Zevra Therapeutics, Inc. Price & Performance (ZVRA)

Today, we will provide an overview of our accomplishments in the fourth quarter and 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. [indiscernible] Actual results may differ materially from those stated or implied by any forward looking statements, due to risks and uncertainties associated with Severe's business. Forward looking statements are not promises or guarantees and are inherently subject to risks, uncertainties, and other important factors that may lead to actual results [indiscernible] materially from the projections made These forward looking statements should be evaluated together with the cautionary statements contained in the Risk Factors section in our most recent quarterly report on Form 10 Q, our annual report on Form 10 ks, and our other filings with the SEC. I'm pleased to welcome Zevra management team members participating in today's call. Neil McFarland, Zevra President and Chief Executive Officer was Wayne Clifton, our Chief Financial Officer and Josh Schafer, our Chief Commercial Officer and EVP of Business Development.

Our Chief Medical Officer, Adrian Cortel, will also be available for today's question and answer session. Now, it's my pleasure to hand the call over to Neil.

Thank you, Nicole. And thank you for joining us this afternoon. As Nicole mentioned, today, we'll provide our fourth quarter and fiscal year twenty twenty four financial results.

And share progress on the execution of our priorities for 2025. Our priorities are guided by Zevra's strategic plan. Unveiled during our third quarter call and categorized under four actionable pillars: commercial excellence, pipeline and innovation, talent and culture, and corporate foundation. 2024 was a transformational year for Zevra. And bringing my plight to the people living with Neiman Pig disease Type C or NPC was a crowning achievement. In the past year, we became a commercial stage company that had the opportunity to positively impact the lives of people living with rare diseases. The approval of My Plifa last year was an outcome of our long standing collaboration included contributions from more than two seventy Neiman PICC disease Type C patients who participated globally in our pivotal studies open label extension studies and expanded access programs. The early days of the MyPlypha launch have exceeded our expectations. In the fourth quarter, we received 109 patient enrollment forms, which we believe reflected the anticipation and unmet need in the MPC community. Additionally, by the end of Q4, all active U. S. EAP participants submitted an enrollment form and our entire organization has been activated to ensure smooth transition to my PLEAFA Commercial Product.

As Previously Reported, We Anticipate That The U. S. EAP will close by the end of Q2. Going forward, our goal is to expand availability of My Plifa outside of The U. S. To provide access to as many people living with MPC as possible. With this goal in mind, we are progressing regulatory submissions. With the focus on submitting a marketing authorization application in Europe during the second half of twenty twenty five where we estimate 1,100 people are living with NPC. Additionally, we will maintain our global expanded access program that currently supports 70 to eighty NPC patients. And we look forward to providing updates in the coming quarters as we seek to expand access [indiscernible] We're leveraging our infrastructure for both urea cycle to leading to efficiencies that drive commercial excellence. The launch of ALPUVA in early twenty twenty four facilitated key learnings as we built our commercial capabilities. During the fourth quarter, we received four ULTRUVA enrollments, As announced in our Q3 call, we refined our strategy to reach the adult onset population for Humo Prima's portability and ease of administration may provide a benefit with a focus on patients receiving payer pushback. Gus will provide more details related to the performance of our commercial products later in the call.

Moving to pipeline and innovation. Which refers to our ambition to develop products that address significant unmet needs. Eliproval is our Phase three investigational clinical candidate for the treatment of vascular Eilers Danlos syndrome or VETs. Which is an inherited connective tissue disorder caused by the CALL 3A1 gene mutation. [indiscernible] can result in spontaneous arterial aneurysms and hollow organ ruptures. There are currently no treatments approved in The U. S. Where there are approximately seven thousand five hundred people living with this disease and the prevailing treatment paradigm is only reactive surgical interventions. Although Soliparol is not approved for VES in any country, it is utilized as a standard of care in several European countries. In Q4, enrolled eight patients in our Phase three DISCOVER trial [indiscernible] bringing the total number of enrolled patients to twenty seven. As an event driven trial, the rate of participant enrollment is integral to the program's success. As a result, we are investing in tactics to accelerate enrollment among genetically confirmed patients with providers and clinics that treat CALL three A1 positive patients. In addition, we have support from the Vets Foundation Professional Advisory Board on our path forward. Moving on to KP1077.

