ZVRA - NASDAQ

Good afternoon, and thank you for joining

Thank you, and welcome to those who are joining us. Today, we will provide an overview of our accomplishments in the fourth quarter and full year of 2024, followed by a review of financial results. I encourage you to read our financial results news release, which we distributed this afternoon, and is available in the Investors section of our website. Before we begin, please note that certain information shared today will include forward-looking statements. Actual results may differ materially from those stated or implied by any forward-looking statements due to risks and uncertainties associated with

Thank you, Nichol, and thank you for joining us this afternoon. As Nichol mentioned today, we'll provide our fourth quarter and fiscal year 2024 financial results, and share progress on the execution of our priorities for 2025. Our priorities are guided by

Thank you, Neil. 2024 was a year of significant milestones for

Thank you, Josh and good afternoon, everyone. In addition to the financial details included in today's call, we encourage you to refer to

Thank you. [Operator Instructions] We'll take our first question from Kristen Kluska with Cantor. Please go ahead.

Hi everyone. Congrats on a really strong start out of the gate, especially around the holidays, I think speaks to how much these patients really wanted that therapy. So congratulations. A few questions from me. I think this is the first time that you've provided us more space specific guidance on the European filing timeline. So can you give us, a sense of the last dialogue that you had with the agency there, and the plan. And then, when we think about the European market, which is more mature partially due to the fact that miglustat's been there for over a decade. How do you think that drug becoming available in use, for patients will - and how that identified more patients over time can translate to some of the efforts in the U.S. now that you have the approval there?

Thanks Kristen, and thanks for the comments. It's been a great 2024, and transformational for sure. But as we mentioned in the remarks, the prepared remarks, bringing MIPLYFFA for the patients with Niemann-Pick is definitely a crowning achievement. Let me quickly touch base on a little bit of the market dynamics for Europe, and then I'll ask Adrian, to talk a little bit about - briefly about our regulatory interactions. In Europe, we see about 1,100 patients in Europe based on a prevalence number and miglustat has been approved there for well over a decade. So our current label in the U.S. and we are still working through what this filing would look like in for our MAA in Europe, as you know, have MIPLYFFA and miglustat in combination, in order to be able to halt progression of the disease versus miglustat alone having an approximate two point progression over 12 months, based on our clinical study. So based on the fact that there has been miglustat in the market, we believe the European market is more mature, there are more patients diagnosed and treated, because of decades worth of work that has been done, and now bringing a product that has the potential in Europe under the MAA filing, to actually halt the progression of the disease. Based on the label that we have and the data we had in our Phase 3 program, we feel like this is a great opportunity to go after in Europe. In regards to the European filing, probably not ready to talk too much about all of the intricacies of the European filing, but to be able to state that 2020, for the second half of 2025, we believe that we're going to be able to file. Adrian, you want to talk a little bit about our last interactions?

Yes. The last interaction with the EMA, obviously [happened via authors], about four years ago when we reviewed the application. Based upon the complete response letter that we received from the FDA, and some of the comments that were received from the EMA in regards to the filing that we had in Europe. We're now obviously in a much better position with long-term data available. We are currently consulting with corporate consultancy group to, how to specifically address some of the things that they had during the original filing. And as said, we are planning to file in the second half of this year. We're confident that, the filing will be accepted by EMA.

Okay. Thanks. And then thanks for providing the cash runway guidance, which I understand excludes the PRV for now, but can you just maybe high level give us a sense of like how conservative, are you being with launch - projections into this? Does this include, if you do get an approval in Europe, adding that territory there? Just any high level would be really helpful? Thank you again.

Yes, of course. Yes, we did not include the PRV proceeds to yourself. And I would just say we have been conservative, as we looked at that cash runway. We have to continue executing and continue into '25 with the plans that Josh and the team have got in place. And so that's definitely where our focus is. But yes, it is safe to call that a conservative, appropriate conservative estimate.

Thanks everyone.

Thank you. We'll next go to Jason Butler with Citizens JMP. Please go ahead.

