPRUVA and arimoclomol's launch, is going to be able to do that for arimoclomol as well. The other one is market access. Are we able to actually get covered lives and at least allow us the ability to fight the good fight on behalf of patients in getting access? We took the program over. We were in market access range in the mid-40s%.
And in just a few quarters, we've been able to actually increase that market access coverage to 75% of covered lives, both on the commercial pay and on the government pay side of the house. The last area is in rare disease, activating patients and making sure that patients understand your product is there and are asking for your product and/or at least know that there's an optionality for your product, is an important determining factor in the launch. I think that last one is an area we have to do better.
We need to be able to go out and make sure that patients are aware that OLPRUVA was developed, you know, to mask the taste and the smell and provide an experience that's differentiated from other products on the marketplace, and we need to do a little bit more on the patient side. But on the first two areas, getting access in the centers of excellence and being able to find and call on those physicians, our team is doing an exceptional job and on coverage. It gives me a lot of really confidence that those two areas are what we're also going to need for arimoclomol.
The third area, in terms of patient awareness, the patient community for Niemann-Pick C is one of the most coordinated, supportive of each other and the patient community that I've ever seen. For the first time in my career, actually, we had a payer actually reach out to us to ask for a clinical presentation of Niemann-Pick C and arimoclomol because they've got a patient that reached out to them saying that, "Hey, we know this product's coming, and we'd like to have it on our plan." That doesn't happen very often. So that's a very, really a big difference between Niemann-Pick C and UCD today for us in the patient activation.
Okay, and how many sales reps do you have selling OLPRUVA, and what's the overlap between the doctor call point for OLPRUVA and for arimoclomol?
There's a high level of institutional overlap with these 40 centers of excellence, where we believe that we've got about 80% synergy between the Niemann-Pick C and the UCD call points. If we really take it down to a more granular level, we may call on a metabolic geneticist or a clinical geneticist on floor two at that center and push the button to floor three and go after the pediatric neurologist in that same center of excellence. So geographically, absolutely, there, high level of overlap. The other question you asked was?
How many do you have?
Oh, how many reps? Yes, thank you. We have about two dozen commercial folks, and commercial and medical affairs team members that are actually supporting all the products today. Half of them are internally, and half of them are split between sales and medical affairs. So we mirror sales and medical affairs, obviously doing two compliantly different jobs, but about a half a dozen a piece in the field.
Okay. And then I saw that you have this partnership with Orsini that you've announced. How does that help you with OLPRUVA?
We did. So this is part of the opportunity to learn as you're commercializing drugs. We inherited a specialty pharmacy that from Acer that, you know, was a good specialty pharmacy. That being said, we were able to, through our transition in launching a product, realize that we really need to focus on more hands-on patient services, ultra-rare disorders, expertise, and made the decision a month or a quarter into our launch that getting Orsini into place really made a lot of sense for us, not only for OLPRUVA, but as we work towards commercializing arimoclomol a nd getting it approved and servicing through the really the white glove service that you need to get for orphan disease patients.
Okay, got it. So before we move to KP1077, I wanted to ask the audience if anybody has any questions on OLPRUVA? Okay. All right, so switching gears to KP1077, can you explain what this product is to the audience, why it's special, and what kind of data have you shown so far for this?
Great. I realize that we got a couple more to hit, and the time is running short.
Yeah.
KP1077 is a program that was developed from one of the previous companies that collectively created Zevra, KemPharm, and it's a serdexmethylphenidate program. It's a prodrug of d-methylphenidate. The hypothesis is, for idiopathic hypersomnia, you can give a very high dose, up to 320 mg of serdexmethylphenidate at night, and then about 10 hours later, based on some of the data that we presented, you get a high level, which is at the time when you need to wake these patients up, and then you have a really nice PK curve during the rest of the day that keeps patients up. The reason why this is important in the idiopathic hypersomnia space is because the unmet need today for the IH space is sleep inertia.
That ability for patients to get up. They can sleep for really, really long periods of time and still not be able to feel refreshed, and/or get up. Alarm clocks, you know, shaking, what have you.
Our goal is, with this very simple hypothesis, which we've demonstrated—sorry—some phase II data at the end of Q2 at the Sleep Conference, that showed that, you know, in the SIVAS score, the Sleep Inertia Visual Analog Scale, and the IHSS score, in a newly created brain fog score, and the standard gold standard in ESS, it allowed us to show that, in the open label phase, where all patients were getting drugged, that we could get them into a place that allows us to now go to the end of phase II meeting, this month, in the next couple of weeks, to actually inform the design of our phase III program in IH, that would bring a differentiated product to market that not a lot of the competition is looking at today.