As outlined on our Q3 call and following a successful end of Phase two meeting with the FDA, we are exploring strategic alternatives to advance clinical development and future [indiscernible] We're focused on maximizing the value of this Phase three ready asset that has regulatory feedback for the potential development in both idiopathic hypersomnia and narcolepsy indications. In 2024, we completed a comprehensive review of our IP portfolio to identify areas for optimization This review led to a decision to rationalize our in house discovery efforts and outsource those activities to focus our investments where we have the greatest potential for impact. To execute our strategic plan, and deliver on our key priorities, it's Palma that we develop a high performing culture and attract and retain talent. In the second quarter of twenty twenty four, we expanded our executive leadership team with the appointment of Rassan Thompson, as Chief Legal Officer Secretary and Compliance Officer. And Alison Peters, Additionally, during the fourth quarter, we consolidated our development and scientific functions under Adrian Cortel, Chief Medical Officer. We believe these changes optimize Zevra for success with cognitive leadership and the appropriate span of control to achieve our objectives. An important element of executing against our strategy is to build and maintain our position of financial strength and disciplined capital allocation.

That we refer to as our corporate foundation. This underpins all other pillars and allows us to responsibly invest in our long term transformation. In 2024, we refinanced existing debt with a new credit facility and completed a modest secondary offering provided financial stability. Recently, we entered into an agreement to monetize our priority review voucher for $150,000,000 which upon closing will provide non dilutive capital to support our future growth Building on the momentum from 2024, we are pleased to start 2025 from a position of strength across our four strategic pillars execute on the tremendous opportunity we have to serve people living with rare diseases. I'll now turn the call over to Josh. Who'll provide an update on our commercial products. Thank you, Neil. In 2024 was a year of significant milestones for Zevra, and the rare disease community. In particular, the FDA's approval of MYPLIFA marked the first product in The U. S. For the treatment of NPC. At that time, we immediately began receiving patient enrollment forms and initiated the benefits verification process. During the fourth quarter, product was available in the last five weeks of the year. While discussing our commercial products, will provide patient enrollments the percent of covered lives and net revenue for the quarter.

As Neil noted, the launch of MyPlifea has gone exceptionally well and carries significant momentum into 2025. From the time of approval through December 31, we received 109 total prescription enrollment forms. And as of the end of the year, we enrolled all of the active U. S. EAP patients. [indiscernible] a reminder, enrollment is a prescription submitted to our specialty pharmacy initiating the benefits investigation process leading to a decision on reimbursement, and paid dispense. Which is a thirty day supply at Miplify. In the fourth quarter, early enrollees may have received both an initial dispense and their first refill depending on the time of their enrollment. We estimate that there are approximately 900 people with MPC in The U. S. [indiscernible] have been diagnosed. To put this in perspective, our fourth quarter performance resulted in approximately one third of diagnosed patients submitted an enrollment to receive My Plifa. NPC is a neurodegisigenerative progressive and fatal lysosomal storage disorder caused by lipid buildup leading to cell death and ultimately organ dysfunction in the spleen, liver and brain. CUSTOMPTION presentation and age onset are heterogeneous disease progression is primarily assessed using the only clinically validated endpoint the Neiman PIC disease Type C Clinical Severity Score.