Hi, thanks for taking those questions, and let me add my congrats on the quarter as well. Great start to the MIPLYFFA launch. Can you maybe give us any more quantitative color on the MIPLYFFA sales during the quarter in terms of the supply amounts to the specialty pharmacies, or what proportion of patients got a refill. And then my second question is, how should we think about the long-term here in terms of net patient ads? You've obviously successfully converted the EAP patients, but should we expect consistent steady net patient adds, or could it be more volatile from month-to-month? Thank you.

Yes, Jason, I'm going to see if I can parse that to LaDuane, to be able to answer the original questions around inventory. And we're not going to get into specifics, but he'll be able to answer that. And then we'll hand it off to Josh, to be able to talk a little bit about, this boldness of patients that we've seen, and what the future may look like. LaDuane?

Yes. So with MIPLYFFA revenue, again, we reported $10.1 million in Q4 that, would have included product to handle the initial patient dispenses. Some early enrollees may have received a second refill late in December. And then, we did allow for an appropriate level of stock, to continue to service patients. It's actually at the target level that we would expect to maintain at this point. And so, Josh, I'll turn it to you.

Yes, Jason, your question about new patients going forward. I think it's really important for us, to kind of reflect on how quickly we were able to get to 109 patients, and how quickly we were able specifically to convert those patients, who were in our expanded access program to enroll into MIPLYFFA. So we had all those patients, plus some patients who had previously not been exposed to MIPLYFFA, all within the fourth quarter. And so, we were really pleased with how quickly we were able to do that. I think it speaks to the demand that there is in the marketplace. I think it also speaks to the execution of the team. And as we look forward into 2025, our focus now is really to be able to find those patients, who have been diagnosed, but aren't currently treated as well as those patients, who have not yet been diagnosed. And so that's really going to be the focus, as we continue into this year.

Great. Thank you.

Next, we'll take our next question from Sumant Kulkarni with Canaccord. Please go ahead.

Good afternoon. Great to see all the progress, and thanks for taking our questions. My first one, is a bit of a follow-up on the last question in terms of your sequential delta and patient enrollment forms from MIPLYFFA that was 19 what are the key variables that we should keep in mind that might influence this trajectory, as we look to the next quarter versus this one?

You're absolutely right. We went from, excuse me, 90 at the end of October to 109 at the end of December. Again, this really reflects many of these patients were really sort of queued up, ready to go from our exposure expanded access program. As we move forward into this quarter, as I just mentioned, we're really focused on trying to expand beyond those expanded access – sites, to where we know that these patients are being treated, have been diagnosed. And we're going to continue to deploy our sales teams into those offices, as we continue to on each of these quarters, we'll be providing enrollment numbers, percent of covered lives and net revenue. And you can expect that we'll continue to do that as we move forward into subsequent quarters.

Yes, Sumant, it's Neil here. I think it's important as we try to answer this question, with a follow-up also to the previous analyst questions as well. When we talked about the transition of our EAP patients, traditionally we would see that over about a 12-month period. And the team, based on all of the work they did prior to launch, into launch and then a combination have been able to exceed every expectation, we had internally on the conversion of those EAP patients, not over a 12-month period, but actually over a one quarter period. And I think that's a true testament, as we mentioned previously, to the built up demand as well as the unmet need in this patient population. So as we go through this trajectory and it has been a rocket ship trajectory, we expect that over the next phase of launch, for us to be able to then take this momentum into Q1, into Q2, executing on all of the tactics and the phased approach that Josh mentioned in his prepared remarks. So, I think there's an important perspective here for us, to be able to show that this has been an outstanding performance on the conversion, and on the launch trajectory. We now are going to take this into executing Phase 2.

That's a point well-made and taken. So on the 300 to 350 or so diagnosed and treated patients with NPC, roughly how many are treated at centers of excellence versus not?

Yes but, many of these patients have some diagnosis that takes place at these centers of excellence. But keep in mind there had previously been no treatments approved for Niemann-Pick. So many of these patients would be diagnosed, and then go back to their local neurologist to. We're finding now that those patients are coming back, to these centers of excellence as they're made aware of MIPLYFFA being approved. And so the vast majority of them have some connection, either being treated at the centers of excellence, or some sort of referral to the centers of excellence.

