KemPharm, Inc.

Good day and welcome to the Zevra Therapeutics fourth quarter and full year 2022 update call. Currently, all callers have been placed in a listen-only mode and following management's prepared remarks, the call will be open for questions. If you would like to ask a question at that time, please press star one on your telephone keypad. If you need to remove yourself from the queue, please press star two. At any time, if you should need operator assistance, please press star zero. Please be advised that today's call is being recorded. I want to hand the call over to Zebra's Vice President of Investor Relations and Corporate Communications, Nicole Oshner. Thank you. You may begin.

Good morning. Thank you for joining us today to review Zebra's fourth quarter and full year 2022 clinical operational progress, and financial results. A few housekeeping items before we start. I invite you to view the webcast slides and the press release, both of which were issued this morning and can be found in the investor section of our website. As outlined on slide two, during today's presentation, we will be making several forward-looking statements. These forward-looking statements include but are not limited to the clinical and regulatory path for Aramaclimal, ASTARs, revenue milestones and expected revenue from the French EAP program, the planned next steps in our pipeline programs, the timing for enrollment, initiation, the completion and reporting of data from our clinical trial, and the upcoming annual meeting of stockholders. These statements are neither promises nor guarantees, and involve risks and uncertainties and other important factors that may cause actual results to differ materially from those discussed here. Important factors that could cause actual results to differ from forward-looking statements can be found in the risk factor section of our annual report on Form 10-K for the full year ended December 31st, 2022, expected to be filed with the SEC today. you can view the agenda for today's call on slide three. I am pleased to welcome Zebra's management team members participating in today's call. I'm joined today by our CEO, Richard Pascoe, our president and co-founder, Dr. Travis Mikkel, our chief financial officer, LaDwayne Clifton, our chief product development officer and co-founder, Crystal Mikkel, and Joshua Schaefer, Chief Commercial Officer and Executive Vice President, Business Development. I will now turn the call over to Rich Pascoe.