Including measurements of ambulation, fine motor, speech, and swallow abilities. [indiscernible] The data included on our label shows MYPLIFER in combination with MYGLOSTAT halted disease progression through twelve months demonstrated by more than a two point improvement in patients receiving this combination compared to those receiving miglucat alone. Where only a one point improvement is needed to demonstrate clinically meaningful difference. In a disease like NPC, access to data covering a twelve month duration is critical to establishing treatments as disease modifying. [indiscernible] treatment effect had been evaluated in an open label extension study and through multiple center EAPs. With some patients having as many as five to seven years of experience on therapy. We are pleased with MyPlifo's data and its indication for use in combination [indiscernible] And our market intelligence suggests that healthcare providers prefer multi therapeutic approach to treating this heterogeneous disease. Based on early market experience and feedback, we believe providers will use a disease modifying treatment such as MyPlife Plus MigliStat as the cornerstone of therapy and then potentially add therapies or supplements to provide symptomatic treatment if needed. Many commercial plans have not yet formalized reimbursement coverage. [indiscernible] it's too early in the launch to provide a meaningful market access and reimbursement update in terms of the percentage of covered lives.

However, our team is actively engaged with payers and we have been addressing coverage hurdles to gain reimbursement through either direct formulary coverage or via the medical exception process thus far.

We will continue meeting with payers and presenting clinical data to support My Plifa's use as the cornerstone of therapy for MPC and we'll report progress in future calls. As we look forward to 2025, our focus will be to grow enrollments of currently diagnosed and untreated We recognize the impact of prompt diagnosis and treatment to halt the progression of disease for people living with MPC. And have invested in educational resources and tactics drive patient identification and early intervention. As an example, we commenced a media campaign working with local outlets and key opinion leaders to educate about early signs and symptoms of NPC This program led to the identification of three new patients who had not been previously treated. We are also using advanced analytics to understand what recently diagnosed MPC patients are treated and to ensure new patients have an opportunity to receive treatment. Our rare disease sales and reimbursement specialists are actively engaged in raising awareness of MPC diagnosis, and available treatments with Miplify. Our efforts to increase disease awareness and are multifaceted And on February twenty eight of this year, timed with Rare Disease Day, we launched a disease state awareness campaign entitled Learn NPC Read Between the Signs.

To educate healthcare professionals unfamiliar with MPC to support the identification and diagnosis of people living with NPC. In addition, we entered into an agreement with a leading diagnostic company to provide genetic testing options for individuals with suspected lysosomal storage disorders. [indiscernible] including MPC. [indiscernible] We believe this program will lead to the identification of new patients and will allow us to support earlier diagnosis and treatment. [indiscernible] Our sales and reimbursement teams regularly meet with prescribers to provide education on the strength of Mycoplifida and to support the reimbursement processes. And currently, under the direction of Adrian Cortell, our Chief Medical Officer, our medical liaisons are engaging with key opinion leaders and patient advocacy groups to build a body of evidence demonstrating the need to treat patients early to delay progression and to position MYPLIFA as the cornerstone of treatment. Additionally, our medical affairs team is prioritizing our publication strategy further drive awareness of the need to treat MPC patients. For example, during the twenty first Annual World Symposium, including new data assessing the safety and tolerability of Myclife, in MPC patients six months to twenty four months as evaluated a pediatric sub study of the pivotal Phase three trial.

In conclusion from my platelet, we're in encouraged by the initial signs of the launch and are excited to provide future updates on our progress in reaching patients who can benefit the most. Now let's turn to APPROVA. Our commercial product for the treatment of certain UCDs UCDs are a group of rare inherited metabolic disorders caused by defect in one of the six enzymes or two transporters the urea cycle leading to an accumulation of ammonia. Elevated ammonia or hyperammoniaemia can be toxic leading to neurocognitive damage or even death. Apruva is a nitrogen scavenger that removes excess ammonia thus reducing harmful accumulation. The approval launch has progressed slower than we would like for this differentiated product. During the fourth quarter, we saw new enrollments increase to four as compared to three in the third quarter. And our market access for approval remains consistent at 76% of covered lives. Zevra launched uprova a little over a year ago into a mature UCD market At that time, we were able to build initial demand with clinicians and patients looking for alternative therapies that could improve adherence and better control ammonia levels. However, limited patient pull through and reimbursement support experienced early in the launch necessitated a change to improve the patient experience.