And last one, before I hop into the queue back on OLPRUVA, roughly how many quarters are you giving yourselves with the new patient targeting strategy, to see a potential inflection?

Yes, we haven't really put any timeframe on that. We know that OLPRUVA can provide benefit to patients. We have revised our strategy, to be able to bring that to specific patients, who will benefit from the portability and the personalized dose. And these are the adult patients, and in particular those - where there's some reimbursement challenges. So we're continuing to - monitor this. It's early in kind of assessing the impact of that. But we also know that there's great synergy within our sales team, within our broader commercial team, in having both of these products. It's opening a lot of doors for MIPLYFFA. It's allowing us to foster relationships across the entire commercial spectrum. So we're watching this very closely, and we're allowing some time to see the impact of this change in our strategy.

Thanks.

We'll take our next question from Oren Livnat with H.C. Wainwright. Please go ahead.

Thanks. I have a couple on MIPLYFFA. Can you just characterize that initial bolus of 90 patient referrals that came in really fast in that first month? Did you get the lion's share of NPC patients in a concentrated group of centers? And so now you're more gradually expanding to a broader set of treaters and centers to penetrate those? Or was that 90, including, I guess, just a fraction of the patients at a broader set of sites, if you understand my question. Just trying to figure out, like, what the heavy lifting is here going forward. And also I think on the last call you had mentioned that 30% of those initial 90 had already been "approved" which is really fast in the first month, either, I assume, via some formal coverage, or more likely, medical exemption. Do you have any updates on those percentages for the initial wave, continuing approval rate or the cumulative approval rate for this entire 109 through December? And I do have a follow-up?

Yes. So I'll take your question about the 90. So, as we reported in our last call, of those 90, 69 of them were from the Expanded Access Program, and 21 were from other sites that were naive to MIPLYFFA had not previously received MIPLYFFA. Majority of those patients were still treated within one of those centers of excellence. As we've moved forward now to 109, we've gotten the remainder of those EAP patients. We have also expanded beyond the centers of excellence, to find other prescribers and patients. And we're going to continue to do that as we move into this next phase of launch. Your second question was around the percent of patients that had received authorization for payment, and at the time of our last call, it was 30%. We're continuing to see improvement in that. And what we're seeing is that many commercial payers have not yet made decisions around policy, but the vast majority of our patients are able to get reimbursed either through direct formulary, or through a medical acceptance. Our team is out in front of these payers talking about the clinical benefits of MIPLYFFA, sharing with them the new data that's been generated since the approval. And so, we expect that's going to continue to improve, as we move down the launch.

And as you have these reimbursement conversations, can you just maybe give us more color on, how that's going if there's any pushback? It's obviously ultra-rare, so I would assume that's somewhat limited, but obviously we're talking about both two expensive drugs in combination, so just maybe a little more color there. And are you able to give us a sense of what your, I guess, average net dollar per patient per year, expectation is going forward?

So in terms of the conversations that we're having with payers right now, we are really getting in there, and we're talking about the benefits that MIPLYFFA offers to these patients. We're talking about the halting of progression of disease after 12 months. We are the only product that has been approved, with based on a clinically meaningful endpoint, and the 2.1 improvement in that endpoint. So that's really where the conversations are taking us, and we're continuing to drive that message home. And as I mentioned, most of these patients are getting covered either through formulary, or through some sort of medical exception process. And that's really continuing. So that's really the tone. A lot of additional doors are being opened, for continued clinical conversations, as it relates to the net pricing. I'm going to turn that over to LaDuane here.

Yes, Oren, I would just say we don't generally discuss, or comment too much on the gross to net details. But at this point in time, I would say our strategy is still underway in terms of how we get the data story in front of payers, it's not clear yet if we need to even be that aggressive in that concept. So I think, it's early days there. But I expect that gross to net is going to be. We're going to have. I'm sorry, gross to net is going to be in a solid place, and I don't expect we'll be very aggressive there at this point.

Okay. Thank you so much.

Our next question comes from Sami Corwin with William Blair. Please go ahead.

