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spk01: Good afternoon, everyone. Thank you for joining the Zebra Therapeutics Q4 2023 Corporate Updates and Financial Results Call. Today's call is being recorded and will be made available on the company's website following the conclusion of the calls. With that, I'll now turn the call over to Nicole Oshner, Vice President of Investor Relations and Corporate Communications for Zebra Therapeutics.
spk02: Good afternoon, and thank you for joining us today to review Zebra Therapeutics' progress in the fourth quarter and full year of 2023, outlining our clinical advances, operational achievements, and financial results. Before we get started, let me take a moment to provide some important information. I encourage you to access the news release, which was just published and available in the investor relations section of Zebra's website. As we proceed with this call, it's important to highlight that today's discussion will include forward-looking statements. Forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties, and other significant factors that may lead to actual results differing materially from the projections made. Please refer to the risk factors section in our most recent quarterly report on Form 10-2 and our other filings with the SEC and annual report on Form 10-K. I'm pleased to welcome Zevra's management team members participating in today's call. I'm joined by Neal McFarling, President and Chief Executive Officer, LaDwayne Clifton, our Chief Financial Officer, Joshua Schaefer, our Chief Commercial Officer and EVP of Business Development, Crystal Mickel, our Chief Development Officer, and Adrian Cortell, our Chief Medical Officer. Now, I'll turn the call over to you.
spk08: Thank you, Nicole, and thank you all for making the time to join us today. During the fourth quarter and into 2024, we made solid progress towards transforming Zevra into a commercial stage company. On our last call, we announced that we were focused on three key priorities. First, to close the ACER acquisition and deliver value to patients by commercializing Olpruva. Second, to resubmit the Arimathamol NDA. Third, to complete the Phase II trial in idiopathic hypersomnia and prepare to advance KP1077 into Phase III. I'm happy to report that we executed on all of these objectives. And I would like to take the opportunity to recognize the extraordinary effort from our entire team to deliver for people living with rare diseases. Before discussing our results, it's important to note that our financial statements for fiscal year 22, including all interim periods and the interim periods of 2023, will be restated due to a change in our warrant accounting. LaJoy will provide more details later on the call, but we believe the restatement will have no impact on the company's cash or ability to execute on our strategic priorities. Turning to the fourth quarter corporate highlights, let me start with the completion of the ACER acquisitions, which propelled us into becoming a commercial stage company, diversifying our revenue potential and providing scale. The acquisition was a natural fit with Zebra's mission, bolstering the talent on our team and bringing complementary rare disease assets, including commercially available Opruba. Opruba is indicated for the treatment of certain urea cycle disorders, or UCDs, which are a group of rare genetic disorders that can cause harmful levels of ammonia to build up in the blood, potentially resulting in neurocognitive impairments, brain damage, and in some cases, coma or death. We estimate that there are approximately 2,000 people in the U.S. with UCDs, of which roughly half are diagnosed and treated. The UCD market in the U.S. is estimated at approximately $350 million annually. Despite the available therapies, unmet needs for people living with UCD persists. We believe that Olkruva is well-suited to address these needs as it provides personalized dosage for each patient's requirements, It's portable and easy for a patient to take, and most importantly, it is palatable, as it was formulated to overcome the challenging taste and smell that is associated with other formulations of sodium phenylbutyrate. Our commercial launch strategy is comprised of two major components. One, establishing a customer-facing team, and two, building awareness. Since the completion of the ACER acquisition in mid-November, we have made significant progress towards executing on these priorities, ensuring that people who suffer from UCDs have access to and are aware of the benefits of Olpruva. As of the end of January, we have a customer-facing team with decades of rare disease experience to support the launch of Olpruva. This team was built to be targeted and able to reach the needs of our customers and partners. most of whom are located in approximately 40 centers of excellence across the country. In addition to the sales specialists, we have marketers, patient services, and market access professionals, as well as medical science liaisons and patient advocates for engaging with key customers. While initially built to support the launch of Oprima, this same group of professionals will launch Aramacamal if approved. We've initiated several strategies that are being utilized to