And we transitioned to a new specialty pharmacy. We also refined our strategy to target specific patient segments who will receive the greatest benefit from ulpruva. And who may face fewer reimbursement hurdles. We believe that the adult female OTC deficient carrier population as well as those UCD patients, who may seek additional lifestyle independence will receive the greatest benefit from the ammonia control on the go that Alprova provides. Another resource we have added includes field reimbursement managers who work with physician teams to assist with reimbursement challenges. We've also identified payer plans that have moved other therapies to the exclusion list and are working with payers to provide a smoother reimbursement process for Alprova. These efforts are in early stage and we look forward to reporting our progress on future calls. Finally, we are proud to highlight our sponsorship of the National Urea Cycle Disorders Foundation, Techemonia Campaign, to raise awareness of the critical importance of recognizing the signs and symptoms of hyperammonia anemia and the need to treat early and persistently. Patients remain at the center of what we do and supporting the rare disease community through patient advocacy organizations like NUCDF, is one of our highest priorities.

I will now turn the call over to LaDuane, to discuss the fourth quarter and fiscal year twenty twenty four financial results. Thank you, Josh, and good afternoon, everyone. In addition to the financial details included in today's call, we encourage you to refer to Zevra's annual report on Form 10 ks for more detailed information which we intend to file within the next few days. In the fourth quarter of twenty twenty four, we reported net revenue of $12,000,000 which includes 10,100,000.0 in My Plifa revenue, $100,000 in Opruva revenue, 1.1 in net reimbursements from the French EAP for Aramarklimol and 0.7 of royalties and other reimbursements under the Astares license. This was a record level of quarterly product revenue for Zevra, For our commercial products, MYPLIFTA and DELLPUVA, we recognize revenue when shipments are received by the specialty pharmacy. For MyPlifeHub, Q4 was a partial period and revenue included initial patient dispensers refills for some early enrollees, and target supply levels at the specialty pharmacy. French EAP reimbursements were reduced during Q4 due to a true up in program access fees and we continue to expect net reimbursements will continue to be approximately 2.1 per quarter. Our operating expenses for the fourth quarter were $24,500,000 which includes non cash stock compensation expense of four of which 2,100,000.0 was accelerated vesting expense related to severance arrangements, and severance expenses of 1.6 recognized within R and D expenses.

R and D expenses for Q4 twenty twenty four were $8,400,000 dollars which was a decrease of $3,000,000 compared to Q4 twenty twenty three due primarily to a decrease in third party costs upon completion of the KP1077 Phase two trial offset in part by an increase in personnel related costs. SG and A expenses were 16.1 for Q4 twenty twenty four which was an increase of 1.4 compared to 14.7 for Q4 twenty twenty three. Due primarily to an increase in personnel related costs as our full team was in place and actively engaged in commercial launch activities for the entire quarter. Net loss for the fourth quarter twenty twenty four was $35,700,000 or $0.67 per basic and diluted share compared to $19,600,000 or $0.51 per basic and diluted share for the same quarter a year ago. For our full year 2024 results, net revenue was $23,600,000 which included $10,100,000 of My Plata net revenue 0.1 of Ulpura net revenue, 9.1 in net reimbursements from the French EAP for Aramarkimo, and 4.3 royalties and other reimbursements under the Astarus license agreement. Our full year operating expenses were $97,000,000 $14,900,000 of non cash stock compensation expense. R and D expenses were $42,100,000 was an increase of 2.3 compared to full year 2023 due to an increase of 6.3% in personnel related costs offset by a decrease of 3.6% in third party costs primarily as a result of the completion of the KP-ten 77 Phase two trial.