Thank you, Nicole, and thank you all for joining us today to review our Q4 and full year 2022 results. Before we get into the highlights of the successful year, I want to take a step back and talk about where we are today and provide an overview of our strategic evolution over the past 18 months. A lot has happened and with a new name and focus, It is important to walk our investors through how we got here and share my enthusiasm for our future. Today we are Zebra Therapeutics, a nimble and focused rare disease company. Our team has a successful track record of success in championing patients in need, as well as tackling and overcoming challenges in drug development and regulatory approval. We are leveraging our years of expertise and unique insights to chart a new course for drug development And forging pathways to success for promising product candidates. As we move Zavra forward, we will continue to leverage our legacy platform to target internally discovered rare disease product opportunities and extend our pipeline assets exclusivity through lifecycle management. In this way, we bring transformational therapies and hope to patients with rare diseases and their families and create value for our shareholders. Importantly, we are well positioned for success We have a robust pipeline of promising rare disease product candidates with multiple value-creating milestones expected over the coming year. We have a world-class leadership team with the experience of numerous successful product approvals and an equally accomplished board of directors that align with our strategic trajectory in rare disease. Supporting it all, we have a strong balance sheet. So how did we get here? We've worked hard to evolve the company's strategy over the past two years, thoughtfully led by our management team in collaboration with our board of directors and supported by our shareholders. After the approval, licensing, and commercialization of Astaris and our actions to put the company on a firmer financial footing, the management team and board paused to evaluate where we were and what we learned in getting Astaris to the market. Our objective was to determine our best path forward to create value in a timeframe and at a scale that our shareholders deserve. We concluded that we have strong capabilities and success in the scientific, development, and regulatory areas. However, focusing exclusively on a pipeline of product candidates that will eventually compete in heavily generic markets and outlicensing those products as a commercial strategy would likely fail to meet our objective of delivering a significant return on investment to our shareholders. We then worked to thoughtfully set a new course for the company, focusing on bringing the organization's existing strengths together with a refined strategic focus on rare disease indications with the goal of commercializing our products in the United States. We took a series of transformative actions that aligned perfectly with our strategy, highlighted by the acquisition of Aramoclomol, an NDA stage product candidate, upon which we intend to build commercial capabilities that will allow Zebra to create value for the benefit of shareholders. This new direction capitalizes on our strengths and cash position to enable us to retain the value of our hard-earned approvals and control our commercial destiny while delivering much needed therapeutics to patients with limited or no treatment options. It is important to note that rare disease is not an entirely new focus for us. We were already working in rare disease with our prodrug technology applied in rare sleep disorders with KP1077 for idiopathic hypersomnia. From that experience, we recognized that rare disease drug development offers several significant advantages over development in large mass market indications. First and foremost, we have the privilege of partnering with patients, families, and advocacy groups to deeply understand their needs and ensure that our therapeutic approaches are answering their biggest quality of life and disease management concerns. This ensures our products are relevant and capable of commercial success. Rare disease drug development timelines are often shorter and involve much smaller studies than larger indications, resulting in lower costs of research and development. Through the Orphan Drug Act, the company benefits from incentives such as priority review voucher, and a six-month review window for pursuing therapeutics for rare diseases. And the resulting products receive extended patent protection for longer market extensivity. Rare disease products also do not experience significant generic competition once patents expire. Moreover, with a small patient population treated primarily by specialist clinicians, we can bring those products to commercialization with our own in-house commercial team. Taking this together, we saw that rare disease drug development creates an ideal platform for maximizing value creation for patients and shareholders. This led to our decision to focus exclusively on rare disease and our strategic acquisition of Aramaquamol. Through that acquisition, we acquired a high potential product candidate for Niemann-Pick disease type C. We also onboarded an amazing European team with deep connections to the MPC patient community and significant rare disease drug development expertise. As we began focusing on rare diseases, we recognized that our name and branding as ChemPharm no longer reflected who we are as a company. So we underwent a process to redefine our messaging and brand story. The outcome of that process is our new name, Zevra Therapeutics, and branding to reflect our commitment to the rare disease patients we deserve. The word Zevra is Greek for zebra, which is the internationally recognized symbol for rare disease community. Interestingly, a group of zebras is also called a zeal or a dazzle. These expressions capture our team perfectly as we are zealous about empowering people with rare diseases. We are confident that Zebra is a name that will resonate with patients, and we envision a dazzling future for the rare disease communities that we serve. Zebra is better positioned today than at any point in its history as we work towards our key priorities to secure regulatory approval for our pipeline assets build top-tier commercial capabilities, and enhance our pipeline through internal and external efforts. We have two very strong product candidates with multiple value-creating milestones expected this year. We continue to explore new product opportunities, both through our pro-drug platform and business development activities focused on rare disease. We are a rare beast in that we already have a growing revenue stream as a development stage company, which bolsters our already strong financial position. I am confident in the team and our strong financial foundation and diverse portfolio of multiple clinical programs and in our ability to deliver value in 2023 and beyond. Importantly, we have a fully engaged and supported board of directors that has been deeply involved in our strategic evolution and can help us to advance our company. 2022 is a pivotal year for our organization and our evolution into a rare disease company with the acquisition of Aramaka Mall. and the completion of a four-year safety study of that product candidate in NPC. Our ongoing collaborative dialogue with the FDA around the program has been highly productive in preparing us for NDA resubmission. We've also made tremendous headway in our KP1077 program for rare sleep disorders over the last year, including positive data from our cardiovascular trial of SDX, a primary component of KP1077, and a Phase II trial initiation in idiopathic hypersomnia. Orphan drug designation for this product candidate in IH provides the advantages I highlighted earlier, including regulatory incentives and extended market exclusivity after approval. We continue to bolster our strong financial position, earning a one-time fee of nearly $2 million from Corium following the FDA approval of Adlarity. Our net revenue for the full year was $10.5 million. Cash equivalents and investments as of December 31st, 2022 were $102.9 million. Our available capital is expected to extend our cash runway into 2026, an enviable position for any biotech company in today's capital markets. In 2022, we began our efforts to further build our team by appointing Nicole Oshner as VP of Investor Relations and Corporate Communications. In addition, the board appointed Christopher Posner as an independent director, another great addition to the team. As you can see from this slide, we've had tremendous momentum in the fourth quarter of 2022 and the beginning of 2023 on several fronts. I want to point out a few of those. Notably, a recent development in the Aramaka Mall program was a presentation of the data from the interim analysis of the Phase 2-3 four-year safety study at the 2023 World Symposium. These data, which demonstrate the clinical benefit of Aramoclomol, will be a cornerstone of our resubmission of a new drug application expected as early as the third quarter of this year. Notably, the data suggests that Aramoclomol may reduce the progression of NPC. This underscores our understanding that if you can improve lysosomal function, you can improve outcomes for patients. We also underwent our strategic rebrand to Zebra Therapeutics in alignment with our identity as a rare disease company. and to further engage with the rare disease community we joined, the Nord Corporate Council. Since the beginning of the year, we have made several additional key appointments and changes to our leadership and board of directors, strengthening a team that I'm confident can lead Zevra into the future with success. Shown here are our executive team and our board of directors. Not only are we an accomplished group with decades of experience in R&D and commercialization leadership, but we are also a blend of legacy team members and new talent with skills that can take us into the future. The team is aligned with our direction and transformation into a rare disease company. Now I'd like to turn our attention to our Aromacromol program for Nevin Pick Disease Type C. Aromacromol is administered orally and is formulated for ease of use in varying patient circumstances. This product candidate has been studied in 10 Phase I, 4 Phase II, and three pivotal phase 2-3 trials. Aramoclomol has received orphan drug designation for NPC in the United States and the European Union, and fast track designation, breakthrough therapy designation, and rare pediatric disease designation from the FDA for NPC. If approved in the U.S., Aramoclomol would also be eligible to receive a pediatric priority review voucher. We are on track to submit the new drug application to the FDA as early as the third quarter of this year for Aramaka Mall. One of the most attractive aspects of the Aramaka Mall program is that should it be approved, we have the near-term opportunity to commercialize the product ourselves and retain the full market value for our shareholders. We believe a small and nimble commercial team could fully serve the specialists and medical centers treating the MPC patient population. The benefit of a small commercial team is the lower cost of market entry, We believe that our established and new advocacy relationships in the NPC community will help support the adoption of Aramoclomol. And we have already established market entry with this patient population through our U.S. and EU early access programs. Beyond our immediate focus on a successful U.S. commercial launch, we also see the commercial potential for Aramoclomol outside of the U.S. in the EU, Japan, China, and other geographies. Now I will highlight our KP-1077 program for rare sleep disorders, beginning with idiopathic hypersomnia, which is currently enrolling patients and dosing patients in a Phase II clinical study in the US. The market potential for idiopathic hypersomnia is also highly compelling, with limited treatment options available for this small, underserved patient segment. KP-1077 has been designated by the FDA as an orphan drug, as well as possible eligibility for fast-track review status and designation as a breakthrough treatment. In addition, we believe that if differentiated from other treatment options, pricing KP-1077 in between products like Teva Pharmaceuticals ProVisual, which is approximately a $24,000 per year treatment at the highest dose, and Jazz Pharmaceuticals Zywave, which is approximately $187,000 per year at the highest dose, could lead you to capture capturing significant market share. Because this is a rare indication, our intent is the commercialization of this product ourselves, which is aligned with our strategy for Aramocamol, and therefore allows us to keep a larger portion of the economic value. We expect interim data from the phase two trial of KP1077 in idiopathic hypersomnia by the third quarter of this year, and top line data by the end of 2023. Importantly, the interim data will also be an open-label titration phase, which is meaningful because it will allow us to start designing the Phase III study in IH. We are also planning a development program for KP1077 and narcolepsy. The IND filing for this additional program is expected during the second quarter of 2023. With that, I will turn the call over to our CFO, LeDwayne Clifton. LeDwayne?