build awareness for El Provo, which is currently quite low. For example, we have established Quick Start, which is a 30-day free trial to allow patients and physicians to gain experience with El Provo. We're working with patient advocacy groups, the patient community, and UCD centers of excellence to drive brand recognition. We're also working with payers to ensure broad market access for patients. We've seen a meaningful growth in reimbursement coverage which was approximately 55% at the time of acquisition, to now more than 70% of covered lives. While it's too early in the launch to provide data on today's call, we're monitoring key launch performance indicators, including new patient enrollments, number of covered lives, and net revenues. As previously mentioned, the commercial footprint we established provides a high strategic fit for Aramothymol as the majority of prescribers for both products work within the same centers of excellence. If Aramothymol is approved, we believe this close proximity and overlap in patient care will allow us to realize synergies and scale with the infrastructure that we've built. As a reminder, Aromalcumol is our drug candidate in development for the treatment of Niemann-Pick disease type C, or MPC. MPC is a rare genetic, progressive, and potentially fatal neurologic disease. Earlier this month, the FDA assigned a new PDUCA date of September 21, 2024, and reaffirmed its intent to present the resubmission or discussion at an advisory committee meeting. If approved, We intend to utilize our clinical data as well as real-world evidence and the data from our expanded access program to support market access, reimbursement, and treatment decisions to establish Aramatha Mall as the foundation of treatment for people with MPC. We will continue to work closely with key opinion leaders to educate on Aramatha Mall's clinical profile and raise awareness of the heterogeneous presentation of MPC. which may include neurological and psychiatric symptoms, all of which make MPC difficult to identify and diagnose. Because of this, the time to diagnosis remains a significant unmet need in the MPC community. Therefore, we're working with patient advocates to drive early diagnosis and supporting efforts for MPC to be included in newborn screening. Together with an approved indication, these initiatives will help drive the evolution of treatment guidelines and accelerate the time to diagnosis and treatment initiation. We will continue to work with all stakeholders to develop patient services that will provide access and a positive experience. We applaud the NPC patient advocacy community who united and submitted a compelling response through an informal petition to the FDA in support of Aramathamal's approval. They received nearly 1,000 signatures from 47 states forcing their support. As the FDA review continues, Zebra will maintain our expanded access program for Aromalconol and continue working tirelessly to bring this potential therapy to patients as soon as possible. Now I'd like to turn your attention to KP1077, our clinical candidate being developed as a treatment for idiopathic hypersomnia, or IH. IH is a rare chronic sleep disorder characterized by excessive daytime sleepiness an uncontrollable need to sleep, and difficulty waking up from sleep in most instances, despite average or longer amounts of nocturnal sleep. As you may recall, Kp1077, Sert-X methylphenidate, or SDX, was designed to steadily release D-methylphenidate, its active ingredient. This unique pharmacokinetic profile allows for flexible dosing to overcome these primary IH symptoms. The design also ensures that patients receive the highest drug concentration when they need it most. SDX is designated as a Schedule IV controlled substance by the U.S. Drug Enforcement Administration. Earlier this week, we announced positive top-line data from our placebo-controlled, double-blind, proof-of-concept Phase II study evaluating the safety and tolerability of Kp1077 in patients with IH. Consistent with the interim data that we previously reported in Q4, KP1077 was well tolerated at all dose levels evaluated in the study, including the highest dose of 320 milligrams daily and at dosing regimens of either once or twice daily. The most common adverse events were insomnia, headache, anxiety, nausea, and decreased appetite. Due to KP1077's unique pharmacokinetic profile, adverse events were mostly mild in severity despite higher overall exposure levels. These data support the study's primary endpoint of safety and tolerability. Topline results from the Phase II study also showed that KP1077 produced clinically meaningful improvement in excessive daytime sleepiness, or EDS, as assessed by change from baseline in the F4 sleepiness scale during the five-week open-label titration period, which was maintained throughout the two-week double-blind withdrawal period for both dose regimens. Additionally, patients administered KP1077 showed benefit in change from baseline at the end of the open-label titration. and at the end of the double-blind withdrawal period for the IH severity scale, the sleep inertia visual analog scale, and brain fog severity scale. The study successfully fulfilled the objectives by providing key information for the design of a potentially