SG and A expenses were $54,900,000 for 2024 compared to $34,300,000 for 2023 and this reflects the commercial team fully in place and actively engaged in our launch activities. For fiscal year twenty twenty four, net loss was $105,500,000 or $2.28 per basic and diluted share compared to net loss of $46,000,000 or 1.3 per basic and diluted share for 2023. As of 12/31/2024, total cash, cash equivalents and investments were $75,500,000 which was a decrease of $20,000,000 compared to the end of Q3 twenty twenty four. Total long term debt was approximately $60,000,000 and announced on February 27, we have entered into an agreement to sell the priority review voucher we received [indiscernible] for $150,000,000 Upon closing, we expect to receive net proceeds of approximately $148,300,000 net of fees and our pro form a balance of cash cash equivalents and investments will be approximately $223,800,000 This non dilutive capital adds a significant stream to execute on our strategic priorities with our immediate focus on executing the commercial launches [indiscernible] investments in Solipril and our other development programs and building our corporate foundation while we earn the right to make disciplined growth investments in the future. Based on our execution to date, our Form 10 ks will not include a going concern disclosure.

And our current operating forecast combined with existing resources extends our cash runway into Our cash run rate guidance does not include the potential proceeds from the sale of the PRV but it does include anticipated net revenue from MYPLIFTA and ELPUVA sales, net reimbursements from the French EAP for Aramarkimo, royalties under the Astaurus license agreement, and continued investments into our development pipeline programs. Our financial results for 2024 reflect the solid execution of our strategic plan, and demonstrates our commitment to our mission to serve patients and generate meaningful value for shareholders. We are pleased with the opportunities we have in 2025 and beyond to drive value creation, through disciplined investments where we can win. Now, let's open the call to questions. Operator?

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 for me I think this is the first time that you've provided us more specific guidance on the European filing timelines. 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 And then when we think about the European market, which is more mature, how do you think about the European market? And then when we think about the European market, which is more mature, how do you think about the European market? And then when we think about the European market, which is more mature, partially due to the fact that Miglustas in there for over a decade. How do you think that drug becoming available and used 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 the remarks, the prepared remarks with Neiman Pixy 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 eleven hundred patients in based on a prevalence number. And myglastat has been a approved there for well over a decade. So our our current label in The U. S. And we are still working through what this filing would look like for our MAA in Europe, as you know, have MyPiper and Myglistat in combination in order to be able to halt progression of the disease versus myglostat alone having an approximate two point progression over twelve months based on our clinical study. So based on the fact that there has been minglestat 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 had in our Phase three program.

We feel like this is a great opportunity to go after in Europe. Regards to the European filing, probably not ready to talk too much about all of the the intricacies of the European filing, but to be able to state that for the second half of twenty twenty five, we believe that we're going to be able to file talk a little bit about our last interactions? Yes. So the last interaction with the EMA obviously happened, but the office I mean about four years ago when we withdrew the application based upon the complete response letter that we received from the FDA Some of the comments that we received from the EMA in regards to the filing that we had in Europe. We're now seeing a much better position with long term data available We are currently consulting with Copper Consulting Group to how to specifically address some of the problems 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 the EMA.

Okay, thanks. And then thanks for providing the cash runway guidance, which I understand ex 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 projects [indiscernible] 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 2025 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 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 stuff for the MyFICO launch. Can you maybe give us any more quantitative color on the My Plicia sales during the quarter in terms of the supply amounts to to specialty pharmacies or what proportion of patients got a refill? And then my my second question is, how should we think about the long term here in terms of net patient adds? 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 LeDuane 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 bolus of patients that we've seen and what future may look like? [indiscernible] Yes. So with my PlaidFA revenue, again, we reported $10,100,000 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 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 MyPlife. And so we had all those patients plus some patients would previously not been exposed to MYPLIFER 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 that aren't currently treated as well as those patients who've 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 my questions.

My first one is a bit of a follow-up on the last question. In terms of your sequential delta and patient enrollments [indiscernible] 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?

So you're absolutely right. We went from excuse me, 90 at the October so 109 at the December. Again, this really reflects many of these patients were really sort of queued up ready to go from our 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 to deploy our sales teams into those offices. As we continue to do 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 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 twelve 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 in internally on the conversion of those EAP patients, not over a twelve 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 and as well as the unmet need in this patient population. So as we go through this trajectory 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 be able to show that this has been an outstanding performance on the conversion and on the launch trajectory. Now are going to take this into executing Phase two.