Thank you, Rich, and good morning, everyone. Let's jump right into the numbers with an update on the commercial progress of Astaris. Like many of you, we closely track the prescription trends for Astaris, and the trend line since the third quarter of last year has become more encouraging. While the early days of the launch were impacted by COVID-related challenges and the need for greater formulary coverage with the largest PBMs, there has been a meaningful change in prescription volume starting in July of 2022. You may recall that we had reported to you that as of Q3 2022, Corium had achieved coverage with the three largest PBMs and doubled the size of their field force to 175 reps. The growth trajectory of the product since that time has continued, and we are optimistic about the possibility of reaching one or more milestones during 2023. With an improving prescription trend, The amount of the royalties realized from the license is meaningful, though modest. The table provided here shows actual royalties earned by quarter and the corresponding prescription count estimates based on publicly available data. These trends suggest that royalties will contribute more revenue in the future. Still, we realize that achieving the sales milestones may be a more significant driver of value from this license. This leads to another critical point. Our legacy model for developing an asset and then outlicense for commercialization is not expected to drive strong growth for Zebra in the short or medium term. Back in 2021, as we began thinking strategically about rebuilding our pipeline, we knew this had to be addressed. The ability to directly commercialize a product we develop and get approved became a primary criterion in evaluating where we would focus our pipeline investments. Our decision to focus on the rare disease space positions us to field a small, nimble commercial team that can be highly effective and drive better return on capital than the results we have had to date with the out-licensed model. We see the ASTARs license as foundational to where we are as a company, but we also look forward to the potential for growth that we may be able to unlock with the direct commercialization of both Aramacamo and KP-1077, if approved. Now, let's focus on the financial results for Q4 and full year 2022. In 2022, we took significant steps to improve our financial position. We continue to have a solid balance sheet, and adding the Aramacamo program has begun to provide a steady revenue stream to support our ongoing regulatory and product development initiatives. For Q4, net revenue was $2.3 million, driven primarily by reimbursements from the French EAP program. Full-year net revenue was $10.5 million. We reported a Q4 net loss of $9 million, or $0.26 per share, which was driven by our R&D investments and increased G&A, all associated with the CAP 1077 and Aramacamo programs. For the full year, net loss was $41.5 million, or $1.20 per share, which includes a one-time non-cash charge of $17.7 million related to the in-process R&D assets we acquired from Orpahzyne. On a non-GAAP basis, FY 2022 net loss excluding the one-time non-cash charge was $23.9 million or 69 cents per basic and diluted share. And as Rich has already noted, our cash position remains solid. with 102.9 million on the balance sheet as of December 31st, 2022. Looking ahead to 2023, we reiterate our guidance that our existing available capital on the balance sheet is expected to extend our cash runway into 2026. This includes the reimbursements from the French EAP, what we need for the Aramacamo NDA resubmission, the completion of the development program for KP 1077, through its NDA submission and potential PDUCA, as well as our preparations for the possible U.S. launch of Aramacumul if approved. In addition, we anticipate that the prescription trend for Astaris will allow us to earn at least one and possibly two of the sales milestones under that license agreement during 2023. Net revenue from the French EAP program is expected to continue at the rate of about $2 million per quarter throughout the year. To conclude, we believe we are in a solid financial position with numerous opportunities to create value for our shareholders as we execute our business plans. And now I return the call back to Rich.