pivotal efficacy trial, and the results of the secondary efficacy endpoints are supportive of initiating a Phase III trial of KP1077. We plan to request and end the Phase II meeting with the FDA to seek guidance on the Phase III clinical trial design. We are pleased with the top-line data and believe that KP-1077 could provide a significant benefit to the estimated 37,000 people in the U.S. who are currently diagnosed with IH. With only one FDA-approved treatment for IH, there remains an unmet need for therapies with different mechanisms of action to address symptoms including sleep inertia, excessive daytime sleepiness, and cognitive dysfunction. We look forward to presenting the results from our phase two study at the upcoming Sleep 2024 conference this summer. And in summary, we're pleased with our progress in the fourth quarter. As we enter 2024, we have three areas of focus. First, to successfully launch Olpruva and ensure access for patients. Second, to prepare for the potential launch of Arumacumab. And third, to advance KP-1077 in sleep disorders. We believe that we are all, we believe that we are well positioned to continue to execute and deliver on these key strategic objectives. Now I'll hand the call over to LeBlanc who will provide an update on our financial results and outlook.
spk07: Thank you and good afternoon. 2023 was a time of incredible progress as we seek to make therapies available to people living with rare diseases. Our financial results for the quarter and full year reflect our continued investments in advancing our development programs and building out our commercial capabilities. As Neil pointed out at the beginning of the call, we are restating our previously issued financial statements for the fiscal year into 2022, including all interim periods, and the interim period in 2023, due to a change in the accounting for warrants with certain cash settlement features. Warrants from 2021 have been classified as equity and are now accounted for as a liability, resulting in non-cash fair value adjustments that will be recognized at the end of each reporting period. This change and the related non-cash adjustments are expected to have no direct impact on the company's cash, cash equivalents, and investments, our forecasted runway, or our business operations. Now, focusing on our financial results for Q4 2023, we reported net revenue of $13.2 million. This was a solid quarter in which we earned the net sales milestone of $10 million under the Astorias License Agreement as annual net sales for that product surpassed $50 million for the year. Revenue also included royalties under the license, which rose to $1.3 million for the period, comparing to $900,000 in Q3 2023. Net reimbursements from the French Expanded Access Program for Aramacimo was $1.8 million, and there was recognition of some initial sales of approval. R&D expenses for the quarter were $11.4 million, which was primarily driven by the Phase II study in KP 1077 that has since been completed, along with the work to prepare the Aramocamo MDA for resubmission. General and administrative expenses were $14.7 million. The period-over-period increase was primarily related to personnel costs and professional fees associated with our investments and our commercial infrastructure, as well as our business development activities, which included the closing of the ACERT acquisition. Net loss for Q4 2023 was $19.6 million, or 51 cents per basic and diluted share. Our full year 2023 results included net revenue of $27.5 million, which was primarily driven by the $15 million in total net sales milestones earned under the ASTARs License Agreement, royalties of $3.8 million, and net reimbursements from the French Early Access Program for Aramacamo, totaling $8.6 million for the year. With total R&D expenses of $39.8 million and G&A expenses of $34.3 million, we reported a net loss of $46 million, or $1.30 for basic and diluted share for 2023, which includes the non-cash impact of the change in fair value adjustment for the warrant liability of $1.4 million, or $0.04 for basic and diluted share. As of year end, total cash, cash equivalents and securities were $67.7 million, which was a decrease of $15.7 million compared to September 30th, 2023. Total shares of common stock outstanding were 41.5 million and fully diluted shares outstanding was 58.2 million. which includes approximately 5.6 million shares, issuable upon exercise of warrants. Looking ahead, our available resources are expected to support our forecasted operating cash runway into 2026, and we intend to evaluate optimization of our debt structure. Our forecast includes commercial revenue from sales of Okruba and ongoing reimbursements from the French EAP for Aramacamo, but it does not include commercial revenue from sales of Aramacamo or the sale of the priority review voucher, which would follow potential FDA approval. We remain optimistic about the opportunities we have in store during 2024, and our focus is on creating long-term value for shareholders by consistently executing against our plan in support of our mission to becoming a leading rare disease company. Now, our colleagues Josh, Crystal, and Adrian will join us for our Q&A session. Operator, please open the line for questions.