That's a point well made and taken. So on the 300 to three fifty or so diagnosed and treated patients with MPC, roughly how many are treated at centers of excellence versus not? [indiscernible] 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 Neiman PIK. So many of these patients would be diagnosed and then go back to their their local neurologists to continue being monitored are finding now that those patients are coming back to these centers of excellence as they're made aware of My Plifa 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, Beck. On Ultruva, roughly how many quarters are you giving for the new patient targeting strategy to see a potential inflection?

Yes. We haven't really put any timeframe on that. We know that ALTRUVA can provide benefit to patients. We have revised our strategy to be able to to bring that to specific patients 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 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 MYPLIFER 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 Lebnath with H. C. Wainwright. Please go ahead.

Thanks. I have a couple on my Can you just characterize that initial bolus of 90 patient referrals that came in really fast in that first month Can 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 center to penetrate those? Or was that ninety percent including, I guess, just the 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 thirty percent of those initial ninety had already been quote unquote approved, which is really fast in the first month either I assume via some formal coverage or more likely medical extension. Do you have any updates on those percentages for the initial wave, a continuing approval rate? Or the cumulative approval rate for this entire 109 through December? And I do follow-up. Thanks.

Yes. So I'll take your question about the 90.

As we reported in our last call, of those ninety, sixty nine of them were from the expanded access program. And 21 were from other other sites as we're naive to my point for had not previously received My Plifor. 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 in And at the time of our last call, it was 30% We're continuing to see improvement in that and And what we're seeing is that many commercial payers have not yet made decisions around [indiscernible] But the vast majority of our patients are able to get reimbursed either through direct formulary or through a medical exception process. And importantly, our team is out in front of these payers talking about the clinical benefits of MyGlifa 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 going, if there's any pushback, it's obviously ultra rare. So I'd assume that's somewhat limited, but obviously we're talking about about both two expensive drugs and combinations. 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 we are really getting in there and we're talking about the benefits that Miplify offers to these patients. We're talking about the halting of progression of disease after twelve 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. And 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 Duane here.

Yes. Orin, I would just say, we don't generally discuss 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 sorry. Gross to net, it's going to be in the at this point. Okay. Thank you so much. Our next question comes from Sami Korwin with William Blair. Please Hi there. Congrats on the great quarter and thank you for taking our questions. I guess I was curious what the average time you're kind of seeing from the start enrollment form to the approval of reimbursement as you're kind of thinking about expanding your targeted population, and going beyond the 300 to three fifty 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 pebble in population? Thank you.

Hey, Sammy, 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 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 market and multiple treatments in the market for that matter, physicians that actually have NVC or have other diseases that will start to think about MPC in their diagnostic cascade in these rare diseases that will really allow us to be able to then increase that number from the three hundred to three fifty into nine hundred. And then if Europe has a marketplace of the eleven hundred patients from a prevalence perspective, and the MIGLOSTAT growth has 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 Jack's going 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 Neiman PIC 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 ship drug 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 those 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 then a quick follow-up. Have you had any patients that have submitted an enrollment form that have been ultimately denied? And do you have any clarity as to what the rationale behind any ultimate denial is?

Yes. So of course, 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 and work through those denials through appeals and other parts of pathways through the medical exception pathway. [indiscernible] 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.

We'll next go to Eddie Hickman with Guggenheim Securities. Please go ahead.

Hey, good afternoon. I'll add my congratulations on a really nice quarter.

What can you tell us about how we should model discontinuation rate 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. [indiscernible] 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 remain in our EAP five years and patients went through OLE to EAP now on the 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 myPLIFO and miglostat.

Again, we're just a few months in. We're reporting on five weeks of patient shipments in Q4. It's going to be a little early to talk about discontinuation rates. But if history repeats itself, once patients are on, with the side effect profile that myclife and miglizdat 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 the transformational 2024. We're pleased to start 2025 from a position of strength and look forward to executing on our mission to serve people living with rare diseases. Have a great day.

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