Thank you, LeDwayne. As we look to 2023, I'm excited about what lies ahead as we continue to transform Zebra and work to enhance value creation for our shareholders. We continue our ongoing discussions with regulatory agencies and are preparing to refile the Aramoclomol new drug application as soon as the third quarter of this year. For the KP-1077 program in rare sleep disorders, we are on track to file an IND for 1077 in narcolepsy in the second quarter of this year. And we also anticipate interim data from the phase two trial in idiopathic hypersomnia as early as the third quarter, with top line results in that trial by the end of this year. Those data have the potential to not just support the advancement of Kp1077 into a Phase III study in IH, but also may support a Phase III trial in narcolepsy. We anticipate ongoing revenue from our Aramoclomol Expanded Access Program in France, and we have the potential to realize additional sales milestones and revenue for SARS. This provides further capital flexibility and the potential to further extend our cash runway, which already extends into 2026. In closing, I want to reiterate our commitment to creating value for our shareholders and bringing life-enhancing products to patients suffering from rare diseases. As I look around our industry, I see small-cap biotech companies dealing with failed clinical programs, employee layoffs, toxic financings, and bankruptcies, among other challenges. In contrast, Zebra is financially sound with two promising late-stage assets, and we are growing the company in a thoughtful and measured fashion. Before we open the call for questions, I want to briefly address the alternative slate of three director candidates proposed by one of our shareholders. The Zebra board believes that electing any of these candidates would diminish the overall quality of and experience represented on the board. By contrast, the three incumbent directors collectively bring decades of biotech and pharmaceutical experiences, both as senior executives and as public company board members. Their backgrounds cover a range of relevant areas, including drug development, medical, finance, business development, and commercialization, all of which are essential to driving continued momentum and shareholder value as we execute our transformative growth strategy. Your board regularly seeks to maintain open communication with our shareholders and values constructive input. In fact, many of the changes I discussed on this call today are in direct response to feedback received from our shareholders. We heard you loud and clear that you want to change, that you value revenue, and that you wanted the board and management to be bold. We heeded that call. We took a hard look at our organizational strengths, We invested in a better understanding of where and how to invest the resources entrusted to us by our shareholders. We continued to leverage the team that got us to higher ground, and we added new talent where needed. We undertook an ongoing board refreshment program to bring new and critical thinking to the boardroom, and we focused on creating value through the commercialization of rare novel disease products in areas of significant unmet need. I believe that today the company is in the strongest position to succeed at any time in its history, and I'm so excited for our future as a company and what we aim to accomplish for patients and shareholders alike. Thank you for your continued support as we work to transform lives with new therapies for rare diseases with limited or no treatment options. Please note that we will not be commenting further on the proxy matter during the Q&A, and I would appreciate it if you would keep your questions directed to our performance results, and strategy. With that, I will now return the call to the operator for questions. Operator?