Okay, got it. And what do you say to the bears that say that despite your mechanism of action, you're just another stimulant?
Yeah. Well, I think that the mechanistic nature of how serdexmethylphenidate works as a prodrug allows us to do something that not a lot of... no other stimulant can do which is giving 320 mg of a stimulant at night before you go to bed. And this prodrug technology that allows for this release of the prodrug, obviously, first pass effect and all of those, that gets you that 10 hours later, which is some of the data that we showed at Sleep. 10 hours later, you get a nice dose response that allows you to get up, that sleep inertia.
So the differentiation that we bring with the prodrug technology, you just can't get with giving, you know, immediate-release stimulants.
Okay, and then just a quick question, because I do want to get to a couple of other products here. You know, how do you think about this versus other drugs that are in development or those that are approved, and are you looking at this for narcolepsy also?
So we did do a phase I study in narcolepsy. Part of the data that we got out of our phase II study with idiopathic hypersomnia, we presented at Sleep, really allows us to say: How can we move this program forward in a clinically differentiated way to get a phase III? You know, our hope is that we get a small number of patients, a single trial and all of the things that we're hopeful to be able to do in a rare disease patient population. But it also helps to inform whether or not we should be moving forward in narcolepsy. So we've got to get through this end of phase II meeting, answer some of those questions, and understand how we can move forward.
Okay, got it. All right, so you have a product, celiprolol, for vEDS. Can you tell us more about that product, what the opportunity is for you there, and how did you come across this product?
Let me start at the end and see if I can work my way back quickly.
Okay.
Vascular Ehlers-Danlos syndrome is a rare collagen disorder that leads to stiffness of basically hollow organs and vessels. Usually, these patients will get dissections or aneurysms, or they'll burst a colon or a liver or what have you, and pass away. Celiprolol is a selective adrenergic receptor blocker that allows you to be able to not get the shear forces that you get in vasculature and allows you for some flexibility in terms of mean arterial pressure and so on and so forth. I won't get into a lot of the specifics. I realize we got four minutes left. The standard of care in a lot of European countries is actually celiprolol.
And the previous company, Acer, that we acquired the product from, had actually done a paper filing to try and get the BBEST study, which showed about a 76% response rate with celiprolol across the US. It did not get through. There was a CRL. However, the current program that's being done under a SPA in a phase III program, single phase III program, is actually being run in a decentralized fashion.
Previous sponsors started the trial. They got 17 patients of 150 patients enrolled and then ran into resource constraints. As part of our preliminary evaluation of the program and the ability for us to actually understand what is the pent-up demand, are these patients there, we decided to reopen enrollment in the trial. We have been pleasantly surprised in regards to the screening, number of screenings that are happening. That's got to now turn itself into randomized patients that are actually enrolled in the trial. We're gonna know in the next couple of months as to what that demand is and to understand whether or not we've got a program that's worthwhile investing in on our own, or something that may actually be better in the hands of somebody else.
Okay, got it. So last but not least, AZSTARYS. What's the latest on that product? How are you thinking about the future sales of this? Is this more of a sort of non-dilutive way of funding the rest of your business, or do you actually see prospects in this opportunity for you?
Right. So AZSTARYS is commercialized by a partner in Corium that we have. Very pleased with the partnership. They are in the process of new management that we feel is a great opportunity to continue to drive the AZSTARYS program, and that's for ADHD. But we receive royalties and milestones. We don't have a lot of control over the you know day-to-day operations, but we're very pleased with what they've done so far and the continued growth in the program.
Okay, great. Two minutes left here. Any questions from the audience? All right, I have one question left for you. How much cash do you have, and how long will it last you?
So we had a pro forma cash balance of $113.8 million after a very modest raise that we did last month, which we felt would provide us the flexibility to be able to, as we mentioned about the, the PRV earlier on, do we have to monetize it? Can we wait to see what happens? The ability for us to be able to capitalize on our pipeline, if in the event that we see that we can really double down and accelerate enrollment in celiprolol and get that program moving, or if we get an end of phase II meeting that says, "Hey, you can do your small trial," that allows you to be able to go after a label in IH. We're very well funded.
That $113.8 million gets into the Q1 of 2027.
Yeah.
That's without AZSTARYS... Sorry, that's without arimoclomol revenue and no PRV. We're well capitalized. We feel like the optionality that the small raises has allowed us is a big asset at this juncture when we have all these catalysts that are coming in the next, let's call it, you know, three months.
Okay, great. Thank you very much, Neil. This is wonderful. Thank you to the audience for joining, and we're looking forward to some great news on Friday.
Thank you.