spk01: At this time, if you'd like to ask a question, please press the star and 1 on your telephone keypad. Keep in mind, you may remove yourself from the question queue by pressing star and 2. We'll take our first question from Oren Leibniz with H.C. Wainwright. Please go ahead. Your line is open.
spk10: Thanks. It's helpful. I'm really curious about this old Pruva launch. It sounds like you've got your infrastructure in place and, you know, maybe are just now trying to build awareness. you know, I know you're not giving guidance and certainly not on a product-specific basis, but should we expect material revenue growth for that product this year, or is this more about just like a sampling and awareness-building year and just getting all the patient support processes worked out, especially ahead of Aramaclimal? And on Aramaclimal, can you talk about what If anything you can say about your expectations around an adcom as far as what areas of focus, you know, you are most preparing for, where you think the agency might be most interested, whether it be, you know, the connection between real-world data and your clinical data or validation and statistical issues, you know, anything you can provide on that probably would be really helpful. Yeah.
spk07: Hey, Ron. It's Josh. Thanks for the question. With regards to the Alproova performance, as you noted, we are in full launch. And as Neil just mentioned, it affected the end of January. We had an entire commercial and medical team out engaging with our customers. We knew at the beginning of all of this that awareness for Alprova and Zebra was quite low, but Alprova in particular, if you recall, it was approved through a 505 pathway, which meant that it had very little clinical experience. And so our priorities have really been around driving awareness and ensuring that patients have access to Alproova. And to do that, you know, our team is working with physicians to identify the appropriate patients. We have a quick start program in place to make sure that patients can experience the benefits of Alproova. And our reimbursement is increasing from 55% to over 75%. So it is too early for us to give any guidance on performance and revenue. We will be watching new patient enrollments, covered lives, and net sales as we go, and we'll be providing updates on a quarterly basis.
spk08: I was going to ask Adrian to comment a little bit on the agency and the potential focus of the ad comp.
spk09: that we not confirmed the adcom, so there's an intention to hold an adcom and no date has been set. We're obviously clearly preparing for the adcom. As part of the initial submission and the CRL, we kind of know what the questions were that the agency were looking for. We're focusing on addressing those telling the story that the clinical data clearly shows, which is a significant benefit for patients. Some additional information that we got during the two Type B meetings prior to our resubmission will also be included. But we're really mostly looking forward to having a healthy debate about what we consider clear efficacy in these patients and a clear benefit of this profile.
spk10: All right, thanks. I appreciate it. I'll drop back in the queue.
spk01: We'll take our next question from Jonathan Ashcroft with Roth MKM. Please go ahead. Your line is open.
spk05: Thank you very much. I haven't had a chance to read the press release. It came out a little late, and there's a whole bunch of calls. But can you help us better understand the magnitude of benefit in IH and thus your optimism for an end-of-Phase II meeting that will go well and inform Phase III design?
spk09: Absolutely. on what that phase 2 trial was trying to achieve. This is a trial that was designed to demonstrate safety and tolerability and inform us for what the data would say into how to design a development program in IH. Part of the secondary endpoints was looking at the daytime sleepiness and the idiopathic hyposomnia scoring scale. We saw clinically meaningful improvements, not only in the lactation phase, but also in the lower-blind phase. As I said, this trial was not designed to show statistical significance. We are planning to present this data at Sleep24 meeting, and because of that, we're on data embargo, so we will discuss the data. there with the sleep experts that will attend that meeting.
spk05: Okay. So when you did this trial, you optimized these people to, you know, any one of the four different doses. So it's a complete random smattering, like it's not 16 patients per dose. It's, you know, it's whatever was their optimum dose. That's where they landed. There's no balance among those four groups. That is correct. Okay. So after seeing the phase two press release, are you still contemplating a narcolepsy trial? Because the word narcolepsy is not in that press release on Tuesday. I was just curious why that was.