Thank you, sir. At this time, if you wish to ask a question, please press star 1 on your telephone keypad. You may remove yourself from the queue at any time by pressing star 2. Again, to ask a question, please press star 1 now. Our first question comes from Sumant Kulkarni with Kenaccord Genuity.

Hello, this is Kyle speaking for Sumant Kulkarni. Two questions from us. Have there been any specific interactions with the FDA since your last update that gives you more confidence in your ability to potentially refile the Aramacamo MDA as early as 3Q? And then the second question. Has the FDA already seen the open label extension data presented recently? If not, when do you expect the agency to see that data? Would it be prior to the filing or as part of the filing package?

Rich, thanks for the question. I'm going to ask Travis Mickle to address those questions.

Yeah, sure. No problem. So, as far from our last update, we have not had a more formal interaction with the FDA as to the resubmission. And then, which really answers the next part of your question as well, which is no, the FDA hasn't seen the data yet. We do plan to submit the information, the ongoing clinical data, the four-year wrap-up study, as well as additional confirmatory evidence that was collected. And we will either provide that to them in a form of a formal meeting or we will actually just provide that to them and ask questions. So the format of that in our ongoing dialogue hasn't been decided yet, but we will update as soon as we have any new information. Todd, thank you.

Thank you. Our next question comes from Jonathan Ashoff with Roth MKM.

Thank you. Good morning. What sales thresholds? trigger that first and second STARS milestone, and I think they're $10 and $20 million each, if I remember correctly. When in 2023 do you think you would intend to achieve those two sales thresholds that would trigger the 10 and the 20?

Yeah, good morning, Jonathan. Thank you for the questions. So, while we tried to provide more information today than we have in the past from publicly available data, we're still not able to give the exact sales thresholds or the actual amount of the milestones. So, but with that said, we do expect likely if we achieve one or possibly two of those, it would most likely be toward the second half of 2023.

And Jonathan, Rich, I might just add, you know, the way that deal is constructed, which is good for the company, there were, you know, lower thresholds than you might typically find in a license agreement for the achievement of certain milestones. And so, you know, we tried to front load as much of it as we could with respect to those types of outcomes. And so I think it's why, in large part, we're very, you know, optimistic that we'll hit one, perhaps more than one this year.

Okay. You mentioned narcolepsy once in the in the press release, so will you be waiting for the outcome in IH before starting perhaps a phase three trial in narcolepsy, or are you still going to start a phase two, three trial before getting any data in IH?

So this is Crystal Nichol. We are actually, we will look to see what data we get from this phase two study with IH and determine whether or not we go with a parallel program with narcolepsy and IH for a phase three study. That would help with enrollment and other, you know, cost savings there. But, again, we will wait for the readout with the Phase 2 study before we make any of those decisions.

Okay. Thank you. And I'm guessing just briefly the Aramacla Mall 4Q data. I mean, 4Q revenue was about $1.9 million, or was there a bunch of, you know, other non-drug revenue in there?