Hi there. Congrats on the great quarter, and thank you for taking our question. I guess, I was curious what the average time you're kind of seeing from the start enrollment form to the approval of reimbursement, and then after kind of thinking about expanding your targeted population, and going beyond the 300 to 350 patients that are currently seeking treatment, I guess to what extent do you think you can further expand that and penetrate into the estimated 900 patient population? Thank you.

Hi, Sami, it's Neil. I'm going to kick this one off, because I think we're really pleased so far with what we've seen, not just in those patients who were diagnosed, but in our prepared remarks, we talked about the fact that one of the areas we've been investing in has been media. And those three patients that we talked about, were actually patients who were diagnosed, but not treated. And this gets back down, to this expanding the market population. And we believe that as we continue to get a treatment in the market, and multiple treatments in the market, for that matter, physicians that actually have NPC, or have other diseases that will start to think about NPC, and their diagnostic cascade in these rare diseases, that will really allow us, to be able to then increase that number from the 300 to 350 in the 900. And if Europe as a marketplace of the 1,100 patients from a prevalence perspective, and the miglustat growth that's happened over a decade plus. We think it's a great information, it's great information for us to inform what our market possibility is in the U.S. So Josh, want to talk a little bit about enrollment, time to reimbursement and those things?

Sure. And I was just going to add to this that as we mentioned in our prepared remarks, we've employed a number of other tactics, to really identify these patients, including some collaboration with genetic testing, education around the Niemann-Pick, all of which is going to lead to some market expansion. In terms of the average time - from enrollment to reimbursement, it's too early into the launch to be able to really give you specifics on that. But I would mention again that in the fourth quarter, in those five weeks, from the time that we shipped drugs until the end of the year, we did have a number of patients who not only received their first fill, but also refill in that period of time. So I think that really speaks to, how quickly our team was able to get some of these patients reimbursed, and reauthorized. And I anticipate that that's just going to continue as we work our way through those patients, who are pending approval now.

Great. That's very helpful. And a quick follow-up. Have you had any patients that have submitted an enrollment form, but have been ultimately denied? And do you have any clarity, as to what the rationale behind any ultimate denial is?

Yes so, of course, you know, in any rare disease, there are some initial denials, and we work through those with patients, to make sure that we can help them navigate and work through those denials. Through appeals and other parts of pathways, through the medical exception pathway. We've only had a couple of patients who have been denied, but again, we continue to support those patients. We're continuing to help them work through the reimbursement challenges. And any patient who is experiencing those challenges, we have a very robust patient services plan and patient assistance plan, so that no patient would go without drug.

Got it. Thank you.

Perfect. [Operator Instructions] We'll next go to Eddie Hickman with Guggenheim Securities. Please go ahead.

Hi, good afternoon. I'll add my congratulations on a really nice quarter. What can you tell us about how we should model discontinuation rates so far? And then going forward, do you expect the rate to meaningfully change as we get further outside of the EAP? And then, of these sort of current bolus of patients, like, how many of them do you expect to retain sort of in the long-term? Thanks.

Yes, thanks for that question. I think it's just - it's way too early in the launch to be able to address or answer that question.

Yes, Eddie, maybe I'll give you a comp, though, that you can actually think about. As we look at our EAP data and we think about the patients and the continuity. We had patients that remained in our EAP five years, and patients went through OLE to EAP, now onto commercial product five, six, seven years. You heard that also in the open public forum during our advisory committee. So what we've seen, and continue to see also in our European Expanded Access Program, is a really high level of continuity of care. Once patients are on MIPLYFFA and miglustat. Again, we're just a few months in. We're reporting on five weeks of patient shipments in Q4, so it's going to be a little early to talk about this continuation rates. But if history repeats itself once patients are on, with the side effect profile that MIPLYFFA and miglustat have, we see longevity.

Great. I appreciate all that color. Thanks, guys.

Thank you. I'd now like to turn the call back over to Neil McFarlane for any closing remarks, please.

Thank you, operator. Thanks for joining us today to review what was a transformational 2024. We're pleased to start 2025, from a position of strength and look forward, to execute on our mission to serve people living with rare diseases. Have a great day.