spk08: Yeah, thanks Jonathan. It's Neil. You know, we're taking this data that we've got now on our phase two to inform a phase three in IH, but we're also understanding our phase one data, some of our phase one data and other data to understand how to unlock the value of the broader sleep disorder opportunity. So we're evaluating that, but we have no further comment today on if we're going to move forward into narcolepsy.
spk05: Okay. And just a yes or no. I'll prove a, you know, MSUD is going to wait until you see how you track with the first indication, correct? Or do you have development plans for MSUD such that you could even give us a timeline?
spk07: So you are correct. We're waiting to do a full evaluation of our portfolio and strategic plan before we make any decisions on maple syrup uranus seeds.
spk05: Okay. You know, lastly, when it comes to your adcom, do companies typically have any sort of back and forth with the patient advocates and, you know, strategize in any way? And if so, do you intend to do anything like that? Or is it, you know, just everyone shows up?
spk00: This is Crystal. Yes, we do. It is very common for the companies to engage with the patient advocacy groups, and that we are doing that. You know, one of the ways was to, you know, petitions that came through. You know, certainly that was something that we were very happy to see, and so we will continue to engage and make sure that the voices of the patients are being heard at the adcoms in their own way.
spk05: I mean, I think that'll be an important part of an adcom, so that's good to hear. Thank you very much. Thank you, Jonathan.
spk01: We'll take our next question from Suman Kulkarni with Conaccord. Please go ahead. Your line is open.
spk04: Good afternoon. Thanks for taking that question. I have two. The first one is, have you had any interactions with the FDA on the pending Aramoclomol filing since you announced the three-month pushout of the action date, and how are those discussions gone?
spk08: Thank you, Suman. Maybe I'll take that one. we get as part of the NDA resubmission information requests from the agency, which we've been able to satisfy and return in a timely way. One of those requests, as we've announced previously, was to satisfy the requirement of becoming a major amendment, which then caused the delay of three months on our September 21st PDUFA. So we are having those discussions. Information requests are coming in, and we're able to satisfy those information requests in a timely fashion.
spk04: Got it. And then on the recent phase two data for 1077 in IH, we're yet to see any quantitative details because of the sleep eating related embargo, but qualitatively, would you say there was anything counterintuitive either in a positive or negative way in the data relative to your original expectation?
spk09: I think the most important So we dosed patients up to 320 milligrams, which is a pretty high dose, higher than we've dosed before in patients. And we saw no increase in the safety profile and safety risk. More importantly, the cardiovascular safety profile is exactly as we had expected, and there's no changes in the cardiovascular safety profile, showing that we, in principle, have a compound that can be safely administered to patients with idiopathic hypersomnia. Thank you.
spk01: We'll take our next question from Luis Chen with Kantor. Please go ahead. Your line is open.
spk06: Hi. Good afternoon. This is . Congrats and thank you for taking our questions. Our first question is on KP1077. post positive phase two results one is closest competitors in ih what differentiates kp 1077 our second question is on air makamo the rare pediatric disease prv program is expected to end this year if our makamo gets approved and a program does become terminated how might that impact the value of our makamos prv thank you so much
spk08: You were a little challenging to hear. I understood the question to be if we were going to get a PRV with the approval of Aramatha Mall. Is that correct? And then the other 1077 program in regards to the differentiation from competitors?
spk06: Yes, that's correct.
spk08: Thank you. okay so so so yes uh we we have a prv that will be issued upon approval uh with our amaca malls uh nba uh approval so uh that does i would add neil that uh and carby i think what he said is what is the likelihood or what do we think the value change would be if the program governing that would be ending this year
spk07: And I think the analysis we've seen or the information we've heard from a variety of sources says that the potential, if that program ends, the value could go up. So I think we're going to assess that and look at that, but that's our current thinking on that point.