No, that's right, Jonathan. That was the email. And just keep in mind that that includes this callback liability that we have to record. So we often talk about gross revenue of a million dollars a month from that or about a million euros a month, and then we have to call back the liability. I think you may be familiar with that from prior quarters.

Yeah, thank you very much, guys.

Thank you. Thank you. As a reminder, to ask a question, please press star 1. Our next question comes from Louise Chen with Cantor Fitzgerald.

Hi. Congratulations on all the progress this quarter, and thanks for taking my questions here. So, I have two questions for you. I wanted to ask you about IH and the readouts that are coming, the interim and then the top-line data readout. later this year, and what would you consider a successful outcome that would make you competitive in the market? And then also, the other question I have for you is when you think about expanding your rare disease pipeline, you know, are you going to do that through M&A, internal development? What kind of resources can you put behind it, and when can we see additional products being added? I know you're very busy with what you have on your plate right now, but just kind of curious, thinking longer term. Thank you.

So, this is Crystal Mickle. To answer your first question, with the interim data, we're really looking at a number of things such as, you know, do we have the right amount of, you know, patients to power a study, a future study, and really looking at what a future study would look like, dosing regimen, things like that. So those are all still playing out. Obviously, we expect with our STX profile looking different than, say, what's on the market as far as, you know, off-label use of methylphenidate and things like that. We look to that as a differentiator with our product as we have with Astaris in the past.

And this is Josh Schaefer. I'll take the second question. We are very actively looking to add new products to the portfolio, whether that would be through internal development and leveraging our ProDrug platform to bring new products into the pipeline. But we're also looking very actively at potential M&A, licensing deals, any number of constructs to bring additional products into our portfolio that can really accelerate and advance our transition into a rare disease company. Having said that, we're looking for opportunities that are synergistic with Aramaclimo and where we can leverage a commercial organization and a development organization that is really focused on the rare disease capabilities that we're building.

Luis, this is Rich. Just to add to all of that, I think clearly the priorities today are the resubmission and approval and potential launch for Aramoclomol, followed closely by completing the Phase II program in idiopathic hypersomnia for 1077 and advancing that into a Phase III trial. To your question, you know, we want to generate the necessary data in this Phase II program for 1077 to tee up a Phase III pivotal program that can differentiate the product in the marketplace, and that's the goal there. Beyond that, you know, we're always looking for good opportunities. At the same time, we understand the priorities are advancing the existing pipeline.

Thank you.

Thank you.

Thank you. Our next question comes from Oren Livnet with HC Rainwright.

Thanks for taking the questions. I have a few, actually. You mentioned, actually, in your press release and in the script, specifically extending exclusivity of your pipeline assets with lifecycle management. That kind of jumped out at me, and I was wondering, can you just remind us, what is the current, I guess, IP landscape of your development assets, and what are we thinking about in terms of lifecycle management? Is this just new IP you're working on, or are there actual product innovations that are already in the hopper longer term? And then I have follow-ups. Thanks.

Yeah, Oren, I'll ask Travis to address specifically, but, you know, one of the things, I'll preface it by saying one of the things that really excited me about these opportunities in rare diseases and looking at products like Aromacamol is we have this, you know, terrific internal capability to not only discover new assets, but to extend the life cycle of those assets. And so we are very intent on doing both. And so unlike a lot of companies I mentioned in my prepared remarks, we're a development stage company with revenue. We're also a development stage company focusing on rare diseases with this internal capability that I'm not sure other companies can mimic. So bringing all of that to bear in terms of creating value for the future is really important to us. And so I think that's the underpinnings, if you will, behind those statements. With that, Travis, do you want to address maybe a little more specifically the mechanics of what we're doing?

Yeah. As far as the IP question, Oren, Air Makamal has patents issued and pending that would run well into the 2040s. Now, those patents are not based on composition of matter like we would like to focus on. Rich is alluding to our ability to expand upon IP. You're always aware, too, with a rare drug in a pediatric area, it's going to be seven and a half years of orphan exclusivity. For KP-1077, those patents run until 2037 and beyond. Those are, of course, composition of matter-based patents.

Okay, appreciate it. So we're thinking primarily about extending Aramaclomol exclusivity well beyond the orphan period is how I'm interpreting that, correct? That's right. Right, okay. And on Aramaclomol, I guess to build upon the first question today regarding that, you know, confirmatory evidence and the four-year safety data that, you know, and everything you need to do for the FDA filing. Should I think of this four-year data as sort of clearing the lane and in and of itself potentially addressing any FDA skepticism to the extent that it might have existed at some point going forward? Or is there significantly more, quote, unquote, confirmatory evidence that you still need to do separate from that? And, you know, where does that stand? Can you give us any clarity on sort of progress on that front? Thanks. Travis, you want to field that?

Sure. No more clarity, unfortunately, Oren, than what we kind of stated before, what I said before. The data, I believe, from the four-year extension arm is very helpful, especially if you look in light of the AMLEX approval earlier this year, where they used the extension arm to show increased survivability. Here, we're looking at kind of the robustness of the effect and how it sustain kind of this lower trend of progression in the disease for a long period of time. Now, of course, there's without a placebo in that portion. But for the most part, you know, that's the additional step of what's not been disclosed, the additional information that we have available to us to provide. I think that and everything that Orphezyme generated in the past, as well as, you know, putting that all together in a cohesive story, will be compelling, more compelling certainly than at the time of the CRL, and certainly something that we will at least in part, if not in its entirety, discuss with the agency before the resubmission.

Okay. And lastly, on KP-1077, I think you mentioned brain fog on multiple occasions as a key endpoint you're looking at. Can you just remind us Based on your interactions with the FDA or understanding of the landscape in general, what do you see as the necessary hurdle in terms of endpoints for approvability? And to what extent do you believe you need to show additional endpoints like brain fog or others to differentiate from off-label wakefulness agents or stimulants?

Hi, Oren. It's Rich. I'll just maybe preface the comment here by stating that clearly that, you know, the brain fog and other exploratory endpoints are being looked at in this Phase II trial. You know, we're obviously focusing on approvability, which will be driven by the primary, but then enhancing the label and the commercial opportunity for the product in a competitive set or a competitive world with some of these other endpoints. I think it's perhaps too early to comment specifically on the magnitude of effect, but clearly we'll assess that in this phase two program and build whatever is appropriate into the phase three protocol, which will then serve as a basis for, you know, approvability in the label. But fair to say that it's a little too early to call, but I want to, you know, reemphasize that, you know, as we think about the company moving forward and we think about commercializing these assets ourselves, we want to ensure that we're creating products that can be highly competitive, command premium pricing in the market, and moreover, allow us to go out and create the sort of value that we foresee for the company through that process.

Okay. Well, good luck. Look forward to updates.

Thank you for being on the call. Thank you. Our next question comes from Sumant Kulkarni with Canaccord Genuity.

Oh, this is Kyle for Sumant again. A quick follow-up. On EAP gross revenue, we see that the new guidance is roughly 8 million annualized versus a prior estimate of 12 million. We are curious, what are the factors affecting this number, and do you think this new guidance is driven more so by a function of price or a function of patient size? Thanks.

Well, thanks for the question. And really, it's actually not new guidance. I think sometimes when we've spoken, we talk about gross revenue being about a million euros per month, and that really is unchanged. What we tried to do in today's guidance, though, is to account for the around 30 or 35% clawback liability, which we always have to recognize when we put out our financial statements. So that's really the difference there is simply giving you guidance of net revenue, which is around $2.25 million versus the gross revenue that we've sometimes spoken about before.

Thanks.

Thank you. This concludes the Q&A portion of today's call. I would now like to turn the call over back to Richard Pascoe for any additional or closing remarks.

Thank you, operator. And first of all, I want to thank all of our employees and leaders, in particular my colleagues here today around the table, for their tireless efforts to bring Zebra Therapeutics into a very strong position for 2023 and beyond. It's an exciting time for us. And I appreciate their support and hard efforts to get us to where we want to be. I also want to thank all of our shareholders for your continued support. And for all of those that have joined us today on the call, we appreciate your interest in your questions and we look forward to speaking with you in the future. Thank you.

This concludes today's several therapeutics, fourth quarter and full year 2022 earnings call and webcast. You may disconnect your line at this time. And have a wonderful day.