spk09: Adrian? Okay. Adrian here. So in regards to the competition in the idiopathic hypersomnia space. So KP-1077 hasn't different pharmacokinetic profile than other products in the market, and also a specific mode of action being a stimulant. There's only a Schedule IV program, and as I said previously, the cardiovascular safety really jumps out when you look at the benefit of this program compared to other drugs currently on the market.
spk01: Great. Thank you so much. And as a reminder, if you'd like to ask a question today, please press the star and one keys on your telephone keypad. We'll take our next question from Tim Lugo with William Blair. Please go ahead. Your line is open.
spk03: Hey, guys. This is Lachlan. I'm for Tim. Thanks for taking the question. I guess the first one is just on the operable launch. It sounds like obviously it's been low awareness. You maybe don't have a ton of experience, but can you maybe talk about the feedback that you've got thus far from those who do have experience? And then second, I understand Revicti is meant to lose exclusivity at some point in the next year or two. So can you just talk about your expectations for that and what it might mean for the market and for Allprover and maybe what the sort of scenarios there are?
spk07: Sure, thanks for the question. Yes, so awareness has been more for the reasons that I stated and our primary objective now is to really build that awareness working with physicians to identify those appropriate patients and to The initial feedback that we're getting is those patients who have had experience with Alprova are continuing on that. We have a number of patients who are continuing to get refills of Alprova, and that really bodes well for future uptake. In terms of Reviki and their patent expiration, or I guess it's really the entrance of authorized generics, We are aware that later next year it's likely that a first authorized generic for Revicti will come into the market and potentially a second thereafter. We view that really as entrance into the higher end of the market, specifically products competing with Revicti in the same formulation. I'll prove it. very much clinically differentiated from Revicti and any authorized generic that comes into the market. And we believe that we've got a great clinical benefit and we're well-priced to be able to compete in this market.
spk01: And next we have a follow-up question from Warren Liveduck with H.C. Wainwright. Please go ahead.
spk10: Thank you. Just to follow up again on Old Prover, I know it's quite early, but as you get more patients, hopefully, into the funnel, into the referral network, and then as you try to get them through adjudication to paid therapy, are you finding that you're being held to the hurdle of being compared to a generic Bufinil from a cost perspective, or is the bar more likely lower in that you're essentially being benchmarked against market-leading Revicti? And Regarding the patients, you know, you're going after, are you assuming current Revicti patients are low-hanging fruit given you've got a presumably much superior product here from the patient perspective? Or conversely, are they maybe the stable business and not your target patient?
spk07: Yeah, thanks. So all products, all branded products in this, And so it's not unique for Altruva to have a step edit where a generic D-Phenyl is required first. But we're seeing patients stepping through that very, very quickly. And then physicians and patients are making a decision as to what's the next best clinical opportunity for patients. Many of the physicians that we've been speaking with, albeit it's been just a few short weeks that we've had that clinically differentiated and beneficial profile for these patients. So it's a little too early to give you the definitive answers to that one, but the early signals are that, again, the profile of Alprova is really lending itself towards patients switching both from Febrane and Revit B2 Alprova.
spk08: Warren, I might add one additional comment to that. I think that's an important perspective. As Josh mentioned, the approach to getting patients on therapy is fairly consistent. Our improvement of the reimbursement of covered lives from 55% up to 70% really puts us close to par also in that area, which then, you know, we then can drive that awareness and clinical differentiation from the other products in the market. And with the Quick Start program and other awareness campaigns that we're moving forward with will allow us to be able to give patients an option, physicians an option.
spk10: Thanks. Good luck.
spk07: Thank you.
spk01: And this does conclude the Q&A portion for today's call. I'd now like to turn the call back over to Neil McFarlane for any closing remarks.
spk08: Thank you, Operator. The fourth quarter of 2023 was a period of tremendous transformation for Zemra. We made solid progress towards achieving our mission of building a leading patient-focused rare disease company. As we look to 2024, our key strategic priorities are clear, and we look forward to updating you in the future. Thanks for joining us today.
spk01: This does conclude today's program. Thank you for your participation and you may disconnect.
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